Reliability of two behavioral tools to assess pain in preterm neonates

CONTEXT: One of the main difficulties in adequately treating the pain of neonatal patients is the scarcity of validated pain evaluation methods for this population. OBJECTIVE: To analyze the reliability of two behavioral pain scales in neonates. TYPE OF STUDY: Cross-sectional. SETTING: University hospital neonatal intensive care unit. PARTICIPANTS: 22 preterm neonates were studied, with gestational age of 34 ± 2 weeks, birth weight of 1804 ± 584 g, 68% female, 30 ± 12 hours of life, and 30% intubated. PROCEDURES: Two neonatologists (A and B) observed the patients at the bedside and on video films for 10 minutes. The Neonatal Facial Coding System and the Clinical Scoring System were scored at 1, 5, and 10 minutes. The final score was the median of the three values for each observer and scale. A and B were blinded to each other. Video assessments were made three months after bedside evaluations. MAIN MEASUREMENTS: End scores were compared between the observers using the intraclass correlation coefficient and bias analysis (paired t test and signal test). RESULTS: For the Neonatal Facial Coding System, at the bedside and on video, A and B showed a significant correlation of scores (intraclass correlation score: 0.62), without bias between them (t test and signal test: p > 0.05). For the Clinical Scoring System bedside assessment, A and B showed correlation of scores (intraclass correlation score: 0.55), but bias was also detected between them: A scored on average two points higher than B (paired t test and signal test: p 0,05). Para a Escala de Conforto Clínico à beira do leito, os escores obtidos por A e B mostraram uma correlação significante (0,55), foi detectado: o escore obtido por A foi, em média, dois pontos superior ao de B (teste t e do sinal: p < 0,05). Para a mesma escala aplicada em vídeo, os escores obtidos por A e B não mostraram correlação (0,25) e detectou-se viés (teste t e do sinal: p < 0,05). CONCLUSÃO: Os resultados reforçam a confiabilidade do Sistema de Codificação da Atividade Facial Neonatal aplicado à beira do leito para a avaliação da dor no recém-nascido pré-termo.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Neonatal DivisionUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Department of EpidemiologyUNIFESP, EPM, Neonatal DivisionUNIFESP, EPM, Department of EpidemiologySciEL

Is there life inside black holes?

Bound inside rotating or charged black holes, there are stable periodic planetary orbits, which neither come out nor terminate at the central singularity. Stable periodic orbits inside black holes exist even for photons. These bound orbits may be defined as orbits of the third kind, following the Chandrasekhar classification of particle orbits in the black hole gravitational field. The existence domain for the third kind orbits is rather spacious, and thus there is place for life inside supermassive black holes in the galactic nuclei. Interiors of the supermassive black holes may be inhabited by civilizations, being invisible from the outside. In principle, one can get information from the interiors of black holes by observing their white hole counterparts.Comment: 11 pages, 5 figures; references adde

Epigenetics as a mechanism driving polygenic clinical drug resistance

Aberrant methylation of CpG islands located at or near gene promoters is associated with inactivation of gene expression during tumour development. It is increasingly recognised that such epimutations may occur at a much higher frequency than gene mutation and therefore have a greater impact on selection of subpopulations of cells during tumour progression or acquisition of resistance to anticancer drugs. Although laboratory-based models of acquired resistance to anticancer agents tend to focus on specific genes or biochemical pathways, such 'one gene : one outcome' models may be an oversimplification of acquired resistance to treatment of cancer patients. Instead, clinical drug resistance may be due to changes in expression of a large number of genes that have a cumulative impact on chemosensitivity. Aberrant CpG island methylation of multiple genes occurring in a nonrandom manner during tumour development and during the acquisition of drug resistance provides a mechanism whereby expression of multiple genes could be affected simultaneously resulting in polygenic clinical drug resistance. If simultaneous epigenetic regulation of multiple genes is indeed a major driving force behind acquired resistance of patients' tumour to anticancer agents, this has important implications for biomarker studies of clinical outcome following chemotherapy and for clinical approaches designed to circumvent or modulate drug resistance

Simulation of Flow of Mixtures Through Anisotropic Porous Media using a Lattice Boltzmann Model

We propose a description for transient penetration simulations of miscible and immiscible fluid mixtures into anisotropic porous media, using the lattice Boltzmann (LB) method. Our model incorporates hydrodynamic flow, diffusion, surface tension, and the possibility for global and local viscosity variations to consider various types of hardening fluids. The miscible mixture consists of two fluids, one governed by the hydrodynamic equations and one by diffusion equations. We validate our model on standard problems like Poiseuille flow, the collision of a drop with an impermeable, hydrophobic interface and the deformation of the fluid due to surface tension forces. To demonstrate the applicability to complex geometries, we simulate the invasion process of mixtures into wood spruce samples.Comment: Submitted to EPJ

Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications.

Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA binding domain sequencing (MBD-seq). We applied all four methods to biological replicates of human embryonic stem cells to assess their genome-wide CpG coverage, resolution, cost, concordance and the influence of CpG density and genomic context. The methylation levels assessed by the two bisulfite methods were concordant (their difference did not exceed a given threshold) for 82% for CpGs and 99% of the non-CpG cytosines. Using binary methylation calls, the two enrichment methods were 99% concordant and regions assessed by all four methods were 97% concordant. We combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost. This, along with RNA-seq and ChIP-seq of the ES cells enabled us to detect regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression

Numerical study of wetting transitions on biomimetic surfaces using a lattice Boltzmann approach with large density ratio

The hydrophobicity of natural surfaces have drawn much attention of scientific communities in recent years. By mimicking natural surfaces, the manufactured biomimetic hydrophobic surfaces have been widely applied to green technologies such as self-cleaning surfaces. Although the theories for wetting and hydrophobicity have been developed, the mechanism of wetting transitions between heterogeneous wetting state and homogeneous wetting state is still not fully clarified. As understanding of wetting transitions is crucial for manufacturing a biomimetic superhydrophobic surface, more fundamental discussions in this area should be carried out. In the present work the wetting transitions are numerically studied using a phase field lattice Boltzmann approach with large density ratio, which should be helpful in understanding the mechanism of wetting transitions. The dynamic wetting transition processes between Cassie-Baxter state and Wenzel state are presented, and the energy barrier and the gravity effect on transition are discussed. It is found that the two wetting transition processes are irreversible for specific inherent contact angles and have different transition routes, the energy barrier exists on an ideally patterned surface and the gravity can be crucial to overcome the energy barrier and trigger the transition

Parallel and Distributed Exact Single-Source Shortest Paths with Negative Edge Weights

This paper presents parallel and distributed algorithms for single-sourceshortest paths when edges can have negative weights (negative-weight SSSP). Weshow a framework that reduces negative-weight SSSP in either setting to$n^{o(1)}$ calls to any SSSP algorithm that works with a virtual source. Morespecifically, for a graph with $m$ edges, $n$ vertices, undirected hop-diameter$D$, and polynomially bounded integer edge weights, we show randomizedalgorithms for negative-weight SSSP with (i) $W_{SSSP}(m,n)n^{o(1)}$ work and$S_{SSSP}(m,n)n^{o(1)}$ span, given access to an SSSP algorithm with$W_{SSSP}(m,n)$ work and $S_{SSSP}(m,n)$ span in the parallel model, (ii)$T_{SSSP}(n,D)n^{o(1)}$, given access to an SSSP algorithm that takes$T_{SSSP}(n,D)$ rounds in $\mathsf{CONGEST}$. This work builds off the recentresult of [Bernstein, Nanongkai, Wulff-Nilsen, FOCS'22], which gives anear-linear time algorithm for negative-weight SSSP in the sequential setting. Using current state-of-the-art SSSP algorithms yields randomized algorithmsfor negative-weight SSSP with (i) $m^{1+o(1)}$ work and $n^{1/2+o(1)}$ span inthe parallel model, (ii) $(n^{2/5}D^{2/5} + \sqrt{n} + D)n^{o(1)}$ rounds in$\mathsf{CONGEST}$. Our main technical contribution is an efficient reduction for computing alow-diameter decomposition (LDD) of directed graphs to computations of SSSPwith a virtual source. Efficiently computing an LDD has heretofore only beenknown for undirected graphs in both the parallel and distributed models. TheLDD is a crucial step of the algorithm in [Bernstein, Nanongkai, Wulff-Nilsen,FOCS'22], and we think that its applications to other problems in parallel anddistributed models are far from being exhausted.<br

Museum epigenomics: Characterizing cytosine methylation in historic museum specimens

Museum genomics has transformed the field of collections‐based research, opening up a range of new research directions for paleontological specimens as well as natural history specimens collected over the past few centuries. Recent work demonstrates that it is possible to characterize epigenetic markers such as DNA methylation in well preserved ancient tissues. This approach has not yet been tested in traditionally prepared natural history specimens such as dried bones and skins, the most common specimen types in vertebrate collections. In this study, we developed and tested methods to characterize cytosine methylation in dried skulls up to 76 years old. Using a combination of ddRAD and bisulphite treatment, we characterized patterns of cytosine methylation in two species of deer mouse (Peromyscus spp.) collected in the same region in Michigan in 1940, 2003, and 2013–2016. We successfully estimated methylation in specimens of all age groups, although older specimens yielded less data and showed greater interindividual variation in data yield than newer specimens. Global methylation estimates were reduced in the oldest specimens (76 years old) relative to the newest specimens (1–3 years old), which may reflect post‐mortem hydrolytic deamination. Methylation was reduced in promoter regions relative to gene bodies and showed greater bimodality in autosomes relative to female X chromosomes, consistent with expectations for methylation in mammalian somatic cells. Our work demonstrates the utility of historic specimens for methylation analyses, as with genomic analyses; however, studies will need to accommodate the large variance in the quantity of data produced by older specimens.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162784/5/men13115.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162784/4/men13115-sup-0003-AppendixS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162784/3/men13115-sup-0001-FigS1-S2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162784/2/men13115_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162784/1/men13115-sup-0002-TableS1-S2.pd

Management of intra-abdominal infections : recommendations by the WSES 2016 consensus conference

This paper reports on the consensus conference on the management of intra-abdominal infections (IAIs) which was held on July 23, 2016, in Dublin, Ireland, as a part of the annual World Society of Emergency Surgery (WSES) meeting. This document covers all aspects of the management of IAIs. The Grading of Recommendations Assessment, Development and Evaluation recommendation is used, and this document represents the executive summary of the consensus conference findings.Peer reviewe