Publications by authors named "Mark Arnold"

253 Publications

Selectivity and Sensitivity of Near-Infrared Spectroscopic Sensing of β-Hydroxybutyrate, Glucose, and Urea in Ternary Aqueous Solutions.

Anal Chem 2021 04 24;93(13):5586-5595. Epub 2021 Mar 24.

Department of Chemistry, University of Iowa, Iowa City, Iowa 52242, United States.

The next-generation artificial pancreas is under development with the goal to enhance tight glycemic control for people with type 1 diabetes. Such technology requires the integration of a chemical sensing unit combined with an insulin infusion device controlled by an algorithm capable of autonomous operation. The potential of near-infrared spectroscopic sensing to serve as the chemical sensing unit is explored by demonstrating the ability to quantify multiple metabolic biomarkers from a single near-infrared spectrum. Independent measurements of β-hydroxy-butyrate, glucose, and urea are presented based on analysis of near-infrared spectra collected over the combination spectral range of 5000-4000 cm for a set of 50 ternary aqueous standard solutions. Spectra are characterized by a 1 μAU root-mean-square (RMS) noise for 100% lines with a resolution of 4 cm and an optical path length of 1 mm. Calibration models created by the net analyte signal (NAS) and the partial least squares (PLS) methods provide selective measurements for each analyte with standard errors of prediction in the upper micromolar concentration range. The NAS method is used to determine both the selectivity and sensitivity for each analyte and their values are consistent with these standard errors of prediction. The NAS method is also used to characterize the background spectral variance associated with instrumental and environmental variations associated with buffer spectra collected over a multiday period.
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http://dx.doi.org/10.1021/acs.analchem.1c00300DOI Listing
April 2021

Crystal Structure-Free Method for Dielectric and Polarizability Characterization of Crystalline Materials at Terahertz Frequencies.

Appl Spectrosc 2021 Mar 8:3702821991594. Epub 2021 Mar 8.

Department of Chemistry and Optical Science and Technology Center, 4083University of Iowa, Iowa City, IA, USA.

Terahertz (THz) time-domain spectroscopy provides a direct and nondestructive method for measuring the dielectric properties of materials directly from the phase delay of coherent electromagnetic radiation propagating through the sample. In cases when crystals are embedded within an inert polymeric pellet, the Landau, Lifshitz, and Looyenga (LLL) effective medium model can be used to extract the intrinsic dielectric constant of the crystalline sample. Subsequently, polarizability can be obtained from the Clausius-Mossotti (CM) relationship. Knowledge of the crystal structure density is required for an analytical solution to the LLL and CM relationships. A novel crystal structure-free graphical method is presented as a way to estimate both dielectric constants and polarizability values for the situation when the crystal structure density is unknown, and the crystals are embedded within a pellet composed of a non-porous polymer. The utility of this crystal structure-free method is demonstrated by analyzing THz time-domain spectra collected for a set of amino acids (L-alanine, L-threonine, and L-glutamine) embedded within pellets composed of polytetrafluoroethylene. Crystal structures are known for each amino acid, thereby enabling a direct comparison of results using the analytical solution and the proposed crystal structure-free graphical method. For each amino acid, the intrinsic dielectric constant is extracted through the LLL effective medium model without using information of their crystal structure densities. THz polarizabilities are then calculated with the CM relationship by using the determined intrinsic dielectric constant for each amino acid coupled with its crystal density as determined graphically. Comparison between the analytical and graphical solutions reveal relative differences between dielectric constants of 3.7, 5.1, and 13.6% for threonine, alanine, and glutamine, respectively, and relative differences between polarizability of 0.6, 0.9, and 5.4%, respectively. These values were determined over the 10-20 cm THz frequency range. The proposed method requires no prior knowledge of crystal structure information.
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http://dx.doi.org/10.1177/0003702821991594DOI Listing
March 2021

Production of bio-xylitol from D-xylose by an engineered Pichia pastoris expressing a recombinant xylose reductase did not require any auxiliary substrate as electron donor.

Microb Cell Fact 2021 Feb 22;20(1):50. Epub 2021 Feb 22.

Center for Biocatalysis & Bioprocessing, University of Iowa, Iowa City, IA, 52241, USA.

Background: Xylitol is a five-carbon sugar alcohol that has numerous beneficial health properties. It has almost the same sweetness as sucrose but has lower energy value compared to the sucrose. Metabolism of xylitol is insulin independent and thus it is an ideal sweetener for diabetics. It is widely used in food products, oral and personal care, and animal nutrition as well. Here we present a two-stage strategy to produce bio-xylitol from D-xylose using a recombinant Pichia pastoris expressing a heterologous xylose reductase gene. The recombinant P. pastoris cells were first generated by a low-cost, standard procedure. The cells were then used as a catalyst to make the bio-xylitol from D-xylose.

Results: Pichia pastoris expressing XYL1 from P. stipitis and gdh from B. subtilis demonstrated that the biotransformation was very efficient with as high as 80% (w/w) conversion within two hours. The whole cells could be re-used for multiple rounds of catalysis without loss of activity. Also, the cells could directly transform D-xylose in a non-detoxified hemicelluloses hydrolysate to xylitol at 70% (w/w) yield.

