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The proliferation of sensors in smart homes makes it possible to monitor human activities, routines, and complex behaviors in an unprecedented way. Hence, human activity recognition has gained increasing attention over the last few years as a tool to improve healthcare and well-being in several applications. However, most existing activity recognition systems rely on cameras or wearable sensors, which may be obtrusive and may invade the user’s privacy, especially at home. Moreover, extracting expressive features from a stream of data provided by heterogeneous smart-home sensors is still an open challenge. In this paper, we investigate a novel method to detect activities of daily living by exploiting unobtrusive smart-home sensors (i.e., passive infrared position sensors and sensors attached to everyday objects) and vision-based deep learning algorithms, without the use of cameras or wearable sensors. Our method relies on depicting the locomotion traces of the user and visual clues about their interaction with objects on a floor plan map of the home, and utilizes pre-trained deep convolutional neural networks to extract features for recognizing ongoing activity. One additional advantage of our method is its seamless extendibility with additional features based on the available sensor data. Extensive experiments with a real-world dataset and a comparison with state-of-the-art approaches demonstrate the effectiveness of our method.

Motor rehabilitation strategies after unilateral stroke suggest that the immobilization of the healthy, unimpaired limb can promote the functional recovery of a paretic limb. In rodents, this has been modeled using casts, harnesses, and other means of restricting the use of the non-paretic forelimb in models of experimental stroke. Here, we evaluated an alternative approach, using botulinum toxin injections to limit the function of the non-paretic forelimb. Adult male rats were subjected to permanent ligation of the left distal middle cerebral artery, resulting in right forelimb paresis. The rats were then subjected to: (1) no treatment; (2) botulinum toxin injections 1 day post stroke; or (3) cast placement 5 days post stroke. Casts were removed after 5 weeks, while the botulinum toxin injection effectively immobilized subjects for approximately the same duration. Rats with bilateral forelimb impairment due to the stroke plus casting or botulinum injections were still able to feed and groom normally. Both immobilization groups showed modest recovery following the stroke compared to those that did not receive immobilization, but the casting approach led to unacceptable levels of animal stress. The botulinum toxin approach to limb immobilization had both advantages and disadvantages over traditional physical limb immobilization. The major advantage was that it was far less stress-inducing to the subject animals and appeared to be well tolerated. A disadvantage was that the paresis took roughly 10 weeks to fully resolve, and any degree of residual paresis could confound the interpretation of the behavioral assessments.

Purpose To evaluate if a web-based telemedicine system (the Glucoonline® system) is effective to improve glucose control in insulin-treated patients with type 1 and type 2 diabetes, as compared to standard of care. Methods This was a prospective, randomized, controlled trial, carried out at three tertiary referral centers for diabetes in Italy. Adults with insulin-treated type 1 and type 2 diabetes, inadequate glycemic control, and no severe diabetes-related complications and/or comorbidities were eligible for this study. Patients were randomized to either perform telemedicine-assisted (Group A) or standard (Group B) self-monitoring blood glucose (SMBG) for 6 months. In Group A, patients received prompt feedback about their blood glucose levels and therapy suggestions from the study staff via phone/SMS, when appropriate. In Group B, patients had no remote assistance from the study staff between planned visits. Results 123 patients were included in the final analysis. After 6 months, patients achieved a significant reduction in HbA1c in Group A (−0.38%, p p = 0.53). A significant difference in the percentage of patients with HbA1c p = 0.02). Also, fewer patients (p 8.5% were found in Group A vs Group B, respectively, after both 3 months (14.3% vs 35.2%) and 6 months (21.8% vs 42.9%). Conclusions The use of the Glucoonline™ system resulted in improved metabolic control. Telemedicine services have potential to support diabetes self-management and provide the patients with remote, prompt assistance using affordable technological equipment. Trial registration This study was registered at clinicaltrials.gov (NCT01804803) on March 5, 2013.

