Differentiating lower motor neuron syndromes

Lower motor neuron (LMN) syndromes typically present with muscle wasting and weakness and may arise from pathology affecting the distal motor nerve up to the level of the anterior horn cell. A variety of hereditary causes are recognised, including spinal muscular atrophy, distal hereditary motor neuropathy and LMN variants of familial motor neuron disease. Recent genetic advances have resulted in the identification of a variety of disease-causing mutations. Immune-mediated disorders, including multifocal motor neuropathy and variants of chronic inflammatory demyelinating polyneuropathy, account for a proportion of LMN presentations and are important to recognise, as effective treatments are available. The present review will outline the spectrum of LMN syndromes that may develop in adulthood and provide a framework for the clinician assessing a patient presenting with predominantly LMN features

Ribosomal protein S6 mRNA is a biomarker upregulated in multiple sclerosis, downregulated by interferon treatment, and affected by season

Background

Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination.

Abstract OBJECTIVE: We characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination. METHODS: We evaluated clinical phenotypes, annualised relapse rates (ARR) prior and on immunotherapy and Expanded Disability Status Scale (EDSS), in 218 demyelinating episodes from 33 paediatric and 26 adult patients. RESULTS: The most common initial presentation in the cohort was optic neuritis (ON) in 54% (bilateral (BON) 32%, unilateral (UON) 22%), followed by acute disseminated encephalomyelitis (ADEM) (20%), which occurred exclusively in children. ON was the dominant phenotype (UON 35%, BON 19%) of all clinical episodes. 109/226 (48%) MRIs had no brain lesions. Patients were steroid responsive, but 70% of episodes treated with oral prednisone relapsed, particularly at doses <10\u2009mg daily or within 2 months of cessation. Immunotherapy, including maintenance prednisone (P=0.0004), intravenous immunoglobulin, rituximab and mycophenolate, all reduced median ARRs on-treatment. Treatment failure rates were lower in patients on maintenance steroids (5%) compared with non-steroidal maintenance immunotherapy (38%) (P=0.016). 58% of patients experienced residual disability (average follow-up 61 months, visual loss in 24%). Patients with ON were less likely to have sustained disability defined by a final EDSS of 652 (OR 0.15, P=0.032), while those who had any myelitis were more likely to have sustained residual deficits (OR 3.56, P=0.077). CONCLUSION: Relapsing MOG antibody-associated demyelination is strongly associated with ON across all age groups and ADEM in children. Patients are highly responsive to steroids, but vulnerable to relapse on steroid reduction and cessation

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Persistence on therapy and propensity matched outcome comparison of two subcutaneous interferon beta 1a dosages for multiple sclerosis

To compare treatment persistence between two dosages of interferon &beta;-1a in a large observational multiple sclerosis registry and assess disease outcomes of first line MS treatment at these dosages using propensity scoring to adjust for baseline imbalance in disease characteristics. Treatment discontinuations were evaluated in all patients within the MSBase registry who commenced interferon &beta;-1a SC thrice weekly (n = 4678). Furthermore, we assessed 2-year clinical outcomes in 1220 patients treated with interferon &beta;-1a in either dosage (22 &micro;g or 44 &micro;g) as their first disease modifying agent, matched on propensity score calculated from pre-treatment demographic and clinical variables. A subgroup analysis was performed on 456 matched patients who also had baseline MRI variables recorded. Overall, 4054 treatment discontinuations were recorded in 3059 patients. The patients receiving the lower interferon dosage were more likely to discontinue treatment than those with the higher dosage (25% vs. 20% annual probability of discontinuation, respectively). This was seen in discontinuations with reasons recorded as &ldquo;lack of efficacy&rdquo; (3.3% vs. 1.7%), &ldquo;scheduled stop&rdquo; (2.2% vs. 1.3%) or without the reason recorded (16.7% vs. 13.3% annual discontinuation rate, 22 &micro;g vs. 44 &micro;g dosage, respectively). Propensity score was determined by treating centre and disability (score without MRI parameters) or centre, sex and number of contrast-enhancing lesions (score including MRI parameters). No differences in clinical outcomes at two years (relapse rate, time relapse-free and disability) were observed between the matched patients treated with either of the interferon dosages. Treatment discontinuations were more common in interferon &beta;-1a 22 &micro;g SC thrice weekly. However, 2-year clinical outcomes did not differ between patients receiving the different dosages, thus replicating in a registry dataset derived from &ldquo;real-world&rdquo; database the results of the pivotal randomised trial. Propensity score matching effectively minimised baseline covariate imbalance between two directly compared sub-populations from a large observational registry

