A study of the social adjustment of a group of first grade children and factors bearing upon that adjustment

Thesis (Ed.M.)--Boston Universit

Anti-CD20 therapy depletes activated myelin-specific CD8+ T cells in multiple sclerosis.

CD8+ T cells are believed to play an important role in multiple sclerosis (MS), yet their role in MS pathogenesis remains poorly defined. Although myelin proteins are considered potential autoantigenic targets, prior studies of myelin-reactive CD8+ T cells in MS have relied on in vitro stimulation, thereby limiting accurate measurement of their ex vivo precursor frequencies and phenotypes. Peptide:MHC I tetramers were used to identify and validate 5 myelin CD8+ T cell epitopes, including 2 newly described determinants in humans. The validated tetramers were used to measure the ex vivo precursor frequencies and phenotypes of myelin-specific CD8+ T cells in the peripheral blood of untreated MS patients and HLA allele-matched healthy controls. In parallel, CD8+ T cell responses against immunodominant influenza epitopes were also measured. There were no differences in ex vivo frequencies of tetramer-positive myelin-specific CD8+ T cells between MS patients and control subjects. An increased proportion of myelin-specific CD8+ T cells in MS patients exhibited a memory phenotype and expressed CD20 compared to control subjects, while there were no phenotypic differences observed among influenza-specific CD8+ T cells. Longitudinal assessments were also measured in a subset of MS patients subsequently treated with anti-CD20 monoclonal antibody therapy. The proportion of memory and CD20+ CD8+ T cells specific for certain myelin but not influenza epitopes was significantly reduced following anti-CD20 treatment. This study, representing a characterization of unmanipulated myelin-reactive CD8+ T cells in MS, indicates these cells may be attractive targets in MS therapy

Primary versus delayed repair for bile duct injuries sustained during cholecystectomy: results of a survey of the Association Francaise de Chirurgie

BACKGROUND: Bile duct injuries (BDIs) sustained during a cholecystectomy still remain a major surgical problem, and it is still not clear whether the injury should be repaired immediately or a delayed repair is preferred. METHODS: A retrospective national French survey was conducted to compare the results of immediate (at time of cholecystectomy), early (within 45 days after a cholecystectomy) and late (beyond 45 days after a cholecystectomy) surgical repair for BDI sustained during a cholecystectomy. RESULTS: Forty-seven surgical centres provided 640 cases of bile duct injury sustained during a cholecystectomy of which 543 were analysed for the purpose of the present study. The timing of repair was immediate in 194 cases (35.7%), early in 216 cases (39.8%) and late in 133 cases (24.5%). The type of repair was a suture repair in 157 cases (81%), and a bilio-digestive reconstruction in 37 cases (19%) for immediate repair; a suture repair in 119 cases (55.1%) and a bilio-digestive anastomosis in 96 cases (44.9%) for the early repair; and a bilio-digestive reconstruction in 129 cases (97%) and a suture repair in 4 cases (3%) for late repair. A second procedure was required in 110 cases (56.7%) for immediate repair, 80 cases (40.7%) for early repair (P < 0.05) and in 9 cases (6.8%) for late repair (P < 0.001). CONCLUSION: The timing of surgical repair for a bile duct injury sustained during a cholecystectomy influences significantly the rate of a second procedure and a late repair should be preferred option

The internal structure of the velvet worm projectile slime : a small-angle scattering study

For prey capture and defense, velvet worms eject an adhesive slime which has been established as a model system for recyclable complex liquids. Triggered by mechanical agitation, the liquid bio‐adhesive rapidly transitions into solid fibers. In order to understand this mechanoresponsive behavior, here, the nanostructural organization of slime components are studied using small‐angle scattering with neutrons and X‐rays. The scattering intensities are successfully described with a three‐component model accounting for proteins of two dominant molecular weight fractions and nanoscale globules. In contrast to the previous assumption that high molecular weight proteins—the presumed building blocks of the fiber core—are contained in the nanoglobules, it is found that the majority of slime proteins exist freely in solution. Only less than 10% of the slime proteins are contained in the nanoglobules, necessitating a reassessment of their function in fiber formation. Comparing scattering data of slime re‐hydrated with light and heavy water reveals that the majority of lipids in slime are contained in the nanoglobules with homogeneous distribution. Vibrating mechanical impact under exclusion of air neither leads to formation of fibers nor alters the bulk structure of slime significantly, suggesting that interfacial phenomena and directional shearing are required for fiber formation

