Learned Garbage Collection

Several programming languages use garbage collectors (GCs) to automatically manage memory for the programmer. Such collectors must decide when to look for unreachable objects to free, which can have a large performance impact on some applications. In this preliminary work, we propose a design for a learned garbage collector that autonomously learns over time when to perform collections. By using reinforcement learning, our design can incorporate user-defined reward functions, allowing an autonomous garbage collector to learn to optimize the exact metric the user desires (e.g., request latency or queries per second). We conduct an initial experimental study on a prototype, demonstrating that an approach based on tabular Q learning may be promising

Clinical Role of CA125 in Worsening Heart Failure A BIOSTAT-CHF Study Subanalysis

OBJECTIVES The aim of this study was to evaluate the association between antigen carbohydrate 125 (CA125) and the risk of 1-year clinical outcomes in patients with worsening heart failure (HF).BACKGROUND CA125 is a widely available biomarker that is up-regulated in patients with acute HF and has been postulated as a useful marker of congestion and risk stratification.METHODS hi a large multicenter cohort of patients with worsening HF, either in-hospital or in the outpatient setting, the independent associations between CA125 and 1-year death and the composite of death/HF readmission (adjusted for outcome-specific prognostic risk score [BIOSTAT risk score]) were determined by using the Royston-Parmar method (N = 2356). In a sensitivity analysis, the prognostic implications of CA125 were also adjusted for a composite congestion score (CCS). Data were validated in the B1OSTAT-CHF (Biology Study to Tailored Treatment in Chronic Heart Failure validation) cohort (N = 1,630).RESULTS Surrogates of congestion, such as N-terminal pro-B-type natriuretic peptide and CCS, emerged as independent predictors of CA125. In muttivariabte survival analyses, higher CA125 was associated with an increased risk of mortality and the composite of death/HF readmission (p &lt;0.001 for both comparisons), even after adjustment for the CCS (p &lt;0.010 for both comparisons). The addition of CA125 to the B1OSTAT score led to a significant risk reclassification for both outcomes (category-free net reclassification improvement 0.137 [p &lt;0.001] and 0.104 [p 0.003] respectively). AR outcomes were confirmed in an independent validation cohort.CONCLUSIONS In patients with worsening HF, higher levels of CA125 were positively associated with parameters of congestion. Furthermore, CA125 remained independently associated with a higher risk of clinical outcomes, even beyond a predefined risk model and clinical surrogates of congestion. (C) 2020 by the American College of Cardiology Foundation.</p

Deeper Seated Than Skin Deep: Report of a Rare Case of Follicular Occlusion Tetrad and a Literature Review

Follicular occlusion tetrad (FOT) is a clinical syndrome consisting of hidradenitis suppurativa (HS), acne conglobata (AC), dissecting cellulitis of the scalp (DCS), and pilonidal cyst (PC). These entities typically occur independently, but occasionally present simultaneously comprising FOT. The four components share similar pathophysiology affecting the apocrine glands, follicular hyperkeratinization being the hallmark of each entity.Understanding shared similarities of each disease is paramount for the treatment approach as the relapsing and chronic nature of this syndrome can be burdening to patients. We present the case of a 22- year-old obese Hispanic man with a history of tobacco use who presented with worsening skin lesions. The patient developed extensive facial cystic acne 5 years before presentation, followed by left axillary hidradenitis suppurativa lesions two years before the presentation and right axillary involvement one year after. Skin manifestations then expanded to include the lower back, gluteal and perineal areas. The patient was diagnosed with FOT and despite conservative medical management, his lesions failed to improve. He ultimately underwent multiple staged excisional debridement surgeries and skin grafts. Our case underlines the presence of a syndromic association of cutaneous lesions that share a common pathogenesis and emphasizes that this entity requires a multidisciplinary approach. New biologic therapies continue to emerge and may potentially prevent the need for surgical intervention and the burden associated with it

Lynch Syndrome Associated with Two MLH1 Promoter Variants and Allelic Imbalance of MLH1 Expression

© 2015 The Authors. **Human Mutation published by Wiley Periodicals, Inc. Lynch syndrome is a hereditary cancer syndrome caused by a constitutional mutation in one of the mismatch repair genes. The implementation of predictive testing and targeted preventative surveillance is hindered by the frequent finding of sequence variants of uncertain significance in these genes. We aimed to determine the pathogenicity of previously reported variants (c.-28A > G and c.-7C > T) within the MLH1 5â²untranslated region (UTR) in two individuals from unrelated suspected Lynch syndrome families. We investigated whether these variants were associated with other pathogenic alterations using targeted high-throughput sequencing of the MLH1 locus. We also determined their relationship to gene expr ession and epigenetic alterations at the promoter. Sequencing revealed that the c.-28A > G and c.-7C > T variants were the only potentially pathogenic alterations within the MLH1 gene. In both individuals, the levels of transcription from the variant allele were reduced to 50% compared with the wild-type allele. Partial loss of expression occurred in the absence of constitutional epigenetic alterations within the MLH1 promoter. We propose that these variants may be pathogenic due to constitutional partial loss of MLH1 expression, and that this may be associated with intermediate penetrance of a Lynch syndrome phenotype. Our findings provide further evidence of the potential importance of noncoding variants in the MLH1 5â²UTR in the pathogenesis of Lynch syndrome.Link_to_subscribed_fulltex

Vacuolated neuroblastoma cells mimicking FAB L 3 lymphoblasts in bone marrow aspirates

