Private hospital energy performance benchmarking using energy audit data: an Italian case study

The increased focus on energy efficiency, both at the national and international levels, has fostered the diffusion and development of specific energy consumption benchmarks for most relevant economic sectors. In this context, energy-intensive facilities, such as hospitals and health structures, represent a unique case. Indeed, despite the high energy consumption of these structures, scientific literature lacks the presence of adequate energy performance benchmarks, especially in regard to the European context. Thus, this study aimed at defining energy benchmark indicators for the Italian private healthcare sector using data collected from the Italian mandatory energy audits according to Art.8 EU Directive 27/2012. The benchmark indicators’ definition was made using a methodology proposed by the Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA). This methodology provided the calculation of specific energy performance indicators (EnPIs) by considering the global energy consumption of the different sites and the sector’s relevant variables. The results obtained were compared with those obtained from a consolidated but more complex methodology: the one envisaged by the Environmental Protection Agency. The results obtained allowed us to validate the reliability of the proposed methodology, as well as the validity and future usability of the calculated indicators. Relying on a significant database containing actual data from recent energy audits, this study was thus able to provide an up-to-date and reliable benchmark for the private healthcare sector

TDP-43 promotes the formation of neuromuscular synapses through the regulation of Disc-large expression in Drosophila skeletal muscles

Background: The ribonuclear protein TDP-43 has been implicated in the pathophysiology of amyotrophic lateral sclerosis (ALS), with genetic mutations being linked to the neurological symptoms of the disease. Though alterations in the intracellular distribution of TDP-43 have been observed in skeletal muscles of patients suffering from ALS, it is not clear whether such modifications play an active role in the disease or merely represent an expression of muscle homeostatic mechanisms. Also, the molecular and metabolic pathways regulated by TDP-43 in the skeletal muscle remain largely unknown. Here, we analyze the function of TBPH, the Drosophila melanogaster ortholog of TDP-43, in skeletal muscles. Results: We modulated the activity of TDP-43 in Drosophila muscles by means of RNA interference and observed that it is required to promote the formation and growth of neuromuscular synapses. TDP-43 regulated the expression levels of Disc-large (Dlg), and restoring Dlg expression either in skeletal muscles or in motoneurons was sufficient to suppress the locomotive and synaptic defects of TDP-43-null flies. These results were validated by the observation of a decrease in Dlg levels in human neuroblastoma cells and iPSC-differentiated motoneurons derived from ALS patients, suggesting similar mechanisms may potentially be involved in the pathophysiology of the disease. Conclusions: Our results help to unveil the physiological role of TDP-43 in skeletal muscles as well as the mechanisms responsible for the autonomous and non-autonomous behavior of this protein concerning the organization of neuromuscular synapses

Multiple intracerebroventricular injections of human umbilical cord mesenchymal stem cells delay motor neurons loss but not disease progression of SOD1G93A mice

Stem cell therapy is considered a promising approach in the treatment of amyotrophic lateral sclerosis (ALS) and mesenchymal stem cells (MSCs) seem to be the most effective in ALS animal models. The umbilical cord (UC) is a source of highly proliferating fetal MSCs, more easily collectable than other MSCs. Recently we demonstrated that human (h) UC-MSCs, double labeled with fluorescent nanoparticles and Hoechst-33258 and transplanted intracerebroventricularly (ICV) into SOD1G93A transgenic mice, partially migrated into the spinal cord after a single injection. This prompted us to assess the effect of repeated ICV injections of hUC-MSCs on disease progression in SOD1G93A mice. Although no transplanted cells migrated to the spinal cord, a partial but significant protection of motor neurons (MNs) was found in the lumbar spinal cord of hUC-MSCs-treated SOD1G93A mice, accompanied by a shift from a pro-inflammatory (IL-6, IL-1\u3b2) to anti-inflammatory (IL-4, IL-10) and neuroprotective (IGF-1) environment in the lumbar spinal cord, probably linked to the activation of p-Akt survival pathway in both motor neurons and reactive astrocytes. However, this treatment neither prevented the muscle denervation nor delayed the disease progression of mice, emphasizing the growing evidence that protecting the motor neuron perikarya is not sufficient to delay the ALS progression

NF-κB1 Inhibits TLR-Induced IFN-β Production in Macrophages Through TPL-2-dependent ERK Activation

available in PMC 2012 February 15.Although NF-κB1 p50/p105 has critical roles in immunity, the mechanism by which NF-κB1 regulates inflammatory responses is unclear. In this study, we analyzed the gene expression profile of LPS-stimulated Nfkb1−/− macrophages that lack both p50 and p105. Deficiency of p50/p105 selectively increased the expression of IFN-responsive genes, which correlated with increased IFN-β expression and STAT1 phosphorylation. IFN Ab-blocking experiments indicated that increased STAT1 phosphorylation and expression of IFN-responsive genes observed in the absence of p50/p105 depended upon autocrine IFN-β production. Markedly higher serum levels of IFN-β were observed in Nfkb1−/− mice than in wild-type mice following LPS injection, demonstrating that Nfkb1 inhibits IFN-β production under physiological conditions. TPL-2, a mitogen-activated protein kinase kinase kinase stabilized by association with the C-terminal ankyrin repeat domain of p105, negatively regulates LPS-induced IFN-β production by macrophages via activation of ERK MAPK. Retroviral expression of TPL-2 in Nfkb1−/− macrophages, which are deficient in endogenous TPL-2, reduced LPS-induced IFN-β secretion. Expression of the C-terminal ankyrin repeat domain of p105 in Nfkb1−/− macrophages, which rescued LPS activation of ERK, also inhibited IFN-β expression. These data indicate that p50/p105 negatively regulates LPS-induced IFN signaling in macrophages by stabilizing TPL-2, thereby facilitating activation of ERK.National Institutes of Health (U.S.) (NIH AI52267)National Institutes of Health (U.S.) (NIH CA108854)National Institutes of Health (U.S.) (NIH CA67529)Medical Research Council (Great Britain

