808 research outputs found
Execution Wetering Park (Amsterdam, March 2, 1945, 9:15-9:35 a.m.)
Poem by Jan H. de Groot, translated by Case J. Boot from Modern Koren
Філософсько-правові проблеми реалізації права на працю
Розкривається зміст категорії «праця». Досліджуються філософсько-правові проблеми у сфері здійснення права на працю.Раскрывается содержание категории «труд». Исследуются философско-правовые проблемы в сфере осуществления права на труд.In the article the content of the category «labour» is revealed. The philosophical and legal problems in the field of realization of the right to work are being researched
Critical factors for liposome-incorporated tumour-associated antigens to induce protective tumour immunity to SL2 lymphoma cells in mice
Physical
and
immunogenic
properties
of
re-
constituted
membranes
designed
for
the
presentation
of
tumour-associated
antigens
(TAA)
to
the
immune
system
are
described.
Proteins
and
lipids
of
crude
membranes
of
SL2
routine
lymphosarcoma
cells
were
partially
solubi-
lized
with
octylglucoside.
Reconstituted
membranes,
con-
sisting
mainly
of
unilamellar
vesicles
with
a
diameter
of
0.03-0.15
gm,
were
formed
by
detergent
removal
and
were
purified
by
floatation
in
a
discontinuous
sucrose
gra-
dient
to
remove
non-lipid-bound
protein.
Subcutaneous
immunization
of
syngeneic
mice
with
reconstituted
mem-
branes
or
with
purified
reconstituted
membranes
induced
protection
against
an
intraperitoneal
challenge
with
103
viable
SL2
cells.
Reconstituted
membranes
were
more
im-
munogenic
than
crude
membranes
in
immunoprotection
experiments
when
compared
on
the
basis
of
protein
dose.
Detergent
removal
was
required
to
obtain
an
immunogenic
presentation
form
of
SL2
membrane
antigens
and
to
avoid
toxicity
associated
with
the
detergent.
Reconstitution
of
SL2
membranes
in
the
presence
of
exogenous
phos-
pholipid
slightly
increased
the
fraction
of
protein
that
as-
sociated
with
the
reconstituted
membranes.
However,
the
immunogenicity
of
the
solubilized
membrane
TAA
was
not
significantly
affected
by
the
presence
of
exogenous
phospholipid.
The
reconstitution
procedure
described
may
be
useful
in
identifying
membrane
factors
required
for
the
induction
of
immune
responses
against
TAA.
The
versatil-
ity
of
the
system
may
be
employed
to
develop
safe
alterna-
tives
for
whole-cell
vaccines
The Relationship of Coronary Artery Calcium and Clinical Coronary Artery Disease with Cognitive Function:A Systematic Review and Meta-Analysis
AIM: Coronary artery disease (CAD) and cognitive impairment are common in the elderly, with evidence for shared risk factors and pathophysiological processes. The coronary artery calcium (CAC) score is a marker of subclinical CAD, which may allow early detection of individuals prone to cognitive decline. Prior studies on associations of CAC and clinical CAD with cognitive impairment had discrepant results. This systematic review aims to evaluate the association of (sub)clinical CAD with cognitive function, cognitive decline, and diagnosis of mild cognitive impairment (MCI) or dementia. METHODS: A systematic search was conducted in MEDLINE, Embase, and Web of Science until February 2019, supplemented with citations tracking. Two reviewers independently screened studies and extracted information including odds ratios (ORs) and hazard ratios (HRs). RESULTS: Forty-six studies, 10 on CAC and 36 on clinical CAD, comprising 1,248,908 participants were included in the systematic review. Studies about associations of (sub)clinical CAD with cognitive function and cognitive decline had heterogeneous methodology and inconsistent findings. Two population-based studies investigated the association between CAC and risk of dementia over 6-12.2 years using different CAC scoring methods. Both found a tendency toward higher risk of dementia as CAC severity increased. Meta-analysis in 15 studies (663,250 individuals) showed an association between CAD and MCI/dementia (pooled OR 1.32, 95%CI 1.17-1.48) with substantial heterogeneity (I2=87.0%, p<0.001). Pooled HR of CAD for incident MCI/dementia over 3.2-25.5 years in six longitudinal studies (70,060 individuals) was 1.51 (95%CI 1.24-1.85), with low heterogeneity (I2=14.1%, p=0.32). Sensitivity analysis did not detect any study that was of particular influence on the pooled OR or HR. CONCLUSIONS: Limited evidence suggests the CAC score is associated with risk of dementia. In clinical CAD, risk of MCI and dementia is increased by 50%, as supported by stronger evidence
Comparison of [18F]DOPA and [68Ga]DOTA-TOC as a PET imaging tracer before peptide receptor radionuclide therapy
