Search

The corticofugal tracts (CFT) are key agents of upper limb motor function. Although the tracts form high-intensity regions relative to surrounding tissue in T2-weighted magnetic resonance images (T2WI), the precise relations of signal intensities of the left and right CFT regions to hand function are unknown. Here, we tested the hypothesis that the different signal intensities between the left and right CFT signify clinically important differences of hand motor function. Eleven right-handed and eleven left-handed healthy volunteers participated in the study. Based on horizontal T2WI estimates, we confirmed the relationship between the signal intensity ratios of the peak values of each CFT in the posterior limbs of the internal capsules (right CFT vs. left CFT). The ratios included the asymmetry indices of the hand motor functions, including grip and pinch strength, as well as the target test (TT) that expressed the speed and accuracy of hitting a target ([right-hand score − left-hand score]/[right-hand score + left-hand score]), using simple linear regression. The signal intensity ratios of each CFT structure maintained significant linear relations with the asymmetry index of the speed (R2 = 0.493, P = 0.0003) and accuracy (R2 = 0.348, P = 0.004) of the TT. We found no significant association between left and right CFT structures for grip or pinch strengths. The findings are consistent with the hypothesis that the different signal intensities of the left and right CFT images captured by T2WI serve as biological markers that reflect the dominance of manual dexterity. The corticofugal tracts (CFT) are key agents of upper limb motor function. Although the tracts form high-intensity regions relative to surrounding tissue in T2-weighted magnetic resonance images (T2WI), the precise relations of signal intensities of the left and right CFT regions to hand function are unknown. Here, we tested the hypothesis that the different signal intensities between the left and right CFT signify clinically important differences of hand motor function. Eleven right-handed and eleven left-handed healthy volunteers participated in the study. Based on horizontal T2WI estimates, we confirmed the relationship between the signal intensity ratios of the peak values of each CFT in the posterior limbs of the internal capsules (right CFT vs. left CFT). The ratios included the asymmetry indices of the hand motor functions, including grip and pinch strength, as well as the target test (TT) that expressed the speed and accuracy of hitting a target ([right-hand score − left-hand score]/[right-hand score + left-hand score]), using simple linear regression. The signal intensity ratios of each CFT structure maintained significant linear relations with the asymmetry index of the speed (R2 = 0.493, P = 0.0003) and accuracy (R2 = 0.348, P = 0.004) of the TT. We found no significant association between left and right CFT structures for grip or pinch strengths. The findings are consistent with the hypothesis that the different signal intensities of the left and right CFT images captured by T2WI serve as biological markers that reflect the dominance of manual dexterity.

Objective Cocaine is a highly addictive psychostimulant that affects synaptic activity with structural and functional adaptations of neurons. The transmembrane synaptic vesicle glycoprotein 2A (SV2A) of pre-synaptic vesicles is commonly used to measure synaptic density, as a novel approach to the detection of synaptic changes. We do not know if a single dose of cocaine suffices to affect pre-synaptic SV2A density, especially during adolescence when synapses undergo intense maturation. Here, we explored potential changes of pre-synaptic SV2A density in target brain areas associated with the cocaine-induced boost of dopaminergic neurotransmission, specifically testing if the effects would last after the return of dopamine levels to baseline. Methods: We administered cocaine (20 mg/kg i.p.) or saline to rats in early adolescence, tested their activity levels and removed the brains 1 hour and 7 days after injection. To evaluate immediate and lasting effects, we did autoradiography with [3H]UCB-J, a specific tracer for SV2A, in medial prefrontal cortex, striatum, nucleus accumbens, amygdala, and dorsal and ventral areas of hippocampus. We also measured the striatal binding of [3H]GBR-12935 to test cocaine’s occupancy of the dopamine transporter at both times of study. Results: We found a significant increase of [3H]UCB-J binding in the dorsal and ventral sections of hippocampus 7 days after the cocaine administration compared to saline-injected rats, but no differences 1 hour after the injection. The [3H]GBR-12935 binding remained unchanged at both times. Conclusion: Cocaine provoked lasting changes of hippocampal synaptic SV2A density after a single exposure during adolescence

Values of binding potentials (BPND) of dopamine D2/3 receptors differ in different regions of the brain, but we do not know with certainty how much of this difference is due either to different receptor numbers, or to different affinities of tracers to the receptors, or to both. We tested the claim that both striatal and extrastriatal dopamine D2/3 receptor availabilities vary with age in vivo in humans by determining the values of BPND of the specific radioligand [11C]raclopride. We determined values of BPND in striatal and extrastriatal volumes-of-interest (VOI) with the same specific receptor radioligand. We estimated values of BPND in individual voxels of brains of healthy volunteers in vivo, and we obtained regional averages of VOI by dynamic positron emission tomography (PET). We calculated average values of BPND in caudate nucleus and putamen of striatum, and in frontal, occipital, parietal, and temporal cortices of the forebrain, by means of four methods, including the ERLiBiRD (Estimation of Reversible Ligand Binding and Receptor Density) method, the tissue reference methods of Logan and Logan-Ichise, respectively, and the SRTM (Simplified Reference Tissue Method). Voxelwise generation of parametric maps of values of BPND used the multi-linear regression version of SRTM. Age-dependent changes of the binding potential presented with an inverted U-shape with peak binding potentials reached between the ages of 20 and 30. The estimates of BPND declined significantly with age after the peak in both striatal and extrastriatal regions, as determined by all four methods, with the greatest decline observed in posterior (occipital and parietal) cortices (14% per decade) and the lowest decline in caudate nucleus (3% per decade). The sites of the greatest declines are of particular interest because of the clinical implications.

Introduction: Autonomic nervous system dysfunction (ANSD) is associated with negative prognosis of ischemic heart disease (IHD) and has been found also to be related to elevated measures of sensitivity to pain from pressure (PPS) at the sternum. Previously, we found that non-pharmacological intervention by peripheral sensory nerve stimulation, monitored by repeated home-based PPS measurements, consistently was associated with lowered PPS measures. Compared to the general Danish population, the intervention reduced the all-cause mortality in two prospective observations, one of 103 patients with IHD followed for 3 years, and one of 73 patients with stroke followed for 4.5 years. Here, we test if we can reproduce lower all-cause mortality associated with lowered PPS measures in a randomized controlled trial (RCT). Methods: Of 361 consecutively followed patients with stable IHD, 65% had elevated PPS, suggestive of ANSD. Of these, 213 participated in a randomized controlled trial (RCT) with active (n=106) or passive intervention (n=107). We compared the 5-year all-cause mortality of both groups with two corresponding subsections of approximately 35.000 members of the general population of Denmark, matching patients for gender, age, and observation period with data from Statistics Denmark, and we compared the 5-year mortality of the two RCT groups. In separate analyses, we pooled mortality data from the active group of the RCT with data from two observational studies. We registered the pooled active intervention mortality of 1.168 person-years, compared to approximately 40 million person-years of the pooled general population. Results: We observed fewer than three deaths in the active RCT group (exact number and 95% CI not available according to GDRP rules), compared to eight deaths of passive RCT group members (P=0.035). Based on the predicted mortality from the general population of eight deaths in both groups, the result is consistent with significantly reduced mortality of recipients of active intervention (P=0.011). The separate analyses of pooled data from three consecutive studies demonstrated a mean reduction of the 4.2-year all-cause mortality of 50% (P Conclusions: The predicted attenuation of ANSD associated with lowering of elevated PPS matched the lower all-cause mortality of patients with IHD.

