Publications by authors named "Mark Andrews"

108 Publications

Microwave Radiometry at Frequencies From 500 to 1400 MHz: An Emerging Technology for Earth Observations.

IEEE J Sel Top Appl Earth Obs Remote Sens 2021 14;14:4894-4914. Epub 2021 Apr 14.

NASA Jet Propulsion Laboratory, Pasadena, CA 91109 USA.

Microwave radiometry has provided valuable spaceborne observations of Earth's geophysical properties for decades. The recent SMOS, Aquarius, and SMAP satellites have demonstrated the value of measurements at 1400 MHz for observing surface soil moisture, sea surface salinity, sea ice thickness, soil freeze/thaw state, and other geophysical variables. However, the information obtained is limited by penetration through the subsurface at 1400 MHz and by a reduced sensitivity to surface salinity in cold or wind-roughened waters. Recent airborne experiments have shown the potential of brightness temperature measurements from 500-1400 MHz to address these limitations by enabling sensing of soil moisture and sea ice thickness to greater depths, sensing of temperature deep within ice sheets, improved sensing of sea salinity in cold waters, and enhanced sensitivity to soil moisture under vegetation canopies. However, the absence of significant spectrum reserved for passive microwave measurements in the 500-1400 MHz band requires both an opportunistic sensing strategy and systems for reducing the impact of radio-frequency interference. Here, we summarize the potential advantages and applications of 500-1400 MHz microwave radiometry for Earth observation and review recent experiments and demonstrations of these concepts. We also describe the remaining questions and challenges to be addressed in advancing to future spaceborne operation of this technology along with recommendations for future research activities.
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http://dx.doi.org/10.1109/jstars.2021.3073286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244653PMC
April 2021

Inter and intra-observer errors for postoperative total hip radiographic assessment using computer aided design.

Acta Orthop Belg 2021 Mar;87(1):65-71

Plain radiographic assessment of primary total hip arthroplasty following surgery remains to be the commonest radiological assessment. The current paper, studies the accuracy and concordance between observers reviewing these radiographs. A prospective radiographic and medical note review of ten patients who underwent total hip replacement for primary osteoarthritis, with a mean age of 69 years. Early and 6 weeks postoperative x-rays were assessed for hip profile and version profile using computer aided design (CAD) by two observers on two different occasions. The observers were Orthopaedic surgeons who perform arthroplasty of the hip. The results were analyzed statistically. Dimensions, including Femoral offset, medial offset and ilioischial offset showed a high degree of inter- film and intra-film correlation, with inter-class cor- relation (ICC) over 0.8. Except of the intra-film correlation of ilioischial offset measured on the post- operative films (p=0.067) by the first rater, all the intra and inter film correlation were significantly over the benchmark of 0.6. In terms of stem alignment, cup inclination and cup version, the intra-film correlation by rater n°2 ranges from 0.574 to 0.975 and were significantly over the benchmark of 0.6, except in the case of cup inclination measured on the 6 th​ week follow-up ; meanwhile the intra-film correlation by rater n°1 ranges from 0.581 to 0.819 and none were significantly over the benchmark of 0.6. The inter-rater reliability and inter-film correlation showed a dichotomy of results among different dimensions of the measurement. Dimensions of femoral offset, medial offset and ilioischial offset showed a substantial degree of reliability in terms of inter-rater reliability, inter-film correlation, and intra-rater/film reliability.
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March 2021

A model for calculating the mechanical demands of overground running.

Sports Biomech 2020 Sep 21:1-22. Epub 2020 Sep 21.

School of Human Movement and Nutrition Sciences, University of Queensland, St Lucia, QLD, Australia.

An energy-based approach to quantifying the mechanical demands of overground, constant velocity and/or intermittent running patterns is presented. Total mechanical work done () is determined from the sum of the four sub components: work done to accelerate the centre of mass horizontally (), vertically (), to overcome air resistance () and to swing the limbs (). These components are determined from established relationships between running velocity and running kinematics; and the application of work-energy theorem. The model was applied to constant velocity running (2-9 m/s), a hard acceleration event and a hard deceleration event. The estimated and each sub component were presented as mechanical demand (work per unit distance) and power (work per unit time), for each running pattern. The analyses demonstrate the model is able to produce estimates that: 1) are principally determined by the absolute running velocity and/or acceleration; and 2) can be attributed to different mechanical demands given the nature of the running bout. Notably, the proposed model is responsive to varied running patterns, producing data that are consistent with established human locomotion theory; demonstrating sound construct validity. Notwithstanding several assumptions, the model may be applied to quantify overground running demands on flat surfaces.
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http://dx.doi.org/10.1080/14763141.2020.1795238DOI Listing
September 2020

Letter to the editor "The influence of obesity on clinical outcomes following primary total knee arthroplasty: A prospective cohort study".

