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Background Our community-based clinic decided to implement routine screening for anorectal Gonorrhea (GC) and Chlamydia (CT) for patients undergoing HRA for anal cancer prevention, due to high risk for asymptomatic GC and CT among our patient population (predominantly HIV+ MSM in NYC) and the impact undiagnosed GC/CT infection may have on recovery after biopsy or ablation of HPV-related lesions. In 2016, the CDC reported a prevalence of anorectal GC and CT of 0.146% and 0.497% in the general population nationally, and 12.1% and 12.7% in MSM in NYC clinics in the STD Surveillance Network. Methods Retrospective chart review for all HRA completed in 2017 using associated CPT and testing codes. Results 839 HRA procedures were done in 2017. Of the anorectal NAATs performed, 6.6% were positive for either GC and/or CT (4% for GC and 3% for CT). Conclusions Implementing routine screening for anorectal GC/CT at every HRA for HPV-related disease revealed a prevalence of concurrent anorectal GC and/or CT infection well above national prevalence for the general population, though at a lower rate than anorectal GC/CT among MSM seeking screening or treatment in NYC DOH clinics. We were unable to make conclusions about how treating these incidental infections impacted recovery after the procedure, as this was outside the scope of this limited chart review. But the prevalence of GC/CT infection discovered in this analysis supports the importance of adding routine GC/CT screening for all patients undergoing HRA for the diagnosis or treatment of HPV-related anal neoplasia.

A management construct cannot be used effectively by practitioners and researchers if a common agreement on its definition is lacking. Such is the case with the term “supply chain management”—so many definitions are used that there is little consensus on what it means. Thus, the purpose of this paper is to examine the existing research in an effort to understand the concept of “supply chain management.” Various definitions of SCM and “supply chain” are reviewed, categorized, and synthesized. Definitions of supporting constructs of SCM and a framework are then offered to establish a consistent means to conceptualize SCM. Antecedents and consequences of SCM are identified, and the boundaries of SCM in terms of business functions and organizations are proposed. A conceptual model and unified definition of SCM are then presented that indicate the nature, antecedents, and consequences of the phenomena.

Une construction manageriale ne peut pas etre utilisee efficacement par les gestionnaires et les chercheurs si tous ne sont pas d’accord sur sa definition. C’est le cas du terme “Supply Chain Management” (Management de la chaine logistique) - il existe tellement de definitions differentes qu’il y a peu de consensus sur ce qu’il signifie. L’objet de cet article est de faire le point sur la recherche afin de comprendre le concept de SCM. Plusieurs definitions de SCM et de Supply Chain (chaine logistique) sont passes en revue, classees et synthetisees. Des definitions des constructions qui sous-tendent le SCM et un cadre sont proposes afin de conceptualiser le SCM. Apres avoir identifie les conditions et les consequences du SCM, ainsi que les limites en terme de fonctions et d’organisation, les auteurs proposent un modele conceptuel et une definition unifiee du SCM.

We investigated the public T cell response to cytomegalovirus by sequencing rearranged T cell receptors (TCRs) in 640 subjects (287 with & 353 without CMV). We performed an experiment similar to a GWAS study, assessing the concordance of millions of unique TCRs with CMV serostatus, looking for significant associations. With CMV serostatus and TCR sequencing data, we identify 142 public T cell responses to CMV (each with p ≤ 1.0 x 10-4; FDR ≈ 0.20). Using this method to identify public clones, we predict CMV serostatus in a leave-one-out cross-validation experiment with a diagnostic odds ratio of 66. Using HLA typing, we then estimate the HLA-association of each public CMV clone by assessing the over-representation of particular HLA types in associated subjects. Of 142 CMV public clones, 26 were HLA-associated at p < 10-6; no clones were significantly associated with multiple HLA alleles. When comparing our results to the literature, we find substantial concordance; most previously-reported public CMV clones are seen in our data, though only 2 are significantly associated with CMV serostatus in this cohort; both were significantly HLA-associated and in both cases the associated allele confirms previous findings. We demonstrate the validity of association studies using immunosequencing for detection and HLA-association of public T cell responses to infection, and report that assessing the presence of public T cell responses can serve as a powerful diagnostic classifier.

During an acute viral infection T cells specific to viral antigens, as determined by the T-cell receptor (TCR), activate and expand. To determine the breadth of immune response to infection, and to understand recruitment to immunological memory, characterizing the TCR repertoire before, during, and after a model of acute viral infection is necessary. Here we use the yellow fever vaccine (YFV) to model acute viral infection. Blood was collected from 9 subjects at 0, 14, and 90 days after YFV administration. In addition to isolating PBMC for all time points, we sorted for YFV-specific effector T-cells at day 14 and for central and effector memory T-cells in 6 of 9 subjects at day 90. For each sample, gDNA was extracted and the TCR repertoire was assayed by high-throughput TCRβ sequencing. Expanded T cell clones can specifically bind a pathogen-derived epitope (specific), or receive proliferation signals without antigen-specificity (bystander). YFV-specific clones were identified by enrichment in the YFV-specific day 14 sort vs. day 14 PBMC; in each subject, we estimate that the antigen-specific immune response comprises approximately 103 T cell clones. Bystanders were identified as clones expanding from day 0 to day 14 PBMC that are not YFV-specific. Many more YFV-specific clones were recruited to memory at day 90 than bystander clones (40% vs. 3%), indicating that antigen specificity, rather than just proliferation, is a major determinant of memory recruitment.

Immunosequencing is emerging as a new technology with substantial scientific and clinical relevance in immunology, hematology and oncology. Thanks to the highly-randomized somatic rearrangement of antigen receptor genes in lymphocytes, each clonal population of lymphocytes bears a receptor rearrangement that is essentially unique. Thus, sequencing of rearranged antigen receptors in B and T cells can provide a thorough characterization of the diversity and clonal structure of the adaptive immune system. Despite the significant promise of immunosequencing, accurate and consistent methods for data generation and cleaning have proven elusive in practice. Outstanding issues include biased amplification of rearranged antigen receptor genes; computational correction of PCR and sequencing errors in raw sequencing data; alignment of receptor sequences to germline gene receptor loci for accurate reconstruction of rearrangement events; and methods for extrapolation from sequencing reads attributed to each unique rearrangement to absolute input cell numbers. Using a set of robust experiments in which carefully-controlled conditions and synthetic molecules are utilized to precisely determine correct output, we have developed an experimental paradigm and data analysis pipeline that address these concerns and set a new standard for accuracy and data quality in the field of immunosequencing.