BACKGROUND: In treatment of neuroendocrine neoplasms (NENs), confirmation of somatostatin receptor expression with 68Ga-DOTA somatostatin analogues is mandatory to determine eligibility for peptide receptor radionuclide therapy (PRRT). [18F]DOPA can detect additional lesions compared to [68Ga]DOTA-TOC. The aim of this study was to explore differences in tumour detection of both tracers and their relevance for selecting patients for PRRT. We retrospectively studied eight patients with NENs who underwent both [68Ga]DOTA-TOC and carbidopa-enhanced [18F]DOPA PET/CT, before first-time PRRT with [177Lu]DOTA-TATE. Tracer order was influenced due to stock availability or to detect suspected metastases with a second tracer. On CT, disease control was defined as a lesion showing complete response, partial response, or stable disease, according to RECIST 1.1. CRITERIA: RESULTS: Seven patients with in total 89 lesions completed four infusions of 7.4 GBq [177Lu]DOTA-TATE, one patient received only two cycles. Before treatment, [18F]DOPA PET/CT detected significantly more lesions than [68Ga]DOTA-TOC PET/CT (79 vs. 62, p < .001). After treatment, no difference in number of lesions with disease control was found for [18F]DOPA-only (5/27) and [68Ga]DOTA-TOC-only lesions (4/10, p = .25). [18F]DOPA detected more liver metastases (24/27) compared to [68Ga]DOTA-TOC (7/10, p = .006). Six patients showed inpatient heterogeneity in treatment response between [18F]DOPA-only and [68Ga]DOTA-TOC-only lesions. CONCLUSIONS: Response to PRRT with [177Lu]DOTA-TATE was comparable for both [68Ga]DOTA-TOC- and [18F]DOPA-only NEN lesions. [18F]DOPA may be capable of predicting response to PRRT while finding more lesions compared to [68Ga]DOTA-TOC, although these additional lesions are often small of size and undetected by diagnostic CT
Molecular imaging to support cancer immunotherapy
The advent of immune checkpoint inhibitors has reinvigorated the field of immuno-oncology. These monoclonal antibody-based therapies allow the immune system to recognize and eliminate malignant cells. This has resulted in improved survival of patients across several tumor types. However, not all patients respond to immunotherapy therefore predictive biomarkers are important. There are only a few Food and Drug Administration-approved biomarkers to select patients for immunotherapy. These biomarkers do not consider the heterogeneity of tumor characteristics across lesions within a patient. New molecular imaging tracers allow for whole-body visualization with positron emission tomography (PET) of tumor and immune cell characteristics, and drug distribution, which might guide treatment decision making. Here, we summarize recent developments in molecular imaging of immune checkpoint molecules, such as PD-L1, PD-1, CTLA-4, and LAG-3. We discuss several molecular imaging approaches of immune cell subsets and briefly summarize the role of FDG-PET for evaluating cancer immunotherapy. The main focus is on developments in clinical molecular imaging studies, next to preclinical studies of interest given their potential translation to the clinic
Early motor learning changes in upper-limb dynamics and shoulder complex loading during handrim wheelchair propulsion
Background: To propel in an energy-efficient manner, handrim wheelchair users must learn to control the bimanually applied forces onto the rims, preserving both speed and direction of locomotion. Previous studies have found an increase in mechanical efficiency due to motor learning associated with changes in propulsion technique, but it is unclear in what way the propulsion technique impacts the load on the shoulder complex. The purpose of this study was to evaluate mechanical efficiency, propulsion technique and load on the shoulder complex during the initial stage of motor learning. Methods: 15 naive able-bodied participants received 12-minutes uninstructed wheelchair practice on a motor driven treadmill, consisting of three 4-minute blocks separated by two minutes rest. Practice was performed at a fixed belt speed (v = 1.1 m/s) and constant low-intensity power output (0.2 W/ kg). Energy consumption, kinematics and kinetics of propulsion technique were continuously measured. The Delft Shoulder Model was used to calculate net joint moments, muscle activity and glenohumeral reaction force. Results: With practice mechanical efficiency increased and propulsion technique changed, reflected by a reduced push frequency and increased work per push, performed over a larger contact angle, with more tangentially applied force and reduced power losses before and after each push. Contrary to our expectations, the above mentioned propulsion technique changes were found together with an increased load on the shoulder complex reflected by higher net moments, a higher total muscle power and higher peak and mean glenohumeral reaction forces. Conclusions: It appears that the early stages of motor learning in handrim wheelchair propulsion are indeed associated with improved technique and efficiency due to optimization of the kinematics and dynamics of the upper extremity. This process goes at the cost of an increased muscular effort and mechanical loading of the shoulder complex. This seems to be associated with an unchanged stable function of the trunk and could be due to the early learning phase where participants still have to learn to effectively use the full movement amplitude available within the wheelchair-user combination. Apparently whole body energy efficiency has priority over mechanical loading in the early stages of learning to propel a handrim wheelchair
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