Willpower and Conscious Percept: Volitional Switching in Binocular Rivalry

When dissimilar images are presented to the left and right eyes, awareness switches spontaneously between the two images, such that one of the images is suppressed from awareness while the other is perceptually dominant. For over 170 years, it has been accepted that even though the periods of dominance are subject to attentional processes, we have no inherent control over perceptual switching. Here, we revisit this issue in response to evidence that top-down attention can target perceptually suppressed ‘vision for action’ representations in the dorsal stream. We investigated volitional control over rivalry between apparent motion (AM), drifting (DM) and stationary (ST) grating pairs. Observers demonstrated a remarkable ability to generate intentional switches in the AM and D conditions, but not in the ST condition. Corresponding switches in the pursuit direction of optokinetic nystagmus verified this finding objectively. We showed it is unlikely that intentional perceptual switches were triggered by saccadic eye movements, because their frequency was reduced substantially in the volitional condition and did not change around the time of perceptual switches. Hence, we propose that synergy between dorsal and ventral stream representations provides the missing link in establishing volitional control over rivalrous conscious percepts

A synthesis of past, current and future research for protection and management of papyrus (Cyperus papyrus L.) wetlands in Africa

Papyrus wetlands (dominated by the giant sedge Cyperus papyrus L.) occur throughout eastern, central and southern Africa and are important for biodiversity, for water quality and quantity regulation and for the livelihoods of millions of people. To draw attention to the importance of papyrus wetlands, a special session entitled ‘‘The ecology of livelihoods in papyrus wetlands’’ was organized at the 9th INTECOL Wetlands Conference in Orlando, Florida in June 2012. Papers from the session, combined with additional contributions, were collected in a special issue of Wetlands Ecology and Management. The current paper reviews ecological and hydrological characteristics of papyrus wetlands, summarizes their ecosystem services and sustainable use, provides an overview of papyrus research to date, and looks at policy development for papyrus wetlands. Based on this review, the paper provides a synthesis of research and policy priorities for papyrus wetlands and introduces the contributions in the special issue. Main conclusions are that (1) there is a need for better estimates of the area covered by papyrus wetlands. Limited evidence suggests that the loss of papyrus wetlands is rapid in some areas; (2) there is a need for a better understanding and modelling of the regulating services of papyrus wetlands to support trade-off analysis and improve economic valuation; (3) research on papyrus wetlands should include assessment of all ecosystem services (provisioning, regulating, habitat, cultural) so that trade-offs can be determined as the basis for sustainable management strategies (‘wise use’); (4) more research on the governance, institutional and socio-economic aspects of papyrus wetlands is needed to assist African governments in dealing with the challenges of conserving wetlands in the face of growing food security needs and climate change. The papers in the special issue address a number of these issues

Intraoperative Multispectral Fluorescence Imaging for the Detection of the Sentinel Lymph Node in Cervical Cancer: A Novel Concept

PURPOSE: Real-time intraoperative near-infrared fluorescence (NIRF) imaging is a promising technique for lymphatic mapping and sentinel lymph node (SLN) detection. The purpose of this technical feasibility pilot study was to evaluate the applicability of NIRF imaging with indocyanin green (ICG) for the detection of the SLN in cervical cancer. PROCEDURES: In ten patients with early stage cervical cancer, a mixture of patent blue and ICG was injected into the cervix uteri during surgery. Real-time color and fluorescence videos and images were acquired using a custom-made multispectral fluorescence camera system. RESULTS: Real-time fluorescence lymphatic mapping was observed in vivo in six patients; a total of nine SLNs were detected, of which one (11%) contained metastases. Ex vivo fluorescence imaging revealed the remaining fluorescent signal in 11 of 197 non-sentinel LNs (5%), of which one contained metastatic tumor tissue. None of the non-fluorescent LNs contained metastases. CONCLUSIONS: We conclude that lymphatic mapping and detection of the SLN in cervical cancer using intraoperative NIRF imaging is technically feasible. However, the technique needs to be refined for full applicability in cervical cancer in terms of sensitivity and specificity

Adherence to colorectal cancer screening: Four rounds of faecal immunochemical test-based screening

