Displaying publications 1 - 20 of 31 in total

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  1. Smith TM, Arora M, Austin C, Nunes Ávila J, Duval M, Lim TT, et al.
    Elife, 2024 Mar 08;12.
    PMID: 38457350 DOI: 10.7554/eLife.90217
    Studies of climate variation commonly rely on chemical and isotopic changes recorded in sequentially produced growth layers, such as in corals, shells, and tree rings, as well as in accretionary deposits-ice and sediment cores, and speleothems. Oxygen isotopic compositions (δ18O) of tooth enamel are a direct method of reconstructing environmental variation experienced by an individual animal. Here, we utilize long-forming orangutan dentitions (Pongo spp.) to probe recent and ancient rainfall trends on a weekly basis over ~3-11 years per individual. We first demonstrate the lack of any consistent isotopic enrichment effect during exclusive nursing, supporting the use of primate first molar teeth as environmental proxies. Comparisons of δ18O values (n=2016) in twelve molars from six modern Bornean and Sumatran orangutans reveal a high degree of overlap, with more consistent annual and bimodal rainfall patterns in the Sumatran individuals. Comparisons with fossil orangutan δ18O values (n=955 measurements from six molars) reveal similarities between modern and late Pleistocene fossil Sumatran individuals, but differences between modern and late Pleistocene/early Holocene Bornean orangutans. These suggest drier and more open environments with reduced monsoon intensity during this earlier period in northern Borneo, consistent with other Niah Caves studies and long-term speleothem δ18O records in the broader region. This approach can be extended to test hypotheses about the paleoenvironments that early humans encountered in southeast Asia.
  2. Tyler L, Kennelly PJ, Engelman S, Block KF, Bobenko JC, Catalano J, et al.
    Biochem Mol Biol Educ, 2024;52(1):58-69.
    PMID: 37815098 DOI: 10.1002/bmb.21789
    We present as a case study the evolution of a series of participant-centered workshops designed to meet a need in the life sciences education community-the incorporation of best practices in the assessment of student learning. Initially, the ICABL (Inclusive Community for the Assessment of Biochemistry and Molecular Biology/BMB Learning) project arose from a grass-roots effort to develop material for a national exam in biochemistry and molecular biology. ICABL has since evolved into a community of practice in which participants themselves-through extensive peer review and reflection-become integral stakeholders in the workshops. To examine this evolution, this case study begins with a pilot workshop supported by seed funding and thoughtful programmatic assessment, the results of which informed evidence-based changes that, in turn, led to an improved experience for the community. Using participant response data, the case study also reveals critical features for successful workshops, including participant-centered activities and the value of frequent peer review of participants' products. Furthermore, we outline a train-the-trainer model for creating a self-renewing community by bringing new perspectives and voices into an existing core leadership team. This case study, then, offers a blueprint for building a thriving, evolving community of practice that not only serves the needs of individual scientist-educators as they seek to enhance student learning, but also provides a pathway for elevating members to positions of leadership.
  3. Gamalo LE, Ilham K, Jones-Engel L, Gill M, Sweet R, Aldrich B, et al.
    Am J Primatol, 2023 Sep 04.
    PMID: 37667504 DOI: 10.1002/ajp.23547
    In 2022, long-tailed macaques (Macaca fascicularis), a once ubiquitous primate species, was elevated to Endangered on the International Union for Conservation of Nature (IUCN) Red List of Threatened Species. In 2023, recognizing that the long-tailed macaque is threatened by multiple factors: (1) declining native habitats across Southeast Asia; (2) overutilization for scientific, commercial, and recreational purposes; (3) inadequate regulatory mechanisms; and (4) culling due to human-macaque conflicts, a petition for rulemaking was submitted to the United States Fish and Wildlife Service to add the species to the US Endangered Species Act, the nation's most effective law to protect at risk species. The long-tailed macaque remains unprotected across much of its geographical range despite the documented continual decline of the species and related sub-species and the recent IUCN reassessment. This commentary presents a review of the factors that have contributed to the dramatic decline of this keystone species and makes a case for raising the level of protection they receive.
  4. Dave RV, Elsberger B, Taxiarchi VP, Gandhi A, Kirwan CC, Kim B, et al.
    PMID: 37010651 DOI: 10.1007/s10549-023-06893-4
    PURPOSE: The B-MaP-C study investigated changes to breast cancer care that were necessitated by the COVID-19 pandemic. Here we present a follow-up analysis of those patients commenced on bridging endocrine therapy (BrET), whilst they were awaiting surgery due to reprioritisation of resources.

