The Hankie Probe: A Materialistic Approach to Mobile UX Research

Mobile user experience (UX) research can benefit from unexplored opportunities from theory and practice. Contemporary sociology has developed sophisticated understandings of mobilities that can expand the scope of mobile HCI research. At the same time, we need to extend the scope of mobile experience beyond its current main foci on the portable device and moments of experience. We report the interim results of exploratory pilot studies of a fabric based probe that has been developed to extend the scope of mobile experience research both theoretically and in the range of insights that can be collected in mobile user studies. We report our initial experiences with a 'hankie' (handkerchief) probe that aims to gather rich usage and experience insights for early stages of design

Episomal Viral cDNAs Identify a Reservoir That Fuels Viral Rebound after Treatment Interruption and That Contributes to Treatment Failure

Viral reservoirs that persist in HIV-1 infected individuals on antiretroviral therapy (ART) are the major obstacle to viral eradication. The identification and definition of viral reservoirs in patients on ART is needed in order to understand viral persistence and achieve the goal of viral eradication. We examined whether analysis of episomal HIV-1 genomes provided the means to characterize virus that persists during ART and whether it could reveal the virus that contributes to treatment failure in patients on ART. For six individuals in which virus replication was highly suppressed for at least 20 months, proviral and episomal genomes present just prior to rebound were phylogenetically compared to RNA genomes of rebounding virus after therapy interruption. Episomal envelope sequences, but not proviral envelope sequences, were highly similar to sequences in rebounding virus. Since episomes are products of recent infections, the phylogenetic relationships support the conclusion that viral rebound originated from a cryptic viral reservoir. To evaluate whether the reservoir revealed by episomal sequence analysis was of clinical relevance, we examined whether episomal sequences define a viral population that contributes to virologic failure in individuals receiving the CCR5 antagonist, Vicriviroc. Episomal envelope sequences at or near baseline predicted treatment failure due to the presence of X4 or D/M (dual/mixed) viral variants. In patients that did not harbor X4 or D/M viruses, the basis for Vicriviroc treatment failure was indeterminate. Although these samples were obtained from viremic patients, the assay would be applicable to a large percentage of aviremic patients, based on previous studies. Summarily, the results support the use of episomal HIV-1 as an additional or alternative approach to traditional assays to characterize virus that is maintained during long-term, suppressive ART

Programmed Death-1 Expression on Epstein Barr Virus Specific CD8+ T Cells Varies by Stage of Infection, Epitope Specificity, and T-Cell Receptor Usage

BACKGROUND: Programmed Death-1 (PD-1) is an inhibitory member of the CD28 family of molecules expressed on CD8+ T cells in response to antigenic stimulation. To better understand the role of PD-1 in antiviral immunity we examined the expression of PD-1 on Epstein-Barr virus (EBV) epitope-specific CD8+ T cells during acute infectious mononucleosis (AIM) and convalescence. METHODOLOGY/PRINCIPAL FINDINGS: Using flow cytometry, we observed higher frequencies of EBV-specific CD8+ T cells and higher intensity of PD-1 expression on EBV-specific CD8+ T cells during AIM than during convalescence. PD-1 expression during AIM directly correlated with viral load and with the subsequent degree of CD8+ T cell contraction in convalescence. Consistent differences in PD-1 expression were observed between CD8+ T cells with specificity for two different EBV lytic antigen epitopes. Similar differences were observed in the degree to which PD-1 was upregulated on these epitope-specific CD8+ T cells following peptide stimulation in vitro. EBV epitope-specific CD8+ T cell proliferative responses to peptide stimulation were diminished during AIM regardless of PD-1 expression and were unaffected by blocking PD-1 interactions with PD-L1. Significant variability in PD-1 expression was observed on EBV epitope-specific CD8+ T cell subsets defined by V-beta usage. CONCLUSIONS/SIGNIFICANCE: These observations suggest that PD-1 expression is not only dependent on the degree of antigen presentation, but also on undefined characteristics of the responding cell that segregate with epitope specificity and V-beta usage

Episomal Viral cDNAs Identify a Reservoir That Fuels Viral Rebound after Treatment Interruption and That Contributes to Treatment Failure

