Digital Signal Processing: State-of-the-Art at CERN and Recommendations

Dramatic hardware performance improvements over the last decades have paved the way to the ascent of digital techniques for processing signals, with a concurrent and parallel interest in Digital Signal Processing (DSPing) and in the use of Digital Signal Processors (DSPs). Recent discussions within PS showed that there are needs for DSP-qualified manpower in new projects that cannot be fully satisfied internally. In order to determine how PS can best profit from the growing importance and efficiency of DSP technologies, with an effort compatible with the available divisional resources, a DSP working group was created. Its mandate is to advise PS management on the best way to proceed in the DSPs and DSPing domains. In particular, the issues targeted are wide-ranging, from evaluating the state-of-the-art at CERN to hardware standardisation and required training. This report gives the findings of the working group and presents its closing recommendations

Development of an Activity Patterns Scale (APS)

Six activity patterns were identified across various self-report measures in participants with chronic pain: Pain Avoidance, Activity Avoidance; Task Contingent Persistence; Excessive Persistence, Pain Contingent Persistence and Pacing (Kindermans et al., 2011). It was proposed that instruments assessing “pacing” should include items addressing one specific pacing behavior (breaking tasks into smaller pieces; taking frequent short rests and speeding up or slowing down) with a single goal (increasing activity level, conserve energy for valued activities and pain reduction) (Nielson et al., 2013). The aim of the present study was to develop an instrument to assess the activity patterns identified by Kindermans et al. (2011). The instrument also included three pacing scales one for each of the aforementioned goals. Methods A sample of 229 patients with fibromyalgia and 62 suffering other rheumatic diseases answered online the APS and the “Patterns of Activity Measure-Pain” (POAM-P) (Cane et al., 2007). Three alternative factor structures were tested by confirmatory factor analyses performed via structural equation modelling. . Results The structure with the best fit had 8 factors corresponding to the hypothesized scales: Pain Avoidance (α=.60), Activity Avoidance (α=.60); Task Contingent Persistence (α=.81); Excessive Persistence (α=.84), Pain Contingent Persistence (α=.70), Pacing for increasing activity (α=.76), Pacing for energy conservation (α=.72) and Pacing for pain reduction (α=.65). The correlations with the POAM-P scales were high and in the postulated direction. Conclusions The APS showed adequate reliability and structural validity. According to these results, Avoidance, Persistence and Pacing seem to be multidimensional constructs.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

A Head Start Farm to Family Pilot Program Increased Fruit and Vegetable Intake among Families

Fresh Produce, Fresh Start was a pilot farm to family study which tested the effectiveness of a local produce delivery program on dietary intake of Head Start participants. Utilizing a pre-test/post-test design, measures collected from Head Start parents included 24-hour recall of dietary intake, height and weight, and a food security questionnaire. Intent-to-treat analysis was conducted using paired t-tests. Significant increases were found in intake of vitamin A, vitamin C, fiber, vegetable, and fruit and vegetable servings combined (p \u3c .05) for participants (N = 51). In particular, fruit and vegetable intake increased by 1.4 servings per day. Food security status and weight status did not significantly change. Results indicate that a produce delivery program has potential to improve dietary intake of Head Start families and, possibly, other populations, impacting lifelong consumption habit

Low-Income Mothers\u27 Perceptions of Barriers to Using Farmers Markets: A SNAP-Ed Initiative to Understand Access Points to Local Foods

The study reported here describes a Virginia Family Nutrition Program\u27s target population\u27s perceptions of barriers to using a farmers market to access local foods. Mothers from a rural county photographed their shopping experience. Using a photo elicitation process to develop themes related to food access, the mothers identified barriers to shopping at farmers markets. The results can provide guidance to agents, program assistants, and farmers market coordinators on promoting use of farmers markets by low-income populations. The development of experiential learning opportunities to overcome barriers is critical if farmers markets are encouraged as an avenue for promoting healthy eating

Developing a conceptual framework for the relationship between food security status and mental health among low-income mothers

