Explore the vast range of titles available.

Background Unambiguous human leukocyte antigen (HLA) typing is important in transplant matching and disease association studies. High-resolution HLA typing that is not restricted to the peptide-binding region can decrease HLA allele ambiguities. Cost and technology constraints have hampered high-throughput and efficient high resolution unambiguous HLA typing. We have developed a method for HLA genotyping that preserves the very high-resolution that can be obtained by next-generation sequencing (NGS) but also achieves substantially increased efficiency. Unambiguous HLA-A, B, C and DRB1 genotypes can be determined for 96 individuals in a single run of the Illumina MiSeq. Results Long-range amplification of full-length HLA genes from four loci was performed in separate polymerase chain reactions (PCR) using primers and PCR conditions that were optimized to reduce co-amplification of other HLA loci. Amplicons from the four HLA loci of each individual were then pooled and subjected to enzymatic library generation. All four loci of an individual were then tagged with one unique index combination. This multi-locus individual tagging (MIT) method combined with NGS enabled the four loci of 96 individuals to be analyzed in a single 500 cycle sequencing paired-end run of the Illumina-MiSeq. The MIT-NGS method generated sequence reads from the four loci were then discriminated using commercially available NGS HLA typing software. Comparison of the MIT-NGS with Sanger sequence-based HLA typing methods showed that all the ambiguities and discordances between the two methods were due to the accuracy of the MIT-NGS method. Conclusions The MIT-NGS method enabled accurate, robust and cost effective simultaneous analyses of four HLA loci per sample and produced 6 or 8-digit high-resolution unambiguous phased HLA typing data from 96 individuals in a single NGS run.

Antitoxins are needed that can be produced economically with improved safety and shelf life compared to conventional antisera-based therapeutics. Here we report a practical strategy for development of simple antitoxin therapeutics with substantial advantages over currently available treatments. The therapeutic strategy employs a single recombinant 'targeting agent' that binds a toxin at two unique sites and a 'clearing Ab' that binds two epitopes present on each targeting agent. Co-administration of the targeting agent and the clearing Ab results in decoration of the toxin with up to four Abs to promote accelerated clearance. The therapeutic strategy was applied to two Botulinum neurotoxin (BoNT) serotypes and protected mice from lethality in two different intoxication models with an efficacy equivalent to conventional antitoxin serum. Targeting agents were a single recombinant protein consisting of a heterodimer of two camelid anti-BoNT heavy-chain-only Ab V(H) (VHH) binding domains and two E-tag epitopes. The clearing mAb was an anti-E-tag mAb. By comparing the in vivo efficacy of treatments that employed neutralizing vs. non-neutralizing agents or the presence vs. absence of clearing Ab permitted unprecedented insight into the roles of toxin neutralization and clearance in antitoxin efficacy. Surprisingly, when a post-intoxication treatment model was used, a toxin-neutralizing heterodimer agent fully protected mice from intoxication even in the absence of clearing Ab. Thus a single, easy-to-produce recombinant protein was as efficacious as polyclonal antiserum in a clinically-relevant mouse model of botulism. This strategy should have widespread application in antitoxin development and other therapies in which neutralization and/or accelerated clearance of a serum biomolecule can offer therapeutic benefit.

