Differences in the transduction of canonical wnt signals demarcate effector and memory CD8 T cells with distinct recall proliferation capacity.

Protection against reinfection is mediated by Ag-specific memory CD8 T cells, which display stem cell-like function. Because canonical Wnt (Wingless/Int1) signals critically regulate renewal versus differentiation of adult stem cells, we evaluated Wnt signal transduction in CD8 T cells during an immune response to acute infection with lymphocytic choriomeningitis virus. Whereas naive CD8 T cells efficiently transduced Wnt signals, at the peak of the primary response to infection only a fraction of effector T cells retained signal transduction and the majority displayed strongly reduced Wnt activity. Reduced Wnt signaling was in part due to the downregulation of Tcf-1, one of the nuclear effectors of the pathway, and coincided with progress toward terminal differentiation. However, the correlation between low and high Wnt levels with short-lived and memory precursor effector cells, respectively, was incomplete. Adoptive transfer studies showed that low and high Wnt signaling did not influence cell survival but that Wnt high effectors yielded memory cells with enhanced proliferative potential and stronger protective capacity. Likewise, following adoptive transfer and rechallenge, memory cells with high Wnt levels displayed increased recall expansion, compared with memory cells with low Wnt signaling, which were preferentially effector-like memory cells, including tissue-resident memory cells. Thus, canonical Wnt signaling identifies CD8 T cells with enhanced proliferative potential in part independent of commonly used cell surface markers to discriminate effector and memory T cell subpopulations. Interventions that maintain Wnt signaling may thus improve the formation of functional CD8 T cell memory during vaccination.

Subjective Memory Deficits in People with and without Dementia: Findings from the 10/66 Dementia Research Group Pilot Studies in Low- and Middle-Income Countries

OBJECTIVES To compare subjective memory deficit (SMD) in older adults with and without dementia or depression across multiple centers in low- and middle-income countries (LAMICs). DESIGN Secondary analysis of data from 23 case control studies. SETTING Twenty-three centers in India, Southeast Asia (including China), Latin America and the Caribbean, Nigeria, and Russia. PARTICIPANTS Two thousand six hundred ninety-two community-dwelling people aged 60 and older in one of three groups: people with dementia, people with depression, and controls free of dementia and depression. MEASUREMENTS SMD was derived from the Geriatric Mental State examination. RESULTS Median SMD frequency was lowest in participants without dementia (26.2%) and higher in those with depression (50.0%) and dementia (66.7%). Frequency of SMD varied between centers. Depression and dementia were consistently associated with SMD. Older age and hypochondriasis were associated with SMD only in subjects without dementia. In those with dementia, SMD was associated with better cognitive function, whereas the reverse was the case in controls. CONCLUSION Associations with SMD may differ between subjects with and without dementia living in LAMICs.

The Digital Memory of Catalonia, Consortium of Academic Libraries of Catalonia

The Digital Memory of Catalonia, Consortium of Academic Libraries of Catalonia, contains open-access digitized collections of photographs, drawings, maps, posters, pamphlets, incunabula, ancient Catalan periodicals and many other items with a total of over two million documents related to Catalonia from 18 different institutions (universities, specialized libraries, institutes, archives, etc.).

Evolutionary ecology of learning: insights from fruit flies

Ecologically and evolutionarily oriented research on learning has traditionally been carried out on vertebrates and bees. While less sophisticated than those animals, fruit flies (Drosophila) are capable of several forms of learning, and have an advantage of a short generation time, which makes them an ideal system for experimental evolution studies. This review summarizes the insights into evolutionary questions about learning gained in the last decade from evolutionary experiments on Drosophila. These experiments demonstrate that Drosophila have the genetic potential to evolve substantially improved learning performance in ecologically relevant learning tasks. In at least one set of selected populations the improved learning generalized to another task than that used to impose selection, involving a different behavior, different stimuli, and a different sensory channel for the aversive reinforcement. This improvement in learning ability was associated with reduction in other fitness-related traits, such as larval competitive ability and lifespan, pointing out to evolutionary trade-offs of improved learning. These trade-offs were confirmed by other evolutionary experiments where reduction in learning performance was observed as a correlated response to selection for tolerance to larval nutritional stress or for delayed aging. Such trade-offs could be one reason why fruit flies have not fully used up their evolutionary potential for learning ability. Finally, another evolutionary experiment with Drosophila provided the first direct evidence for the long-standing ideas that learning can under some circumstances accelerate and in other slow down genetically-based evolutionary change. These results demonstrate the usefulness of fruit flies as a model system to address evolutionary questions about learning.