Background: The autonomic nervous system (ANS) maintains glucose homeostasis. While higher than normal glucose levels stimulate the ANS toward reduction, previous findings suggest an association between sensitivity to, or pain from, pressure at the chest bone (pressure or pain sensitivity, PPS) and activity of the ANS. A recent randomized controlled trial (RCT) of type 2 diabetes (T2DM) suggested that addition of an experimental, non-pharmacological intervention more effectively than conventional treatment lowered the levels of both PPS and HbA1c.Materials and analyses: We tested the null hypothesis that conventional treatment (n = 60) would reveal no association between baseline HbA1c and normalization of HbA1c in 6 months, related to change of PPS. We compared the changes of HbA1c in PPS reverters who experienced a minimum reduction of 15 units of PPS and in PPS non-reverters who experienced no reduction. Depending on the result, we tested the association in a second group of participants with addition of the experimental program (n = 52).Results: In the conventional group, PPS reverters experienced normalization of HbA1c that corrected the basal increase, thus disproving the null hypothesis. With the addition of the experimental program, PPS reverters experienced similar reduction. The reduction of HbA1c among reverters averaged 0.62 mmol/mol per mmol/mol increase of baseline HbA1c (P < 0.0001 compared to non-reverters). For baseline HbA1c ≥ 64 mmol/mol, reverters averaged 22% reduction of HbA1c (P < 0.01).Conclusion: In consecutive analyses of two different populations of individuals with T2DM, we demonstrated that the higher the baseline HbA1c, the greater the reduction of HbA1c but only in individuals with a concomitant reduction of sensitivity to PPS, suggesting a homeostatic effect of the autonomic nervous system on glucose metabolism. As such, ANS function, measured as PPS, is an objective measure of HbA1c homeostasis. This observation may be of great clinical importance. BACKGROUND: The autonomic nervous system (ANS) maintains glucose homeostasis. While higher than normal glucose levels stimulate the ANS toward reduction, previous findings suggest an association between sensitivity to, or pain from, pressure at the chest bone (pressure or pain sensitivity, PPS) and activity of the ANS. A recent randomized controlled trial (RCT) of type 2 diabetes (T2DM) suggested that addition of an experimental, non-pharmacological intervention more effectively than conventional treatment lowered the levels of both PPS and HbA1c.MATERIALS AND ANALYSES: We tested the null hypothesis that conventional treatment (n = 60) would reveal no association between baseline HbA1c and normalization of HbA1c in 6 months, related to change of PPS. We compared the changes of HbA1c in PPS reverters who experienced a minimum reduction of 15 units of PPS and in PPS non-reverters who experienced no reduction. Depending on the result, we tested the association in a second group of participants with addition of the experimental program (n = 52).RESULTS: In the conventional group, PPS reverters experienced normalization of HbA1c that corrected the basal increase, thus disproving the null hypothesis. With the addition of the experimental program, PPS reverters experienced similar reduction. The reduction of HbA1c among reverters averaged 0.62 mmol/mol per mmol/mol increase of baseline HbA1c (P < 0.0001 compared to non-reverters). For baseline HbA1c ≥ 64 mmol/mol, reverters averaged 22% reduction of HbA1c (P < 0.01).CONCLUSION: In consecutive analyses of two different populations of individuals with T2DM, we demonstrated that the higher the baseline HbA1c, the greater the reduction of HbA1c but only in individuals with a concomitant reduction of sensitivity to PPS, suggesting a homeostatic effect of the autonomic nervous system on glucose metabolism. As such, ANS function, measured as PPS, is an objective measure of HbA1c homeostasis. This observation may be of great clinical importance.

Hypothesis and predictions: Here, we claim that amyloid beta (Aβ) accumulation is a protective mechanism that ultimately fails. We predict that more Aβ accumulates in regions with higher rates of glucose metabolism, reaching a maximum followed by progression of pathology. Background: Aβ accumulation is characteristic of Alzheimer's disease (AD) but the accumulation does not correlate with cognitive decline, unlike the rates of glucose metabolism. Strategy: We compared averaged and individual estimates of regional binding potentials of [11C]Pittsburgh compound B to regionally averaged and individual values of metabolism of [18F]fluorodeoxyglucose in brain regions of volunteers with AD. Significance: The claim explains the cognitive decline in some patients at a significantly lower level of Aβ deposition than in other patients, as well as the presence of cognitively healthy individuals with high Aβ accumulation. With further support of the hypothesis, the significance of Aβ accumulation in brains of patients with AD may require revision.

Three genotypes of wheat grown at two CO2 concentrations were used in a drought experiment, where water was withheld from the pots at anthesis until stomatal conductance (gs) dropped below 10% of the control and photosynthesis (A) approached zero. The genotypes had different leaf area (Gladius < LM19 < LM62) and while photosynthesis and shoot growth were boosted by elevated CO2, the water use and drying rate were more determined by canopy size than by stomatal density and conductance. The genotypes responded differently regarding number of fertile tillers, seeds per spike and 1000 kernel weight and, surprisingly, the largest genotype (LM62) with high water use showed the lowest relative decrease in grain yield. The maximum photochemical efficiency of photosystem II (Fv/Fm) was only affected on the last day of the drought when the stomata were almost closed although some variation in A was still seen between the genotypes. A close correlation was found between Fv/Fm and % loss of grain yield. It indicates that the precise final physiological stress level measured by Fv/Fm at anthesis/early kernel filling could effectively predict percentage final yield loss, and LM62 was slightly less stressed than the other genotypes, due to only a small discrepancy in finalising the drying period. Therefore, Fv/Fm can be used as a proxy for estimating the yield performance of wheat after severe drought at anthesis.

Long-term alteration of dopaminergic neurotransmission is known to modulate the D2/D3 receptor expression in the brain. The modulation can occur as a response to pathological processes or pharmacological intervention. The receptor density can be monitored by in vivo positron emission tomography (PET) of [11C] raclopride. To obtain accurate measurements of receptor-ligand interaction, it is essential to estimate binding parameters at true (if transient) equilibrium of bound and unbound ligand quantities. We designed this study as a comparison of two quantitative approaches to transient equilibrium, the TRansient EquilibriuM BoLus Estimation (TREMBLE) method and the Transient Equilibrium Model (TEM) method, to determine binding parameters at transient equilibrium with bolus injection of the radioligand. The data demonstrates that TREMBLE unlike TEM identified the time at which equilibrium existed. TREMBLE revealed that equilibrium prevailed at one or more times after bolus injection and identified differences of receptor density among regions such as putamen and caudate nucleus. We demonstrated that TREMBLE is a quantitative approach suitable for the study of pathophysiological conditions of certain types of neurotransmission the brain.