    METHODS: This multicentre, multinational cohort study recruited 6045 patients from the UK, Spain and Portugal during the peak pandemic period (Feb-July 2020). Patients on BrET were followed up to investigate the duration of, and response to, BrET. This included changes in tumour size to reflect downstaging potential, and changes in cellular proliferation (Ki67), as a marker of prognosis.

    RESULTS: 1094 patients were prescribed BrET, over a median period of 53 days (IQR 32-81 days). The majority of patients (95.6%) had strong ER expression (Allred score 7-8/8). Very few patients required expedited surgery, due to lack of response (1.2%) or due to lack of tolerance/compliance (0.8%). There were small reductions in median tumour size after 3 months' treatment duration; median of 4 mm [IQR - 20, 4]. In a small subset of patients (n = 47), a drop in cellular proliferation (Ki67) occurred in 26 patients (55%), from high (Ki67 ≥ 10%) to low (

  5. Lam MQ, Oates NC, Leadbeater DR, Goh KM, Yahya A, Md Salleh M, et al.
    Genes (Basel), 2022 Nov 17;13(11).
    PMID: 36421811 DOI: 10.3390/genes13112135
    Robertkochia solimangrovi is a proposed marine bacterium isolated from mangrove soil. So far, the study of this bacterium is limited to taxonomy only. In this report, we performed a genomic analysis of R. solimangrovi that revealed its lignocellulose degrading ability. Genome mining of R. solimangrovi revealed a total of 87 lignocellulose degrading enzymes. These enzymes include cellulases (GH3, GH5, GH9 and GH30), xylanases (GH5, GH10, GH43, GH51, GH67, and GH115), mannanases (GH2, GH26, GH27 and GH113) and xyloglucanases (GH2, GH5, GH16, GH29, GH31 and GH95). Most of the lignocellulolytic enzymes encoded in R. solimangrovi were absent in the genome of Robertkochia marina, the closest member from the same genus. Furthermore, current work also demonstrated the ability of R. solimangrovi to produce lignocellulolytic enzymes to deconstruct oil palm empty fruit bunch (EFB), a lignocellulosic waste found abundantly in palm oil industry. The metabolic pathway taken by R. solimangrovi to transport and process the reducing sugars after the action of lignocellulolytic enzymes on EFB was also inferred based on genomic data. Collectively, genomic analysis coupled with experimental studies elucidated R. solimangrovi to serve as a promising candidate in seawater based-biorefinery industry.
  6. Hakkaart C, Pearson JF, Marquart L, Dennis J, Wiggins GAR, Barnes DR, et al.
    Commun Biol, 2022 Oct 06;5(1):1061.
    PMID: 36203093 DOI: 10.1038/s42003-022-03978-6
    The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.
  7. Dareng EO, Tyrer JP, Barnes DR, Jones MR, Yang X, Aben KKH, et al.
    Eur J Hum Genet, 2022 May;30(5):630-631.
    PMID: 35314806 DOI: 10.1038/s41431-022-01085-y
  8. Dareng EO, Tyrer JP, Barnes DR, Jones MR, Yang X, Aben KKH, et al.
    Eur J Hum Genet, 2022 Jan 14.
    PMID: 35027648 DOI: 10.1038/s41431-021-00987-7
    Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
  9. Lakeman IMM, van den Broek AJ, Vos JAM, Barnes DR, Adlard J, Andrulis IL, et al.
    Genet Med, 2021 Sep;23(9):1726-1737.
    PMID: 34113011 DOI: 10.1038/s41436-021-01198-7
    PURPOSE: To evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes.

    METHODS: We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS313 and CBC risk.

    RESULTS: For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06-1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS313, HR = 1.15, 95% CI (1.07-1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC 

