Emotional response inhibition is greater in older than younger adults

Emotional information rapidly captures our attention and also often invokes automatic response tendencies, whereby positive information motivates approach, while negative information encourages avoidance. However, many circumstances require the need to override or inhibit these automatic responses. Control over responses to emotional information remains largely intact in late life, in spite of age-related declines in cognitive control and inhibition of responses to non-emotional information. The goal of this behavioral study was to understand how the aging process influences emotional response inhibition for positive and negative information in older adults. We examined emotional response inhibition in 36 healthy older adults (ages 60–89) and 44 younger adults (ages 18–22) using an emotional Go/No-Go task presenting happy (positive), fearful (negative), and neutral faces. In both younger and older adults, happy faces produced more approach-related behavior (i.e., fewer misses), while fearful faces produced more avoidance-related behavior, in keeping with theories of approach/avoidance-motivated responses. Calculation of speed/accuracy trade-offs between response times and false alarm rates revealed that younger and older adults both favored speed at the expense of accuracy, most robustly within blocks with fearful faces. However, there was no indication that the strength of the speed/accuracy trade-off differed between younger and older adults. The key finding was that although younger adults were faster to respond to all types of faces, older adults had greater emotional response inhibition (i.e., fewer false alarms). Moreover, younger adults were particularly prone to false alarms for happy faces. This is the first study to directly test effects of aging on emotional response inhibition. Complementing previous literature in the domains of attention and memory, these results provide new evidence that in the domain of response inhibition older adults may more effectively employ emotion regulatory ability, albeit on a slower time course, compared to younger adults. Older adults’ enhanced adaptive emotion regulation strategies may facilitate resistance to emotional distraction. The present study extends the literature of emotional response inhibition in younger adulthood into late life, and in doing so further elucidates how cognitive aging interacts with affective control processes

Transcriptome and proteome analysis of tyrosine Kinase inhibitor treated canine mast cell tumour cells identifies potentially kit signaling-dependent genes.

Background Canine mast cell tumor proliferation depends to a large extent on the activity of KIT, a tyrosine kinase receptor. Inhibitors of the KIT tyrosine kinase have recently been introduced and successfully applied as a therapeutic agent for this tumor type. However, little is known on the downstream target genes of this signaling pathway and molecular changes after inhibition. Results Transcriptome analysis of the canine mast cell tumor cell line C2 treated for up to 72 hours with the tyrosine kinase inhibitor masitinib identified significant changes in the expression levels of approximately 3500 genes or 16% of the canine genome. Approximately 40% of these genes had increased mRNA expression levels including genes associated with the pro-proliferative pathways of B- and T-cell receptors, chemokine receptors, steroid hormone receptors and EPO-, RAS and MAP kinase signaling. Proteome analysis of C2 cells treated for 72 hours identified 24 proteins with changed expression levels, most of which being involved in gene transcription, e.g. EIA3, EIA4, TARDBP, protein folding, e.g. HSP90, UCHL3, PDIA3 and protection from oxidative stress, GSTT3, SELENBP1. Conclusions Transcriptome and proteome analysis of neoplastic canine mast cells treated with masitinib confirmed the strong important and complex role of KIT in these cells. Approximately 16% of the total canine genome and thus the majority of the active genes were significantly transcriptionally regulated. Most of these changes were associated with reduced proliferation and metabolism of treated cells. Interestingly, several pro-proliferative pathways were up-regulated, which may represent attempts of masitinib treated cells to activate alternative pro-proliferative pathways. These pathways may contain hypothetical targets for a combination therapy with masitinib to further improve its therapeutic effect

Patient active time during therapy sessions in postacute rehabilitation: Development and validation of a new measure