Agricultural nitrogen (N) application to soils is the main source of atmospheric ammonia (NH3) emissions. Ammonia negatively impacts the environment on a large scale. These emissions are affected by spatiotemporal heterogeneities of parameters within the soil on a microscale. Some key parameters controlling processes of the N cycle are soil oxygen (O2) and pH. To better understand biogeochemical soil processes and NH3 emissions we propose the application of optical chemical sensors (optodes) in soils. The use of optodes in soil science is in its infancy. In this study, we investigated the possibilities and challenges of using optodes in non-waterlogged soils with the extended application of a recently developed NH3 optode in combination with pH and O2 optodes in two different soils and with different fertilizers. Our results demonstrated the possibility to visualize reductions of NH3 concentrations by 76 % and 87 % from the incorporation of sludge compared to the surface application of sludge. We showed in 2D how soil pH and fertilizer composition correlate with NH3 volatilization. Our measurements revealed that pH optodes show certain advantages over conventional methods when measuring pH in soils in-situ. Lastly, we investigated spatiotemporal dynamics of O2 at different soil water contents and discussed potential challenges, which can lead to measuring artifacts.

Decryption of brain images is the basis for the necessary translation of the findings from imaging to information required to meet the demands of clinical intervention. Tools of brain imaging, therefore, must satisfy the conditions dictated by the needs for interpretation in terms of diagnosis and prognosis. In addition, the applications must serve as fundamental research tools that enable the understanding of new therapeutic drugs, including compounds as diverse as antipsychotics, antidepressants, anxiolytics, and drugs serving the relief of symptoms from neurochemical disorders as unrelated as multiple sclerosis, stroke, and dementia. Here we review and explain the kinetics of methods that enable researchers to describe the brain’s work and functions. We focus on methods invented by neurokineticists and expanded upon by practitioners during decades of experimental work and on the methods that are particularly useful to predict possible future approaches to the treatment of neurochemical disorders. We provide an overall description of the basic elements of kinetics and the underlying quantification methods, as well as the mathematics of modeling the recorded brain dynamics embedded in the images we obtain in vivo. The complex presentation to follow is necessary to justify the contribution of modeling to the development of methods and to support the specifications dictated by the proposed use in clinical settings. The quantification and kinetic modeling processes are equally essential to image reconstruction and labeling of brain regions of structural or functional interest. The procedures presented here are essential tools of scientific approaches to all conventional and novel forms of brain imaging. The foundations of the kinetic and quantitative methods are keys to the satisfaction of clinicians that actively engage in treating the neurochemical disorders of mammalian brains in the fields of neurology, neurosurgery, and neuropsychiatry.

We derived three widely used linearizations from the definition of receptor availability in molecular imaging with positron emission tomography (PET). The purpose of the present research was to determine the convergence of the results of the 3 methods in terms of 3 parameters—occupancy (s), distribution volume of the nondisplaceable reference binding compartment (V(ND)), and nondisplaceable reference binding potential (BP(ND)) of the radioligand—in the absence of a gold standard. We tested 104 cases culled from the literature and calculated the goodness of fit of the least-squares and Deming II methods of linear regression when applied to the determination of s, V(ND), and BP(ND) using the goodness-of-fit parameters R(2), coefficient of variation (root-mean-square error [RMSE]), and the infinity norm (‖X‖(∞)) with both regression methods. We observed superior convergence among the values of s, V(ND), and BP(ND) for the inhibition and occupancy plots. The inhibition plot emerged as the plot with a slightly higher degree of convergence (based on R(2), RMSE, and ‖X‖(∞) value). With two regression methods (the least-squares method [LSM] and the Deming II [DM] method), the estimated values of s, V(ND), and BP(ND) generally converged. The inhibition and occupancy plots yielded the best fits to the data, according to the goodness-of-fit parameters, due primarily to absence of commingling of the dependent and independent variables tested with the saturation (original Lassen) plot. In the presence of noise, the inhibition and occupancy plots yielded higher convergences.

Background: Values of binding potentials (BPND) of dopamine D2/3 receptors differ in different regions of the brain, but we do not know with certainty how much of this difference is due either to different receptor numbers, or to different affinities of tracers to the receptors, or to both. Method: We tested the claim that both striatal and extrastriatal dopamine D2/3 receptor availabilities vary with age in vivo in humans by determining the values of BPND of the specific radioligand [11C]raclopride. We determined values of BPND in striatal and extrastriatal volumes-of-interest (VOI) with the same specific receptor radioligand. Results: We estimated values of BPND in individual voxels of brains of healthy volunteers in vivo, and we obtained regional averages of VOI by dynamic positron emission tomography (PET). We calculated average values of BPND in caudate nucleus and putamen of striatum, and in frontal, occipital, parietal, and temporal cortices of the forebrain, by means of four methods, including the ERLiBiRD (Estimation of Reversible Ligand Binding and Receptor Density) method, the tissue reference methods of Logan and Logan-Ichise, respectively, and the SRTM (Simplified Reference Tissue Method). Voxelwise generation of parametric maps of values of BPND used the multi-linear regression version of SRTM. Conclusions: The estimates of BPND declined significantly with age in both striatal and extrastriatal regions, as determined by all four methods, with the greatest decline observed in posterior (occipital and parietal) cortices (14% per decade) and the lowest decline in caudate nucleus (3% per decade).

Values of binding potentials (BP

Rationale: After alcohol ingestion, the brain partly switches from consumption of glucose to consumption of the alcohol metabolite acetate. In heavy drinkers, the switch persists after abrupt abstinence, leading to the hypothesis that the resting brain may be “starved” when acetate levels suddenly drop during abstinence, despite normal blood glucose, contributing to withdrawal symptoms. We hypothesized that ketone bodies, like acetate, could act as alternative fuels in the brain and alleviate withdrawal symptoms. Objectives: We previously reported that a ketogenic diet during alcohol exposure reduced acute withdrawal symptoms in rats. Here, our goals were to test whether (1) we could reproduce our findings, in mice and with longer alcohol exposure; (2) ketone bodies alone are sufficient to reduce withdrawal symptoms (clarifying mechanism); (3) introduction of ketogenic diets at abstinence (a clinically more practical implementation) would also be effective. Methods: Male C57BL/6NTac mice had intermittent alcohol exposure for 3 weeks using liquid diet. Somatic alcohol withdrawal symptoms were measured as handling-induced convulsions; anxiety-like behavior was measured using the light-dark transition test. We tested a ketogenic diet, and a ketone monoester supplement with a regular carbohydrate-containing diet. Results: The regular diet with ketone monoester was sufficient to reduce handling-induced convulsions and anxiety-like behaviors in early withdrawal. Only the ketone monoester reduced handling-induced convulsions when given during abstinence, consistent with faster elevation of blood ketones, relative to ketogenic diet. Conclusions: These findings support the potential utility of therapeutic ketosis as an adjunctive treatment in early detoxification in alcohol-dependent patients seeking to become abstinent. Trial registration: clinicaltrials.gov NCT03878225, NCT03255031

The corticofugal tracts (CFT) are key agents of upper limb motor function. Although the tracts form high-intensity regions relative to surrounding tissue in T2-weighted magnetic resonance images (T2WI), the precise relations of signal intensities of the left and right CFT regions to hand function are unknown. Here, we tested the hypothesis that the different signal intensities between the left and right CFT signify clinically important differences of hand motor function. Six right-handed and six left-handed healthy volunteers participated in the study. Based on horizontal T2WI estimates, we confirmed the relationship between the signal intensity ratios of the peak values of each CFT in the posterior limbs of the internal capsules (right CFT vs. left CFT). The ratios included the asymmetry indices of the hand motor functions, including grip and pinch strength, as well as the target test (TT) that expressed the speed and accuracy of hitting a target ([right-hand score – left-hand score]/[right-hand score + left-hand score]), using simple linear regression. The signal intensity ratios of each CFT structure maintained significant linear relations with the asymmetry index of the speed (R2 = 0.542, P = 0.006) and accuracy (R2 = 0.408, P = 0.025) of the TT. We found no significant association between left and right CFT structures for grip or pinch strengths. The findings are consistent with the hypothesis that the different signal intensities of the left and right CFT images captured by T2WI serve as biological markers that reflect the dominance of manual dexterity.

Decryption of brain images is the basis for the necessary translation of the findings from imaging to information required to meet the demands of clinical intervention. Tools of brain imaging, therefore, must satisfy the conditions dictated by the needs for interpretation in terms of diagnosis and prognosis. In addition, the applications must serve as fundamental research tools that enable the understanding of new therapeutic drugs, including compounds as diverse as antipsychotics, antidepressants, anxiolytics, and drugs serving the relief of symptoms from neurochemical disorders as unrelated as multiple sclerosis, stroke, and dementia. Here we review and explain the kinetics of methods that enable researchers to describe the brain's work and functions. We focus on methods invented by neurokineticists and expanded upon by practitioners during decades of experimental work and on the methods that are particularly useful to predict possible future approaches to the treatment of neurochemical disorders. We provide an overall description of the basic elements of kinetics and the underlying quantification methods, as well as the mathematics of modeling the recorded brain dynamics embedded in the images we obtain

BackgroundDisturbances in presynaptic dopamine activity and levels of GABA (gamma-aminobutyric acid) and glutamate plus glutamine collectively may have a role in the pathophysiology of psychosis, although separately they are poor diagnostic markers. We tested whether these neurotransmitters in combination improve the distinction of antipsychotic-naïve patients with first-episode psychosis from healthy control subjects.MethodsWe included 23 patients (mean age 22.3 years, 9 male) and 20 control subjects (mean age 22.4 years, 8 male). We determined dopamine metabolism in the nucleus accumbens and striatum from 18F-fluorodopa (18F-FDOPA) positron emission tomography. We measured GABA levels in the anterior cingulate cortex (ACC) and glutamate plus glutamine levels in the ACC and left thalamus with 3T proton magnetic resonance spectroscopy. We used binominal logistic regression for unimodal prediction when we modeled neurotransmitters individually and for multimodal prediction when we combined the 3 neurotransmitters. We selected the best combination based on Akaike information criterion.ResultsIndividual neurotransmitters failed to predict group. Three triple neurotransmitter combinations significantly predicted group after Benjamini-Hochberg correction. The best model (Akaike information criterion 48.5) carried 93.5% of the cumulative model weight. It reached a classification accuracy of 83.7% (p = .003) and included dopamine synthesis capacity (Ki4p) in the nucleus accumbens (p = .664), GABA levels in the ACC (p = .019), glutamate plus glutamine levels in the thalamus (p = .678), and the interaction term Ki4p × GABA (p = .016).ConclusionsOur multimodal approach proved superior classification accuracy, implying that the pathophysiology of patients represents a combination of neurotransmitter disturbances rather than aberrations in a single neurotransmitter. Particularly aberrant interrelations between Ki4p in the nucleus accumbens and GABA values in the ACC appeared to contribute diagnostic information.

Globally, to ensure food security bio-based fertilizers must replace a percentage of chemical fertilizers. Such replacement must be deemed sustainable from agronomic and greenhouse gas (GHG) emission perspectives. For agronomic performance several controlled protocols are in place but not for testing GHG emissions. Herein, a pre-screening tool is presented to examine GHG emissions from bio-waste as fertilizers. The various treatments examined are as follows: soil with added mineral nitrogen (N, 140 kg N ha−1) fertilizer (MF), the same amount of MF combined with dairy processing sludge (DS), sludge-derived biochar produced at 450 °C (BC450) and 700 °C (BC700) and untreated control (CK). These treatments were combined with Danish (sandy loam) or Irish (clay loam) soils, with carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) emissions and soil inorganic-N contents measured on selected days. During the incubation, biochar mitigated N2O emissions by regulating denitrification. BC450 reduced N2O emissions from Danish soil by 95.5% and BC700 by 97.7% compared to emissions with the sludge application, and for Irish soil, the N2O reductions were 93.6% and 32.3%, respectively. For both soils, biochar reduced CO2 emissions by 50% as compared to the sludge. The lower N2O reduction potential of BC700 for Irish soil could be due to the high soil organic carbon and clay content and pyrolysis temperature. For the same reasons emissions of N2O and CO2 from Irish soil were significantly higher than from Danish soil. The temporal variation in N2O emissions was correlated with soil inorganic-N contents. The CH4 emissions across treatments were not significantly different. This study developed a simple and cost-effective pre-screening method to evaluate the GHG emission potential of new bio-waste before its field application and guide the development of national emission inventories, towards achieving the goals of circular economy and the European Green Deal.

In recent years, the field of neuroimaging dramatically moved forward by means of the expeditious development of specific radioligands of novel targets. Among these targets, the synaptic vesicle glycoprotein 2A (SV2A) is a transmembrane protein of synaptic vesicles, present in all synaptic terminals, irrespective of neurotransmitter content. It is involved in key functions of neurons, focused on the regulation of neurotransmitter release. The ubiquitous expression in gray matter regions of the brain is the basis of its candidacy as a marker of synaptic density. Following the development of molecules derived from the structure of the anti-epileptic drug levetiracetam, which selectively binds to SV2A, several radiolabeled markers have been synthetized to allow the study of SV2A distribution with positron emission tomography (PET). These radioligands permit the evaluation of in vivo changes of SV2A distribution held to be a potential measure of synaptic density in physiological and pathological conditions. The use of SV2A as a biomarker of synaptic density raises important questions. Despite numerous studies over the last decades, the biological function and the expressional properties of SV2A remain poorly understood. Some functions of SV2A were claimed, but have not been fully elucidated. While the expression of SV2A is ubiquitous, stronger associations between SV2A and Υ amino butyric acid (GABA)-ergic rather than glutamatergic synapses were observed in some brain structures. A further issue is the unclear interaction between SV2A and its tracers, which reflects a need to clarify what really is detected with neuroimaging tools. Here, we summarize the current knowledge of the SV2A protein and we discuss uncertain aspects of SV2A biology and physiology. As SV2A expression is ubiquitous, but likely more strongly related to a certain type of neurotransmission in particular circumstances, a more extensive knowledge of the protein would greatly facilitate the analysis and interpretation of neuroimaging results by allowing the evaluation not only of an increase or decrease of the protein level, but also of the type of neurotransmission involved.

Exposure to moderate hypoxia in humans leads to cerebral lactate production, which occurs even when the cerebral metabolic rate of oxygen (CMRO2) is unaffected. We searched for the mechanism of this lactate production by testing the hypothesis of upregulation of cerebral glycolysis mediated by hypoxic sensing. Describing the pathways counteracting brain hypoxia could help us understand brain diseases associated with hypoxia. A total of 65 subjects participated in this study: 30 subjects were exposed to poikilocapnic hypoxia, 14 were exposed to isocapnic hypoxia, and 21 were exposed to carbon monoxide (CO). Using this setup, we examined whether lactate production reacts to an overall reduction in arterial oxygen concentration or solely to reduced arterial oxygen partial pressure. We measured cerebral blood flow (CBF), CMRO2, and lactate concentrations by magnetic resonance imaging and spectroscopy. CBF increased (P 0.076) in all groups, as expected. Lactate increased in groups inhaling hypoxic air (poikilocapnic hypoxia: $0.0136\ \frac{\mathrm{mmol}/\mathrm{L}}{\Delta{\mathrm{S}}_{\mathrm{a}}{\mathrm{O}}_2}$, P Lactate production was not associated with reduced CMRO2. These results point toward a mechanism of lactate production by upregulation of glycolysis mediated by sensing a reduced arterial oxygen pressure. The released lactate may act as a signaling molecule engaged in vasodilation.