Higher memory responses in HIV-infected and kidney transplanted patients than in healthy subjects following priming with the pandemic vaccine.

BACKGROUND: Memory responses require immune competence. We assessed the influence of priming with AS03-adjuvanted pandemic vaccine (Pandemrix®) on memory responses of HIV patients, kidney recipients (SOT) and healthy controls (HC). METHOD: Participants (HIV: 197, SOT: 53; HC: 156) were enrolled in a prospective study and 390/406 (96%) completed it. All had been primed in 2009/2010 with 1 (HC) or 2 (patients) doses of Pandemrix®, and were boosted with the 2010/2011 seasonal influenza vaccine. Geometric mean titres and seroprotection rates were measured 12 months after priming and 4 weeks after boosting. Primary and memory responses were directly compared in 191 participants (HCW: 69, HIV: 71, SOT: 51) followed during 2 consecutive seasons. RESULTS: Most participants (HC: 77.8%, HIV: 77.6%, SOT: 66%) remained seroprotected at 12 months post-priming. Persisting A/09/H1N1 titers were high in HIV (100.2) and HC (120.1), but lower in SOT (61.4) patients. Memory responses reached higher titers in HIV (507.8) than in HC (253.5) and SOT (136.9) patients. Increasing age and lack of HAART reduced persisting and memory responses, mainly influenced by residual antibody titers. Comparing 2009/2010 and 2010/2011 titers in 191 participants followed for 2 seasons indicated lower post-2010/2011 titers in HC (240.2 vs 313.9), but higher titers in HIV (435.7 vs 338.0) and SOT (136 vs 90.3) patients. CONCLUSIONS: Priming with 2 doses of Pandemrix® elicited persistent antibody responses and even stronger memory responses to non-adjuvanted seasonal vaccine in HIV patients than 1 dose in healthy subjects. Adjuvanted influenza vaccines may improve memory responses of immunocompromised patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01022905.

Northern Ireland Speech and Language Therapy Task Force report (PDF 1,016 KB)

Speech and Language task force report

Performance on a Virtual Reality Angled Laparoscope Task Correlates with Spatial Ability of Trainees

The aim of the present study was to investigate whether trainees' performance on a virtual reality angled laparoscope navigation task correlates with scores obtained on a validated conventional test of spatial ability. 56 participants of a surgery workshop performed an angled laparoscope navigation task on the Xitact LS 500 virtual reality Simulator. Performance parameters were correlated with the score of a validated paper-and-pencil test of spatial ability. Performance at the conventional spatial ability test significantly correlated with performance at the virtual reality task for overall task score (p < 0.001), task completion time (p < 0.001) and economy of movement (p = 0.035), not for endoscope travel speed (p = 0.947). In conclusion, trainees' performance in a standardized virtual reality camera navigation task correlates with their innate spatial ability. This VR session holds potential to serve as an assessment tool for trainees.

The efficacy of single-trial multisensory memories.

This review article summarizes evidence that multisensory experiences at one point in time have long-lasting effects on subsequent unisensory visual and auditory object recognition. The efficacy of single-trial exposure to task-irrelevant multisensory events is its ability to modulate memory performance and brain activity to unisensory components of these events presented later in time. Object recognition (either visual or auditory) is enhanced if the initial multisensory experience had been semantically congruent and can be impaired if this multisensory pairing was either semantically incongruent or entailed meaningless information in the task-irrelevant modality, when compared to objects encountered exclusively in a unisensory context. Processes active during encoding cannot straightforwardly explain these effects; performance on all initial presentations was indistinguishable despite leading to opposing effects with stimulus repetitions. Brain responses to unisensory stimulus repetitions differ during early processing stages (-100 ms post-stimulus onset) according to whether or not they had been initially paired in a multisensory context. Plus, the network exhibiting differential responses varies according to whether or not memory performance is enhanced or impaired. The collective findings we review indicate that multisensory associations formed via single-trial learning exert influences on later unisensory processing to promote distinct object representations that manifest as differentiable brain networks whose activity is correlated with memory performance. These influences occur incidentally, despite many intervening stimuli, and are distinguishable from the encoding/learning processes during the formation of the multisensory associations. The consequences of multisensory interactions that persist over time to impact memory retrieval and object discrimination.

Distinct profiles of cytotoxic granules in memory CD8 T cells correlate with function, differentiation stage, and antigen exposure.