Knee 2020 12 22;27(6):2019-2020. Epub 2020 Aug 22.

Scarborough Hospital, Woodlands Drive, Scarborough YO12 6QL, United Kingdom.

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http://dx.doi.org/10.1016/j.knee.2020.07.103DOI Listing
December 2020

Quantification of maximal power output in well-trained cyclists.

J Sports Sci 2021 Jan 13;39(1):84-90. Epub 2020 Aug 13.

Griffith Sports Physiology and Performance, School of Allied Health Sciences, Griffith University , Gold Coast, Australia.

This study aimed to compare mechanical variables derived from torque-cadence and power-cadence profiles established from different cycle ergometer modes (isoinertial and isokinetic) and modelling procedures (second- and third-order polynomials), whilst employing a novel method to validate the theoretical maximal power output (P). Nineteen well-trained cyclists ( = 12 males) completed two experimental sessions comprising six, 6-s maximal isoinertial or isokinetic cycling sprints. Maximal pedal strokes were extracted to construct power-cadence relationships using second- and third-order polynomials. A 6-s sprint at the optimal cadence (F) or optimal resistance (T) was performed to assess construct validity of P. No differences were found in the mechanical parameters when derived from isokinetic (P = 1311 ± 415, F = 118 ± 12) or isoinertial modes (P = 1320 ± 421, F = 116 ± 19). However, R improved ( < 0.02) when derived from isoinertial sprints. Third-order polynomial modelling improved goodness of fit values (Standard Error, adjusted R), but derived similar mechanical parameters. Finally, peak power output during the optimised sprint did not significantly differ from the theoretical P in both cycling modes, thus providing construct validity. The most accurate P-C profile can be derived from isoinertial cycling sprints, modelled using third-order polynomial equations.
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http://dx.doi.org/10.1080/02640414.2020.1805251DOI Listing
January 2021

Project Gatekeeper: An Entrance Control System Embedded Radiation Detection Capability for Security Applications.

Sensors (Basel) 2020 May 23;20(10). Epub 2020 May 23.

Interface Analysis Centre, School of Physics, HH Wills Physics Laboratory, University of Bristol, Tyndall Avenue, Bristol BS8 1TL, UK.

Threat assessments continue to conclude that terrorist groups and individuals as well as those wanting to cause harm to society have the ambition and increasing means to acquire unconventional weapons such as improvised nuclear explosive devices and radiological disposal devices. Such assessments are given credence by public statements of intent by such groups/persons, by reports of attempts to acquire radioactive material and by law enforcement actions which have interdicted, apprehended or prevented attempts to acquire such material. As a mechanism through which to identify radioactive materials being transported on an individual's person, this work sought to develop a detection system that is of lower-cost, reduced form-factor and more covert than existing infrastructure, while maintaining adequate sensitivity and being retrofittable into an industry standard and widely utilised Gunnebo Speed Gate system. The system developed comprised an array of six off-set Geiger-Muller detectors positioned around the gate, alongside a single scintillator detector for spectroscopy, triggered by the systems inbuilt existing IR proximity sensor. This configuration served to not only reduce the cost for such a system but also allowed for source localisation and identification to be performed. Utilising the current setup, it was possible to detect a 1 µSv/h source carried into the Speed Gate in all test scenarios, alongside locating and spectrally analysing the material in a significant number.
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http://dx.doi.org/10.3390/s20102957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285256PMC
May 2020

Age-related differences in postural adjustments during limb movement and motor imagery in young and older adults.

Exp Brain Res 2020 Apr 27;238(4):771-787. Epub 2020 Feb 27.

Department of Psychology, Nottingham Trent University, Nottingham, UK.

Recent research has shown that systematic postural adjustments occur during periods of manual motor imagery (MI), but the timing (anticipatory or reactive) and directionality (against or in the direction of arm extension) of these postural motions relative to individual manual actions or imagery are not well understood. This study analyzed the anteroposterior hip and head motion of healthy young and older participants, while they imagined bilateral arm raises under self-initiated or environmentally triggered performance conditions. When MI was self-initiated, both age groups showed significant forward postural motion during the second prior to MI initiation. When MI (or physical arm movement) was environmentally triggered, however, older people did not show anticipatory forward postural motion, but did show compensatory backward head motion. These results suggest that manual MI is indeed accompanied by anticipatory postural motion, but this anticipation is attenuated in older people when they do not have control over the timing of manual movement onset.
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http://dx.doi.org/10.1007/s00221-020-05751-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181438PMC
April 2020

Extension of the Notch intracellular domain ankyrin repeat stack by NRARP promotes feedback inhibition of Notch signaling.

Sci Signal 2019 11 5;12(606). Epub 2019 Nov 5.

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.

