Application of support vector machines for T-cell epitopes prediction

Motivation: The T-cell receptor, a major histocompatibility complex (MHC) molecule, and a bound antigenic peptide, play major roles in the process of antigen-specific T-cell activation. T-cell recognition was long considered exquisitely specific. Recent data also indicate that it is highly flexible, and one receptor may recognize thousands of different peptides. Deciphering the patterns of peptides that elicit a MHC restricted T-cell response is critical for vaccine development. Results: For the first time we develop a support vector machine (SVM) for T-cell epitope prediction with an MHC type I restricted T-cell clone. Using cross-validation, we demonstrate that SVMs can be trained on relatively small data sets to provide prediction more accurate than those based on previously published methods or on MHC binding. Supplementary information: Data for 203 synthesized peptides is available at http://linus.nci.nih.gov/Data/LAU203_Peptide.pd

Perinatal Group B Streptococcal Disease Prevention, Minnesota

In 2002, revised guidelines for preventing perinatal group B streptococcal disease were published. In 2002, all Minnesota providers surveyed reported using a prevention policy. Most screen vaginal and rectal specimens at 34–37 weeks of gestation. The use of screening-based methods has increased dramatically since 1998

Pre-Exposure to an Electrical Stimulus Primes Associative Pairing of Audio and Electrical Stimuli for Dairy Heifers in a Virtual Fencing Feed Attractant Trial

This experiment examined whether pre-exposure to an electrical stimulus from electric fencing attenuates associative pairing of audio and electrical stimuli in dairy heifers. Two treatments were applied to 30 weaned heifers naive to electric fencing. Heifers in the ‘electric-fence’ treatment were exposed to an electrified perimeter fence and two periods of strip-grazing using electrified poly-wire. Control heifers remained naïve to electric fencing. The pairing of audio and electrical stimuli was assessed in a feed attractant trial using manually controlled training collars. Heifers received an audio stimulus (2 s; 84 dB) when they breached a virtual fence after which a short electrical stimulus (0.5 s; 120 mW) was administered if they continued to move forward. If the animal stopped moving forward no further stimuli were applied. By the third training session, electric-fence heifers received a lower proportion of electrical stimuli than control heifers (p = 0.03). The more exploratory interactions a heifer had with the electric fence, the lower the proportion of electrical stimuli she received during training (rs = −0.77, p = 0.002). We conclude that experience with electrical fencing enhanced the salience of the electrical stimulus delivered by manual collars used for virtual fence training

Broad-Range Bacterial Detection and the Analysis of Unexplained Death and Critical Illness

Broad-range rDNA polymerase chain reaction (PCR) provides an alternative, cultivation-independent approach for identifying pathogens. In 1995, the Centers for Disease Control and Prevention initiated population-based surveillance for unexplained life-threatening infections (Unexplained Death and Critical Illness Project [UNEX]). To address the causes of UNEX cases, we examined 59 specimens from 46 cases by using broad-range bacterial 16S rDNA PCR and phylogenetic analysis of amplified sequences. Specimens from eight cases yielded sequences from Neisseria meningitidis (cerebrospinal fluid from two patients with meningitis), Streptococcus pneumoniae (cerebrospinal fluid from one patient with meningitis and pleural fluid from two patients with pneumonia), or Stenotrophomonas maltophilia (bone marrow aspirate from one patient with pneumonia). Streptococcus pneumoniae rDNA sequence microheterogeneity was found in one pleural fluid specimen, suggesting the presence of multiple strains. In conclusion, known bacterial pathogens cause some critical illnesses and deaths that fail to be explained with traditional diagnostic methods

Evaluation of Surveillance Methods for Staphylococcal Toxic Shock Syndrome

We compared passive surveillance and International Classification of Diseases, 9th Revision, codes for completeness of staphylococcal toxic shock syndrome (TSS) surveillance in the Minneapolis–St. Paul area, Minnesota, USA. TSS-specific codes identified 55% of cases compared with 30% by passive surveillance and were more sensitive (p = 0.0005, McNemar χ2 12.25)

Degeneracy of Antigen Recognition as the Molecular Basis for the High Frequency of Naive A2/Melan-A Peptide Multimer+ CD8+ T Cells in Humans

In contrast with the low frequency of most single epitope reactive T cells in the preimmune repertoire, up to 1 of 1,000 naive CD8+ T cells from A2+ individuals specifically bind fluorescent A2/peptide multimers incorporating the A27L analogue of the immunodominant 26–35 peptide from the melanocyte differentiation and melanoma associated antigen Melan-A. This represents the only naive antigen-specific T cell repertoire accessible to direct analysis in humans up to date. To get insight into the molecular basis for the selection and maintenance of such an abundant repertoire, we analyzed the functional diversity of T cells composing this repertoire ex vivo at the clonal level. Surprisingly, we found a significant proportion of multimer+ clonotypes that failed to recognize both Melan-A analogue and parental peptides in a functional assay but efficiently recognized peptides from proteins of self- or pathogen origin selected for their potential functional cross-reactivity with Melan-A. Consistent with these data, multimers incorporating some of the most frequently recognized peptides specifically stained a proportion of naive CD8+ T cells similar to that observed with Melan-A multimers. Altogether these results indicate that the high frequency of Melan-A multimer+ T cells can be explained by the existence of largely cross-reactive subsets of naive CD8+ T cells displaying multiple specificities

Experience with telemedicine among rheumatology clinicians during the COVID-19 pandemic: an international survey

Objective: The aim was to assess rheumatology clinicians' perceptions of telemedicine and their experiences before and during the coronavirus disease 2019 (COVID-19) pandemic. Methods: We conducted a cross-sectional online survey and collected responses from rheumatology clinicians worldwide, between November 2020 and February 2021, regarding use and perceptions of telemedicine in rheumatology. We summarized data with descriptive statistics and qualitative analysis for free-text responses. Results: The survey was completed by 349 rheumatology clinicians from 49 countries; 59% were female and about two-thirds were in the 30-50 years age group. Academic affiliations were held by 55% of participants, and 44% were from North America. Before the pandemic, 24% of participants had experience with telemedicine, whereas about three-quarters used telemedicine for the first time during the pandemic. Overall, 56% thought they provided less adequate care with telemedicine. More than half of clinicians felt that telemedicine was adequate for evaluating crystalline arthritis, inflammatory arthritis and lupus flares. Telemedicine was felt to be inadequate for flares of myositis, vasculitis and scleroderma. Technical problems were reported in 29% of telemedicine encounters and were most commonly related to patient-encountered difficulties. Conclusion: Most rheumatology clinicians used telemedicine for the first time during the pandemic. The quality of care provided was thought to be inferior to that provided in person for specific clinical situations. Additional efforts are needed to address barriers to effective telemedicine, such as patient-related technology issues, challenges with building rapport and performing a physical examination, and to define the appropriate scope of clinical scenarios conducive to telemedicine