112,087 research outputs found
Introducing Amyotrophic lateral sclerosis.
No full textIntroducing ALS at present times leads to re-define the concept of motor neuron selectivity which characterizes this
disorder. In fact, multiple systems including skin, liver, and bone marrow are altered in ALS patients. The motor
neuron is still the focus of the disorder and the extended pathology did not modify the concept of ALS as a devastating
disorder based on motor neuron loss. Nonetheless, the involvement of non-motor neurons as well as areas
outside the central nervous system leads to a different perspective to understand the causes, pathophysiology and
therapy of ALS. For this reason a specific issue is dedicated to understand whether intersecting basic, pre-clinical
and clinical knowledge of ALS may lead to a coherent novel scenario allowing to translate basic findings into clinical
practice. Several pre-clinical issues described in this volume appear robust enough to indicate that we should
modify a number of approaches when designing future therapeutic strategies. Similarly, novel investigations based
on altered cell to cell communication are needed to further progress in understanding amyotrophic lateral sclerosis
Future therapeutical strategies dictated by pre-clinical evidence in ALS.
No full textClassic concepts on amyotrophic lateral sclerosis led to define the disease as a selective degeneration of upper
and lower motor neurons. At present such selectivity is questioned by novel findings. For instance, the occurrence
of frontotemporal dementia is now increasingly recognized in the course of ALS. Again, areas outside the central
nervous system are targeted in ALS. In keeping with motor areas other cell types surrounding motor neurons
such as glia and interneurons are key in the pathogenesis of ALS. This multiple cell involvement may be due to a
prion-like diffusion of specific misfolded proteins which are altered in ALS. This is the case of FUS and TDP-43
which harbor a prion domain prone to pathological misfolding. These misfolded proteins are metabolized by the
autophagy, but in ALS there is evidence for a specific deficit of autophagy which impedes the clearance of these
proteins. These concepts lead to re-analyze the potential therapeutics of ALS. In fact, mere cell substitution (stem
cell) therapy appears insufficient to contrast all the alterations in the various pathways affected by ALS. Although
preclinical data speed the application of stem cells in human clinical trials, several hurdles limit their translation
into new therapies. Future treatments are expected to consider the need to target both motor neurons and neighboring
cells which may contribute to the diffusion and persistence of the disease. On this basis the present manuscript
describes which future strategies need to be pursued in order to design optimal therapeutic trial in ALS
author-bios-SRD-19-0063.R1 – Supplemental material for The Network Structure of Police Misconduct
No full textSupplemental material, author-bios-SRD-19-0063.R1 for The Network Structure of Police Misconduct by George Wood, Daria Roithmayr and Andrew V. Papachristos in Socius</p
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Glatiramer Acetate has no impact on disease progression in ALS at 40 mg/day: a double blind, randomized, multicenter, placebo controlled trial
No full textOur objective was to assess the efficacy and safety of 40 mg/day glatiramer acetate (GA) in patients with ALS. We conducted a double-blind, randomized, placebo-controlled, multicentre trial. Three hundred and sixty-six patients with definite, probable or probable laboratory supported ALS and a slow vital capacity ≥ 70% were randomly assigned to treatment with placebo or 40 mg GA daily. The primary intention-to-treat analysis was the comparison between the two treated groups of the rates of deterioration on the ALSFRSR scale. The secondary outcome measure was time to death, tracheostomy or permanent assisted ventilation. Safety and tolerability of GA were evaluated. After 52 weeks of follow-up, the slope of the ALSFRSR score was comparable in the both groups (placebo,-1.00±0.06/month; GA,-1.05±0.06/month; p=0.48). The secondary endpoint was non-significant with 159 patients (87.4%) alive in the placebo group and 162 patients (88.1%) in the GA group (log rank, p=0.75). The most common events were the injection site reactions (76.1% in the GA group, 14.8% in the placebo group), comparable to the known profile of 20 mg GA. In conclusion, GA at a dose of 40 mg/day did not show any beneficial effect in ALS patients, and safety and tolerability of GA were good in this population
Variations on the Author
No full text“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Využití sociálních médií v B2B prodeji
No full textTato diplomová práce se zabývá tím, jak mohou B2B obchodníci využívat sociální média v prodeji. Na základě systematické rešerše literatury, autor zjistil, že akademici, zkoumající danou problematiku, navrhují další výzkum, a to: v kterých konkrétních krocích se dají využít sociální média v prodeji (Salo, 2017). Autor se na základě toho rozhodl zjistit, jaké sociální sítě, různé technologie a pluginy se dají využít v B2B prodeji - tzv. social sellingu. Social selling se v této práci týká primárně procesu akvizice a okrajově péčí o stávající zákazníky. Autor si vybral kvalitativní průzkum pomocí 10 hloubkových polo-strukturovaných rozhovorů, aby odhalil jak, která sociální média to jsou, tak i motivaci prodejců, proč tato média používat/nepoužívat. Aby autor dodržel správnost vyhodnocení výsledků, data byla analyzována pomocí Tématické analýzy, která v této studii vykrystalizovala 2 hlavní strategické přístupy v social sellingu. Tyto přístupy (tzv. Push a Pull strategie) obsahují praktické příklady a konkrétní aktivity, které mohou prodejci využívat v každodenní praxi. Tyto výsledky jsou prezentovány s důrazem na praktičnost a jednoduchost implementace. Tvoří proto hlavní přínos autorovo výzkumu. V poslední části autor zmiňuje