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Abstract We present the use of whole‐genome sequencing to correctly diagnose progressive pseudorheumatoid dysplasia in patients with atypical clinical and radiologic findings and prior diagnosis of juvenile idiopathic arthritis.

Abstract Background The Sudden Unexpected Infant Death Syndrome (SUID) is one of the leading causes of mortality in the first year of life. The aim of this work was the retrospective evaluation of the incidence of SUID and the effectiveness of the multiagency approach to this phenomenon in the Tuscany Region. Methods Data were obtained from the regional registry of SUID cases in the period 2009–2019. The registry contains both sudden unexpected deaths in the first week of life (Sudden Unexpected Early Neonatal Deaths - SUEND), and those occurring after the first week up to 1 year of age (SUID). Results In this timeframe a total of 73 sudden unexpected deaths occurred in our region; 32 were Unexplained (i.e. Sudden Infant Death Syndrome - SIDS), 24 Explained, 10 Undetermined, and 7 SUEND. Autopsies were performed in 91% of cases, and in 95% of these by three groups of selected pathologists according to our protocol. We found a low incidence of SUID (0.21 ‰), and SIDS deaths accounted for 0.1‰ of live births (48% of cases) with a high prevalence of infants of non-Italian ethnicity (38% of cases). Bereaved families were able to receive psychological support from mental health professionals and have contact with the family association, Seeds for SIDS. Audits were organized when post-mortem examinations were not carried out or carried out incorrectly in procedural terms, and when the diagnosis was particularly uncertain. Conclusions This paper first provides data on SUID mortality based on complete post-mortems in an Italian region. According to these findings we can state that our approach is effective both in terms of correctly performed autopsies and support for bereaved families. Future efforts are necessary to further reduce the incidence of SUID especially among non- Italian infants. An improvement action is also recommended for ensuring a more accurate and consistent picture of the circumstances of death. The final approval of the National Protocol for the management of SUID cases is therefore strongly advocated in order to improve surveillance in this specific field and abolish disparities among the Italian regions.

Lo studio prende in considerazione la pratica di Mario Giacomelli di comporre serie fotografiche in relazione a testi poetici. Vengono indagati in particolare gli intrecci semantici generati dall’incontro tra gli scatti del maestro marchigiano e i versi di Mario Luzi. Keywords: Mario Giacomelli, Mario Luzi, La notte lava la mente, ipertesto visuale, transito.

Summary: Microendoscopic calcium imaging with one-photon miniature microscopes enables unprecedented readout of neural circuit dynamics during active behavior in rodents. In this study, we describe successful application of this technology in the rhesus macaque, demonstrating plug-and-play, head-mounted recordings of cellular-resolution calcium dynamics from large populations of neurons simultaneously in bilateral dorsal premotor cortices during performance of a naturalistic motor reach task. Imaging is stable over several months, allowing us to longitudinally track individual neurons and monitor their relationship to motor behavior over time. We observe neuronal calcium dynamics selective for reach direction, which we could use to decode the animal’s trial-by-trial motor behavior. This work establishes head-mounted microendoscopic calcium imaging in macaques as a powerful approach for studying the neural circuit mechanisms underlying complex and clinically relevant behaviors, and it promises to greatly advance our understanding of human brain function, as well as its dysfunction in neurological disease.

Matching iPSC donors’ and patients’ HLA haplotypes has been proposed as a way to generate cell therapy products with enhanced immunological compatibility. Here the authors show that MHC matching alone is insufficient to grant long-term survival of neuronal grafts in the lesioned brain of non-human primates.