Conclusions: We demonstrated here that the recombinant P. pastoris expressing xylose reductase could transform D-xylose, either in pure form or in crude hemicelluloses hydrolysate, to bio-xylitol very efficiently. This biocatalytic reaction happened without the external addition of any NAD(P)H, NAD(P), and auxiliary substrate as an electron donor. Our experimental design & findings reported here are not limited to the conversion of D-xylose to xylitol only but can be used with other many oxidoreductase reactions also, such as ketone reductases/alcohol dehydrogenases and amino acid dehydrogenases, which are widely used for the synthesis of high-value chemicals and pharmaceutical intermediates.
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http://dx.doi.org/10.1186/s12934-021-01534-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898734PMC
February 2021

Reusable vs disposable nasopharyngolaryngoscopes: Cost analysis and resident survey.

Laryngoscope Investig Otolaryngol 2021 Feb 10;6(1):88-93. Epub 2020 Dec 10.

SUNY Upstate Medical University Syracuse New York USA.

Objective: Assess the quality of a new disposable nasopharyngolaryngoscope (NPL) through resident feedback at multiple academic institutions and provide a cost analysis of reusable and disposable NPLs at a single academic center.

Study Design: An online survey was distributed to residents at institutions throughout the United States that have implemented use of a disposable NPL (Ambu aScope 4 Rhinolaryngo).

Setting: Cost analysis performed at a single academic center. Resident survey distributed to multiple residency programs throughout the United States.

Subjects And Methods: The survey collected demographic information and asked residents to rate the new disposable NPL and other reusable NPLs using a 5-point Likert scale. A cost analysis was performed of both reusable and disposable NPLs using information obtained at a single academic center.

Results: The survey was distributed to 109 residents throughout the country and 37 were completed for a response rate of 33.9%. The disposable NPL was comparable to reusable NPLs based on ergonomics and maneuverability, inferior in imaging quality ( < .001), and superior in setup ( < .001), convenience ( < .001), and rated better overall ( < .04). The disposable NPL was found to be cheaper per use than reusable NPLs at $171.82 and $170.36 compared to $238.17 and $197.88 per use for the reusable NPL if the life span is 1 year and 5 years respectively.

Conclusion: Disposable NPLs may offer an alternative option and initial feedback obtained from resident physicians is favorable. Cost analysis favors disposable NPLs as the cost-effective option.

Level Of Evidence: NA.
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http://dx.doi.org/10.1002/lio2.500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883614PMC
February 2021

Bayesian Source Attribution of Typhimurium Isolates From Human Patients and Farm Animals in England and Wales.

Front Microbiol 2021 28;12:579888. Epub 2021 Jan 28.

Department of Bacteriology, Animal and Plant Health Agency (APHA), Addlestone, United Kingdom.

The purpose of the study was to apply a Bayesian source attribution model to England and Wales based data on Typhimurium (ST) and monophasic variants (MST), using different subtyping approaches based on sequence data. The data consisted of laboratory confirmed human cases and mainly livestock samples collected from surveillance or monitoring schemes. Three different subtyping methods were used, 7-loci Multi-Locus Sequence Typing (MLST), Core-genome MLST, and Single Nucleotide Polymorphism distance, with the impact of varying the genetic distance over which isolates would be grouped together being varied for the latter two approaches. A Bayesian frequency matching method, known as the modified Hald method, was applied to the data from each of the subtyping approaches. Pigs were found to be the main contributor to human infection for ST/MST, with approximately 60% of human cases attributed to them, followed by other mammals (mostly horses) and cattle. It was found that the use of different clustering methods based on sequence data had minimal impact on the estimates of source attribution. However, there was an impact of genetic distance over which isolates were grouped: grouping isolates which were relatively closely related increased uncertainty but tended to have a better model fit.
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http://dx.doi.org/10.3389/fmicb.2021.579888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876086PMC
January 2021

A comparison of the value of two machine learning predictive models to support bovine tuberculosis disease control in England.

Prev Vet Med 2021 Mar 15;188:105264. Epub 2021 Jan 15.

Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire, AL9 7TA, United Kingdom.

Nearly a decade into Defra's current eradication strategy, bovine tuberculosis (bTB) remains a serious animal health problem in England, with c.30,000 cattle slaughtered annually in the fight against this insidious disease. There is an urgent need to improve our understanding of bTB risk in order to enhance the current disease control policy. Machine learning approaches applied to big datasets offer a potential way to do this. Regularized regression and random forest machine learning methodologies were implemented using 2016 herd-level data to generate the best possible predictive models for a bTB incident in England and its three surveillance risk areas (High-risk area [HRA], Edge area [EA] and Low-risk area [LRA]). Their predictive performance was compared and the best models in each area were used to characterize herds according to risk. While all models provided excellent discrimination, random forest models achieved the highest balanced accuracy (i.e. average of sensitivity and specificity) in England, HRA and LRA, whereas the regularized regression LASSO model did so in the EA. The time since the last confirmed incident was resolved was the only variable in the top-ten ranking in all areas according to both types of models, which highlights the importance of bTB history as a predictor of a new incident. Risk categorisation based on Receiver Operating Characteristic (ROC) analysis was carried out using the best predictive models in each area setting a 99 % threshold value for sensitivity and specificity (97 % in the LRA). Thirteen percent of herds in the whole of England as well as in its HRA, 14 % in its EA and 31 % in its LRA were classified as high-risk. These could be selected for the deployment of additional disease control measures at national or area level. In this way, low-risk herds within the area considered would not be penalised unnecessarily by blanket control measures and limited resources be used more efficiently. The methodology presented in this paper demonstrates a way to accurately identify high-risk farms to inform a targeted disease control and prevention strategy in England that supplements existing population strategies.
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http://dx.doi.org/10.1016/j.prevetmed.2021.105264DOI Listing
March 2021

Wide distribution of prion infectivity in the peripheral tissues of vCJD and sCJD patients.