IntroductionBuilding household resiliency is one strategy that may help insulate households from the effects of food system volatility that contributes to in food insecurity. A stronger understanding of the relationship between food security and mental health is needed to identify potential factors for intervention to improve household resiliency to food system stressors. Because mothers often make household food decisions, they are an important population for building household resiliency. The purpose of this study was to develop and test a conceptual framework for the relationship between food security and mental health for low-income mothers and to identify potential targets for intervention.MethodsA conceptual framework was developed based on the existing literature on mental health and food security, as well as factors that impact both constructs. This framework was tested by a path analysis using data from a 2021 cross-sectional survey of low-income Virginia mothers that used validated scales to assess food security status, indicators of mental and physical health, food coping strategies, and social support.Results and discussionThe initial model was systematically adapted to develop the final retained model. The retained model did not include a direct effect of food security on mental health, but highlighted two significant mediators of the relationship, food coping strategies and social support. While the effect of social support was not practically significant, the effects of food coping strategies as a mediator from food security to perceived stress and life satisfaction were small (β = 0.21, 0.14, respectively; p < 0.001). The retained model provides a framework for understanding the relationship between food security and mental health and highlights potential targets for intervention. Notably, reducing the need for mothers to utilize food coping strategies should be targeted on multiple levels to reduce the impact on mental health and ultimately improve resiliency to future food system shocks

SynGAP splice variants display heterogeneous spatio-temporal expression and subcellular distribution in the developing mammalian brain

Altres ajuts: Financial support for this work was provided by: Career Integration Grant (ref. 304111), Ramón y Cajal Fellowship (RYC-2011-08391p) IEDI-2017-00822; ; BES-2013-063720 (MINECO) to GG; MH096847 (NIH), MH108408 (NIH) and NS064079 (NIH) to GR and RO1 MH112151 (NIH) to RLH. All experiments were conducted in compliance with the ARRIVE guidelines.The SynGAP protein is a major regulator of synapse biology and neural circuit function. Genetic variants linked to epilepsy and intellectual disability disrupt synaptic function and neural excitability. SynGAP has been involved in multiple signaling pathways and can regulate small GTPases with very different roles. Yet, the molecular bases behind this pleiotropy are poorly understood. We hypothesize that different SynGAP isoforms will mediate different sets of functions and that deciphering their spatio-temporal expression and subcellular localization will accelerate understanding their multiple functions. Using isoform-specific antibodies recognizing SynGAP in mouse and human samples we found distinctive developmental expression patterns for all SynGAP isoforms in five mouse brain areas. Particularly noticeable was the delayed expression of SynGAP-α1 isoforms, which directly bind to postsynaptic density-95, in cortex and hippocampus during the first 2 weeks of postnatal development. Suggesting that during this period other isoforms would have a more prominent role. Furthermore, we observed subcellular localization differences between isoforms, particularly throughout postnatal development. Consistent with previous reports, SynGAP was enriched in the postsynaptic density in the mature forebrain. However, SynGAP was predominantly found in non-synaptic locations in a period of early postnatal development highly sensitive to SynGAP levels. While, α1 isoforms were always found enriched in the postsynaptic density, α2 isoforms changed from a non-synaptic to a mostly postsynaptic density localization with age and β isoforms were always found enriched in non-synaptic locations. The differential expression and subcellular distribution of SynGAP isoforms may contribute to isoform-specific regulation of small GTPases, explaining SynGAP pleiotropy. Syngap1 gene encodes for different synaptic Ras/Rap GTPase-activating (SynGAP) isoforms which are key for brain function. SynGAP C-termini splice variants show different spatio-temporal expression and subcellular localization in the developing mouse brain. This study reveals a non-synaptic and heterogenous role of SynGAP spliced variants. Depicted abundance differences only allow relative comparison within a given tissue (top panel), postnatal age (PND, middle panel), or subcellular distribution (bottom panel). Ctx, cortex; Hip, hippocampus; Str, striatum; OB, Olfactory Bulb; Crb, cerebellum and tSynGAP, total SynGAP

HPV infection and immunochemical detection of cell-cycle markers in verrucous carcinoma of the penis

Penile verrucous carcinoma is a rare disease and little is known of its aetiology or pathogenesis. In this study we examined cell-cycle proteins expression and correlation with human papillomavirus infection in a series of 15 pure penile verrucous carcinomas from a single centre. Of 148 penile tumours, 15 (10%) were diagnosed as pure verrucous carcinomas. The expression of the cell-cycle-associated proteins p53, p21, RB, p16INK4A and Ki67 were examined by immunohistochemistry. Human papillomavirus infection was determined by polymerase chain reaction to identify a wide range of virus types. The expression of p16INK4A and Ki67 was significantly lower in verrucous carcinoma than in usual type squamous cell carcinoma, whereas the expression of p53, p21 and RB was not significantly different. p53 showed basal expression in contrast to usual type squamous cell carcinoma. Human papillomavirus infection was present in only 3 out of 13 verrucous carcinomas. Unique low-risk, high-risk and mixed viral infections were observed in each of the three cases. In conclusion, lower levels of p16INK4A and Ki67 expressions differentiate penile verrucous carcinoma from usual type squamous cell carcinoma. The low Ki67 index reflects the slow-growing nature of verrucous tumours. The low level of p16INK4A expression and human papillomavirus detection suggests that penile verrucous carcinoma pathogenesis is unrelated to human papillomavirus infection and the oncogenes and tumour suppressor genes classically altered by virus infection.Peer reviewedFinal Accepted Versio