Background:The effectiveness of faecal immunochemical test (FIT)-based screening programs is highly dependent on consistent participation over multiple rounds. We evaluated adherence to FIT screening over four rounds and aimed to identify determinants of participation behaviour.Methods:A total of 23 339 randomly selected asymptomatic persons aged 50-74 years were invited for biennial FIT-based colorectal cancer screening between 2006 and 2014. All were invited for every consecutive round, except for those who had moved out of the area, passed the upper age limit, or had tested positive in a previous screening round. A reminder letter was sent to non-responders. We calculated participation rates per round, response rates to a reminder letter, and differences in participation between subgroups defined by age, sex, and socioeconomic status (SES).Results:Over the four rounds, participation rates increased significantly, from 60% (95% CI 60-61), 60% (95% CI 59-60), 62% (95% CI 61-63) to 63% (95% CI 62-64; P for trend<0.001) with significantly higher participation rates in women in all rounds (P<0.001). Of the 17 312 invitees eligible for at least two rounds of FIT screening, 12 455 (72%) participated at least once, whereas 4857 (28%) never participated; 8271 (48%) attended all rounds when eligible. Consistent participation was associated with older age, female sex, and higher SES. Offering a reminder letter after the initial invite in the first round increased uptake with 12%; in subsequent screening rounds this resulted in an additional uptake of up to 10%.Conclusions:In four rounds of a pilot biennial FIT-screening program, we observed a consistently high and increasing participation rate, whereas sending reminders remain effective. The substantial proportion of inconsistent participants suggests the existence of incidental barriers to participation, which, if possible, should be identified and removed

The Urokinase Receptor (uPAR) Facilitates Clearance of Borrelia burgdorferi

The causative agent of Lyme borreliosis, the spirochete Borrelia burgdorferi, has been shown to induce expression of the urokinase receptor (uPAR); however, the role of uPAR in the immune response against Borrelia has never been investigated. uPAR not only acts as a proteinase receptor, but can also, dependently or independently of ligation to uPA, directly affect leukocyte function. We here demonstrate that uPAR is upregulated on murine and human leukocytes upon exposure to B. burgdorferi both in vitro as well as in vivo. Notably, B. burgdorferi-inoculated C57BL/6 uPAR knock-out mice harbored significantly higher Borrelia numbers compared to WT controls. This was associated with impaired phagocytotic capacity of B. burgdorferi by uPAR knock-out leukocytes in vitro. B. burgdorferi numbers in vivo, and phagocytotic capacity in vitro, were unaltered in uPA, tPA (low fibrinolytic activity) and PAI-1 (high fibrinolytic activity) knock-out mice compared to WT controls. Strikingly, in uPAR knock-out mice partially backcrossed to a B. burgdorferi susceptible C3H/HeN background, higher B. burgdorferi numbers were associated with more severe carditis and increased local TLR2 and IL-1β mRNA expression. In conclusion, in B. burgdorferi infection, uPAR is required for phagocytosis and adequate eradication of the spirochete from the heart by a mechanism that is independent of binding of uPAR to uPA or its role in the fibrinolytic system

Opposite Influence of Perceptual Memory on Initial and Prolonged Perception of Sensory Ambiguity

Observers continually make unconscious inferences about the state of the world based on ambiguous sensory information. This process of perceptual decision-making may be optimized by learning from experience. We investigated the influence of previous perceptual experience on the interpretation of ambiguous visual information. Observers were pre-exposed to a perceptually stabilized sequence of an ambiguous structure-from-motion stimulus by means of intermittent presentation. At the subsequent re-appearance of the same ambiguous stimulus perception was initially biased toward the previously stabilized perceptual interpretation. However, prolonged viewing revealed a bias toward the alternative perceptual interpretation. The prevalence of the alternative percept during ongoing viewing was largely due to increased durations of this percept, as there was no reliable decrease in the durations of the pre-exposed percept. Moreover, the duration of the alternative percept was modulated by the specific characteristics of the pre-exposure, whereas the durations of the pre-exposed percept were not. The increase in duration of the alternative percept was larger when the pre-exposure had lasted longer and was larger after ambiguous pre-exposure than after unambiguous pre-exposure. Using a binocular rivalry stimulus we found analogous perceptual biases, while pre-exposure did not affect eye-bias. We conclude that previously perceived interpretations dominate at the onset of ambiguous sensory information, whereas alternative interpretations dominate prolonged viewing. Thus, at first instance ambiguous information seems to be judged using familiar percepts, while re-evaluation later on allows for alternative interpretations