Canonical Notch signaling relies on regulated proteolysis of the receptor Notch to generate a nuclear effector that induces the transcription of Notch-responsive genes. In higher organisms, one Notch-responsive gene that is activated in many different cell types encodes the Notch-regulated ankyrin repeat protein (NRARP), which acts as a negative feedback regulator of Notch responses. Here, we showed that NRARP inhibited the growth of Notch-dependent T cell acute lymphoblastic leukemia (T-ALL) cell lines and bound directly to the core Notch transcriptional activation complex (NTC), requiring both the transcription factor RBPJ and the Notch intracellular domain (NICD), but not Mastermind-like proteins or DNA. The crystal structure of an NRARP-NICD1-RBPJ-DNA complex, determined to 3.75 Å resolution, revealed that the assembly of NRARP-NICD1-RBPJ complexes relied on simultaneous engagement of RBPJ and NICD1, with the three ankyrin repeats of NRARP extending the Notch1 ankyrin repeat stack. Mutations at the NRARP-NICD1 interface disrupted entry of the proteins into NTCs and abrogated feedback inhibition in Notch signaling assays in cultured cells. Forced expression of NRARP reduced the abundance of NICD in cells, suggesting that NRARP may promote the degradation of NICD. These studies establish the structural basis for NTC engagement by NRARP and provide insights into a critical negative feedback mechanism that regulates Notch signaling.
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http://dx.doi.org/10.1126/scisignal.aay2369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212804PMC
November 2019

Stretch Receptor and Somatic Dysfunction: A Narrative Review.

Authors:
Mark A W Andrews

J Am Osteopath Assoc 2019 Aug;119(8):511-519

From its founding by Andrew Taylor Still, MD, DO, through the work of many contributors, one of the cornerstones of osteopathic medicine has been its ability to aid health by promoting neuromuscular homeostasis. As part of the understanding of osteopathic medicine since the time of Still, the proper functioning of stretch receptor organs (SROs) of skeletal muscle have been recognized as having a central role in this homeostasis. In doing so, the complexities of these numerous and vital sensors are described, including recent findings regarding their structure, function, and the nature of their neural connections. In their homeostatic role, SROs conduct information centrally for integration in proprioceptive and autonomic reflexes. By virtue of their integral role in muscle reflexes, they are putatively involved in somatic dysfunction and segmental facilitation. In reviewing some well-established knowledge regarding the SRO and introducing more recent scientific findings, an attempt is made to offer insights on how this knowledge may be applied to better understand somatic dysfunction.
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http://dx.doi.org/10.7556/jaoa.2019.094DOI Listing
August 2019

Routine monitoring for heparin-induced thrombocytopenia following lower limb arthroplasty: Is it necessary? A prospective study in a UK district general hospital.

Orthop Traumatol Surg Res 2019 05 13;105(3):497-501. Epub 2019 Mar 13.

York Hospital NHS Foundation Trust, Wiggington Road, York, YO31 8HE, United Kingdom.

Introduction: Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening condition associated with heparin administration. Many orthopaedic units routinely prescribe low-molecular-weight heparins as thromboprophylaxis after hip and knee arthroplasty.

Hypothesis: We postulated that routine platelet monitoring following heparin administration is of no clinical benefit. We therefore asked: firstly, what was the rate of thrombocytopenia in a large population of patients undergoing lower limb arthroplasty? Secondly, did this rate justify routine platelet monitoring?

Materials And Methods: Unless contraindicated, all patients (n=1999, 53.05% female, mean age 69.23 years) at a UK district general hospital undergoing hip and knee arthroplasty were given daily prophylactic enoxaparin. Platelet counts were obtained between the 8th and 10th postoperative days and compared to preoperative baseline. A > 50% fall in platelet count was classified as "possible HIT". The minimal acceptable risk of thrombocytopenia was defined using The American College of Chest Physicians (ACCP) 2012 guidelines, which recommend monitoring platelet counts in patients receiving heparin where the expected risk of HIT is>1% and by descriptive cost-benefit analysis based on the cost of routine platelet monitoring in the clinical setting.

Results: Complete results were available for 1361 (68.1%) patients, comprising: 653 primary hips, 22 revision hips, 1 hip resurfacing, 665 primary knees, 19 revision knees and 1 unicompartmental knee replacement. Mean platelet level was 281.9×109/L preoperatively and 527.83×109/L postoperatively. Forty-four patients (3.2%) experienced a postoperative fall in platelet levels. However, no patient experienced a drop in platelets to less than 50% of the preoperative value.

Discussion: The incidence of HIT in the elective arthroplasty population is low. Therefore, routine postoperative monitoring of platelets is not necessary in this population of patients.

Level Of Evidence: II, prospective study.
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http://dx.doi.org/10.1016/j.otsr.2018.12.012DOI Listing
May 2019

Perceptual Errors Support the Notion of Masking by Object Substitution.

Perception 2019 Feb;48(2):138-161

Nottingham Trent University, UK.

