Immune complex relay by subcapsular sinus macrophages and noncognate B cells drives antibody affinity maturation.

Subcapsular sinus (SCS) macrophages capture antigens from lymph and present them intact for B cell encounter and follicular delivery. However, the properties of SCS macrophages are poorly defined. Here we show SCS macrophage development depended on lymphotoxin-alpha1beta2, and the cells had low lysosomal enzyme expression and retained opsonized antigens on their surface. Intravital imaging revealed immune complexes moving along macrophage processes into the follicle. Moreover, noncognate B cells relayed antigen opsonized by newly produced antibodies from the subcapsular region to the germinal center, and affinity maturation was impaired when this transport process was disrupted. Thus, we characterize SCS macrophages as specialized antigen-presenting cells functioning at the apex of an antigen transport chain that promotes humoral immunity

Sphingosine-1-phosphate receptor 2 restrains egress of γδ T cells from the skin.

Maintenance of a population of IL-17-committed γδ T cells in the dermis is important in promoting tissue immunity. However, the signals facilitating γδ T cell retention within the dermis remain poorly understood. Here, we find that sphingosine-1-phosphate receptor 2 (S1PR2) acts in a cell-intrinsic manner to oppose γδ T cell migration from the dermis to the skin draining lymph node (dLN). Migration of dermal γδ T cells to the dLN under steady-state conditions occurs in an S1PR1-dependent manner. S1PR1 and CD69 are reciprocally expressed on dermal γδ T cells, with loss of CD69 associated with increased S1PR1 expression and enhanced migration to the dLN. γδ T cells lacking both S1PR2 and CD69 are impaired in their maintenance within the dermis. These findings provide a mechanism for how IL-17+ γδ T cells establish residence within the dermis and identify a role for S1PR2 in restraining the egress of tissue-resident lymphocytes

"You Know You Are Sick, Why Do You Carry A Pregnancy Again?" Applying the Socio-Ecological Model to Understand Barriers to PMTCT Service Utilization in Western Kenya.

ObjectiveThroughout most of sub-Saharan Africa (SSA), prevention of mother-to-child transmission (PMTCT) services are readily available. However, PMTCT programs in SSA have had suboptimal performance compared to other regions of the world. The main objective of this study is to explore the socio-ecological and individual factors influencing the utilization of PMTCT services among HIV-positive pregnant women in western Kenya using a social ecological model as our analytical lens.MethodsData were collected using in-depth interviews with 33 HIV-infected women attending government health facilities in rural western Kenya. Women with HIV-infected infants aged between 6 weeks to 6 months with a definitive diagnosis of HIV in the infant, as well as those with an HIV-negative test result in the infant were interviewed between November 2012 and June 2013. Coding and analysis of the transcripts followed grounded theory tenets. Coding reports were discussed in a series of meetings held among the authors. We then employed constant comparative analysis to discover dominant individual, family, society and structural determinants of PMTCT use.ResultsBarriers to women's utilization of PMTCT services fell within the broad constructs of the socio-ecological model of individual, family, society and structural determinants. Several themes cut across the different steps of PMTCT cascade and relate to different constructs of the socio-ecological model. These themes include: self-motivation, confidence and resilience, family support, absence or reduced stigma, right provider attitude and quality of health services provided. We also found out that these factors ensured enhanced maternal health and HIV negative children.ConclusionThe findings of this study suggest that a woman's social environment is an important determinant of MTCT. PMTCT Interventions must comprehensively address multiple factors across the different ecological levels. More research is however required for the development of multi-component interventions that combine strategies at different ecological levels

Nesting Behavior of Palila, as Assessed from Video Recordings

We quantified nesting behavior of Palila (Loxioides bailleui), an endangered Hawaiian honeycreeper, by recording at nests during three breeding seasons using a black-and-white video camera connected to a videocassette recorder. A total of seven nests was observed. We measured the following factors for daylight hours: percentage of time the female was on the nest (attendance), length of attendance bouts by the female, length of nest recesses, and adult provisioning rates. Comparisons were made between three stages of the 40-day nesting cycle: incubation (day 1–day 16), early nestling stage (day 17–day 30 [i.e., nestlings ≤ 14 days old]), and late nestling stage (day 31–day 40 [i.e., nestlings \u3e 14 days old]). Of seven nests observed, four fledged at least one nestling and three failed. One of these failed nests was filmed being depredated by a feral cat (Felis catus). Female nest attendance was near 82% during the incubation stage and decreased to 21% as nestlings aged. We did not detect a difference in attendance bout length between stages of the nesting cycle. Mean length of nest recesses increased from 4.5 min during the incubation stage to over 45 min during the late nestling stage. Mean number of nest recesses per hour ranged from 1.6 to 2.0. Food was delivered to nestlings by adults an average of 1.8 times per hour for the early nestling stage and 1.5 times per hour during the late nestling stage and did not change over time. Characterization of parental behavior by video had similarities to but also key differences from findings taken from blind observations. Results from this study will facilitate greater understanding of Palila reproductive strategies

Analysis of Emergency Department Use In Maine: A Study Conducted on Behalf of the Emergency Department Use Work Group of the Maine Advisory Council on Health System Development

This report presents additional statewide analysis of emergency department (ED) utilization and also the results of a comparative analysis of six health service areas in Maine, three selected for above average rates of emergency department visits, and three selected for below average rates of emergency department visits