Acta Neuropathol 2021 03 2;141(3):383-397. Epub 2021 Feb 2.

UMR INRA ENVT 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Vétérinaire de Toulouse, 23 Chemin des Capelles, 31076, Toulouse, France.

Sporadic Creutzfeldt-Jakob disease (sCJD) is the commonest human prion disease, occurring most likely as the consequence of spontaneous formation of abnormal prion protein in the central nervous system (CNS). Variant Creutzfeldt-Jakob disease (vCJD) is an acquired prion disease that was first identified in 1996. In marked contrast to vCJD, previous investigations in sCJD revealed either inconsistent levels or an absence of PrP in peripheral tissues. These findings contributed to the consensus that risks of transmitting sCJD as a consequence of non-CNS invasive clinical procedures were low. In this study, we systematically measured prion infectivity levels in CNS and peripheral tissues collected from vCJD and sCJD patients. Unexpectedly, prion infectivity was detected in a wide variety of peripheral tissues in sCJD cases. Although the sCJD infectivity levels varied unpredictably in the tissues sampled and between patients, these findings could impact on our perception of the possible transmission risks associated with sCJD.
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http://dx.doi.org/10.1007/s00401-021-02270-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882550PMC
March 2021

A Bayesian analysis of a Test and Vaccinate or Remove study to control bovine tuberculosis in badgers (Meles meles).

PLoS One 2021 28;16(1):e0246141. Epub 2021 Jan 28.

Veterinary Epidemiology Unit, Department of Agriculture, Environment and Rural Affairs, Belfast, Northern Ireland.

A novel five year Test and Vaccinate or Remove (TVR) wildlife research intervention project in badgers (Meles meles) commenced in 2014 in a 100km2 area of Northern Ireland. It aimed to increase the evidence base around badgers and bovine TB and help create well-informed and evidence-based strategies to address the issue of cattle-to-cattle spread and spread between cattle and badgers. It involved real-time trap-side testing of captured badgers and vaccinating those that tested negative for bTB (BadgerBCG-BCG Danish 1331) and removal of those that tested bTB positive using the Dual-Path Platform VetTB test (DPP) for cervids (Chembio Diagnostic Systems, Medford, NY USA). Four diagnostic tests were utilised within the study interferon gamma release assay (IGRA), culture (clinical samples and post mortem), DPP using both whole blood and DPP using serum. BCG Sofia (SL222) was used in the final two years because of supply issues with BadgerBCG. Objectives for this study were to evaluate the performance of the DPP in field conditions and whether any trend was apparent in infection prevalence over the study period. A Bayesian latent class model of diagnostic test evaluation in the absence of a gold standard was applied to the data. Temporal variation in the sensitivity of DPP and interferon gamma release assay (IGRA) due to the impact of control measures was investigated using logistic regression and individual variability was assessed. Bayesian latent class analysis estimated DPP with serum to have a sensitivity of 0.58 (95% CrI: 0.40-0.76) and specificity of 0.97 (95% CrI: 0.95-0.98). The DPP with whole blood showed a higher sensitivity (0.69 (95% CrI: 0.48-0.88)) but similar specificity (0.98 (95% Crl: 0.96-0.99)). The change from BCG Danish to BCG Sofia significantly impacted on DPP serum test characteristics. In addition, there was weak evidence of increasing sensitivity of IGRA over time and differences in DPP test sensitivity between adults and cubs. An exponential decline model was an appropriate representation of the infection prevalence over the 5 years, with a starting prevalence of 14% (95% CrI: 0.10-0.20), and an annual reduction of 39.1% (95% CrI: 26.5-50.9). The resulting estimate of infection prevalence in year 5 of the study was 1.9% (95% CrI: 0.8-3.8). These results provide field evidence of a statistically significant reduction in badger TB prevalence supporting a TVR approach to badger intervention. They give confidence in the reliability and reproducibility in the DPP Whole Blood as a real time trap-side diagnostic test for badgers, and describe the effect of vaccination and reduced infection prevalence on test characteristics.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246141PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842978PMC
January 2021

Association of Prolonged-Duration Chemoprophylaxis With Venous Thromboembolism in High-risk Patients With Head and Neck Cancer.

JAMA Otolaryngol Head Neck Surg 2021 Apr;147(4):320-328

Department of Otolaryngology, State University of New York Upstate Medical University, Syracuse.

Importance: Venous thromboembolism (VTE) is associated with substantial morbidity and is the most common factor associated with preventable death among hospitalized patients. Data from otolaryngologic studies suggest that the risk of VTE may be underestimated among high-risk patients, particularly among those undergoing oncologic procedures. The incorporation of prolonged-duration chemoprophylaxis (PDC) into preventive therapy has been associated with substantial decreases in VTE incidence among patients undergoing oncologic surgery. However, bleeding remains a major concern among otolaryngologists, and substantial variation exists in the use of thromboprophylaxis.

Objective: To assess the association between PDC and VTE in high-risk patients with head and neck cancer undergoing oncologic procedures.

Design, Setting, And Participants: This retrospective cohort study identified 750 patients with biopsy-confirmed head and neck cancer and a Caprini risk score of 8 or higher who underwent inpatient oncologic surgery at a tertiary care referral center between January 1, 2014, and February 1, 2020. After exclusions, 247 patients were included in the study; patients were divided into 2 cohorts, traditional and PDC, based on the duration of prophylaxis. Univariate and multivariate analyses were performed to examine the development of VTE and bleeding-associated complications during the 30-day postoperative period. Data were analyzed from April 1 to April 30, 2020.