  10. Ho JY, Jong MC, Acharya K, Liew SSX, Smith DR, Noor ZZ, et al.
    J Hazard Mater, 2021 03 05;405:124687.
    PMID: 33301976 DOI: 10.1016/j.jhazmat.2020.124687
    River systems in developing and emerging countries are often fragmented relative to land and waste management in their catchment. The impact of inconsistent waste management and releases is a major challenge in water quality management. To examine how anthropogenic activities and estuarine effects impact water quality, we characterised water conditions, in-situ microbiomes, profiles of faecal pollution indicator, pathogenic and antibiotic resistant bacteria in the River Melayu, Southern Malaysia. Overall, upstream sampling locations were distinguished from those closer to the coastline by physicochemical parameters and bacterial communities. The abundances of bacterial DNA, total E. coli marker genes, culturable bacteria as well as antibiotic resistance ESBL-producing bacteria were elevated at upstream sampling locations especially near discharge of a wastewater oxidation pond. Furthermore, 85.7% of E. faecalis was multidrug-resistant (MDR), whereas 100% of E. cloacae, E. coli, K. pneumoniae were MDR. Overall, this work demonstrates how pollution in river estuaries does not monotonically change from inland towards the coast but varies according to local waste releases and tidal mixing. We also show that surrogate markers, such dissolved oxygen, Bacteroides and Prevotella abundances, and the rodA qPCR assay for total E. coli, can identify locations on a river that deserve immediate attention to mitigate AMR spread through improved waste management.
  11. Barnes DR, Rookus MA, McGuffog L, Leslie G, Mooij TM, Dennis J, et al.
    Genet Med, 2020 10;22(10):1653-1666.
    PMID: 32665703 DOI: 10.1038/s41436-020-0862-x
    PURPOSE: We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers.

    METHODS: Retrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort.

    RESULTS: The ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33], P = 3×10-72). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36], P = 7×10-50). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25-1.40], P = 3×10-22) and BRCA2 (HR = 1.44 [95% CI 1.30-1.60], P = 4×10-12) carriers. The associations in the prospective cohort were similar.

    CONCLUSION: Population-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes.

  12. Silvestri V, Leslie G, Barnes DR, CIMBA Group, Agnarsson BA, Aittomäki K, et al.
    JAMA Oncol, 2020 Aug 01;6(8):1218-1230.
    PMID: 32614418 DOI: 10.1001/jamaoncol.2020.2134
    IMPORTANCE: The limited data on cancer phenotypes in men with germline BRCA1 and BRCA2 pathogenic variants (PVs) have hampered the development of evidence-based recommendations for early cancer detection and risk reduction in this population.

    OBJECTIVE: To compare the cancer spectrum and frequencies between male BRCA1 and BRCA2 PV carriers.

    DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 6902 men, including 3651 BRCA1 and 3251 BRCA2 PV carriers, older than 18 years recruited from cancer genetics clinics from 1966 to 2017 by 53 study groups in 33 countries worldwide collaborating through the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Clinical data and pathologic characteristics were collected.

    MAIN OUTCOMES AND MEASURES: BRCA1/2 status was the outcome in a logistic regression, and cancer diagnoses were the independent predictors. All odds ratios (ORs) were adjusted for age, country of origin, and calendar year of the first interview.

    RESULTS: Among the 6902 men in the study (median [range] age, 51.6 [18-100] years), 1634 cancers were diagnosed in 1376 men (19.9%), the majority (922 of 1,376 [67%]) being BRCA2 PV carriers. Being affected by any cancer was associated with a higher probability of being a BRCA2, rather than a BRCA1, PV carrier (OR, 3.23; 95% CI, 2.81-3.70; P 

  13. Zhang S, Ching CK, Huang D, Liu YB, Rodriguez-Guerrero DA, Hussin A, et al.
    Heart Rhythm, 2020 03;17(3):468-475.
    PMID: 31561030 DOI: 10.1016/j.hrthm.2019.09.023
    BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are underutilized in Asia, Latin America, Eastern Europe, the Middle East, and Africa. The Improve SCA Study is the largest prospective study to evaluate the benefit of ICD therapy in underrepresented geographies. This analysis reports the primary objective of the study.

    OBJECTIVES: The objectives of this study was to determine whether patients with primary prevention (PP) indications with specific risk factors (1.5PP: syncope, nonsustained ventricular tachycardia, premature ventricular contractions >10/h, and low ventricular ejection fraction <25%) are at a similar risk of life-threatening arrhythmias as patients with secondary prevention (SP) indications and to evaluate all-cause mortality rates in 1.5PP patients with and without devices.

    METHODS: A total of 3889 patients were included in the analysis to evaluate ventricular tachycardia or fibrillation therapy and mortality rates. Patients were stratified as SP (n = 1193) and patients with PP indications. The PP cohort was divided into 1.5PP patients (n = 1913) and those without any 1.5PP criteria (n = 783). The decision to undergo ICD implantation was left to the patient and/or physician. The Cox proportional hazards model was used to compute hazard ratios.

