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.

This article offers a unified approach for studying political violence whether it emerges as repression or civil war. We formulate a model where an incumbent or opposition can use violence to maintain or acquire power to study which political and economic factors drive one-sided or two-sided violence (repression or civil war). The model predicts a hierarchy of violence states from peace via repression to civil war; and suggests a natural empirical approach. Exploiting only within-country variation in the data, we show that violence is associated with shocks that can affect wages and aid. As in the theory, these effects are only present where political institutions are noncohesive.

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.

There is growing understanding that the environment plays an important role both in the transmission of antibiotic resistant pathogens and in their evolution. Accordingly, researchers and stakeholders world-wide seek to further explore the mechanisms and drivers involved, quantify risks and identify suitable interventions. There is a clear value in establishing research needs and coordinating efforts within and across nations in order to best tackle this global challenge. At an international workshop in late September 2017, scientists from 14 countries with expertise on the environmental dimensions of antibiotic resistance gathered to define critical knowledge gaps. Four key areas were identified where research is urgently needed: 1) the relative contributions of different sources of antibiotics and antibiotic resistant bacteria into the environment; 2) the role of the environment, and particularly anthropogenic inputs, in the evolution of resistance; 3) the overall human and animal health impacts caused by exposure to environmental resistant bacteria; and 4) the efficacy and feasibility of different technological, social, economic and behavioral interventions to mitigate environmental antibiotic resistance. 1

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.

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.

BACKGROUND: The efficacy of antireflux surgery (ARS) and proton pump inhibitor therapy in the control of gastroesophageal reflux disease is well established. A direct comparison between these therapies is warranted to assess the benefits of respective therapies. STUDY DESIGN: There were 310 patients with erosive esophagitis enrolled in the trial. There were 155 patients randomized to continuous omeprazole therapy and 155 to open antireflux surgery, of whom 144 later had an operation. Because of various withdrawals during the study course, 122 patients originally having an antireflux operation completed the 5-year followup; the corresponding figure in the omeprazole group was 133. Symptoms, endoscopy, and quality-of-life questionnaires were used to document clinical outcomes. Treatment failure was defined to occur if at least one of the following criteria were fulfilled: Moderate or severe heartburn or acid regurgitation during the last 7 days before the respective visit; Esophagitis of at least grade 2; Moderate or severe dysphagia or odynophagia symptoms reported in combination with mild heartburn or regurgitation; If randomized to surgery and subsequently required omeprazole for more than 8 weeks to control symptoms, or having a reoperation; If randomized to omeprazole and considered by the responsible physician to require antireflux surgery to control symptoms; If randomized to omeprazole and the patient, for any reason, preferred antireflux surgery during the course of the study. Treatment failure was the primary outcomes variable. RESULTS: When the time to treatment failure was analyzed by use of the intention to treat approach, applying the life table analysis technique, a highly significant difference between the two strategies was revealed (p < 0.001), with more treatment failures in patients who originally were randomized to omeprazole treatment. The protocol also allowed dose adjustment in patients allocated to omeprazole therapy to either 40 or 60 mg daily in case of symptom recurrence. The curves subsequently describing the failure rates still remained separated in favor of surgery, although the difference did not reach statistical significance (p = 0.088). Quality of life assessment revealed values within normal ranges in both therapy arms during the 5 years. CONCLUSIONS: In this randomized multicenter trial with a 5-year followup, we found antireflux surgery to be more effective than omeprazole in controlling gastroesophageal reflux disease as measured by the treatment failure rates. But if the dose of omeprazole was adjusted in case of relapse, the two therapeutic strategies reached levels of efficacy that were not statistically different.

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 identify ethnic differences in the incidence of first ever stroke. DESIGN: A prospective community stroke register (1995-6) with multiple notification sources. Pathological classification of stroke in all cases was based on brain imaging or necropsy data. Rates were standardised to European and world populations and adjusted for age, sex, and social class in multivariate analysis. SETTING: A multi-ethnic population of 234 533 in south London, of whom 21% are black. RESULTS: 612 strokes were registered. The crude annual incidence rate was 1.3 strokes per 1000 population per year (95% confidence interval 1.20 to 1.41) and 1.25 per 1000 population per year (1.15 to 1.35) age adjusted to the standard European population. Incidence rates adjusted for age and sex were significantly higher in black compared with white people (P<0.0001), with an incidence rate ratio of 2.21 (1.77 to 2.76). In multivariable analysis increasing age (P<0.0001), male sex (P<0.003), black ethnic group (P<0.0001), and lower social class (P<0.0001) in people aged 35-64 were independently associated with an increased incidence of stroke. CONCLUSIONS: Incidence rates of stroke are higher in the black population; this is not explained by confounders such as social class, age, and sex. Ethnic differences in genetic, physiological, and behavioural risk factors for stroke require further elucidation to aid development of effective strategies for stroke prevention in multi-ethnic communities.

Fifty-seven patients, all over the age of 64, with femoral neck fracture were randomized to receive epidural or halothane anesthesia to see if the anesthetic technique influenced the incidence of postoperative confusion. All patients were lucid on admission. Using the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-III) as criteria for confusion, we found that 44% of the patients developed confusion that correlated closely to a history of mental depression (P < 0.01) and to the use of drugs with anticholinergic effect (P < 0.005). There was no difference in the incidence of confusion between the two anesthetic groups. In patients given halothane, however, early postoperative hypoxemia was associated with confusion (P < 0.05). Patients with confusion had significantly more postoperative complications and almost four times longer hospitalization times. It is concluded that anticholinergic medication and a history of mental depression are predominant risk factors for development of postoperative confusion and in this respect are more important than the anesthetic technique.

In the present epidemiologic study 80 car or industrial spray painters with long-term low level exposure to organic solvents were examined and compared with two matched reference groups of nonexposed industrial workers (80 persons in each group). The aim of the study was to investigate the possible effects of the solvent exposure on health. The investigation included psychiatric interviews, psychometric tests, neurological, neurophysiological and ophthalmologic examinations, and computed tomography of the brain. The painters' previous and present exposure was carefully assessed by interviews and on-the-job measurements both at modern places of work and in a reconstructed model of a workshop from 1955. On the basis of the psychiatric interviews the psychiatric symptoms were rated according to a specially designed scale of 46 different items, graded in seven steps of increasing severity. The psychological performance was assessed by a battery of 18 tests. The neurological and neurophysiological examinations comprised visual evoked responses (VER), electroencephalography (EEG), and computerized EEG analysis (SPA) for the central nervous system and electroneurography (ENeG), the estimation of vibration sense thresholds, and a quantified neurological examination for the peripheral nervous system. The ophthamologic examination concentrated on the condition of the lens. Statistically significant differences between the exposed individuals and referents were found for psychiatric items indicative of a slight cerebral lesion (ie, a neurasthenic syndrome). The psychometric tests revealed statistically significant differences between the groups with respect to reaction time, manual dexterity, perceptual speed, and short-term memory. No differences were found with respect to performance on verbal, spatial, and reasoning tests. Significant differences between the groups were also found for the majority of the neurophysiological parameters measuring peripheral nerve functions, the most pronounced occurring in the long, sensory fibers. Moreover EEG and VER showed some differences between the groups, as did the results of the ophthalmologic examination and the computed tomography. Finally, it should be emphasized that the exposure levels, as measured at modern places of work and in the reconstructed workshop from 1955, were found to be considerably lower than the valid threshold limit values in Sweden.

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.