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DeepFakes pose a problem, not only in their scope for enabling crime or promoting disinformation, but also in their status as evidence. Although, to date, actual reports of DeepFake crimes are few, their potential is alarming. This article explores the current state of affairs with regard to the creation and detection of DeepFakes and what that means for criminal justice. It offers insights into the technology and considers the different techniques, current and proposed, for distinguishing the real from the unreal. How can the interests of justice be preserved when the technology so rigorously outpaces the law? [ABSTRACT FROM AUTHOR]

This article proposes an independent framework for the monitoring, oversight and regulation of hacking techniques used by law enforcement at the international level. Such techniques exert a direct impact on the sovereignty and enforcement jurisdiction of other States, but are currently only subject to unilateral and purely local authorization. Constitutional law at the national level prescribes close judicial scrutiny, but similar controls are generally lacking in virtual space. This article is intended to promote discussion on an area of criminal justice that currently operates in the shadows, but which should be brought further into the light. [ABSTRACT FROM AUTHOR]

Purpose : Surgical pyloroplasty or pyloromyotomy are often performed during esophagectomy with a view of improving gastric conduit drainage. However, the clinical importance of this is not clear, and some centers opt to omit this step. The aim of this meta-analysis is to compare the rates of pulmonary complications, anastomotic leak, mortality, delayed gastric emptying, and the need for further pyloric intervention, in patients undergoing esophagectomy with and without a drainage procedure. Methods: A database search of Medline, EMBASE, and Cochrane Library was performed to identify randomized control trials and cohort studies published between 2000 and 2020 which compared outcomes of esophagectomy with and without drainage procedures. A random-effects meta-analysis model was used to compare the rates of pulmonary complications, anastomotic leak, mortality, delayed gastric emptying, and the need for further pyloric intervention. Results: Three randomized and 12 non-randomized publications were identified, comprising a total of 2339 patients. No significant differences were found between the two groups with regard to pulmonary complications (RR 1.02 [95% CI, 0.78–1.33], p = 0.91), anastomotic leak (RR 1.14 [95% CI, 0.80–1.62], p = 0.48), mortality (RR 0.53 [95% CI, 0.23–1.26], p = 0.15), delayed gastric emptying (RR 0.98 [95% CI, 0.59–1.62], p = 0.93), and the need for further pyloric intervention (RR 1.99 [95% CI, 0.56–7.08], p = 0.29). Conclusion: Where post-operative pyloric treatment is available on demand, surgical pyloric drainage procedures may not have any significant clinical impact on patient outcomes for patients undergoing esophagectomy, though further good-quality randomized controlled trials are needed to confirm this. [ABSTRACT FROM AUTHOR]

There are a range of sphincter-preserving procedures available to treat anorectal fistula, some of which can be precluded, or rendered more optimal by specific features of fistula anatomy. Magnetic resonance imaging (MRI) is the gold standard modality for assessing anorectal fistula. To maximise clinical utility, the MRI report should accurately describe these clinically relevant features. We aimed to develop a minimum dataset for reporting MRI of anorectal fistula, in order to improve the assessment and management of these patients. A longlist of 70 potential items for the minimum dataset was generated through systematic review of the literature. This longlist was presented to radiologists, surgeons and gastroenterologists in an online survey to understand the features that shape current clinical practice. The longlist and survey results were then presented to an expert consensus panel to generate the final minimum dataset through discussion and anonymous voting. The final minimum dataset details the general characteristics, features of the internal and external openings, path of the fistula through the sphincters and any associated extensions and collections that should be described in all MRI reports for anal fistula. Additional surgical and perianal Crohn's disease subsets were developed to indicate the features that aid decision-making for these patients, in addition to a minimum dataset for the clinical request. This study represents a multi-disciplinary approach to developing a minimum dataset for MRI reporting of anal fistula, highlighting the most important features to report that can assist in clinical decision-making. Key Points: • This paper recommends the minimum features that should be included in all MRI reports for the assessment of anal fistula, including Parks classification, number of tracts, features of the internal and external opening, path of the tract through the sphincters, the presence and features of extensions and collections. • Additional features that aid decision-making for surgery or in the presence of Crohn's disease have been identified. • The items that should be included when requesting an MRI are specified. [ABSTRACT FROM AUTHOR]