High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells

Tyrosine kinase inhibitors (TKIs), despite their efficacy as anticancer therapeutics, are associated with cardiovascular side effects ranging from induced arrhythmias to heart failure. We used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), generated from 11 healthy individuals and 2 patients receiving cancer treatment, to screen U.S. Food and Drug Administration-approved TKIs for cardiotoxicities by measuring alterations in cardiomyocyte viability, contractility, electrophysiology, calcium handling, and signaling. With these data, we generated a "cardiac safety index" to reflect the cardiotoxicities of existing TKIs. TKIs with low cardiac safety indices exhibit cardiotoxicity in patients. We also derived endothelial cells (hiPSC-ECs) and cardiac fibroblasts (hiPSC-CFs) to examine cell type-specific cardiotoxicities. Using high-throughput screening, we determined that vascular endothelial growth factor receptor 2 (VEGFR2)/platelet-derived growth factor receptor (PDGFR)-inhibiting TKIs caused cardiotoxicity in hiPSC-CMs, hiPSC-ECs, and hiPSC-CFs. With phosphoprotein analysis, we determined that VEGFR2/PDGFR-inhibiting TKIs led to a compensatory increase in cardioprotective insulin and insulin-like growth factor (IGF) signaling in hiPSC-CMs. Up-regulating cardioprotective signaling with exogenous insulin or IGF1 improved hiPSC-CM viability during cotreatment with cardiotoxic VEGFR2/PDGFR-inhibiting TKIs. Thus, hiPSC-CMs can be used to screen for cardiovascular toxicities associated with anticancer TKIs, and the results correlate with clinical phenotypes. This approach provides unexpected insights, as illustrated by our finding that toxicity can be alleviated via cardioprotective insulin/IGF signaling

BRAIN & SPINAL CORD DAMAGE & REHABILITATION

Stroke and traumatic injury in brain or spinal cord are often life-threating conditions and major causes of death or permanent disability with high impact in the health care system. There are several stages of intervention to improve the neurological outcome. Acutely, fast interventions aiming to reestablish cerebral blood flow in ischemic stroke, to stop bleeding after brain hemorrhage, and to reduce edema after contusions are amongst mandatory actions. Current studies aim to develop accompanying strategies for brain cell protection based on enhancing endogenous protective mechanism, blocking cell death pathways, or through immunomodulation. After the acute phase, interventions are intended to promote recovery of function using rehabilitation with state-of-the-art technologies enabled by robotics. Other advanced strategies include cell, gene, and immune therapies, and brain function modulation with the aid of smart nanotechnologies. There is great expectation in the fast evolving novel approaches for improvement of neurological deficits in these unpredictable and devastating conditionPeer reviewe

Prognostic significance of FLT3-ITD length in AML patients treated with intensive regimens

FLT3-ITD mutations are detected in approximately 25% of newly diagnosed adult acute myeloid leukemia (AML) patients and confer an adverse prognosis. The FLT3-ITD allelic ratio has clear prognostic value. Nevertheless, there are numerous manuscripts with contradictory results regarding the prognostic relevance of the length and insertion site (IS) of the FLT3-ITD fragment. We aimed to assess the prognostic impact of these variables on the complete remission (CR) rates, overall survival (OS) and relapse-free survival (RFS) of AML patients with FLT3-ITDmutations. We studied the FLT3-ITD length of 362 adult AML patients included in the PETHEMA AML registry. We tried to validate the thresholds of ITD length previously published (i.e., 39 bp and 70 bp) in intensively treated AML patients (n = 161). We also analyzed the mutational profile of 118 FLT3-ITD AML patients with an NGS panel of 39 genes and correlated mutational status with the length and IS of ITD. The AUC of the ROC curve of the ITD length for OS prediction was 0.504, and no differences were found when applying any of the thresholds for OS, RFS or CR rate. Only four out of 106 patients had ITD IS in the TKD1 domain. Our results, alongside previous publications, confirm that FLT3-ITD length lacks prognostic value and clinical applicability. © 2021, The Author(s)