Showing papers by "Tel Aviv University published in 2022"

Maternal-neonatal transfer of SARS-CoV-2 immunoglobulin G antibodies among parturient women treated with BNT162b2 messenger RNA vaccine during pregnancy.

Abstract: BACKGROUND The exclusion of pregnant women from initial COVID-19 messenger RNA vaccine trials raised hesitancy regarding the benefits of vaccination for pregnant women, hence little is known about vaccines’ efficacy in this population. OBJECTIVE To determine the maternal-neonatal transplacental transfer of SARS-CoV-2 antibodies among vaccinated parturient women. A control group of COVID-19-recovered patients was included to compare the immunoglobulin G levels between vaccinated and recovered patients. STUDY DESIGN This is a prospective cohort study conducted in a single tertiary medical center in Israel between February and March 2021; parturient women vaccinated with the BNT162b2 messenger RNA vaccine during pregnancy were included and compared with COVID-19-recovered parturient women. SARS-CoV-2 immunoglobulin G antibodies were measured in maternal and cord sera, dried blood spot samples taken from newborns, and breast milk samples. The primary aim was to determine whether neonatal cord and dried blood spot samples were positive for SARS-CoV-2 antibodies and to evaluate the transfer ratio, defined as cord blood immunoglobulin G divided by maternal immunoglobulin G levels. RESULTS The study included 64 vaccinated parturient women and 11 parturient women who had COVID-19 during pregnancy. All maternal blood sera samples and 98.3% of the cord blood sera samples were positive for SARS-Cov-2 immunoglobulin G with median concentrations of 26.1 (interquartile range, 22.0–39.7) and 20.2 (interquartile range, 12.7–29.0), respectively. Similarly, 96.4% of neonatal blood spot samples and all breast milk samples were positive for SARS-CoV-2 immunoglobulin G with median concentrations of 11.0 (interquartile range, 7.2–12.8) and 4.9 (interquartile range, 3.8–6.0), respectively. There was a significant positive correlation between maternal serum levels of SARS-CoV-2 immunoglobulin G and cord blood (r=0.483; P=.0001), neonatal blood spot (r=0.515; P=.004), and breast milk levels (r=0.396; P=.005) of SARS-CoV-2 immunoglobulin G. The median placental transfer ratio of SARS-COV-2 immunoglobulin G was 0.77. Comparison of vaccinated and recovered COVID-19 patients revealed significantly higher SARS-CoV-2 immunoglobulin G levels in maternal serum and cord blood among vaccinated women (P CONCLUSION Our study demonstrated the efficient transfer of SARS-CoV-2 immunoglobulin G across the placenta in women, vaccinated with the BNT162b2 messenger RNA vaccine during pregnancy, to their neonates, with a positive correlation between maternal serum and cord blood antibody concentrations. In addition to maternal protection against COVID-19, the vaccine may also provide neonatal humoral immunity.

DestVI identifies continuums of cell types in spatial transcriptomics data

Abstract: Most spatial transcriptomics technologies are limited by their resolution, with spot sizes larger than that of a single cell. Although joint analysis with single-cell RNA sequencing can alleviate this problem, current methods are limited to assessing discrete cell types, revealing the proportion of cell types inside each spot. To identify continuous variation of the transcriptome within cells of the same type, we developed Deconvolution of Spatial Transcriptomics profiles using Variational Inference (DestVI). Using simulations, we demonstrate that DestVI outperforms existing methods for estimating gene expression for every cell type inside every spot. Applied to a study of infected lymph nodes and of a mouse tumor model, DestVI provides high-resolution, accurate spatial characterization of the cellular organization of these tissues and identifies cell-type-specific changes in gene expression between different tissue regions or between conditions. DestVI is available as part of the open-source software package scvi-tools ( https://scvi-tools.org ).

The BNT162b2 mRNA Covid-19 vaccine does not impair sperm parameters

Abstract:

Abstract

Research question

Does the BNT162b2 COVID-19 vaccine affect sperm parameters of patients with a normal or an abnormal semen analysis?

Design

Data were collected from male patients undergoing IVF treatment after completing vaccination between February 2021 and June 2021 (post-vaccine). For comparison, records of the same patients were reviewed before the vaccination (pre-vaccine) back to January 2017. Patients with azoospermia were excluded. Sperm parameters were compared between pre- and post-vaccine groups. Each patient served as self-control.

Results

Seventy-two patients were included in the study (median interquartile range [IQR] age 35.7 [33.0–43.0] years), of whom 57 had a normal semen analysis. The time between the first vaccine and the post-vaccine sperm analysis was 71.0 (40.5–104.8) days. The sperm parameters before and after the vaccination were as follows: sperm volume before 3.0 (2.0–4.0) and after 3.0 (1.6–3.9) ml, P = 0.02; sperm concentration before 26.5 (14.0–64.7) and after 31.0 (14.2–80.0) 10⁶/ml, P = 0.35; and total motile sperm count before 33.7 (9.0–66.0) and after 29 (6.0–97.5)10⁶, P = 0.96. Sub-group analyses were conducted for patients with male infertility and patients with a normal semen analysis. Neither of the sub-groups showed significant changes after vaccination.