Molecular mechanisms of cell death:recommendations of the Nomenclature Committee on Cell Death 2018

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.</p

Future Internet as a Driver for Virtualization, Connectivity and Intelligence of Agri-Food Supply Chain Networks

The food and agribusiness is an important sector in European logistics with a share in the EU road transport of about 20%. One of the main logistic challenges in this sector is to deal with the high dynamics and uncertainty in supply and demand. This paper discusses the opportunities of Future Internet (FI) technologies to addresses the specific demands on information systems for logistics in the food and agribusiness domain. More specifically, it presents a Future Internet (FI) based design for smart agri-food logistic information systems. This design aims to enable new types of efficient and responsive logistics networks with flexible chain-encompassing tracking and tracing systems and decision support based on that information. These systems effectively virtualise the logistics flows from farm to fork, support a timely and error-free exchange of logistics information and provide functionality for intelligent analysis and reporting of exchanged data to enable early warning and advanced forecasting

Fractional flow reserve in patients with intermediate values of Duke Treadmill Score and borderline coronary lesions

Despite the wide usage of exercise ECG tests and Duke Treadmill Score (DTS) in clinical practice, no comparison between this scoring system and Fractional Flow Reserve (FFR) has yet been made, particularly in cases of angiographically verified borderline lesions. Thirty patients with single coronary lesions and angiographically assessed borderline stenosis (between 30-70%) and previously calculated intermediate values of DTS between -10 to +4 were examined using FFR. Adequate specificity and sensitivity (0.769 and 0.556, respectively) were in a more narrow range of -0.5 to -10. Sex and age did not have an influence on the DTS values. There was a correlation between the values of FFR and age (r=0.395, p=0.031) and between angiographic assessment of stenosis and quantitative coronary angiography (QCA) (r=0.648, p<0.0001). In the study population, a decision on revascularization could not be based solely on angiographic or QCA assessment of the artery or on the values of DTS

MiNDAUS partnership: a roadmap for the cure and management of motor Neurone disease

An innovative approach to patient management, evidence-based policy development, and clinical drug trials is required to provide personalized care and to improve the likelihood of finding an effective treatment for Motor Neurone Disease (MND). The MiNDAus Partnership builds on and extends existing national collaborations in a targeted approach to improve the standard and coordination of care for people living with MND in Australia, and to enhance the prospects of discovering a cure or treatment. Relationships have been developed between leading clinical and research groups as well as patient-centered organizations, care providers, and philanthropy with a shared vision. MiNDAus has established a corporate structure and meets at least biannually to decide on how best to progress research, drug development, and patient management. The key themes are; (i) empowering patients and their family carers to engage in self-management and ensure personalized service provision, treatment, and policy development, (ii) integration of data collection so as to better inform policy development, (iii) unifying patients and carers with advocacy groups, funding bodies, clinicians and academic institutions so as to inform policy development and research, (iv) coordination of research efforts and development of standardized national infrastructure for conducting innovative clinical MND trials that can be harmonized within Australia and with international trials consortia. Such a collaborative approach is required across stakeholders in order to develop innovative management guidelines, underpinned by necessary and evidence-based policy change recommendations, which, will ensure the best patient care until a cure is discovered

Implementacija digitalnog generatora obojenog šuma bez množila

Colored noise can be generated by filtering of the white noise. It is a simple task. However, it becomes challenging if high operating speed of the generator is required. The realization of digital filter generally requires one multiplication per coefficient. Therefore, a high operating speed is achieved only with the cost of several generalpurpose multipliers. In this paper, a multiplierless realization of the colored noise generator is proposed. It is based on the filtering of 1-bit random signal by a finite impulse response filter. The design of the generator is described and its implementation is considered. Furthermore, an application is described in which the proposed generator is used in mitigation of undesired effects caused by nonlinearities in an analog to digital converter.Obojeni šum može se generirati filtriranjem bijelog šuma. To je jednostavan postupak. Međutim, on postaje izazovan ako se od generatora traži velika brzina rada. Realizacija digitalnog filtra u pravilu zahtijeva jedno množenje po koeficijentu. Zato se velika brzina rada može postići samo uz cijenu većeg broja množila opće namjene. U ovom radu predložena je realizacija generatora obojenog šuma koja ne sadrži množila. Ona se temelji se na filtraciji 1-bitnog slučajnog signala pomoću filtra s konačnim impulsnim odzivom. Opisano je projektiranje generatora te je razmotrena njegova implementacija. Nadalje, opisana je primjena u kojoj je predloženi generator iskorišten za smanjivanje utjecaja nelinearnosti u analogno digitalnom pretvorniku