Cytotoxic CD8 T cells exert their antiviral and antitumor activity primarily through the secretion of cytotoxic granules. Degranulation activity and cytotoxic granules (perforin plus granzymes) generally define CD8 T cells with cytotoxic function. In this study, we have investigated the expression of granzyme K (GrmK) in comparison to that of GrmA, GrmB, and perforin. The expression of the cytotoxic granules was assessed in virus-specific CD8 T cells specific to influenza virus, Epstein-Barr virus (EBV), cytomegalovirus (CMV), or human immunodeficiency virus type 1 (HIV-1). We observed a dichotomy between GrmK and perforin expression in virus-specific CD8 T cells. The profile in influenza virus-specific CD8 T cells was perforin(-) GrmB(-) GrmA(+/-) GrmK(+); in CMV-specific cells, it was perforin(+) GrmB(+) GrmA(+) GrmK(-/+); and in EBV- and HIV-1-specific cells, it was perforin(-/+) GrmB(+) GrmA(+) GrmK(+). On the basis of the delineation of memory and effector CD8 T cells with CD45RA and CD127, the GrmK(+) profile was associated with early-stage memory CD8 T-cell differentiation, the perforin(+) GrmB(+) GrmA(+) profile with advanced-stage differentiation, and the GrmB(+) GrmA(+) Grmk(+) profile with intermediate-stage differentiation. Furthermore, perforin and GrmB but not GrmA and GrmK correlated with cytotoxic activity. Finally, changes in antigen exposure in vitro and in vivo during primary HIV-1 infection and vaccination modulated cytotoxic granule profiles. These results advance our understanding of the relationship between distinct profiles of cytotoxic granules in memory CD8 T cells and function, differentiation stage, and antigen exposure.

Strategic Task Force on Alcohol - Interim Report

The Commission on Liquor Licensing was established by the Minister for Justice, Equality and Law Reform in November 2000 to review the Liquor Licensing system in Ireland. The Commission published an Interim Report with a set of recommendations1, one of which was the establishment of a task force. A High Level Inter-DepartmentalWorking Group considered the report and certain actions were agreed by different Government Departments.The Department of Health and Children agreed to establish a Strategic Task Force on Alcohol. This is their interim report.    

Age differences in the EEG N2 and P3 components during an interference task

The age-related increase in interference susceptibility has been well documented and largely attributed to a deficit in inhibition. In the present study, event-related potentials were used to investigate EEG correlates of inhibitory processing in an interference "Arrow" task. A specific interest was addressed to theN2 and P3 components that respectively refers to conflict monitoring and to efficiency of inhibition processes (Anguera et al,. 2011). Younger (N=10, Mage=24.6) and older (N=10, Mage=65.5) participants were invited to perform a task consisting in deciding, as fast and accurately as possible, whether an arrow presented on a computer screen points to the left or the right, irrespective of its position on the screen (left, middle or right). Responses were provided by key-presses using the left and right indexes. Three conditions were considered: congruent (arrow pointing to the same direction as that of the side of the screen on which it appears), incongruent (arrow pointing to the opposite direction), and neutral (arrow presented at the center of the screen). A total of 56 trials per conditions were performed. Behaviorally, the results showed that in the incongruent condition the percent of correct responses significantly decreased in both groups. After adjustment with simple RT (additional control task), the increased RTs obtained in the old group were significantly more pronounced in the incongruent condition. With respect to electrophysiological data, results showed that frontal site (Fz), the N2 amplitude was significantly larger for the younger as compared to the older (- 2.55 μV vs. -0.62 μV respectively) whatever the condition. At central site (Cz), the P3 amplitude significantly decreased in the older compared to the younger in the incongruent condition only. Our findings suggest that the increased RTs observed in older participants during the incongruent condition is more specifically linked to late cognitive resources involved in inhibiting prepotent response tendencies rather than associated with earlier stages of treatment dedicated to conflict monitoring.

Flexible Training Strategy (National Task Force on Medical Staffing)

Flexible Training Strategy (National Task Force on Medical Staffing) The Flexible Training Strategy, while endorsing flexible/part-time options recognises that the preferred option for the majority of doctors-in-training and consultants is most likely to continue to be full-time training and work. Click here to download PDF

Report of the National Task Force on Medical Staffing (Hanly report)

Report of the National Task Force on Medical Staffing (Hanly report) Patients deserve the best possible care that the Irish health services can deliver. At present, most frontline medical care in hospitals is delivered by non-consultant hospital doctors (NCHDs), the majority of whom work excessively long hours. Patients have limited access to consultant care. NCHDs will soon be required by law to work fewer hours. This will have significant benefits for both doctors and patients. Click here to download PDF 1.7mb

Report of the National Task Force on Medical Staffing (Hanly report)

Click here to download PDF