BACKGROUND AND PURPOSE: The accurate measurement of therapy intensity in postacute rehabilitation is important for research to improve outcomes in this setting. We developed and validated a measure of Patient Active Time during physical (PT) and occupational therapy (OT) sessions, as a proxy for therapy intensity. METHODS: This measurement validity study was carried out with 26 older adults admitted to a skilled nursing facility (SNF) for postacute rehabilitation with a variety of main underlying diagnoses, including hip fracture, cardiovascular diseases, stroke, and others. They were participants in a randomized controlled trial that compared an experimental high-intensity therapy to standard-of-care therapy. Patient Active Time was observed by research raters as the total number of minutes that a patient was actively engaging in therapeutic activities during PT and OT sessions. This was compared to patient movement (actigraphy) quantified during some of the same PT/OT sessions using data from three-dimensional accelerometers worn on the patient’s extremities. RESULTS: Activity measures were collected for 136 therapy sessions. Patient Active Time had high interrater reliability in both PT (r = 0.995, p < 0.001) and OT (r = 0.95, p = 0.012). Active time was significantly correlated with actigraphy in both PT (r = 0.73, p < 0.001) and OT (r = 0.60, p < 0.001) and discriminated between a high-intensity experimental condition and standard of care rehabilitation: in PT, 47.0 ± 13.5 min versus 16.7 ± 10.1 min (p < 0.001) and in OT, 46.2 ± 15.2 versus 27.7 ± 6.6 min (p < 0.001). CONCLUSIONS: Systematic observation of Patient Active Time provides an objective, reliable, and valid index of physical activity during PT and OT treatment sessions that has utility as a real-world alternative to the measurement of treatment intensity. This measure could be used to differentiate higher from lower therapy treatment intensity and to help determine the optimal level of active therapy time for patients in postacute and other settings

D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: a systematic review and meta-analysis of individual participant data

Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.2018-05-0

Gene conversion in human rearranged immunoglobulin genes

Over the past 20 years, many DNA sequences have been published suggesting that all or part of the V&lt;sub&gt;H&lt;/sub&gt; segment of a rearranged immunoglobulin gene may be replaced in vivo. Two different mechanisms appear to be operating. One of these is very similar to primary V(D)J recombination, involving the RAG proteins acting upon recombination signal sequences, and this has recently been proven to occur. Other sequences, many of which show partial V&lt;sub&gt;H&lt;/sub&gt; replacements with no addition of untemplated nucleotides at the V&lt;sub&gt;H&lt;/sub&gt;–V&lt;sub&gt;H&lt;/sub&gt; joint, have been proposed to occur by an unusual RAG-mediated recombination with the formation of hybrid (coding-to-signal) joints. These appear to occur in cells already undergoing somatic hypermutation in which, some authors are convinced, RAG genes are silenced. We recently proposed that the latter type of V&lt;sub&gt;H&lt;/sub&gt; replacement might occur by homologous recombination initiated by the activity of AID (activation-induced cytidine deaminase), which is essential for somatic hypermutation and gene conversion. The latter has been observed in other species, but not in human Ig genes, so far. In this paper, we present a new analysis of sequences published as examples of the second type of rearrangement. This not only shows that AID recognition motifs occur in recombination regions but also that some sequences show replacement of central sections by a sequence from another gene, similar to gene conversion in the immunoglobulin genes of other species. These observations support the proposal that this type of rearrangement is likely to be AID-mediated rather than RAG-mediated and is consistent with gene conversion

Investing in late-life Brain Capital

Within many societies and cultures around the world, older adults are too often undervalued and underappreciated. This exacerbates many key challenges that older adults may face. It also undermines the many positive aspects of late life that are of tremendous value at both an individual and societal level. We propose a new approach to elevate health and well-being in late life by optimizing late-life Brain Capital. This form of capital prioritizes brain skills and brain health in a brain economy, which the challenges and opportunities of the 21st-century demands. This approach incorporates investing in late-life Brain Capital, developing initiatives focused on building late-life Brain Capital

Positive information facilitates response inhibition in older adults only when emotion is task-relevant