výzvy a manažerská doporučení, které mohou obchodníci využít v každodenním pracovním životě.This diploma thesis focuses on social media usage in B2B sales. Based on the systematic literature review conducted by the author, he has found out that recent researchers (Salo, 2017) suggest further research in the area of how and in which sales phase should various social networking sites, technologies and plugins used. To further fill this research gap, author decided to identify these social media and their usage among B2B salespeople in the so-called social selling process. The social selling process in this thesis applies mainly to acquiring new prospects and tangentially to taking care of existing clients (follow-up step). Author has chosen a qualitative research method via conducting 10 in-depth semi-structured interviews to reveal these instruments as well as motivation of a sales person on why to use social media in the selling process. The collected data was analyzed using Thematic analysis to ensure the right procedure and to identify main themes which crystalized into 2 main strategic approaches in social selling. These approaches (Push and Pull) include practical examples of concrete activities which sales people can use in their daily jobs and are presented with focus on practicality and ease of implementation. These also form the main contribution of author`s research. In the last part, author mentions challenges in social selling and recommended managerial implications for salesforce
TeX v jednoduchém unixovém prostředí
No full textsummary:Při ladění TeXového dokumentu potřebujeme mnohokrát opakovaně pouštět TeX, podívat se, jak dopadl výsledek v prohlížeči DVI nebo PDF souboru, mrknout na výpis TeXu na terminálu, podívat se případně do logu a celou činnost opakovat. V tomto článku je ukázáno, jak tuto práci dělá autor článku. Proces "editor-TeX-kuk" je zde podporován jednoduchými unixovými nástroji: bashovým skriptem texloop, který si autor pro tyto účely vytvořil, dále terminálem Xterm a jednoduchým editorem, který umí navázat na klávesovou zkratku spuštění příkazu v systému. Čtenář se zde může inspirovat a přizpůsobit tyto nástroje svým vlastním potřebám. V článku je popsána funkce skriptu texloop, dále je neformálně rozveden dlouholetý vývoj autorova vztahu k textovým editorům a konečně je zde uvedena konfigurace terminálu Xterm, aby vyhovoval českému prostředí jak v kódování ISO-8859-2, tak v kódování UTF-8. Pro kódování UTF-8 si v závěru článku vygenerujeme TeXový formát csplain.summary:By debugging a TeX document it is necessary many times repeatedly to run TeX, to look for the result in DVI or PDF file, to gander the TeX output on the terminal, or eventually to have a look in the log-file, and all that action to repeat. In the paper it is show, how this work is made by author. The process '‘'editor-TeX-look' is supported by simple Unix tools: bash script texloop, created by author for these purposes, Xterm terminal and a simple editor, which is able to link to the shortcut key the activation of a system command. The reader could be inspired with the solution and to adapt these tools to his/her own needs. In the paper the function of the texloop script is described, and further the longstanding evolution of the author's relation to text editors is informal elaborated and finally a configuration of Xterm terminal, suitable for the czech environment with both ISO-8859-2 and UTF-8 encoding is introduced. For UTF-8 encoding the TeX format csplain is generated at the end of the paper
Bausteine zu einer Geschichte der Stadt Meiningen
No full textBAUSTEINE ZU EINER GESCHICHTE DER STADT MEININGEN
Bausteine zu einer Geschichte der Stadt Meiningen ( - )
Title page ( - )
Title page ( - )
Preface ( - )
I. Die Entstehung der Jahrmärkte und die Wochenmärkte in Meiningen ( - )
II. Inschriften und Denkmäler der Stadtkirche in Meiningen ( - )
III. Die Beziehungen des letzten Fürstbischofs von Würzburg zur Stadt Meiningen ( - )
IV. Die Gast- und Unterkunftshäuser im alten Meiningen ( - )
V. Ein Leprahaus in Meiningen ( - )
VI. Meininger Gelehrte und andere hervorragende Meininger Stadtkinder aus alter und neuer Zeit ( - )
VII. Übersicht über Herkunft und Bedeutung der Meininger Straßennamen ( - )
VIII. Die Bevölkerungszahlen der Stadt Meiningen sonst und jetzt ( - )
Verzeichnis der benutzten Bücher und Handschriften ( - )
Remarks ( - )
Table of contents ( -
Analýza perspektivy vedoucích prodeje na řízení pojišťovacích agentů v etnicky různorodých zastoupeních v Organizaci G, Malajsie.
No full textCílem této práce je odhalit klíčové faktory a výzvy spojené s řízením etnicky různorodého pojišťovacího zastoupení v oboru životního pojištění v Malajsii. Autor si klade za cíl zkoumat pohled vedoucích prodeje v Organizaci G v Malajsii na jejich způsob řízení agentů. Kombinované kvantitativní a kvalitativní metody budou použity prostřednictvím průzkumu a rozhovorů se 79 agenty a 12 vedoucími prodeje. Odpovědi budou analyzovány za účelem porozumění výzvám, kterým čelí vedoucí prodeje při řízení etnicky různorodého zastoupení, a zkoumat potenciální řešení. Autor navrhuje iniciativy a metody k posílení stylů vedení a zlepšení procesů pro udržení úspěšného zastoupení v kontextu etnické rozmanitosti.The goal of this thesis is to uncover the key factors and challenges in managing an ethnically diverse insurance agency in Malaysia's life insurance industry. The author aims to examine the sales managers' perspective in Organisation G, Malaysia, regarding their expression of managing their agents. Quantitative and qualitative methods will be employed through surveys and interviews among 79 agents and 12 sales managers. The responses will be analysed to understand the challenges sales managers face in managing a multi-ethnic agency and explore potential solutions. The author proposes initiatives and methods to enhance leadership styles and improve the processes for maintaining a successful agency in the context of multi-ethnicity
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