Exposures: PDC, defined as 7 or more postoperative days of chemoprophylaxis.

Main Outcomes And Measures: VTE and bleeding events during the 30-day postoperative period.

Results: Among 247 patients (mean [SD] age, 63.1 [11.1] years; 180 men [72.9%]) included in the study, 106 patients (42.9%) received traditional prophylaxis, and 141 patients (57.1%) received PDC. The incidence of VTE was 5 of 106 patients (4.7%) in the traditional cohort and 1 of 141 patients (0.7%) in the PDC cohort (odds ratio [OR], 0.15; 95% CI, 0.003-1.33). In the multivariate logistic regression analysis, PDC was independently associated with reductions in the risk of VTE (OR, 0.04; 95% CI, 0.001-0.46). The incidence of bleeding events was 1 of 106 patients (0.9%) in the traditional cohort and 6 of 141 patients (4.3%) in the PDC cohort (OR, 4.64; 95% CI, 0.55-217.00).

Conclusions And Relevance: The use of chemoprophylaxis for high-risk patients with head and neck cancer remains a high-priority topic. The results of this study suggest that PDC may be associated with reductions in VTE among this patient population. However, the associated increase in nonfatal bleeding events warrants careful consideration and further highlights the need to determine an optimal duration for chemoprophylaxis among this distinct cohort.
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http://dx.doi.org/10.1001/jamaoto.2020.5151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809613PMC
April 2021

Teasing out Artificial Intelligence in Medicine: An Ethical Critique of Artificial Intelligence and Machine Learning in Medicine.

J Bioeth Inq 2021 Mar 7;18(1):121-139. Epub 2021 Jan 7.

School of Rural Health (Dubbo/Orange), Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.

The rapid adoption and implementation of artificial intelligence in medicine creates an ontologically distinct situation from prior care models. There are both potential advantages and disadvantages with such technology in advancing the interests of patients, with resultant ontological and epistemic concerns for physicians and patients relating to the instatiation of AI as a dependent, semi- or fully-autonomous agent in the encounter. The concept of libertarian paternalism potentially exercised by AI (and those who control it) has created challenges to conventional assessments of patient and physician autonomy. The unclear legal relationship between AI and its users cannot be settled presently, an progress in AI and its implementation in patient care will necessitate an iterative discourse to preserve humanitarian concerns in future models of care. This paper proposes that physicians should neither uncritically accept nor unreasonably resist developments in AI but must actively engage and contribute to the discourse, since AI will affect their roles and the nature of their work. One's moral imaginative capacity must be engaged in the questions of beneficence, autonomy, and justice of AI and whether its integration in healthcare has the potential to augment or interfere with the ends of medical practice.
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http://dx.doi.org/10.1007/s11673-020-10080-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790358PMC
March 2021

Impact of clinical practice guidelines: trends in antibiotic prescriptions for acute rhinosinusitis.

Int Forum Allergy Rhinol 2020 Dec 4. Epub 2020 Dec 4.

Department of Otolaryngology and Communication Sciences, SUNY Upstate Medical University, Syracuse, NY.

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http://dx.doi.org/10.1002/alr.22750DOI Listing
December 2020

Using stochastic dynamic modelling to estimate the sensitivity of current and alternative surveillance program of Salmonella in conventional broiler production.

Sci Rep 2020 11 10;10(1):19441. Epub 2020 Nov 10.

Division for Global Surveillance, Research Group for Genomic Epidemiology, National Food Institute, Technical University of Denmark, Kongens Lyngby, Denmark.

Since 2018, the EU commission has declared the Danish broiler industry to be Salmonella free. However, there is continuous Salmonella pressure from the environment, and a number of parent flocks and broiler flocks become infected annually. When a parent flock becomes infected, the infection can be transmitted vertically to the broiler flocks, before the parent flock is detected and destroyed, including the eggs at the hatchery. To address this issue, we developed stochastic dynamic modelling of transmission of Salmonella in parent flocks and combined that with the relation between flock prevalence and test sensitivity for environmental samples in the flock. Results suggested that after 10 and 100 infected hens were seeded, the likelihood of detecting an infected parent flock within the three first weeks after the infection was strongly influenced by the taking of five boot swabs (95% CI 70-100) instead of two (95% CI 40-100) or the supplementing of the two boot swabs by a dust sample (95% CI 43-100). Results suggest that the likelihood of detecting the broiler flock as infected in the program was estimated to at least 99% in broiler flock even if only one chicken was initially infected. These findings are of relevance for managing parent flocks and eggs at the hatchery in case of Salmonella infection in parent flocks in the Danish poultry.
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http://dx.doi.org/10.1038/s41598-020-76514-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655952PMC
November 2020

Understanding the ethical implications of the rituals of medicine.

Intern Med J 2020 09;50(9):1123-1131

Sydney Health Ethics, School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.

