In the 1980s, Orion Pharma, then a mid-ranking Nordic area pharmaceutical company, established a drug development programme on the inhibition of catechol O-methyltransferase (COMT). This enzyme, ...which plays an important role in the inactivation of catecholamine neurotransmitters and drugs with a catechol structure, thus came under consideration as a target in the innovative translational and clinical programme we describe in this historical review. The starting point was the conjecture that a peripherally acting COMT inhibitor might improve entry of levodopa into the brain. This had potentially significant implications for the medical treatment of Parkinson’s disease (PD). The rationale was that more efficient delivery of levodopa to the brain might allow the high therapeutic doses of levodopa to be reduced and the dose interval to be extended. Elucidation of structure–activity relations paved the way for the discovery and development of entacapone, a 5-nitrocatechol that was a potent and highly specific inhibitor of COMT. Experience in phase III clinical trials established that entacapone, used as an adjunct to regular or controlled-release levodopa preparations (also including a peripherally acting dopa-decarboxylase inhibitor), increased ON-time and reduced OFF-time and improved clinical condition in patients with PD experiencing wearing-off, often with a reduced daily levodopa dose. Several of these studies also identified that entacapone improved patients’ quality of life and was cost-effective. Subsequently, entacapone has been amalgamated into a triple-combination preparation (Stalevo®) with levodopa and carbidopa to create a flexible and convenient drug therapy for patients with PD who have end-of-dose motor fluctuations not stabilised on levodopa/dopa-decarboxylase inhibitor treatment. This review offers a historical perspective on a successful programme of drug development by researchers who played central roles in the progress from exploratory hypothesis to registered pharmaceutical product.
.
The masses of the astrophysically relevant nuclei
25
Al and
30
P have been measured with a Penning trap for the first time. The mass-excess values for
25
Al (
keV) and
30
P (
keV) obtained with the ...JYFLTRAP double Penning trap mass spectrometer are in good agreement with the Atomic Mass Evaluation 2012 values but
5-10 times more precise. A high precision is required for calculating resonant proton-capture rates of astrophysically important reactions
25
Al (
p
,
)
26
Si and
30
P(
p
,
)
31
S . In this work,
keV and
keV were obtained for
25
Al and
30
P , respectively. The effect of the more precise values on the resonant proton-capture rates has been studied. In addition to nuclear astrophysics, the measured Q
EC
value of
25
Al , 4276.805(45) keV, is relevant for studies of
T
= 1/2 mirror beta decays which have a potential to be used to test the Conserved Vector Current hypothesis.
Developments for neutron-induced fission at IGISOL-4 Gorelov, D.; Penttilä, H.; Al-Adili, A. ...
Nuclear instruments & methods in physics research. Section B, Beam interactions with materials and atoms,
06/2016, Letnik:
376
Journal Article
Recenzirano
Odprti dostop
At the IGISOL-4 facility, neutron-rich, medium mass nuclei have usually been produced via charged particle-induced fission of natural uranium and thorium. Neutron-induced fission is expected to have ...a higher production cross section of the most neutron-rich species. Development of a neutron source along with a new ion guide continues to be one of the major goals since the commissioning of IGISOL-4. Neutron intensities at different angles from a beryllium neutron source have been measured in an on-line experiment with a 30MeV proton beam. Recently, the new ion guide coupled to the neutron source has been tested as well. Details of the neutron source and ion guide design together with preliminary results from the first neutron-induced fission experiment at IGISOL-4 are presented in this report.
Recognition of tree species and geospatial information of tree species composition is essential for forest management. In this study we test tree species recognition using hyperspectral imagery from ...VNIR and SWIR camera sensors in combination with 3D photogrammetric canopy surface model based on RGB camera stereo-imagery. An arboretum forest with a high number of tree species was used as a test area. The imagery was acquired from the test area using UAV-borne cameras. Hyperspectral imagery was calibrated for providing a radiometrically corrected reflectance mosaic, which was tested along with the original uncalibrated imagery. Alternative estimators were tested for predicting tree species and genus, as well as for selecting an optimal set of remote sensing features for this task. All tested estimators gave similar trend in the results: the calibrated reflectance values performed better in predicting tree species and genus compared to uncorrected hyperspectral pixel values. Furthermore, the combination of VNIR, SWIR and 3D features performed better than any of the data sets individually, with calibrated reflectances and original pixel values alike. The highest proportion of correctly classified trees was achieved using calibrated reflectance features from VNIR and SWIR imagery together with 3D point cloud features: 0.823 for tree species and 0.869 for tree genus.
Unmanned airborne systems (UAS) based remote sensing offers flexible tool for environmental monitoring. Novel lightweight Fabry-Perot interferometer (FPI) based, frame format, hyperspectral imaging ...in the spectral range from 400 to 1600 nm was used for identifying different species of trees in a forest area. To the best of the authors’ knowledge, this was the first research where stereoscopic, hyperspectral VIS, NIR, SWIR data is collected for tree species identification using UAS. The first results of the analysis based on fusion of two FPI-based hyperspectral imagers and RGB camera showed that the novel FPI hyperspectral technology provided accurate geometric, radiometric and spectral information in a forested scene and is operational for environmental remote sensing applications.
.
Half-lives and branching ratios for the two mirror
β
decays of
23
Mg and
27
Si have been measured at the University of Jyväskylä with the IGISOL facility. The results obtained,
T
1
/
2
=
11
.
303
(
...3
)
s and
T
1
/
2
=
4
.
112
(
2
)
s for the half-lives of
23
Mg and
27
Si , respectively, are 7 and 8 times more precise than the averages of previous measurements. The values obtained for the super-allowed branching ratios of
23
Mg and
27
Si are
B
.
R
.
=
92
.
18
(
8
)
%
and
B
.
R
.
=
99
.
74
(
2
)
%
, respectively. The result for
23
Mg is three times more precise than the average of the previous measurements, while for
27
Si the precision has not been improved, the average of the previous measurements being already very precise. Isospin-symmetry-breaking corrections have been calculated for the two nuclei to determine the corrected
F
t
value.
Background
Ischemic heart disease (IHD) caused every fourth death in the European region in 2017. Furthermore, it accounted for about 12% of total disease burden estimated with disability adjusted ...life years (DALYs). DALYs summarize premature mortality (years of life lost, YLL) and morbidity (years lived with disease, YLD) in a specific cause. These disease burden estimates are customarily used to examine time trends or differences between countries or regions. However, they have seldom been calculated by socio-economic position (SEP), especially using individual-level SEP indicators.
Methods
We calculated DALYs for the Finnish 30+ year-old population in 2017. For YLL, we used Statistics Finland database for total population. For YLD, we used individual level data from the cross-sectional health examination FinHealth 2017 survey (n = 6538), which was linked with administrative register data. Population attributable fractions (PAFs) for selected IHD risk factors (smoking, blood pressure, total cholesterol and body mass index, BMI) were also calculated. Methodology published by the Global Burden of Disease study, such as disability weights for YLD and relative risks for PAFs, was applied where applicable.
Results
DALYs for IHD per 1000 population were 61.1 for men and 31.0 for women. Premature mortality (YLL) caused over 80% of DALYs. Burden of IHD morbidity (YLD) was higher in low education groups. In the total population, PAFs for IHD risk factors for men and women, respectively, were as follows: 17% and 8% for smoking, 56% and 58% for elevated systolic blood pressure, 25% and 28% for high cholesterol, and 27% and 24% for high BMI.
Conclusions
IHD morbidity was higher among low education groups. A large part of IHD burden was attributable to major cardiovascular risk factors, most markedly to elevated systolic blood pressure. In the future, the burden of disease could be increasingly assessed also by SEP.