Two experiments examined the effect of object substitution masking (OSM) on the perceptual errors in reporting the orientation of a target. In Experiment 1, a four-dot trailing mask was compared with a simultaneous-noise mask. In Experiment 2, the four-dot and noise masks were factorially varied. Responses were modelled using a mixture regression model and Bayesian inference to deduce whether the relative impacts of OSM on guessing and precision were the same as those of a noise mask, and thus whether the mechanism underpinning OSM is based on increasing noise rather than a substitution process. Across both experiments, OSM was associated with an increased guessing rate when the mask trailed target offset and a reduction in the precision of the target representation (although the latter was less reliable across the two experiments). Importantly, the noise mask also influenced both guessing and precision, but in a different manner, suggesting that OSM is not simply caused by increasing noise. In Experiment 2, the effects of OSM and simultaneous-noise interacted, suggesting the two manipulations involve common mechanisms. Overall results suggest that OSM is often a consequence of a substitution process, but there is evidence that the mask increases noise levels on trials where substitution does not occur.
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http://dx.doi.org/10.1177/0301006619825782DOI Listing
February 2019

Earthquake lubrication and healing explained by amorphous nanosilica.

Nat Commun 2019 01 18;10(1):320. Epub 2019 Jan 18.

Sezione di Tettonofisica e Sismologia, Istituto Nazionale di Geofisica e Vulcanologia, Roma, Italy.

During earthquake propagation, geologic faults lose their strength, then strengthen as slip slows and stops. Many slip-weakening mechanisms are active in the upper-mid crust, but healing is not always well-explained. Here we show that the distinct structure and rate-dependent properties of amorphous nanopowder (not silica gel) formed by grinding of quartz can cause extreme strength loss at high slip rates. We propose a weakening and related strengthening mechanism that may act throughout the quartz-bearing continental crust. The action of two slip rate-dependent mechanisms offers a plausible explanation for the observed weakening: thermally-enhanced plasticity, and particulate flow aided by hydrodynamic lubrication. Rapid cooling of the particles causes rapid strengthening, and inter-particle bonds form at longer timescales. The timescales of these two processes correspond to the timescales of post-seismic healing observed in earthquakes. In natural faults, this nanopowder crystallizes to quartz over 10s-100s years, leaving veins which may be indistinguishable from common quartz veins.
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http://dx.doi.org/10.1038/s41467-018-08238-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338773PMC
January 2019

Discovery of Potent, Selective, and Peripherally Restricted Pan-Trk Kinase Inhibitors for the Treatment of Pain.

J Med Chem 2018 08 27;61(15):6779-6800. Epub 2018 Jul 27.

Pfizer Worldwide R&D, Groton Laboratories , Eastern Point Road , Groton , Connecticut 06340 , United States.

Hormones of the neurotrophin family, nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4), are known to activate the family of Tropomyosin receptor kinases (TrkA, TrkB, and TrkC). Moreover, inhibition of the TrkA kinase pathway in pain has been clinically validated by the NGF antibody tanezumab, leading to significant interest in the development of small molecule inhibitors of TrkA. Furthermore, Trk inhibitors having an acceptable safety profile will require minimal brain availability. Herein, we discuss the discovery of two potent, selective, peripherally restricted, efficacious, and well-tolerated series of pan-Trk inhibitors which successfully delivered three candidate quality compounds 10b, 13b, and 19. All three compounds are predicted to possess low metabolic clearance in human that does not proceed via aldehyde oxidase-catalyzed reactions, thus addressing the potential clearance prediction liability associated with our current pan-Trk development candidate PF-06273340.
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http://dx.doi.org/10.1021/acs.jmedchem.8b00633DOI Listing
August 2018

Implementing the access and waiting time standard for early intervention in psychosis in the United Kingdom: An evaluation of referrals and post-assessment outcomes over the first year of operation.

Early Interv Psychiatry 2018 10 26;12(5):979-986. Epub 2018 Mar 26.

Early Intervention in Psychosis Team, Lincolnshire Partnership NHS Foundation Trust, Lincoln, UK.

Aim: Improving timely access to evidence-based treatment for people aged 14-65 years experiencing a first episode psychosis (FEP) or an at-risk mental state (ARMS) for psychosis is a national priority within the United Kingdom. An early intervention in psychosis (EIP) access and waiting time standard has been set which has extended the age range and acceptance criteria for services.

Methods: This descriptive evaluation reports upon the referrals and access to treatment times within an EIP service over the first year of operating in line with the access and waiting time standard. Patient pathways and post-assessment status are also described.

Results: The service received 406 referrals, of which 88% (n = 357) were assessed. The mean length of time to treatment was 1.5 weeks, with 88% being seen within 2 weeks. Of those who engaged in an assessment, 34% (n = 138) were identified as ARMS cases and 30% (n = 123) were identified as FEP. Over 35 year olds accounted for 22% (n = 80) of the total accepted cases.

