Understanding person acquisition using an interactive activation and competition network

Face perception is one of the most developed visual skills that humans display, and recent work has attempted to examine the mechanisms involved in face perception through noting how neural networks achieve the same performance. The purpose of the present paper is to extend this approach to look not just at human face recognition, but also at human face acquisition. Experiment 1 presents empirical data to describe the acquisition over time of appropriate representations for newly encountered faces. These results are compared with those of Simulation 1, in which a modified IAC network capable of modelling the acquisition process is generated. Experiment 2 and Simulation 2 explore the mechanisms of learning further, and it is demonstrated that the acquisition of a set of associated new facts is easier than the acquisition of individual facts in isolation of one another. This is explained in terms of the advantage gained from additional inputs and mutual reinforcement of developing links within an interactive neural network system. <br/

Carbon dioxide and ocean acidification observations in UK waters. Synthesis report with a focus on 2010–2015

Key messages: 1.1 The process of ocean acidification is now relatively well-documented at the global scale as a long-term trend in the open ocean. However, short-term and spatial variability can be high. 1.2 New datasets made available since Charting Progress 2 make it possible to greatly improve the characterisation of CO2 and ocean acidification in UK waters. 3.1 Recent UK cruise data contribute to large gaps in national and global datasets. 3.2 The new UK measurements confirm that pH is highly variable, therefore it is important to measure consistently to determine any long term trends. 3.3 Over the past 30 years, North Sea pH has decreased at 0.0035±0.0014 pH units per year. 3.4 Upper ocean pH values are highest in spring, lowest in autumn. These changes reflect the seasonal cycles in photosynthesis, respiration (decomposition) and water mixing. 3.5 Carbonate saturation states are minimal in the winter, and lower in 7 more northerly, colder waters. This temperature-dependence could have implications for future warming of the seas. 3.6 Over the annual cycle, North-west European seas are net sinks of CO2. However, during late summer to autumn months, some coastal waters may be significant sources. 3.7 In seasonally-stratified waters, sea-floor organisms naturally experience lower pH and saturation states; they may therefore be more vulnerable to threshold changes. 3.8 Large pH changes (0.5 - 1.0 units) can occur in the top 1 cm of sediment; however, such effects are not well-documented. 3.9 A coupled forecast model estimates the decrease in pH trend within the North Sea to be -0.0036±0.00034 pH units per year, under a high greenhouse gas emissions scenario (RCP 8.5). 3.10 Seasonal estimates from the forecast model demonstrate areas of the North Sea that are particularly vulnerable to aragonite undersaturation

Prevalence of the HOXB13 G84E prostate cancer risk allele in men treated with radical prostatectomy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106912/1/bju12522.pd

Permafrost Landscape History Shapes Fluvial Chemistry, Ecosystem Carbon Balance, and Potential Trajectories of Future Change

Intensifying permafrost thaw alters carbon cycling by mobilizing large amounts of terrestrial substrate into aquatic ecosystems. Yet, few studies have measured aquatic carbon fluxes and constrained drivers of ecosystem carbon balance across heterogeneous Arctic landscapes. Here, we characterized hydrochemical and landscape controls on fluvial carbon cycling, quantified fluvial carbon fluxes, and estimated fluvial contributions to ecosystem carbon balance across 33 watersheds in four ecoregions in the continuous permafrost zone of the western Canadian Arctic: unglaciated uplands, ice-rich moraine, and organic-rich lowlands and till plains. Major ions, stable isotopes, and carbon speciation and fluxes revealed patterns in carbon cycling across ecoregions defined by terrain relief and accumulation of organics. In previously unglaciated mountainous watersheds, bicarbonate dominated carbon export (70% of total) due to chemical weathering of bedrock. In lowland watersheds, where soil organic carbon stores were largest, lateral transport of dissolved organic carbon (50%) and efflux of biotic CO2 (25%) dominated. In watersheds affected by thaw-induced mass wasting, erosion of ice-rich tills enhanced chemical weathering and increased particulate carbon fluxes by two orders of magnitude. From an ecosystem carbon balance perspective, fluvial carbon export in watersheds not affected by thaw-induced wasting was, on average, equivalent to 6%–16% of estimated net ecosystem exchange (NEE). In watersheds affected by thaw-induced wasting, fluvial carbon export approached 60% of NEE. Because future intensification of thermokarst activity will amplify fluvial carbon export, determining the fate of carbon across diverse northern landscapes is a priority for constraining trajectories of permafrost region ecosystem carbon balance

An investigation to assess ankle mobility in healthy individuals from the application of multi-component compression bandages and compression hosiery

Background An investigation was undertaken to compare the effect of multi-component compression bandages and compression hosiery kits on individuals’ range of ankle motion whilst wearing typical and medical footwear, and barefoot. Methods A convenience sample of 30 healthy individuals recruited from the staff and student population at the University of Huddersfield, UK. Plantarflexion/dorsiflexion range of ankle motion (ROAM) was measured in participants over 6 steps in every combination of typical, medical and no footwear; and multi-component bandages, compression hosiery and no garments. Results Controlling for age, gender and garments, the use of typical footwear was associated with a mean increase in ROAM of 2.54° at best estimate compared with barefoot; the use of medical footwear was associated with a mean decrease in ROAM of 1.12° at best estimate compared with barefoot. Controlling for age, gender and footwear, the use of bandaging was associated with a mean decrease in ROAM of 2.51° at best estimate compared with no garments. Controlling for age, gender and footwear, the use of hosiery was not associated with a significant change in ROAM compared with no garments. Conclusions Bandages appear to restrict ROAM more than hosiery when used in conjunction with a variety of footwear types

