A response to “Likelihood ratio as weight of evidence: a closer look” by Lund and Iyer

Recently, Lund and Iyer (L&I) raised an argument regarding the use of likelihood ratios in court. In our view, their argument is based on a lack of understanding of the paradigm. L&I argue that the decision maker should not accept the expert’s likelihood ratio without further consideration. This is agreed by all parties. In normal practice, there is often considerable and proper exploration in court of the basis for any probabilistic statement. We conclude that L&I argue against a practice that does not exist and which no one advocates. Further we conclude that the most informative summary of evidential weight is the likelihood ratio. We state that this is the summary that should be presented to a court in every scientific assessment of evidential weight with supporting information about how it was constructed and on what it was based

Molecular diversity of anthracnose pathogen populations associated with UK strawberry production suggests multiple introductions of three different Colletotrichum species.

Fragaria × ananassa (common name: strawberry) is a globally cultivated hybrid species belonging to Rosaceae family. Colletotrichum acutatum sensu lato (s.l.) is considered to be the second most economically important pathogen worldwide affecting strawberries. A collection of 148 Colletotrichum spp. isolates including 67 C. acutatum s.l. isolates associated with the phytosanitary history of UK strawberry production were used to characterize multi-locus genetic variation of this pathogen in the UK, relative to additional reference isolates that represent a worldwide sampling of the diversity of the fungus. The evidence indicates that three different species C. nymphaeae, C. godetiae and C. fioriniae are associated with strawberry production in the UK, which correspond to previously designated genetic groups A2, A4 and A3, respectively. Among these species, 12 distinct haplotypes were identified suggesting multiple introductions into the country. A subset of isolates was also used to compare aggressiveness in causing disease on strawberry plants and fruits. Isolates belonging to C. nymphaeae, C. godetiae and C. fioriniae representative of the UK anthracnose pathogen populations showed variation in their aggressiveness. Among the three species, C. nymphaeae and C. fioriniae appeared to be more aggressive compared to C. godetiae. This study highlights the genetic and pathogenic heterogeneity of the C. acutatum s.l. populations introduced into the UK linked to strawberry production

Dimensions of Liberal Education at Brockport

Editor: H. Larry Humm (College at Brockport emeritus). Editorial board: Robert W. Strayer (professor emeritus, College at Brockport) ; W. Bruce Leslie, (College at Brockport faculty member) ; Robert S. Getz (professor emeritus, College at Brockport) ; J. Douglas Hickerson (former Director of Student Affairs, College at Brockport), Kenneth L. Jones (former College at Brockport faculty member) ; Charles R. Edwards (professor emeritus, College at Brockport). Also includes chapters by the following emeriti and former faculty members and professionals of The College at Brockport: Donald S. Douglas (former provost), Harold L. Rakov (emeritus), Roger M. Weir (emeritus), Owen S. Ireland (current), Edward J. Gucker (emeritus), Warren Fraleigh (emeritus), Lynn H. Parsons (emeritus), Ian H. Henderson (emeritus), Robert J. Gemmett (emeritus), J. Emory Morris (emeritus), Beth E. VanFossen (former faculty member), Peter L. Marchant (emeritus), Gladdys W. Church (former Director of the Learning Skills Center). An instructional development project of the Educational Communications Center, State University College at Brockport, Brockport, New York. Contents: On coming to college for the first time : Great expectations, yours and ours / Donald S. Douglas -- High school and college, what’s the difference? / Harold L. Rakov -- Living in a college community / Roger M. Weir -- A liberal arts education: what, why and how: The liberating arts and personal freedom / J. Douglas Hickerson -- The liberal arts, preparation for a career / Roger M. Weir -- Liberally educated people, knowing them when you see them: Perspective 1, Gaining knowledge, discipline, and values / Owen S. Ireland -- Perspective 2, Nurturing curiosity, creativity, and commitment / Edward J. Gucker -- Perspective 3, Cultivating freedom / Warren Fraleigh -- Democracy and the liberal arts, Is there a connection? / Lynn H. Parsons -- From Socrates to Brockport, your place in a long tradition / W. Bruce Leslie -- Why study the fine arts? / Ian H. Henderson -- Why study the humanities? / Robert J. Gemmett -- Why study the sciences? / J. Emory Morris -- Why study the social sciences? / Beth E. VanFossen -- More than making it: getting the most out of college : Where am I going? How do I get there? Some thoughts on academic planning / Robert S. Getz -- Thinking about thinking / H. Larry Humm -- How not to be a victim of time, a first letter to an anxious student / Peter L. Marchant -- Reading in college, more than turning pages / Charles R. Edwards -- Going to class-- being there is not enough / H. Larry Humm -- How not to be a victim of essay assignments, a second letter to an anxious student / Peter L. Marchant -- Making the most of tests / Gladdys W. Church.https://digitalcommons.brockport.edu/bookshelf/1328/thumbnail.jp