Rituals may be understood broadly as stereotyped behaviours carrying symbolic meanings, which play a crucial role in defining relationships, legitimating authority, giving meaning to certain life events and stabilising social structures. Despite intense interest in the subject, and an extensive literature, relatively little attention has been given to the nature, role and function of ritual in contemporary medicine. Medicine is replete with ritualistic behaviours and imperatives, which play a crucial role in all aspects of clinical practice. Rituals play multiple, complex functions in clinical interactions and have an important role in shaping interactions, experiences and outcomes. Longstanding medical rituals have been disrupted in the wake of coronavirus disease 2019 (COVID-19). Medical rituals may be evident or invisible, often overlap with or operate alongside instrumentalised practices, and play crucial roles in establishing, maintaining and guaranteeing the efficacy of clinical practices. Rituals can also inhibit progress and change, by enforcing arbitrary authority. Physicians should consider when they are undertaking a ritual practice and recognise when the exigencies of contemporary practice are affecting that ritual with or without meaning or intention. Physicians should reflect on whether aspects of their ritual interactions are undertaken on the basis of sentiment, custom or evidence-based outcomes, and whether rituals should be defended, continued in a modified fashion or even abandoned in favour of new behaviours suitable for and salient with contemporary practice in the interests of patient care.
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http://dx.doi.org/10.1111/imj.14990DOI Listing
September 2020

Accelerating the De-Personalization of Medicine: The Ethical Toxicities of COVID-19.

J Bioeth Inq 2020 Dec 25;17(4):815-821. Epub 2020 Aug 25.

Sydney Health Ethics, Faculty of Medicine and Health, Haematology Department, Royal North Shore Hospital, University of Sydney, Sydney, NSW, Australia.

The COVID-19 pandemic has, of necessity, demanded the rapid incorporation of virtual technologies which, suddenly, have superseded the physical medical encounter. These imperatives have been implemented in advance of evaluation, with unclear risks to patient care and the nature of medical practice that might be justifiable in the context of a pandemic but cannot be extrapolated as a new standard of care. Models of care fit for purpose in a pandemic should not be generalized to reconfigure medical care as virtual by default, and personal by exception at the conclusion of the emergency.
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http://dx.doi.org/10.1007/s11673-020-10026-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445805PMC
December 2020

Update on evidence in craniomaxillofacial surgery.

Curr Opin Otolaryngol Head Neck Surg 2020 Aug;28(4):241-245

Department of Otolaryngology at SUNY Upstate Medical University, Syracuse, New York, USA.

Purpose Of Review: Evidence-based medicine underpins clinical practice. Ideally, our clinical decision-making stems from systematic reviews of randomized controlled trials. However, in practice, this is not often the case, and we must instead rely on the best available evidence.

Recent Findings: We review the history of evidence-based research, the development of the levels of evidence, and the relationship of evidence and bias present in craniomaxillofacial surgery. We also discuss the recent trends in CMF publications and identify areas for improvement.

Summary: Because of inherent challenges, the quality of evidence in craniomaxillofacial surgery lags behind other surgical and medical specialties. However, over recent years this has improved significantly, with better reporting of data and a higher rate of randomized controlled trials.
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http://dx.doi.org/10.1097/MOO.0000000000000642DOI Listing
August 2020

Identifying cohort differences in children undergoing partial intracapsular tonsillectomy vs traditional tonsillectomy for sleep disordered breathing.

Int J Pediatr Otorhinolaryngol 2020 Oct 20;137:110183. Epub 2020 Jun 20.

SUNY Upstate Medical University, Department of Otolaryngology, USA. Electronic address:

Objective: Partial intracapsular tonsillectomy (PIT) is a well-established technique for reducing post-operative morbidity in pediatric patients with sleep disordered breathing (SDB). Although tonsillar re-growth rates are reported as low, risks of symptom recurrence or need for completion tonsillectomy are clear disadvantages when compared to traditional tonsillectomy (TT). We aim to identify cohort differences to better guide clinical decision making and identify patient-specific factors that may influence this decision. A secondary aim was to evaluate potential risk factors for tonsillar regrowth.

Methods: Retrospective chart review of pediatric patients who underwent TT or PIT for SDB between 2015 and 2019 at a tertiary care academic medical center. Records were reviewed for age, gender, race, body mass index, comorbidities, diagnosis, apnea-hypopnea index, pre-operative Brodsky tonsil size, length of stay, post-operative hemorrhage, tonsillar regrowth, symptom recurrence, and need for completion tonsillectomy.

Results: 315 patients were included: 174 underwent TT and 141 underwent PIT. Patients undergoing TT were more likely to have a sleep study showing OSA (OR 3.01, p < 0.0001), asthma (OR 4.28, p = 0.000124), and other comorbidities (OR 4.06, p = 0.0258). The overall complication rate was 4.44% (14/315). Tonsillar regrowth was exclusive to the PIT group, occurring in 7/141 patients (4.96%). Age ≤4 years was significantly associated with increased risk of tonsillar regrowth (≤4 years: 7.69%, >4 years: 0%; p = 0.049). Race and pre-operative tonsil size were not associated with regrowth.

Conclusions: Our study supports the low incidence of tonsillar regrowth in PIT and suggests an association with younger age. Moreover, we found that patients undergoing TT are more likely to be older, have OSA, asthma, and other comorbidities.
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http://dx.doi.org/10.1016/j.ijporl.2020.110183DOI Listing
October 2020

An Exploration of Knowledge and Attitudes of Medical Students and Rheumatologists to Placebo and Nocebo Effects: Threshold Concepts in Clinical Practice.

J Med Educ Curric Dev 2020 Jan-Dec;7:2382120520930764. Epub 2020 Jun 22.

Sydney Health Ethics, Faculty of Medicine and Health, University of Sydney, and Department of Haematology, Royal North Shore Hospital, NSW, Australia.

Introduction: Understanding placebo and nocebo responses (context/meaning effects [CMEs]) is fundamental to physician agency. Specific instruction in CMEs is often lacking in medical education. Patient-practitioner interactions may challenge medical students' understanding of biomedical causality and the nexus between this, practical ethics and professionalism across various conceptual and applied aspects of CMEs. This study compared the corpus of knowledge and phronesis related to CMEs between Australian graduate medical students and rheumatologists to gain a sophisticated understanding of this relationship to inform curriculum development.