RV144 is the first phase 3 HIV vaccine clinical trial to demonstrate efficacy. This study consisted of more than 8,000 individuals in each arm of the trial, representing the four major regions of Thailand. Human leukocyte antigen (HLA) class I and killer cell immunoglobulin-like receptor (KIR) genes, as well as 96 genome-wide ancestry informative markers (AIMs) were genotyped in 450 placebo HIV-1-uninfected individuals to identify the immunogenetic diversity and population structure of this cohort. High-resolution genotyping identified the common HLA alleles as A*02:03, A*02:07, A*11:01, A*24:02, A*24:07, A*33:03, B*13:01, B*15:02, B*18:01, B*40:01, B*44:03, B*46:01, B*58:01, C*01:02, C*03:02, C*03:04, C*07:01, C*07:02, C*07:04, and C*08:01. The most frequent three-loci haplotype was B*46:01-C*01:02-A*02:07. Framework genes KIR2DL4, 3DL2, and 3DL3 were present in all samples, and KIR2DL1, 2DL3, 3DL1, 2DS4, and 2DP1 occurred at frequencies greater than 90 %. The combined HLA and KIR profile suggests admixture with neighboring Asian populations. Principal component and correspondence analyses comparing the RV144 samples to the phase 3 International HapMap Project (HapMap3) populations using AIMs corroborated these findings. Structure analyses identified a distinct profile in the Thai population that did not match the Asian or other HapMap3 samples. This shows genetic variability unique to Thais in RV144, making it essential to take into account population stratification while performing genetic association studies. The overall analyses from all three genetic markers indicate that the RV144 samples are representative of the Thai population. This will inform subsequent host genetic analyses in the RV144 cohort and provide insight for future genetic association studies in the Thai population.

Botulinum neurotoxin (BoNT) is responsible for causing botulism, a potentially fatal disease characterized by paralysis of skeletal muscle. Existing specific treatments include polyclonal antisera derived from immunized humans or horses. Both preparations have similar drawbacks, including limited supply, risk of adverse effects and batch to batch variation. Here, we describe a panel of six highly protective sheep monoclonal antibodies (SMAbs) derived from sheep immunized with BoNT/A1 toxoid (SMAbs 2G11, 4F7) or BoNT/A1 heavy chain C-terminus (HcC) (SMAbs 1G4, 5E2, 5F7, 16F9) with or without subsequent challenge immunization with BoNT/A1 toxin. Although each SMAb bound BoNT/A1 toxin, differences in specificity for native and recombinant constituents of BoNT/A1 were observed. Structural differences were suggested by pI (5E2 = 8.2; 2G11 = 7.1; 4F7 = 8.8; 1G4 = 7.4; 5F7 = 8.0; 16F9 = 5.1). SMAb protective efficacy vs. 10,000 LD50 BoNT/A1 was evaluated using the mouse lethality assay. Although not protective alone, divalent and trivalent combinations of SMabs, IG4, 5F7 and/or 16F9 were highly protective. Divalent combinations containing 0.5–4 μg/SMAb (1–8 μg total SMAb) were 100% protective against death with only mild signs of botulism observed; relative efficacy of each combination was 1G4 + 5F7 > 1G4 + 16F9 >> 5F7 + 16F9. The trivalent combination of 1G4 + 5F7 + 16F9 at 0.25 μg/SMAb (0.75 μg total SMAb) was 100% protective against clinical signs and death. These results reflect levels of protective potency not reported previously.

The purpose of this study was to describe the reported perceptions of six midwife participants at different stages of their engagement in a multiphase process of adopting a new model of prenatal care. Midwives were interviewed at five different stages during the process of implementing CenteringPregnancy, a model of group prenatal care. The research methodology used in this study was phenomenology. The conceptual framework for exploring the participants' perceptions was based on the Institute for Healthcare Improvement's patient-centered model and on the International Institute for Restorative Practices' empowerment model. The five themes that emerged from the midwives' experiences mirrored the stages of change health education model. Suggestions for the implementation and sustainability of the CenteringPregnancy model of care are provided based on the five themes that emerged from this study's findings.

Adolescent mothers experience many factors that affect their ability to securely attach to their infants and are therefore considered a high-risk population. In addition, infants of adolescent mothers are at an increased risk of developing insecure attachment. FirstPlay@ Therapy Infant Storytelling Massage is an attachment-based, parent-infant adjunctive play therapy model founded on the theoretical underpinning of attachment theory. The current study implemented a one-time intervention with an adolescent mother population in a group home setting. A pretest/postest design was utilized to measure the impact of FirstPlay@ Therapy on the variables of an adolescent mother's level of maternal attachment and comfort with physical touch. Participants in this study (N = 5) were adolescent mothers ages 18-21 years old, who were recruited from four maternity group homes in two counties in South Florida. Five adolescent mothers completed the FirstPlay@ Therapy for pre and posttest data. No significant differences were found in the areas of maternal attachment and predisposition to touch before and 2 weeks after the intervention. There were some significant relationships found among the demographic variables specific to an adolescent mothers' history of employment status and her child welfare history as well as the age of the mother and the age of her infant. In addition, at posttest, a significant relationship was found between the sex of the infant and the total score on the PCAQ. Although no statistically significant findings were presented, recommendations for further research include extending this intervention to a broader population of adolescent mothers across a variety of settings to focus on early infant-attachment relationships. Although further studies are needed to expand on the current one, this study provides insight into the feasibility of teaching infant massage storytelling as a component of a group maternity-home curriculum. The findings of the study can be used to guide the implementation of future attachment intervention research addressing the maternal-attachment relationship with an adolescent mother population.