Exploring Women’s Oxytocin Responses to Interactions With Their Pet Cats

Background. Extensive research has evaluated the involvement of the neuropeptide oxytocin (OT) in human social behaviors, including parent-infant relationships. Studies have investigated OT’s connection to human attachment to nonhuman animals, with the majority of the literature focusing on domestic dogs (Canis lupis familiaris). Utilizing what is known about OT and its role in maternal-infant and human-dog bonding, we apply these frameworks to the study of human-domestic cat (Felis catus) interactions. Methods. We investigated changes in salivary OT levels in 30 U.S. women of reproductive age before and after two conditions: reading a book (control) and interacting with their pet cat. Participant and cat behavioral patterns during the cat interaction condition were also quantified to determine if differences in women’s OT concentrations were associated with specific human and cat behaviors. Results. Our results revealed no changes in women’s OT levels during the cat interaction, relative to the control condition, and pre-cat interaction OT levels. However, differences in women’s OT concentrations were correlated with some human-cat interactions (e.g., positively with petting cat and cat approach initiation, negatively with cat agonistic behavior) but not all observed behaviors (e.g., use of gentle or baby voice) coded during human-cat interactions. Discussion. This study is the first to explore women’s OT in response to interactions with their pet cat and has identified distinct human and cat behaviors that influence OT release in humans

Emergency supply of prescription-only medicines to patients by community pharmacists: a mixed methods evaluation incorporating patient, pharmacist and GP perspectives

Objective To evaluate and inform emergency supply of prescription-only medicines by community pharmacists (CPs), including how the service could form an integral component of established healthcare provision to maximise adherence. Design Mixed methods. 4 phases: prospective audit of emergency supply requests for prescribed medicines (October–November 2012 and April 2013); interviews with CPs (February–April 2013); follow-up interviews with patients (April–May 2013); interactive feedback sessions with general practice teams (October–November 2013). Setting 22 community pharmacies and 6 general practices in Northwest England. Participants 27 CPs with experience of dealing with requests for emergency supplies; 25 patients who received an emergency supply of a prescribed medicine; 58 staff at 6 general practices. Results Clinical audit in 22 pharmacies over two 4-week periods reported that 526 medicines were requested by 450 patients. Requests peaked over a bank holiday and around weekends. A significant number of supplies were made during practice opening hours. Most requests were for older patients and for medicines used in long-term conditions. Difficulty in renewing repeat medication (forgetting to order, or prescription delays) was the major reason for requests. The majority of medicines were ‘loaned’ in advance of a National Health Service (NHS) prescription. Interviews with CPs and patients indicated that continuous supply had a positive impact on medicines adherence, removing the need to access urgent care. General practice staff were surprised and concerned by the extent of emergency supply episodes. Conclusions CPs regularly provide emergency supplies to patients who run out of their repeat medication, including during practice opening hours. This may aid adherence. There is currently no feedback loop, however, to general practice. Patient care and interprofessional communication may be better served by the introduction of a formally structured and funded NHS emergency supply service from community pharmacies, with ongoing optimisation of repeat prescribing

Quantifying and resolving multiple vector transformants in S. cerevisiae plasmid libraries

<p>Abstract</p> <p>Background</p> <p>In addition to providing the molecular machinery for transcription and translation, recombinant microbial expression hosts maintain the critical genotype-phenotype link that is essential for high throughput screening and recovery of proteins encoded by plasmid libraries. It is known that <it>Escherichia coli </it>cells can be simultaneously transformed with multiple unique plasmids and thusly complicate recombinant library screening experiments. As a result of their potential to yield misleading results, bacterial multiple vector transformants have been thoroughly characterized in previous model studies. In contrast to bacterial systems, there is little quantitative information available regarding multiple vector transformants in yeast. <it>Saccharomyces cerevisiae </it>is the most widely used eukaryotic platform for cell surface display, combinatorial protein engineering, and other recombinant library screens. In order to characterize the extent and nature of multiple vector transformants in this important host, plasmid-born gene libraries constructed by yeast homologous recombination were analyzed by DNA sequencing.</p> <p>Results</p> <p>It was found that up to 90% of clones in yeast homologous recombination libraries may be multiple vector transformants, that on average these clones bear four or more unique mutant genes, and that these multiple vector cells persist as a significant proportion of library populations for greater than 24 hours during liquid outgrowth. Both vector concentration and vector to insert ratio influenced the library proportion of multiple vector transformants, but their population frequency was independent of transformation efficiency. Interestingly, the average number of plasmids born by multiple vector transformants did not vary with their library population proportion.</p> <p>Conclusion</p> <p>These results highlight the potential for multiple vector transformants to dominate yeast libraries constructed by homologous recombination. The previously unrecognized prevalence and persistence of multiply transformed yeast cells have important implications for yeast library screens. The quantitative information described herein should increase awareness of this issue, and the rapid sequencing approach developed for these studies should be widely useful for identifying multiple vector transformants and avoiding complications associated with cells that have acquired more than one unique plasmid.</p

Hilbert Series for Flavor Invariants of the Standard Model

The Hilbert series is computed for the lepton flavor invariants of the Standard Model with three generations including the right-handed neutrino sector needed to generate light neutrino masses via the see-saw mechanism. We also compute the Hilbert series of the quark flavor invariants for the case of four generations.Comment: 6 page