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The circular economy can be understood as one of the sustainability narratives (along with, e.g., the bioeconomy, the green economy and the sharing economy), currently relevant in academia, business and policymaking. Sustainability narratives are characterized by a distinctive set of transferable and scalable solutions, addressing resource/services use and distribution in social-ecological-technical systems. Core solutions in the circular economy are technologically-driven improvements towards reductions of inputs/outputs in production and consumption systems.However, the conceptual diversity of the circular economy is such that it can, like other sustainability narratives, serve multiple sustainability discourses (e.g., ecological modernization, sustainable development and degrowth). In order to cater to societal needs within the planet’s biophysical boundaries, the contribution of the circular economy needs to be strengthened in regard to the protection of biodiversity and ecosystems and to the just distribution of resources, opportunities and prosperity. Socio-cultural change should be understood as complementary to technology- and private sector-driven solutions. While circular economy principles are meant to be translated into tailored micro- and macro- level strategies based on context-specific characteristics and needs, the causal connections between units or geographical regions are a crucial issue for sustainability. The overall co-evolution and harmonization of multiple narratives towards coherent sustainability pathways should strive towards decreasing dependence on fossil resources, reversing biodiversity loss and ecosystems degradation and enabling a quality life for all people. The conclusions of this article provide key points that can further guide analyses and implementation of the circular economy in the context of sustainability transformations.

In many societies, the majority of adults regularly consume alcohol. However, only a small proportion develops alcohol addiction. Individuals at risk often show a high sensation-seeking/low-anxiety behavioural phenotype. Here we asked which role EF hand domain containing 2 (EFhd2; Swiprosin-1) plays in the control of alcohol addiction-associated behaviours. EFhd2 knockout (KO) mice drink more alcohol than controls and spontaneously escalate their consumption. This coincided with a sensation-seeking and low-anxiety phenotype. A reversal of the behavioural phenotype with β-carboline, an anxiogenic inverse benzodiazepine receptor agonist, normalized alcohol preference in EFhd2 KO mice, demonstrating an EFhd2-driven relationship between personality traits and alcohol preference. These findings were confirmed in a human sample where we observed a positive association of the EFhd2 single-nucleotide polymorphism rs112146896 with lifetime drinking and a negative association with anxiety in healthy adolescents. The lack of EFhd2 reduced extracellular dopamine levels in the brain, but enhanced responses to alcohol. In confirmation, gene expression analysis revealed reduced tyrosine hydroxylase expression and the regulation of genes involved in cortex development, Eomes and Pax6, in EFhd2 KO cortices. These findings were corroborated in Xenopus tadpoles by EFhd2 knockdown. Magnetic resonance imaging (MRI) in mice showed that a lack of EFhd2 reduces cortical volume in adults. Moreover, human MRI confirmed the negative association between lifetime alcohol drinking and superior frontal gyrus volume. We propose that EFhd2 is a conserved resilience factor against alcohol consumption and its escalation, working through Pax6/Eomes. Reduced EFhd2 function induces high-risk personality traits of sensation-seeking/low anxiety associated with enhanced alcohol consumption, which may be related to cortex function.