Conclusions: The findings indicate clinical and operational issues, which will need careful consideration in the future planning of services. The high number of ARMS cases highlights the importance of clear treatment pathways and targeted interventions and may suggest a need to commission distinct ARMS services. The number of people who met the extended age and service acceptance criteria may suggest a need to adapt or redesign clinical services to meet the age-specific needs of over 35 year olds and those with an ARMS. It is unclear how changes to the remit of EIP services will impact upon future clinical outcomes.
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http://dx.doi.org/10.1111/eip.12548DOI Listing
October 2018

The Discovery of a Potent, Selective, and Peripherally Restricted Pan-Trk Inhibitor (PF-06273340) for the Treatment of Pain.

J Med Chem 2016 11 4;59(22):10084-10099. Epub 2016 Nov 4.

Pfizer Global Research & Development , The Portway Building, Granta Park, Great Abington, Cambridge, CB21 6GS, U.K.

The neurotrophin family of growth factors, comprised of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4), is implicated in the physiology of chronic pain. Given the clinical efficacy of anti-NGF monoclonal antibody (mAb) therapies, there is significant interest in the development of small molecule modulators of neurotrophin activity. Neurotrophins signal through the tropomyosin related kinase (Trk) family of tyrosine kinase receptors, hence Trk kinase inhibition represents a potentially "druggable" point of intervention. To deliver the safety profile required for chronic, nonlife threatening pain indications, highly kinase-selective Trk inhibitors with minimal brain availability are sought. Herein we describe how the use of SBDD, 2D QSAR models, and matched molecular pair data in compound design enabled the delivery of the highly potent, kinase-selective, and peripherally restricted clinical candidate PF-06273340.
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http://dx.doi.org/10.1021/acs.jmedchem.6b00850DOI Listing
November 2016

Clinical Aspects of Type 3 Long-QT Syndrome: An International Multicenter Study.

Circulation 2016 Sep 26;134(12):872-82. Epub 2016 Aug 26.

From AMC Heart Centre, Department of Clinical and Experimental Cardiology (A.A.M.W., C.R.B.) and Department of Clinical Genetics (N.H., M.A.), Academic Medical Center, Amsterdam, The Netherlands; Cardiology Division of the Department of Medicine (A.J.M., C.L., W.Z., I.G., J.L.R., M.L.A., S.M., B.P.), the Department of Biostatistics (D.R.P.), and the Department of Pathology (M.Q.), University of Rochester School of Medicine and Dentistry, Rochester, NY; Heart and Vascular Research Center, MetroHealth Campus of Case Western Reserve University, Cleveland, OH (E.S.K.); Department of Cardiovascular Medicine, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan (W.S.); Department of Cardiology Bikur Cholim Hospital, Jerusalem, Israel (J.B.); Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH (J.A.T.); IRCCS Istituto Auxologico Italiano, Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, Milan, Italy (C.P. L.C., P.J.S.); Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (J.K.K.); Departments of Medicine, Pediatrics, and Molecular Pharmacology & Experimental Therapeutics, Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, MN (D.J.T., M.J.A.); Division of Arrhythmia and Electrophysiology, Department of Cardiovascular Medicine (W.S.) and Department of Preventive Cardiology (Y.M.), National Cerebral and Cardiovascular Center, Suita, Japan; Department of Molecular Medicine, University of Pavia, Italy (L.C.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.A.M.W.); and Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital IRCCS Istituto Auxologico Italiano, Milan, Italy (L.C., P.J.S.).

Background: Risk stratification in patients with type 3 long-QT syndrome (LQT3) by clinical and genetic characteristics and effectiveness of β-blocker therapy has not been studied previously in a large LQT3 population.

Methods: The study population included 406 LQT3 patients with 51 sodium channel mutations; 391 patients were known to be event free during the first year of life and were the focus of our study. Clinical, electrocardiographic, and genetic parameters were acquired for patients from 7 participating LQT3 registries. Cox regression analysis was used to evaluate the independent contribution of clinical, genetic, and therapeutic factors to the first occurrence of time-dependent cardiac events (CEs) from age 1 to 41 years.

Results: Of the 391 patients, 118 (41 males, 77 females) patients (30%) experienced at least 1 CE (syncope, aborted cardiac arrest, or long-QT syndrome-related sudden death), and 24 (20%) suffered from LQT3-related aborted cardiac arrest/sudden death. The risk of a first CE was directly related to the degree of QTc prolongation. Cox regression analysis revealed that time-dependent β-blocker therapy was associated with an 83% reduction in CEs in females (P=0.015) but not in males (who had many fewer events), with a significant sex × β-blocker interaction (P=0.04). Each 10-ms increase in QTc duration up to 500 ms was associated with a 19% increase in CEs. Prior syncope doubled the risk for life-threatening events (P<0.02).