Potential Genetic Risk Factors for Chronic TMD: Genetic Associations from the OPPERA Case Control Study

Genetic factors play a role in the etiology of persistent pain conditions, putatively by modulating underlying processes such as nociceptive sensitivity, psychological well-being, inflammation, and autonomic response. However, to date, only a few genes have been associated with temporomandibular disorders (TMD). This study evaluated 358 genes involved in pain processes, comparing allelic frequencies between 166 cases with chronic TMD and 1442 controls enrolled in the OPPERA (Orofacial Pain: Prospective Evaluation and Risk Assessment) study cooperative agreement. To enhance statistical power, 182 TMD cases and 170 controls from a similar study were included in the analysis. Genotyping was performed using the Pain Research Panel, an Affymetrix gene chip representing 3295 single nucleotide polymorphisms, including ancestry-informative markers that were used to adjust for population stratification. Adjusted associations between genetic markers and TMD case status were evaluated using logistic regression. The OPPERA findings provided evidence supporting previously-reported associations between TMD and two genes: HTR2A and COMT. Other genes were revealed as potential new genetic risk factors for TMD, including NR3C1, CAMK4, CHRM2, IFRD1, and GRK5. While these findings need to be replicated in independent cohorts, the genes potentially represent important markers of risk for TMD and they identify potential targets for therapeutic intervention

Proximal adductor avulsions are rarely isolated but usually involve injury to the PLAC and pectineus: Descriptive MRI findings in 145 athletes

Purpose The purpose of the study is to review the MRI findings in a cohort of athletes who sustained acute traumatic avulsions of the adductor longus fibrocartilaginous entheses, and to investigate related injuries namely the pyramidalis- anterior pubic ligament - adductor longus complex (PLAC). Associated muscle and soft tissue injuries were also assessed. Methods The MRIs were reviewed for a partial or complete avulsion of the adductor longus fibrocartilage, as well as continuity or separation of the adductor longus from the pyramidalis. The presence of a concurrent partial pectineus tear was noted. Demographic data was analysed. Linear and logistic regression was used to examine associations between injuries. Results The mean age was 32.5 (SD 10.9). The pyramidalis was absent in 3 of 145 patients. 85 of 145 athletes were professional and 52 competed in the football Premier League. 132 had complete avulsions and 13 partial. The adductor longus was in continuity with pyramidalis in 55 athletes, partially separated in seven and completely in 81 athletes. 48 athletes with a PLAC injury had a partial pectineus avulsion. Six types of PLAC injuries patterns were identified. Associated rectus abdominis injuries were rare and only occurred in five patients (3.5%). Conclusion The proximal adductor longus forms part of the PLAC and is rarely an isolated injury. The term PLAC injury is more appropriate term. MRI imaging should assess all the anatomical components of the PLAC post-injury, allowing recognition of the differentpatterns of injury

Quantitative Analysis of Single Nucleotide Polymorphisms within Copy Number Variation

BACKGROUND: Single nucleotide polymorphisms (SNPs) have been used extensively in genetics and epidemiology studies. Traditionally, SNPs that did not pass the Hardy-Weinberg equilibrium (HWE) test were excluded from these analyses. Many investigators have addressed possible causes for departure from HWE, including genotyping errors, population admixture and segmental duplication. Recent large-scale surveys have revealed abundant structural variations in the human genome, including copy number variations (CNVs). This suggests that a significant number of SNPs must be within these regions, which may cause deviation from HWE. RESULTS: We performed a Bayesian analysis on the potential effect of copy number variation, segmental duplication and genotyping errors on the behavior of SNPs. Our results suggest that copy number variation is a major factor of HWE violation for SNPs with a small minor allele frequency, when the sample size is large and the genotyping error rate is 0~1%. CONCLUSIONS: Our study provides the posterior probability that a SNP falls in a CNV or a segmental duplication, given the observed allele frequency of the SNP, sample size and the significance level of HWE testing