Objectives: To assess the effectiveness, safety and feasibility of the revised, simplified nurse-managed version of our insulin infusion protocol, adapted to the new recommended glycaemic target of 140 to 180 mg/dL (Desio Diabetes Diagram i.v. 140–180).Methods: All clinical responses to the Desio Diabetes Diagram i.v. 140–180 in use for 3 years were recorded in patients with diabetes or hyperglycaemia admitted to our intensive cardiac care unit. To assess the feasibility, we asked nurses to complete an ad hoc questionnaire anonymously when the new insulin infusion protocol had been in use for 2 years.Results: From December 2010 to December 2013, 276 patients (173 men, median age 75 years) were treated according to the Desio Diabetes Diagram i.v. 140–180. The median time to reach glycaemic target was 4 h (Q1–Q3 2–8) in 128 patients with blood glucose >180 mg/dL and 2 h (Q1–Q3 1–4) in 82 patients with blood glucose <140 mg/dL. Once the target had been reached, insulin infusion was maintained for a median of 38 h (Q1–Q3 24–48) with blood glucose between 140 and 180 mg/dL for 58.3% of the infusion time. Over a total of 11,863 h of infusion, seven blood glucose <70 mg/dL occurred. The Desio Diabetes Diagram i.v. 140–180 protocol was considered easy to use by 93% of nurses.Conclusions: The Desio Diabetes Diagram i.v. 140–180 protocol, fully managed by nurses, with insulin and glucose intravenous infusion proved effective, safe and feasible in maintaining blood glucose between 140 and 180 mg/dL in patients with diabetes or hyperglycaemia admitted to the intensive cardiac care unit for acute cardiac events.

Total hip replacement in patients with Gaucher’s disease with symptomatic osteonecrosis of the femoral head is controversial because of the high early failure rates. We describe four patients who had an uncemented total hip replacement following enzyme replacement therapy for a median of two years and one month (1 to 9.8 years) prior to surgery, and who remained on treatment. At operation, the bone had a normal appearance and consistency. Histopathological examination showed that, compared with previous biopsies of untreated Gaucher’s disease, the Gaucher cell infiltrate had decreased progressively with therapy, being replaced by normal adipose tissue. The surfaces of viable bone beyond the osteonecrotic areas showed osteoblasts, indicating remodelling. In one case acetabular revision was carried out after 11 years and eight months. The three remaining patients had a mean follow-up of six years and four months (3.3 to 12 years). We recommend initiating enzyme replacement therapy at least one to two years prior to total hip replacement to facilitate bone remodelling and to allow implantation of uncemented components in these young patients.

RHESSI is the sixth in the NASA line of Small Explorer (SMEX) missions and the first managed in the Principal Investigator mode, where the PI is responsible for all aspects of the mission except the launch vehicle. RHESSI is designed to investigate particle acceleration and energy release in solar flares, through imaging and spectroscopy of hard X-ray/gamma-ray continua emitted by energetic electrons, and of gamma-ray lines produced by energetic ions. The single instrument consists of an imager, made up of nine bi-grid rotating modulation collimators (RMCs), in front of a spectrometer with nine cryogenically-cooled germanium detectors (GeDs), one behind each RMC. It provides the first high-resolution hard X-ray imaging spectroscopy, the first high-resolution gamma-ray line spectroscopy, and the first imaging above 100 keV including the first imaging of gamma-ray lines. The spatial resolution is as fine as ∼ 2.3 arc sec with a full-Sun (≳ 1°) field of view, and the spectral resolution is ∼ 1–10 keV FWHM over the energy range from soft X-rays (3 keV) to gamma-rays (17 MeV). An automated shutter system allows a wide dynamic range (>107) of flare intensities to be handled without instrument saturation. Data for every photon is stored in a solid-state memory and telemetered to the ground, thus allowing for versatile data analysis keyed to specific science objectives. The spin-stabilized (∼ 15 rpm) spacecraft is Sun-pointing to within ∼ 0.2° and operates autonomously. RHESSI was launched on 5 February 2002, into a nearly circular, 38° inclination, 600-km altitude orbit and began observations a week later. The mission is operated from Berkeley using a dedicated 11-m antenna for telemetry reception and command uplinks. All data and analysis software are made freely and immediately available to the scientific community.

The Transition Region and Coronal Explorer (TRACE) satellite, launched 2 April 1998, is a NASA Small Explorer (SMEX) that images the solar photosphere, transition region and corona with unprecedented spatial resolution and temporal continuity. To provide continuous coverage of solar phenomena, TRACE is located in a sun-synchronous polar orbit. The ∼700 Mbytes of data which are collected daily are made available for unrestricted use within a few days of observation. The instrument features a 30-cm Cassegrain telescope with a field of view of 8.5×.5 arc min and a spatial resolution of 1 arc sec (0.5 arc sec pixels). TRACE contains multilayer optics and a lumogen-coated CCD detector to record three EUV wavelengths and several UV wavelengths. It observes plasmas at selected temperatures from 6000 K to 10 MK with a typical temporal resolution of less than 1 min.

