Publications by authors named "Jonathan King"

350 Publications

Characterizing Continuous Manipulation Families for Dexterous Soft Robot Hands.

Front Robot AI 2021 13;8:645290. Epub 2021 Apr 13.

Foam Robotics Lab, The Robotics Institute, Carnegie Mellon University, Pittsburgh, PA, United States.

There has been an explosion of ideas in soft robotics over the past decade, resulting in unprecedented opportunities for end effector design. Soft robot hands offer benefits of low-cost, compliance, and customized design, with the promise of dexterity and robustness. The space of opportunities is vast and exciting. However, new tools are needed to understand the capabilities of such manipulators and to facilitate manipulation planning with soft manipulators that exhibit free-form deformations. To address this challenge, we introduce a sampling based approach to discover and model continuous families of manipulations for soft robot hands. We give an overview of the soft foam robots in production in our lab and describe novel algorithms developed to characterize manipulation families for such robots. Our approach consists of sampling a space of manipulation actions, constructing Gaussian Mixture Model representations covering successful regions, and refining the results to create continuous successful regions representing the manipulation family. The space of manipulation actions is very high dimensional; we consider models with and without dimensionality reduction and provide a rigorous approach to compare models across different dimensions by comparing coverage of an unbiased test dataset in the full dimensional parameter space. Results show that some dimensionality reduction is typically useful in populating the models, but without our technique, the amount of dimensionality reduction to use is difficult to predict ahead of time and can depend on the hand and task. The models we produce can be used to plan and carry out successful, robust manipulation actions and to compare competing robot hand designs.
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http://dx.doi.org/10.3389/frobt.2021.645290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077230PMC
April 2021

Determination of the route of excretion of robenacoxib (Onsior™) in cats and dogs: A pilot study.

J Vet Pharmacol Ther 2021 Apr 21. Epub 2021 Apr 21.

Elanco Animal Health Inc., Basel, Switzerland.

The objective of the studies was to determine the route of excretion, faecal or urinary, of the nonsteroidal anti-inflammatory drug (NSAID) robenacoxib (Onsior™) in cats and dogs. The studies employed a two-part crossover design in 4 beagle dogs (2 female and 2 male, age 36-41 months and body weight 9.0-10.3 kg) and a parallel group comparison of two groups each of 3 domestic short-hair cats (2 female and 4 castrated male, age 35-73 months and body weight 3.0-5.7 kg). Animals were administered single doses of 1 (dog) or 2 (cat) mg/kg of [ C]-robenacoxib by intravenous (IV) and oral routes. Venous blood samples were taken and analysed for robenacoxib concentration. Faeces and urine were collected for 4 (cats) or 7 (dogs) days and analysed for radioactivity. Robenacoxib was eliminated rapidly from blood (≤ 8 hr). In dogs, expressed as the percentage of the administered dose and adjusted so that faecal plus urine recovery was 100%, the mean (SD) excretion in faeces and urine was, respectively, 64.6% (4.30) and 35.4% (4.3) after IV and 66.7% (6.9) and 33.3% (6.9) after oral administration. The respective values in cats, in faeces and urine, were 72.5% (4.6) and 27.5% (4.6) after IV and 78.5% (2.6) and 21.5% (2.6) after oral administration. In conclusion, excretion of systemically available robenacoxib in cats and dogs was mixed via both faeces and urine, but predominately faecal (~64.6% in dogs and ~72.5% in cats) and assumed to be via biliary excretion.
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http://dx.doi.org/10.1111/jvp.12973DOI Listing
April 2021

Evaluation of Promega PowerSeq™ Auto/Y systems prototype on an admixed sample of Rio de Janeiro, Brazil: Population data, sensitivity, stutter and mixture studies.

Forensic Sci Int Genet 2021 Apr 6;53:102516. Epub 2021 Apr 6.

Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address:

Forensic DNA typing typically relies on the length-based (LB) separation of PCR products containing short tandem repeat loci (STRs). Massively parallel sequencing (MPS) elucidates an additional level of STR motif and flanking region variation. Also, MPS enables simultaneous analysis of different marker-types - autosomal STRs, SNPs for lineage and identification purposes, reducing both the amount of sample used and the turn-around-time of analysis. Therefore, MPS methodologies are being considered as an additional tool in forensic genetic casework. The PowerSeq™ Auto/Y System (Promega Corp), a multiplex forensic kit for MPS, enables analysis of the 22 autosomal STR markers (plus Amelogenin) from the PowerPlex® Fusion 6C kit and 23 Y-STR markers from the PowerPlex® Y23 kit. Population data were generated from 140 individuals from an admixed sample from Rio de Janeiro, Brazil. All samples were processed according to the manufacturers' recommended protocols. Raw data (FastQ) were generated for each indexed sample and analyzed using STRait Razor v2s and PowerSeqv2.config file. The subsequent population data showed the largest increase in expected heterozygosity (23%), from LB to sequence-based (SB) analyses at the D5S818 locus. Unreported allele was found at the D21S11 locus. The random match probability across all loci decreased from 5.9 × 10 to 7.6 × 10. Sensitivity studies using 1, 0.25, 0.062 and 0.016 ng of DNA input were analyzed in triplicate. Full Y-STR profiles were detected in all samples, and no autosomal allele drop-out was observed with 62 pg of input DNA. For mixture studies, 1 ng of genomic DNA from a male and female sample at 1:1, 1:4, 1:9, 1:19 and 1:49 proportions were analyzed in triplicate. Clearly resolvable alleles (i.e., no stacking or shared alleles) were obtained at a 1:19 male to female contributor ratio. The minus one stutter (-1) increased with the longest uninterrupted stretch (LUS) allele size reads and according to simple or compound/complex repeats. The haplotype-specific stutter rates add more information for mixed samples interpretation. These data support the use of the PowerSeq Auto/Y systems prototype kit (22 autosomal STR loci, 23 Y-STR loci and Amelogenin) for forensic genetics applications.
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http://dx.doi.org/10.1016/j.fsigen.2021.102516DOI Listing
April 2021

Robenacoxib shows efficacy for the treatment of chronic degenerative joint disease-associated pain in cats: a randomized and blinded pilot clinical trial.

Sci Rep 2021 Apr 8;11(1):7721. Epub 2021 Apr 8.

Translational Research in Pain (TRiP) Program, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.

The main objective of this pilot clinical trial was to evaluate outcome measures for the assessment of the nonsteroidal anti-inflammatory drug (NSAID) robenacoxib in cats with degenerative joint disease-associated pain (DJD-pain). Otherwise healthy cats (n = 109) with DJD-pain entered a parallel group, randomized, blinded clinical trial. Cats received placebo (P) or robenacoxib (R) for two consecutive 3-week periods. Treatment groups were PP, RR, and RP. Actimetry and owner-assessment data were collected. Data were analyzed using mixed-effects and generalized mixed-effects linear models. Activity data showed high within-cat and between-cat variability, and 82.4% of the values were zero. Compared to placebo, mean total activity was higher (5.7%) in robenacoxib-treated cats (p = 0.24); for the 80th percentile of activity, more robenacoxib-treated cats had a > 10% increase in activity after 3 (p = 0.046) and 6 weeks (p = 0.026). Robenacoxib treatment significantly decreased owner-assessed disability, (p = 0.01; 49% reduction in disability; effect size ~ 0.3), and improved temperament (p = 0.0039) and happiness (p = 0.021) after 6 weeks. More robenacoxib-treated cats were successes at 6 weeks (p = 0.018; NNT: 3.8). Adverse effect frequencies were similar across groups. Results identified suitable endpoints for confirmatory studies, while also indicating efficacy of robenacoxib in cats with DJD-pain.
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http://dx.doi.org/10.1038/s41598-021-87023-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032665PMC
April 2021

Hydro-epidemiological modelling of bacterial transport and decay in nearshore coastal waters.

Water Res 2021 May 15;196:117049. Epub 2021 Mar 15.

Hydro-environmental Research Centre (HRC), School of Engineering, Cardiff University, Cardiff CF24 3AA, UK.

In recent years, society has become more aware and concerned with the environmental and human health impacts of population growth and urbanisation. In response, a number of legislative measures have been introduced within Europe (and globally), which have sparked much cross-disciplinary research aimed at predicting and quantifying these impacts, and suggesting mitigation measures. In response to such measures this paper is focused on improving current understanding of, and simulating water quality, in the form of bacterial transport and decay, in the aquatic environment and particularly in macro-tidal environments. A number of 2D and 3D hydro-epidemiological models were developed using the TELEMAC suite to predict faecal bacterial levels for a data rich pilot site, namely Swansea Bay, located in the south west of the UK, where more than 7,000 FIO samples were taken and analysed over a two year period. A comparison of 2D and 3D modelling approaches highlights the importance of accurately representing source momentum terms in hydro-epidemiological models. Improvements in 2D model bacterial concentration predictions were achieved by the application of a novel method for representing beach sources within the nearshore zone of a macro-tidal environment. In addition, the use of a depth-varying decay rate was found to enhance the prediction of Faecal Indicator Organism concentrations in 3D models. Recommendations are made for the use of these novel approaches in future modelling studies.
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http://dx.doi.org/10.1016/j.watres.2021.117049DOI Listing
May 2021

Autosomal STR and SNP characterization of populations from the Northeastern Peruvian Andes with the ForenSeq™ DNA Signature Prep Kit.

Forensic Sci Int Genet 2021 May 23;52:102487. Epub 2021 Feb 23.

Department of Forensic Medicine, University of Helsinki, PO Box 40, FI-00014 Helsinki, Finland; Forensic Medicine Unit, Finnish Institute for Health and Welfare, PO Box 30, FI-00271 Helsinki, Finland. Electronic address:

Autosomal DNA data from Peru for human identity testing purposes are scarce in the scientific literature, which hinders obtaining an appropriate portrait of the genetic variation of the resident populations. In this study we genetically characterize five populations from the Northeastern Peruvian Andes (Chachapoyas, Awajún, Wampís, Huancas and Cajamarca). Autosomal short tandem repeat (aSTR) and identity informative single nucleotide polymorphism (iiSNP) data from a total of 233 unrelated individuals are provided, and forensic genetic parameters are calculated for each population and for the combined set Northeastern Peruvian Andes. After correction for multiple testing in the whole dataset of the Northeastern Peruvian Andes, the only departure from Hardy-Weinberg equilibrium was observed in locus rs2111980. Twenty one out of 27 aSTR loci exhibited an increased number of alleles due to sequence variation in the repeat motif and flanking regions. For iiSNPs 33% of the loci displayed flanking region variation. The combined random match probability (RMP), assuming independence of all loci (aSTRs and iiSNPs), in the Chachapoyas, the population with the largest samples size (N = 172), was 8.14 × 10 for length-based data while for sequence-based was 4.15 × 10. In the merged dataset (Northeastern Peruvian Andes; N = 233), the combined RMP when including all markers were 2.96 × 10 (length-based) and 3.21 × 10 (sequence-based). These new data help to fill up some of the gaps in the genetic canvas of South America and provide essential length- and sequence-based background information for other forensic genetic studies in Peru.
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http://dx.doi.org/10.1016/j.fsigen.2021.102487DOI Listing
May 2021

Graph Algorithms for Mixture Interpretation.