Congenital central hypoventilation syndrome (CCHS) is a rare neurological genetic disorder that affects sleep-related respiratory control. Currently, no drug therapy is available. In light of this, there is a need for lifelong ventilation support, at least during sleep, for these patients. The pathogenesis of several chronic diseases is influenced by oxidative stress. Thus, determining oxidative stress in CCHS may indicate further disorders in the course of this rare genetic disease. Liquid biopsies are widely used to assess circulating biomarkers of oxidative stress. In this study, ferric reducing ability of plasma, thiobarbituric acid-reactive substances, advanced oxidation protein products (AOPPs), and advanced glycation end-products were measured in the serum of CCHS patients to investigate the relationship between oxidative stress and CCHS and the significance of this balance in CCHS. Here, AOPPs were found to be the most relevant serum biomarker to monitor oxidative stress in CCHS patients. According to this communication, CCHS patients may suffer from other chronic pathophysiological processes because of the persistent levels of AOPPs.

Introduction Direct-to-family clinical trials efficiently provide data while reducing the participation burden for children and their families. Although these trials can offer significant advantages over traditional clinical trials, the process of designing and implementing direct-to-family studies is poorly defined, especially in children with rheumatic disease. This paper provides lessons learnt from the design and implementation of a self-controlled, direct-to-family pilot trial aimed to evaluate the effects of a medication management device on adherence to hydroxychloroquine in paediatric SLE.Methods Several design features accommodate a direct-to-family approach. Participants meeting eligibility criteria from across the USA were identified a priori through a disease registry, and all outcome data are collected remotely. The primary outcome (medication adherence) is evaluated using electronic medication event-monitoring, plasma drug levels, patient questionnaires and pill counts. Secondary and exploratory endpoints include (1) lupus disease activity measured by a remote SLE Disease Activity Index examination and the Systemic Lupus Activity Questionnaire; and (2) hydroxychloroquine pharmacokinetics and pharmacodynamics. Recruitment of the initial target of 20 participants was achieved within 10 days. Due to initial recruitment success, enrolment was increased to 26 participants. Additional participants who were interested were placed on a waiting list in case of dropouts during the study.Discussion and dissemination Direct-to-family trials offer several advantages but present unique challenges. Lessons learnt from the protocol development, design, and implementation of this trial will inform future direct-to-family trials for children and adults with rheumatic diseases. Additionally, the data collected remotely in this trial will provide critical information regarding the accuracy of teleresearch in lupus, the impact of adherence to hydroxychloroquine on disease activity and a pharmacokinetic analysis to inform paediatric-specific dosing of hydroxychloroquine.Trial registration number ClinicalTrials.gov Registry (NCT04358302).

Congenital Central Hypoventilation Syndrome (CCHS) is a rare genetic disorder of the autonomic nervous system and in particular of the respiratory control during sleep. No drug therapy is, to date, available; therefore, the survival of these patients depends on lifelong ventilatory support during sleep. Reactive oxygen species (ROS)-induced oxidative stress is a recognized risk factor involved in the pathogenesis of several chronic diseases. Therefore, monitoring systemic oxidative stress could provide important insights into CCHS outcomes. Because ROS-induced oxidative products are excreted as stable metabolites in urine, we performed an HPLC-MS/MS analysis for the quantitative determination of the three main representative oxidative biomarkers (i.e., diY, MDA, and 8-OHdG) in the urine of CCHS patients. Higher levels of urinary MDA were found in CCHS patients compared with age-matched control subjects. The noteworthy finding is the identification of urinary MDA as relevant biomarker of systemic oxidative status in CCHS patients. This study is a concise and smart communication about the impact that oxidative stress has in CCHS, and suggests the monitoring of urinary MDA levels as a useful tool for the management of these patients.

Driving under the influence of alcohol is a widespread phenomenon in the US where it is considered a major cause of fatal accidents. In this research, we present Virtual Breathalyzer, a novel approach for detecting intoxication from the measurements obtained by the sensors of smartphones and wrist-worn devices. We formalize the problem of intoxication detection as the supervised machine learning task of binary classification (drunk or sober). In order to evaluate our approach, we conducted a field experiment and collected 60 free gait samples from 30 patrons of three bars using a Microsoft Band and Samsung Galaxy S4. We validated our results against an admissible breathalyzer used by the police. A system based on this concept successfully detected intoxication and achieved the following results: 0.97 AUC and 0.04 FPR, given a fixed TPR of 1.0. Our approach can be used to analyze the free gait of drinkers when they walk from the car to the bar and vice versa, using wearable devices which are ubiquitous and more widespread than admissible breathalyzers. This approach can be utilized to alert people, or even a connected car, and prevent people from driving under the influence of alcohol.

