Accelerated life tests as an integrated methodology for product design, qualification and production control: a case study in household appliances

Cost reduction and product quality are key factors in the present competitive market. Product reliability is strongly correlated with customer satisfaction. Accelerated life tests (ALTs) represent a methodology able to investigate product reliability performance in a short time with respect to the classical testing methods in the design. The aim of this paper is the proposal and development of an integrated procedure based on ALTs in order to evaluate the reliability performance of a new product; the use of such testing methods is useful to systematically support the design and qualification phases and to help the service demand forecasting before the product launch. The smart choice of the acceleration parameter and the knowledge developed during the upstream phase in the product lifecycle can be useful and cost effective for its utilization in the downstream lifecycle, as an acceptable substitute of specific advanced final inspection methodologies. The methodology has been tested during the development ..

Italian guidelines for primary headache: 2012 revised version

The first edition of the Italian diagnostic and therapeutic guidelines for primary headaches in adults was published in J Headache Pain 2(Suppl. 1):105-190 (2001). Ten years later, the guideline committee of the Italian Society for the Study of Headaches (SISC) decided it was time to update therapeutic guidelines. A literature search was carried out on Medline database, and all articles on primary headache treatments in English, German, French and Italian published from February 2001 to December 2011 were taken into account. Only randomized controlled trials (RCT) and meta-analyses were analysed for each drug. If RCT were lacking, open studies and case series were also examined. According to the previous edition, four levels of recommendation were defined on the basis of levels of evidence, scientific strength of evidence and clinical effectiveness. Recommendations for symptomatic and prophylactic treatment of migraine and cluster headache were therefore revised with respect to previous 2001 guidelines and a section was dedic

Robot-mediated overground gait training for transfemoral amputees with a powered bilateral hip orthosis: a pilot study

Background: Transfemoral amputation is a serious intervention that alters the locomotion pattern, leading to secondary disorders and reduced quality of life. The outcomes of current gait rehabilitation for TFAs seem to be highly dependent on factors such as the duration and intensity of the treatment and the age or etiology of the patient. Although the use of robotic assistance for prosthetic gait rehabilitation has been limited, robotic technologies have demonstrated positive rehabilitative effects for other mobility disorders and may thus offer a promising solution for the restoration of healthy gait in TFAs. This study therefore explored the feasibility of using a bilateral powered hip orthosis (APO) to train the gait of community-ambulating TFAs and the effects on their walking abilities. Methods: Seven participants (46–71 years old with different mobility levels) were included in the study and assigned to one of two groups (namely Symmetry and Speed groups) according to their prosthesis type, mobility level, and prior experience with the exoskeleton. Each participant engaged in a maximum of 12 sessions, divided into one Enrollment session, one Tuning session, two Assessment sessions (conducted before and after the training program), and eight Training sessions, each consisting of 20 minutes of robotically assisted overground walking combined with additional tasks. The two groups were assisted by different torque-phase profiles, aiming at improving symmetry for the Symmetry group and at maximizing the net power transferred by the APO for the Speed group. During the Assessment sessions, participants performed two 6-min walking tests (6mWTs), one with (Exo) and one without (NoExo) the exoskeleton, at either maximal (Symmetry group) or self-selected (Speed group) speed. Spatio-temporal gait parameters were recorded by commercial measurement equipment as well as by the APO sensors, and metabolic efficiency was estimated via the Cost of Transport (CoT). Additionally, kinetic and kinematic data were recorded before and after treatment in the NoExo condition. Results: The one-month training protocol was found to be a feasible strategy to train TFAs, as all participants smoothly completed the clinical protocol with no relevant mechanical failures of the APO. The walking performance of participants improved after the training. During the 6mWT in NoExo, participants in the Symmetry and Speed groups respectively walked 17.4% and 11.7% farther and increased walking speed by 13.7% and 17.9%, with improved temporal and spatial symmetry for the former group and decreased energetic expenditure for the latter. Gait analysis showed that ankle power, step width, and hip kinematics were modified towards healthy reference levels in both groups. In the Exo condition metabolic efficiency was reduced by 3% for the Symmetry group and more than 20% for the Speed group. Conclusions: This study presents the first pilot study to apply a wearable robotic orthosis (APO) to assist TFAs in an overground gait rehabilitation program. The proposed APO-assisted training program was demonstrated as a feasible strategy to train TFAs in a rehabilitation setting. Subjects improved their walking abilities, although further studies are required to evaluate the effectiveness of the APO compared to other gait interventions. Future protocols will include a lighter version of the APO along with optimized assistive strategies

Soluble CD40 ligand and prolactin levels in migraine patients during interictal period