Conclusion

Sperm parameters showed no significant changes after vaccination among men with a normal and abnormal semen analysis. Therefore, the BNT162b2 vaccine does not seem to affect sperm parameters. The preliminary results are reassuring for the entire global population, currently undergoing intense vaccination campaigns against COVID-19.

Observation of a correlated free four-neutron system

Abstract: A long-standing question in nuclear physics is whether chargeless nuclear systems can exist. To our knowledge, only neutron stars represent near-pure neutron systems, where neutrons are squeezed together by the gravitational force to very high densities. The experimental search for isolated multi-neutron systems has been an ongoing quest for several decades1, with a particular focus on the four-neutron system called the tetraneutron, resulting in only a few indications of its existence so far2-4, leaving the tetraneutron an elusive nuclear system for six decades. Here we report on the observation of a resonance-like structure near threshold in the four-neutron system that is consistent with a quasi-bound tetraneutron state existing for a very short time. The measured energy and width of this state provide a key benchmark for our understanding of the nuclear force. The use of an experimental approach based on a knockout reaction at large momentum transfer with a radioactive high-energy 8He beam was key.

The geometric phase in nonlinear frequency conversion

Abstract: The geometric phase of light has been demonstrated in various platforms of the linear optical regime, raising interest both for fundamental science as well as applications, such as flat optical elements. Recently, the concept of geometric phases has been extended to nonlinear optics, following advances in engineering both bulk nonlinear photonic crystals and nonlinear metasurfaces. These new technologies offer a great promise of applications for nonlinear manipulation of light. In this review, we cover the recent theoretical and experimental advances in the field of geometric phases accompanying nonlinear frequency conversion. We first consider the case of bulk nonlinear photonic crystals, in which the interaction between propagating waves is quasi-phase-matched, with an engineerable geometric phase accumulated by the light. Nonlinear photonic crystals can offer efficient and robust frequency conversion in both the linearized and fully-nonlinear regimes of interaction, and allow for several applications including adiabatic mode conversion, electromagnetic nonreciprocity and novel topological effects for light. We then cover the rapidly-growing field of nonlinear Pancharatnam-Berry metasurfaces, which allow the simultaneous nonlinear generation and shaping of light by using ultrathin optical elements with subwavelength phase and amplitude resolution. We discuss the macroscopic selection rules that depend on the rotational symmetry of the constituent meta-atoms, the order of the harmonic generations, and the change in circular polarization. Continuous geometric phase gradients allow the steering of light beams and shaping of their spatial modes. More complex designs perform nonlinear imaging and multiplex nonlinear holograms, where the functionality is varied according to the generated harmonic order and polarization. Recent advancements in the fabrication of three dimensional nonlinear photonic crystals, as well as the pursuit of quantum light sources based on nonlinear metasurfaces, offer exciting new possibilities for novel nonlinear optical applications based on geometric phases.

Long COVID-19 Liver Manifestation in Children

Abstract: Objectives: Severe acute respiratory syndrome coronavirus 2, the novel coronavirus responsible for coronavirus disease (COVID-19), has been a major cause of morbidity and mortality worldwide. Gastrointestinal and hepatic manifestations during acute disease have been reported extensively in the literature. Post-COVID-19 cholangiopathy has been increasingly reported in adults. In children, data are sparse. Our aim was to describe pediatric patients who recovered from COVID-19 and later presented with liver injury. Methods: This is a retrospective case series study of pediatric patients with post-COVID-19 liver manifestations. We collected data on demographics, medical history, clinical presentation, laboratory results, imaging, histology, treatment, and outcome. Results: We report 5 pediatric patients who recovered from COVID-19 and later presented with liver injury. Two types of clinical presentation were distinguishable. Two infants aged 3 and 5 months, previously healthy, presented with acute liver failure that rapidly progressed to liver transplantation. Their liver explant showed massive necrosis with cholangiolar proliferation and lymphocytic infiltrate. Three children, 2 aged 8 years and 1 aged 13 years, presented with hepatitis with cholestasis. Two children had a liver biopsy significant for lymphocytic portal and parenchyma inflammation, along with bile duct proliferations. All 3 were started on steroid treatment; liver enzymes improved, and they were weaned successfully from treatment. For all 5 patients, extensive etiology workup for infectious and metabolic etiologies was negative. Conclusions: We report 2 distinct patterns of potentially long COVID-19 liver manifestations in children with common clinical, radiological, and histopathological characteristics after a thorough workup excluded other known etiologies.