International audience; The success of the Belle II experiment in Japan relies on the very high instantaneous luminosity, close to 6 × 1035cm−2s−1, expectedfrom the SuperKEKB collider. The corresponding beam conditions at such luminosity levels generate large rates of backgroundparticles and creates stringent constraints on the vertex detector, adding to the physics requirements. Current prospects for theoccupancy rates in the present vertex detector (VXD) at full luminosity fall close to the acceptable limits and bear large uncertainties.In this context, the Belle II collaboration is considering the possibility to install an upgraded VXD system around 2027 to providea sufficient safety margin with respect to the expected background rate and possibly enhance tracking and vertexing performance.The VTX collaboration has started the design of a fully pixelated VXD, called VTX, based on fast and highly granular DepletedMonolithic Active Pixel Sensors (DMAPS) integrated on light support structures.The two main technical features of the VTX proposal are the usage of a single sensor type over all the layers of the system and theoverall material budget below 2 % of radiation length, compared to the current VXD which has two different sensor technologiesand about 3 % of radiation length. A dedicated sensor (OBELIX), taylored to the specific needs of Belle II, is under development,evolving from the existing TJ-Monopix2 sensor. The time-stamping precision below 100 ns will allow all VTX layers to take part inthe track finding strategy contrary to the current situation. The first two detection layers are designed according to a self-supportedall-silicon ladder concept, where 4 contiguous sensors are diced out of a wafer, thinned and interconnected with post-processedredistribution layers. The outermost detection layers follow a more conventional approach with a cold plate and carbon fibresupport structure, and light flex cables interconnecting the sensors.This document will review the context, technical details and development status of the proposed Belle II VTX.

Unhealthy behaviors regarding nutrition are a global risk for health. Therefore, the healthiness of an individual’s nutrition should be monitored in the medium and long term. A powerful tool for monitoring nutrition is a food diary; i.e., a daily list of food taken by the individual, together with portion information. Unfortunately, frail people such as the elderly have a hard time filling food diaries on a continuous basis due to forgetfulness or physical issues. Existing solutions based on mobile apps also require user’s effort and are rarely used in the long term, especially by elderly people. For these reasons, in this paper we propose a novel architecture to automatically recognize the preparation of food at home in a privacy-preserving and unobtrusive way, by means of air quality data acquired from a commercial sensor. In particular, we devised statistical features to represent the trend of several air parameters, and a deep neural network for recognizing cooking activities based on those data. We collected a large corpus of annotated sensor data gathered over a period of 8 months from different individuals in different homes, and performed extensive experiments. Moreover, we developed an initial prototype of an interactive system for acquiring food information from the user when a cooking activity is detected by the neural network. To the best of our knowledge, this is the first work that adopts air quality sensor data for cooking activity recognition.

et al., Feedhorn- and orthomode transducer- (OMT) coupled transition edge sensor (TES) bolometers have been designed and micro-fabricated to meet the optical specifications of the LiteBIRD high frequency telescope (HFT) focal plane. We discuss the design and optical characterization of two LiteBIRD HFT detector types: dual-polarization, dual-frequency-band pixels with 195/280 GHz and 235/337 GHz band centers. Results show well-matched passbands between orthogonal polarization channels and frequency centers within 3% of the design values. The optical efficiency of each frequency channel is conservatively reported to be within the range 0.64−0.72, determined from the response to a cryogenic, temperature-controlled thermal source. These values are in good agreement with expectations and either exceed or are within 10% of the values used in the LiteBIRD sensitivity forecast. Lastly, we report a measurement of loss in Nb/SiNx/Nb microstrip at 100 mK and over the frequency range 200–350 GHz, which is comparable to values previously reported in the literature., This work is supported by NASA under grant no. 80NSSC18K0132.

Degeneration of basal forebrain cholinergic neurons (BFCNs) in the nucleus basalis of Meynert (NBM) and vertical diagonal band (VDB) along with their connections is a key pathological event leading to memory impairment in Alzheimer's disease (AD). Aberrant neurotrophin signaling via Trks and the p75 neurotrophin receptor (p75NTR) contributes importantly to BFCN dystrophy. While NGF/TrkA signaling has received the most attention in this regard, TrkB and TrkC signaling also provide trophic support to BFCNs and these receptors may be well located to preserve BFCN connectivity. We previously identified a small molecule TrkB/TrkC ligand, LM22B-10, that promotes cell survival and neurite outgrowth in vitro and activates TrkB/TrkC signaling in the hippocampus of aged mice when given intranasally, but shows poor oral bioavailability. An LM22B-10 derivative, PTX-BD10-2, with improved oral bioavailability has been developed and this study examined its effects on BFCN atrophy in the hAPPLond/Swe (APPL/S) AD mouse model. Oral delivery of PTX-BD10-2 was started after appreciable amyloid and cholinergic pathology was present to parallel the clinical context, as most AD patients start treatment at advanced pathological stages. PTX-BD10-2 restored cholinergic neurite integrity in the NBM and VDB, and reduced NBM neuronal atrophy in symptomatic APPL/S mice. Dystrophy of cholinergic neurites in BF target regions, including the cortex, hippocampus, and amygdala, was also reduced with treatment. Finally, PTX-BD10-2 reduced NBM tau pathology and improved the survival of cholinergic neurons derived from human induced pluripotent stem cells (iPSCs) after amyloid-β exposure. These data provide evidence that targeting TrkB and TrkC signaling with PTX-BD10-2 may be an effective disease-modifying strategy for combating cholinergic dysfunction in AD. The potential for clinical translation is further supported by the compound's reduction of AD-related degenerative processes that have progressed beyond early stages and its neuroprotective effects in human iPSC-derived cholinergic neurons.

