Combining random mutagenesis, structure-guided design and next-generation sequencing to mitigate polyreactivity of an anti-IL-21R antibody.

Despite substantial technological advances in antibody library and display platform development, the number of approved biotherapeutics from displayed libraries remains limited. , 20-50% of peripheral B cells undergo a process of receptor editing, which modifies the variable and junctional regions of light chains to delete auto-reactive clones. However, antibody evolution relies primarily on interaction with antigen, with no in-built checkpoints to ensure that the selected antibodies have not acquired additional specificities or biophysical liabilities during the optimization process.

Enrichment sampling for a multi-site patient survey using electronic health records and census data.

Objective: We describe a stratified sampling design that combines electronic health records (EHRs) and United States Census (USC) data to construct the sampling frame and an algorithm to enrich the sample with individuals belonging to rarer strata.

Materials And Methods: This design was developed for a multi-site survey that sought to examine patient concerns about and barriers to participating in research studies, especially among under-studied populations (eg, minorities, low educational attainment). We defined sampling strata by cross-tabulating several socio-demographic variables obtained from EHR and augmented with census-block-level USC data.

Public Attitudes toward Consent and Data Sharing in Biobank Research: A Large Multi-site Experimental Survey in the US.

Individuals participating in biobanks and other large research projects are increasingly asked to provide broad consent for open-ended research use and widespread sharing of their biosamples and data. We assessed willingness to participate in a biobank using different consent and data sharing models, hypothesizing that willingness would be higher under more restrictive scenarios. Perceived benefits, concerns, and information needs were also assessed.

Conducting a large, multi-site survey about patients' views on broad consent: challenges and solutions.

Background: As biobanks play an increasing role in the genomic research that will lead to precision medicine, input from diverse and large populations of patients in a variety of health care settings will be important in order to successfully carry out such studies. One important topic is participants' views towards consent and data sharing, especially since the 2011 Advanced Notice of Proposed Rulemaking (ANPRM), and subsequently the 2015 Notice of Proposed Rulemaking (NPRM) were issued by the Department of Health and Human Services (HHS) and Office of Science and Technology Policy (OSTP). These notices required that participants consent to research uses of their de-identified tissue samples and most clinical data, and allowing such consent be obtained in a one-time, open-ended or "broad" fashion.

Validation of a metabolite panel for early diagnosis of type 2 diabetes.

Background: Accurate, early diagnosis of type 2 diabetes (T2D) would enable more effective clinical management and a reduction in T2D complications. Therefore, we sought to identify plasma metabolite and protein biomarkers that, in combination with glucose, can better predict future T2D compared with glucose alone.

Methods: In this case-control study, we used plasma samples from the Bavarian Red Cross Blood Transfusion Center study (61 T2D cases and 78 non-diabetic controls) for discovering T2D-associated metabolites, and plasma samples from the Personalized Medicine Research Project in Wisconsin (56 T2D cases and 445 non-diabetic controls) for validation.

A rural community's involvement in the design and usability testing of a computer-based informed consent process for the Personalized Medicine Research Project.

Many informed consent studies demonstrate that research subjects poorly retain and understand information in written consent documents. Previous research in multimedia consent is mixed in terms of success for improving participants' understanding, satisfaction, and retention. This failure may be due to a lack of a community-centered design approach to building the interventions.

Association between participation in life situations of children with cerebral palsy and their physical, social, and attitudinal environment: a cross-sectional multicenter European study.

Objective: To evaluate how participation of children with cerebral palsy (CP) varied with their environment.

Design: Home visits to children. Administration of Assessment of Life Habits and European Child Environment Questionnaires.

The science of intervention development for type 1 diabetes in childhood: systematic review.

Aim: This paper is a report of a review of the science of intervention development for type 1 diabetes in childhood and its implications for improving health outcomes in children, adolescents, and/or their families.

Background: Previous reviewers have identified insufficient evidence to support the application of effective interventions for type 1 diabetes in clinical practice. The need for quality randomized controlled trials to address shortcomings in previous study designs has been highlighted as a priority for future intervention research.

Narratives of deprivation: Women's life stories around Maori sudden infant death syndrome.

Maori babies in Aotearoa/New Zealand die of Sudden Infant Death Syndrome (SIDS) at over five times the rate of their non-Maori peers. Research and health promotion around modifiable risk factors has produced only a small improvement in this situation since the mid-1990s. This paper reports on life story interviews, conducted between 2002 and 2004, with nineteen mothers of Maori infants who have died of SIDS.

Access of children with cerebral palsy to the physical, social and attitudinal environment they need: a cross-sectional European study.

Purpose: The UN Convention on the Rights of Persons with Disabilities requires states 'to ensure to persons with disabilities access, on an equal basis with others, to the physical environment, transportation, information and communications.' We explored whether this convention was respected for disabled children in Europe.

Method: One thousand one-hundred and seventy-four children aged 8-12 years were randomly selected from population-based registers of children with cerebral palsy in eight European regions.

Hardship, dedication and investment: an exploration of Irish mothers commitment to communicating with their children with cerebral palsy.

This qualitative study investigated the experiences of mothers who have a child with communication difficulties resulting from cerebral palsy (CP). There is a dearth of information about parents' experiences of having a child with CP and communication difficulties. Three participants, whose children had moderate or severe CP and communication difficulties, were recruited from a voluntary organization.

Dyskinetic cerebral palsy in Europe: trends in prevalence and severity.

Objective: To describe the trends for and severity of dyskinetic cerebral palsy in a European collaborative study between cerebral palsy registers, the Surveillance of Cerebral Palsy in Europe (SCPE).