Background: Dopamine activity has been associated with the response to antipsychotic treatment. Our study used a four-parameter model to test the association between the striatal decarboxylation rate of 18F-DOPA to 18F-dopamine (k3) and the effect of treatment on psychotic symptoms in antipsychotic-naïve patients with first-episode psychosis. We further explored the effect of treatment with a partial dopamine D2 receptor agonist (aripiprazole) on k3 and dopamine synthesis capacity (DSC) determined by the four-parameter model and by the conventional tissue reference method. Methods: Sixty-two individuals (31 patients and 31 control subjects) underwent 18F-DOPA positron emission tomography at baseline, and 15 patients were re-examined after 6 weeks. Clinical re-examinations were completed after 6 weeks (n = 28) and 6 months (n = 15). Symptoms were evaluated with the Positive and Negative Syndrome Scale. Results: High baseline decarboxylation rates (k3) were associated with more positive symptoms at baseline (p < .001) and with symptom improvement after 6 weeks (p = .006). Subregion analyses showed that baseline k3 for the putamen (p = .003) and nucleus accumbens (p = .013) and DSC values for the nucleus accumbens (p = .003) were associated with psychotic symptoms. The tissue reference method yielded no associations between DSC and symptoms or symptom improvement. Neither method revealed any effects of group or treatment on average magnitudes of k3 or DSC, whereas changes in dopamine synthesis were correlated with higher baseline values, implying a potential effect of treatment. Conclusions: Striatal decarboxylation rate at baseline was associated with psychotic symptoms and treatment response. The strong association between k3 and treatment effect potentially implicate on new treatment strategies.

Supplemental material, sj-docx-1-taw-10.1177_20420986221103918 for Polypharmacy and potential drug–drug interactions among Greenland’s care home residents by Nadja Albertsen, Tine Gjedde Sommer, Thomas Mikkel Olsen, Anna Prischl, Hans Kallerup and Stig Andersen in Therapeutic Advances in Drug Safety

We asked if sensation-seeking is linked to premorbid personality characteristics in patients with addictive disorders, or the characteristics follow the sensation-seeking activity. We interpreted the former as a state associated with normal rates of dopamine synthesis, and the latter as a trait of individuals with abnormally high rates of synthesis. We previously determined dopaminergic receptor density in striatum, and we now tested the hypothesis that an elevated dopaminergic condition with increased extracellular dopamine and receptor density follows increased dopamine synthesis capacity in highly sensation-seeking individuals, as measured by positron emission tomography of 18 men with tracer fluorodopa (FDOPA). We detected a site in left caudate nucleus where the volume of distribution of FDOPA-derived metabolites correlated negatively with FDOPA metabolite turnover, consistent with decreased metabolite breakdown in highly sensation-seeking subjects. High rates of sensation-seeking attenuated the dopamine turnover in association with a low rate of dopamine recycling, low dopamine oxidation, and elevated extracellular dopamine and receptors in caudate nucleus. In contrast, low rates of sensation-seeking were associated with rapid dopamine recycling, rapid dopamine oxidation, low extracellular dopamine, and low receptor density. We conclude that the modulation of dopaminergic neurotransmission associated with sensation-seeking is a state of sensation-seeking, rather than a trait of personality following abnormal regulation of dopaminergic neurotransmission.

Supplemental material, sj-docx-1-taw-10.1177_20420986221103918 for Polypharmacy and potential drug–drug interactions among Greenland’s care home residents by Nadja Albertsen, Tine Gjedde Sommer, Thomas Mikkel Olsen, Anna Prischl, Hans Kallerup and Stig Andersen in Therapeutic Advances in Drug Safety

The environmental challenges of society today necessitate educational approaches thatmotivate learners toward careers in science and foster creativity and innovation. The urbanizationof society with many children growing up with little opportunity to experience nature in their dailylives has created a need to reconnect with nature, especially for children and youth, in ways thatcan also make natural sciences meaningful to them. This paper presents the first phase of aresearch and development project that explores the potential of participatory media to promotegreater environmental awareness in children and adolescents. In the first phase of the qualitativestudy, the project has collaborated with three schools, and designed interventions where studentsand their teachers employed narrative, role-play and digital media in an interdisciplinary approachto science classes. The project has developed and tested a combination of integrative learningdesigns, including video production and role-play scenarios as well as exploring nature usingscientific methods. The research methods combine observations, interviews, and qualitativesurveys. The results from the first phase of the project are promising but also indicate that furtherresearch in the field is needed. There is a need to further explore the development of creativelearning designs that have the potential to support the development of environmental awareness.

Background: As lifetime expectancy in Greenland is steadily increasing, so is the proportion of elderly Greenlanders. Old age is associated with polypharmacy, and in this study, we aim to describe the prevalence and characteristics of polypharmacy among the care home residents in Greenland. Methods: Eight care homes in Greenland were visited between 2010 and 2016. Questionnaires including information on prescribed medication and comorbidities were collected and analyzed. Drugs were categorized according to Anatomical Therapeutic Chemical (ATC) category, and potential drug–drug interactions (pDDIs) were assessed using the Danish Interaction Database. Polypharmacy was defined as five or more prescribed drugs. Results: All 244 eligible residents were included in the study. The median number of prescribed drugs per resident was six, and women were prescribed more drugs than men (median six versus five). More than 60% of all residents fulfilled the criteria for polypharmacy. The residents in the polypharmacy group had a higher body mass index (26.9 versus 24.3) and more chronic diseases (median two versus one), and more often pulmonary (14% versus 1%) or endocrine disease (22% versus 2%) than in the non-polypharmacy group. The most prescribed drugs belonged to ATC category N (nervous system, 78% of the residents). Finally, pDDIs were found among 61% of the residents and were more common in the capital (77%), which also had the highest proportion of residents with polypharmacy (77%). Conclusion: This is the first study to describe the patterns of polypharmacy and pDDIs among the elderly in care homes in Greenland. Our findings indicate that polypharmacy is as common in Greenland as elsewhere in the Western world, but there are local differences in the prevalence. Plain Language Summary Polypharmacy among the elderly in care homes in Greenland The lifetime expectancy of the Greenlandic population is increasing, and so is the number of elderly Greenlanders. Previous studies have shown that the elderly have a higher risk of being treated with five drugs or more which is called polypharmacy. Polypharmacy can cause unwanted interactions and side effects. In this study, we examine the characteristics of the residents in Greenlandic care homes belonging to this group. Using questionnaires, we gathered information from 244 residents from care homes in eight different towns and settlements in Greenland. Data included types of medication prescribed to the resident, age, gender, cause of stay, and medical history, which allowed us to compare the results between genders and towns. We found that among 244 residents, more than half of all residents were prescribed five or more different drugs, and women were generally prescribed more drugs than men. Those prescribed five or more drugs had a higher body mass index and more diseases than those prescribed fewer drugs. We also found that certain types of medication, mainly painkillers, were the most prescribed. Finally, residents in the care home in Greenland’s capital Nuuk were more often prescribed five or more drugs than elsewhere in Greenland, indicating local differences in Greenland. Our results give an essential insight into the health and medication of the most fragile elderly in Greenland. Polypharmacy seems to be as common here as elsewhere in the Western world and is a point of focus.