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Acquisition of suppressive function by conventional T cells limits antitumor immunity upon Treg depletion

Regulatory T (Treg) cells contribute to immune homeostasis but suppress immune responses to cancer. Strategies to disrupt Treg cell–mediated cancer immunosuppression have been met with limited clinical success, but the underlying mechanisms for treatment failure are poorly understood. By modeling Treg cell–targeted immunotherapy in mice, we find that CD4+ Foxp3− conventional T (Tconv) cells acquire suppressive function upon depletion of Foxp3+ Treg cells, limiting therapeutic efficacy. Foxp3− Tconv cells within tumors adopt a Treg cell–like transcriptional profile upon ablation of Treg cells and acquire the ability to suppress T cell activation and proliferation ex vivo. Suppressive activity is enriched among CD4+ Tconv cells marked by expression of C-C motif receptor 8 (CCR8), which are found in mouse and human tumors. Upon Treg cell depletion, CCR8+ Tconv cells undergo systemic and intratumoral activation and expansion, and mediate IL-10–dependent suppression of antitumor immunity. Consequently, conditional deletion of Il10 within T cells augments antitumor immunity upon Treg cell depletion in mice, and antibody blockade of IL-10 signaling synergizes with Treg cell depletion to overcome treatment resistance. These findings reveal a secondary layer of immunosuppression by Tconv cells released upon therapeutic Treg cell depletion and suggest that broader consideration of suppressive function within the T cell lineage is required for development of effective Treg cell–targeted therapies

Cholangiocyte organoids can repair bile ducts after transplantation in the human liver.

Organoid technology holds great promise for regenerative medicine but has not yet been applied to humans. We address this challenge using cholangiocyte organoids in the context of cholangiopathies, which represent a key reason for liver transplantation. Using single-cell RNA sequencing, we show that primary human cholangiocytes display transcriptional diversity that is lost in organoid culture. However, cholangiocyte organoids remain plastic and resume their in vivo signatures when transplanted back in the biliary tree. We then utilize a model of cell engraftment in human livers undergoing ex vivo normothermic perfusion to demonstrate that this property allows extrahepatic organoids to repair human intrahepatic ducts after transplantation. Our results provide proof of principle that cholangiocyte organoids can be used to repair human biliary epithelium

Human cytomegalovirus latency-associated proteins elicit immune-suppressive IL-10 producing CD4⁺ T cells.

Human cytomegalovirus (HCMV) is a widely prevalent human herpesvirus, which, after primary infection, persists in the host for life. In healthy individuals, the virus is well controlled by the HCMV-specific T cell response. A key feature of this persistence, in the face of a normally robust host immune response, is the establishment of viral latency. In contrast to lytic infection, which is characterised by extensive viral gene expression and virus production, long-term latency in cells of the myeloid lineage is characterised by highly restricted expression of viral genes, including UL138 and LUNA. Here we report that both UL138 and LUNA-specific T cells were detectable directly ex vivo in healthy HCMV seropositive subjects and that this response is principally CD4⁺ T cell mediated. These UL138-specific CD4⁺ T cells are able to mediate MHC class II restricted cytotoxicity and, importantly, show IFNγ effector function in the context of both lytic and latent infection. Furthermore, in contrast to CDCD4⁺ T cells specific to antigens expressed solely during lytic infection, both the UL138 and LUNA-specific CD4⁺ T cell responses included CD4⁺ T cells that secreted the immunosuppressive cytokine cIL-10. We also show that cIL-10 expressing CD4⁺ T-cells are directed against latently expressed US28 and UL111A. Taken together, our data show that latency-associated gene products of HCMV generate CD4⁺ T cell responses in vivo, which are able to elicit effector function in response to both lytic and latently infected cells. Importantly and in contrast to CD4⁺ T cell populations, which recognise antigens solely expressed during lytic infection, include a subset of cells that secrete the immunosuppressive cytokine cIL-10. This suggests that HCMV skews the T cell responses to latency-associated antigens to one that is overall suppressive in order to sustain latent carriage in vivo

Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial

Background Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus.Methods This open-label, randomised clinical trial was undertaken at 30 UK emergency departments at secondary and tertiary care centres. Participants aged 6 months to under 18 years, with convulsive status epilepticus requiring second-line treatment, were randomly assigned (1:1) using a computer-generated randomisation schedule to receive levetiracetam (40 mg/kg over 5 min) or phenytoin (20 mg/kg over at least 20 min), stratified by centre. The primary outcome was time from randomisation to cessation of convulsive status epilepticus, analysed in the modified intention-to-treat population (excluding those who did not require second-line treatment after randomisation and those who did not provide consent). This trial is registered with ISRCTN, number ISRCTN22567894.Findings Between July 17, 2015, and April 7, 2018, 1432 patients were assessed for eligibility. After exclusion of ineligible patients, 404 patients were randomly assigned. After exclusion of those who did not require second-line treatment and those who did not consent, 286 randomised participants were treated and had available data: 152 allocated to levetiracetam, and 134 to phenytoin. Convulsive status epilepticus was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive status epilepticus was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (hazard ratio 1·20, 95% CI 0·91–1·60; p=0·20). One participant who received levetiracetam followed by phenytoin died as a result of catastrophic cerebral oedema unrelated to either treatment. One participant who received phenytoin had serious adverse reactions related to study treatment (hypotension considered to be immediately life-threatening [a serious adverse reaction] and increased focal seizures and decreased consciousness considered to be medically significant [a suspected unexpected serious adverse reaction]). Interpretation Although levetiracetam was not significantly superior to phenytoin, the results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, suggest it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus