Франкова творчість у новітній історико-літературній парадигмі

The aim of this study was to investigate the possible reduced risk of Parkinson Disease (PD) due to coffee, alcohol, and/or cigarette consumption. In addition, we explored the potential effect modification by intensity, duration and time-since-cessation of smoking on the association between cumulative pack-years of cigarette smoking (total smoking) and PD risk. Data of a hospital based case-control study was used including 444 PD patients, diagnosed between 2006 and 2011, and 876 matched controls from 5 hospitals in the Netherlands. A novel modeling method was applied to derive unbiased estimates of the potential modifying effects of smoking intensity, duration, and time-since-cessation by conditioning on total exposure. We observed no reduced risk of PD by alcohol consumption and only a weak inverse association between coffee consumption and PD risk. However, a strong inverse association of total smoking with PD risk was observed (OR = 0.27 (95%CI: 0.18-0.42) for never smokers versus highest quartile of tobacco use). The observed protective effect of total smoking was significantly modified by time-since-cessation with a diminishing protective effect after cessation of smoking. No effect modification by intensity or duration of smoking was observed indicating that both intensity and duration have an equal contribution to the reduced PD risk. Understanding the dynamics of the protective effect of smoking on PD risk aids in understanding PD etiology and may contribute to strategies for prevention and treatment

A prospective open label 2-8 year extension of the randomised controlled ICON trial on the long-term efficacy and safety of occipital nerve stimulation in medically intractable chronic cluster headache

BACKGROUND: We demonstrated in the randomised controlled ICON study that 48-week treatment of medically intractable chronic cluster headache (MICCH) with occipital nerve stimulation (ONS) is safe and effective. In L-ICON we prospectively evaluate its long-term effectiveness and safety. METHODS: ICON participants were enrolled in L-ICON immediately after completing ICON. Therefore, earlier ICON participants could be followed longer than later ones. L-ICON inclusion was stopped after the last ICON participant was enrolled in L-ICON and followed for ≥2 years by completing six-monthly questionnaires on attack frequency, side effects, subjective improvement and whether they would recommend ONS to others. Primary outcome was the change in mean weekly attack frequency 2 years after completion of the ICON study compared to baseline. Missing values for log-transformed attack-frequency were imputed for up to 5 years of follow-up. Descriptive analyses are presented as (pooled) geometric or arithmetic means and 95% confidence intervals. FINDINGS: Of 103 eligible participants, 88 (85%) gave informed consent and 73 (83%) were followed for ≥2 year, 61 (69%) ≥ 3 year, 33 (38%) ≥ 5 years and 3 (3%) ≥ 8.5 years. Mean (±SD) follow-up was 4.2 ± 2.2 years for a total of 370 person years (84% of potentially 442 years). The pooled geometric mean (95% CI) weekly attack frequency remained considerably lower after one (4.2; 2.8-6.3), two (5.1; 3.5-7.6) and five years (4.1; 3.0-5.5) compared to baseline (16.2; 14.4-18.3). Of the 49/88 (56%) ICON ≥50% responders, 35/49 (71%) retained this response and 15/39 (38%) ICON non-responders still became a ≥50% responder for at least half the follow-up period. Most participants (69/88; 78% [0.68-0.86]) reported a subjective improvement from baseline at last follow-up and 70/88 (81% [0.70-0.87]) would recommend ONS to others. Hardware-related surgery was required in 44/88 (50%) participants in 112/122 (92%) events (0.35 person-year-1 [0.28-0.41]). We didn't find predictive factors for effectiveness. INTERPRETATION: ONS is a safe, well-tolerated and long-term effective treatment for MICCH. FUNDING: The Netherlands Organisation for Scientific Research, the Dutch Ministry of Health, the NutsOhra Foundation from the Dutch Health Insurance Companies, and Medtronic.</p

Анализ основных показателей деятельности государственного фонда содействия молодёжному жилищному строительству в 1998-2005 годах

Ипотечный рынок жилья играет важную роль для макроэкономической стабилизации в странах с переходной экономикой. Выступая механизмом привлечения финансовых ресурсов в сектор жилищного строительства, он значительно ускоряет темпы его развития и объемы капиталовложений в эту сферу. Это создает мультипликационный эффект прироста валового внутреннего продукта, производства в смежных с жилищным строительством отраслях, доходов бюджетов. Одна гривня, вложенная в жилищное строительство, трансформируется в шесть гривень ВВП. Если в стране удваиваются объемы строительства, то ВВП в целом возрастает в 2,6 раза

Assessing Cortical Excitability in Migraine: Reliability of Magnetic Suppression of Perceptual Accuracy Technique Over Time Abbreviations: TMS transcranial magnetic stimulation, MSPA magnetic suppression of perceptual accuracy

Objectives.-To examine test-retest reliability of magnetic suppression of perceptual accuracy (MSPA) prior to its use as a marker of cortical excitability in a trial of migraine prophylactic agents. Background.-MSPA is a relatively novel avenue of research in headache, providing an opportunity to study cortical responsiveness objectively and noninvasively. However, little is known about the reliability of magnetic stimulation protocols such as MSPA in longitudinal research designs. Methods.-We tested 10 healthy headache-free volunteers who had no family history of migraine. In 54 trials, they were briefly presented different three-letter combinations, flashed on a computer screen for 24 ms (target). After a brief interval, each target was followed by a single magnetic pulse through a 90-mm circular coil centered 7 cm above inion in the midline. The interval between target and magnetic pulse was systematically varied. Volunteers were requested to report as many letters as they had possibly identified. After 2 weeks, all volunteers were retested using identical methods. Results.-MSPA performance is expressed as a profile of response accuracy (ie, percentage of correctly identified letters) across target-pulse intervals. Profiles were characteristic of normal headache-free subjects at the first test. Analysis of variance revealed no significant difference in profiles between test and retest (F = 2.05; P = .136): the retest profiles are almost coincidental with the test profiles. Conclusions.-MSPA is a safe and objective measure of cortical excitability, which is reliable over time. MSPA, therefore, shows excellent promise as a biological marker of cortical response in trials of migraine prophylactics

Visual cortex excitability in migraine with and without aura.

Objectives.—Previous research using transcranial magnetic stimulation has produced equivocal findings concerning thresholds for the generation of visual phosphenes in migraine with aura. These studies were methodologically varied and did not systematically address cortical excitability in migraine without aura. We therefore studied magnetophosphene thresholds in both migraine with aura and migraine without aura compared with headache-free controls. Methods.—Sixteen subjects with migraine with aura and 12 subjects with migraine without aura were studied and compared with 16 sex- and age-matched controls. Using a standardized transcranial magnetic stimulation protocol of the occipital cortex, we assessed the threshold stimulation intensity at which subjects just perceived phosphenes via a method of alternating course and fine-tuning of stimulator output. Results.—There were no significant differences across groups in the proportion of subjects seeing phosphenes. However, the mean threshold at which phosphenes were reported was significantly lower in both migraine groups (migraine with aura=47%, migraine without aura=46%) than in controls (66%). Moreover, there was no significant correlation between individual phosphene threshold and the time interval to the closest migraine attack. Conclusion.—Our findings confirm that the occipital cortex is hyperexcitable in the migraine interictum, both in migraine with and without aura

Suppression of perceptual accuracy in migraineurs: a transcranial magnetic stimulation study of visual cortex excitability.

BACKGROUND: Results from transcranial magnetic stimulation (TMS) studies of visual cortex have confirmed visual cortical hyperexcitability in patients with migraine. It has been speculated that this may be due to deficient intracortical inhibitory tone. However, the TMS induction of phosphenes relies on the reporting of a subjective experience, and may thus be subject to bias. METHODS: Seven migraineurs with visual aura and seven sex- and age-matched controls were studied. Fifty-four different three-letter combinations were briefly displayed and followed by a magnetic pulse at 40, 70, 100, 130, 160, and 190 msec. Subjects were required to report as many letters as they thought they had recognized. RESULTS: In the migraine group, the mean proportion of correctly identified letters was significantly higher at 100 msec, as was the proportion of trials with two or three letters correctly reported. The time window in which perceptual suppression could be introduced was narrower in migraineurs compared to controls. CONCLUSION: These findings suggest that inhibitory systems are activated to a lesser extent by TMS pulses in patients. This observation is in agreement with the hypothesized deficiency of intracortical inhibition of the visual cortex, at least in migraineurs with aura