Genes (Basel) 2021 Jan 27;12(2). Epub 2021 Jan 27.

Center for Human Identification, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107, USA.

The scale of genetic methods are presently being expanded: forensic genetic assays previously were limited to tens of loci, but now technologies allow for a transition to forensic genomic approaches that assess thousands to millions of loci. However, there are subtle distinctions between genetic assays and their genomic counterparts (especially in the context of forensics). For instance, forensic genetic approaches tend to describe a locus as a haplotype, be it a microhaplotype or a short tandem repeat with its accompanying flanking information. In contrast, genomic assays tend to provide not haplotypes but sequence variants or differences, variants which in turn describe how the alleles apparently differ from the reference sequence. By the given construction, mitochondrial genetic assays can be thought of as genomic as they often describe genetic differences in a similar way. The mitochondrial genetics literature makes clear that sequence differences, unlike the haplotypes they encode, are not comparable to each other. Different alignment algorithms and different variant calling conventions may cause the same haplotype to be encoded in multiple ways. This ambiguity can affect evidence and reference profile comparisons as well as how "match" statistics are computed. In this study, a graph algorithm is described (and implemented in the MMDIT (Mitochondrial Mixture Database and Interpretation Tool) R package) that permits the assessment of forensic match statistics on mitochondrial DNA mixtures in a way that is invariant to both the variant calling conventions followed and the alignment parameters considered. The algorithm described, given a few modest constraints, can be used to compute the "random man not excluded" statistic or the likelihood ratio. The performance of the approach is assessed in in silico mitochondrial DNA mixtures.
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http://dx.doi.org/10.3390/genes12020185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911948PMC
January 2021

A Continuous Statistical Phasing Framework for the Analysis of Forensic Mitochondrial DNA Mixtures.

Genes (Basel) 2021 Jan 20;12(2). Epub 2021 Jan 20.

Center for Human Identification, University of North Texas Health Science Center, 3500 Camp, Bowie Blvd., Fort Worth, TX 76107, USA.

Despite the benefits of quantitative data generated by massively parallel sequencing, resolving mitotypes from mixtures occurring in certain ratios remains challenging. In this study, a bioinformatic mixture deconvolution method centered on population-based phasing was developed and validated. The method was first tested on 270 in silico two-person mixtures varying in mixture proportions. An assortment of external reference panels containing information on haplotypic variation (from similar and different haplogroups) was leveraged to assess the effect of panel composition on phasing accuracy. Building on these simulations, mitochondrial genomes from the Human Mitochondrial DataBase were sourced to populate the panels and key parameter values were identified by deconvolving an additional 7290 in silico two-person mixtures. Finally, employing an optimized reference panel and phasing parameters, the approach was validated with in vitro two-person mixtures with differing proportions. Deconvolution was most accurate when the haplotypes in the mixture were similar to haplotypes present in the reference panel and when the mixture ratios were neither highly imbalanced nor subequal (e.g., 4:1). Overall, errors in haplotype estimation were largely bounded by the accuracy of the mixture's genotype results. The proposed framework is the first available approach that automates the reconstruction of complete individual mitotypes from mixtures, even in ratios that have traditionally been considered problematic.
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http://dx.doi.org/10.3390/genes12020128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909279PMC
January 2021

STRait Razor Online: An enhanced user interface to facilitate interpretation of MPS data.

Forensic Sci Int Genet 2021 May 13;52:102463. Epub 2021 Jan 13.

Center for Human Identification, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX, 76107, USA; Department of Microbiology, Immunology, and Genetics, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX, 76107, USA.

Since 2013, STRait Razor has enabled analysis of massively parallel sequencing (MPS) data from various marker systems such as short tandem repeats, single nucleotide polymorphisms, insertion/deletions, and mitochondrial DNA. In this paper, STRait Razor Online (SRO), available at https://www.unthsc.edu/straitrazor, is introduced as an interactive, Shiny-based user interface for primary analysis of MPS data and secondary analysis of STRait Razor haplotype pileups. This software can be accessed from any common browser via desktop, tablet, or smartphone device. SRO is available also as a standalone application and open-source R script available at https://github.com/ExpectationsManaged/STRaitRazorOnline. The local application is capable of batch processing of both fastq files and primary analysis output. Processed batches generate individual report folders and summary reports at the locus- and haplotype-level in a matter of minutes. For example, the processing of data from ∼700 samples generated with the ForenSeq Signature Preparation Kit from allsequences.txt to a final table can be performed in ∼40 min whereas the Excel-based workbooks can take 35-60 h to compile a subset of the tables generated by SRO. To facilitate analysis of single-source, reference samples, a preliminary triaging system was implemented that calls potential alleles and flags loci suspected of severe heterozygote imbalance. When compared to published, manually curated data sets, 98.72 % of software-assigned allele calls without manual interpretation were consistent with curated data sets, 0.99 % loci were presented to the user for interpretation due to heterozygote imbalance, and the remaining 0.29 % of loci were inconsistent due to the analytical thresholds used across the studies.
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http://dx.doi.org/10.1016/j.fsigen.2021.102463DOI Listing
May 2021

Medicine donation programmes supporting the global drive to end the burden of neglected tropical diseases.