Carbon-negative synthesis of biochemical products has the potential to mitigate global CO2 emissions. An attractive route to do this is the reverse β-oxidation (r-BOX) pathway coupled to the Wood-Ljungdahl pathway. Here, we optimize and implement r-BOX for the synthesis of C4-C6 acids and alcohols. With a high-throughput in vitro prototyping workflow, we screen 762 unique pathway combinations using cell-free extracts tailored for r-BOX to identify enzyme sets for enhanced product selectivity. Implementation of these pathways into Escherichia coli generates designer strains for the selective production of butanoic acid (4.9 ± 0.1 gL−1), as well as hexanoic acid (3.06 ± 0.03 gL−1) and 1-hexanol (1.0 ± 0.1 gL−1) at the best performance reported to date in this bacterium. We also generate Clostridium autoethanogenum strains able to produce 1-hexanol from syngas, achieving a titer of 0.26 gL−1 in a 1.5 L continuous fermentation. Our strategy enables optimization of r-BOX derived products for biomanufacturing and industrial biotechnology. An attractive route for carbon-negative synthesis of biochemical products is the reverse β-oxidation pathway coupled to the Wood-Ljungdahl pathway. Here the authors use a high-throughput in vitro prototyping workflow to screen 762 unique pathway combinations using cell-free extracts tailored for r-BOX to identify enzyme sets for enhanced product selectivity. [ABSTRACT FROM AUTHOR]

Actors are required to engage in multimodal modulations of their body, face, and voice in order to create a holistic portrayal of a character during performance. We present here the first trimodal analysis, to our knowledge, of the process of character portrayal in professional actors. The actors portrayed a series of stock characters (e.g., king, bully) that were organized according to a predictive scheme based on the two orthogonal personality dimensions of assertiveness and cooperativeness. We used 3D motion capture technology to analyze the relative expansion/contraction of 6 body segments across the head, torso, arms, and hands. We compared this with previous results for these portrayals for 4 segments of facial expression and the vocal parameters of pitch and loudness. The results demonstrated significant cross-modal correlations for character assertiveness (but not cooperativeness), as manifested collectively in a straightening of the head and torso, expansion of the arms and hands, lowering of the jaw, and a rise in vocal pitch and loudness. These results demonstrate what communication theorists refer to as "multichannel reinforcement". We discuss this reinforcement in light of both acting theories and theories of human communication more generally. [ABSTRACT FROM AUTHOR]

Juxtacellular interactions play an essential but still not fully understood role in both normal tissue development and tumour invasion. Using proliferating cell fronts as a model system, we explore the effects of cell–cell interactions on the geometry and dynamics of these one-dimensional biological interfaces. We observe two distinct scaling regimes of the steady state roughness of in-vitro propagating Rat1 fibroblast cell fronts, suggesting different hierarchies of interactions at sub-cell lengthscales and at a lengthscale of 2–10 cells. Pharmacological modulation significantly affects the proliferation speed of the cell fronts, and those modulators that promote cell mobility or division also lead to the most rapid evolution of cell front roughness. By comparing our experimental observations to numerical simulations of elastic cell fronts with purely short-range interactions, we demonstrate that the interactions at few-cell lengthscales play a key role. Our methodology provides a simple framework to measure and characterise the biological effects of such interactions, and could be useful in tumour phenotyping. [ABSTRACT FROM AUTHOR]

The accumulation of adenosine is strongly correlated with the need for sleep and the detection of sleep pressure is antagonised by caffeine. Caffeine also affects the circadian timing system directly and independently of sleep physiology, but how caffeine mediates these effects upon the circadian clock is unclear. Here we identify an adenosine-based regulatory mechanism that allows sleep and circadian processes to interact for the optimisation of sleep/wake timing in mice. Adenosine encodes sleep history and this signal modulates circadian entrainment by light. Pharmacological and genetic approaches demonstrate that adenosine acts upon the circadian clockwork via adenosine A1/A2A receptor signalling through the activation of the Ca2+ -ERK-AP-1 and CREB/CRTC1-CRE pathways to regulate the clock genes Per1 and Per2. We show that these signalling pathways converge upon and inhibit the same pathways activated by light. Thus, circadian entrainment by light is systematically modulated on a daily basis by sleep history. These findings contribute to our understanding of how adenosine integrates signalling from both light and sleep to regulate circadian timing in mice. Sleep pressure and circadian rhythms influence one another. However, the regulatory mechanisms are unclear. Here, the authors show that adenosine A1/A2A receptor antagonists, such as caffeine, shift circadian rhythms and enhance the effects of light, providing a molecular link between sleep pressure and circadian rhythm. [ABSTRACT FROM AUTHOR]