Intra- and interindividual attack frequency variability of chronic cluster headache

Background: The lack of knowledge about the intra- and interindividual attack frequency variability in chronic cluster headache complicates power and sample size calculations for baseline periods of trials, and consensus on their most optimal duration. Methods: We analyzed the 12-week baseline of the ICON trial (occipital nerve stimulation in medically intractable chronic cluster headache) for: (i) weekly vs. instantaneous recording of attack frequency; (ii) intra-individual and seasonal variability of attack frequency; and (iii) the smallest number of weeks to obtain a reliable estimate of baseline attack frequency. Results: Weekly median (14.4 [8.2–24.0]) and instantaneous (14.2 [8.0–24.5]) attack frequency recordings were similar (p = 0.20; Bland-Altman plot). Median weekly attack frequency was 15.3 (range 4.2–140) and highest during spring (p = 0.001) compared to the other seasons. Relative attack frequency variability decreased with increasing attack frequency (p = 0.010). We tabulated the weekly attack frequency estimation accuracies compared to, and the associated deviations from, the 12-week gold standard for different lengths of the observation period. Conclusion: Weekly retrospective attack frequency recording is as good as instantaneous recording and more convenient. Attack frequency is highest in spring. Participants with ≥3 daily attacks show less attack frequency variability than those with <3 daily attacks. An optimal balance between 90% accuracy and feasibility is achieved at a baseline period of seven weeks. The ICON trial is registered in ClinicalTrials.gov under number NCT01151631

Extremely low-frequency magnetic field exposure, electrical shocks and risk of Parkinson's disease

Previous studies did not provide strong evidence for an increased Parkinson's disease (PD) risk after exposure to extremely low-frequency magnetic fields (ELF-MF), but were limited in their scope to address other exposures related to the use of electricity such as electrical shocks. We evaluated the associations of PD with exposure to ELF-MF, electrical shocks and having worked in "electrical occupations."We conducted a hospital-based case-control study, including 444 PD patients and 876 age- and sex-matched controls. Occupational histories were collected in telephone interviews and were linked to job-exposure matrices on ELF-MF exposure and on electrical shocks. In addition, questions on use of household appliances involving ELF-MF exposure, experienced electrical shocks and potential confounders were asked.No association of PD risk with any of the evaluated exposures related to electricity was observed. We did, however, observe quite consistently reduced risk estimates across the majority of the exposure categories explored. Given the results of the previous studies and the absence of any postulated mechanism, this is unlikely to represent a true protective effect of ELF-MF or electrical shocks on the occurrence of PD.The results of this study suggest that no association exists between PD and exposure to ELF-MF, electrical shocks or having worked in "electrical occupations.".</p

Occupational exposure to solvents, metals and welding fumes and risk of Parkinson's disease

OBJECTIVES: The aim of this study was to investigate the potential association between occupational exposure to solvents, metals and/or welding fumes and risk of developing Parkinson's disease (PD). METHODS: Data of a hospital based case-control study including 444 PD patients and 876 age and sex matched controls was used. Occupational histories and lifestyle information of cases and controls were collected in a structured telephone interview. Exposures to aromatic solvents, chlorinated solvents and metals were estimated by linking the ALOHA+ job-exposure matrix to the occupational histories. Exposure to welding fumes was estimated using self-reported information on welding activities. RESULTS: No statistically significant associations with any of the studied metal and solvent exposures were found. However, for self-reported welding activities we observed non-statistically significant reduced risk estimates (third tertile cumulative exposure: OR = 0.51 (95% CI: 0.21-1.24)). CONCLUSIONS: The results of our study did not provide support for an increased chance on developing PD after occupational exposure to aromatic solvents, chlorinated solvents or exposure to metals. The results showed reduced risk estimates for welding, which is in line with previous research, but no clear explanation for these findings is available