Approximate logic synthesis: a survey

Approximate computing is an emerging paradigm that, by relaxing the requirement for full accuracy, offers benefits in terms of design area and power consumption. This paradigm is particularly attractive in applications where the underlying computation has inherent resilience to small errors. Such applications are abundant in many domains, including machine learning, computer vision, and signal processing. In circuit design, a major challenge is the capability to synthesize the approximate circuits automatically without manually relying on the expertise of designers. In this work, we review methods devised to synthesize approximate circuits, given their exact functionality and an approximability threshold. We summarize strategies for evaluating the error that circuit simplification can induce on the output, which guides synthesis techniques in choosing the circuit transformations that lead to the largest benefit for a given amount of induced error. We then review circuit simplification methods that operate at the gate or Boolean level, including those that leverage classical Boolean synthesis techniques to realize the approximations. We also summarize strategies that take high-level descriptions, such as C or behavioral Verilog, and synthesize approximate circuits from these descriptions

Exploratory analysis of transposable elements expression in the C. elegans early embryo

Background: Transposable Elements (TE) are mobile sequences that make up large portions of eukaryote genomes. The functions they play within the complex cellular architecture are still not clearly understood, but it is becoming evident that TE have a role in several physiological and pathological processes. In particular, it has been shown that TE transcription is necessary for the correct development of mice embryos and that their expression is able to finely modulate transcription of coding and non-coding genes. Moreover, their activity in the central nervous system (CNS) and other tissues has been correlated with the creation of somatic mosaicisms and with pathologies such as neurodevelopmental and neurodegenerative diseases as well as cancers. Results: We analyzed TE expression among different cell types of the Caenorhabditis elegans (C. elegans) early embryo asking if, where and when TE are expressed and whether their expression is correlated with genes playing a role in early embryo development. To answer these questions, we took advantage of a public C. elegans embryonic single-cell RNA-seq (sc-RNAseq) dataset and developed a bioinformatics pipeline able to quantify reads mapping specifically against TE, avoiding counting reads mapping on TE fragments embedded in coding/non-coding transcripts. Our results suggest that i) canonical TE expression analysis tools, which do not discard reads mapping on TE fragments embedded in annotated transcripts, may over-estimate TE expression levels, ii) Long Terminal Repeats (LTR) elements are mostly expressed in undifferentiated cells and might play a role in pluripotency maintenance and activation of the innate immune response, iii) non-LTR are expressed in differentiated cells, in particular in neurons and nervous system-Associated tissues, and iv) DNA TE are homogenously expressed throughout the C. elegans early embryo development. Conclusions: TE expression appears finely modulated in the C. elegans early embryo and different TE classes are expressed in different cell types and stages, suggesting that TE might play diverse functions during early embryo development

Analysis of LINE1 Retrotransposons in Huntington’s Disease

Transposable elements (TEs) are mobile genetic elements that made up about half the human genome. Among them, the autonomous non-LTR retrotransposon long interspersed nuclear element-1 (L1) is the only currently active TE in mammals and covers about 17% of the mammalian genome. L1s exert their function as structural elements in the genome, as transcribed RNAs to influence chromatin structure and as retrotransposed elements to shape genomic variation in somatic cells. L1s activity has been shown altered in several diseases of the nervous system. Huntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by an expansion of a CAG repeat in the HTT gene which leads to a gradual loss of neurons most prominently in the striatum and, to a lesser extent, in cortical brain regions. The length of the expanded CAG tract is related to age at disease onset, with longer repeats leading to earlier onset. Here we carried out bioinformatic analysis of public RNA-seq data of a panel of HD mouse models showing that a decrease of L1 RNA expression recapitulates two hallmarks of the disease: it correlates to CAG repeat length and it occurs in the striatum, the site of neurodegeneration. Results were then experimentally validated in HttQ111 knock-in mice. The expression of L1-encoded proteins was independent from L1 RNA levels and differentially regulated in time and tissues. The pattern of expression L1 RNAs in human HD post-mortem brains showed similarity to mouse models of the disease. This work suggests the need for further study of L1s in HD and adds support to the current hypothesis that dysregulation of TEs may be involved in neurodegenerative diseases

Emergency surgery for recurrent intraabdominal cancer

Recurrent abdominal cancer can manifest in many ways but there are certain situations that are a great challenge to clinicians. Emergency presentation is one such situation. Surgeons are faced with a therapeutic dilemma that on the one hand most of these patients have a limited life expectancy, and on the other surgical procedures are unavoidable. We reviewed our experience of recurrent abdominal cancers presenting with acute abdominal symptoms requiring emergency

The added value of operator’s judgement in thyroid nodule ultrasound classification arising from histologically based comparison of different risk stratification systems.