Background: Crohn's anal fistula is a challenging condition, and may require multiple surgical procedures. To replicate successful procedures, these must be adequately reported in the literature. The aim of this study was to review the quality of reporting of components of surgical interventions for Crohn's anal fistula. Methods: A systematic review was conducted. It was registered with PROSPERO (CRD:42019135157). The Medline and EMBASE databases were searched for studies reporting interventions intended to close fistula in patients with Crohn's disease, published between 1999 and August 2019. Abstracts and full texts were screened for inclusion by two reviewers. Dual extraction of data was performed to compare reporting to the TIDiER and Blencowe frameworks for reporting of interventions. Results: Initial searches identified 207 unique studies; 38 full texts were screened for inclusion and 33 were included. The most common study design was retrospective cohort (17/33), and the most frequently reported interventions were anal fistula plug (n = 8) and fibrin glue (n = 6). No studies showed coverage of all domains of TIDieR. Reporting was poor among domains related to who provided an intervention, where it was provided, and how it was tailored. Reporting of domains in the Blencowe framework was poor; the majority of studies did not report the component steps of procedures or efforts to standardise them. Conclusions: This study demonstrates that reporting on technical aspects of interventions for Crohn's anal fistula is poor. Surgeons should aim to improve reporting to allow accurate reproduction of techniques both in clinical practice and in clinical trials. [ABSTRACT FROM AUTHOR]

Law enforcement use of hacking techniques has become well-established and is an inevitable consequence not only of endemic anonymization used by computer-based criminals, but also of the increasing dominance of cloud-based computing models that challenge traditional notions of jurisdiction. Whilst recognising the many and legitimate concerns of privacy watchdogs this article explores how and why law enforcement uses malware to target criminals who would otherwise operate with virtual impunity. [ABSTRACT FROM AUTHOR]

We are developing a one-sided tomographic method for imaging prompt gamma rays, without moving the source, sample, or detector, in a standard prompt gamma activation analysis setting. Dual-plane pixelated CdZnTe detectors developed from a commercial system with external timing synchronization electronics are used to measure prompt gamma rays that are scattered in the first plane and subsequently absorbed in the second plane. Tomographic images have been reconstructed from the 2.2 MeV gamma rays from H in 3 mm plastic balls using inter-plane events for the first time, demonstrating the feasibility of spatially resolving mm scale H features. [ABSTRACT FROM AUTHOR]

Subjectivity is ubiquitous and implies perspectives that range in scope from the intrapersonal (as in individual musings and daydreams) to the intercultural (as in communication between and among identities) and in sophistication from the inchoate babblings of infants to the theoretical pronouncements of philosophers and mathematicians. Q methodology is a philosophical and conceptual framework that, in tandem with its technical and analytical procedures, provides the basis for a science of subjectivity that is applicable across all humanities and sciences as well as their extensions into public policy. This article presents the basic principles and procedures of Q methodology (rooted in the fundamentals of factor-analytic developments of the past century) and demonstrates its applicability to a variety of subject-matter domains, including literary interpretation, strategic planning and decision making, scientific creativity, program evaluation, and the intensive analysis of single cases. [ABSTRACT FROM AUTHOR]

Economically important softwood from conifers is mainly composed of the polysaccharides cellulose, galactoglucomannan and xylan, and the phenolic polymer, lignin. The interactions between these polymers lead to wood mechanical strength and must be overcome in biorefining. Here, we use 13C multidimensional solid-state NMR to analyse the polymer interactions in never-dried cell walls of the softwood, spruce. In contrast to some earlier softwood cell wall models, most of the xylan binds to cellulose in the two-fold screw conformation. Moreover, galactoglucomannan alters its conformation by intimately binding to the surface of cellulose microfibrils in a semi-crystalline fashion. Some galactoglucomannan and xylan bind to the same cellulose microfibrils, and lignin is associated with both of these cellulose-bound polysaccharides. We propose a model of softwood molecular architecture which explains the origin of the different cellulose environments observed in the NMR experiments. Our model will assist strategies for improving wood usage in a sustainable bioeconomy. Understanding the interactions between the constituents of the cell walls in wood is important for understanding the mechanical properties. Here, the authors report on a solid-state NMR study of never-dried softwood, noticing differences to previous reports and develop a model of softwood architecture. [ABSTRACT FROM AUTHOR]