Conclusions: Prolonged QTc and syncope predispose patients with LQT3 to life-threatening CEs. However, β-blocker therapy reduces this risk in females; efficacy in males could not be determined conclusively because of the low number of events.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.116.021823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030177PMC
September 2016

New Mexico Community Health Councils: Documenting Contributions to Systems Changes.

Prog Community Health Partnersh 2015 ;9(4):471-81

Context: Coalition research has shifted from delineating structures and processes to identifying intermediate, systems changes (e.g., changes in policies) that contribute to longterm community health improvement.

Objective: The University of New Mexico, the New Mexico Department of Health, and community health councils entered a multiyear participatory evaluation process to answer: What actions did health councils take that led to improving health through intermediate, systems changes?

Design: The evaluation system was created over several phases through an iterative, participatory process. Data were collected for councils' health priority areas (e.g., substance abuse) from 2009 to 2011.

Participants: Twenty-three community health councils participated.

Main Outcome Measures: Intermediate systems changes were measured: 1) networking and partnering, 2) joint planning of strategies, programs, and services, 3) leveraging resources, and 4) policy initiatives.

Results: Health councils reported data for each intermediate outcome by health priority area. Data showed councils identified local public health priorities and addressed those priorities through strengthening networks and partnerships, which lead to the creation and enhancement of strategies, services, and programs. Data also showed councils influenced policies in several ways (e.g., developing policy, identifying new policy, or sponsoring informational forums). Additionally, data showed councils leveraged $1.10 for every dollar invested by the state. When funding was suspended in July 2010, data showed dramatic decreases in activity levels from 2010 to 2011.

Conclusions: The data demonstrate the feasibility and utility of an Internet-based system designed to gather intermediate systems changes evaluation data. This process is a model for similar efforts to capture common outcomes across diverse coalitions and partnerships.
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http://dx.doi.org/10.1353/cpr.2015.0072DOI Listing
February 2016

What are the implications of implementation science for medical education?

Med Educ Online 2015 23;20:27003. Epub 2015 Apr 23.

Continuing Medical Education, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Background: Derived from multiple disciplines and established in industries outside of medicine, Implementation Science (IS) seeks to move evidence-based approaches into widespread use to enable improved outcomes to be realized as quickly as possible by as many as possible.

Methods: This review highlights selected IS theories and models, chosen based on the experience of the authors, that could be used to plan and deliver medical education activities to help learners better implement and sustain new knowledge and skills in their work settings.

Results: IS models, theories and approaches can help medical educators promote and determine their success in achieving desired learner outcomes. We discuss the importance of incorporating IS into the training of individuals, teams, and organizations, and employing IS across the medical education continuum. Challenges and specific strategies for the application of IS in educational settings are also discussed.

Conclusions: Utilizing IS in medical education can help us better achieve changes in competence, performance, and patient outcomes. IS should be incorporated into curricula across disciplines and across the continuum of medical education to facilitate implementation of learning. Educators should start by selecting, applying, and evaluating the teaching and patient care impact one or two IS strategies in their work.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4409632PMC
http://dx.doi.org/10.3402/meo.v20.27003DOI Listing
November 2015

Discovery of a Selective TRPM8 Antagonist with Clinical Efficacy in Cold-Related Pain.

ACS Med Chem Lett 2015 Apr 30;6(4):419-24. Epub 2015 Jan 30.

Worldwide Medicinal Chemistry and Biology, Pfizer Global Research and Development, Sandwich Laboratories , Ramsgate Road, Sandwich, Kent CT13 9NJ, United Kingdom.

The transient receptor potential (TRP) family of ion channels comprises nonselective cation channels that respond to a wide range of chemical and thermal stimuli. TRPM8, a member of the melastatin subfamily, is activated by cold temperatures (<28 °C), and antagonists of this channel have the potential to treat cold induced allodynia and hyperalgesia. However, TRPM8 has also been implicated in mammalian thermoregulation and antagonists have the potential to induce hypothermia in patients. We report herein the identification and optimization of a series of TRPM8 antagonists that ultimately led to the discovery of PF-05105679. The clinical finding with this compound will be discussed, including both efficacy and its ability to affect thermoregulation processes in humans.
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http://dx.doi.org/10.1021/ml500479vDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394344PMC
April 2015

Total variation regularization via continuation to recover compressed hyperspectral images.

IEEE Trans Image Process 2015 Jan 26;24(1):284-93. Epub 2014 Nov 26.

In this paper, we investigate a low-complexity scheme for decoding compressed hyperspectral image data. We have exploited the simplicity of the subgradient method by modifying a total variation-based regularization problem to include a residual constraint, employing convex optimality conditions to provide equivalency between the original and reformed problem statements. A scheme that utilizes spectral smoothness by calculating informed starting points to improve the rate of convergence is introduced. We conduct numerical experiments, using both synthetic and real hyperspectral data, to demonstrate the effectiveness of the reconstruction algorithm and the validity of our method for exploiting spectral smoothness. Evidence from these experiments suggests that the proposed methods have the potential to improve the quality and run times of the future compressed hyperspectral image reconstructions.
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http://dx.doi.org/10.1109/TIP.2014.2376273DOI Listing
January 2015

Inhibition of TRPM8 channels reduces pain in the cold pressor test in humans.