Studying interrelations of computational thinking and creativity: A scoping review (2011–2020)

Abstract: Both computational thinking (CT) and creativity have been recognized as key skills for today's learners. Over the last decade, research of both skills in a single context has emerged. In this paper, we present a scoping review of 62 such empirical from 2011 to 2020. Our goal was to have a thorough understanding of the educational settings in which research on both CT and creativity was conducted, the theoretical foundations it has laid down, and the research tools used. Our findings indicate a geographical bias (dominance of the US and prominence of developed European countries), as well as a focus on secondary education and on STEM-related disciplines; this could be explained by the current situation of CT spread. We also found that when studying CT and creativity jointly, it is most common to define CT in a broader perspective than merely programming of computer science. Additionally, while creativity is largely referred to as product-related, CT is barely referred to as such. Taken together, our findings point out some gaps in the current research of CT and creativity and suggest how it should be expended on the fertile grounds of creativity, as the latter crosses geographical, age, and subject borders. Doing so may build a bridge between CT and creativity in a way that will benefit both.

Limitations of Plain Film Radiography in Identification of Hyperextension Fractures in Patients With Ankylosing Spinal Disorders

Abstract: Study Design:Efficacy study.Objectives:To elucidate the limitations of radiography in patients with spinal ankylosing disorders (SAD) with an emphasis on thoracolumbar injuries, which have been les...