Trans R Soc Trop Med Hyg 2021 Jan;115(2):136-144

NTD Support Centre, Task Force for Global Health Atlanta, USA.

Neglected tropical diseases (NTDs) are targeted for global control or elimination. Recognising that the populations most in need of medicines to target NTDs are those least able to support and sustain them financially, the pharmaceutical industry created mechanisms for donating medicines and expertise to affected countries through partnerships with the WHO, development agencies, non-governmental organisations and philanthropic donors. In the last 30 y, companies have established programmes to donate 17 different medicines to overcome the burden of NTDs. Billions of tablets, capsules, intravenous and oral solutions have been donated, along with the manufacturing, supply chains and research necessary to support these efforts. Industry engagement has stimulated other donors to support NTDs with funds and oversight so that the 'heath benefit' return on investment in these programmes is truly a 'best value in public health'. Many current donations are 'open-ended', promising support as long as necessary to achieve defined health targets. Extraordinary global health advances have been made in filariasis, onchocerciasis, trachoma, trypanosomiasis, leishmaniasis, schistosomiasis, intestinal parasites and others; and these advances are taking place in the context of strengthening health systems and meeting the global development goals espoused by the WHO. The pharmaceutical manufacturers, already strong collaborators in initiating or supporting these disease-targeted programmes, have committed to continuing their partnership roles in striving to meet the targets of the WHO's new NTD roadmap to 2030.
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http://dx.doi.org/10.1093/trstmh/traa167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842096PMC
January 2021

Reducing noise and stutter in short tandem repeat loci with unique molecular identifiers.

Forensic Sci Int Genet 2021 Mar 25;51:102459. Epub 2020 Dec 25.

Center for Human Identification, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107, USA; Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107, USA.

Unique molecular identifiers (UMIs) are a promising approach to contend with errors generated during PCR and massively parallel sequencing (MPS). With UMI technology, random molecular barcodes are ligated to template DNA molecules prior to PCR, allowing PCR and sequencing error to be tracked and corrected bioinformatically. UMIs have the potential to be particularly informative for the interpretation of short tandem repeats (STRs). Traditional MPS approaches may simply lead to the observation of alleles that are consistent with the hypotheses of stutter, while with UMIs stutter products bioinformatically may be re-associated with their parental alleles and subsequently removed. Herein, a bioinformatics pipeline named strumi is described that is designed for the analysis of STRs that are tagged with UMIs. Unlike other tools, strumi is an alignment-free machine learning driven algorithm that clusters individual MPS reads into UMI families, infers consensus super-reads that represent each family and provides an estimate the resulting haplotype's accuracy. Super-reads, in turn, approximate independent measurements not of the PCR products, but of the original template molecules, both in terms of quantity and sequence identity. Provisional assessments show that naïve threshold-based approaches generate super-reads that are accurate (∼97 % haplotype accuracy, compared to ∼78 % when UMIs are not used), and the application of a more nuanced machine learning approach increases the accuracy to ∼99.5 % depending on the level of certainty desired. With these features, UMIs may greatly simplify probabilistic genotyping systems and reduce uncertainty. However, the ability to interpret alleles at trace levels also permits the interpretation, characterization and quantification of contamination as well as somatic variation (including somatic stutter), which may present newfound challenges.
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http://dx.doi.org/10.1016/j.fsigen.2020.102459DOI Listing
March 2021

High throughput instrument to screen fluorescent proteins under two-photon excitation.

Biomed Opt Express 2020 Dec 17;11(12):7192-7203. Epub 2020 Nov 17.

Department of Cell Biology & Neuroscience, Montana State University, 109 Lewis Hall, Bozeman, MT 59717, USA.

Two-photon microscopy together with fluorescent proteins and fluorescent protein-based biosensors are commonly used tools in neuroscience. To enhance their experimental scope, it is important to optimize fluorescent proteins for two-photon excitation. Directed evolution of fluorescent proteins under one-photon excitation is common, but many one-photon properties do not correlate with two-photon properties. A simple system for expressing fluorescent protein mutants is colonies on an agar plate. The small focal volume of two-photon excitation makes creating a high throughput screen in this system a challenge for a conventional point-scanning approach. We present an instrument and accompanying software that solves this challenge by selectively scanning each colony based on a colony map captured under one-photon excitation. This instrument, called the GIZMO, can measure the two-photon excited fluorescence of 10,000 colonies in 7 hours. We show that the GIZMO can be used to evolve a fluorescent protein under two-photon excitation.
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http://dx.doi.org/10.1364/BOE.409353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747914PMC
December 2020

Genetic assessment reveals no population substructure and divergent regional and sex-specific histories in the Chachapoyas from northeast Peru.

PLoS One 2020 31;15(12):e0244497. Epub 2020 Dec 31.

Department of Forensic Medicine, University of Helsinki, Helsinki, Finland.