Evidence for Reduced Drug Susceptibility without Emergence of Major Protease Mutations following Protease Inhibitor Monotherapy Failure in the SARA Trial

Background Major protease mutations are rarely observed following failure with protease inhibitors (PI), and other viral determinants of failure to PI are poorly understood. We therefore characterized Gag-Protease phenotypic susceptibility in subtype A and D viruses circulating in East Africa following viral rebound on PIs. Methods Samples from baseline and treatment failure in patients enrolled in the second line LPV/r trial SARA underwent phenotypic susceptibility testing. Data were expressed as fold-change in susceptibility relative to a LPV-susceptible reference strain. Results We cloned 48 Gag-Protease containing sequences from seven individuals and performed drug resistance phenotyping from pre-PI and treatment failure timepoints in seven patients. For the six patients where major protease inhibitor resistance mutations did not emerge, mean fold-change EC50 to LPV was 4.07 fold (95% CI, 2.08–6.07) at the pre-PI timepoint. Following viral failure the mean fold-change in EC50 to LPV was 4.25 fold (95% CI, 1.39–7.11, p = 0.91). All viruses remained susceptible to DRV. In our assay system, the major PI resistance mutation I84V, which emerged in one individual, conferred a 10.5-fold reduction in LPV susceptibility. One of the six patients exhibited a significant reduction in susceptibility between pre-PI and failure timepoints (from 4.7 fold to 9.6 fold) in the absence of known major mutations in protease, but associated with changes in Gag: V7I, G49D, R69Q, A120D, Q127K, N375S and I462S. Phylogenetic analysis provided evidence of the emergence of genetically distinct viruses at the time of treatment failure, indicating ongoing viral evolution in Gag-protease under PI pressure. Conclusions Here we observe in one patient the development of significantly reduced susceptibility conferred by changes in Gag which may have contributed to treatment failure on a protease inhibitor containing regimen. Further phenotype-genotype studies are required to elucidate genetic determinants of protease inhibitor failure in those who fail without traditional resistance mutations whilst PI use is being scaled up globally

Non-additive genome-wide association scan reveals a new gene associated with habitual coffee consumption

Coffee is one of the most consumed beverages world-wide and one of the primary sources of caffeine intake. Given its important health and economic impact, the underlying genetics of its consumption has been widely studied. Despite these efforts, much has still to be uncovered. In particular, the use of non-additive genetic models may uncover new information about the genetic variants driving coffee consumption. We have conducted a genome-wide association study in two Italian populations using additive, recessive and dominant models for analysis. This has uncovered a significant association in the PDSS2 gene under the recessive model that has been replicated in an independent cohort from the Netherlands (ERF). The identified gene has been shown to negatively regulate the expression of the caffeine metabolism genes and can thus be linked to coffee consumption. Further bioinformatics analysis of eQTL and histone marks from Roadmap data has evidenced a possible role of the identified SNPs in regulating PDSS2 gene expression through enhancers present in its intron. Our results highlight a novel gene which regulates coffee consumption by regulating the expression of the genes linked to caffeine metabolism. Further studies will be needed to clarify the biological mechanism which links PDSS2 and coffee consumption

Expression profile of genes regulated by activity of the Na-H exchanger NHE1

BACKGROUND: In mammalian cells changes in intracellular pH (pH(i)), which are predominantly controlled by activity of plasma membrane ion exchangers, regulate a diverse range of normal and pathological cellular processes. How changes in pH(i )affect distinct cellular processes has primarily been determined by evaluating protein activities and we know little about how pH(i )regulates gene expression. RESULTS: A global profile of genes regulated in mammalian fibroblasts by decreased pH(i )induced by impaired activity of the plasma membrane Na-H exchanger NHE1 was characterized by using cDNA microarrays. Analysis of selected genes by quantitative RT-PCR, TaqMan, and immunoblot analyses confirmed results obtained from cDNA arrays. Consistent with established roles of pH(i )and NHE1 activity in cell proliferation and oncogenic transformation, grouping regulated genes into functional categories and biological pathways indicated a predominant number of genes with altered expression were associated with growth factor signaling, oncogenesis, and cell cycle progression. CONCLUSION: A comprehensive analysis of genes selectively regulated by pH(i )provides insight on candidate targets that might mediate established effects of pH(i )on a number of normal and pathological cell functions