Swedish Research Council

Meeting fundamental human needs while preserving Earth's life support systems will require an accelerated transition toward sustainability. A new field of sustainability science is emerging that seeks to understand the fundamental character of interactions between nature and society and to encourage those interactions along more sustainable trajectories. Such an integrated, place-based science will require new research strategies and institutional innovations to enable them especially in developing countries still separated by deepening divides from mainstream science. Sustainability science needs to be widely discussed in the scientific community, reconnected to the political agenda for sustainable development, and become a major focus for research.

A statistical approach to a posteriori blockmodeling for digraphs and valued digraphs is proposed. The probability model assumes that the vertices of the digraph are partitioned into several unobserved (latent) classes and that the probability distribution of the relation between two vertices depends only on the classes to which they belong. A Bayesian estimator based on Gibbs sampling is proposed. The basic model is not identified, because class labels are arbitrary. The resulting identifiability problems are solved by restricting inference to the posterior distributions of invariant functions of the parameters and the vertex class membership. In addition, models are considered where class labels are identified by prior distributions for the class membership of some of the vertices. The model is illustrated by an example from the social networks literature (Kapferer's tailor shop).

Folke, C., L. Pritchard, F. Berkes, J. Colding, and U. Svedin. 2007. The problem of fit between ecosystems and institutions: ten years later. Ecology and Society 12(1): 30. https://doi.org/10.5751/ES-02064-120130

Treating germ-free mice with short-chain fatty acids (microbial metabolites) partly reversed skeletal muscle impairments. Our results suggest a role for the gut microbiota in regulating skeletal muscle mass and function in mice.

Six cysteine proteinase inhibitors were isolated from human urine by affinity chromatography on insolubilized carboxymethylpapain followed by ion-exchange chromatography and immunosorption. Physicochemical and immunochemical measurements identified one as cystatin A, one as cystatin B, one as cystatin C, one as cystatin S, and one as low molecular weight kininogen. The sixth inhibitor displayed immunochemical cross-reactivity with salivary cystatin S but had a different pI (6.85 versus 4.68) and a different (blocked) N-terminal amino acid. This inhibitor was tentatively designated cystatin SU. The isolated inhibitors accounted for nearly all of the cysteine proteinase inhibitory activity of the urinary pool used as starting material. The enzyme inhibitory properties of the inhibitors were investigated by measuring inhibition and rate constants for their interactions with papain and human cathepsin B. Antisera raised against the inhibitors were used in immunochemical determinations of their concentrations in several biological fluids. The combined enzyme kinetic and concentration data showed that several of the inhibitors have the capacity to play physiologically important roles as cysteine proteinase inhibitors in many biological fluids. Cystatin C had the highest molar concentration of the inhibitors in seminal plasma, cerebrospinal fluid, and milk; cystatin S in saliva and tears; and kininogen in blood plasma, synovial fluid, and amniotic fluid.

Epidural application of autologous nucleus pulposus in pigs, without mechanical nerve root compression, induced a pronounced reduction in nerve conduction velocity in the cauda equina nerve roots after 1-7 days, compared to epidural application of retroperitoneal fat in control experiments. Histologically, the nerve fiber injury was more pronounced after application of nucleus pulposus than after control tissue application. The results demonstrate that nucleus pulposus may induce nerve tissue injury by mechanisms other than mechanical compression. Such mechanisms may be based on direct biochemical effects of nucleus pulposus components on nerve fiber structure and function and microvascular changes including inflammatory reactions in the nerve roots.