The relationship of migraine with cardiovascular diseases has been clarified by many studies, and currently, migraine is suggested to be a systematic vasculopathy. Inflammation, thrombosis and impaired vascular reactivity are the underlying pathophysiological mechanisms of the vasculopathy. In the present study, we aimed to investigate the relationship between prolactin levels and subclinical atherosclerosis risk factors such as soluble CD40 ligand (sCD40L) and high-sensitivity CRP (hsCRP) in migraine patients during interictal period. Fifty female migraine patients and age-matched 25 female control cases were enrolled in the study. Migraine diagnosis was settled according to the ICHD-II diagnostic criteria. A questionnaire was completed about the existence of vascular risk factors. Serum samples were used to measure sCD40L, hsCRP and prolactin levels. No difference was found between the prolactin levels of the migraine patients and the controls. The sCD40L levels were significantly higher in migraine patients (p < 0.001). High-sensitivity CRP levels showed no difference between the groups. There was no correlation between prolactin, sCD40L, and hs-CRP levels in migraine patients. We consider that the migraine patients are prone to subclinical atherosclerosis, but this tendency is independent of prolactin levels

Antidromic vasodilatation and the migraine mechanism

Despite the fact that an unprecedented series of new discoveries in neurochemistry, neuroimaging, genetics and clinical pharmacology accumulated over the last 20 years has significantly increased our current knowledge, the underlying mechanism of the migraine headache remains elusive. The present review article addresses, from early evidence that emerged at the end of the nineteenth century, the role of ‘antidromic vasodilatation’ as part of the more general phenomenon, currently defined as neurogenic inflammation, in the unique type of pain reported by patients suffering from migraine headaches. The present paper describes distinctive orthodromic and antidromic properties of a subset of somatosensory neurons, the vascular- and neurobiology of peptides contained in these neurons, and the clinical–pharmacological data obtained in recent investigations using provocation tests in experimental animals and human beings. Altogether, previous and recent data underscore that antidromic vasodilatation, originating from the activation of peptidergic somatosensory neurons, cannot yet be discarded as a major contributing mechanism of the throbbing head pain and hyperalgesia of migraine

IL-1β Stimulates COX-2 Dependent PGE2 Synthesis and CGRP Release in Rat Trigeminal Ganglia Cells

OBJECTIVE: Pro-inflammatory cytokines like Interleukin-1 beta (IL-1β) have been implicated in the pathophysiology of migraine and inflammatory pain. The trigeminal ganglion and calcitonin gene-related peptide (CGRP) are crucial components in the pathophysiology of primary headaches. 5-HT1B/D receptor agonists, which reduce CGRP release, and cyclooxygenase (COX) inhibitors can abort trigeminally mediated pain. However, the cellular source of COX and the interplay between COX and CGRP within the trigeminal ganglion have not been clearly identified. METHODS AND RESULTS: 1. We used primary cultured rat trigeminal ganglia cells to assess whether IL-1β can induce the expression of COX-2 and which cells express COX-2. Stimulation with IL-1β caused a dose and time dependent induction of COX-2 but not COX-1 mRNA. Immunohistochemistry revealed expression of COX-2 protein in neuronal and glial cells. 2. Functional significance was demonstrated by prostaglandin E2 (PGE(2)) release 4 hours after stimulation with IL-1β, which could be aborted by a selective COX-2 (parecoxib) and a non-selective COX-inhibitor (indomethacin). 3. Induction of CGRP release, indicating functional neuronal activation, was seen 1 hour after PGE(2) and 24 hours after IL-1β stimulation. Immunohistochemistry showed trigeminal neurons as the source of CGRP. IL-1β induced CGRP release was blocked by parecoxib and indomethacin, but the 5-HT1B/D receptor agonist sumatriptan had no effect. CONCLUSION: We identified a COX-2 dependent pathway of cytokine induced CGRP release in trigeminal ganglia neurons that is not affected by 5-HT1B/D receptor activation. Activation of neuronal and glial cells in the trigeminal ganglion by IL-β leads to an elevated expression of COX-2 in these cells. Newly synthesized PGE(2) (by COX-2) in turn activates trigeminal neurons to release CGRP. These findings support a glia-neuron interaction in the trigeminal ganglion and demonstrate a sequential link between COX-2 and CGRP. The results could help to explain the mechanism of action of COX-2 inhibitors in migraine

Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

<p>Abstract</p> <p>Background</p> <p>Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics.</p> <p>Discussion</p> <p>In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect.</p> <p>As an example the fixesd-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy.</p> <p>Summary</p> <p>Multitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness of the therapeutic effect, and allow doctors (and, in self-medication with OTC medications, the patients themselves) to customize treatment to the patient's specific needs. There is substantial clinical evidence that such a multi-component therapy is more effective than mono-component therapies.</p

Italian guidelines for primary headaches: 2012 revised version

The first edition of the Italian diagnostic and therapeutic guidelines for primary headaches in adults was published in J Headache Pain 2(Suppl. 1):105–190 (2001). Ten years later, the guideline committee of the Italian Society for the Study of Headaches (SISC) decided it was time to update therapeutic guidelines. A literature search was carried out on Medline database, and all articles on primary headache treatments in English, German, French and Italian published from February 2001 to December 2011 were taken into account. Only randomized controlled trials (RCT) and meta-analyses were analysed for each drug. If RCT were lacking, open studies and case series were also examined. According to the previous edition, four levels of recommendation were defined on the basis of levels of evidence, scientific strength of evidence and clinical effectiveness. Recommendations for symptomatic and prophylactic treatment of migraine and cluster headache were therefore revised with respect to previous 2001 guidelines and a section was dedicated to non-pharmacological treatment. This article reports a summary of the revised version published in extenso in an Italian version