    RESULTS: Patients had predominantly nonischemic cardiomyopathy. The rate of ventricular tachycardia or fibrillation in 1.5PP patients was not equivalent (within 30%) to that in patients with SP indications (hazard ratio 0.47; 95% confidence interval 0.38-0.57) but was higher than that in PP patients without any 1.5PP criteria (hazard ratio 0.67; 95% confidence interval 0.46-0.97) (P = .03). There was a 49% relative risk reduction in all-cause mortality in ICD implanted 1.5PP patients. In addition, the number needed to treat to save 1 life over 3 years was 10.0 in the 1.5PP cohort vs 40.0 in PP patients without any 1.5PP criteria.

    CONCLUSION: These data corroborate the mortality benefit of ICD therapy and support extension to a selected PP population from underrepresented geographies.

  14. Patel VL, Busch EL, Friebel TM, Cronin A, Leslie G, McGuffog L, et al.
    Cancer Res, 2020 Feb 01;80(3):624-638.
    PMID: 31723001 DOI: 10.1158/0008-5472.CAN-19-1840
    Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 3' region of BRCA2 (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001-c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25-2.52; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63-5.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71-4.68; P = 0.00004) and elevated risk of Gleason 8+ prostate cancer (HR = 4.95; 95% CI, 2.12-11.54; P = 0.0002). No genotype-phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer. SIGNIFICANCE: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.
  15. Fachal L, Aschard H, Beesley J, Barnes DR, Allen J, Kar S, et al.
    Nat Genet, 2020 01;52(1):56-73.
    PMID: 31911677 DOI: 10.1038/s41588-019-0537-1
    Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes.
  16. Gustafsson DR, Malysheva OD, Tolstenkov OO, Bush SE
    J Parasitol, 2019 12;105(6):846-857.
    PMID: 31730418
    Five new species of Guimaraesiella Eichler, 1949 are described and illustrated from hosts in the Eurylaimidae and Calyptomenidae. They are Guimaraesiella corydoni n. sp. from Corydon sumatranus laoensis Meyer de Schauensee, 1929 ; Guimaraesiella latirostris n. sp. from Eurylaimus ochromalus Raffles, 1822 ; Guimaraesiella cyanophoba n. sp. from Cymbirhynchus macrorhynchus malaccensis Salvadori, 1874 and C. m. siamensis Meyer de Schauensee and Ripley, 1940 ; Guimaraesiella altunai n. sp. from Calyptomena viridis caudacuta Swainson, 1838 ; and Guimaraesiella forcipata n. sp. from Eurylaimus steerii steerii Sharpe, 1876 . These represent the first species of Guimaraesiella described from the Calyptomenidae and Eurylaimidae, as well as the first species of this genus described from the Old World suboscines.
  17. Swanson DR
    Zootaxa, 2019 Nov 19;4700(2):zootaxa.4700.2.2.
    PMID: 32229981 DOI: 10.11646/zootaxa.4700.2.2
    Herein are erected several new taxa and taxonomic changes based on a study of the Old World genera of Peiratinae: Sphodrembas gen. nov. is erected for a single new species, Sphodrembas fumipennis sp. nov. from Kenya and Tanzania. Ectomocoris caccabatus sp. nov. is newly described and represents the first record of the genus from the Korean Peninsula. Chaulioleistes gen. nov. is erected for Peirates singularis Stål, 1874, resulting in Chaulioleistes singularis (Stål, 1874) comb. nov. Isdegardes Distant, 1909, described in Acanthaspidinae (=Reduviinae), is considered a junior synonym of the peiratine genus Phalantus Stål, 1863 syn. nov., resulting in Phalantus melanocephalus (Distant, 1909) comb. nov. for the type species of Isdegardes. Lestomerus wroughtoni Bergroth, 1915 is transferred to Brachysandalus Stål, 1866, resulting in Brachysandalus wroughtoni (Bergroth, 1915) comb. nov. The previously proposed synonymy of Polychitonocoris formosus Miller, 1940 with Calistocoris caesareus Reuter, 1881 is corroborated. All of the above taxonomic acts are supplemented with a key to the species of Calistocoris, a key to the species of Pachysandalus, and a key to the peiratine genera of the Old World. Also reported are thirteen new country records for eleven other species: Brachysandalus bicolor (Villiers, 1948) (Kenya, Tanzania); Ectomocoris bimaculatus Schouteden, 1909 (Ghana); Ectomocoris fenestratus (Klug, 1830) (Ghana); Ectomocoris maculicrus (Fairmaire, 1858) (Uganda, Zimbabwe); Lestomerus affinis (Audinet-Serville, 1831) (Malaysia); Lestomerus basilewskyi Villiers, 1962 (Kenya); Lestomerus bicolor (Villiers, 1948) (Kenya); Lestomerus dubius Villiers, 1948 (Cameroon); Pachysandalus schoutedeni Villiers, 1962 (Sudan); Peirates collarti Schouteden, 1931 (Cameroon); Peirates quadrinotatus (Fabricius, 1798) (Malaysia); and Phalantus africanus Stål, 1874 (Ghana).