A Global Positioning System (GPS) spoofing attack can be launched against any commercial GPS sensor in order to interfere with its navigation capabilities. These sensors are installed in a variety of devices and vehicles (e.g., cars, planes, cell phones, ships, UAVs, and more). In this study, we focus on micro UAVs (drones) for several reasons: (1) they are small and inexpensive, (2) they rely on a built-in camera, (3) they use GPS sensors, and (4) it is difficult to add external components to micro UAVs. We propose an innovative method, based on the video stream captured by a drone’s camera, for the real-time detection of GPS spoofing attacks targeting drones. The proposed method collects frames from the video stream and their location (GPS coordinates); by calculating the correlation between each frame, our method can detect GPS spoofing attacks on drones. We first analyze the performance of the suggested method in a controlled environment by conducting experiments on a flight simulator that we developed. Then, we analyze its performance in the real world using a DJI drone. Our method can provide different levels of security against GPS spoofing attacks, depending on the detection interval required; for example, it can provide a high level of security to a drone flying at altitudes of 50–100 m over an urban area at an average speed of 4 km/h in conditions of low ambient light; in this scenario, the proposed method can provide a level of security that detects any GPS spoofing attack in which the spoofed location is a distance of 1–4 m (an average of 2.5 m) from the real location.

This paper aims at exploring Yemeni instructors' perceptions on the role that ICTs play in developing EFL students' communicative competence components. The study pursued a quantitative research design as a method for data collection. A closed-ended questionnaire was constructed, developed, and shared with 60 Yemeni EFL instructors using Google forms. The validity of the questionnaire was checked by referees whereas Cronbach's Alpha was run to measure the questionnaire reliability (R=.86). SPSS 21st edition was used to analyse the data. The study revealed that Yemeni EFL instructors have positive perceptions on the role of using ICTs in developing students' communicative competence. The findings also reported no statistically significant differences in the instructors' perceptions of ICTs that can be found across the four components of communicative competence. Moreover, it was revealed that there are no statistically significant differences in the instructors' perceptions that can be attributed to gender across the components. This study encourages EFL instructors to help their students to use the ICT tools in developing their communicative competence.

Abstract Five years after the first edition, we have revised and updated the guidelines, re-examining the queries and relative recommendations, expanding the issues addressed with the introduction of a new entity, recently proposed by the American Academy of Pediatrics: BRUE, an acronym for Brief Resolved Unexplained Events. In this manuscript we will use the term BRUE only to refer to mild, idiopathic cases rather than simply replace the acronym ALTE per se. In our guidelines the acronym ALTE is used for severe cases that are unexplainable after the first and second level examinations. Although the term ALTE can be used to describe the common symptoms at the onset, whenever the aetiology is ascertained, the final diagnosis may be better specified as seizures, gastroesophageal reflux, infection, arrhythmia, etc. Lastly, we have addressed the emerging problem of the so-called Sudden Unexpected Postnatal Collapse (SUPC), that might be considered as a severe ALTE occurring in the first week of life.