Device-related pressure ulcers: SECURE prevention. Second edition

Abstract: Journal of Wound CareVol. 31, No. Sup3a International Consensus DocumentFree AccessDevice-related pressure ulcers: SECURE prevention. Second editionAmit Gefen, Paulo Alves, Guido Ciprandi, Fiona Coyer, Catherine T Milne, Karen Ousey, Norihiko Ohura, Nicola Waters, Peter Worsley, Joyce Black, Michelle Barakat-Johnson, Dimitri Beeckman, Jacqui Fletcher, Holly Kirkland-Kyhn, Nils A. Lahmann, Zena Moore, Yohan Payan, Anna-Barbara SchlüerAmit GefenProfessor of Biomedical Engineering, The Herbert J. Berman Chair in Vascular Bioengineering, Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, IsraelSearch for more papers by this author, Paulo AlvesAssistant Professor and Coordinator, Wounds Research Laboratory, Catholic University of Portugal, Institute of Health Sciences, Centre for Interdisciplinary Research in Health, Lisbon, PortugalSearch for more papers by this author, Guido CiprandiChief Wound Care, Surgical Unit, Division of Plastic and Maxillofacial Surgery, Bambino Gesu’ Children's Hospital, Research Institute, Rome, ItalySearch for more papers by this author, Fiona CoyerProfessor of Nursing (joint appointment), Intensive Care Services, Royal Brisbane and Women's Hospital, School of Nursing, Queensland University of Technology, Brisbane, Australia. Visiting Professor, Institute for Skin Integrity and Infection Prevention, University of Huddersfield, UKSearch for more papers by this author, Catherine T MilneConnecticut Clinical Nursing Associates, Bristol Hospital Wound and Hyperbaric Medicine, Bristol, Connecticut, USSearch for more papers by this author, Karen OuseyProfessor of Skin Integrity, Director, Institute of Skin Integrity and Infection Prevention, School of Human and Health Sciences, Huddersfield University, UK; Clinical Professor, Queensland University of Technology, Australia; Visiting Professor, Royal College of Surgeons in Ireland, Dublin, Republic of IrelandSearch for more papers by this author, Norihiko OhuraProfessor, Department of Plastic, Reconstructive and Aesthetic Surgery, Kyorin University School of Medicine, Tokyo, JapanSearch for more papers by this author, Nicola WatersSenior Research Associate, Health, The Conference Board of Canada; Adjunct Professor, School of Nursing, University of British Columbia Okanagan, Kelowna, British Columbia, CanadaSearch for more papers by this author, Peter WorsleyAssociate Professor in Rehabilitative Bioengineering, Clinical Academic Facility in the School of Health Sciences, University of Southampton, UKSearch for more papers by this author, Joyce BlackProfessor, College of Nursing, University of Nebraska Medical Center. Nebraska, USSearch for more papers by this author, Michelle Barakat-JohnsonClinical Lead and Skin Integrity Lead, HAC Pressure Injury Coordinator, Sydney Local Health District; Adj Associate Professor, Faculty of Medicine and Health, University of Sydney, AustraliaSearch for more papers by this author, Dimitri BeeckmanProfessor, Skin Integrity Research Group (SKINT), Ghent University, Belgium; Professor and Vice-Head, School for Research and Internationalisation, Örebro University, SwedenSearch for more papers by this author, Jacqui FletcherIndependent Nurse Consultant, UKSearch for more papers by this author, Holly Kirkland-KyhnDirector of Wound Care. University of California Davis Medical Center, USSearch for more papers by this author, Nils A. LahmannDeputy Director, Geriatrics Research Group, Charité University Berlin, GermanySearch for more papers by this author, Zena MooreProfessor and Head, School of Nursing and Midwifery. Director, Skin Wounds and Trauma Research Centre, Royal College of Surgeons in Ireland, Dublin, Republic of IrelandSearch for more papers by this author, Yohan PayanResearch Director, Laboratoire TIMC-IMAG, Grenoble Alpes University, FranceSearch for more papers by this author, Anna-Barbara SchlüerAdvanced Nurse Practitioner, Paediatric Skin and Wound Management, Head of the Paediatric Skin Centre, Skin and Wound Management and Department of Nursing Science, University Children's Hospital, Zurich, SwitzerlandSearch for more papers by this authorAmit Gefen; Paulo Alves; Guido Ciprandi; Fiona Coyer; Catherine T Milne; Karen Ousey; Norihiko Ohura; Nicola Waters; Peter Worsley; Joyce Black; Michelle Barakat-Johnson; Dimitri Beeckman; Jacqui Fletcher; Holly Kirkland-Kyhn; Nils A. Lahmann; Zena Moore; Yohan Payan; Anna-Barbara SchlüerPublished Online:26 May 2022https://doi.org/10.12968/jowc.2022.31.Sup3a.S1AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail Executive summaryAlthough great strides have been made to tackle hospital-acquired pressure ulcers (HAPUs), there is a need for greater recognition of device-related pressure ulcers (DRPUs), including their causes, management and prevention. This consensus statement, an updated second edition, aims to continue raising awareness of these largely preventable injuries and, crucially, to stimulate action.DRPUs are relatively common and account for a growing proportion of HAPUs. Updated information on the incidence of DRPUs is described in chapter 1. Although it is recognised that DRPUs increase the financial burden of healthcare, there is little formal analysis of their economic impact. This needs to be addressed; robust evidence on the burden of DRPUs and the value that can be released by adopting prevention strategies is needed to help drive action.Our understanding of the pathophysiology of DRPUs has improved significantly over the past few years; this is described in chapter 2. One crucial difference between PUs and DRPUs is that body-weight forces are less significant in DRPUs, with the force being exerted from a device that is typically strapped or taped onto the body. Devices and their securement may generate high stress concentrations in tissues, leading to cell and tissue-damage pathways associated with sustained deformation.As more evidence is published on DRPUs, recurring themes are emerging, as outlined in chapter 3:The most vulnerable patients are bearing the brunt of DRPUs; paediatric and neonatal patients, and all those needing critical care are particularly susceptible. During the COVID-19 pandemic, a new high-risk population (people with severe COVID-19 infection) emerged. They are at increased risk of DRPUs because of their need for prolonged ventilatory support, especially when ‘proning’Devices associated with DRPUs are often used to perform essential, life-saving functions. They include continuous positive airway pressure (CPAP) masks or endotracheal tubes. Minimising their use is clearly not an option, so practice innovation is neededAlthough the most common locations for DRPUs are the face, ears, lower legs and heels, any location where a device comes into close contact with the skin can be at risk. In the same vein, any device, whether needed for a medical purpose or not, has the capacity to cause injury if its use is not properly managed. Vigilance is needed for all patients.What can be done? The importance of routine risk assessment is covered in chapter 4. Although use of a validated risk assessment tool is the vital first step, this will not be enough on its own. Several steps can be taken to ensure the safe use of devices. These are described in chapter 5 and include device repositioning, cushioning with prophylactic dressings and moisture control (only where