Many native populations in South America have been severely impacted by two relatively recent historical events, the Inca and the Spanish conquest. However decisive these disruptive events may have been, the populations and their gene pools have been shaped markedly also by the history prior to the conquests. This study focuses mainly on the Chachapoya peoples that inhabit the montane forests on the eastern slopes of the northern Peruvian Andes, but also includes three distinct neighboring populations (the Jívaro, the Huancas and the Cajamarca). By assessing mitochondrial, Y-chromosomal and autosomal diversity in the region, we explore questions that have emerged from archaeological and historical studies of the regional culture (s). These studies have shown, among others, that Chachapoyas was a crossroads for Coast-Andes-Amazon interactions since very early times. In this study, we examine the following questions: 1) was there pre-Hispanic genetic population substructure in the Chachapoyas sample? 2) did the Spanish conquest cause a more severe population decline on Chachapoyan males than on females? 3) can we detect different patterns of European gene flow in the Chachapoyas region? and, 4) did the demographic history in the Chachapoyas resemble the one from the Andean area? Despite cultural differences within the Chachapoyas region as shown by archaeological and ethnohistorical research, genetic markers show no significant evidence for past or current population substructure, although an Amazonian gene flow dynamic in the northern part of this territory is suggested. The data also indicates a bottleneck c. 25 generations ago that was more severe among males than females, as well as divergent population histories for populations in the Andean and Amazonian regions. In line with previous studies, we observe high genetic diversity in the Chachapoyas, despite the documented dramatic population declines. The diverse topography and great biodiversity of the northeastern Peruvian montane forests are potential contributing agents in shaping and maintaining the high genetic diversity in the Chachapoyas region.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244497PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774974PMC
March 2021

A decentralised point-of-care testing model to address inequities in the COVID-19 response.

Lancet Infect Dis 2020 Dec 23. Epub 2020 Dec 23.

Kirby Institute, University of New South Wales, Sydney, NSW, Australia.

The COVID-19 pandemic is growing rapidly, with over 37 million cases and more than 1 million deaths reported by mid-October, 2020, with true numbers likely to be much higher in the many countries with low testing rates. Many communities are highly vulnerable to the devastating effects of COVID-19 because of overcrowding in domestic settings, high burden of comorbidities, and scarce access to health care. Access to testing is crucial to globally recommended control strategies, but many communities do not have adequate access to timely laboratory services. Geographic dispersion of small populations across islands and other rural and remote settings presents a key barrier to testing access. In this Personal View, we describe a model for the implementation of decentralised COVID-19 point-of-care testing in remote locations by use of the GeneXpert platform, which has been successfully scaled up in remote Aboriginal and Torres Strait Islander communities across Australia. Implementation of the decentralised point-of-care testing model should be considered for communities in need, especially those that are undertested and socially vulnerable. The decentralised testing model should be part of the core global response towards suppressing COVID-19.
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http://dx.doi.org/10.1016/S1473-3099(20)30859-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758179PMC
December 2020

Evolution of the monitoring and evaluation strategies to support the World Health Organization's Global Programme to Eliminate Lymphatic Filariasis.

Int Health 2020 Dec;13(Supplement_1):S65-S70

NTD Support Center, Task Force for Global Health, 325 Swanton Way, Decatur, GA 30030, USA.

The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was established with the ambitious goal of eliminating LF as a public health problem. The remarkable success of the GPELF over the past 2 decades in carrying out its principal strategy of scaling up and scaling down mass drug administration has relied first on the development of a rigorous monitoring and evaluation (M&E) framework and then the willingness of the World Health Organization and its community of partners to modify this framework in response to the practical experiences of national programmes. This flexibility was facilitated by the strong partnership that developed among researchers, LF programme managers and donors willing to support the necessary research agenda. This brief review summarizes the historical evolution of the GPELF M&E strategies and highlights current research needed to achieve the elimination goal.
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http://dx.doi.org/10.1093/inthealth/ihaa084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753166PMC
December 2020

A triple-drug treatment regimen to accelerate elimination of lymphatic filariasis: From conception to delivery.

Int Health 2020 Dec;13(Supplement_1):S60-S64

Department of Control of Neglected Tropical Diseases, World Health Organization, Geneva, Switzerland.

The Global Programme to Eliminate Lymphatic Filariasis (LF) is using mass drug administration (MDA) of antifilarial medications to treat filarial infections, prevent disease and interrupt transmission. Almost 500 million people receive these medications each year. Clinical trials have recently shown that a single dose of a triple-drug combination comprised of ivermectin, diethylcarbamazine and albendazole (IDA) is dramatically superior to widely used two-drug combinations for clearing larval filarial parasites from the blood of infected persons. A large multicenter community study showed that IDA was well-tolerated when it was provided as MDA. IDA was rapidly advanced from clinical trial to policy and implementation; it has the potential to accelerate LF elimination in many endemic countries.
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http://dx.doi.org/10.1093/inthealth/ihaa046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753162PMC
December 2020

Congressional Budget Responses to the Pandemic: Fund Health Care, Not Warfare.

Am J Public Health 2021 02 19;111(2):200-201. Epub 2020 Nov 19.

Jonathan King is with the Department of Biology, Massachusetts Institute of Technology, Cambridge. David Goldenberg is with the Department of Biology, University of Utah, Salt Lake City. Gary Goldstein is with the Department of Physics, Tufts University, Medford, MA. William Hartung is with the Center for International Policy, Washington, DC. Catherine Royer is with the Department of Chemistry, Renssalaer Polytechnic Institute, Troy, NY. Eric Sundberg is with the Department of Biochemistry, Emory University School of Medicine, Atlanta, GA. Cornelia van der Ziel is unaffiliated. Michael Van Elzakker is with the Department of Neuroscience, Mass General Hospital, Boston, MA. Sir Richard Roberts is with New England Biolabs Inc., Ipswich, MA.

