Investigating human audio-visual object perception with a combination of hypothesis-generating and hypothesis-testing fMRI analysis tools

Primate multisensory object perception involves distributed brain regions. To investigate the network character of these regions of the human brain, we applied data-driven group spatial independent component analysis (ICA) to a functional magnetic resonance imaging (fMRI) data set acquired during a passive audio-visual (AV) experiment with common object stimuli. We labeled three group-level independent component (IC) maps as auditory (A), visual (V), and AV, based on their spatial layouts and activation time courses. The overlap between these IC maps served as definition of a distributed network of multisensory candidate regions including superior temporal, ventral occipito-temporal, posterior parietal and prefrontal regions. During an independent second fMRI experiment, we explicitly tested their involvement in AV integration. Activations in nine out of these twelve regions met the max-criterion (A < AV > V) for multisensory integration. Comparison of this approach with a general linear model-based region-of-interest definition revealed its complementary value for multisensory neuroimaging. In conclusion, we estimated functional networks of uni- and multisensory functional connectivity from one dataset and validated their functional roles in an independent dataset. These findings demonstrate the particular value of ICA for multisensory neuroimaging research and using independent datasets to test hypotheses generated from a data-driven analysis

The return trip effect: Why the return trip often seems to take less time

Three studies confirm the existence of the return trip effect: The return trip often seems shorter than the initial trip, even though the distance traveled and the actual time spent traveling are identical. A pretest shows that people indeed experience a return trip effect regularly, and the effect was found on a bus trip (Study 1), a bicycle trip (Study 2), and when participants watched a video of someone else traveling (Study 3). The return trip effect also existed when another, equidistant route was taken on the return trip, showing that it is not familiarity with the route that causes this effect. Rather, it seems that a violation of expectations causes this effect

High susceptibility of c-KIT+CD34+ precursors to prolonged doxorubicin exposure interferes with Langerhans cell differentiation in a human cell line model

As neoadjuvant and adjuvant chemotherapy schedules often consist of multiple treatment cycles over relatively long periods of time, it is important to know what effects protracted drug administration can have on the immune system. Here, we studied the long-term effects of doxorubicin on the capacity of dendritic cell (DC) precursors to differentiate into a particular DC subset, the Langerhans cells (LC). In order to achieve high telomerase activity as detected in hematological stem cells, precursor cells from the acute-myeloid leukemia (AML)-derived cell line MUTZ3 were stably transduced with human telomerase reverse transcriptase (hTERT) to facilitate their growth potential, while preventing growth, and drug-induced senescence, and preserving their unique capacity for cytokine-dependent DC and LC differentiation. The hTERT-MUTZ3 cells were selected with increasing concentrations of the anthracyclin doxorubicin. After 1–2 months of selection with 30–90 nM doxorubicin, the cells completely lost their capacity to differentiate into LC. This inhibition turned out to be reversible, as the cells slowly regained their capacity to differentiate after a 3- to 4-month drug-free period and with this became capable again of priming allogeneic T cells. Of note, the loss and gain of this capacity to differentiate coincided with the loss and gain of a subpopulation within the CD34+ proliferative compartment with surface expression of the stem cell factor receptor (SCF-R/CD117/c-Kit). These data are in favor of cytostatic drug-free intervals before applying autologous DC-based vaccination protocols, as specific DC precursors may need time to recover from protracted chemotherapy treatment and re-emerge among the circulating CD34+ hematopoietic stem and precursor cells

Willingness to volunteer in a Phase I/II HIV vaccine trial: a study among police officers in Dar es Salaam, Tanzania

Background: As HIV infection continues to be a public health problem, development of an effective preventive HIV vaccine is a priority. For the ultimate development of an AIDS vaccine, clinical trials are being conducted throughout the world. However, the process of developing the vaccine does not only depend on identification of suitable trial candidates, but also requires knowledge of incentives to participate in the community where the trial is being conducted. Therefore, the studies presented in this thesis are components of a HIV/AIDS and HIV vaccine trial project in Dar es Salaam, Tanzania to address motivations and deterrents of participating in an HIV vaccine trial. Aim: To examine the motivations and deterrents for participating in preventive HIV vaccine trials. Methods: Data were collected from participants and volunteers who were considered for participation or participated in a phase I/II HIV vaccine trial. Four studies with different designs were conducted. In Study I, a semi-structured interview administered questionnaire was used to assess willingness to volunteer for a phase I/II HIV vaccine trial. A convenience sample of 329 individuals from the police force cohort was recruited for the study in 2005-2006. In Study II, focus group discussions were conducted to explore factors that would influence participation in an HIV vaccine trial among members of the police force in 2006-2007. In Study III, face-to-face interviews were used to identify reasons for declining to enrol in an HIV vaccine trial among those who agreed to enrol at the start and were randomized for the trial in 2007-2009. In Study IV, we used focus group discussions to evaluate the experiences of those who participated in the phase I/II trial in 2009. Results: Willingness to volunteer for an HIV vaccine trial was associated with intention to tell others, positive outcome of the trial, personal decision and expectation of obtaining protection against HIV infection. Participation in an HIV vaccine trial would be negatively influenced by sexual partners, friends, family members, relatives or parents (significant others) and fear of vaccine side-effects. Personal fears and negative influences from significant others were the main reasons for declining to enrol in an HIV vaccine trial. Despite the negative comments from significant others, volunteers in the HIV vaccine trial managed to stay on until the end of the trial as a result of personal decision and trial-related interventions. Conclusion: Personal decision is both a motivation to participate in an HIV vaccine trial and a reason to stay on until the end of trial. On the contrary, significant others are the deterrents to participation in the HIV vaccine trial and the reason for declining to enrol in the HIV vaccine trial. Awareness of these issues before trial implementation may help to maximize resource use and enhance retention of those who volunteer in the HIV vaccine trials

