Innovation in immediate neonatal care: development of the Bedside Assessment, Stabilisation and Initial Cardiorespiratory Support (BASICS) trolley

OBJECTIVE: Babies receive oxygen through their umbilical cord while in the uterus and for a few minutes after birth. Currently, if the baby is not breathing well at birth, the cord is cut so as to transfer the newborn to a resuscitation unit. We sought to develop a mobile resuscitation trolley on which newly born babies can be resuscitated while still receiving oxygenated blood and the 'placental transfusion' through the umbilical cord. This would also prevent separation of the mother and baby in the first minutes after birth. DESIGN: Multidisciplinary iterative product development. SETTING: Clinical Engineering Department of a University Teaching Hospital. METHODS: Following an initial design meeting, a series of prototypes were developed. At each stage, the prototype was reviewed by a team of experts in the laboratory and in the hospital delivery suite to determine ease of use and fitness for purpose. A commercial company was identified to collaborate on the trolley's development and secure marking with the Conformite Europeenne mark, allowing the trolley to be introduced into clinical practice. RESULTS: The trolley is a small mobile resuscitation unit based on the concept of an overbed hospital table. It can be manoeuvred to within 50 cm of the mother's pelvis so that the umbilical cord can remain intact during resuscitation, irrespective of whether the baby is born naturally, by instrumental delivery or by caesarean section. Warmth for the newborn comes from a heated mattress and the trolley has the facility to provide suction, oxygen and air. CONCLUSIONS: This is the first mobile resuscitation device designed specifically to facilitate newborn resuscitation at the bedside and with an intact cord. The next step is to assess its safety, its acceptability to clinicians and parents, and to determine whether it allows resuscitation with an intact cord

Does stakeholder involvement really benefit biodiversity conservation?

The establishment of protected areas, such as Natura 2000, is a common approach to curbing biodiversity loss. But many of these areas are owned or managed by private actors. Policies indicate that their involvement should be encouraged to ensure long term success. However, to date there have been no systematic evaluations of whether local actor involvement in the management of protected areas does in fact contribute to the conservation of biodiversity, which is the expressed policy goal. Research incorporating both qualitative and quantitative data was carried out in three case studies in Scotland where local actor input was required in the development and/or implementation of Natura 2000 management plans. No relationship was found between the characteristics of the process of stakeholder involvement and stakeholders’ perceptions of future biodiversity outcomes. Social outcomes of increased stakeholder involvement, such as increased trust, did however increase the perceived likelihood of positive future biodiversity outcomes. The findings indicate that efforts aimed at increasing stakeholder involvement in the management of protected areas need to consider making processes more independent, and acknowledge and address underlying biodiversity conflicts. The findings also emphasise the need to evaluate multi-level conservation efforts in terms of processes, social outcomes and biodiversity outcomes

The Seroepidemiology of Haemophilus influenzae Type B Prior to Introduction of an Immunization Programme in Kathmandu, Nepal.

Haemophilus influenzae type b (Hib) is now recognized as an important pathogen in Asia. To evaluate disease susceptibility, and as a marker of Hib transmission before routine immunization was introduced in Kathmandu, 71 participants aged 7 months-77 years were recruited and 15 cord blood samples were collected for analysis of anti-polyribosylribitol phosphate antibody levels by enzyme-linked immunosorbent assay. Only 20% of children under 5 years old had levels considered protective (>0.15 µg/ml), rising to 83% of 15-54 year-olds. Prior to introduction of Hib vaccine in Kathmandu, the majority of young children were susceptible to disease

Visual Speech Recognition with Lightweight Psychologically Motivated Gabor Features

Extraction of relevant lip features is of continuing interest in the visual speech domain. 1 Using end-to-end feature extraction can produce good results, but at the cost of the results being 2 difficult for humans to comprehend and relate to. We present a new, lightweight feature extraction 3 approach, motivated by human-centric glimpse based psychological research into facial barcodes, 4 and demonstrate that these simple, easy to extract 3D geometric features (produced using Gabor 5 based image patches), can successfully be used for speech recognition with LSTM based machine 6 learning. This approach can successfully extract low dimensionality lip parameters with a minimum 7 of processing. One key difference between using these Gabor-based features and using other features 8 such as traditional DCT, or the current fashion for CNN features is that these are human-centric 9 features that can be visualised and analysed by humans. This means that it is easier to explain and 10 visualise the results. They can also be used for reliable speech recognition, as demonstrated using the 11 Grid corpus. Results for overlapping speakers using our lightweight system gave a recognition rate 12 of over 82%, which compares well to less explainable features in the literature. 1

A view through a window: Social relations, material objects and locality

In this article the authors ask what it would mean to think sociologically about the window as a specific material and symbolic object. Drawing on qualitative analysis of a series of comparative interviews with residents in three different streets in a diverse local area of Glasgow, they explore what the use and experience of windows tells us about their respondents’ very different relationships to the places where they live. On the one hand, the window, as a material feature of the home, helps us grasp the lived reality of class inequality and how such inequality shapes people’s day-to-day experience. On the other hand, windows are symbolically charged objects, existing at the border of the domestic and public world. For this reason, they feature in important ways in local debates over the appearance, ownership and conservation of the built environment. The article explores these struggles, and shows what they reveal about the construction of belonging in the neighbourhood, a process which is both classed and racialised at one and the same time.ESR