BACKGROUND: Tau protein and the 42-amino acid form of beta-amyloid (Abeta42) measured in cerebrospinal fluid (CSF) have been proposed as potential biochemical diagnostic markers for Alzheimer disease. For the introduction of these assays in clinical practice, adequate reference values are of importance. METHODS: CSF samples were obtained from 231 neurologically and psychiatrically healthy individuals, 21-93 years of age, all with a MiniMental State examination score of 28 or above. Standardized ELISAs were used to measure tau and Abeta42 in CSF. Following IFCC recommendations, we used a rank-based method; the 0.90 and 0.10 fractiles were estimated to establish reference values for CSF-tau and CSF-Abeta42, respectively. Putative confounding factors, such as the influence of the passage of proteins from peripheral blood to CSF, influence of dysfunction of the blood-brain barrier, and freezing and thawing of CSF, were investigated. RESULTS: A correlation with age was found for CSF-tau (r = 0.60; P <0.001). Therefore, separate reference values for different age groups were established for CSF-tau: <300 ng/L in the group 21-50 years of age, <450 ng/L in the group 51-70 years of age, and <500 ng/L in the group 71-93 years of age. CSF-Abeta42 did not correlate with age (r = -0.045), and the reference value was set to >500 ng/L. No correlation was found between blood-brain barrier function and CSF-tau or CSF-Abeta42. CONCLUSIONS: These reference values can be applied when using CSF-tau and CSF-Abeta42 in clinical practice.

1. Kinetic experiments suggested the possible existence of at least two different NAD(+)-dependent aldehyde dehydrogenases in rat liver. Distribution studies showed that one enzyme, designated enzyme I, was exclusively localized in the mitochondria and that another enzyme, designated enzyme II, was localized in both the mitochondria and the microsomal fraction. 2. A NADP(+)-dependent enzyme was also found in the mitochondria and the microsomal fraction and it is suggested that this enzyme is identical with enzyme II. 3. The K(m) for acetaldehyde was apparently less than 10mum for enzyme I and 0.9-1.7mm for enzyme II. The K(m) for NAD(+) was similar for both enzymes (20-30mum). The K(m) for NADP(+) was 2-3mm and for acetaldehyde 0.5-0.7mm for the NADP(+)-dependent activity. 4. The NAD(+)-dependent enzymes show pH optima between 9 and 10. The highest activity was found in pyrophosphate buffer for both enzymes. In phosphate buffer there was a striking difference in activity between the two enzymes. Compared with the activity in pyrophosphate buffer, the activity of enzyme II was uninfluenced, whereas the activity of enzyme I was very low. 5. The results are compared with those of earlier investigations on the distribution of aldehyde dehydrogenase and with the results from purified enzymes from different sources.

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Antipsychotics are effective in preventing relapses of schizophrenia, but it is generally believed that their long-term use is harmful for patients' physical well-being. However, there are no long-term studies which have verified this view. This nationwide, register-based cohort study aimed to assess the risk of hospitalization due to physical health problems, as a marker for severe physical morbidity, and the risk of all-cause mortality, as well as of cardiovascular and suicidal death, associated with antipsychotic use in all patients treated for schizophrenia in inpatient care between 1972 and 2014 in Finland (N=62,250), with up to 20 years of follow-up (median: 14.1 years). The use of antipsychotic drugs (i.e., use of any antipsychotic compared with non-use) and the use of specific antipsychotics were investigated, and outcomes were somatic and cardiovascular hospitalization, and all-cause, cardiovascular and suicide death. Hospitalization-based outcomes were analyzed by a within-individual design to eliminate selection bias, comparing use and non-use periods in the same individual by stratified Cox model. Mortality outcomes were assessed by traditional between-individual Cox multivariate models. The adjusted hazard ratios (aHRs) for any somatic hospitalization and cardiovascular hospitalization were 1.00 (95% CI: 0.98-1.03) and 1.00 (95% CI: 0.92-1.07) during use of any antipsychotic compared to non-exposure periods within the same individual. The aHRs were 0.48 (95% CI: 0.46-0.51) for all-cause mortality, 0.62 (95% CI: 0.57-0.67) for cardiovascular mortality, and 0.52 (95% CI: 0.43-0.62) for suicide mortality during use vs. non-use of any antipsychotic. The most beneficial mortality outcome was associated with use of clozapine in terms of all-cause (aHR=0.39, 95% CI: 0.36-0.43), cardiovascular (aHR=0.55, 95% CI: 0.47-0.64) and suicide mortality (aHR=0.21, 95% CI: 0.15-0.29). The cumulative mortality rates during maximum follow-up of 20 years were 46.2% for no antipsychotic use, 25.7% for any antipsychotic use, and 15.6% for clozapine use. These data suggest that long-term antipsychotic use does not increase severe physical morbidity leading to hospitalization, and is associated with substantially decreased mortality, especially among patients treated with clozapine.

