The respiratory syncytial virus fusion protein-specific B cell receptor repertoire reshaped by post-fusion subunit vaccination

Respiratory syncytial virus (RSV) is the major cause of acute lower respiratory illness in children of less than 5 years of age which usually results in hospitalization or even in death. Vaccine development is hampered in consequence of a failed vaccine trial with fatalities in the 1960s. Even though research has been more focused on the RSV fusion protein in its pre-fusion conformation, maternal vaccination with post-fusion protein (post F) was considered as a promising vaccine strategy for passive immunization of babies, because post F preserves very potent neutralizing epitopes. We extensively analyzed post F-binding B cell receptor (BCR) repertoires of three vaccinees who received a post F-subunit vaccine in the context of a first-in-human, Phase 1, randomized, observer-blind, placebo-controlled clinical trial (ClinicalTrials.gov Identifier: NCT02298179). In order to compare the vaccine-induced BCR repertoires with BCR repertoires induced by natural infection, we also analyzed pre F- and post F-binding BCRs isolated from a healthy blood donor with relatively high F-binding memory B cell (MBC) frequencies. Analysis of the vaccine-induced repertoires revealed that preferentially V_H4-encoded BCRs were expanded in response to vaccination. Estimation of antigen-driven selection further demonstrated that expanded BCRs accumulated positively selected replacement mutations which substantiated the hypothesis that post F-vaccination induces diversification of V_H4-encoded BCRs in germinal centers. Comparison of the vaccine-induced BCR repertoires with clonally related pre and post F-binding BCRs of the healthy blood donor suggested that the vaccine expanded pre/post F cross-reactive MBCs. Interestingly, several vaccine-induced BCRs shared stereotypic VDJ gene junctions with known neutralizing Abs. Once expressed for functional characterization, the selected monoclonal Abs demonstrated the predicted neutralization activities in plaque reduction neutralization assays indicating that the post F-vaccine induced expansion of neutralizing BCRs.     

Temporal integration as “common currency” of brain and self‐scale‐free activity in resting‐state EEG correlates with temporal delay effects on self‐relatedness

The self is a multifaceted phenomenon that integrates information and experience across multiple time scales. How temporal integration on the psychological level of the self is related to temporal integration on the neuronal level remains unclear. To investigate temporal integration on the psychological level, we modified a well‐established self‐matching paradigm by inserting temporal delays. On the neuronal level, we indexed temporal integration in resting‐state EEG by two related measures of scale‐free dynamics, the power law exponent and autocorrelation window. We hypothesized that the previously established self‐prioritization effect, measured as decreased response times or increased accuracy for self‐related stimuli, would change with the insertion of different temporal delays between the paired stimuli, and that these changes would be related to temporal integration on the neuronal level. We found a significant self‐prioritization effect on accuracy in all conditions with delays, indicating stronger temporal integration of self‐related stimuli. Further, we observed a relationship between temporal integration on psychological and neuronal levels: higher degrees of neuronal integration, that is, higher power‐law exponent and longer autocorrelation window, during resting‐state EEG were related to a stronger increase in the self‐prioritization effect across longer temporal delays. We conclude that temporal integration on the neuronal level serves as a template for temporal integration of the self on the psychological level. Temporal integration can thus be conceived as the “common currency” of neuronal and psychological levels of self.     

A model of event-generated dependence in older adults

Aims and objectives.  The proposed model of event-generated dependence characterizes dependence in older adults as an emergent phenomenon that may arise from interaction between the older adult with compromised health and the social environment, resulting in altered reciprocity.
Background.  Pejorative characterizations of dependence in older adults influence nursing care negatively. Concept analyses recommend the recognition that dependence is interactive in nature, not an inherent trait of the individual, and that dependence involves changes in interpersonal reciprocity.
Conclusions.  The model provides a testable causal path between dependence and psychological outcomes.
Relevance to clinical practice.  The event generated dependence model can sensitize nurses to an alternative view of dependence. It is important for nurses to recognize their role in determining the social environment of care, attend to the promotion of reciprocity with older adults as care is provided, and incorporate changes in their attitudes toward inequitable reciprocity.     

Disentangling Family Life and Hair Pulling: Trichotillomania and Relatedness

ABSTRACT

Trichotillomania (hair pulling) remains a relatively unknown form of body-focused repetitive behavior (BFRB). Sufferers tend to conceal both the action and its effects from others because of stigmatization, which is strong in both public and domestic spheres. Negative responses from close family members can add significantly to the suffering. Based on fieldwork in the United Kingdom and United States, we explore how hair pulling troubles ties even among close family members. We show why ethnographic methods reveal impacts of hair pulling that structured assessments do not yet capture and argue for a more nuanced study of BFRBs through anthropologies of relatedness.     

Unmet core needs for self-determination in HIV-infected women of color in medical care

The levels of satisfaction of the core self-determination needs (relatedness, autonomy and competence) among HIV-infected women of color as well as the association between need fulfillment and patient characteristics were examined. Having less than a high-school education was associated with lowest need satisfaction: autonomy (β?=??1.90; 95%CI?=??3.20, ?0.60), relatedness (β?=??2.70; 95%CI?=??4.30, ?1.10) and competency (β?=??2.50; 95%CI?=??3.60, ?1.30). Each additional point increase in affective symptoms of depression was associated with decrements in need satisfaction (?.61 autonomy, ?.68 relatedness and ?.59 competency). Relatedness satisfaction was lower with higher responses on all three measures of violence (psychological abuse: β?=??0.13, 95%CI?=??0.19 to ?0.07; adult traumatic experiences: β?=??0.24, 95%CI?=??0.35 to ?0.13 and childhood traumatic experiences: β?=??0.24, 95%CI?=??0.40 to ?0.08). Interventions that address core self-determination needs, and the characteristics that influence them, may enhance the motivation for self-care of HIV-infected women.     