The UCSC cancer genomics browser: update 2011

The UCSC Cancer Genomics Browser (https://genome-cancer.ucsc.edu) comprises a suite of web-based tools to integrate, visualize and analyze cancer genomics and clinical data. The browser displays whole-genome views of genome-wide experimental measurements for multiple samples alongside their associated clinical information. Multiple data sets can be viewed simultaneously as coordinated ‘heatmap tracks’ to compare across studies or different data modalities. Users can order, filter, aggregate, classify and display data interactively based on any given feature set including clinical features, annotated biological pathways and user-contributed collections of genes. Integrated standard statistical tools provide dynamic quantitative analysis within all available data sets. The browser hosts a growing body of publicly available cancer genomics data from a variety of cancer types, including data generated from the Cancer Genome Atlas project. Multiple consortiums use the browser on confidential prepublication data enabled by private installations. Many new features have been added, including the hgMicroscope tumor image viewer, hgSignature for real-time genomic signature evaluation on any browser track, and ‘PARADIGM’ pathway tracks to display integrative pathway activities. The browser is integrated with the UCSC Genome Browser; thus inheriting and integrating the Genome Browser’s rich set of human biology and genetics data that enhances the interpretability of the cancer genomics data

Chronic kidney disease and arrhythmias: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Patients with chronic kidney disease (CKD) are predisposed to heart rhythm disorders, including atrial fibrillation (AF)/atrial flutter, supraventricular tachycardias, ventricular arrhythmias, and sudden cardiac death (SCD). While treatment options, including drug, device, and procedural therapies, are available, their use in the setting of CKD is complex and limited. Patients with CKD and end-stage kidney disease (ESKD) have historically been under-represented or excluded from randomized trials of arrhythmia treatment strategies,1 although this situation is changing.2 Cardiovascular society consensus documents have recently identified evidence gaps for treating patients with CKD and heart rhythm disorders [...

Suppression of Lung Adenocarcinoma Progression by Nkx2-1

Despite the high prevalence and poor outcome of patients with metastatic lung cancer the mechanisms of tumour progression and metastasis remain largely uncharacterized. Here we modelled human lung adenocarcinoma, which frequently harbours activating point mutations in KRAS and inactivation of the p53 pathway, using conditional alleles in mice. Lentiviral-mediated somatic activation of oncogenic Kras and deletion of p53 in the lung epithelial cells of Kras[superscript LSL-G12D/+];p53[superscript flox/flox] mice initiates lung adenocarcinoma development4. Although tumours are initiated synchronously by defined genetic alterations, only a subset becomes malignant, indicating that disease progression requires additional alterations. Identification of the lentiviral integration sites allowed us to distinguish metastatic from non-metastatic tumours and determine the gene expression alterations that distinguish these tumour types. Cross-species analysis identified the NK2-related homeobox transcription factor Nkx2-1 (also called Ttf-1 or Titf1) as a candidate suppressor of malignant progression. In this mouse model, Nkx2-1 negativity is pathognomonic of high-grade poorly differentiated tumours. Gain- and loss-of-function experiments in cells derived from metastatic and non-metastatic tumours demonstrated that Nkx2-1 controls tumour differentiation and limitsmetastatic potential in vivo. Interrogation of Nkx2-1-regulated genes, analysis of tumours at defined developmental stages, and functional complementation experiments indicate that Nkx2-1 constrains tumours in part by repressing the embryonically restricted chromatin regulator Hmga2. Whereas focal amplification of NKX2-1 in a fraction of human lung adenocarcinomas has focused attention on its oncogenic function, our data specifically link Nkx2-1 downregulation to loss of differentiation, enhanced tumour seeding ability and increased metastatic proclivity. Thus, the oncogenic and suppressive functions ofNkx2-1 in the sametumourNational Institutes of Health (U.S.) (grant U01-CA84306 )National Institutes of Health (U.S.) (grant K99-CA151968)Howard Hughes Medical InstituteLudwig Center for Molecular OncologyNational Cancer Institute (U.S.) (Cancer Center Support (core) grant P30-CA14051

Multi-ancestry genome-wide association study accounting for gene-psychosocial factor interactions identifies novel loci for blood pressure traits

Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP, taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from five ancestry groups. In the combined meta-analyses of stages 1 and 2, we identified 59 loci (p value < 5e−8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response (PLCL2), synaptic function and neurotransmission (LIN7A and PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5 and CHODL). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations