196,569 research outputs found
Target population for clinical trials on sarcopenia
No full textThe term "sarcopenia" describes the progressive decline of muscle mass, strength and function occurring with aging. It is not considered a disease, but the direct consequence of the aging process on the skeletal muscle. Multiple demographic (e.g. gender, race), biological (e.g. inflammatory status) and clinical (e.g. diabetes, metabolic syndrome, congestive heart failure, medications) factors are able to influence (positively or negatively) the skeletal muscle quality and quantity. The extreme paucity of clinical trials on sarcopenia in literature is mainly due to difficulties in designing studies able to isolate the aging process from its multiple and interconnected consequences. In the present review, we present the major factors to consider as potential sources of biased results when evaluating potential candidates for clinical trials on sarcopenia. The development of clinical trials exploring the nature of the sarcopenia process is urgent, but several controversial issues on this hallmark of aging still need clarification
Designing Phase II B trials in sarcopenia : the best target population
No full textDespite the existing limitations and controversies regarding the definition of sarcopenia and its clinical consequences, the current scientific evidence strongly suggests that muscle decline is a primary determinant of the disabling process (and likely of other major health-related events). In fact, the muscle loss (in terms of mass as well as strength) occurring with aging has been growingly associated with mobility impairment and disability in older persons. Unfortunately, current evidence is mainly from observational studies. Times are mature to begin testing interventions aimed at modifying the sarcopenia process through the design and development of specific clinical trials. Considering the emergence of many promising interventions towards this age-related condition (e.g., physical exercise [in particular, resistance training], testosterone, antioxidant supplementations), the need for Phase II trial designs is high. In the present report, we discuss which are the major issues related to the design of Phase II clinical trials on sarcopenia with particular focus on the participant's characteristics to be considered as possible inclusion and exclusion criteria
TRANSFER PRICING - EU TAX POLICY CHALLENGE
No full textNastanek prvih multinacionalnih družb povezujemo z obdobjem kolonializma v 16. stoletju. Družbe, kot je bila Britanska vzhodnoindijska družba, ki je bila ena prvih delniških družb na svetu, so pospešeno začele trgovati z družbami v kolonijah. V obdobju po prvi svetovni vojni so bila multinacionalna podjetja v večini industrijska podjetja in to je tudi obdobje, ko se je izoblikoval sedanji sistem obdavčitve pravnih oseb. Če je bilo takrat relativno enostavno obdavčiti takšno multinacionalno družbo po načelu obdavčitve po viru, pa je danes v obdobju intenzivno globaliziranega in digitaliziranega sveta to vse prej kot enostavno.
Če je v začetku globalizacije za države in gospodarske družbe bil največji izziv preprečiti dvojno obdavčenje, se v sedanjem času vedno bolj pojavlja težava zaradi neučinkovitega sistema obdavčitve gospodarskih družb in hkrati težnja po izgradnji davčnega sistema, ki bi zagotovil plačevanje davčne obveznosti tam, kjer dobiček dejansko nastaja.
V želji po pravični porazdelitvi davčnega prihodka med države, v katerih poslujejo povezane osebe, je bil izoblikovan sistem pravil o transfernih cenah, pri razvoju katerega je imela veliko vlogo Organizacija za gospodarsko sodelovanje in razvoj. Oblikovala je Smernice OECD za določanje transfernih cen za mednarodna podjetja in davčne uprave, ki jih je večina razvitih držav implementirala v svojo nacionalno zakonodajo. Temu je sledila tudi Slovenija. Prvi del diplomskega dela tako obravnava zgodovino transfernih cen, smernice OECD in ureditev transfernih cen v Sloveniji.
V EU se je problematika o obdavčitvi pravnih oseb začela obravnavati že v 60. letih prejšnjega stoletja. Z vzpostavitvijo enotnega trga je problem dvojnega obdavčevanja postal ključna ovira za njegovo nemoteno delovanje. Tako se je v 90. letih prejšnjega stoletja glavnina pozornosti delovanja EU usmerjala v odstranjevanje ovir za nemoteno delovanje enotnega trga.
Aferi »LuxLeaks« in »Panama Papers« pa sta pokazali, da mednarodni sistem obdavčevanja pravnih oseb, ki temelji na načelih, ki so bila izoblikovana v povsem drugačnih okoliščinah pred skoraj sto leti, čeprav s »korekcijami«, ni več učinkovit v sedanjih okoliščinah globalno digitaliziranega sveta, v katerem je prisotna tudi močna davčna konkurenca med državami. To je uvidela tudi EU, ki si je zastavila ambiciozne cilje v leta 2015 sprejetem Akcijskem načrtu in na tej podlagi leta 2016 predstavila paket ukrepov zoper izogibanje davkov.
Eden ključnih ukrepov je vzpostavitev sistema, ki bi temeljil na konsolidirani davčni osnovi. Sistem bo upošteval celotni prihodek večnacionalne družbe kot celote, nato pa po vnaprej znani formuli razdelil davčne prihodke med države, kjer je družba dejansko opravljala poslovne aktivnosti in dejansko ustvarjala dobiček.
Želja EU kot tudi OECD in njenega programa BEPS je torej reformirati mednarodni davčni sistem in izgraditi takšnega, ki bo izničil učinke agresivnega davčnega načrtovanja ter omogočil, da se dobiček obdavči v državi, kjer dejansko nastaja. Drugi del diplomskega dela tako obravnava transferne cene kot izziv davčne politike EU, preusmeritev dobička večnacionalnih družb v jurisdikcije z ugodnejšim davčnim okoljem, finančne učinke takšnih ravnanj na proračune držav članic, predstavlja pa tudi sheme agresivnega davčnega načrtovanja in ukrepe EU za preprečitev erozije davčne osnove in preusmeritve dobička.The occurrence of the first multinational companies is associated with the colonial period in the 16th century. Companies like the East India Company, one of the first stock corporations in the world, began to accelerate trade with the companies within their colonies. The period after the First World War was characterized by multinational companies that were mostly industrial. It was also a period in which the current system of corporate taxation was established. In those times it was relatively simple to impose source taxation on such multinational companies, whereas this is far from easy to do in the intensely digitized and globalized world of today.
If preventing double taxation was the biggest challenge for countries and corporations at the beginning of globalization, the problems of modern times are increasingly connected with ineffectiveness of corporation taxation and the tendency to establish a tax system that will ensure taxes are paid where profits are actually made.
In an attempt of fair tax revenue distribution, among countries where related companies operate, a system of transfer pricing rules was established. OECD (Organization for Economic Cooperation and Development) played one of the central roles in the establishment of this system. It issued guidelines for multinational enterprises and tax administrations that most of the developed countries implemented in their national legislation. This was also done by Slovenia. The first part of the thesis therefore deals with the history of transfer pricing, OECD guidelines and transfer pricing regulation in Slovenia.
The European Union already began addressing problems of corporate taxation in the 1960s. With the establishment of the single market the problem of double taxation became a key obstacle for its smooth functioning. Thus, in the 1990s, the majority of attention of the EU was directed towards removing obstacles for smooth functioning of the single market.
The LuxLeaks and Panama Papers scandals revealed that the international system of corporate taxation, based on principles formed in entirely different circumstances a hundred years ago, is no longer effective in the modern world of digitalization and globalization, which is characterized by fierce tax competition among the countries. This was realized by the EU and in 2015 it set itself an ambitious goal called the Action Plan for Fair and Efficient Corporate Taxation in the EU that formed a basis for new measures against corporate tax avoidance. One of this measures was presented in January as the Anti Tax Avoidance Package.
Another key measure is the establishment of a system based on consolidated corporate tax base. The system will take into account the total income of a multinational company as a whole and, according to a known formula, distribute tax revenue among countries where the company actually carried out business activities and generated profits.
The aim of the EU as well as the OECD and its program called BEPS (Base Erosion and Profit Shifting) is to reform the international tax system by establishing one that will neutralize the effects of aggressive tax planning and enable taxation of profit in the countries where it is actually made. The second part of the thesis deals with transfer pricing as a challenge for EU tax policy, multinational companies profit shifting to more favorable tax environments, the financial effects of such practices on member states budgets, schemes of aggressive tax planning and measures taken by the EU to prevent base erosion and profit shifting
Analiza elementov sistema kakovosti v STO d.o.o. Ravne na Koroškem : diplomsko delo [univerzitetnega študijskega programa]
No full textReliability of the 400-M usual-pace walk test as as assessment of mobility limitation in older adults
No full textOBJECTIVES:
To assess the test-retest reliability of the 400-m usual-pace walk test (400-MWT), and to determine whether the 4-m walk test predicts inability to walk 400 m.