The activation mechanism of the ErbB family of receptors is of considerable medical interest as they are linked to a number of human cancers, including an aggressive form of breast cancer. In the rat analogue of the human ErbB2 receptor, referred to as Neu, a point mutation in the transmembrane domain (V664E) has been shown to trigger oncogenic transformation. While the structural impact of this mutation has been widely studied in the past to yield models for the active state of the Neu receptor, little is known about the impact of cholesterol on its structure. Given previous reports of the influence of cholesterol on other receptor tyrosine kinases (RTKs), as well as the modulation of lipid composition in cancer cells, we wished to investigate how cholesterol content impacts the structure of the Neu transmembrane domain. We utilized high-resolution magic angle spinning solid-state NMR to measure 13C-13C coupling of selectively labelled probe residues in the Neu transmembrane domain in lipid bilayers containing cholesterol. We observe inter-helical coupling between residues that support helix-helix interactions on both dimerization motifs reported in the literature (A661-XXX-G665 and I659-XXX-V663). We further explore how changes in cholesterol concentration alter transmembrane domain interactions and the properties and mechanics of the bilayer. We interpret our results in light of previous studies relating RTK activity to cholesterol enrichment and/or depletion, and propose a novel model to explain our data that includes the recognition and binding of cholesterol by the Neu transmembrane domain through a putative cholesterol-recognition/interaction amino acid consensus sequence. [ABSTRACT FROM AUTHOR]