Nurses are in a unique position to evaluate acute care quality. The authors describe common problems and challenges related to selection of variables and choice of databases for quality evaluations. Practical strategies to address these concerns also are discussed.

This study examined the effect of positive reciprocity, reciprocity based on a sense of the need to repay, as the primary motivator of alumni giving to a 4-year, public flagship institution in the Southeast. It investigated the of role positive experiences, when one was a student at the University, as a primary motivator for alumni donor support. Although the review of existing scholarly literature is limited in information on philanthropy and donor motivation, there have been many popular articles written on and dissertation topics focused on, donor behavior (i.e., why people give). Likewise, there have been many studies conducted to test reciprocity theory. However, there have been relatively few, if any, studies testing the reciprocity theory as a motivation for donor behavior. Therefore, it was important to examine the role of positive reciprocity to better understand its influence on donor behavior. Regardless of the findings of studies on motivation, all of the literature suggested that determining and understanding the motivators for charitable givers is an important element in the success of fundraising. It is not uncommon to hear donors cite repeatedly that their contributions were based on their desire to \"give back\" to their institutions. This concept of \"giving back\" is central to the importance of reciprocity as a motive for giving. Understanding which donors possess this philanthropic value can be central to an institution's ability to increase significantly charitable giving. The researcher used a qualitative method of one-on-one interviews with an interview protocol. The interview protocol was designed for open-ended questions to elicit responses about the influence of reciprocity as a motivator for major gift contributions by alumni. Findings indicated reciprocity is a substantial motivator for alumni giving. The findings of this study determined that positive reciprocity does, in fact, have an impact on donor motivation. By using the information in this study, institutions of higher education may be able to develop and implement more targeted, successful fundraising strategies that should increase their amount of charitable contributions from alumni.

Health care organizations are under increasing demands to demonstrate the level of quality in the services they provide from federal, state, regulatory agencies and third party payers. Most healthcare organizations are ill equipped to handle these demands due to the costs in time and manpower needed to retrieve data from health care databases. The medical record is considered a ‘gold standard’ of clinical databases in health care due to the breadth and depth of clinically relevant data. Data from the electronic medical record (EMR) are often required to demonstrate quality of health care services, although these data are difficult to retrieve without incurring the costs related to the traditional method of manual data retrieval. Natural language processing (NLP) presents a framework for understanding and retrieving narrative data from the medical record. Based on concepts of semantics and syntax of language, this framework provides a means for organizing data retrieval using an automated software technology. The study method incorporated principles of NLP to guide the automated retrieval of quality of care data from electronic medical records. The purpose of the study was to evaluate the efficiency and effectiveness of the study NLP method, as well as test the reliability and validity of the retrieved data compared to manual retrieval of the same data. The study NLP method used a qualitative software program (Nudist) to retrieve and code narrative quality of care data from the EMR. The study NLP method performed with acceptable reliability (.73) when the narrative variables were documented in a consistent format in the EMR. The format of the EMR and consistent narrative format of the documented variables were key factors related to accurate data retrieval using the study NLP system. Although the study NLP method did not perform as well as manual data retrieval in terms of efficiency and accuracy, subsequent trials with the study NLP method data may demonstrate levels of efficiency and reliability to rival manual data retrieval methods. This study demonstrated the potential usefulness of NLP in the retrieval of quality of care data from the EMR.