Emotional information is integral to everyday life and impacts a variety of cognitive abilities including response inhibition, a critical skill for maintaining appropriate and flexible behaviour. However, reported effects of emotion on response inhibition are inconsistent in younger adults, and very limited in older adults. Effects of aging are especially relevant because emotion regulation improves with aging despite declining inhibitory control over neutral information. Across three studies, we assessed the impact of emotional facial expressions on response inhibition in younger and older adults while manipulating attention to task stimuli. Emotional faces (versus neutral faces) altered response inhibition only when task instructions required explicit attention to emotional attributes of the faces. When directly comparing fear faces to happy faces, both age groups had better response inhibition to happy faces. Age further influenced differences across conditions, in that happy faces enhanced response inhibition relative to neutral faces in older adults but not younger adults. Thus, emotional response inhibition for task-relevant (but not task-irrelevant) positive information is enhanced in late life compared to early adulthood. The present work extends the nascent literature on emotional response inhibition in aging, and proffers a framework to reconcile the mixed literature on this topic in younger adults

Combined Patterns of IGHV Repertoire and Cytogenetic/Molecular Alterations in Monoclonal B Lymphocytosis versus Chronic Lymphocytic Leukemia

Background:Chronic lymphocytic leukemia (CLL)-like monoclonal B lymphocytosis (MBL) with (MBLhi) or without (MBLlo) absolute B-lymphocytosis precedes most CLL cases,the specific determinants for malignant progression remaining unknown.Methodology/Principal Findings:For this purpose, simultaneous iFISH and molecular analysis of well-established cytogenetic alterations of chromosomes 11, 12, 13, 14 and 17 together with the pattern of rearrangement of the IGHV genes were performed in CLL-like cells from MBL and CLL cases. Our results based on 78 CLL-like MBL and 117 CLL clones from 166 subjects living in the same geographical area, show the existence of three major groups of clones with distinct but partially overlapping patterns of IGHV gene usage, IGHV mutational status and cytogenetic alterations. These included a group enriched in MBLloclones expressing specific IGHV subgroups (e.g. VH3-23) with no or isolated good-prognosis cytogenetic alterations, a second group which mainly consisted of clinical MBLhiand advanced stage CLL with a skewed but different CLL-associated IGHV gene repertoire (e.g. VH1-69), frequently associated with complex karyotypes and poor-prognosis cytogenetic alterations, and a third group of clones with intermediate features, with prevalence of mutated IGHV genes, and higher numbers of del(13q)+clonal B-cells.Conclusions/Significance:These findings suggest that the specific IGHV repertoire and IGHV mutational status of CLL-like B-cell clones may modulate the type of cytogenetic alterations acquired, their rate of acquisition and/or potentially also their clinical consequences. Further long-term follow-up studies investigating the IGHV gene repertoire of MBLloclones in distinct geographic areas and microenvironments are required to confirm our findings and shed light on the potential role of some antigen-binding BCR specificities contributing to clonal evolution

Framework for predictive sales and demand planning in customer-oriented manufacturing systems using data enrichment and machine learning

Companies with Make to Order MTO manufacturing have always faced the conflict of meeting a large volume of individual customer orders on time while remaining as flexible as possible Unlike Make to Stock MTS manufacturing planning the production requirements for MTO is a challenging task since incoming orders may vary in time and quantity while also being subject to a number of variables In some cases the delivery time allocated by the customer can be less than the required Order Lead Time to fulfil the order Manufacturers can respond to this with either with approached from production management or from data science This paper presents a framework to leverage the benefit of both domains We conduct a literature review and present the results of an expert workshop We propose criteria for a suitable data enrichment and the application of Machine Learning ML methods in sales and demand forecasting In conclusion the proposed framework helps to equip manufacturing companies with a structured strategy for data management and to utilize the benefit of ML for sales and demand forecastin

Cellular senescence predicts treatment outcome in metastasised colorectal cancer

Background: Cellular senescence is a terminal cell-cycle arrest that occurs in response to activated oncogenes and DNA-damaging chemotherapy. Whether cancer cell senescence at diagnosis might be predictive for treatment outcome is unknown. Methods: A senescence index (SI) was developed and used to retrospectively correlate the treatment outcome of 30 UICC stage IV colorectal cancer (CRC) patients with their SI at diagnosis. Results: 5-Fluorouracil/leucovorin-treated CRC patients achieved a significantly longer progression-free survival when presenting with SI-positive tumours before therapy (median 12.0 vs 6.0 months; P=0.044). Conclusion: Cancer cell senescence predicts treatment outcome in metastasised CRC. Prospective analyses of larger patient cohorts are needed