ABSTRACT An improved in vitro bioassay method for the measurement of LH activity is presented. The method is based on the assay of testosterone produced by "Leydig cell" preparations from mouse testes in the presence of added gonadotrophin. The method is significantly improved in terms of sensitivity, precision and practicability when compared to the previously described bioassay method employing decapsulated testes from adult mice. The sensitivity of the improved method is 15 μIU for HCG and 50 μIU for HMG. The useful range of the method is 15–260 μIU for HCG and 50–900 μIU for HMG. Using a 3 + 3 point assay design with each dose in quadruplicate, a mean index of precision (λ̅) of 0.044 was obtained in 19 assays. Human FSH, TSH, ACTH, LTH, STH, oxytocin, vasopressin and LHRH preparations did not influence the bioassay method at levels likely to be found in biological samples. A good correlation was found between estimates obtained by the "Leydig cell" method and by the method using decapsulated testes when various HCG and HMG preparations were used. With the proposed method at least 30 samples can be assayed each week by 2 persons, with a marked reduction in cost.

BACKGROUND: Atelectasis, an important cause of impaired gas exchange during general anesthesia, may be eliminated by a vital capacity maneuver. However, it is not clear whether such a maneuver will have a sustained effect. The aim of this study was to determine the impact of gas composition on reappearance of atelectasis and impairment of gas exchange after a vital capacity maneuver. METHODS: A consecutive sample of 12 adults with healthy lungs who were scheduled for elective surgery were studied. Thirty minutes after induction of anesthesia with fentanyl and propofol, the lungs were hyperinflated manually up to an airway pressure of 40 cmH2O. FIO2 was either kept at 0.4 (group 1, n = 6) or changed to 1.0 (group 2, n = 6) during the recruitment maneuver. Atelectasis was assessed by computed tomography. The amount of dense areas was measured at end-expiration in a transverse plane at the base of the lungs. The ventilation-perfusion distributions (VA/Q) were estimated with the multiple inert gas elimination technique. The static compliance of the total respiratory system (Crs) was measured with the flow interruption technique. RESULTS: In group 1 (FIO2 = 0.4), the recruitment maneuver virtually eliminated atelectasis for at least 40 min, reduced shunt (VA/Q < 0.005), and increased at the same time the relative perfusion to poorly ventilated lung units (0.005 < VA/Q < 0.1; mean values are given). The arterial oxygen tension (PaO2) increased from 137 mmHg (18.3 kPa) to 163 mmHg (21.7 kPa; before and 40 min after recruitment, respectively; P = 0.028). In contrast to these findings, atelectasis recurred within 5 min after recruitment in group 2 (FIO2 = 1.0). Comparing the values before and 40 min after recruitment, all parameters of VA/Q were unchanged. In both groups, Crs increased from 57.1/55.0 ml.cmH2O-1 (group 1/group 2) before to 70.1/67.4 ml.cmH2O-1 after the recruitment maneuver. Crs showed a slow decrease thereafter (40 min after recruitment: 61.4/60.0 ml.cmH2O-1), with no difference between the two groups. CONCLUSIONS: The composition of inspiratory gas plays an important role in the recurrence of collapse of previously reexpanded atelectatic lung tissue during general anesthesia in patients with healthy lungs. The reason for the instability of these lung units remains to be established. The change in the amount of atelectasis and shunt appears to be independent of the change in the compliance of the respiratory system.