The application of the electronic algorithm developed by the Mig-Healthcare project was pilot tested in a sample of migrants and refugees in 2 Reception and Identification Centres (RICs), temporary settlements, in Greece using portable devices. The questions relate to health literacy issues, to mental health, to vaccination history, to lifestyle habits such as smoking, alcohol intake, diet, to the presence of diseases such as heart disease or diabetes, to the use of prevention services and to dental care. A total of 82 adults, 50 women and 32 men, participated. Data analysis showed that 67.1% (55) of the respondents had difficulty in understanding medical information and 57.3% (47) did not know where to seek medical help for a specific health problem. Four main areas of health problems were identified and further action is required: (A) mental health concerns, (B) vaccinations, (C) obesity, and (D) dental hygiene. Direct linkage with the “Roadmap and Toolbox” section of the project’s website gave the respondents access to many sources and tools, while through the use of the interactive map, specific referral points of healthcare delivery in their area were identified. IT-based intervention in migrant and refugee populations in Greece are effective in increasing health literacy levels and identifying areas for health promotion interventions in these groups. Through linkage with the project’s database, access to healthcare provision points and action to seek appropriate healthcare when necessary are encouraged. Given the attenuated vulnerability profile of people living in temporary settlements, this algorithm can be easily used in primary care settings to improve migrant and refugee health.

Abstract Researchers on metallic iron (Fe0) for environmental remediation and water treatment are walking in a valley of confusion for 25 years. This valley is characterized by the propagation of different beliefs that have resulted from a partial analysis of the Fe0/H2O system as (1) a reductive chemical reaction was considered an electrochemical one and (2) the mass balance of iron has not been really addressed. The partial analysis in turn has been undermining the scientific method while discouraging any real critical argumentation. This communication re-establishes the complex nature of the Fe0/H2O system while recalling that, finally, proper system analysis and chemical thermodynamics are the most confident ways to solve any conflicting situation in Fe0 environmental remediation.

Le but de cet article est d’ examiner les transformations qui ont lieu au sein de la presse grecque au cours de la deuxième moitié du XIXe siècle et, en particulier, le processus complexe de sa politisation. Par l’ examen du contexte politique, idéologique et institutionnel de l’ époque, et à partir des exemples caractéristiques précis, l’ article vise à examiner le fonctionnement politique de la presse d’ opinion grecque pendant cette période charnière.

The hippocampus, a structure essential for spatial navigation and memory undergoes anatomical and functional changes during chronic stress. Here, we investigate the effects of chronic stress on the ability of place cells to encode the neural representation of a linear track. To model physiological conditions of chronic stress on hippocampal function, transgenic mice expressing the genetically encoded calcium indicator GCaMP6f in CA1 pyramidal neurons were chronically administered with 40 μg/ml of cortisol for 8 weeks. Cortisol-treated mice exhibited symptoms typically observed during chronic stress, including diminished reward seeking behavior and reduced adrenal gland and spleen weights. In vivo imaging of hippocampal cellular activity during linear track running behavior revealed a reduced number of cells that could be recruited to encode spatial position, despite an unchanged overall number of active cells, in cortisol-treated mice. The properties of the remaining place cells that could be recruited to encode spatial information, however, was unperturbed. Bayesian decoders trained to estimate the mouse’s position on the track using single neuron activity data demonstrated reduced performance in a cue richness-dependent fashion in cortisol-treated animals. The performance of decoders utilizing data from the entire neuronal ensemble was unaffected by cortisol treatment. Finally, to test the hypothesis that an antidepressant drug could prevent the effects of cortisol, we orally administered a group of mice with 10 mg/kg citalopram during cortisol administration. Citalopram prevented the cortisol-induced decrease in single-neuron decoder performance but failed to significantly prevent anhedonia and the cortisol-induced reduction in the proportion place cells. The dysfunction observed at the single-neuron level indicates that chronic stress may impair the ability of the hippocampus to encode individual neural representations of the mouse’s spatial position, a function pivotal to forming an accurate navigational map of the mouse’s external environment; however, the hippocampal ensemble as a whole is resilient to any cortisol-induced insults to single neuronal place cell function on the linear track.

