Clinical trials for elderly patients with multiple diseases (CHROMED) pilot study

The problem COPD (Chronic Obstructive Pulmonary Disease) is a significant socioeconomic burden which, particularly when associated with comorbidities such as Chronic Heart Failure (CHF), markedly affects patient outcomes. Care models based on telemedicine systems that enable early diagnosis and treatment of exacerbations are advocated to reduce the impact of chronic diseases on patient outcomes and health service costs. CHROMED (www.chromed.eu) is an international EU-funded project aimed at developing a multi-centre clinical trial to evaluate the impact of a new integrated home care approach to reduce care costs and improve quality of life in COPD. The approach We collaborated in a pilot study prior to the main trial which will include 300 patients from seven European countries (Italy, Spain, UK, Estonia, Slovenia, Sweden and Norway) with nine partners. The home monitoring system includes a novel forced oscillation technique (FOT) device for self-measurement of lung mechanics (RESMONPRO DIARY, Restech srl, Italy), a touch screen for collecting patients' symptoms and, where COPD is associated with CHF, by a device for measuring heart rate (HR), blood pressure (BP), pulse oximetry (SpO2) and body temperature (WRIST CLINIC, Medic4all, Israel). Findings The pilot included 16 patients (n=11 COPD, 5 COPD+CHF). The average monitoring period was 48.3±23.4 days resulting in a total of 504 patient days. The percentage of data correctly received within the period was: lung impedance and breathing pattern 90.0%; HR 91.7%, BP 91.7%; SpO2 74.0% and body temperature 71.4%. During the pilot, one patient was treated pharmacologically for an exacerbation of COPD. Offline processing demonstrated that the system identified warning of an exacerbation five days prior to admission. We also analysed qualitative data from patients and professionals about the acceptability of the telemedicine system and the interaction between patients, professionals and the monitoring system. Consequences The data suggest good acceptability and short-term compliance among patients with COPD. Lung function, HR and BP provided the most reliable data. The full RCT is currently under way and will be completed in August 2015

RFC1 expansions are a common cause of idiopathic sensory neuropathy

After extensive evaluation, one-third of patients affected by polyneuropathy remain undiagnosed and are labelled as having chronic idiopathic axonal polyneuropathy, which refers to a sensory or sensory-motor, axonal, slowly progressive neuropathy of unknown origin. Since a sensory neuropathy/neuronopathy is identified in all patients with genetically confirmed RFC1 cerebellar ataxia, neuropathy, vestibular areflexia syndrome, we speculated that RFC1 expansions could underlie a fraction of idiopathic sensory neuropathies also diagnosed as chronic idiopathic axonal polyneuropathy. We retrospectively identified 225 patients diagnosed with chronic idiopathic axonal polyneuropathy (125 sensory neuropathy, 100 sensory-motor neuropathy) from our general neuropathy clinics in Italy and the UK. All patients underwent full neurological evaluation and a blood sample was collected for RFC1 testing. Biallelic RFC1 expansions were identified in 43 patients (34%) with sensory neuropathy and in none with sensory-motor neuropathy. Forty-two per cent of RFC1-positive patients had isolated sensory neuropathy or sensory neuropathy with chronic cough, while vestibular and/or cerebellar involvement, often subclinical, were identified at examination in 58%. Although the sensory ganglia are the primary pathological target of the disease, the sensory impairment was typically worse distally and symmetric, while gait and limb ataxia were absent in two-thirds of the cases. Sensory amplitudes were either globally absent (26%) or reduced in a length-dependent (30%) or non-length dependent pattern (44%). A quarter of RFC1-positive patients had previously received an alternative diagnosis, including Sj\uf6gren's syndrome, sensory chronic inflammatory demyelinating polyneuropathy and paraneoplastic neuropathy, while three cases had been treated with immune therapies

Apolipoprotein A-II Influences Apolipoprotein E-Linked Cardiovascular Disease Risk in Women with High Levels of HDL Cholesterol and C-Reactive Protein