J Pharmacol Exp Ther 2014 11 14;351(2):259-69. Epub 2014 Aug 14.

Pfizer Limited, Neusentis Research Unit, Granta Park, Cambridge, United Kingdom (W.J.W., K.G., S.G., D.S.R.); Genito-Urinary Research Unit (W.J.W., J.C.G., K.C., M.P., P.-P.S., D.S.R.), Research Statistics (K.G., S.C.), Drug Safety, Research and Development (S.R.), Pharmacokinetics, Dynamics and Metabolism (J.R.G., T.M., K.B.), and Worldwide Medicinal Chemistry (M.D.A., P.A.G., M.J.P.), Pfizer Global Research and Development, Sandwich, Kent, United Kingdom; Pfizer Clinical Research Unit, Lenniksebaan, Brussels, Belgium (W.P.); and PharmaTherapeutics Pharmaceutical Sciences, Pfizer Limited, Sandwich, United Kingdom (N.C.).

The transient receptor potential (subfamily M, member 8; TRPM8) is a nonselective cation channel localized in primary sensory neurons, and is a candidate for cold thermosensing, mediation of cold pain, and bladder overactivity. Studies with TRPM8 knockout mice and selective TRPM8 channel blockers demonstrate a lack of cold sensitivity and reduced cold pain in various rodent models. Furthermore, TRPM8 blockers significantly lower body temperature. We have identified a moderately potent (IC50 = 103 nM), selective TRPM8 antagonist, PF-05105679 [(R)-3-[(1-(4-fluorophenyl)ethyl)(quinolin-3-ylcarbonyl)amino]methylbenzoic acid]. It demonstrated activity in vivo in the guinea pig bladder ice water and menthol challenge tests with an IC50 of 200 nM and reduced core body temperature in the rat (at concentrations >1219 nM). PF-05105679 was suitable for acute administration to humans and was evaluated for effects on core body temperature and experimentally induced cold pain, using the cold pressor test. Unbound plasma concentrations greater than the IC50 were achieved with 600- and 900-mg doses. The compound displayed a significant inhibition of pain in the cold pressor test, with efficacy equivalent to oxycodone (20 mg) at 1.5 hours postdose. No effect on core body temperature was observed. An unexpected adverse event (hot feeling) was reported, predominantly periorally, in 23 and 36% of volunteers (600- and 900-mg dose, respectively), which in two volunteers was nontolerable. In conclusion, this study supports a role for TRPM8 in acute cold pain signaling at doses that do not cause hypothermia.
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http://dx.doi.org/10.1124/jpet.114.216010DOI Listing
November 2014

Reconciling embodied and distributional accounts of meaning in language.

Top Cogn Sci 2014 Jul 17;6(3):359-70. Epub 2014 Jun 17.

Division of Psychology, Nottingham Trent University.

Over the past 15 years, there have been two increasingly popular approaches to the study of meaning in cognitive science. One, based on theories of embodied cognition, treats meaning as a simulation of perceptual and motor states. An alternative approach treats meaning as a consequence of the statistical distribution of words across spoken and written language. On the surface, these appear to be opposing scientific paradigms. In this review, we aim to show how recent cross-disciplinary developments have done much to reconcile these two approaches. The foundation to these developments has been the recognition that intralinguistic distributional and sensory-motor data are interdependent. We describe recent work in philosophy, psychology, cognitive neuroscience, and computational modeling that are all based on or consistent with this conclusion. We conclude by considering some possible directions for future research that arise as a consequence of these developments.
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http://dx.doi.org/10.1111/tops.12096DOI Listing
July 2014

New diamino-diheterophenol ligands coordinate iron(III) to make structural and functional models of protocatechuate 3,4-dioxygenase.

Dalton Trans 2014 May;43(18):6610-3

Department of Chemistry, College of the Holy Cross, Worcester, MA 01610, USA.

Three diamino, dihetero-phenol ligands were synthesized by sequential Mannich condensations. These ligands were combined with FeCl3 to produce three five-coordinate Fe(III) complexes that are structural models for the enzyme 3,4-PCD. The three Fe(III) complexes were characterized by elemental analysis, single crystal X-ray diffraction studies, UV-vis spectroscopy, and cyclic voltammetry. Combining the Fe(III) complexes with 3,5-di-t-butylcatechol and O2 resulted in oxidative cleavage similar to the function of 3,4-PCD.
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http://dx.doi.org/10.1039/c3dt53431fDOI Listing
May 2014

Author response: Venous ulcer treatment.