This chapter examines the interaction between tracer glucose uptake and phosphor-ylation in brain. It derives the equations for the use of labeled deoxyglucose, fluorodeoxyglucose, or glucose itself to calculate brain glucose phosphorylation. The chapter estimates the value of the “lumped constant” as a function of the glucose phosphorylation rate, the plasma glucose concentration, the maximal transport capacity of the cerebral capillary endothelium, and the plasma flow of the brain. The driving force of the loss of tracer from a compartment is the aqueous concentration of the tracer in the compartment, if the tracer is in aqueous solution. Compartmental analysis of tracer uptake in vivo serves to measure the size of the different compartments of the tracer, that is, the relative abundance of its different states, and the magnitude of the transfer coefficient or relaxation constant of each compartment. The brain has two kinetic compartments, the vascular space and an extra-vascular space, separated by a blood-brain barrier.

A paradigm shift in the approaches to teaching and learning has been underway fordecades, moving towards a more learner-centered and participatory classroom, with the teacherspotentially acquiring new roles as learning experience designers and agents for change towards 21 st .Century learning.This shift is being advanced by the advent of new technologies that can facilitate learner;s self-expression, collaboration and new ways of knowledge representation. A gap between the potentials of these new approaches to learning - and the actual morecomprehensive implementation of it by teachers in the European classrooms - has, however, yet tobe fully overcome.This paper presents preliminary experiences from a European Erasmus+ project tasked withdeveloping a digital resource for teacher competence development to answer the needs for 21st -Century learning offered as a MOOC.

Excessive sucrose consumption elicits addiction-like craving that may underpin the obesity epidemic. Opioids and dopamine mediate the rewarding effects of drugs of abuse, and of natural rewards from stimuli such as palatable food. We investigated the effects of sucrose using PET imaging with [11C]carfentanil (μ-opioid receptor agonist) and [11C]raclopride (dopamine D2/3 receptor antagonist) in seven female anesthetized Göttingen minipigs. We then gave minipigs access to sucrose solution for one hour on 12 consecutive days and performed imaging again 24 hours after the final sucrose access. In a smaller sample of five minipigs, we performed an additional [11C]carfentanil PET session after the first sucrose exposure. We calculated voxel-wise binding potentials (BPND) using the cerebellum as a region of non-displaceable binding, analyzed differences with statistical non-parametric mapping, and performed a regional analysis. After 12 days of sucrose access, BPND of both tracers had declined significantly in striatum, nucleus accumbens, thalamus, amygdala, cingulate cortex and prefrontal cortex, consistent with down-regulation of receptor densities. After a single exposure to sucrose, we found decreased binding of [11C]carfentanil in nucleus accumbens and cingulate cortex, consistent with opioid release. The lower availability of opioid and dopamine receptors may explain the addictive potential associated with intake of sucrose.

Background: Workplace-based assessment (WPBA) is widely accepted, but few studies have investigated implementation issues during general practice (GP) placements. This study explored possible barriers and identified key elements for successful implementation of a WPBA-programme in Danish GP specialist training.Methods: Supervisors had attended a one-day course in WPBA and trainees had received a short introduction. Questionnaires on experiences with implementation of WPBA were distributed to 106 GP supervisors and 110 trainees after the rotation was finished.Results: The response rate was 61/96 (64%) for trainees and 67/94 (71%) for supervisors. Supervisors were generally more positive towards WPBA and saw fewer barriers than trainees. Lack of planning was most often reported as an impediment to WPBA. Supervisors did not identify trainees’ uneasiness of being observed as a problem as often as trainees. A total of 34% of trainees reported uneasiness as an obstacle to WPBA.Conclusions: It seems that the education of supervisors positively influenced supervisors’ perception and use of WPBA. Adequate planning of WPBA may be just as big a problem as assigning the time. Further investigations on the impact of education on trainees’ perception of WPBA are needed.

Dopamine activity has been associated with the response to antipsychotic treatment. Our study used a four-parameter model to test the association between the striatal decarboxylation rate ofSixty-two individuals (31 patients and 31 control subjects) underwentHigh baseline decarboxylation rates (kStriatal decarboxylation rate at baseline was associated with psychotic symptoms and treatment response. The strong association between k

BackgroundAutonomic nervous system dysfunction (ANSD) is known to affect glucose metabolism in the mammalian body. Tradition holds that glucose homeostasis is regulated by the peripheral nervous system, and contemporary therapeutic intervention reflects this convention.ObjectivesThe present study tested the role of cerebral regulation of ANSD as consequence of novel understanding of glucose metabolism and treatment target in type 2 diabetes (T2D), suggested by the claim that the pressure pain sensitivity (PPS) of the chest bone periosteum may be a measure of cerebral ANSD.DesignIn a randomized controlled trial of 144 patients with T2D, we tested the claim that 6 months of this treatment would reduce PPS and improve peripheral glucose metabolism.ResultsIn the active treatment group, mean glycated hemoglobin A1c (HbA1c) declined from 53.8 to 50.5 mmol/mol (intragroup p = 0.001), compared with the change from 53.8 to 53.4 mmol/mol in the control group, with the same level of diabetes treatment but not receiving the active treatment (between group p = 0.036). Mean PPS declined from 76.6 to 56.1 units (p < 0.001) in the active treatment group and from 77.5 to 72.8 units (p = 0.02; between group p < 0.001) in the control group. Changes of PPS and HbA1c were correlated (r = 0.37; p < 0.001).ConclusionWe conclude that the proposed approach to treatment of T2D is a potential supplement to conventional therapy.Clinical Trial Registration:www.clinicaltrials.gov (NCT 03576430).