Protrudin functions from the endoplasmic reticulum to support axon regeneration in the adult CNS

Funder: Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation); doi: https://doi.org/10.13039/100000865Funder: Christopher and Dana Reeve Foundation (Christopher & Dana Reeve Foundation); doi: https://doi.org/10.13039/100001305Funder: International Foundation for Research in Paraplegia (Internationale Stiftung für Forschung in Paraplegie); doi: https://doi.org/10.13039/501100001708Funder: Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.); doi: https://doi.org/10.13039/100000009Funder: Christopher and Dana Reeve Foundation (Christopher & Dana Reeve Foundation)Abstract: Adult mammalian central nervous system axons have intrinsically poor regenerative capacity, so axonal injury has permanent consequences. One approach to enhancing regeneration is to increase the axonal supply of growth molecules and organelles. We achieved this by expressing the adaptor molecule Protrudin which is normally found at low levels in non-regenerative neurons. Elevated Protrudin expression enabled robust central nervous system regeneration both in vitro in primary cortical neurons and in vivo in the injured adult optic nerve. Protrudin overexpression facilitated the accumulation of endoplasmic reticulum, integrins and Rab11 endosomes in the distal axon, whilst removing Protrudin’s endoplasmic reticulum localization, kinesin-binding or phosphoinositide-binding properties abrogated the regenerative effects. These results demonstrate that Protrudin promotes regeneration by functioning as a scaffold to link axonal organelles, motors and membranes, establishing important roles for these cellular components in mediating regeneration in the adult central nervous system

GLA-modified RNA treatment lowers GB3 levels in iPSC-derived cardiomyocytes from Fabry-affected individuals

Recent studies in non-human model systems have shown therapeutic potential of nucleoside-modified messenger RNA (modRNA) treatments for lysosomal storage diseases. Here, we assessed the efficacy of a modRNA treatment to restore the expression of the galactosidase alpha (GLA), which codes for α-Galactosidase A (α-GAL) enzyme, in a human cardiac model generated from induced pluripotent stem cells (iPSCs) derived from two individuals with Fabry disease. Consistent with the clinical phenotype, cardiomyocytes from iPSCs derived from Fabry-affected individuals showed accumulation of the glycosphingolipid Globotriaosylceramide (GB3), which is an α-galactosidase substrate. Furthermore, the Fabry cardiomyocytes displayed significant upregulation of lysosomal-associated proteins. Upon GLA modRNA treatment, a subset of lysosomal proteins were partially restored to wild-type levels, implying the rescue of the molecular phenotype associated with the Fabry genotype. Importantly, a significant reduction of GB3 levels was observed in GLA modRNA-treated cardiomyocytes, demonstrating that α-GAL enzymatic activity was restored. Together, our results validate the utility of iPSC-derived cardiomyocytes from affected individuals as a model to study disease processes in Fabry disease and the therapeutic potential of GLA modRNA treatment to reduce GB3 accumulation in the heart.</p

Identification of Rigosertib for the Treatment of Recessive Dystrophic Epidermolysis Bullosa–Associated Squamous Cell Carcinoma

PURPOSE: Squamous cell carcinoma (SCC) of the skin is the leading cause of death in patients with the severe generalized form of the genetic disease recessive dystrophic epidermolysis bullosa (RDEB). Although emerging data are identifying why patients suffer this fatal complication, therapies for treatment of RDEB SCC are in urgent need. EXPERIMENTAL DESIGN: We previously identified polo-like kinase 1 (PLK1) as a therapeutic target in skin SCC, including RDEB SCC. Here, we undertake a screen of 6 compounds originally designated as PLK1 inhibitors, and detail the efficacy of the lead compound, the multipathway allosteric inhibitor ON-01910, for targeting RDEB SCC in vitro and in vivo. RESULTS: ON-01910 (or rigosertib) exhibited significant specificity for RDEB SCC: in culture rigosertib induced apoptosis in 10 of 10 RDEB SCC keratinocyte populations while only slowing the growth of normal primary skin cells at doses 2 orders of magnitude higher. Furthermore, rigosertib significantly inhibited the growth of two RDEB SCC in murine xenograft studies with no apparent toxicity. Mechanistically, rigosertib has been shown to inhibit multiple signaling pathways. Comparison of PLK1 siRNA with MEK inhibition, AKT inhibition, and the microtubule-disrupting agent vinblastine in RDEB SCC shows that only PLK1 reduction exhibits a similar sensitivity profile to rigosertib. CONCLUSIONS: These data support a “first in RDEB” phase II clinical trial of rigosertib to assess tumor targeting in patients with late stage, metastatic, and/or unresectable SCC