possible and clinically appropriate). Of key importance is the development of an institutional protocol and champions to ensure all necessary steps are adopted.For any of these changes to be put into practice, awareness of DRPUs needs to increase. A number of proposals are outlined in chapter 6. A change of focus among health professionals and policy makers, along with more investment in education and training, are needed. All patients being managed with a medical device must be considered as at high risk.The pandemic introduced the world to the problem of DRPUs in health professionals caused by the extended wear of personal protective equipment. Health professionals also have a right to expect institutional protocols and provision of devices that protect them from DRPUs.Cutting-edge ideas and technologies that may be available in the future are described in chapter 7. When designing new products, manufacturers of medical devices have a duty of care to investigate the risks of DRPUs associated with their products and mitigate them, wherever possible. Our developing understanding of how the design, structure and materials used in medical devices contribute to DRPUs will help us develop new solutions for tomorrow.The first step is for everyone involved to ask themselves, ‘what can I do to help?’ There is work to be done—your journey to reduce DRPUs starts here!ForewordIn February 2019, an international group of medical, clinical and bioengineering experts met in London to develop the first edition of an international consensus statement on device-related pressure ulcers (DRPUs). Following a rigorous process of scientific discussion, the statement was drafted, reviewed by an international independent committee of external experts and published in JWC in February 20201 shortly before the breakout of the COVID-19 pandemic. It was, at the time, the most comprehensive synthesis of understanding of the aetiology of DRPUs and the technologies and clinical protocols that can be used to mitigate them.The pandemic was, and still is, a game-changer, as it instantly brought the effects of DRPUs into sharp focus, particularly in regard to the use of ventilation equipment and the management of critically ill patients in the prone position for prolonged periods.With the rise in reports of DRPUs and the change in global circumstances, the topic of prevention and treatment of this form of skin damage became more time-sensitive than ever. The expert panel recognised this early during the pandemic and, as a first reaction to the change in circumstances, published an update article, to complement the consensus statement. This focused on skin damage under personal protective equipment (PPE) in health professionals—a new category of DRPUs that had not been widely experienced in our lifetime prior to the pandemic.2This was not sufficient to capture the knowledge generated over the course of the pandemic. To continue supporting patients and health professionals, the consensus panel gathered in March 2021 to update their consensus statement, sharing the knowledge collected and the lessons learned since the first edition was published. The aim was to provide frontline staff with updated, clear, simple guidance on how to mitigate the risk of DRPUs during the pandemic and beyond, with in-depth content on the development and implementation of long-term prevention strategies.Like its predecessor, this second edition is aimed at generalists and specialists, as well as biomedical and non-biomedical engineers and other health professionals in clinical practice, academia, research and industry. It starts by updating the aetiology and pathophysiology of DRPUs, explaining how medical devices and objects that encounter the skin and apply forces onto it can cause cell and tissue deformation. This is followed by the assessment, prevention and management of DRPUs, including under the current pandemic circumstances.The consensus statement discusses the devices that are most associated with DRPUs and the biomechanical reasons for the risks they pose, with reference to the most recent scientific and medical literature. It also aims to inform policymakers and health professionals at all levels on the critical need for DRPU prevention through identification of the root causes, the scale of the problem, the damage they pose to quality of life, and the financial implications for institutions, insurers and governments.Greater awareness of the growing problem of DRPU formation will lead to better adoption of prevention protocols and much-needed new preventive technologies and design improvements. This edition, therefore, specifies the revised requirements that should inform the development of medical technologies for the prophylaxis of DRPUs; these relate to the shape, materials and construction features of medical devices, with reference to their effects on the skin and underlying tissues.In conclusion, under the historical circumstances of the COVID-19 pandemic, we felt it was critical to regroup the team of global experts to record their detailed advice on the prevention and treatment of DRPUs. We are pleased to present this second edition, which reflects these multidisciplinary international efforts. It is a cornerstone in our persistent struggle to mitigate DRPUs during the pandemic and beyond.Professor Amit Gefen — Panel ChairAims and terminologyPurpose of this documentFor this second edition, the panel met virtually to address the need for greater recognition of device-related pressure ulcers (DRPUs) and their causes, management and prevention. This document is intended to stimulate action and covers:The anatomy and composition of tissue in relation to the patient's ageThe pathogenesis of DRPUs, with a focus on why devices are associated with pressure ulcerationDevices, both medical and non-medical, associated with DRPU formationAssessment of patients with DRPUsSafe use of devices to prevent or manage DRPUs, including the impact of altered processes of care that have occurred as a result of the COVID-19 pandemic for both patients (eg, the increased use of proning), health professionals (eg, the prolonged use of personal protective equipment (PPE)) and the general publicInitiatives to raise awareness of DRPUs among health professionalsMedical-device design characteristics and features relevant to DRPUs and their preventionFuture research required on the prevention of DRPUs, with particular reference to product design, regulation and monitoring technologies.The ultimate objective of this consensus statement is to improve patients' outcomes and safety during episodes of care.A note on terminologyGlobally, several different names are used to describe pressure ulcers (PUs). Pressure injury (PI) is currently used by the National Pressure Injury Advisory Panel (NPIAP; formerly National Pressure Ulcer Advisory Panel)1 and the Pan Pacific Pressure Injury Alliance (PPPIA). Other terms proposed are ‘deformation injury’, ‘pressure damage’ and ‘decubitus’. To date, PI has been adopted in Australasia, although not entirely in the US and Canada and not in Europe. The terminology used is often site-specific. The different categories of PUs have been summarised by the NPIAP.1 The term ‘deformation injury’ focuses on the primary fast-acting damage mechanism—tissue deformation—that leads to rapid cell death and tissue breakdown.Throughout this document, the term PU is used. It