Method: In 2013 and 2014, the authors surveyed third-year medical students undertaking a graduate programme in an Australian medical school and Australian rheumatologists to ascertain their understanding of placebo and nocebo responses. The survey ascertained (1) the alignment of the respondents' understanding of CMEs with accepted facts and concepts; (2) opinions on the ethical status of CMEs; and (3) responses to 2 scenarios designed to explore matters of biomedical causality, practical ethics and professionalism.

Results: There were 88 completed surveys returned, 53 rheumatologists and 35 students. Similar proportions within each group identified CMEs, with most (n = 79/88 [89.8%]) correctly recognising a placebo (rheumatologists: 50 [94.3%], students: 29 [82.9%]) and approximately three-quarters (n = 65/88 [73.9%]) correctly recognising nocebo effects (rheumatologists: 39 [73.6%], students: 26 [74.3%]). Statistically significant differences between practitioners and students were observed in relation to the following: placebo responders and placebo responsiveness; placebos as a 'diagnostic tool'; placebos usage in clinical practice and research, and nocebo effects.

Conclusions: Physicians require an awareness of CMEs and the fact that they arise from and influence the effective agency of health care professionals. Curricular emphasis is needed to permit an honest assessment of the components that influence when, how and why patient outcomes arise, and how one's agency might have neutral or negative effects but could be inclined towards positive and away from negative patient outcomes.
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http://dx.doi.org/10.1177/2382120520930764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309386PMC
June 2020

Redesigning a Department of Surgery during the COVID-19 Pandemic.

J Gastrointest Surg 2020 08 28;24(8):1852-1859. Epub 2020 Apr 28.

Department of Surgery, Divisions of General and Gastrointestinal Surgery and Surgical Oncology, The Ohio State University, Columbus, OH, USA.

Background: COVID-19 has created an urgent need for reorganization and surge planning among departments of surgery across the USA.

Methods: Review of the COVID-19 planning process and work products in preparation for a patient surge. Organizational and process changes, workflow redesign, and communication plans are presented.

Results: The planning process included widespread collaboration among leadership from many disciplines. The department of surgery played a leading role in establishing clinical protocols, guidelines, and policies in preparation for a surge of COVID-19 patients. A multidisciplinary approach with input from clinical and nonclinical stakeholders is critical to successful crisis planning. A clear communication plan should be implemented early and input from trainees, staff, and faculty should be solicited.

Conclusion: Major departmental and health system reorganization is required to adapt academic surgical practices to a widespread crisis. Surgical leadership, innovation, and flexibility are critical to successful planning and implementation.
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http://dx.doi.org/10.1007/s11605-020-04608-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187802PMC
August 2020

Comparing Kadish and Modified Dulguerov Staging Systems for Olfactory Neuroblastoma: An Individual Participant Data Meta-analysis.

Otolaryngol Head Neck Surg 2020 09 14;163(3):418-427. Epub 2020 Apr 14.

SUNY Upstate Medical University, Syracuse, New York, USA.

Objective: To compare the Kadish and the modified Dulguerov staging of individual participants to determine the impact of stage and other prognostic factors on disease-free (DFS) and overall survival (OS).

Data Sources: Systematic review of EMBASE, MEDLINE, Cochrane Library, and CINAHL databases.

Review Methods: The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) was followed for this study. Articles including patients with olfactory neuroblastoma (ONB) staged with both Kadish and Dulguerov staging systems were reviewed. The raw data from eligible studies were requested to perform an individual participant data (IPD) meta-analysis.

Results: Pooled data from 21 studies representing 399 patients with ONB undergoing treatment with curative intent showed that increasing age, treatment with chemotherapy, and positive or unreported margin status portended worse DFS ( < .05). Increasing stage for both Kadish and Dulguerov staging systems was prognostic for worse DFS and OS ( < .05), with Kadish C representing a heterogeneous group with regard to outcome and corresponding Dulguerov T stage. Using the Akaike information criterion, the Dulguerov staging system had superior performance to the Kadish system for DFS (1088.72 vs 1092.54) and OS (632.71 vs 644.23).

Conclusion: This study represents the first IPD meta-analysis of ONB directly comparing the outcomes of Kadish and Dulguerov staging systems in patients treated with primary surgery. Both systems correlated with DFS and OS, with superior performance in the Dulguerov system. Furthermore, the Kadish C group represented a heterogeneous group with regard to outcomes after stratification by the Dulguerov system. Dulguerov T4 patients had the worst outcome, with most being approached with open resection.
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http://dx.doi.org/10.1177/0194599820915487DOI Listing
September 2020

Phase I Trial of Trametinib with Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer.

Clin Cancer Res 2020 07 6;26(13):3117-3125. Epub 2020 Apr 6.

Moffitt Cancer Center, Tampa, Florida.

Purpose: The RAS/RAF/MEK/ERK signaling pathway is critical to the development of colorectal cancers, and , , and mutations foster resistance to radiation. We performed a phase I trial to determine the safety of trametinib, a potent MEK1/2 inhibitor, with 5-fluorouracil (5-FU) chemoradiation therapy (CRT) in patients with locally advanced rectal cancer (LARC).