  18. Putsathit P, Neela VK, Joseph NMS, Ooi PT, Ngamwongsatit B, Knight DR, et al.
    Vet Microbiol, 2019 Oct;237:108408.
    PMID: 31585650 DOI: 10.1016/j.vetmic.2019.108408
    Information on the epidemiology of C. difficile infection (CDI) in South-East Asian countries is limited, as is data on possible animal reservoirs of C. difficile in the region. We investigated the prevalence and molecular epidemiology of C. difficile in piglets and the piggery environment in Thailand and Malaysia. Piglet rectal swabs (n = 224) and piggery environmental specimens (n = 23) were collected between 2015 and 2016 from 11 farms located in Thailand and Malaysia. All specimens were tested for the presence of C. difficile with toxigenic culture. PCR assays were performed on isolates to determine the ribotype (RT), and the presence of toxin genes. Whole genome sequencing was used on a subset of isolates to determine the evolutionary relatedness of RT038 (the most prevalent RT identified) common to pigs and humans from Thailand and Indonesia. C. difficile was recovered from 35% (58/165) and 92% (54/59) of the piglets, and 89% (8/9) and 93% (13/14) of the environmental specimens from Thailand and Malaysia, respectively. All strains from Thailand, and 30 strains from Malaysia (23 piglet and 7 environmental isolates) were non-toxigenic. To our knowledge, this is the first and only report with a complete lack of toxigenic C. difficile among piglets, a feature which could have a protective effect on the host. The most common strain belonged to RT038 (ST48), accounting for 88% (51/58) of piglet and 78% (7/9) of environmental isolates from Thailand, and all 30 isolates tested from Malaysia. Piglet RT038 isolates from Thailand and Malaysia differed by only 18 core-genome single nucleotide variants (cgSNVs) and both were, on average, 30 cgSNVs different from the human strains from Thailand and Indonesia, indicating a common ancestor in the last two decades.
  19. Goodson ML, Smith DR, Thomson PJ
    J Oral Pathol Med, 2019 Sep;48(8):662-668.
    PMID: 31125457 DOI: 10.1111/jop.12881
    BACKGROUND: Nomograms are graphical calculating devices used to predict risk of malignant transformation (MT) or response to treatment during cancer management. To date, a nomogram has not been used to predict clinical outcome during oral potentially malignant disorder (PMD) treatment. The aim of this study was to create a nomogram for use by clinicians to predict the probability of MT, thereby facilitating accurate assessment of risk and objective decision-making during individual patient management.

    METHODS: Clinico-pathological data from a previously treated cohort of 590 newly presenting PMD patients were reviewed and clinical outcomes categorized as disease free, persistent PMD or MT. Multiple logistic regression was used to predict the probability of MT in the cohort using age, gender, lesion type, site and incision biopsy histopathological diagnoses. Internal validation and calibration of the model was performed using the bootstrap method (n = 1000), and bias-corrected indices of model performance were computed.

    RESULTS: Potentially malignant disorders were predominantly leukoplakias (79%), presenting most frequently at floor of mouth and lateral tongue sites (51%); 99 patients (17%) developed oral squamous cell carcinoma during the study period. The nomogram performed well when MT predictions were compared with patient outcome data, demonstrating good bias-corrected discrimination and calibration (Dxy  = 0.58; C = 0.790), with a sensitivity of 87% and specificity 63%, and a positive predictive value of 32% and negative predictive value 96%.

    CONCLUSION: The "Newcastle Nomogram" has been developed to predict the probability of MT in PMD, based on an internally validated statistical model. Based upon readily available and patient-specific clinico-pathological data, it provides clinicians with a pragmatic diagrammatic aid for clinical decision-making during diagnosis and management of PMD.

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