should be taken to encompass the other terminologies used to cover tissue damage or injury caused by pressure, shear and tissue deformation.Glossary of abbreviationsBIPAP: bilevel positive airway pressureCPAP: continuous positive airway pressureDRPU: device-related pressure ulcerDVT: deep vein thrombosisECG: electrocardiogramECMO: extracorporeal membrane oxygenationEEG: electroencephalogramEPUAP: European Pressure Ulcer Advisory PanelHAPU: hospital-acquired pressure ulcerICU: intensive care unitIPC: intermittent pneumatic compressionMDRPU: medical device-related pressure ulcerMMP: matrix metalloproteinasesNIBP: non-invasive blood pressure cuffsNIPPV: non-invasive positive pressure ventilationNIV: non-invasive ventilationNPIAP: National Pressure Injury Advisory PanelNPWT: negative pressure wound therapyNSRAS: neonatal skin risk assessment scalePPE: personal protective equipmentPPPIA: Pan Pacific Pressure Injury AlliancePPUPET: paediatric pressure ulcer prediction and evaluation toolPU: pressure ulcerRCT: randomised controlled trialROS: reactive oxygen speciesSEM: sub-epidermal moistureSIRA+P: skin injury risk assessment and preventionTEWL: transepidermal water lossChapter 1: introductionPressure ulcers (PUs) are defined by the European Pressure Ulcer Advisory Panel (EPUAP), the National Pressure Injury Advisory Panel (NPIAP, formerly known as the NPUAP) and the Pan Pacific Pressure Injury Alliance (PPPIA) as:1‘Localised damage to the skin and underlying soft tissue usually over a bony prominence or related to a medical or other device. The injury can present as intact skin or an open ulcer and may be painful. The injury occurs as a result of intense and/or prolonged pressure or pressure in combination with shear. The tolerance of soft tissue for pressure and shear may also be affected by microclimate, nutrition, perfusion, comorbidities and condition of the soft tissue’.This general definition defines all PU types and encompasses various causal factors. However, the focus of this consensus statement is pressure ulceration related to device use.The key causal components of PU formation are exposure to pressure and shear. Friction contributes to shear, but on its own is not a direct cause of pressure ulceration. In many PUs, the main cause of pressure and the associated shear forces is body weight—for example, when a patient is immobilised in a semi-Fowler's position for extended periods on a support surface. Such pressure, friction and shear cause tissue deformation, local microcirculatory impairment and inflammation that, together, lead to pressure ulceration, typically observed in bony anatomical sites such as the sacrum, ischium, trochanter and heel. In contrast, the NPIAP states that medical device-related pressure ulcers (MDRPUs):2‘…result from the use of devices designed and applied for diagnostic or therapeutic purposes. The resultant pressure injury generally conforms to the pattern or shape of the device.’The NPIAP extended the definition of a medical device to include objects such as spectacles and devices without a medical purpose. To differentiate device-related pressure ulcers (DRPU) from PUs arising from body-weight forces, the panel proposes the following definition of and explanation for DRPU:‘A DRPU involves interaction with a device or object that is in direct contact with skin … or is transdermally implanted under the skin, causing focal and localised forces that deform the superficial and deep underlying tissues. A DRPU, which is caused by a device or object, is distinct from a PU, which is caused primarily by body-weight forces. The localised nature of the device's interaction with the patient's tissue results in the appearance of skin and deeper tissue damage that mimics that of the device in shape and distribution.’The term DRPU focuses the health professional and others on pressure ulceration caused by contact with medical devices only. Importantly, a DRPU may be caused by a medical device, object or product without a medical purpose. Throughout this consensus statement, the term DRPU is used to emphasise the importance of understanding that pressure ulceration may be related either to medical or non-medical devices. This is covered in more detail in chapter 3.Briefly, medical devices associated with pressure ulceration may include products used to sustain life in sick patients—for example, continuous positive airway pressure (CPAP) masks, oxygen therapy tubing, endotracheal tubes, bilevel positive airway pressure (BIPAP) equipment, indwelling lines, monitoring devices such as pulse oximetry, or assistive devices such as orthotics, prosthetics and bed frames. Paediatric patients are particularly susceptible. Devices or objects associated with PUs that do not have a specific medical purpose may include the patient's own property and objects left on their bed or support surface, such as mobile/cell phones and jewellery. During the COVID-19 pandemic, many forms of skin damage resulted from PPE and the prolonged use of respirators.Like a PU, a DRPU can be categorised as I–IV, unstageable or deep tissue pressure injury, depending on its depth and the number of tissue layers involved.2 However, DRPUs can be difficult to classify as they often occur in regions with minimal soft tissue, such as the nasal bridge and ears. Nevertheless, most DRPUs are category I and II, but up to a quarter may be unstageable.3 A DRPU on the bridge of the nose, where the tissue has no padding, may rapidly progress from category I to category IV or unstageable once the skin integrity has been compromised. Damage to mucosal tissue, for example on the lips or nares, from medical devices is not staged but referred to as a mucosal DRPU.4International pressure ulcer guidelinesGuidelines on the prevention and management of PUs, including to varying extents DRPUs, have been published by several international consensus groups and wound management societies.The 2019 EPUAP/NPIAP/PPPIA guideline is the most widely cited. This consensus statement has taken account of guidelines used globally, including those from the EPUAP/NPIAP/PPPIA.1,2EpidemiologyPatients managed using medical devices are more likely to develop a PU or skin breakdown; DRPUs are relatively common.3,5 For example, in an US hospital setting, the overall rate of PUs in inpatients was 5.4%, of which 34.5% were DRPUs.3 Elsewhere, it has been observed that DRPUs may account for as much as 61–81% of all hospital-acquired PUs (HAPUs), depending on the care setting and patient subpopulations.6,7 A recent systematic review and meta-analysis reported that the estimated pooled incidence and prevalence of DRPUs in over 126,000 patients in 29 studies was 12% and 10%, respectively,8 although, as the authors state, these data are limited by the heterogeneity of the data collection.During the first waves of the COVID-19 pandemic, many care settings observed a sharp increase in the incidence or prevalence of DRPUs over and above these numbers.9,10,11 Some studies reported that around three-quarters of all DRPUs were among patients with a COVID-19-positive diagnosis.10,12Some trends quickly emerged. One concern was the development of DRPUs related to the use of invasive and non-invasive ventilation equipment.9 Another was the widespread use of proning, in which critically ill individuals are laid face-down for long periods, resulting in higher rates of DRPUs on the face and PUs