Bauxit rester eller redmud er gruvedriften rester (tailing) fra Bayer-prosessen med bauxittmalm, og med 4,6 milliarder tonn i reserver av farlige avfallsverdier er det nødvendig å inkludere det som restressurs i sirkulær økonomi. Denne studien refererer kort til gjeldende behandlings- og utnyttelsesmetoder for residuet med fokus på tre teknologier: Avalkalisering, jordstabilisering og høytytende bindemiddel (geopolymer). For hver teknologi identifiseres prosesser som har betydning for miljøpåvirkningen, og forbedringer og anbefalinger foreslås. Det blir evaluert om stedsspesifikke faktorer og sammensetning av bauxit resten påvirker miljøpåvirkningen av teknologiene. En attribusjons livssyklusanalyse ved bruk av APOS ecoinvent-databasen og ReCiPe-konsekvensanalysemetoden ble brukt til å evaluere hver prosess på effekt kategorier for endepunkter og sammenligne dem på midtpunkt effekt kategorier. Resultatene ble diskutert sammen med en gjennomgang av noen sensitive materialer og prosesser, spesielt flyveaske i jordstabilisering og geopolymer. Den "hybrid" versjonen av høyytelses bindemiddel og jordstabiliseringsteknologi har positiv innflytelse på miljøet, men selv da avalkalisering reduserer farerisiko knyttet til fyllinger av bauxitt, forårsaker den også miljøpåvirkninger i andre områder. Det argumenteres for at jordstabilisering ikke skal krediteres for bruk av flyveaske fordi den allerede brukes til veibygging og trender til å være mer ressurs enn avfall. Det anbefales derfor å bruke det hybride høytytende bindemidlet, men suksessen avhenger av kvaliteten som avhenger av bauxit resten, i hvilken grad bør studeres nærmere. En break-even transportavstand for hver teknologi basert på midtpunktpåvirkninger og transporttype viser at det hybride høytytende bindemiddel produktet potensielt kan distribueres internasjonalt uten å forårsake byrdeforskyvning, noe som fører til en nedgang i konvensjonell betongproduksjon i skala med den årlige restproduksjonen og reserver. Imidlertid er det en risiko for giftig Cr (VI) utvasking og farer fra alkalinitet som må analyseres videre for å kunne markedsføre hybrid høyytelsesbindemiddel. Bauxite residue or red mud is the mine waste (tailing) from the Bayer process of bauxite ore, and with 4.6 billion tonnes in reserves of the hazardous waste valorisation pathways are needed to include it as residual resource in circular economy. This study shortly benchmarks current treatment and utilization methods of the residue with focus on three technologies: De-alkalization, soil stabilization, and high performance binder (geopolymer). For each technology, processes significant to environmental impacts are identified and improvements and recommendations are suggested. It is evaluated if location-specific factors and residue composition affects the environmental impacts of the technologies. An attributional life cycle analysis using the APOS ecoinvent database and ReCiPe impact assessment method was used to evaluate each process on endpoint impact categories and compare them on midpoint impact categories. The results were discussed together with a review on some sensitive materials and processes, especially fly ash in soil stabilization and geopolymer. The “hybrid” version of the high performance binder and soil stabilization technologies have positive influence on the environment, but while de-alkalization reduce hazard risk related to bauxite landfills it also cause environmental impacts in other areas. It is argued that soil stabilization should not be credited for using fly ash because it is already used for road construction and trending to be more resource than waste. The hybrid high performance binder is therefore recommended, but the success depends on its quality which depends on bauxite residue composition, to what degree should be studied further. A break-even transport distance for each technology based on midpoint impacts and transport type show that the hybrid high performance binder product potentially can be distributed internationally without causing burden-shifting, leading to a decrease of conventional concrete production in scale with the residue production and reserves. However, there is a risk of toxic Cr(VI) leaching and alkalinity hazards that must be analysed further for the hybrid high performance binder to be marketed.

Tema for oppgaven er «trær på naboeiendommen», med særlig fokus på den vederlags- og berikelsesproblematikken som kan oppstå ved ulovlig felling av naboens trær. Uberettiget berikelse betyr at en som ulovlig feller trær på naboeiendom, gjennom dette oppnår verdiøkning på egen eiendom. Oppgaven behandler flere problemstillinger knyttet til en slik situasjon. Oppgaven omhandler et juridisk område, og ulike rettskilder blir benyttet til å søke kunnskap om rettstilstanden. Antall nabokonflikter øker, og uenigheter rundt naboens trær er en av de vanligste årsakene til konflikt. Dagens utbyggingspolitikk legger opp til økt fortetting i by og sentrale strøk. Høyere arealutnyttelse vil kunne bidra til at konfliktnivået om trær mellom naboer øker. Samtidig er det i dag fra samfunnets side et ønske om sterkere vern av trær i tettbygde/sentrale strøk både fra statlig og kommunalt hold. På mange måter kan man si at trær har kommet inn som en tredjepart når det oppstår konflikt om trær i naboforhold. Så fremt ikke grunneier og nabo kommer frem til en frivillig avtale om felling av trær, skal det relativt mye til for at en nabo får rett til å hugge ned naboens trær med hjemmel i nabolovens bestemmelser. Dagens lovgivning regulerer ikke spørsmålet om uberettiget berikelse ved ulovlig felling av trær på naboeiendom. Det er heller ikke tatt direkte stilling til dette spørsmålet i rettspraksis. Hovedregelen i erstatningsretten i Norge er at skadelidte skal ha full erstatning. Med full erstatning menes skadelidtes økonomiske tap. At skadelidte, i dette tilfelle grunneier, skal ha krav på kompensasjon for en nabos uberettiget berikelse, strider således mot dette grunnprinsippet. Opphavs-, patent- og varemerkerett har bestemmelser som kan tjene som illustrasjon for at det i visse tilfeller er åpning for å tilkjenne vederlag svarende til vinningen som er oppnådd ved overtredelsen. Det er også inndragningsbestemmelser i strafferetten. Oppgaven avslutter med refleksjoner knyttet til oppgavens tema, og om det er behov for endringer i dagens regler, såkalte de lege ferenda betraktninger. The topic of this thesis is “threes on a neighboring property”, with particular focus on issues related to remuneration and unwarranted enrichment in relation to unlawful chopping of neighbor’s threes. Unwarranted enrichment can be explained as the “unfair” increase in the property value gained as a result of an unlawful act. The thesis handles several related subjects, and a number of legal sources to address the current legal status are used. There is an increase in neighbor conflicts, and disagreements related to threes are among the most common ones. Today´s urban developments policies aim for higher use in centrally located areas. This may increase the number of such disputes and comes at a time where there is also a stronger sense of the need for stronger protection of threes by the authorities. One might say that threes have become “a third part” in such conflicts. If the owner of the property where the threes are located and the neighbor are unable to reach an agreement on the issue, it is relatively difficult to have a legal right to conduct chopping, reference is here made to the Norwegian legislation on neighbor relations. And this legislation does not contain provisions on unwarranted enrichment, nor has the issue been clarified by jurisprudence. The main rule in Norwegian tort law states that the injured party is to be fully compensated for the economic loss. A claim related to unlawful enrichment may be in conflict with this principle. Norwegian legislation on copyright, patent and trademarks do however contain provisions on unlawful enrichments, that may serve as an illustration. There is also legislation in Norwegian criminal law on confiscation. The thesis will assess the current legal situation and do contain de lege ferenda considerations. M-EUTV

Quantitative measurements of resting cerebral blood flow (CBF) and metabolic rate of oxygen (CMRO2) show large between-subject and regional variability, but the relationships between CBF and CMRO2 measurements regionally and globally are not fully established. Here, we investigated the between-subject and regional associations between CBF and CMRO2 measures with independent and quantitative PET techniques. We included resting CBF and CMRO2 measurements from 50 healthy volunteers (aged 22–81yr), and calculated the regional and global values of oxygen delivery (DO2) and oxygen extraction fraction (OEF). Linear mixed-model analysis showed that CBF and CMRO2 measurements were closely associated regionally, but no significant between-subject association could be demonstrated, even when adjusting for arterial PCO2 and hemoglobin concentration. The analysis also showed regional differences of OEF, reflecting variable relationship between DO2 and CMRO2, resulting in lower estimates of OEF in thalami, brainstem, and mesial temporal cortices and higher estimates of OEF in occipital cortex. In the present study, we demonstrated no between-subject association of quantitative measurements of CBF and CMRO2 in healthy subjects. Thus, quantitative measurements of CBF did not reflect the underlying between-subject variability of oxygen metabolism measures, mainly because of large interindividual OEF variability not accounted for by PCO2 and hemoglobin concentration. NEW & NOTEWORTHY Using quantitative PET-measurements in healthy human subjects, we confirmed a regional association of CBF and CMRO2, but did not find an association of these values across subjects. This suggests that subjects have an individual coupling between perfusion and metabolism and shows that absolute perfusion measurements does not serve as a surrogate measure of individual measures of oxygen metabolism. The analysis further showed smaller, but significant regional differences of oxygen extraction fraction at rest.