Patients And Methods: Patients with stage II/III rectal cancer were enrolled on a phase I study with 3+3 study design, with an expansion cohort of 9 patients at the MTD. Following a 5-day trametinib lead-in, with pre- and posttreatment tumor biopsies, patients received trametinib and CRT, surgery, and adjuvant chemotherapy. Trametinib was given orally daily at 3 dose levels: 0.5 mg, 1 mg, and 2 mg. CRT consisted of infusional 5-FU 225 mg/m/day and radiation dose of 28 daily fractions of 1.8 Gy (total 50.4 Gy). The primary endpoint was to identify the MTD and recommended phase II dose. IHC staining for phosphorylated ERK (pERK) and genomic profiling was performed on the tumor samples.

Results: Patients were enrolled to all dose levels, and 18 patients were evaluable for toxicities and responses. Treatment was well tolerated, and there was one dose-limiting toxicity of diarrhea, which was attributed to CRT rather than trametinib. At the 2 mg dose level, 25% had pathologic complete response. IHC staining confirmed dose-dependent decrease in pERK with increasing trametinib doses.

Conclusions: The combination of trametinib with 5-FU CRT is safe and well tolerated, and may warrant additional study in a phase II trial, perhaps in a -mutant selected population.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-4193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334091PMC
July 2020

By Various Ways We Arrive at the Same End.

Am J Bioeth 2020 03;20(3):81-83

University of Sydney.

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http://dx.doi.org/10.1080/15265161.2020.1714799DOI Listing
March 2020

The management of diverticulitis: a review of the guidelines.

Authors:
Mark H Arnold

Med J Aust 2020 05 1;212(9):434-434.e1. Epub 2020 Mar 1.

School of Rural Health, University of Sydney, Dubbo, NSW.

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http://dx.doi.org/10.5694/mja2.50526DOI Listing
May 2020

Between roost contact is essential for maintenance of European bat lyssavirus type-2 in Myotis daubentonii bat reservoir: 'The Swarming Hypothesis'.

Sci Rep 2020 02 3;10(1):1740. Epub 2020 Feb 3.

Animal and Plant Health Agency (Weybridge), Surrey, KT15 3NB, United Kingdom.

Many high-consequence human and animal pathogens persist in wildlife reservoirs. An understanding of the dynamics of these pathogens in their reservoir hosts is crucial to inform the risk of spill-over events, yet our understanding of these dynamics is frequently insufficient. Viral persistence in a wild bat population was investigated by combining empirical data and in-silico analyses to test hypotheses on mechanisms for viral persistence. A fatal zoonotic virus, European Bat lyssavirus type 2 (EBLV-2), in Daubenton's bats (Myotis daubentonii) was used as a model system. A total of 1839 M. daubentonii were sampled for evidence of virus exposure and excretion during a prospective nine year serial cross-sectional survey. Multivariable statistical models demonstrated age-related differences in seroprevalence, with significant variation in seropositivity over time and among roosts. An Approximate Bayesian Computation approach was used to model the infection dynamics incorporating the known host ecology. The results demonstrate that EBLV-2 is endemic in the study population, and suggest that mixing between roosts during seasonal swarming events is necessary to maintain EBLV-2 in the population. These findings contribute to understanding how bat viruses can persist despite low prevalence of infection, and why infection is constrained to certain bat species in multispecies roosts and ecosystems.
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http://dx.doi.org/10.1038/s41598-020-58521-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997190PMC
February 2020

Using species distribution models to predict potential hot-spots for Rift Valley Fever establishment in the United Kingdom.

PLoS One 2019 23;14(12):e0225250. Epub 2019 Dec 23.

Animal and Plant Health Agency, New Haw, Surrey, United Kingdom.

Vector borne diseases are a continuing global threat to both human and animal health. The ability of vectors such as mosquitos to cover large distances and cross country borders undetected provide an ever-present threat of pathogen spread. Many diseases can infect multiple vector species, such that even if the climate is not hospitable for an invasive species, indigenous species may be susceptible and capable of transmission such that one incursion event could lead to disease establishment in these species. Here we present a consensus modelling methodology to estimate the habitat suitability for presence of mosquito species in the UK deemed competent for Rift Valley fever virus (RVF) and demonstrate its application in an assessment of the relative risk of establishment of RVF virus in the UK livestock population. The consensus model utilises observed UK mosquito surveillance data, along with climatic and geographic prediction variables, to inform six independent species distribution models; the results of which are combined to produce a single prediction map. As a livestock host is needed to transmit RVF, we then combine the consensus model output with existing maps of sheep and cattle density to predict the areas of the UK where disease is most likely to establish in local mosquito populations. The model results suggest areas of high suitability for RVF competent mosquito species across the length and breadth of the UK. Notable areas of high suitability were the South West of England and coastal areas of Wales, the latter of which was subsequently predicted to be at higher risk for establishment of RVF due to higher livestock densities. This study demonstrates the applicability of outputs of species distribution models to help predict hot-spots for risk of disease establishment. While there is still uncertainty associated with the outputs we believe that the predictions are an improvement on just using the raw presence points from a database alone. The outputs can also be used as part of a multidisciplinary approach to inform risk based disease surveillance activities.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225250PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927579PMC
March 2020

Decision tree machine learning applied to bovine tuberculosis risk factors to aid disease control decision making.

Prev Vet Med 2020 Feb 30;175:104860. Epub 2019 Nov 30.

Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Hertfordshire, AL9 7TA, United Kingdom.