The trend of environmental and clinical methicillin-resistant Staphylococcus aureus in a hospital in Taiwan: Impact of USA300

BackgroundThe environment may facilitate transmission of health care-associated methicillin-resistant Staphylococcus aureus (MRSA) and the pathogen is frequently shed by patients. However, the molecular characteristics and genetic relatedness between clinical and environmental MRSA isolates remain largely unclear in the clinical setting.MethodsA total of 100 hospitalized patients with MRSA infection and 25 hospitalized patients without MRSA infection were enrolled in a medical center, Taiwan in 2019. Environmental and clinical MRSA isolates were characterized by antibiotic susceptibility testing and molecular methods.ResultsIn the study, we detected 17 MRSA isolates in the environment that surrounded 15 MRSA-infected patients and one environmental MRSA isolate from one patient without MRSA infection. The molecular analysis revealed a high genetic diversity within either environmental or clinical MRSA isolates, while the USA300 clone (pulsotype AI, SCCmec IV, ST8, PVL-positive) accounts for 39% (7/18) of environmental and 33% (7/21) of clinical MRSA isolates. Moreover, 13 of the 15 MRSA-infected patients had identical paired clinical-environmental MRSA isolates, which exhibited indistinguishable genetic relatedness and highly similar antibiotic susceptibility phenotype, suggesting a possible transmission cycle of MRSA in the hospital.ConclusionsThe environmental MRSA was closely linked to MRSA isolated from patients, suggesting that the environment may act as a reservoir of MRSA. Besides, the USA300 MRSA has become a major clone in the hospital setting. An effective and rigorous approach to environmental cleaning and decontamination is suggested to eradicate MRSA in the hospital.     

Genome-wide patterns of identity-by-descent sharing in the French Canadian founder population

In genetics the ability to accurately describe the familial relationships among a group of individuals can be very useful. Recent statistical tools succeeded in assessing the degree of relatedness up to 6–7 generations with good power using dense genome-wide single-nucleotide polymorphism data to estimate the extent of identity-by-descent (IBD) sharing. It is therefore important to describe genome-wide patterns of IBD sharing for more remote and complex relatedness between individuals, such as that observed in a founder population like Quebec, Canada. Taking advantage of the extended genealogical records of the French Canadian founder population, we first compared different tools to identify regions of IBD in order to best describe genome-wide IBD sharing and its correlation with genealogical characteristics. Results showed that the extent of IBD sharing identified with FastIBD correlates best with relatedness measured using genealogical data. Total length of IBD sharing explained 85% of the genealogical kinship''s variance. In addition, we observed significantly higher sharing in pairs of individuals with at least one inbred ancestor compared with those without any. Furthermore, patterns of IBD sharing and average sharing were different across regional populations, consistent with the settlement history of Quebec. Our results suggest that, as expected, the complex relatedness present in founder populations is reflected in patterns of IBD sharing. Using these patterns, it is thus possible to gain insight on the types of distant relationships in a sample from a founder population like Quebec.     

Leaping in the Dark

The paper describes some of the pathology of seriously disturbed young people. It implies that the residential setting can be designed to accomplish psychotherapy, to which those people would usually be too resistant. Its primary discussion concerns the problem of how changes to the comrnunity-especially changes of leadership-affect the youngsters once they have become necessarily dependent on it. It suggests that the staff group has an essential transitional task, which is to maintain contact wth the residents' emotional world and to withstand the youngsters' increased testing out of the staff's reliability. It describes how dificult it is for staff not to get emotionally embroiled in the residents' issues and how essential good consultancy is to help the staff maintain their professional focus. The paper is optimistic though it emphasises how stessful such changes are.     

Identity by descent estimation with dense genome‐wide genotype data

We present a novel method, IBDLD, for estimating the probability of identity by descent (IBD) for a pair of related individuals at a locus, given dense genotype data and a pedigree of arbitrary size and complexity. IBDLD overcomes the challenges of exact multipoint estimation of IBD in pedigrees of potentially large size and eliminates the difficulty of accommodating the background linkage disequilibrium (LD) that is present in high‐density genotype data. We show that IBDLD is much more accurate at estimating the true IBD sharing than methods that remove LD by pruning SNPs and is highly robust to pedigree errors or other forms of misspecified relationships. The method is fast and can be used to estimate the probability for each possible IBD sharing state at every SNP from a high‐density genotyping array for hundreds of thousands of pairs of individuals. We use it to estimate point‐wise and genomewide IBD sharing between 185,745 pairs of subjects all of whom are related through a single, large and complex 13‐generation pedigree and genotyped with the Affymetrix 500 k chip. We find that we are able to identify the true pedigree relationship for individuals who were misidentified in the collected data and estimate empirical kinship coefficients that can be used in follow‐up QTL mapping studies. IBDLD is implemented as an open source software package and is freely available. Genet. Epidemiol. 2011. © 2011 Wiley‐Liss, Inc. 35: 557‐567, 2011