occurring in areas not usually reported, such as the nipples or genitalia.12 A third high-profile observation related to health professionals at the frontline of the pandemic having to wear PPE for prolonged periods, which resulted in DRPUs and other skin reactions.9The COVID-19 pandemic has been, and still is, a game-changer in the context of DRPU formation. Whereas previously, DRPUs were an understudied area, the increasing incidence observed during the pandemic and the changes in ways that patients are positioned—which makes it more complex to position and check devices—has certainly raised the profile of this issue. During the first waves, much was learned about the risks of DRPU formation, and many insights into how the risk can be reduced have since been developed and published, representing a huge and rapid advance in this field.The pandemic is likely to continue to affect global healthcare systems and it is anticipated that the associated increased risk of DRPU formation will remain for several years to come. This is a good time for updated guidance and advice on how to minimise DRPUs, including those challenges specifically associated with a COVID-19-positive diagnosis, so that health professionals are well informed to provide the very best care for their patients and are well prepared to manage the wider issue of device-related pressure ulceration.Occurrence by settingDevices used in intensive care are particularly associated with DRPUs.13,14,15 This is not surprising given that critically ill patients in intensive care units (ICUs) often have the highest number of devices in situ. In a 2019 systematic review of the incidence, prevalence and severity of DRPUs in ICUs, pooled estimates revealed incidence rates of 3.7% and prevalence rates of 33.7%. Again, the wide ranges reflect the heterogeneity of the data collection between the 13 studies evaluated.14 Since this review, Coyer et al. reported a DRPU prevalence of 4.3% in intensive care patients.16 Wille et al. stated that the overall incidence of DRPUs or skin breakdown caused by pulse oximeters in a surgical ICU was 5%.17 Mehta et al. reported that the point prevalence of DRPUs in a ICU setting was 19.2%.18Occurrence rates can be lower in other settings. An unpublished incidence audit of DRPUs in Kyorin University Hospital, Japan, conducted over 12 months from 1 February 2018 to 31 January 2019, demonstrated the difference between ICU and general wards. The incidence of DRPUs in ICUs was 2.8%, which is consistent with published data. On general wards it was 0.4%. This lower incidence is likely to be a result of the higher number of devices used in ICU compared with general wards. Table 1 summarises the key results of DRPU incidence and prevalence data.Table 1. Summary of the incidence and prevalence of DRPUsReferenceSetting detailsFindingOverallBlack et al.3US hospital inpatients (n=2079)PU occurrence: 5.4%DRPU occurrence: 34.5%*Jackson et al.8Systematic review of 29 studies (126,150 eligible patients)Pooled DRPU incidence: 12%Pooled DRPU prevalence: 10%Data from intensive care settingsBarakat-Johnson et al.14Systematic review of 13 studiesPooled DRPU incidence: 3.7% (95% CI: 0–14.4%)Pooled DRPU prevalence: 33.7% (95% CI: 22.6–45.8%)Coyer et al.169Patients in six ICUs in two major medical centres (one in the US and one in Australia)DRPU incidence: 3.1%Wille et al.17125 patients in a surgical ICUFrequency of pulse oximeter-induced digital injury: 5%Data from other settingsKyorin University Hospital unpublished DRPU auditICU and general wards in a Japanese hospitalDRPU incidence in ICUs: 2.8%DRPU incidence in general wards: 0.14%Schlüer et al.274204 children in 13 Swiss hospitalsPrevalence of PUs: 26.5%Prevalence of DRPUs: 38.5%Visscher and Taylor25741 neonatal intensive care patientsPremature neonates: 1.5 PUs per 1000 daysTerm infants: 2.7 PUs per 100 daysJiang et al.229Health and non-healthcare professionals in 161 hospitals in ChinaPrevalence of skin injuries: 42.8%Prevalence of DRPUs: 30%Rosner et al.233Health professionals (n=31) in a New York hospitalPrevalence of skin breakdown: 18.1% within 3 hours; 44% after 3 hours of mask useAcne: 53.1%*Proportion of PUs that were DRPUsDRPUs—device-related pressure ulcers; ICU—intensive care unit; PU—pressure ulcer; CI—confidence intervalTable 1. Summary of the incidence and prevalence of DRPUsView as image HTML Neonates, infants and paediatricsDRPUs have been reported in around 7% of all paediatric patients.19,20 They are more common in younger children and can account for up to one half of all PUs identified in some high-risk patient populations, such as in neonatal and intensive care settings or in persons with conditions such as spina bifida.19,21,23,24 Infants who develop DRPUs are likely to be younger post-partum, with a shorter gestation; they develop DRPUs more rapidly than patients with PUs caused by body weight.25 Mechanical ventilation and a respiratory diagnosis are associated with higher risk of DRPU formation.26 In newborns, devices may severely and permanently affect and distort nasal cartilage.27 The incidence of DRPUs in paediatric patients may be as high as 28%, with non-invasive mechanical ventilation associated with ulceration (relative risk ratio 12.24).15,28,29,30,31,32,33,34Data collected by an author of this document in a single paediatric hospital in Italy during the height of the pandemic suggest that the relative burden of DRPUs in paediatrics is growing. Advances in paediatric medicine over the past decade mean that neonates, infants and children with complex medical conditions can now receive treatment, whereas in the past this option may not have been available. These seriously ill children often need long periods in ICU and interventions involving multiple medical devices. Data presented in Fig 1 show that, as a result of this general trend, there was an increase in DRPUs in paediatrics treated in this hospital. During this three-year period, there were noticeably more DRPUs than PUs during the first year of life (n=69 neonates): 44 (37%) and 25 (14%), respectively. In line with the literature, DRPUs were most commonly observed in the occiput, ear, foot and amputation stump, with orotracheal and nasogastric tubes, central lines and ventilation masks being the main culprits. It is clear that the burden of DRPUs in the paediatric specialty needs particular focus.Fig 1. Change in the proportion of DRPUs in recent years in a single institution. Over a three-year period, despite a small overall decline in the number of PUs generally, the proportion caused by medical devices (DRPU) increased from 32% (33/104) in 2018 to 46% (44/96) in 2020. Data provided by Guido Ciprandi.DRPU–device-related pressure ulcer; PU–pressure ulcerOccurrence by type of deviceAlthough many kinds of devices have the potential to cause DRPUs, there is a high association between DRPUs and respiratory devices, regardless of setting;18,35 up to 68% of DRPUs are associated with respiratory devices,13 of which 20% are linked with BIPAP or CPAP devices, where ulceration occurred on the bridge of the nose, cheeks and/or nasolabial fold.6 The incidence of DRPUs related to non-invasive ventilation (NIV) has been shown to range from 5–50% for 2–4 hours of continuous usage and up to 100% after 48 hours of wearing a face mask.36 Prevalence of skin breakdown may be over 14% in general-hospital patients with respiratory failure