Identifying and understanding the risk factors for endemic bovine tuberculosis (TB) in cattle herds is critical for the control of this disease. Exploratory machine learning techniques can uncover complex non-linear relationships and interactions within disease causation webs, and enhance our knowledge of TB risk factors and how they are interrelated. Classification tree analysis was used to reveal associations between predictors of TB in England and each of the three surveillance risk areas (High Risk, Edge, and Low Risk) in 2016, identifying the highest risk herds. The main classifying predictor for farms in England overall related to the TB prevalence in the 100 nearest cattle herds. In the High Risk and Edge areas it was the number of slaughterhouse destinations and in the Low Risk area it was the number of cattle tested in surveillance tests. How long ago the last confirmed incident was resolved was the most frequent classifier in trees; if within two years, leading to the highest risk group of herds in the High Risk and Low Risk areas. At least two different slaughterhouse destinations led to the highest risk group of herds in England, whereas in the Edge area it was a combination of no contiguous low-risk neighbours (i.e. in a 1 km radius) and a minimum proportion of 6-23 month-old cattle in November. A threshold value of prevalence in 100 nearest neighbours increased the risk in all areas, although the value was specific to each area. Having low-risk contiguous neighbours reduced the risk in the Edge and High Risk areas, whereas high-risk ones increased the risk in England overall and in the Edge area specifically. The best classification tree models informed multivariable binomial logistic regression models in each area, adding statistical inference outputs. These two approaches showed similar predictive performance although there were some disparities regarding what constituted high-risk predictors. Decision tree machine learning approaches can identify risk factors from webs of causation: information which may then be used to inform decision making for disease control purposes.
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http://dx.doi.org/10.1016/j.prevetmed.2019.104860DOI Listing
February 2020

The 'autoimmune screen': More informed but no more enlightened.

Authors:
Mark H Arnold

Aust J Gen Pract 2019 10;48(10):732-734

MBBS, FRACP, MBioethics, GAICD, Associate Dean and Head, School of Rural Health, University of Sydney, NSW; Honorary Associate and PhD student, Sydney Health Ethics, School of Rural Health, Sydney Medical School, University of Sydney, NSW.

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http://dx.doi.org/10.31128/AJGP-03-19-4885DOI Listing
October 2019

Perspectives on the draft ICH-M10 guidance: an interview with Mark Arnold.

Authors:
Mark E Arnold

Bioanalysis 2019 Aug;11(15):1379-1382

Covance, Inc., Princeton, NJ 08540, USA.

Biography Mark E Arnold, PhD, is Director of Science for Covance Laboratories. In that role, he develops the bioanalytical strategy for immune-, cell-based, quantitative polymerase chain reaction (qPCR) and LC-MS/MS assays to quantify drugs and metabolites, antidrug antibodies and biomarkers in animal and clinical samples for pharmacokinetic and pharmacodynamic assessments. Mark was previously Executive Director of Bioanalytical Sciences at Bristol-Myers Squibb. He received a BS (biology) from Indiana University of Pennsylvania and PhD (pharmacology) from the University of Pittsburgh. For more than 30 years, Mark has been involved in the evolving field of bioanalysis, including the science and the review and interpretation of regulations and guidance. He co-chaired the AAPS Crystal City V and VI Workshops on the US 'FDA Draft Revised Guidance on Bioanalytical Method Validation' and 'Biomarkers'. He is actively involved in the Land O'Lakes Bioanalytical Conference and American Association of Pharmaceutical Scientists (AAPS, named Fellow in 2014). Mark has over 100 peer-reviewed publications, and numerous invited podium presentations. This interview was conducted by Sankeetha Nadarajah, Managing Commissioning Editor of .
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http://dx.doi.org/10.4155/bio-2019-0177DOI Listing
August 2019

Characterizing Bone Mineral Density Using Lumbar Spine Computed Tomography Attenuation in Patients With Distal Radius Fractures.

Geriatr Orthop Surg Rehabil 2019 17;10:2151459319847408. Epub 2019 May 17.

Department of Neurosurgery, Regions Hospital, St. Paul, MN, USA.

Introduction: This study examines how many patients with distal radius fracture (DRF) eligible for bone health evaluation could potentially be screened using bone mineral density (BMD) estimation by L1 vertebra computed tomography (CT) attenuation obtained for other purposes.

Materials And Methods: For all adult patients with DRF who presented over a 5-year period, we recorded the age, sex, dual-energy X-ray absorptiometry (DXA) results up to 3 years prior to injury or 1 year post-injury, and L1 CT attenuation on any CT including L1 that had been performed within 6 months of their fracture. We compared the availability of L1 CT attenuation measurement to the rate of DXA scan use. We calculated the percentage of patients with osteoporosis and compared attenuation results to DXA results in those patients where both tests were available.

Results: Of 1853 patients with DRF, an L1 CT had been obtained in 195 patients. Of the 685 patients who met criteria for osteoporosis screening, 253 (37%) patients had undergone only DXA screening, 68 (10%) patients had an L1 CT only, and 18 (2%) patients had both tests. Of the 86 patients who met criteria for osteoporosis screening and had an adequate CT, 67 (78%) demonstrated L1 attenuation <135 HU, and 79 (92%) had CT attenuation <160 HU.

Discussion: Our study found that 10% of patients with a distal radius fracture who met the criteria for osteoporosis screening had a CT scan that could be used to estimate bone density and that the majority of those patients met criteria for osteoporosis based on CT attenuation.

Conclusions: Utilization of opportunistic BMD screening with L1 CT attenuation offers the potential to increase osteoporosis screening from 40% to 50% of eligible patients and make the diagnosis of osteoporosis in an additional 8% of patients with DRF at no additional cost.
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http://dx.doi.org/10.1177/2151459319847408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540492PMC
May 2019