Background: In a previous report by our group, high levels of apolipoprotein E (apoE) were demonstrated to be associated with risk of incident cardiovascular disease in women with high levels of C-reactive protein (CRP) in the setting of both low (designated as HR1 subjects) and high (designated as HR2 subjects) levels of high-density lipoprotein cholesterol (HDL-C). To assess whether apolipoprotein A-II (apoA-II) plays a role in apoE-associated risk in the two female groups. Methodology/Principal: Outcome event mapping, a graphical data exploratory tool; Cox proportional hazards multivariable regression; and curve-fitting modeling were used to examine apoA-II influence on apoE-associated risk focusing on HDL particles with apolipoprotein A-I (apoA-I) without apoA-II (LpA-I) and HDL particles with both apoA-I and apoA-II (LpA-I:A-II). Results of outcome mappings as a function of apoE levels and the ratio of apoA-II to apoA-I revealed within each of the two populations, a high-risk subgroup characterized in each situation by high levels of apoE and additionally: in HR1, by a low value of the apoA-II/apoA-I ratio; and in HR2, by a moderate value of the apoA-II/apoA-I ratio. Furthermore, derived estimates of LpA-I and LpA-I:A-II levels revealed for high-risk versus remaining subjects: in HR1, higher levels of LpA-I and lower levels of LpA-I:A-II; and in HR2 the reverse, lower levels of LpA-I and higher levels of LpA-I:A-II. Results of multivariable risk modeling as a function of LpA-I and LpA-I:A-II (dichotomized as highest quartile versus combined three lower quartiles) revealed association of risk only for high levels of LpA-I:A-II in the HR2 subgroup (hazard ratio 5.31, 95% CI 1.12-25.17, p = 0.036). Furthermore, high LpA-I: A-II levels interacted with high apoE levels in establishing subgroup risk. Conclusions/Significance: We conclude that apoA-II plays a significant role in apoE-associated risk of incident CVD in women with high levels of HDL-C and CRP

Back Pressure Congestion Control for CoAP/6LoWPAN Networks

In this paper we address the design of network architectures for the Internet of Things by proposing practical algorithms to augment IETF CoAP/6LoWPAN protocol stacks with congestion control functionalities. Our design is inspired by previous theoretical work on back pressure routing and is targeted toward Web-based architectures featuring bidirectional data flows made up of CoAP request/response pairs. Here, we present three different cross-layer and fully decentralized congestion control schemes and compare them against ideal back pressure and current UDP-based protocol stacks. Hence, we discuss results obtained using ns-3 through an extensive simulation campaign for two different scenarios: unidirectional and upstream flows and bidirectional Web-based CoAP flows. Our results confirm that the proposed congestion control algorithms perform satisfactorily in both scenarios for a wide range of values of their configuration parameters, and are amenable to the implementation onto existing protocol stacks for embedded sensor devices

Interoperable and globally interconnected Smart Grid using IPv6 and 6LoWPAN

The general feeling about ecology is changing worldwide. People all around the world are more careful about problems such as energy provisioning and consumption. New ideas, such as the Smart Grid concept, are trying to give solutions to the energy problems by means of a modern power grid with intelligent management capabilities. In such scenarios, networking solutions, e.g., the Internet Protocol version 6 (IPv6), will allow appliances to be remotely coordinated in order to optimize the total power consumption, and balance the power demand. This paper presents an innovative implementation of the IPv6 stack over the 6LoWPAN adaptation layer. Our 6LoWPAN implementation aims to provide a support platform for IPv6 over interoperable constrained-resources devices, such as those embedded in the electrical appliances. Our main goals are to optimize the memory management and to address the portability problems of the stack. In particular we want to develop a stack which is not tied to a particular data-link protocol. Comparison with existing solutions is also provided

CXCR4 engagement triggers CD47 internalization and antitumor immunization in a mouse model of mesothelioma

Abstract Boosting antitumor immunity has emerged as a powerful strategy in cancer treatment. While releasing T‐cell brakes has received most attention, tumor recognition by T cells is a pre‐requisite. Radiotherapy and certain cytotoxic drugs induce the release of damage‐associated molecular patterns, which promote tumor antigen cross‐presentation and T‐cell priming. Antibodies against the “do not eat me” signal CD47 cause macrophage phagocytosis of live tumor cells and drive the emergence of antitumor T cells. Here we show that CXCR4 activation, so far associated only with tumor progression and metastasis, also flags tumor cells to immune recognition. Both CXCL12, the natural CXCR4 ligand, and BoxA, a fragment of HMGB1, promote the release of DAMPs and the internalization of CD47, leading to protective antitumor immunity. We designate as Immunogenic Surrender the process by which CXCR4 turns in tumor cells to macrophages, thereby subjecting a rapidly growing tissue to immunological scrutiny. Importantly, while CXCL12 promotes tumor cell proliferation, BoxA reduces it, and might be exploited for the treatment of malignant mesothelioma and a variety of other tumors