Authors:
Mark Andrews

J Fam Pract 2013 Nov;62(11):623

Winston-Salem, NC, USA.

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November 2013

Clinical Inquiry: What is the best initial treatment for venous stasis ulcers?

J Fam Pract 2013 Aug;62(8):433-4

Department of Family Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA.

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August 2013

The representation of abstract words: what matters? Reply to Paivio's (2013) comment on Kousta et al. (2011).

J Exp Psychol Gen 2013 Feb;142(1):288-291

Cognitive, Perceptual, and Brain Sciences Research Department.

In Kousta, Vigliocco, Vinson, Andrews, and Del Campo (2011), we presented an embodied theory of semantic representation, which crucially included abstract concepts as internally embodied via affective states. Paivio (2013) took issue with our treatment of dual coding theory, our reliance on data from lexical decision, and our theoretical proposal. Here, we address these different issues and clarify how our findings offer a way to move forward in the investigation of how abstract concepts are represented.
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http://dx.doi.org/10.1037/a0028749DOI Listing
February 2013

Prior approval: the growth of Bayesian methods in psychology.

Br J Math Stat Psychol 2013 Feb;66(1):1-7

Within the last few years, Bayesian methods of data analysis in psychology have proliferated. In this paper, we briefly review the history or the Bayesian approach to statistics, and consider the implications that Bayesian methods have for the theory and practice of data analysis in psychology.
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http://dx.doi.org/10.1111/bmsp.12004DOI Listing
February 2013

Peer health education in Haiti's National Penitentiary: the "Health through Walls" experience.

J Correct Health Care 2013 Jan;19(1):65-8

The Bridging Group, Oakland, CA 94611, USA.

This field report describes Health through Wall's experience working in the largest men's prison in Haiti. Though there have been many reports of prison peer health education programs, this field report further describes how peers can increase the (self-reported) interest and uptake of HIV testing. More than 400 anonymous surveys were collected. Preliminary results indicate that the peers had a significant impact on self-reported interest in taking the HIV test.
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http://dx.doi.org/10.1177/1078345812458258DOI Listing
January 2013

Probability distribution for energy of saturated broadband ocean acoustic transmission: results from Gulf of Maine 2006 experiment.

J Acoust Soc Am 2012 Dec;132(6):3659-72

Department of Electrical and Computer Engineering, Northeastern University, 360 Huntington Avenue, Boston, Massachusetts 02115, USA.

The probability distribution of ocean-acoustic broadband signal energy after saturated multipath propagation is derived using coherence theory. The frequency components obtained from Fourier decomposition of a broadband signal are each assumed to be fully saturated with energy spectral density that obey the exponential distribution with 5.6 dB standard deviation and unity scintillation index. When the signal bandwidth and measurement time are larger than the correlation bandwidth and correlation time, respectively, of its energy spectral density components, the broadband signal energy obtained by integrating the energy spectral density across the signal bandwidth then follows the Gamma distribution with a standard deviation smaller than 5.6 dB and a scintillation index less than unity. The theory is verified with broadband transmissions in the Gulf of Maine shallow water waveguide in the 300 to 1200 Hz frequency range. The standard deviations of received broadband signal energies range from 2.7 to 4.6 dB for effective bandwidths up to 42 Hz, while the standard deviations of individual energy spectral density components are roughly 5.6 dB. The energy spectral density correlation bandwidths of the received broadband signals are found to be larger for signals with higher center frequencies and are roughly 10% of each center frequency.
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http://dx.doi.org/10.1121/1.4763547DOI Listing
December 2012

Reducing the complexity of the N-FINDR algorithm for hyperspectral image analysis.

IEEE Trans Image Process 2013 Jul 28;22(7):2835-48. Epub 2012 Sep 28.

Department of Electrical and Computer Engineering, University of Auckland, Auckland 1142, New Zealand.

The N-FINDR algorithm for unmixing hyperspectral data is both popular and successful. However, opportunities for improving the algorithm exist, particularly to reduce its computational expense. Two approaches to achieve this are examined. First, the redundancy inherent in the determinant calculations at the heart of N-FINDR is reduced using an LDU decomposition to form two new algorithms, one based on the original N-FINDR algorithm and one based on the closely related Sequential N-FINDR algorithm. The second approach lowers complexity by reducing the repetition of the volume calculations by removing pixels unlikely to represent pure materials. This is accomplished at no additional cost through the reuse of the volume calculations inherent in the Sequential N-FINDR algorithm. Various thresholding methods for excluding pixels are considered. The impact of these modifications on complexity and the accuracy is examined on simulated and real data showing that the LDU-based approaches save considerable complexity, while pixel reduction methods, with appropriate threshold selection, can produce a favorable complexity-accuracy trade-off.
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http://dx.doi.org/10.1109/TIP.2012.2219546DOI Listing
July 2013