Deployment of covert attention to a spatial location can cause large decreases in low-frequency correlated variability among neurons in macaque area V4 whose receptive-fields lie at the attended location. It has been estimated that this reduction accounts for a substantial fraction of the attention-mediated improvement in sensory processing. These estimates depend on assumptions about how population signals are decoded and the conclusion that correlated variability impairs perception, is purely hypothetical. Here we test this proposal directly by optogenetically inducing low-frequency fluctuations, to see if this interferes with performance in an attention-demanding task. We find that low-frequency optical stimulation of neurons in V4 elevates correlations among pairs of neurons and impairs the animal’s ability to make fine sensory discriminations. Stimulation at higher frequencies does not impair performance, despite comparable modulation of neuronal responses. These results support the hypothesis that attention-dependent reductions in correlated variability contribute to improved perception of attended stimuli.

Metallic iron (Fe0) has been demonstrated as an excellent material for decentralized safe drinking water provision, wastewater treatment and environmental remediation. An open issue for all these applications is the rational material selection or quality assurance. Several methods for assessing Fe0 quality have been presented, but all of them are limited to characterizing its initial reactivity. The present study investigates H2 evolution in an acidic solution (pH 2.0) as an alternative method, while comparing achieved results to those of uranium removal in quiescent batch experiments at neutral pH values. The unique feature of the H2 evolution experiment is that quantitative H2 production ceased when the pH reached a value of 3.1. A total of twelve Fe0 specimens were tested. The volume of molecular H2 produced by 2.0 g of each Fe0 specimen in 560 mL H2SO4 (0.01 M) was monitored for 24 h. Additionally, the extent of U(VI) (0.084 mM) removal from an aqueous solution (20.0 mL) by 0.1 g of Fe0 was characterized. All U removal experiments were performed at room temperature (22 ± 2 °C) for 14 days. Results demonstrated the difficulty of comparing Fe0 specimens from different sources and confirmed that the elemental composition of Fe0 is not a stand-alone determining factor for reactivity. The time-dependent changes of H2 evolution in H2SO4 confirmed that tests in the neutral pH range just address the initial reactivity of Fe0 materials. In particular, materials initially reacting very fast would experience a decrease in reactivity in the long-term, and this aspect must be incorporated in designing novel materials and sustainable remediation systems. An idea is proposed that could enable the manufacturing of intrinsically long-term efficient Fe0 materials for targeted operations as a function of the geochemistry.

Serviços Médicos de Emergência são considerados elementos críticos dos modernos sistemas de saúde, por precisarem assegurar que seu nível de serviço esteja adequado à população a qual servem. Neste sentido, Problemas de Localização de Facilidades têm sido aplicados com o intuito de indicar locais estratégicos para bases de despacho de ambulâncias que atendem às ocorrências de emergência. Este trabalho tem como objetivo realizar uma avaliação multiobjetivo de atendimentos de emergência, por meio de um modelo matemático, que considera a população atendida, o número de ocorrências e a distância percorrida pelos veículos de emergência para atendimento. Cenários são produzidos para permitir variações do tempo de resposta, do número de bases de despacho e do número de veículos disponíveis. Um estudo de caso envolvendo o município do Rio de Janeiro foi considerado para exemplificar a avaliação multiobjetivo proposta. Foram considerados cerca de 105 mil registros, entre ocorrências gerais e acidentes de trânsito.

Optogenetics has become an important tool for perturbing neural circuitry with unparalleled temporal precision and cell-type specificity. However, direct activation of a specific subpopulation of neurons can rapidly modulate the activity of other neurons within the network and may lead to unexpected and complex downstream effects. Here, we have developed a biologically-constrained computational model that exploits these non-intuitive network responses in order to gain insight into underlying properties of the network. We apply this model to data recorded during optogenetic stimulation in the primary visual cortex of the alert macaque. In these experiments, we found that optogenetic depolarization of excitatory neurons often suppressed neuronal responses, consistent with engagement of normalization circuitry. Our model suggests that the suppression seen in these responses may be mediated by slow excitatory and inhibitory conductance channels. Furthermore, the model predicted that the response of the network to optogenetic perturbation depends critically on the relationship between inherent temporal properties of the network and the temporal properties of the opsin. Consistent with model predictions, stimulation of the C1V1TT opsin, an opsin with a fast time constant (tau = 45 ms), caused faster and stronger suppressive effects after laser offset, as compared to stimulation of the slower C1V1T opsin (tau = 60ms). This work illustrates how the non-intuitive network responses that result from optogenetic stimulation can be exploited to gain insight regarding network properties that underlie fundamental neuronal computations, such as normalization. This novel hybrid opto-theoretical approach can thus enhance the power of optogenetics to dissect complex neural circuits.