Massively parallel reporter perturbation assays uncover temporal regulatory architecture during neural differentiation

Abstract: Gene regulatory elements play a key role in orchestrating gene expression during cellular differentiation, but what determines their function over time remains largely unknown. Here, we perform perturbation-based massively parallel reporter assays at seven early time points of neural differentiation to systematically characterize how regulatory elements and motifs within them guide cellular differentiation. By perturbing over 2,000 putative DNA binding motifs in active regulatory regions, we delineate four categories of functional elements, and observe that activity direction is mostly determined by the sequence itself, while the magnitude of effect depends on the cellular environment. We also find that fine-tuning transcription rates is often achieved by a combined activity of adjacent activating and repressing elements. Our work provides a blueprint for the sequence components needed to induce different transcriptional patterns in general and specifically during neural differentiation.

Evidence integration and decision confidence are modulated by stimulus consistency

Abstract: Evidence integration is a normative algorithm for choosing between alternatives with noisy evidence, which has been successful in accounting for vast amounts of behavioural and neural data. However, this mechanism has been challenged by non-integration heuristics, and tracking decision boundaries has proven elusive. Here we first show that the decision boundaries can be extracted using a model-free behavioural method termed decision classification boundary, which optimizes choice classification based on the accumulated evidence. Using this method, we provide direct support for evidence integration over non-integration heuristics, show that the decision boundaries collapse across time and identify an integration bias whereby incoming evidence is modulated based on its consistency with preceding information. This consistency bias, which is a form of pre-decision confirmation bias, was supported in four cross-domain experiments, showing that choice accuracy and decision confidence are modulated by stimulus consistency. Strikingly, despite its seeming sub-optimality, the consistency bias fosters performance by enhancing robustness to integration noise. Glickman et al. identify an evidence integration bias whereby the relative weighting of incoming information towards a decision is increased based on its consistency with preceding evidence, resulting in a pre-decision confirmation bias.