Methods: The prevalence of dyskinetic cerebral palsy was calculated in children born in 1976-1996. Walking ability, accompanying impairments and perinatal adverse events were analysed.

Participation in life situations of 8-12 year old children with cerebral palsy: cross sectional European study.

Objectives: To evaluate how involvement in life situations (participation) in children with cerebral palsy varies with type and severity of impairment and to investigate geographical variation in participation.

Design: Cross sectional study. Trained interviewers visited parents of children with cerebral palsy; multilevel multivariable regression related participation to impairments, pain, and sociodemographic characteristics.

Health status of children with cerebral palsy living in Europe: a multi-centre study.

Aim: The aim of this report is to describe the health status of 8-12-year-old children with cerebral palsy (CP) of all severities in Europe using the Child Health Questionnaire (CHQ).

Method: A total of 818 children with CP from nine centres in defined geographical areas participated. CP type, gross and fine motor function, additional impairments were classified and family data were obtained.

Frequency of participation of 8-12-year-old children with cerebral palsy: a multi-centre cross-sectional European study.

Participation in home, school and community is important for all children; and little is known about the frequency of participation of disabled children. Frequency of participation is a valuable outcome measure for evaluating habilitation programmes for disabled children and for planning social and health services. We investigated how frequency of participation varied between children with cerebral palsy and the general population; and examined variation across countries to understand better how the environmental factors such as legislation, public attitudes and regulation in different countries might influence participation.

Parent-reported quality of life of children with cerebral palsy in Europe.

Objective: The goal was to determine whether the type and severity of the child's impairments and the family's psychosocial, social, and economic characteristics influence parent-reported child quality of life across the spectrum of severity of cerebral palsy.

Methods: Our population-based, cross-sectional survey conducted in 2004 to 2005 involved 818 children with cerebral palsy, 8 to 12 years of age, from 7 countries (9 regions) in Europe. Child quality of life was assessed through parent reports by using the Kidscreen questionnaire, and data were analyzed separately for each of its 10 domains.

Psychological problems in children with cerebral palsy: a cross-sectional European study.

Objectives: To describe psychological symptoms in 8-12-year-old children with cerebral palsy; to investigate predictors of these symptoms and their impact on the child and family.

Design: A cross-sectional multi-centre survey.

Participants: Eight hundred and eighteen children with cerebral palsy, aged 8-12 years, identified from population-based registers of cerebral palsy in eight European regions and from multiple sources in one further region.

Determinants of child-parent agreement in quality-of-life reports: a European study of children with cerebral palsy.

Objectives: The differences between child self-reports and parent proxy reports of quality of life in a large population of children with cerebral palsy were studied. We examined whether child characteristics, severity of impairment, socioeconomic factors, and parental stress were associated with parent proxy reports being respectively higher or lower than child self-reports of quality of life.

Methods: This study was conducted in 2004-2005 and assessed child quality of life (using the Kidscreen questionnaire, 10 domains, each scored 0-100) through self-reports and parent proxy reports of 500 children aged 8 to 12 years who had cerebral palsy and were living in 7 countries in Europe.

Self-reported quality of life of 8-12-year-old children with cerebral palsy: a cross-sectional European study.

Background: Little is known about the quality of life (QoL) of disabled children. We describe self-reported QoL of children with cerebral palsy, factors that influence it, and how it compares with QoL of the general population.

Methods: 1174 children aged 8-12 years were randomly selected from eight population-based registers of children with cerebral palsy in six European countries and 743 (63%) agreed to participate; one further region recruited 75 children from multiple sources.

Assessment of data quality in a multi-centre cross-sectional study of participation and quality of life of children with cerebral palsy.

Background: SPARCLE is a cross-sectional survey in nine European regions, examining the relationship of the environment of children with cerebral palsy to their participation and quality of life. The objective of this report is to assess data quality, in particular heterogeneity between regions, family and item non-response and potential for bias.

Methods: 1,174 children aged 8-12 years were selected from eight population-based registers of children with cerebral palsy; one further centre recruited 75 children from multiple sources.

SCPE work, standardization and definition--an overview of the activities of SCPE: a collaboration of European CP registers.

The main aim of the Surveillance of Cerebral Palsy in Europe (SCPE) network was to develop a central database of cerebral palsy (CP) cases across Europe. Monitoring trends in prevalence rates of CP should contribute to collaborative studies on risk factors or quality of life for children living with CP. A multi-centre collaboration of CP registries used a clear definition of CP to accurately and consistently identify cases of CP.

Discussion groups with parents of children with cerebral palsy in Europe designed to assist development of a relevant measure of environment.

Background: An instrument to measure environmental factors relevant to physically impaired children is being developed in a European context. Preliminary work in England had identified some potentially important themes. Further inquiry was needed to identify issues important in other European countries.

Case gender and severity in cerebral palsy varies with intrauterine growth.

Background: There is an unexplained excess of cerebral palsy among male babies. There is also variation in the proportion of more severe cases by birth weight. It has recently been shown that the rate of cerebral palsy increases as intrauterine size deviates up or down from an optimum about one standard deviation heavier than population mean weight-for-gestation.

Are hospital based notifications enough? Achieving accurate case ascertainment--the Southern Ireland Cerebral Palsy Register (SICPR).

The Southern Ireland Cerebral Palsy Register (SICPR) attempts to identify all cases of cerebral palsy in the Southern Health Board region. Multiple sources of case ascertainment are necessary to achieve a complete register. The aims of the study were to ensure the accuracy of case ascertainment to this register.