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http://dx.doi.org/10.2105/AJPH.2020.306048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811077PMC
February 2021

Diagnostics and the neglected tropical diseases roadmap: setting the agenda for 2030.

Trans R Soc Trop Med Hyg 2021 Jan;115(2):129-135

Neglected Tropical Diseases Support Center, Task Force for Global Health, Atlanta, GA 30030, USA.

Accurate and reliable diagnostic tools are an essential requirement for neglected tropical diseases (NTDs) programmes. However, the NTD community has historically underinvested in the development and improvement of diagnostic tools, potentially undermining the successes achieved over the last 2 decades. Recognizing this, the WHO, in its newly released draft roadmap for NTD 2021-2030, has identified diagnostics as one of four priority areas requiring concerted action to reach the 2030 targets. As a result, WHO established a Diagnostics Technical Advisory Group (DTAG) to serve as the collaborative mechanism to drive progress in this area. Here, the purpose and role of the DTAG are described in the context of the challenges facing NTD programmes.
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http://dx.doi.org/10.1093/trstmh/traa118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842105PMC
January 2021

Study of potentially preventable hospitalisations (PPH) for chronic conditions: what proportion are preventable and what factors are associated with preventable PPH?

BMJ Open 2020 11 9;10(11):e038415. Epub 2020 Nov 9.

University Centre for Rural Health, University of Sydney, Lismore, New South Wales, Australia

Introduction: The proportion of potentially preventable hospitalisations (PPH) which are actually preventable is unknown, and little is understood about the factors associated with individual preventable PPH. The Diagnosing Potentially Preventable Hospitalisations (DaPPHne) Study aimed to determine the proportion of PPH for chronic conditions which are preventable and identify factors associated with chronic PPH classified as preventable.

Setting: Three hospitals in NSW, Australia.

Participants: Community-dwelling patients with unplanned hospital admissions between November 2014 and June 2017 for congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), diabetes complications or angina pectoris. Data were collected from patients, their general practitioners (GPs) and hospital records.

Outcome Measures: Assessments of the preventability of each admission by an Expert Panel.

Results: 323 admissions were assessed for preventability: 46% (148/323) were assessed as preventable, 30% (98/323) as not preventable and 24% (77/323) as unclassifiable. Statistically significant differences in proportions preventable were found between the three study sites (29%; 47%; 58%; p≤0.001) and by primary discharge diagnosis (p≤0.001).Significant predictors of an admission being classified as preventable were: study site; final principal diagnosis of CHF; fewer diagnoses on discharge; shorter hospital stay; GP diagnosis of COPD; GP consultation in the last 12 months; not having had a doctor help make the decision to go to hospital; not arriving by ambulance; patient living alone; having someone help with medications and requiring help with daily tasks.

Conclusions: That less than half the chronic PPH were assessed as preventable, and the range of factors associated with preventability, including site and discharge diagnosis, are important considerations in the validity of PPH as an indicator. Opportunities for interventions to reduce chronic PPH include targeting patients with CHF and COPD, and the provision of social welfare and support services for patients living alone and those requiring help with daily tasks and medication management.
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http://dx.doi.org/10.1136/bmjopen-2020-038415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654103PMC
November 2020

Is praziquantel preventive chemotherapy associated with visual disorders in Eritrea? A comment on the case series reported by Debesai and Russom.

PLoS Negl Trop Dis 2020 11 5;14(11):e0008827. Epub 2020 Nov 5.

World Health Organization, Department of Control of Neglected Tropical Diseases, Geneva, Switzerland.

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http://dx.doi.org/10.1371/journal.pntd.0008827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643939PMC
November 2020

Poorly differentiated histologic grade correlates with worse survival in SMAD4 negative pancreatic adenocarcinoma patients.

J Surg Oncol 2021 Feb 4;123(2):389-398. Epub 2020 Nov 4.

Department of Surgery, UCLA David Geffen School of Medicine, Los Angeles, California, USA.

Background And Objectives: This study investigated the influence of the transcription factor SMAD4 on overall patient survival following surgical resection of pancreatic ductal adenocarcinoma (PDAC).

Methods: The SMAD4 status of 125 surgically resected PDAC specimens at a large academic center from 2014 to 2017 was routinely determined prospectively and correlated with clinicopathologic characteristics and overall survival.

Results: SMAD4 loss was identified in 62% of patients and was not associated with overall survival (OS). On multivariate Cox proportional hazards survival analysis, histologic grade was the best predictor of survival in the SMAD4(-) population (adjusted hazard ratio = 4.8, p < .0001). In the SMAD4(+) population, histologic grade was not associated with survival on multivariate analysis. In the SMAD4(-) population, median OS for well/moderately differentiated patients and poorly differentiated patients was 39.6 and 8.6 months, respectively.

Conclusion: In this large cohort of resected PDAC, routine SMAD4 assessment identified a subpopulation of patients with SMAD4(-) and histologically poorly differentiated tumors that had significantly poor prognosis with median OS of 8.6 months. Characterization of the role of SMAD4 within the context of poorly differentiated tumors may help settle the controversy regarding SMAD4 in PDAC and lead to identification of personalized therapeutic strategies for subgroups of PDAC.
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http://dx.doi.org/10.1002/jso.26279DOI Listing
February 2021

Reviews on Current Liquid Biopsy for Detection and Management of Pancreatic Cancers.

