Feasibility and Reliability of the Adapted Kagan Scales for Rating Conversations for People With Acquired Brain Injury: A Multiphase Iterative Mixed-Methods Design.

PURPOSE: Rating the quality of conversations can assess communication skills in both people with acquired brain injury and their communication partners. This study explored the clinical feasibility and reliability of two conversation rating scales: the Adapted Measure of Participation in Conversation (MPC) and the Adapted Measure of Support in Conversation (MSC). METHOD: Raters were final-year speech and language therapy students (n = 14) and qualified clinicians (n = 2). Raters attended training on the Adapted MPC and MSC, watched 5 or 10 min of videotaped conversations (n = 23), and then scored them on the MPC and MSC scales. Data were collected over four phases, which varied according to the length of the training, sample length, number of samples rated, and level of clinical expertise. Feasibility data (time taken to score conversations and ease of use) were collected. Interrater reliability was assessed using intraclass correlations (ICCs: absolute agreement, single measures). RESULTS: Raters took 30-45 min to score a 10-min sample, and they took 20-30 min to score a 5-min sample. Ease of use was rated highly across all phases. Overall reliability for rating 5 min of conversation (ICC = .52-.73) was better than for 10 min of conversation (ICC = .33-.68). Reliability for the MPC was moderate for both students (ICC = .69) and clinicians (ICC = .55), and for the MSC, it was moderate for both students (ICC = .73) and clinicians (ICC = .58). Reliability was better for students compared with clinicians. CONCLUSIONS: Rating a 5-min conversation in under 30 min was feasible, with more reliable results for 5-min compared with 10-min conversations. Implications for assessing conversation in the future are discussed

Expression profile of human Fc receptors in mucosal tissue: implications for antibody-dependent cellular effector functions targeting HIV-1 transmission

The majority of new Human Immunodeficiency Virus (HIV)-1 infections are acquired via sexual transmission at mucosal surfaces. Partial efficacy (31.2%) of the Thai RV144 HIV-1 vaccine trial has been correlated with Antibody-dependent Cellular Cytotoxicity (ADCC) mediated by non-neutralizing antibodies targeting the V1V2 region of the HIV-1 envelope. This has led to speculation that ADCC and other antibody-dependent cellular effector functions might provide an important defense against mucosal acquisition of HIV-1 infection. However, the ability of antibody-dependent cellular effector mechanisms to impact on early mucosal transmission events will depend on a variety of parameters including effector cell type, frequency, the class of Fc-Receptor (FcR) expressed, the number of FcR per cell and the glycoslyation pattern of the induced antibodies. In this study, we characterize and compare the frequency and phenotype of IgG (CD16 [FcγRIII], CD32 [FcγRII] and CD64 [FcγRI]) and IgA (CD89 [FcαR]) receptor expression on effector cells within male and female genital mucosal tissue, colorectal tissue and red blood cell-lysed whole blood. The frequency of FcR expression on CD14+ monocytic cells, myeloid dendritic cells and natural killer cells were similar across the three mucosal tissue compartments, but significantly lower when compared to the FcR expression profile of effector cells isolated from whole blood, with many cells negative for all FcRs. Of the three tissues tested, penile tissue had the highest percentage of FcR positive effector cells. Immunofluorescent staining was used to determine the location of CD14+, CD11c+ and CD56+ cells within the three mucosal tissues. We show that the majority of effector cells across the different mucosal locations reside within the subepithelial lamina propria. The potential implication of the observed FcR expression patterns on the effectiveness of FcR-dependent cellular effector functions to impact on the initial events in mucosal transmission and dissemination warrants further mechanistic studies

Feasibility and reliability of the Adapted Kagan Scales for rating conversations for people with acquired brain injury: A multi-phase iterative mixed methods design

PURPOSE: Rating the quality of conversations can assess communication skills in both people with acquired brain injury (ABI) and their communication partners. This study explored the clinical feasibility and reliability of two conversation rating scales: The Adapted Measure of Participation in Conversation (MPC) and Adapted Measure of Support in Conversation (MSC) METHOD: Raters were final-year speech and language therapy students (n = 14) and qualified clinicians (n = 2). Raters attended training on the Adapted MPC and MSC, watched 5 or 10 minutes of videotaped conversations (n = 23) and then scored them on the MPC and MSC scales. Data was collected over four phases which varied according to the length of the training, sample length, number of samples rated and level of clinical expertise. Feasibility data (time taken to score conversations and ease of use) was collected. Inter-rater reliability was assessed using intra-class correlations (ICCs: absolute agreement, single measures). RESULTS: Raters took 30 - 45 minutes to score a 10-minute sample; and 20 - 30 minutes to score a 5-minute sample. Ease of use was rated highly across all phases. Overall reliability for rating 5-minutes of conversation (ICC = 0.52-0.73) was better than for 10-minutes of conversation (ICC = 0.33 - 0.68). Reliability for the MPC was moderate for both students (ICC = 0.69) and clinicians (ICC = 0.55); and for the MSC, moderate for both students (ICC = 0.73) and clinicians (ICC= 0.58). Reliability was better for students compared with clinicians. CONCLUSION: Rating a 5-minute conversation in under 30 minutes was feasible, with more reliable results for 5-minute compared with 10-minute conversations. Implications for assessing conversation in the future are discusse

Modelling pulmonary microthrombosis coupled to metastasis: distinct effects of thrombogenesis on tumorigenesis

Thrombosis can cause localized ischemia and tissue hypoxia, and both of these are linked to cancer metastasis. Vascular micro-occlusion can occur as a result of arrest of circulating tumour cells in small capillaries, giving rise to microthrombotic events that affect flow, creating localized hypoxic regions. To better understand the association between metastasis and thrombotic events, we generated an experimental strategy whereby we modelled the effect of microvascular occlusion in metastatic efficiency by using inert microbeads to obstruct lung microvasculature before, during and after intravenous tumour cell injection. We found that controlled induction of a specific number of these microthrombotic insults in the lungs caused an increase in expression of the hypoxia-inducible transcription factors (HIFs), a pro-angiogenic and pro-tumorigenic environment, as well as an increase in myeloid cell infiltration. Induction of pulmonary microthrombosis prior to introduction of tumour cells to the lungs had no effect on tumorigenic success, but thrombosis at the time of tumour cell seeding increased number and size of tumours in the lung, and this effect was strikingly more pronounced when the micro-occlusion occurred on the day following introduction of tumour cells. The tumorigenic effect of microbead treatment was seen even when thrombosis was induced five days after tumour cell injection. We also found positive correlations between thrombotic factors and expression of HIF2$\alpha$ in human tumours. The model system described here demonstrates the importance of thrombotic insult in metastatic success and can be used to improve understanding of thrombosis-associated tumorigenesis and its treatment.Research was supported through a Wellcome Trust Principal Research Fellowship to R.S.J. (RG59596). C.B. is supported through a Scientific Fellowship from Breast Cancer Now (2014MaySF275). C.E.E. received a Pump-Priming Grant from the University of Cambridge British Heart Foundation Centre of Research Excellence (RG68639)

Track A Basic Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138319/1/jia218438.pd

The HIV-1 transmission bottleneck

It is well established that most new systemic infections of HIV-1 can be traced back to one or a limited number of founder viruses. Usually, these founders are more closely related to minor HIV-1 populations in the blood of the presumed donor than to more abundant lineages. This has led to the widely accepted idea that transmission selects for viral characteristics that facilitate crossing the mucosal barrier of the recipient’s genital tract, although the specific selective forces or advantages are not completely defined. However, there are other steps along the way to becoming a founder virus at which selection may occur. These steps include the transition from the donor’s general circulation to the genital tract compartment, survival within the transmission fluid, and establishment of a nascent stable local infection in the recipient’s genital tract. Finally, there is the possibility that important narrowing events may also occur during establishment of systemic infection. This is suggested by the surprising observation that the number of founder viruses detected after transmission in intravenous drug users is also limited. Although some of these steps may be heavily selective, others may result mostly in a stochastic narrowing of the available founder pool. Collectively, they shape the initial infection in each recipient