Objective: Several ultrasound classifications for thyroid nodules were proposed but their accuracy is still debated, since mainly estimated on cytology and not on histology. The aim of this study was to test the diagnostic accuracy and the inter-classification agreement of AACE/ACE-AME, American Thyroid Association (ATA), British Thyroid Association (BTA), and Modena Ultrasound Thyroid Classification (MUT) that stratifies malignancy risk considering also the clinician subjective impression. Methods: A prospective study collecting thyroid nodule features at ultrasound and histological diagnosis was conducted. Ultrasound features were collected following a preformed checklist in candidates for surgery because of indeterminate, suspicious, or malignant cytology. All the nodules, besides the cytologically suspicious one, were blinded analyzed. MUT score was applied prospectively, and the others retrospectively. Sensitivity, specificity, diagnostic cut-off value, and accuracy of each classification were calculated. The overall agreement between classifications was tested by Bland-Altman, and agreement between single nodule analysis by different classifications by Weighted Cohen's Kappa. Results: In classifying a total of 457 nodules, MUT has the highest accuracy (AUC 0.808) and specificity (89%), followed by ATA and BTA, and finally by AACE/ACE-AME. ATA, BTA, and MUT are highly interchangeable. Considering agreement between single nodule analyses, ATA and BTA had the best (κ = 0.723); AACE/ACE-AME showed slight agreement with BTA (κ = 0.177) and MUT (κ = 0.183), and fair agreement with ATA (κ = 0.282); MUT had fair agreement with both ATA (κ = 0.291) and BTA (κ = 0.271). Conclusion: Classifications have an acceptable overall diagnostic accuracy, improved using a less rigid system that takes into consideration operator subjective impression

Shared decision-making in trauma and emergency surgery settings. A literature review

Emergency teams are made up of professionals of different specialities, including emergency physicians, surgeons, anesthesiologists, and nurses. Such units are characterized by the need to face unexpected situations with little time to make clinical decisions. In trauma and emergency settings, clinicians must act in a coordinated way, ensuring, at the same time, proper knowledge transfer and sharing to reach the best possible result for the patient. While such dynamics must be explicit and clear within the team, involving the patient in the decision-making process may require additional tools and procedures. Indeed, the time to engage with the patient and the family to understand the patient’s wishes and treatment preferences may be limited or absent at all. While the so-called shared decision-making (SDM) stands as one of the pillars of the modern patient-centric healthcare scenario, knowledge translation and transfer dynamics may appear particularly challenging in emergency settings. Starting from an investigation of the recent literature on SDM, the paper presents a literature review of the barriers, facilitators, and knowledge translation dynamics of SDM in trauma and emergency surgery. Results assess the importance, tools, and dynamics of SDM processes

Transposable element activation promotes neurodegeneration in a Drosophila model of Huntington's disease

Huntington's disease (HD) is an autosomal dominant disorder with progressive motor dysfunction and cognitive decline. The disease is caused by a CAG repeat expansion in the IT15 gene, which elongates a polyglutamine stretch of the HD protein, Huntingtin. No therapeutic treatments are available, and new pharmacological targets are needed. Retrotransposons are transposable elements (TEs) that represent 40% and 30% of the human and Drosophila genomes and replicate through an RNA intermediate. Mounting evidence suggests that mammalian TEs are active during neurogenesis and may be involved in diseases of the nervous system. Here we show that TE expression and mobilization are increased in a Drosophila melanogaster HD model. By inhibiting TE mobilization with Reverse Transcriptase inhibitors, polyQ-dependent eye neurodegeneration and genome instability in larval brains are rescued and fly lifespan is increased. These results suggest that TE activation may be involved in polyQ-induced neurotoxicity and a potential pharmacological target

Improving splenic conservation rate after trauma by applying a protocol for non-operative management and follow-up: A propensity-score analysis

Background: There are shared guidelines about Non-Operative Management (NOM) of splenic injuries, but some unanswered questions remain. The aim of the present study is to establish the usefulness of a standardized protocol for management and follow-up of NOM patients with splenic injuries. Methods: Multicenter retrospective observational study including patients with major blunt trauma (ISS.15) with splenic injuries managed between January 1st 2014 and December 31st 2016 in two Italian I level Trauma Centers: one with a standardized management and follow-up protocol for NOM (Bufalini Hospital, Cesena, BH), and the other without it (ASST Papa Giovanni XXIII Hospital, Bergamo, PG23H). Comparison between patients' outcomes were performed and a propensity score model was calculated. Results: 47 patients managed in BH and 49 patients in PG23H were included. In BH, a higher proportion of patients was treated with NOM (72.3 % vs. 53.1 %, p ¼ 0.051). There was no difference in complication rate and mortality in patients treated with NOM in the two hospitals. A borderline significant trend to a higher NOM failure rate in PG23H was found (BH 0.0 % vs. PG23H 11.3 %, p ¼ 0.076). The total splenic conservation rate was significantly higher in BH (BH 72.3 % vs. PG23H 46.9 %, p ¼ 0.011). After the Propensity Score based matching, 72 patients were included and the total splenic conservation rate was significantly higher in BH (BH: 77.8 % vs. PG23H: 50.9 %, p ¼ 0.014). Conclusions: The application of a protocol for in-hospital management and follow-up for NOM of patients with splenic injury could decrease the NOM failure rate and improve splenic conservation rate