We investigate tin (Sn) and tin oxide (SnO2) nanoparticle catalysts deposited on gas diffusion layers for the electrochemical reduction of carbon dioxide (CO2) to formate. The performance and durability of these electrodes was evaluated in a gas-fed electrolysis cell with a flowing liquid electrolyte stream and an integrated reference electrode. The SnO2 electrodes achieved peak current densities of 385 ± 19 mA cm−2 while the Sn electrodes achieved peak current densities of 214 ± 6 mA cm−2, both at a formate selectivity > 70%. The associated peak formate production rates of 7.4 ± 0.6 mmol m−2 s−1 (Sn) and 14.9 ± 0.8 mmol m−2 s−1 (SnO2) were demonstrated for a 1-h electrolysis and compare favorably to prior literature. Post-test analyses reveal chemical and physical changes to both cathodes during electrolysis including oxide reduction at applied potentials more negative than − 0.6 V versus RHE, nanoparticle aggregation, and catalyst layer erosion. Understanding and mitigating these decay processes is key to extending electrode lifetime without sacrificing formate generation rates or process efficiency. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The circadian system plays an essential role in regulating the timing of human metabolism. Indeed, circadian misalignment is strongly associated with high rates of metabolic disorders. The properties of the circadian oscillator can be measured in cells cultured in vitro and these cellular rhythms are highly informative of the physiological circadian rhythm in vivo. We aimed to discover whether molecular properties of the circadian oscillator are altered as a result of type 2 diabetes. Methods: We assessed molecular clock properties in dermal fibroblasts established from skin biopsies taken from nine obese and eight non-obese individuals with type 2 diabetes and 11 non-diabetic control individuals. Following in vitro synchronisation, primary fibroblast cultures were subjected to continuous assessment of circadian bioluminescence profiles based on lentiviral luciferase reporters. Results: We observed a significant inverse correlation (ρ = −0.592; p < 0.05) between HbA1c values and circadian period length within cells from the type 2 diabetes group. RNA sequencing analysis conducted on samples from this group revealed that ICAM1, encoding the endothelial adhesion protein, was differentially expressed in fibroblasts from individuals with poorly controlled vs well-controlled type 2 diabetes and its levels correlated with cellular period length. Consistent with this circadian link, the ICAM1 gene also displayed rhythmic binding of the circadian locomotor output cycles kaput (CLOCK) protein that correlated with gene expression. Conclusions/interpretation: We provide for the first time a potential molecular link between glycaemic control in individuals with type 2 diabetes and circadian clock machinery. This paves the way for further mechanistic understanding of circadian oscillator changes upon type 2 diabetes development in humans. Data availability: RNA sequencing data and clinical phenotypic data have been deposited at the European Genome-phenome Archive (EGA), which is hosted by the European Bioinformatics Institute (EBI) and the Centre for Genomic Regulation (CRG), ega-box-1210, under accession no. EGAS00001003622. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Anal incontinence following childbirth is prevalent and has a significant impact upon quality of life (QoL). Currently, there is no standard assessment for women after childbirth to identify these symptoms. This systematic review aimed to identify non-invasive modalities used to identify women with anal incontinence following childbirth and assess response and reporting rates of anal incontinence for these modalities. Methods: Ovid Medline, Allied and Complementary Medicine Database (AMED), Cumulative Index of Nursing and Allied Health Literature (CINAHL), Cochrane Collaboration, EMBASE and Web of Science databases were searched for studies using non-invasive modalities published from January 1966 to May 2018 to identify women with anal incontinence following childbirth. Study data including type of modality, response rates and reported prevalence of anal incontinence were extracted and critically appraised. Results: One hundred and nine studies were included from 1602 screened articles. Three types of non-invasive modalities were identified: validated questionnaires/symptom scales (n = 36 studies using 15 different instruments), non-validated questionnaires (n = 50 studies) and patient interviews (n = 23 studies). Mean response rates were 92% up to 6 weeks after childbirth. Non-personalised assessment modalities (validated and non-validated questionnaires) were associated with reporting of higher rates of anal incontinence compared with patient interview at all periods of follow-up after childbirth, which was statistically significant between 6 weeks and 1 year after childbirth (p < 0.05). Conclusions: This systematic review confirms that questionnaires can be used effectively after childbirth to identify women with anal incontinence. Given the methodological limitations associated with non-validated questionnaires, assessing all women following childbirth for pelvic-floor symptomatology, including anal incontinence, using validated questionnaires should be considered. [ABSTRACT FROM AUTHOR]

Objective: To develop and prototype a high-throughput microplate assay to assess anaerobic microorganisms and lignocellulosic biomasses in a rapid, cost-effective screen for consolidated bioprocessing potential.Results: Clostridium thermocellum parent Δhpt strain deconstructed Avicel to cellobiose, glucose, and generated lactic acid, formic acid, acetic acid and ethanol as fermentation products in titers and ratios similar to larger scale fermentations confirming the suitability of a plate-based method for C. thermocellum growth studies. C. thermocellum strain LL1210, with gene deletions in the key central metabolic pathways, produced higher ethanol titers in the Consolidated Bioprocessing (CBP) plate assay for both Avicel and switchgrass fermentations when compared to the Δhpt strain.Conclusion: A prototype microplate assay system is developed that will facilitate high-throughput bioprospecting for new lignocellulosic biomass types, genetic variants and new microbial strains for bioethanol production. [ABSTRACT FROM AUTHOR]

Due to its high prevalence and associated risk of poor academic and health outcomes, adverse childhood experiences and trauma are considered a public health epidemic. In response, there has been a surge of initiatives aimed at helping institutions and individuals serving people with histories of trauma to adopt a trauma-informed care (TIC) approach. However, significant roadblocks to TIC research and practice include an unclear operational definition of TIC and the shortage of psychometrically robust instruments to evaluate TIC. To close these gaps, we used a partnership-based approach to develop a direct, efficient, and cost-effective measure of TIC focused on evaluating the TIC-relevant attitudes of staff working in schools, human service systems, and other settings serving individuals with histories of trauma. We then conducted a psychometric evaluation of the resultant measure, the Attitudes Related to Trauma-Informed Care (ARTIC) Scale, with a sample of 760 staff employed in education, human services, and health care. Study findings established support for the psychometric properties of the measure. Specifically, confirmatory factor analysis indicated that the seven-factor structure fit the data well. Scores on the ARTIC demonstrated strong internal consistency and test-retest reliability over 6 months for the 45-item and 35-item composites, the seven subscales, and the 10-item short form. Construct and criterion-related validity were supported by correlations with indicators of familiarity with TIC and staff- and system-level indicators of TIC implementation. The current study has implications for accelerating research on TIC and facilitating data-based decision making related to the adoption and implementation of TIC. [ABSTRACT FROM AUTHOR]