We have developed a Superconducting Quantum Interference Device (SQUID) controller unit for Transition Edge Sensors (TES) readout, designed to be used in a space mission. The unit is made of 8 boards and each board can condition four SQUID array amplifiers. The board design is inspired by a similar one developed for ground based experiments, but specific changes have been made to adopt Components Off The Shelf (COTS) with space grade equivalents, to implement redundancy and cross-strapping capabilities. The design also includes the thermal path to lift the heat off the boards towards an in-house designed monolithic aluminum rack.

Otitis media (OM) encompasses a spectrum of clinical presentations ranging from the readily identifiable Acute OM (AOM), which is characterised by otalgia and fever, to chronic otitis media with effusion (COME) where impaired hearing due to middle ear effusion may be the only clinical symptom. Chronic suppurative OM (CSOM) presents as a more severe form of OM, involving perforation of the tympanic membrane. The pathogenesis of OM in these varied clinical presentations is unclear but activation of the innate inflammatory responses to viral and/or bacterial infection of the upper respiratory tract performs an integral role. This localised inflammatory response can persist even after pathogens are cleared from the middle ear, eustachian tubes and, in the case of respiratory viruses, even the nasal compartment. Children prone to OM may experience an over exuberant inflammatory response that underlies the development of chronic forms of OM and their sequelae, including hearing impairment. Treatments for chronic effusive forms of OM are limited, with current therapeutic guidelines recommending a “watch and wait” strategy rather than active treatment with antibiotics, corticosteroids or other anti-inflammatory drugs. Overall, there is a clear need for more targeted and effective treatments that either prevent or reduce the hyper-inflammatory response associated with chronic forms of OM. Improved treatment options rely upon an in-depth understanding of OM pathogenesis, particularly the role of the host innate immune response during acute OM. In this paper, we review the current literature regarding the innate immune response within the middle ear to bacterial and viral otopathogens alone, and as co-infections. This is an important consideration, as the role of respiratory viruses as primary pathogens in OM is not yet fully understood. Furthermore, increased reporting from PCR-based diagnostics, indicates that viral/bacterial co-infections in the middle ear are more common than bacterial infections alone. Increasingly, the mechanisms by which viral/bacterial co-infections may drive or maintain complex innate immune responses and inflammation during OM as a chronic response require investigation. Improved understanding of the pathogenesis of chronic OM, including host innate immune response within the middle ear is vital for development of improved diagnostic and treatment options for our children.

BackgroundOtitis media (OM) is one of the most common infections in young children, arising from bacterial and/or viral infection of the middle ear. Globally, Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) are the predominant bacterial otopathogens. Importantly, common upper respiratory viruses are increasingly recognized contributors to the polymicrobial pathogenesis of OM. This study aimed to identify predominant bacteria and viruses in the nasopharynx, adenoids and middle ears of peri-urban/urban South-East Queensland Australian children, with and without clinical history of chronic otitis media with effusion (COME) and/or recurrent acute otitis media (RAOM).MethodsSixty children, 43 diagnosed with OM and 17 controls with no clinical history of OM from peri-urban/urban South-East Queensland community were recruited to the study. Respiratory tract bacterial and viral presence were examined within nasopharyngeal swabs (NPS), middle ear effusions (MEE) and adenoids, using real-time polymerase chain reaction (RT-PCR) and bacterial culture.ResultsAt least one otopathogen present was observed in all adenoid samples, 86.1% and 82.4% of NPS for children with and without OM, respectively, and 47.1% of the MEE from the children with OM. NTHi was the most commonly detected bacteria in both the OM and control cohorts within the adenoids (90.0% vs 93.8%), nasopharynx (67.4% vs 58.8%) respectively, and in the MEE (OM cohort 25.9%). Viruses were detected in all adenoid samples, 67.4% vs 47.1% of the NPS from the OM and control cohorts, respectively, and 37% of the MEE. Rhinovirus was the predominant virus identified in the adenoids (85.0% vs 68.8%) and nasopharynx (37.2% vs 41.2%) from the OM and control cohorts, respectively, and the MEE (19.8%).ConclusionsNTHi and rhinovirus are predominant otopathogens within the upper respiratory tract of children with and without OM from peri-urban and urban South-East Queensland, Australia. The presence of bacterial otopathogens within the middle ear is more predictive of concurrent URT infection than was observed for viruses, and the high otopathogen carriage within adenoid tissues confirms the complex polymicrobial environment in children, regardless of OM history.