Key messages
The burden of IHD in Finland was especially high among men, and majority of the burden was due to premature mortality. Over 50% of the IHD burden was attributed to elevated systolic blood pressure.
Assessing the burden of diseases by socio-economic position provides a new perspective for examining socio-economic differences in health.
Abstract
Background
Population in Europe and throughout the world is ageing rapidly. Projections of the work ability of the working-age population are of importance for policy makers to prepare for ...future challenges. The aim of this study is to examine age-group and birth-cohort trends in perceived work ability in Finland in 2000-2020 and make projections of work ability up to 2040 based on the observed birth-cohort development.
Methods
We used a series of population representative cross-sectional surveys conducted in Finland 2000-2020, i.e. the Health 2000 Survey, the Regional Health and Wellbeing Study 2010, 2012, 2013, 2014, 2015, 2017, FinHealth 2017 and FinSote 2018 and 2020. Self-reported estimates of current work ability in relation to the person's lifetime best on a scale from zero to ten were used, scores 8-10 indicating good work ability. For projecting work ability multiple imputation was used (R package mice).
Results
Trends (2000-2020) by 5-year birth-cohorts born between 1961 and 1995 showed that work ability has declined over time among older birth-cohorts while in the two younger cohorts a stable development before 2017 and a steep decline between 2017 and 2020 was observed. Trends by 5-year age-groups showed a declining trend of good work ability among 20-44-year-olds, a stable trend among 45-54-year-olds and an improving trend among over 55-year-olds. Among the under 55-year-olds the prevalence of good work ability ended up around 75% and at 68% among the 55-59-year-olds, 58% among the 60-69-year-olds and 49% among the 70-74-year-olds in 2020. Birth-cohort projections suggest a declining work ability among 30-74-year-olds in the future. By 2040, the prevalence of good work ability is projected to decline 10-15%−points among 45-74-year-olds.
Conclusions
The decreasing work ability seen in younger age groups and the declining projections until 2040 are highly concerning. Efforts to counteract the projected decline in work ability are needed.
Key messages
• The observed decline in perceived work ability in younger age groups and the projected decline in the prevalence of good work ability among the middle aged and older are concerning.
• Efforts to counteract the projected decline in work ability are urgently needed.
To examine the clinical course of age-associated memory impairment (AAMI) and to evaluate the value of neuropsychological tests in predicting cognitive decline in AAMI subjects in a follow-up period ...of more than 3 years.
Prospective cohort study.
The outpatient Memory Research Unit of the Department of Neurology at the University of Kuopio in Eastern Finland.
A sample of 229 subjects (mean age 71.7 years) identified in two screening studies as having AAMI.
A battery of neuropsychological tests and a structured inquiry for health status and subjective memory complaints were performed at baseline and follow-up to diagnose AAMI according to the criteria proposed by a National Institute of Mental Health work group.
Of the 229 subjects, 176 (76.9%) participated in the follow-up for, on average, 3.6 years after the baseline. Of the participants, 104 (59.1%) still met the AAMI criteria. Other subjects were classified into five subgroups: (1) subjects showing decline in cognition meeting dementia diagnosis (16, 9.1% (13 of them AD)); (2) subjects with mild cognitive decline meeting neither dementia nor AAMI criteria (13, 7.4%); (3) subjects with memory performance now superior to AAMI criteria (17, 9.7%); (4) subjects having a disease classified as exclusion in the criteria (15, 8.5%); (5) subjects not now reporting subjective memory loss in everyday life (9, 5.1%). Two subjects (1.1%) were not classified because of incomplete data. Neuropsychological tests predicted which subjects would develop dementia during the follow-up period. The best discriminators between these subjects and those who remained AAMI were memory and verbal fluency tests.
The study suggests that, in general, AAMI is nonprogressive, but the AAMI population also includes subjects with early dementia and subjects without genuine memory loss. However, these subjects can be differentiated with a more detailed neuropsychological evaluation.
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