Abundant cytoplasmic vacuolation of neuroblasts has been noted on bone marrow aspirate (BMA) smears of two patients with metastatic neuroblastoma. Occasional tumor cells were dispersed as individual cells as well as in clumps. These cells had basophilic cytoplasm and several nucleoli, reminiscent of L 3 lymphoblast morphology. Flow cytometric analysis of the bone marrow mononuclear cells and neuron-specific enolase staining of the bone marrow biopsy samples further distinguished the cells as neuroblasts. Cytoplasmic vacuolations of neuroblasts may be a feature of metastatic neuroblastoma cells in BMA smears. Pediatric Blood Cancer © 2006 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49289/1/20738_fta.pd

Brevi spunti sul d.lgs. n. 150/2009 e sulla sua applicabilità agli Enti locali

© 2014 Taylor & Francis Group, LLC. Gene silencing in cancer frequently involves hypermethylation and dense nucleosome occupancy across promoter regions. How a promoter transitions to this silent state is unclear. Using colorectal adenomas, we investigated nucleosome positioning, DNA methylation, and gene expression in the early stages of gene silencing. Genome-wide gene expression correlated with highly positioned nucleosomes upstream and downstream of a nucleosome-depleted transcription start site (TSS). Hypermethylated promoters displayed increased nucleosome occupancy, specifically at the TSS. We investigated 2 genes, CDH1 and CDKN2B, which were silenced in adenomas but lacked promoter hypermethylation. Instead, silencing correlated with loss of nucleosomes from the -2 position upstream of the TSS relative to normal mucosa. In contrast, permanent CDH1 silencing in carcinoma cells was characterized by promoter hypermethylation and dense nucleosome occupancy. Our findings suggest that silenced genes transition through an intermediary stage involving altered promoter nucleosome positioning, before permanent silencing by hypermethylation and dense nucleosome occupancy.Link_to_subscribed_fulltex

A 3D individual-based model to investigate the spatially heterogeneous response of bacterial biofilms to antimicrobial agents

The response of bacterial biofilms to treatment with antimicrobial agents is often characterized by the emergence of recalcitrant cellular microcolonies. We present an individual-based model to investigate the biophysical mechanisms of the selective resistance that arises within the biofilm and leads to a spatially heterogeneous response upon treatment with antibiotics. The response occurs in 3 distinct phases. In the first phase, the subpopulation of metabolically active cells diminishes due to antibiotic-induced cell death. Subsequently, in the second phase, increased nutrient availability allows dormant cells in the lower layers of the biofilm to transform into metabolically active cells. In the third phase, survival of the biofilm is governed by the interplay between 2 contrasting factors: (1) rate of antibiotic-induced cell death and (2) rate of transformation of dormant cells into active ones. Metabolically active cells at the distal edge of the biofilm sacrifice themselves to protect the dormant cells in the interior by (1) reducing local antibiotic concentrations and (2) increasing nutrient availability. In the presence of quorum sensing, biofilms exhibit increased tolerance compared with the quorum sensing-negative strains. Extracellular polymeric substance (EPS) forms a protective layer at the top of the biofilm, thereby limiting antibiotic penetration. The surviving cells, in turn, produce EPS resulting in a feedback-like mechanism of resistance. Whereas resistance in QS- biofilms occurs because of transformation of dormant cells into metabolically active cells, this transformation is less pronounced in QS+ biofilms, and resistance is a consequence of the sequestration of the antibiotic by EPS

Assessing Provisions and Requirements for the Sustainable Production of Plastics: Towards Achieving SDG 12 from the Consumers’ Perspective

Plastics are used widely, and modern civilization would have to behave differently without them. However, plastics pose a threat to sustainable life. This paper focuses on some of the provisions being made for sustainable production to date and focuses on one key sector-plastic manufacturing-where sustainable production patterns are urgently needed. The paper describes the latest trends related to plastic production, its environmental impacts, and how this sector is adjusting its processes in order to meet the current and forthcoming legal requirements and consumer demands. The methodological approach of the study has focused on both a literature review on the one hand and the consumers’ perspective obtained via a survey on the other. These two approaches were then crosschecked in order to assess current trends in plastic manufacturing and to understand how consumers see these trends as being consistent with the aims of the UN Sustainable Development Goal 12. The results obtained suggest that a greater engagement of consumers is needed in supporting the efforts to manage plastic more sustainably. Based on its findings, the paper provides useful insights linked to principles and tools for sustainable plastic production and design, and it demonstrates the usefulness and urgency of a sound materials management in order to tackle plastic pollution, one of today´s major environmental problems

Assessing provisions and requirements for the sustainable production of plastics: towards achieving SDG 12 from the consumers’ perspective

Plastics are used widely, and modern civilization would have to behave differently without them. However, plastics pose a threat to sustainable life. This paper focuses on some of the provisions being made for sustainable production to date and focuses on one key sector-plastic manufacturing-where sustainable production patterns are urgently needed. The paper describes the latest trends related to plastic production, its environmental impacts, and how this sector is adjusting its processes in order to meet the current and forthcoming legal requirements and consumer demands. The methodological approach of the study has focused on both a literature review on the one hand and the consumers’ perspective obtained via a survey on the other. These two approaches were then crosschecked in order to assess current trends in plastic manufacturing and to understand how consumers see these trends as being consistent with the aims of the UN Sustainable Development Goal 12. The results obtained suggest that a greater engagement of consumers is needed in supporting the efforts to manage plastic more sustainably. Based on its findings, the paper provides useful insights linked to principles and tools for sustainable plastic production and design, and it demonstrates the usefulness and urgency of a sound materials management in order to tackle plastic pollution, one of today’s major environmental problems