National and Transnational Security Implications of Asymmetric Access to and Use of Biological Data

Biology and biotechnology have changed dramatically during the past 20 years, in part because of increases in computational capabilities and use of engineering principles to study biology. The advances in supercomputing, data storage capacity, and cloud platforms enable scientists throughout the world to generate, analyze, share, and store vast amounts of data, some of which are biological and much of which may be used to understand the human condition, agricultural systems, evolution, and environmental ecosystems. These advances and applications have enabled: (1) the emergence of data science, which involves the development of new algorithms to analyze and visualize data; and (2) the use of engineering approaches to manipulate or create new biological organisms that have specific functions, such as production of industrial chemical precursors and development of environmental bio-based sensors. Several biological sciences fields harness the capabilities of computer, data, and engineering sciences, including synthetic biology, precision medicine, precision agriculture, and systems biology. These advances and applications are not limited to one country. This capability has economic and physical consequences, but is vulnerable to unauthorized intervention. Healthcare and genomic information of patients, information about pharmaceutical and biotechnology products in development, and results of scientific research have been stolen by state and non-state actors through infiltration of databases and computer systems containing this information. Countries have developed their own policies for governing data generation, access, and sharing with foreign entities, resulting in asymmetry of data sharing. This paper describes security implications of asymmetric access to and use of biological data

Sepsis-induced long-term immune paralysis – results of a descriptive, explorative study

Background: Long-lasting impairment of the immune system is believed to be the underlying reason for delayed deaths after surviving sepsis. We tested the hypothesis of persisting changes to the immune system in survivors of sepsis for the first time. Methods: In our prospective, cross-sectional pilot study, eight former patients who survived catecholamine-dependent sepsis and eight control individuals matched for age, sex, diabetes and renal insufficiency were enrolled. Each participant completed a questionnaire concerning morbidities, medications and infection history. Peripheral blood was collected for determination of i) immune cell subsets (CD4+, CD8+ T cells; CD25+ CD127- regulatory T cells; CD14+ monocytes), ii) cell surface receptor expression (PD-1, BTLA, TLR2, TLR4, TLR5, Dectin-1, PD-1 L), iii) HLA-DR expression, and iv) cytokine secretion (IL-6, IL10, TNF-α, IFN-γ) of whole blood stimulated with either α-CD3/28, LPS or zymosan. Results: After surviving sepsis, former patients presented with increased numbers of clinical apparent infections, including those typically associated with an impaired immune system. Standard inflammatory markers indicated a low-level inflammatory situation in former sepsis patients. CD8+ cell surface receptor as well as monocytic HLA-DR density measurements showed no major differences between the groups, while CD4+ T cells tended towards two opposed mechanisms of negative immune cell regulation via PD-1 and BTLA. Moreover, the post-sepsis group showed alterations in monocyte surface expression of distinct pattern recognition receptors; most pronouncedly seen in a decrease of TLR5 expression. Cytokine secretion in response to important activators of both the innate (LPS, zymosan) and the adaptive immune system (α-CD3/28) seemed to be weakened in former septic patients. Conclusions: Cytokine secretion as a reaction to different activators of the immune system seemed to be comprehensively impaired in survivors of sepsis. Among others, this could be based on trends in the downregulation of distinct cell surface receptors. Based on our results, the conduct of larger validation studies seems feasible, aiming to characterize alterations and to find potential therapeutic targets to engage