The golden circle: A way of arguing and acting about technology in the London ambulance service

This paper analyses the way in which the London Ambulance Service recovered from the events of October 1992, when it implemented a computer-aided despatch system (LASCAD) that remained in service for less than two weeks. It examines the enactment of a programme of long-term organizational change, focusing on the implementation of an alternative computer system in 1996. The analysis in this paper is informed by actor-network theory, both by an early statement of this approach developed by Callon in the sociology of translation, and also by concepts and ideas from Latour’s more recent restatement of his own position. The paper examines how alternative interests emerged and were stabilized over time, in a way of arguing and acting among key players in the change programme, christened the Golden Circle. The story traces four years in the history of the London Ambulance Service, from the aftermath of October 1992 through the birth of the Golden Circle to the achievement of National Health Service (NHS) trust status. LASCAD was the beginning of the story, this is the middle, an end lies in the future, when the remaining elements of the change programme are enacted beyond the Golden Circle

A digital shadow cloud-based application to enhance quality control in manufacturing

In Industry 4.0 era, rapid changes to the global landscape of manufacturing are transforming industrial plants in increasingly more complex digital systems. One of the most impactful innovations generated in this context is the "Digital Twin", a digital copy of a physical asset, which is used to perform simulations, health predictions and life cycle management through the use of a synchronized data flow in the manufacturing plant. In this paper, an innovative approach is proposed in order to contribute to the current collection of applications of Digital Twin in manufacturing: a Digital Shadow cloud-based application to enhance quality control in the manufacturing process. In particular, the proposal comprises a Digital Shadow updated on high performance computing cloud infrastructure in order to recompute the performance prediction adopting a variation of the computer-aided engineering model shaped like the actual manufactured part. Thus, this methodology could make possible the qualification of even not compliant parts, and so shift the focus from the compliance to tolerance requirements to the compliance to usage requirements. The process is demonstrated adopting two examples: the structural assessment of the geometry of a shaft and the one of a simplified turbine blade. Moreover, the paper presents a discussion about the implications of the use of such a technology in the manufacturing context in terms of real-time implementation in a manufacturing line and lifecycle management. Copyright (C) 2020 The Authors

Immunomonitoring of Transplanted Patients Infused With Mesenchymal Stromal Cells (MSC) for Treating Steroid-Refractory GVHD

n/

The polo-like kinase 1 (PLK1) inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia

CD56 is expressed in 15–20% of acute myeloid leukaemias (AML) and is associated with extramedullary diffusion, multidrug resistance and poor prognosis. We describe the establishment and characterisation of a novel disseminated model of AML (AML-NS8), generated by injection into mice of leukaemic blasts freshly isolated from a patient with an aggressive CD56+ monoblastic AML (M5a). The model reproduced typical manifestations of this leukaemia, including presence of extramedullary masses and central nervous system involvement, and the original phenotype, karyotype and genotype of leukaemic cells were retained in vivo. Recently Polo-Like Kinase 1 (PLK1) has emerged as a new candidate drug target in AML. We therefore tested our PLK1 inhibitor NMS-P937 in this model either in the engraftment or in the established disease settings. Both schedules showed good efficacy compared to standard therapies, with a significant increase in median survival time (MST) expecially in the established disease setting (MST = 28, 36, 62 days for vehicle, cytarabine and NMS-P937, respectively). Importantly, we could also demonstrate that NMS-P937 induced specific biomarker modulation in extramedullary tissues. This new in vivo model of CD56+ AML that recapitulates the human tumour lends support for the therapeutic use of PLK1 inhibitors in AML

On Organizing Algorithms

This short paper acts as a comment on Totaro and Ninno's ‘The Concept of Algorithm as an Interpretative Key of Modern Rationality’ and also introduces some new avenues for exploring the organization of algorithms. In recent discussion of algorithms, concerns have been expressed regarding the apparent power, agential capacity and control that algorithms command of our lives (Beer, 2009; Lash, 2007; Slavin, 2011; Spring, 2011; Stalder and Mayer, 2009). The logic of order, if there is one within these discussions, appears somewhat distinct from the metaphor of recursion suggested by Totaro and Ninno. Using this distinction as a starting point, the paper explores alternative metaphors from which to begin an engagement with political questions of algorithmic ordering. The paper argues for engaging with associative metaphors of: algorithmic account, fluidity, absent-presence and sociality. The paper explores these associative metaphors through an important set of emerging questions regarding organizing algorithms: who and what is included or excluded, on what terms and to what ends

Algorithms as folding:Reframing the analytical focus

This article proposes an analytical approach to algorithms that stresses operations of folding. The aim of this approach is to broaden the common analytical focus on algorithms as biased and opaque black boxes, and to instead highlight the many relations that algorithms are interwoven with. Our proposed approach thus highlights how algorithms fold heterogeneous things: data, methods and objects with multiple ethical and political effects. We exemplify the utility of our approach by proposing three specific operations of folding-proximation, universalisation and normalisation. The article develops these three operations through four empirical vignettes, drawn from different settings that deal with algorithms in relation to AIDS, Zika and stock markets. In proposing this analytical approach, we wish to highlight the many different attachments and relations that algorithms enfold. The approach thus aims to produce accounts that highlight how algorithms dynamically combine and reconfigure different social and material heterogeneities as well as the ethical, normative and political consequences of these reconfigurations