Under pressure: Response urgency modulates striatal and insula activity during decision-making under risk

When deciding whether to bet in situations that involve potential monetary loss or gain (mixed gambles), a subjective sense of pressure can influence the evaluation of the expected utility associated with each choice option. Here, we explored how gambling decisions, their psychophysiological and neural counterparts are modulated by an induced sense of urgency to respond. Urgency influenced decision times and evoked heart rate responses, interacting with the expected value of each gamble. Using functional MRI, we observed that this interaction was associated with changes in the activity of the striatum, a critical region for both reward and choice selection, and within the insula, a region implicated as the substrate of affective feelings arising from interoceptive signals which influence motivational behavior. Our findings bridge current psychophysiological and neurobiological models of value representation and action-programming, identifying the striatum and insular cortex as the key substrates of decision-making under risk and urgency

The role of viral genomics in understanding COVID-19 outbreaks in long-term care facilities

We reviewed all genomic epidemiology studies on COVID-19 in long-term care facilities (LTCFs) that had been published to date. We found that staff and residents were usually infected with identical, or near identical, SARS-CoV-2 genomes. Outbreaks usually involved one predominant cluster, and the same lineages persisted in LTCFs despite infection control measures. Outbreaks were most commonly due to single or few introductions followed by a spread rather than a series of seeding events from the community into LTCFs. The sequencing of samples taken consecutively from the same individuals at the same facilities showed the persistence of the same genome sequence, indicating that the sequencing technique was robust over time. When combined with local epidemiology, genomics allowed probable transmission sources to be better characterised. The transmission between LTCFs was detected in multiple studies. The mortality rate among residents was high in all facilities, regardless of the lineage. Bioinformatics methods were inadequate in a third of the studies reviewed, and reproducing the analyses was difficult because sequencing data were not available in many facilities

Ion beam generated surface ripples: new insight in the underlying mechanism

A new hydrodynamic mechanism is proposed for the ion beam induced surface patterning on solid surfaces. Unlike the standard mechanisms based on the ion beam impact generated erosion and mass redistribution at the free surface (proposed by Bradley-Harper (BH) and its extended theories), the new mechanism proposes that the ion beam induced saltation and creep processes, coupled with incompressible solid flow in amorphous layer, leads to the formation of ripple patterns at the amorphous/crystalline (a/c) interface and hence at the free surface. Ion beam stimulated solid flow inside the amorphous layer controls the wavelength, where as the amount of material transported and re-deposited at a/c interface control the amplitude of ripples. The new approach is verified by designed experiments and supported by the discrete simulation method.Comment: 12 pages, 6 figures. arXiv admin note: substantial text overlap with arXiv:1206.082

Development of a complex intervention to test the effectiveness of peer support in type 2 diabetes

BACKGROUND: Diabetes is a chronic illness which requires the individual to assume responsibility for their own care with the aim of maintaining glucose and blood pressure levels as close to normal as possible. Traditionally self management training for diabetes has been delivered in a didactic setting. In recent times alternatives to the traditional delivery of diabetes care have been investigated, for example, the concept of peer support which emphasises patient rather than professional domination. The aim of this paper is to describe the development of a complex intervention of peer support in type 2 diabetes for a randomised control trial in a primary care setting. METHODS: The Medical Research Council (MRC) framework for the development and evaluation of complex interventions for randomised control trials (RCT) was used as a theoretical guide to designing the intervention. The first three phases (Preclinical Phase, Phase 1, Phase 2) of this framework were examined in depth. The Preclinical Phase included a review of the literature relating to type 2 diabetes and peer support. In Phase 1 the theoretical background and qualitative data from 4 focus groups were combined to define the main components of the intervention. The preliminary intervention was conducted in Phase 2. This was a pilot study conducted in two general practices and amongst 24 patients and 4 peer supporters. Focus groups and semi structured interviews were conducted to collect additional qualitative data to inform the development of the intervention. RESULTS: The four components of the intervention were identified from the Preclinical Phase and Phase 1. They are: 1. Peer supporters; 2. Peer supporter training; 3. Retention and support for peer supporters; 4. Peer support meetings. The preliminary intervention was implemented in the Phase 2. Findings from this phase allowed further modeling of the intervention, to produce the definitive intervention. CONCLUSION: The MRC framework was instrumental in the development of a robust intervention of peer support of type 2 diabetes in primary care. TRIAL REGISTRATION: Current Controlled Trials ISRCTN42541690

Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family

The Working After Cancer Study (WACS): a population-based study of middle-aged workers diagnosed with colorectal cancer and their return to work experiences