Abstract Regional blood flow of the cerebral cortex was measured simultaneously with two methods, one being a modification of the discontinuous 85 Krypton clearance method, the other a continuous heat‐clearance method. A correlation could be established between the regional cortical blood flow values obtained with the two methods. It is concluded that the heat‐clearance method can be calibrated by the 85 Krypton method, and that, hence, a combined use of the two methods may be helpful for a quantitative analysis of rapid and transient changes in regional cortical blood flow.

A research project is outlined in which concepts and methods from social psychology and psychophysiology are integrated in the study of human adaptation to underload and overload related to technically advanced work processes. Attempts are made to identify aversive factors in the work process by studying acute stress reactions, e.g., catecholamine excretion, in the course of work and relating these to long term, negative effects on well-being, job satisfaction and health. Data from a pilot study of sawmill workers support the view that machine-paced work characterized by a short work cycle and lack of control over the work process constitutes a threat to health and well being.

OBJECTIVE: To study mortality after appendectomy. SUMMARY BACKGROUND DATA: The management of patients with suspected appendicitis remains controversial, with advocates of early surgery as well as of expectant management. Mortality is not known. METHODS: The authors conducted a complete follow-up of deaths within 30 days after all appendectomies in Sweden (population 8.9 million) during the years 1987 to 1996 (n = 117,424) by register linkage. The case fatality rate (CFR) and the standardized mortality ratio (SMR) were analyzed by discharge diagnosis. RESULTS: The CFR was 2.44 per 1,000 appendectomies. It was strongly related to age (0.31 per 1,000 appendectomies at 0-9 years of age, decreasing to 0.07 at 20-29 years, and reaching 164 among nonagenarians) and diagnosis at surgery (0.8 per 1,000 appendectomies after nonperforated appendicitis, 5.1 after perforated appendicitis, 1.9 after appendectomies for nonsurgical abdominal pain, and 10.0 for those with other diagnoses). The SMR showed a sevenfold excess rate of deaths after appendectomy compared with the general population. The relation to age was less marked (SMR of 44.4 at 0-9 years, decreasing to 2.4 in patients aged 20-29 years. and reaching 8.1 in nonagenarians). The SMR was doubled after perforation compared with nonperforated appendicitis (6.5 and 3.5, respectively). Nonsurgical abdominal pain and other diagnoses were associated with a high excess rate of deaths (9.1 and 14.9, respectively). The most common causes of deaths were appendicitis, ischemic heart diseases and tumors, followed by gastrointestinal diseases. CONCLUSIONS: The CFR after appendectomy is high in elderly patients. The excess rate of death for patients with nonperforated appendicitis and nonsurgical abdominal pain suggests that the deaths may partly be caused by the surgical trauma. Increased diagnostic efforts rather than urgent appendectomy are therefore warranted among frail patients with an equivocal diagnosis of appendicitis.

Around the world, innovative genomic-medicine programs capitalize on singular capabilities arising from local health care systems, cultural or political milieus, and unusual selected risk alleles or disease burdens. Such individual efforts might benefit from the sharing of approaches and lessons learned in other locales. The U.S. National Human Genome Research Institute and the National Academy of Medicine recently brought together 25 of these groups to compare projects, to examine the current state of implementation and desired near-term capabilities, and to identify opportunities for collaboration that promote the responsible practice of genomic medicine. Efforts to coalesce these groups around concrete but compelling signature projects should accelerate the responsible implementation of genomic medicine in efforts to improve clinical care worldwide.

Cerebrospinal fluid (CSF) levels of the indoleamine metabolites, 5‐hydroxyindole‐3‐acetic acid (5‐HIAA) and indole‐3‐acetic acid (IAA) were measured by a specific mass fragmentographic method in 43 depressed psychiatric in‐patients. The mean level of 5‐HIAA was 19.7 ± 7.9 ng per milliliter. The 5‐HIAA concentration was positively correlated to age, and there was a tendency for women to have higher values than men. The distribution of 5‐HIAA concentrations appeared to be bimodal in the 27 patients with a depression of endogenous type. The bimodality could not be explained by differences in age or sex. The mean level of IAA was 6.4 ± 4.1 ng per milliliter. The distribution of IAA was unimodal. The correlation to age was not significant, and there was no sex difference. There was a positive correlation between the concentrations of the two metabolites. Twenty patients were treated with nortriptyline, 50 mg three times daily by mouth. After three weeks treatment, the concentrations of 5‐HIAA and IAA had decreased significantly. The mean decrease was 4.8 and 2.0 ng per milliliter, respectively. The magnitude of the decrease was not cormlated to the plasma level of nortriptyline. The data suggest that endogenous depression is a hiochemically heterogenous disease. There may be a subgroup of patients within the endogenous syndrome where indoleamine metabolism is disturbed. In these patients, treatment with drugs that influence indoleamines more directly than a typical noradrenaline uptake inhibitor like nortriptyline, may lead to better therapeutic results.

Plasma concentrations of indomethacin have been studied in 5 healthy volunteers after single and multiple doses (25 mg intravenously [iv], 25, 50, and 100 mg orally, 100 mg rectally, and 25 mg three times daily [tid]. In 8 other normal subjects and in 5 patients a 50-mg oral dose of indomethacin was given and the indomethacin concentration was followed from 8 to 32 hr after dosing. All analyses were carried out using a new mass fragmentographic method. After oral and rectal doses the plasma decay of indomethacin was biphasic, and the data were interpreted according to a 2-compartment open model. The half-life of the beta-phase varied between 2.6 and 11.2 hr. The volume of distribution ranged from 0.34 to 1.57 L/kg and the plasma clearance from 0.044 to 0.109 L/kg/hr. There was no evidence of dose-dependent elimination. Indomethacin was rapidly and well absorbed after oral dosing with peak plasma concentrations within 2 hr. Comparison with the area under the curve (AUC) after iv dosing indicated complete bioavailability. The AUC after rectal dosing indicated complete bioavailability, but the rate of absorption was slower than after oral administration. Indomethacin, 25 mg three times daily, was also given for 9 days to the same normal subjects; equilibrium concentrations obtained did not differ significantly (p greater than 0.1) from those predicted from single-dose data in the 5 subjects.

Ecological adaptation is of major relevance to speciation and sustainable population management, but the underlying genetic factors are typically hard to study in natural populations due to genetic differentiation caused by natural selection being confounded with genetic drift in subdivided populations. Here, we use whole genome population sequencing of Atlantic and Baltic herring to reveal the underlying genetic architecture at an unprecedented detailed resolution for both adaptation to a new niche environment and timing of reproduction. We identify almost 500 independent loci associated with a recent niche expansion from marine (Atlantic Ocean) to brackish waters (Baltic Sea), and more than 100 independent loci showing genetic differentiation between spring- and autumn-spawning populations irrespective of geographic origin. Our results show that both coding and non-coding changes contribute to adaptation. Haplotype blocks, often spanning multiple genes and maintained by selection, are associated with genetic differentiation.

This paper reviews the evolution of institutional research on performance measurement and management (PMM) in the public sector accounting literature. An assessment of the progress of this research programme is offered in light of some key developments in the broader neo‐institutional sociology (NIS) literature, such as the growing recognition of the role of embedded agency, the need to bridge institutional and rational choice explanations of action and the extension of empirical research across different levels of institutional fields. Some progress has been made in this respect and has contributed to shift the emphasis from a one‐sided focus on institutional effects on PMM, treating institutional pressures as largely exogenous, to recognize its more intricate roles as an outcome of, as well as a medium for, change. However, further research is required into the micro dynamics involved in transforming and reproducing PMM practices at different levels of analysis and how such practices become infused with meanings conditioned by higher‐order institutional logics across various levels of institutional fields. Some research strategies for addressing these issues are outlined.