Pancreas 2020 10;49(9):1141-1152

Center for Pancreatic Diseases, Yale University, New Haven, CT.

Pancreatic cancer is the fourth leading cause of cancer death in the United States. Pancreatic cancer presents dismal clinical outcomes in patients, and the incidence of pancreatic cancer has continuously increased to likely become the second most common cause of cancer-related deaths by as early as 2030. One of main reasons for the high mortality rate of pancreatic cancer is the lack of tools for early-stage detection. Current practice in detecting and monitoring therapeutic response in pancreatic cancer relies on imaging analysis and invasive endoscopic examination. Liquid biopsy-based analysis of genetic alterations in biofluids has become a fundamental component in the diagnosis and management of cancers. There is an urgent need for scientific and technological advancement to detect pancreatic cancer early and to develop effective therapies. The development of a highly sensitive and specific liquid biopsy tool will require extensive understanding on the characteristics of circulating tumor DNA in biofluids. Here, we have reviewed the current status of liquid biopsy in detecting and monitoring pancreatic cancers and our understanding of circulating tumor DNA that should be considered for the development of a liquid biopsy tool, which will greatly aid in the diagnosis and healthcare of people at risk.
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http://dx.doi.org/10.1097/MPA.0000000000001662DOI Listing
October 2020

Glacial cooling and climate sensitivity revisited.

Nature 2020 08 26;584(7822):569-573. Epub 2020 Aug 26.

Department of Earth and Environmental Sciences, University of Michigan, Ann Arbor, MI, USA.

The Last Glacial Maximum (LGM), one of the best studied palaeoclimatic intervals, offers an excellent opportunity to investigate how the climate system responds to changes in greenhouse gases and the cryosphere. Previous work has sought to constrain the magnitude and pattern of glacial cooling from palaeothermometers, but the uneven distribution of the proxies, as well as their uncertainties, has challenged the construction of a full-field view of the LGM climate state. Here we combine a large collection of geochemical proxies for sea surface temperature with an isotope-enabled climate model ensemble to produce a field reconstruction of LGM temperatures using data assimilation. The reconstruction is validated with withheld proxies as well as independent ice core and speleothem δO measurements. Our assimilated product provides a constraint on global mean LGM cooling of -6.1 degrees Celsius (95 per cent confidence interval: -6.5 to -5.7 degrees Celsius). Given assumptions concerning the radiative forcing of greenhouse gases, ice sheets and mineral dust aerosols, this cooling translates to an equilibrium climate sensitivity of 3.4 degrees Celsius (2.4-4.5 degrees Celsius), a value that is higher than previous LGM-based estimates but consistent with the traditional consensus range of 2-4.5 degrees Celsius.
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http://dx.doi.org/10.1038/s41586-020-2617-xDOI Listing
August 2020

Australian Paediatric Surveillance Unit (APSU) Annual Surveillance Report 2019.

Commun Dis Intell (2018) 2020 Aug 17;44. Epub 2020 Aug 17.

Professor of Paediatrics and Child Health and Director of The Australian Paediatric Surveillance Unit, The University of Sydney, Faculty of Medicine and Health, Discipline of Child and Adolescent Health and The Sydney Children's Hospitals Network, Westmead, Sydney, New South Wales.

The Australian Paediatric Surveillance Unit (APSU) has been prospectively collecting national data on rare childhood conditions since 1993, with monthly reporting of cases by paediatricians. In this report we describe annual results from studies for ten communicable diseases and complications of communicable diseases that were conducted using APSU surveillance in 2019 and place these in an historic context. Results are reported on acute flaccid paralysis, congenital cytomegalovirus infection, neonatal herpes simplex virus infection, perinatal exposure to HIV, paediatric HIV infection, severe complications of seasonal influenza, juvenile onset recurrent respiratory papillomatosis (JoRRP), congenital rubella syndrome, congenital varicella syndrome and neonatal varicella infection. APSU provides rich clinical data to complement data collected from other surveillance systems and to improve understanding and response to rare childhood infections.
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http://dx.doi.org/10.33321/cdi.2020.44.60DOI Listing
August 2020

Abdominal Pain and an Appendiceal Mass.

JAMA 2020 Aug;324(6):599-600

Department of General Surgery, University of California, Los Angeles.

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http://dx.doi.org/10.1001/jama.2020.4707DOI Listing
August 2020

Readmission and Resource Use After Robotic-Assisted versus Open Pancreaticoduodenectomy: 2010-2017.

J Surg Res 2020 11 3;255:517-524. Epub 2020 Jul 3.

Department of Surgery, University of California Los Angeles, Los Angeles, California. Electronic address:

Background: Unplanned rehospitalization is considered an adverse quality of care indicator. Minimally invasive operations carry the potential to reduce resource use while enhancing recovery. Robotic-assisted pancreaticoduodenectomy (RAPD) has been used to improve outcomes of its morbid open counterpart. We sought to identify factors associated with readmission between RAPD and open pancreaticoduodenectomy (OPD).

Materials And Methods: We used the 2010-17 National Readmissions Database to identify adults who underwent RAPD or OPD. The primary outcome was 30-day readmission. Secondary outcomes included readmission diagnosis: index, readmission, and total (index + readmission) length of stay, costs, and mortality.