Abstract In this letter, the authors compare the incidence of SUDI and SIDS in the Tuscany Region to the incidence reported by Campi and Bonati in their paper “Can we still do something-and what?- for a seemingly missing syndrome?” that was recently published in this journal. The Tuscany data are directly gathered from the autopsies while the others from the death certificates that are often not reilable, thus causing an understimation of the phenomenon. The real picture of the extent of SIDS is crucial to evaluate the effectiveness of back to sleep campaigns.

The hydrothermal conversion of giant reed (Arundo donax L.) to furfural (FA) and levulinic acid (LA) was investigated in the presence of dilute hydrochloric acid. FA and LA yields were improved by univariate optimization of the main reaction parameters: concentration of the acid catalyst, solid/liquid ratio of the reaction mixture, hydrolysis temperature, and reaction time. The catalytic performances were investigated adopting the efficient microwave (MW) irradiation, allowing significant energy and time savings. The best FA and LA yields were further confirmed using a traditionally heated autoclave reactor, giving very high results, when compared with the literature. Hydrolysis temperature and time were the main reaction variables to be carefully optimized: FA formation needed milder reaction conditions, while LA more severe ones. The effect of the crop management (e.g., harvest time) on FA/LA production was discussed, revealing that harvest time was not a discriminating parameter for the further optimization of both FA and LA production, due to the very high productivity of the giant reed throughout the year. The promising results demonstrate that giant reed represents a very interesting candidate for a very high contemporary production of FA and LA of up to about 70% and 90% of the theoretical yields, respectively.

There are many factors to consider for the design of appropriate water treatment systems including: cost, the concentration and type of biological and/or chemical contamination, concentration limits at which contaminant(s) are required to be removed, required flow rate, level of local expertise for on-going maintenance, and social acceptance. An ideal technology should be effective at producing clean, potable water; however it must also be low-cost, low-energy (ideally energy-free) and require low-maintenance. The use of packed beds containing metallic iron (Fe0 filters) has the potential to become a cheap widespread technology for both safe drinking water provision and wastewater treatment. Fe0 filters have been intensively investigated over the past two decades, however, sound design criteria are still lacking. This article presents an overview of the design of Fe0 filters for decentralized water treatment particularly in the developing world. A design for safe drinking water to a community of 100 people is also discussed as starting module. It is suggested that Fe0 filters have the potential for significant worldwide applicability, but particularly in the developing world. The appropriate design of Fe0 filters, however, is site-specific and dependent upon the availability of local expertise/materials.

This paper analyses the general increase in distances and duration of commuting based on the Household Surveys of 2002 and 2012 from the Rio de Janeiro Metropolitan Area. This increase is unequal between populations, depending in particular on the area of residence and level of education. However, even if the populations with low educational levels and residing in the poorest neighborhoods experience high commute durations, the most significant increases in travel times concern the inhabitants of new neighborhoods or towns occupied by the upper middle class, such as Barra da Tijuca and Niterói.

In this study the results of surveillance activity on döner kebab retailed on the Lucca area are reported. Ten kebab shops were inspected by health officers and food samples, including raw kebab, cooked kebab and sandwiches with kebab, were submitted for microbiological examinations. During surveillance activity some hygiene problems and difficult application of control plan were found. The microbiological analyses showed that döner kebab retailed in Lucca area had acceptable hygienic quality, but further inspections are necessary to improve the hygienic conditions of kebab shops.