<p>Abstract</p> <p>Background</p> <p>The number of middle-aged working individuals being diagnosed with cancer is increasing and so too will disruptions to their employment. The aim of the Working After Cancer Study is to examine the changes to work participation in the 12 months following a diagnosis of primary colorectal cancer. The study will identify barriers to work resumption, describe limitations on workforce participation, and evaluate the influence of these factors on health-related quality of life.</p> <p>Methods/Design</p> <p>An observational population-based study has been designed involving 260 adults newly-diagnosed with colorectal cancer between January 2010 and September 2011 and who were in paid employment at the time they were diagnosed. These cancer cases will be compared to a nationally representative comparison group of 520 adults with no history of cancer from the general population. Eligible cases will have a histologically confirmed diagnosis of colorectal cancer and will be identified through the Queensland Cancer Registry. Data on the comparison group will be drawn from the Household, Income and Labour Dynamics in Australia (HILDA) Survey. Data collection for the cancer group will occur at 6 and 12 months after diagnosis, with work questions also asked about the time of diagnosis, while retrospective data on the comparison group will be come from HILDA Waves 2009 and 2010. Using validated instruments administered via telephone and postal surveys, data will be collected on socio-demographic factors, work status and circumstances, and health-related quality of life (HRQoL) for both groups while the cases will have additional data collected on cancer treatment and symptoms, work productivity and cancer-related HRQoL. Primary outcomes include change in work participation at 12 months, time to work re-entry, work limitations and change in HRQoL status.</p> <p>Discussion</p> <p>This study will address the reasons for work cessation after cancer, the mechanisms people use to remain working and existing workplace support structures and the implications for individuals, families and workplaces. It may also provide key information for governments on productivity losses.</p> <p>Study Registration</p> <p>Australian and New Zealand Clinical Trial Registry No. <a href="http://www.anzctr.org.au/ACTRN12611000530921.aspx">ACTRN12611000530921</a></p

A general process for the development of peptide-based immunoassays for monoclonal antibodies

Monoclonal antibodies (mAb) are an important and growing class of cancer therapeutics, but pharmacokinetic analyses have in many cases been constrained by the lack of standard and robust pharmacologic assays. The goal of this project was to develop a general method for the production of immunoassays that can measure the levels of therapeutic monoclonal antibodies in biologic samples at relevant concentrations. Alemtuzumab and rituximab are monoclonal approved for the treatment of B-cell malignancies and were used as a model system. Phage-displayed peptide libraries were screened for peptide sequences recognized by alemtuzumab (anti-CD52) or rituximab (anti-CD20). Synthetic biotinylated peptides were used in enzyme-linked immunosorbent assays (ELISA). Peptides directly synthesized on polymer resin beads were used in an immunofluorescent-based assay. Peptide mimetope sequences were recovered for both mAb and confirmed by competitive staining and kinetic measurements. A peptide-based ELISA method was developed for each. The assay for rituximab had a limit of detection of 4 μg/ml, and the assay for alemtuzumab had a limit of detection of 1 μg/ml. Antibody-specific staining of peptide conjugated beads could be seen in a dose-dependent manner. Phage-displayed peptide libraries can be a source of highly specific mimetopes for therapeutic mAb. The biotinylated forms of those peptides are compatible with conventional ELISA methods with sensitivities comparable to other assay methods and sufficient for pharmacological studies of those mAb given at high dose. The process outlined here can be applied to any mAb to enable improved pharmacokinetic analysis during the development and clinical use of this class of therapies

CAS-MINE: Providing personalized services in context-aware applications by means of generalized rules

Context-aware systems acquire and exploit information on the user context to tailor services to a particular user, place, time, and/or event. Hence, they allowservice providers to adapt their services to actual user needs, by offering personalized services depending on the current user context. Service providers are usually interested in profiling users both to increase client satisfaction and to broaden the set of offered services. Novel and efficient techniques are needed to tailor service supply to the user (or the user category) and to the situation inwhich he/she is involved. This paper presents the CAS-Mine framework to efficiently discover relevant relationships between user context data and currently asked services for both user and service profiling. CAS-Mine efficiently extracts generalized association rules, which provide a high-level abstraction of both user habits and service characteristics depending on the context. A lazy (analyst-provided) taxonomy evaluation performed on different attributes (e.g., a geographic hierarchy on spatial coordinates, a classification of provided services) drives the rule generalization process. Extracted rules are classified into groups according to their semantic meaning and ranked by means of quality indices, thus allowing a domain expert to focus on the most relevant patterns. Experiments performed on three context-aware datasets, obtained by logging user requests and context information for three real applications, show the effectiveness and the efficiency of the CAS-Mine framework in mining different valuable types of correlations between user habits, context information, and provided services

Cluster Lenses

Clusters of galaxies are the most recently assembled, massive, bound structures in the Universe. As predicted by General Relativity, given their masses, clusters strongly deform space-time in their vicinity. Clusters act as some of the most powerful gravitational lenses in the Universe. Light rays traversing through clusters from distant sources are hence deflected, and the resulting images of these distant objects therefore appear distorted and magnified. Lensing by clusters occurs in two regimes, each with unique observational signatures. The strong lensing regime is characterized by effects readily seen by eye, namely, the production of giant arcs, multiple-images, and arclets. The weak lensing regime is characterized by small deformations in the shapes of background galaxies only detectable statistically. Cluster lenses have been exploited successfully to address several important current questions in cosmology: (i) the study of the lens(es) - understanding cluster mass distributions and issues pertaining to cluster formation and evolution, as well as constraining the nature of dark matter; (ii) the study of the lensed objects - probing the properties of the background lensed galaxy population - which is statistically at higher redshifts and of lower intrinsic luminosity thus enabling the probing of galaxy formation at the earliest times right up to the Dark Ages; and (iii) the study of the geometry of the Universe - as the strength of lensing depends on the ratios of angular diameter distances between the lens, source and observer, lens deflections are sensitive to the value of cosmological parameters and offer a powerful geometric tool to probe Dark Energy. In this review, we present the basics of cluster lensing and provide a current status report of the field.Comment: About 120 pages - Published in Open Access at: http://www.springerlink.com/content/j183018170485723/ . arXiv admin note: text overlap with arXiv:astro-ph/0504478 and arXiv:1003.3674 by other author