Age-related degeneration of basal forebrain cholinergic neurons (BFCNs) is linked to cognitive impairment. The p75 neurotrophin receptor (p75NTR) has been proposed to mediate neuronal degeneration in aging. Therefore, we tested the hypothesis that modifying p75NTR function would prevent or reverse aging-related neuronal degeneration using LM11A-31, a small molecule p75NTR modulator that downregulates degenerative and upregulates trophic receptor-associated signaling. Morphological analysis in mice showed loss of BFCN area detectable by 18 months of age. Oral administration of LM11A-31 from age 15 to 18 months resulted in a dose-related preservation of BFCN area and one month of treatment from 17 to 18 months also preserved cell area. To evaluate reversal of established neuronal atrophy, animals were treated from 21 to 25 months of age. Treatment was associated with an increase of cell size to a mean area larger than that observed at 18 months, accompanied by increases in mean MS/VDB neurite length, as well as increased cholinergic fiber density and synaptophysin pre-synaptic marker levels in the hippocampus. These findings support the idea that modulation of p75NTR activity can prevent and potentially reverse age-associated BFCN degeneration. Moreover, this may be achieved therapeutically with orally bioavailable agents such as LM11A-31.

Artificial intelligence is more and more adopted to complement human activity in solving complex tasks in several domains, including healthcare, security, finance, and automation. In order to be effective, several artificial intelligence tools rely on large training sets of carefully annotated data. Since labeling is mostly performed manually, it is a costly and error-prone process. Hence, there is increasing interest in devising innovative tools to support the annotation task. In this paper, we report an initial investigation on the application of EEG data mining for evaluating the performance of humans carrying out image annotation tasks. Our approach relies on a cheap portable EEG sensor and on supervised learning methods. We collected a dataset from five volunteers, and performed an initial evaluation of our technique. The achieved results are promising, and pave the way to several research directions. To the best of our knowledge, our work is the first one applying EEG data mining for assessing the performance of labelers.

Cyclic di-AMP (c-di-AMP) is an essential and ubiquitous second messenger among bacteria. c-di-AMP regulates many cellular pathways through direct binding to several molecular targets in bacterial cells. c-di-AMP depletion is well known to destabilize the bacterial cell wall, resulting in increased bacteriolysis and enhanced susceptibility to cell wall targeting antibiotics. Using the human pathogen Listeria monocytogenes as a model, we found that c-di-AMP accumulation also impaired cell envelope integrity. An L. monocytogenes mutant deleted for c-di-AMP phosphodiesterases (pdeA pgpH mutant) exhibited a 4-fold increase in c-di-AMP levels and several cell wall defects. For instance, the pdeA pgpH mutant was defective for the synthesis of peptidoglycan muropeptides and was susceptible to cell wall-targeting antimicrobials. Among different muropeptide precursors, we found that the pdeA pgpH strain was particularly impaired in the synthesis of d-Ala–d-Ala, which is required to complete the pentapeptide stem associated with UDP–N-acetylmuramic acid (MurNAc). This was consistent with an increased sensitivity to d-cycloserine, which inhibits the d-alanine branch of peptidoglycan synthesis. Finally, upon examining d-Ala:d-Ala ligase (Ddl), which catalyzes the conversion of d-Ala to d-Ala–d-Ala, we found that its activity was activated by K+. Based on previous reports that c-di-AMP inhibits K+ uptake, we propose that c-di-AMP accumulation impairs peptidoglycan synthesis, partially through the deprivation of cytoplasmic K+ levels, which are required for cell wall-synthetic enzymes. IMPORTANCE The bacterial second messenger c-di-AMP is produced by a large number of bacteria and conditionally essential to many species. Conversely, c-di-AMP accumulation is also toxic to bacterial physiology and pathogenesis, but its mechanisms are largely undefined. We found that in Listeria monocytogenes, elevated c-di-AMP levels diminished muropeptide synthesis and increased susceptibility to cell wall-targeting antimicrobials. Cell wall defects might be an important mechanism for attenuated virulence in bacteria with high c-di-AMP levels.