Testing the effectiveness of a mindfulness-based intervention to reduce emotional distress in outpatients with diabetes (DiaMind): design of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Approximately 20-40% of outpatients with diabetes experience elevated levels of emotional distress, varying from disease-specific distress to general symptoms of anxiety and depression. The patient's emotional well-being is related to other unfavorable outcomes, like reduced quality of life, sub-optimal self-care, impaired glycemic control, higher risk of complications, and increased mortality rates. The purpose of this study is to test the effectiveness of a new diabetes-specific, mindfulness-based psychological intervention. First, with regard to reducing emotional distress; second, with respect to improving quality of life, dispositional mindfulness, and self-esteem of patients with diabetes; third, with regard to self-care and clinical outcomes; finally, a potential effect modification by clinical and personality characteristics will be explored.</p> <p>Methods/Design</p> <p>The Diabetes and Mindfulness study (DiaMind) is a randomized controlled trial. Patients with diabetes with low levels of emotional well-being will be recruited from outpatient diabetes clinics. Eligible patients will be randomized to an intervention group or a wait-list control group. The intervention group will receive the mindfulness program immediately, while the control group will receive the program eight months later. The primary outcome is emotional distress (anxiety, stress, depressive symptoms), for which data will be collected at baseline, four weeks, post intervention, and after six months follow-up. In addition, self-report data will be collected on quality of life, dispositional mindfulness, self-esteem, self-care, and personality, while complications and glycemic control will be assessed from medical files and blood pressure will be measured. Group differences will be analyzed with repeated measures analysis of covariance.</p> <p>The study is supported by grants from the Dutch Diabetes Research Foundation and Tilburg University and has been approved by a medical ethics committee.</p> <p>Discussion</p> <p>It is hypothesized that emotional well-being, quality of life, dispositional mindfulness, self-esteem, self-care, and blood pressure will improve significantly more in the mindfulness group compared to the control group. Results of this study can contribute to a better care for patients with diabetes with lowered levels of emotional well-being. It is expected that the first results will become available in 2012.</p> <p>Trial registration</p> <p>Dutch Trial Register <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2145">NTR2145</a>.</p

High risk behavior for HIV transmission among former injecting drug users: a survey from Indonesia

Contains fulltext : 88347.pdf (publisher's version ) (Open Access)BACKGROUND: Injecting drug use is an increasingly important cause of HIV transmission in most countries worldwide, especially in eastern Europe, South America, and east and southeast Asia. Among people actively injecting drugs, provision of clean needles and opioid substitution reduce HIV-transmission. However, former injecting drug users (fIDUs) are often overlooked as a high risk group for HIV transmission. We compared HIV risk behavior among current and former injecting drug users (IDUs) in Indonesia, which has a rapidly growing HIV-epidemic largely driven by injecting drug use. METHODS: Current and former IDUs were recruited by respondent driven sampling in an urban setting in Java, and interviewed regarding drug use and HIV risk behavior using the European Addiction Severity Index and the Blood Borne Virus Transmission Questionnaire. Drug use and HIV transmission risk behavior were compared between current IDUs and former IDUs, using the Mann-Whitney and Pearson Chi-square test. RESULTS: Ninety-two out of 210 participants (44%) were self reported former IDUs. Risk behavior related to sex, tattooing or piercing was common among current as well as former IDUs, 13% of former IDUs were still exposed to contaminated injecting equipment. HIV-infection was high among former (66%) and current (60%) IDUs. CONCLUSION: Former IDUs may contribute significantly to the HIV-epidemic in Indonesia, and HIV-prevention should therefore also target this group, addressing sexual and other risk behavior

Severe Dengue Is Associated with Consumption of von Willebrand Factor and Its Cleaving Enzyme ADAMTS-13

Severe dengue infections are characterized by thrombocytopenia, clinical bleeding and plasma leakage. Activation of the endothelium, the inner lining of blood vessels, leads to the secretion of storage granules called Weibel Palade bodies (WPBs). We demonstrated that severe dengue in Indonesian children is associated with a strong increase in plasma levels of the WPB constituents von Willebrand factor (VWF), VWF propeptide and osteoprotegerin (OPG). An increased amount of the hemostatic protein VWF was in a hyperreactive, platelet binding conformation, and this was most pronounced in the children who died. VWF levels at enrollment were lower than expected from concurrent VWF propeptide and OPG levels and VWF levels did not correlate well with markers of disease severity. Together, this suggests that VWF is being consumed during severe dengue. Circulating levels of the VWF-cleaving enzyme ADAMTS-13 were reduced. VWF is a multimeric protein and a subset of children had a decrease in large and intermediate VWF multimers at discharge. In conclusion, severe dengue is associated with exocytosis of WPBs with consumption of VWF and low ADAMTS-13 activity levels. This may contribute to the thrombocytopenia and complications of dengue

Making sense of evidence in management decisions: the role of research-based knowledge on innovation adoption and implementation in healthcare. study protocol

<p>Abstract</p> <p>Background</p> <p>We know that patient care can be improved by implementing evidence-based innovations and applying research findings linked to good practice. Successfully implementing innovations in complex organisations, such as the UK's National Health Service (NHS), is often challenging as multiple contextual dynamics mediate the process. Research studies have explored the challenges of introducing innovations into healthcare settings and have contributed to a better understanding of why potentially useful innovations are not always implemented in practice, even if backed by strong evidence. Mediating factors include health policy and health system influences, organisational factors, and individual and professional attitudes, including decision makers' perceptions of innovation evidence. There has been limited research on how different forms of evidence are accessed and utilised by organisational decision makers during innovation adoption. We also know little about how diverse healthcare professionals (clinicians, administrators) make sense of evidence and how this collective sensemaking mediates the uptake of innovations.</p> <p>Methods</p> <p>The study will involve nine comparative case study sites of acute care organisations grouped into three regional clusters across England. Each of the purposefully selected sites represents a variety of trust types and organisational contexts. We will use qualitative methods, in-depth interviews, observation of key meetings, and systematic analysis of relevant secondary data to understand the rationale and challenges involved in sourcing and utilising innovation evidence in the empirical setting of infection prevention and control. We will use theories of innovation adoption and sensemaking in organisations to interpret the data. The research will provide lessons for the uptake and continuous use of innovations in the English and international health systems.</p> <p>Discussion</p> <p>Unlike most innovation studies, which involve single-level analysis, our study will explore the innovation-adoption process at multiple embedded levels: micro (individual), meso (organisational), and macro (interorganisational). By comparing and contrasting across the nine sites, each with different organisational contexts, local networks, leadership styles, and different innovations considered for adoption, the findings of the study will have wide relevance. The research will produce actionable findings responding to the political and economic need for healthcare organisations to be innovation-ready.</p

Tomato Pathogenesis-related Protein Genes are Expressed in Response to Trialeurodes vaporariorum and Bemisia tabaci Biotype B Feeding

The temporal and spatial expression of tomato wound- and defense-response genes to Bemisia tabaci biotype B (the silverleaf whitefly) and Trialeurodes vaporariorum (the greenhouse whitefly) feeding were characterized. Both species of whiteflies evoked similar changes in tomato gene expression. The levels of RNAs for the methyl jasmonic acid (MeJA)- or ethylene-regulated genes that encode the basic β-1,3-glucanase (GluB), basic chitinase (Chi9), and Pathogenesis-related protein-1 (PR-1) were monitored. GluB and Chi9 RNAs were abundant in infested leaves from the time nymphs initiated feeding (day 5). In addition, GluB RNAs accumulated in apical non-infested leaves. PR-1 RNAs also accumulated after whitefly feeding. In contrast, the ethylene- and salicylic acid (SA)-regulated Chi3 and PR-4 genes had RNAs that accumulated at low levels and GluAC RNAs that were undetectable in whitefly-infested tomato leaves. The changes in Phenylalanine ammonia lyase5 (PAL5) were variable; in some, but not all infestations, PAL5 RNAs increased in response to whitefly feeding. PAL5 RNA levels increased in response to MeJA, ethylene, and abscisic acid, and declined in response to SA. Transcripts from the wound-response genes, leucine aminopeptidase (LapA1) and proteinase inhibitor 2 (pin2), were not detected following whitefly feeding. Furthermore, whitefly infestation of transgenic LapA1:GUS tomato plants showed that whitefly feeding did not activate the LapA1 promoter, although crushing of the leaf lamina increased GUS activity up to 40 fold. These studies indicate that tomato plants perceive B. tabaci and T. vaporariorum in a manner similar to baterical pathogens and distinct from tissue-damaging insects