Biogas er vedvarende energiproduceret ved at fordøje biomasse under anaerobe forhold. Husdyrgødning, spildevand og vådt organisk affald fra industrien og husholdningerne kan anvendes i produktionen, som så også fungerer som affaldsbehandling.Når husdyrgødning leveres til biogasproduktion, reduceres udledningen af drivhusgasser fra husdyr. Processen gør også næringsstofferne i gylle mere tilgængelige for planter. Omfanget af biogassens drivhusgas- og miljøpåvirkning afhænger af produktionskarakteristikaene, herunder navnlig de anvendte biomasseer. Desuden er faktorer som transport, procesenergiforbrug og eventuelt metanetab fra anlægget inkluderet. Kvantificeringen af biogasproduktionens drivhusgas- og miljøvirkninger udgør et vigtigt grundlag for at udforme og målrette fremtidig biogasfinansiering for at optimere de klima- og miljømæssige fordele ved produktionen. Rapporten præsenterer en analyse af biogasproduktionens virkninger baseret på husdyrgødning og forskellige relevante typer biomasse fra affaldshåndtering og landbrug. Virkningerne er beskrevet for fem model biogasanlæg med forskellige biomassesammensætninger.

Biogas er vedvarende energi, der fremstilles ved at afgasse biomasse under iltfrie forhold. Husdyrgødning, spildevand og vådt organisk affald fra industri og husholdninger kan bruges i produktionen, der samtidig fungerer som affaldsbehandling. Når husdyrgødning leveres til biogasproduktion, reduceres udledningen af drivhusgasser fra husdyrholdet. Processen gør samtidig næringsstofferne i gødningen lettere tilgængelige for planter. Klima- og miljøeffekternes størrelse afhænger af karakteristika ved produktionen, herunder især hvilke biomasser, der anvendes. Desuden indgår forhold som transport, forbrug af procesenergi og af eventuelle metanudslip fra anlægget. Kvantificering af biogasproduktionens klima- og miljøeffekter udgør et vigtigt grundlag for at kunne designe og målrette fremtidig biogasstøtte med henblik på at optimere klima- og miljøfordelene ved produktionen. Rapporten præsenterer en analyse af effekter af produktion af biogas af husdyrgødning og forskellige relevante typer biomasser fra affaldshåndtering og landbrug. Effekterne beskrives for fem modelanlæg for biogasproduktion med forskellig sammensætning af biomasser

Purpose: Anaesthesia routinely is used in animal neuroimaging in order to reduce head motion artefacts and minimize the influence of stress. However, anaesthetics can modify radioligand binding profiles at receptor targets studied by positron emission tomography (PET). Here, we determined the effects of two routine anaesthetics on the binding of a tracer of the serotonin 5HT2A receptors. Procedures: Isoflurane- and propofol-anesthetised Göttingen minipigs were imaged with [11C]MDL100,907 PET and analysed using regions of interest and statistical non-parametric mapping. Results: The binding potentials of the tracer in striatum under isoflurane anaesthesia significantly exceeded those obtained under propofol anaesthesia, an effect we attribute to the higher blood flow in brain induced by the former. Conclusions: Interactions between radioligands and anaesthesia must be carefully evaluated in the design of in vivo neuroimaging and interpretation of data.

Background: Muscarinic acetylcholine receptor 4 (M4) modulates dopaminergic neurotransmission and is a target for novel treatments of schizophrenia, cognitive deficits, and addiction. Impulsive and compulsive behaviors are key traits of addiction, yet the importance of M4 receptor signaling to these traits is poorly understood. We investigated impulsive action and compulsivity by measuring premature and perseverative responses in the five choice serial reaction time task (5CSRTT). Furthermore, we hypothesized that inter-trial interval (ITI) initiation settings affected training durations and test performances in these experiments. Methods: M4 -/- and wildtype mice were trained and tested on two versions of the 5CSRTT with different ITI initiation settings. One setting, the head-in condition, allowed the ITI to start while the mouse's head remained in the reward receptacle (magazine). The other setting, the head-out condition, required the mouse to remove its head from the magazine to initiate the ITI. Results and discussion: We did not observe differences in premature or perseverative responses in M4 -/- mice in either condition, but found evidence of reward-related compulsive behavior in M4 -/- mice. In the head-in condition, M4 -/- mice were slower to acquire the 5CSRTT, had more omissions, and had longer correct response latencies than wildtype mice. In the head-out condition, genotypes did not differ in training, but M4 -/- mice showed small decreases in accuracy. Our findings demonstrate that ITI initiation settings contribute to different training durations and tested behaviors in M4 -/- mice, suggesting ITI initiation settings are an important consideration for the general use of the 5CSRTT.

Medical residents in difficulty struggle to comply with educational requirements. They pose a liability to patient safety and they have problems to adapt to the professional role of a doctor. Consequently, being a resident in difficulty may cause identity crisis and have the potential to disrupt the resident’s professional identity as a doctor. Only few studies explore the tipping point between becoming a resident in difficulty or not, and these studies rarely reflect the surrounding sociocultural aspects of the residents’ difficulties such as organisational culture in the workplace. This article explores how medical residency training culture influence on residents’ risk of ending in difficulty. Our study was based on six focus-group interviews with residents (n=28) and in-depth interviews with residents in difficulty (n=10). The interpretation of data employed sociologist Pierre Bourdieu’s theoretical framework around dispositions. Across the data, we identified four themes: Conflicting games in the field of medical education, altruism, organisational hierarchy, and coping with stress. We found a (mis)match between legitimate rules in the field of medicine and the residents’ dispositions to appreciate those rules. These results can inform clinical supervisors and consultants in their decisions for supporting residents in difficulty and increasing educational achievement among struggling residents. Medical residents in difficulty struggle to comply with educational requirements. They pose a liability to patient safety and they have problems to adapt to the professional role of a doctor. Consequently, being a resident in difficulty may cause identity crisis and have the potential to disrupt the resident’s professional identity as a doctor. Only few studies explore the tipping point between becoming a resident in difficulty or not, and these studies rarely reflect the surrounding sociocultural aspects of the residents’ difficulties such as organisational culture in the workplace. This article explores how medical residency training culture influence on residents’ risk of ending in difficulty. Our study was based on six focus-group interviews with residents (n=28) and in-depth interviews with residents in difficulty (n=10). The interpretation of data employed sociologist Pierre Bourdieu’s theoretical framework around dispositions. Across the data, we identified four themes: Conflicting games in the field of medical education, altruism, organisational hierarchy, and coping with stress. We found a (mis)match between legitimate rules in the field of medicine and the residents’ dispositions to appreciate those rules. These results can inform clinical supervisors and consultants in their decisions for supporting residents in difficulty and increasing educational achievement among struggling residents.