Results: Of an estimated 84,036 patients undergoing pancreaticoduodenectomy, 96.9% survived index hospitalization. Frequency of both RAPD and OPD increased during the study period with similar mortality (2.5% versus 3.2%, P = 0.46). Compared with OPD, RAPD was not an independent predictor of 30-day readmission (adjusted odds ratio (AOR): 1.0, P = 0.98). Disposition with home health care (AOR: 1.1, P < 0.001) or to a skilled nursing facility (AOR: 1.5, P < 0.001) was significantly associated with increased 30-day readmission.

Conclusions: Readmission after pancreaticoduodenectomy is common, regardless of surgical approach. Although RAPD saves in-patient days on index admission, readmission rates and length of stay are similar between the two modalities. Neither RAPD nor OPD is a risk factor for readmission, highlighting the complexity of pancreaticoduodenectomy, with complications that may result from factors independent of the operative approach.
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http://dx.doi.org/10.1016/j.jss.2020.05.084DOI Listing
November 2020

National Trends in Readmission and Resource Utilization After Pancreatectomy in the United States.

J Surg Res 2020 11 24;255:304-310. Epub 2020 Jun 24.

Department of Surgery, University of California Los Angeles, Los Angeles, California. Electronic address:

Introduction: Pancreatectomy is a complex operation that has been associated with excess morbidity and mortality. Although acute index outcomes have been characterized, there are limited data available on nonelective readmission after pancreatic surgery. We sought to identify factors associated with 30-day and 30- to 90-day readmission after pancreatectomy.

Material And Methods: We utilized the National Readmissions Database between 2010 and 2016 to identify adults who underwent a pancreatectomy. The primary outcomes were 30-day (30DR) and 30- to 90-day (90DR) readmission. Secondary outcomes included nonelective readmission trends, diagnosis, length of stay, charges, and mortality.

Results: Of an estimated 130,267 subjects undergoing pancreatectomy, 97% survived index hospitalization. Eighteen percent of patients had nonelective 30DR while 5.6% experienced 90DR. Readmission at the two time points remained stable during the study period. After adjusting for institution, pancreatectomy volume, mortality (2.0% versus 4.9%, P < 0.001), 30DR length of stay (7.3 d versus 7.8 d, P < 0.001), and 90DR rates (6.9% versus 8.1%, P = 0.003) were significantly decreased at high-volume pancreatectomy centers compared to low-volume hospitals. Discharge to a skilled nursing facility (AOR: 1.52) or with home health care (AOR: 1.2) was associated with 30DR (P < 0.001). Patients undergoing total pancreatectomy (AOR: 1.3) or those with a substance use disorder (AOR: 1.4) among others were associated with 90DR (P ≤ 0.01).

Conclusions: Readmissions are common and costly after pancreatectomy. Approximately 20% of patients experience readmission within 30 d. 30DR and 90DR rates remained stable during the study. Pancreatectomy at a high-volume center was associated with decreased mortality and 90DR. The present analysis confirms associations between pancreatectomy volume, postsurgical complications, comorbidities, and readmission.
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http://dx.doi.org/10.1016/j.jss.2020.04.037DOI Listing
November 2020

Maternal diabetes and obesity influence the fetal epigenome in a largely Hispanic population.

Clin Epigenetics 2020 02 19;12(1):34. Epub 2020 Feb 19.

Pediatrics, University of Texas Health Science Center San Antonio, San Antonio, TX, USA.

Background: Obesity and diabetes mellitus are directly implicated in many adverse health consequences in adults as well as in the offspring of obese and diabetic mothers. Hispanic Americans are particularly at risk for obesity, diabetes, and end-stage renal disease. Maternal obesity and/or diabetes through prenatal programming may alter the fetal epigenome increasing the risk of metabolic disease in their offspring. The aims of this study were to determine if maternal obesity or diabetes mellitus during pregnancy results in a change in infant methylation of CpG islands adjacent to targeted genes specific for obesity or diabetes disease pathways in a largely Hispanic population.

Methods: Methylation levels in the cord blood of 69 newborns were determined using the Illumina Infinium MethylationEPIC BeadChip. Over 850,000 different probe sites were analyzed to determine whether maternal obesity and/or diabetes mellitus directly attributed to differential methylation; epigenome-wide and regional analyses were performed for significant CpG sites.

Results: Following quality control, agranular leukocyte samples from 69 newborns (23 normal term (NT), 14 diabetes (DM), 23 obese (OB), 9 DM/OB) were analyzed for over 850,000 different probe sites. Contrasts between the NT, DM, OB, and DM/OB were considered. After correction for multiple testing, 15 CpGs showed differential methylation from the NT, associated with 10 differentially methylated genes between the diabetic and non-diabetic subgroups, CCDC110, KALRN, PAG1, GNRH1, SLC2A9, CSRP2BP, HIVEP1, RALGDS, DHX37, and SCNN1D. The effects of diabetes were partly mediated by the altered methylation of HOOK2, LCE3C, and TMEM63B. The effects of obesity were partly mediated by the differential methylation of LTF and DUSP22.

Conclusions: The presented data highlights the associated altered methylation patterns potentially mediated by maternal diabetes and/or obesity. Larger studies are warranted to investigate the role of both the identified differentially methylated loci and the effects on newborn body composition and future health risk factors for metabolic disease. Additional future consideration should be targeted to the role of Hispanic inheritance. Potential future targeting of transgenerational propagation and developmental programming may reduce population obesity and diabetes risk.
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http://dx.doi.org/10.1186/s13148-020-0824-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031937PMC
February 2020