Viral reservoirs that persist in HIV-1 infected individuals on antiretroviral therapy (ART) are the major obstacle to viral eradication. The identification and definition of viral reservoirs in patients on ART is needed in order to understand viral persistence and achieve the goal of viral eradication. We examined whether analysis of episomal HIV-1 genomes provided the means to characterize virus that persists during ART and whether it could reveal the virus that contributes to treatment failure in patients on ART. For six individuals in which virus replication was highly suppressed for at least 20 months, proviral and episomal genomes present just prior to rebound were phylogenetically compared to RNA genomes of rebounding virus after therapy interruption. Episomal envelope sequences, but not proviral envelope sequences, were highly similar to sequences in rebounding virus. Since episomes are products of recent infections, the phylogenetic relationships support the conclusion that viral rebound originated from a cryptic viral reservoir. To evaluate whether the reservoir revealed by episomal sequence analysis was of clinical relevance, we examined whether episomal sequences define a viral population that contributes to virologic failure in individuals receiving the CCR5 antagonist, Vicriviroc. Episomal envelope sequences at or near baseline predicted treatment failure due to the presence of X4 or D/M (dual/mixed) viral variants. In patients that did not harbor X4 or D/M viruses, the basis for Vicriviroc treatment failure was indeterminate. Although these samples were obtained from viremic patients, the assay would be applicable to a large percentage of aviremic patients, based on previous studies. Summarily, the results support the use of episomal HIV-1 as an additional or alternative approach to traditional assays to characterize virus that is maintained during long-term, suppressive ART

Alterations in HIV-1 LTR promoter activity during AIDS progression

AbstractHIV-1 variants evolving in AIDS patients frequently show increased replicative capacity compared to those present during early asymptomatic infection. It is known that late stage HIV-1 variants often show an expanded coreceptor tropism and altered Nef function. In the present study we investigated whether enhanced HIV-1 LTR promoter activity might also evolve during disease progression. Our results demonstrate increased LTR promoter activity after AIDS progression in 3 of 12 HIV-1-infected individuals studied. Further analysis revealed that multiple alterations in the U3 core-enhancer and in the transactivation-response (TAR) region seem to be responsible for the enhanced functional activity. Our findings show that in a subset of HIV-1-infected individuals enhanced LTR transcription contributes to the increased replicative potential of late stage virus isolates and might accelerate disease progression

Short-term prospective memory deficits in chronic back pain patients

Objective: Chronic pain, particularly low back pain, is widespread. Although a great deal is known about the impact that this has on quality of life and physical activity, relatively little has been established regarding the more cognitive effects of pain. This study aims to find out whether individuals with chronic pain experience memory deficits in prospective memory (PM), the process of remembering to do things at some future point in time. Examples of PM include remembering to keep an appointment, such as a visit to a clinic, or to perform a particular task, such as paying a bill on time. Methods: The PM of 50 participants with chronic pain was compared with 50 pain-free participants. Each participant completed the Prospective Memory Questionnaire, which assesses three aspects of prospective memory (short-term habitual, long-term episodic, and internally cued), and records the use of strategies to aid remembering. Results: In comparison to those not in pain, participants with chronic pain had significantly impaired short-term prospective memory, an effect which was evident even after co-varying use of analgesics and other drugs. Conclusions: These findings provide new insights into prospective memory dysfunction in people with chronic pain. Possible mechanisms for this dysfunction are discussed and suggestions for future research given

HIV-1 unmasks the plasticity of innate lymphoid cells [preprint]