In tauopathies, phosphorylation, acetylation, cleavage and other modifications of tau drive intracellular generation of diverse forms of toxic tau aggregates and associated seeding activity, which have been implicated in subsequent synaptic failure and neurodegeneration. Suppression of this wide range of pathogenic species, seeding and toxicity mechanisms, while preserving the physiological roles of tau, presents a key therapeutic goal. Identification and targeting of signaling networks that influence a broad spectrum of tau pathogenic mechanisms might prevent or reverse synaptic degeneration and modify disease outcomes. The p75 neurotrophin receptor (p75NTR) modulates such networks, including activation of multiple tau kinases, calpain and rhoA-cofilin activity. The orally bioavailable small-molecule p75NTR modulator, LM11A-31, was administered to tauP301S mice for 3 months starting at 6 months of age, when tau pathology was well established. LM11A-31 was found to reduce: excess activation of hippocampal cdk5 and JNK kinases and calpain; excess cofilin phosphorylation, tau phosphorylation, acetylation and cleavage; accumulation of multiple forms of insoluble tau aggregates and filaments; and, microglial activation. Hippocampal extracts from treated mice had substantially reduced tau seeding activity. LM11A-31 treatment also led to a reversal of pyramidal neuron dendritic spine loss, decreased loss of dendritic complexity and improvement in performance of hippocampal behaviors. These studies identify a therapeutically tractable upstream signaling module regulating a wide spectrum of basic mechanisms underlying tauopathies. Electronic supplementary material The online version of this article (10.1186/s40478-020-01034-0) contains supplementary material, which is available to authorized users.

The automatic discovery of behaviour is of high importance when aiming to assess and improve the quality of life of people. Egocentric images offer a rich and objective description of the daily life of the camera wearer. This work proposes a new method to identify a person's patterns of behaviour from collected egocentric photo-streams. Our model characterises time-frames based on the context (place, activities and environment objects) that define the composition of the image. Based on the similarity among the time-frames that describe the collected days for a user, we propose a new unsupervised greedy method to discover the behavioural pattern set based on a novel semantic clustering approach. Moreover, we present a new score metric to evaluate the performance of the proposed algorithm. We validate our method on 104 days and more than 100k images extracted from 7 users. Results show that behavioural patterns can be discovered to characterise the routine of individuals and consequently their lifestyle.

A recent EU/US CTAD Task Force Report focused on non-amyloid approaches to Alzheimer’s disease (AD) modification (1). While the broad range of targets and therapies highlighted is in some ways sobering, several themes and advances in the field point to principles and technologies that are encouraging and will likely accelerate progress. These themes include: the view that amyloid and non-amyloid approaches might ultimately be complementary or synergistic; the biological diversity of approaches; emerging -omics strategies that might help guide such options; and finally, the incorporation of aging biology into perspectives of target prioritization and disease modification.

The current review summarizes the pathobiology of nerve growth factor (NGF) and its cognate receptors during the progression of Alzheimer’s disease (AD). Both transcript and protein data indicate that cholinotrophic neuronal dysfunction is related to an imbalance between TrkA-mediated survival signaling and the NGF precursor (proNGF)/p75NTR-mediated pro-apoptotic signaling, which may be related to alteration in the metabolism of NGF. Data indicate a spatiotemporal pattern of degeneration related to the evolution of tau pathology within cholinotrophic neuronal subgroups located within the nucleus basalis of Meynert (nbM). Despite these degenerative events the cholinotrophic system is capable of cellular resilience and/or plasticity during the prodromal and later stages of the disease. In addition to neurotrophin dysfunction, studies indicate alterations in epigenetically regulated proteins occur within cholinotrophic nbM neurons during the progression of AD, suggesting a mechanism that may underlie changes in transcript expression. Findings that increased cerebrospinal fluid levels of proNGF mark the onset of MCI and the transition to AD suggests that this proneurotrophin is a potential disease biomarker. Novel therapeutics to treat NGF dysfunction include NGF gene therapy and the development of small molecule agonists for the cognate prosurvival NGF receptor TrkA and antagonists against the pan-neurotrophin p75NTR death receptor for the treatment of AD.

Brand-led transformation is about leveraging the power of a corporate brand to drive fundamental change within organisations. Focused on complex service businesses, the brand serves as the starting point for a systematic process of transformation that drives change down to the level of business operations. This ensures that the principles of the promise are experienced in every interaction that the company has with its customers. Organizations typically struggle with translating brand-led customer-centric strategies into tangible and specific change outcomes at the front line. This chapter melds a practitioner's view with current theory and offers pragmatic and proven approaches to translating these strategies into a framework and a methodology that drives direct customer and company benefits with successful enterprise-wide outcomes that impact the full business. In addition, this structured approach is complemented with insight into a deeper review of the role of agents of change and their impact on implementation across the organization.