DESIGN:
Observational.
SETTING:
Community, 20-m tract course.
PARTICIPANTS:
Sixty study participants (aged>or=65) were enrolled from the community and met the following eligibility criteria: self-reported difficulty in two or more of four functional domains (mobility and exercise tolerance, upper extremity function, basic self-care, higher functional tasks of independent living) and a score of 18 or higher on the Mini-Mental State Examination.
METHODS:
The 400-MWT and 4-m walk test were each repeated within 7 days.
RESULTS:
The mean age+/-standard deviation of the study population was 84.3+/-6.3; 88.3% were women. Nineteen participants (31.7%) failed both 400-MWTs, and 41 successfully completed both tests (kappa=1). Mean walking speed for the 4-m test was 0.87+/-0.18 m/s for those who completed the 400-MWT and 0.53+/-0.17 m/s for those who failed (P<.001). The Spearman correlation coefficient between 4-m and 400-m walking speeds was 0.93. The estimated area under the receiver operating characteristic curve between 4-m walking speed and the ability to perform the 400-MWT was 0.91. The 4-m gait speed averaged less than 0.6 m/s in 80% of subjects who failed the 400-MWT.
CONCLUSION:
The test-retest reliability for inability to complete the 400-MWT is high. Four-m walking speed is highly predictive of ability to perform the 400-MWT. These findings may prove useful to future clinical trials and observational studies that involve assessment of mobility limitations in older adults
Sarcopenia : clinical evaluation, biological markers and other evaluation tools
No full textSarcopenia is characterized by a lower skeletal muscle quantity, higher fat accumulation in the muscle, lower muscle strength, and lower physical performance. The most commonly used, low cost and accessible methods to assess skeletal muscle mass include dual energy X-ray absorptiometry (DEXA), anthropometry and bioelectrical impedance analysis (BIA). Magnetic resonance imaging (MRI), computerized tomography (CT) and creatinine excretion are the most specific golden standards for assessing muscle mass or cross sectional muscle area. Other available measures include peripheral quantitative computerized tomography (pQCT), ultrasound and neutron activation. Skeletal muscle strength is another important component for the assessment of sarcopenia and muscle quality. Several methods are available for the measurement of muscle strength which include simple dynamometers to measure isometric strength and the most complex isokinetic strength measures of power and torque. Standardized physical performance measures complement the measures of muscle mass for the assessment of sarcopenia. A clinical definition of sarcopenia ought to use methods of assessment that are valid, reliable, specific to skeletal muscle, predictive of future health events, non-invasive, practical, low cost and widely accessible
Plasminogen activator inhibitor-1 (PAI-1) : a key factor linking fibrinolysis and age-related subclinical and clinical conditions
No full textIntroduction: The close relationship existing between aging and thrombosis has growingly been studied in this last decade. The age-related development of a prothrombotic imbalance in the fibrinolysis homeostasis has been hypothesized as the basis of this increased cardiovascular and cerebrovascular risk. Fibrinolysis is the result of the interactions among multiple plasminogen activators and inhibitors constituting the enzymatic cascade, and ultimately leading to the degradation of fibrin. The plasminogen activator system plays a key role in a wide range of physiological and pathological processes. Methods: Narrative review. Results: Plasminogen activator inhibitor-1 (PAI-1) is a member of the superfamily of serine-protease inhibitors (or serpins), and the principal inhibitor of both the tissue-type and the urokinase-type plasminogen activator, the two plasminogen activators able to activate plasminogen. Current evidence describing the central role played by PAI-1 in a number of age-related subclinical (i.e., inflammation, atherosclerosis, insulin resistance) and clinical (i.e., obesity, comorbidities, Werner syndrome) conditions is presented. Conclusions: Despite some controversial and unclear issues, PAI-1 represents an extremely promising marker that may become a biological parameter to be progressively considered in the prognostic evaluation, in the disease monitoring, and as treatment target of age-related conditions in the future
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