Pharmaceuticals that suppress HIV-1 viremia preserve CD4+ T cells and prevent AIDS. Nonetheless, HIV-1 infected people taking these drugs have chronic inflammation attributable to persistent disruption of intestinal barrier function with increased rates of cardiovascular mortality. To better understand the etiology of this inflammation we examined the effect of HIV-1 infection on innate lymphoid cells (ILCs). These innate immune counterparts of T cells lack clonotypic antigen receptors, classify according to signature transcription factors and cytokines, and maintain homeostasis in inflamed tissues. ILCs have been defined, in part, by the IL-7Rα, CD127. Here we report that the vast majority of type 1 and 3 ILCs in human adult and placental cord blood are in fact CD127-, as are colon lamina propria ILC1s and many ILC3s. Among ILCs, CD127-ILC1s were the major producer of inflammatory cytokines. In contrast to CD127+ILC3s, CD127-ILC3s did not produce IL-22, a cytokine that maintains epithelial barrier function. In HIV-1+ people taking antivirals that preserve CD4+ T cells, CD127-ILC1s and all homeostatic cytokine-producing CD127+ILCs were decreased in blood and colon. Common γ-chain cytokines that are reported to be elevated in response to HIV-1 infection caused JAK3-dependent downregulation of CD127 and converted CD127-ILC1s into NK cells with heightened cytolytic activity. Consistent with the recent report that human blood CD117+ILCs give rise to both ILC1s and NK cells, pseudotemporal clustering of transcriptomes from thousands of individual cells identified a developmental trajectory from CD127-ILC1s to memory NK cells that was defined by WNT-transcription factor TCF7. WNT inhibition prevented the cytokine-induced transition of CD127-ILC1 cells into memory NK cells. In HIV-1+ people, effector NK cells and TCF7+ memory NK cells were elevated, concomitant with reduction in CD127-ILC1s. These studies describe previously overlooked human ILC subsets that are significant in number and function, identify profound abnormalities in homeostatic ILCs that likely contribute to ongoing inflammation in HIV-1 infection despite control of viremia, provide explanation for increased memory NK cells in HIV-1 infection, and reveal functional plasticity of ILCs

Congenital Diaphragmatic Hernia: 10-Year Evaluation of Survival, Extracorporeal Membrane Oxygenation, and Foetoscopic Endotracheal Occlusion in Four High-Volume Centres

Background: Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly with significant mortality. Objectives: The aim of this study was to determine if there were trends in survival over the last decade and to compare patient populations, treatment options, and survival rates between 4 high-volume centres, and hence determine which factors were associated with survival. Methods: In 4 high-volume CDH centres from the CDH EURO Consortium, data from all CDH patients born between 2004 and 2013 were analysed. The predictive value of variables known at birth and the influence of centre-specific treatments (extracorporeal membrane oxygenation, ECMO, and foetoscopic endotracheal occlusion, FETO) on survival were evaluated in multivariable logistic regression analyses. Results: Nine hundred and seventy-five patients were included in the analysis, of whom 274 (28.1%) died. ECMO was performed in 259 patients, of whom 81 (31.3%) died. One hundred and forty-five patients (14.9%) underwent FETO, and from those 76 patients (52.4%) survived. Survival differed significantly between years (p = 0.006) and between the 4 centres (p < 0.001). In the multivariable logistic regression analysis, lung-to-head ratio, gestational age at birth, ECMO, centre of birth, and year of birth were significantly associated with survival, whereas FETO was not. Conclusions: The patient populations were different between centres, which influenced outcomes. There was a significant variability in survival over time and between centres, which should be taken into consideration in the planning of future trials

Epstein-barr virus latent membrane protein 1 genetic variability in peripheral blood B cells and oropharyngeal fluids

We report the diversity of latent membrane protein 1 (LMP1) gene founder sequences and the level of Epstein-Barr virus (EBV) genome variability over time and across anatomic compartments by using virus genomes amplified directly from oropharyngeal wash specimens and peripheral blood B cells during acute infection and convalescence. The intrahost nucleotide variability of the founder virus was 0.02% across the region sequences, and diversity increased significantly over time in the oropharyngeal compartment (P = 0.004). The LMP1 region showing the greatest level of variability in both compartments, and over time, was concentrated within the functional carboxyl-terminal activating regions 2 and 3 (CTAR2 and CTAR3). Interestingly, a deletion in a proline-rich repeat region (amino acids 274 to 289) of EBV commonly reported in EBV sequenced from cancer specimens was not observed in acute infectious mononucleosis (AIM) patients. Taken together, these data highlight the diversity in circulating EBV genomes and its potential importance in disease pathogenesis and vaccine design. IMPORTANCE: This study is among the first to leverage an improved high-throughput deep-sequencing methodology to investigate directly from patient samples the degree of diversity in Epstein-Barr virus (EBV) populations and the extent to which viral genome diversity develops over time in the infected host. Significant variability of circulating EBV latent membrane protein 1 (LMP1) gene sequences was observed between cellular and oral wash samples, and this variability increased over time in oral wash samples. The significance of EBV genetic diversity in transmission and disease pathogenesis are discussed