Purpose: Faecal incontinence is a physically, psychologically and socially disabling condition. NICE guidance (2007) recommends surgical intervention, including sacral nerve stimulation (SNS), after failed conservative therapies. The FENIX™ magnetic sphincter augmentation (MSA) device is a novel continence device consisting of a flexible band of interlinked titanium beads with magnetic cores that is placed around the anal canal to augment anal sphincter tone through passive attraction of the beads. Preliminary studies suggest the FENIX™ MSA is safe, but efficacy data is limited. Rigorous evaluation is required prior to widespread adoption. Method and design: The SaFaRI trial is a National Institute of Health Research (NIHR) Health Technology Assessment (HTA)-funded UK multi-site, parallel group, randomised controlled, unblinded trial that will investigate the use of the FENIX™ MSA, as compared to SNS, for adult faecal incontinence resistant to conservative management. Twenty sites across the UK, experienced in the treatment of faecal incontinence, will recruit 350 patients randomised equally to receive either SNS or FENIX™ MSA. Participants will be followed-up at 2 weeks post-surgery and at 6, 12 and 18months post-randomisation. The primary endpoint is success, as defined by device in use and ≥50 % improvement in the Cleveland Clinic Incontinence Score (CCIS) at 18 months post-randomisation. Secondary endpoints include complications, quality of life and cost effectiveness. Discussion: SaFaRI will rigorously evaluate a new technology for faecal incontinence, the FENIX™ MSA, allowing its safe and controlled introduction into current clinical practice. These results will inform the future surgical management of adult faecal incontinence. [ABSTRACT FROM AUTHOR]

The critical audit of Q methodology by Kampen and Tamás contains many errors of fact and understanding-indeed, a resistance to understanding that is compared to the Medicis' stance toward Galileo. Following a brief historical summary of similar ill-advised critiques of Q methodology in the 80 years since its introduction, responses are presented to various of the points raised: on the nature of subjectivity, the universe of subjective communicability (concourse) and samples drawn from it, the role of factor analysis and factor interpretation, the forced Q-sort distribution, the ratio between the number of participants and the number of statements in the Q sample, and sources of researcher bias. [ABSTRACT FROM AUTHOR]

PlexinA is a neuronal receptor protein that facilitates axon guidance during embryogenesis. This gene is associated with several neurological disorders including Alzheimer's disease, Parkinson's disease and autism. However, the effect of variants of PlexinA on brain structure remains unclear. We demonstrate that single-nucleotide polymorphisms within the intron and 3′-untranslated region segments of several human PlexinA genes alter the post-natal developmental trajectory of corpus callosum microstructure. This is the first demonstration that PLXNA mediation of neuroanatomical traits can be detected in humans using in vivo neuroimaging techniques. This result should encourage future research that targets specific disease-related polymorphisms and their relevant neural pathways. [ABSTRACT FROM AUTHOR]

The nature of daytime sources and night-time sinks of nitrous acid is a key uncertainty in understanding atmospheric oxidation and radical cycling. The accumulation of nitrous acid in the air has been observed to slow down during the night, implying the presence of a night-time sink. In addition, there may be a photochemical source of nitrous acid during the daytime. We used flow tube experiments, measurements of acid displacement efficiencies, and field monitoring of nitrous acid and nitrite concentrations to study the exchange of nitrous acid with soils. Here we show that nitrous acid can react with carbonates or soil at night and subsequently be displaced from soils during the day by air-to-soil transfer of hydrogen chloride and nitric acid, which are generated in the atmosphere photochemically. These processes provide a critical link between the sink of nitrous acid at night and its emission the following day. We conclude that the acid displacement process could contribute a substantial fraction of daytime nitrous acid emissions in numerous environments, including agricultural, urban and vegetated regions, and in any location subject to deposition of soil-derived mineral dust. [ABSTRACT FROM AUTHOR]