Southeast Asian ovalocytosis (SAO) is an asymptomatic trait characterized by rigid, poorly deformable red cells that resist invasion by several strains of malaria parasites. The underlying molecular genetic defect involves simple heterozygous state for a mutant band 3 protein, which contains a deletion of amino acids 400 through 408, linked with a Lys 56-to-Glu substitution (band 3-Memphis polymorphism). To elucidate the contribution of the mutant SAO band 3 protein to increased SAO red blood cell (RBC) rigidity, we examined the participation of the mutant SAO band 3 protein in increased band 3 attachment to the skeleton and band 3 oligomerization. We found first that SAO RBC skeletons retained more band 3 than normal cells and that this increased retention preferentially involved the mutant SAO band 3 protein. Second, SAO RBCs contained a higher percentage of band 3 oligomer-ankyrin complexes than normal cells, and these oligomers were preferentially enriched by the mutant SAO protein. At the ultrastructural level, the increased oligomer formation of SAO RBCs was reflected by stacking of band 3-containing intramembrane particles (IMP) into longitudinal strands. The IMP stacking was not reversed by treating SAO RBCs in alkaline pH (pH 11), which is known to weaken ankyrin-band 3 interactions, or by removing the cytoplasmic domain of band 3 from SAO membranes with trypsin. Finally, we found that band 3 protein in intact SAO RBCs exhibited a markedly decreased rotational mobility, presumably reflecting the increased oligomerization and the membrane skeletal association of the SAO band 3 protein. We propose that the mutant SAO band 3 has an increased propensity to form oligomers, which appear as longitudinal strands of IMP and exhibit increased association with membrane skeleton. This band 3 oligomerization underlies the increase in membrane rigidity by precluding membrane skeletal extension, which is necessary for membrane deformation.

We evaluated whether type of response to the migraine-induction test with a nitroglycerin ointment applied to the frontotemporal head region could predict the efficacy of antimigraine therapy. Forty-two patients with migraine without aura underwent the test before and 2 months after antimigraine therapy. Two and 4 months after treatment withdrawal, most subjects with a negative response to the post-treatment test maintained treatment benefit, whereas benefit was lost in patients with an early onset migraine response.

Hereditary ovalocytosis in Papua New Guinea is restricted to areas of endemic malaria and may confer increased resistance to the disease. The incidence of malaria was investigated in 1616 Melanesians of known red cell morphology and severity of infection determined in a smaller subsample. Ovalocytics tended to be more resistant to severe malarial infections than normocytics. The ratio of parasitaemia in 112 ovalocytics compared with 741 normocytic children was 1.05 for P. falciparum; 0.90 for P.vivax; 0.54 for P. malariae, and 0.91 for infection with any species. The difficulties in conclusively demonstrating any selective advantage of the condition are discussed.

Among 63 patients with intermediate or high grade non Hodgkin's lymphoma (NHL) seen at our institution in a five-year period, 19 were aged 70 years or older. For various reasons, four of these patients were either not treated or received only minimal treatment. Three of the patients remain well without evidence of disease for 1 to 3 years, and the fourth has relapsed in an indolent fashion after 3 years. These observations suggest that existence of a subset of patients with histologically aggressive non-Hodgkin's lymphoma whose disease behaves mildly. Because of the high incidence of treatment-related morbidity and mortality in elderly lymphoma patients treated with combination chemotherapy, it is important to try to identify prospectively this subset of patients clinically and to avoid overtreatment in this category of cases.

We have studied the behavior in culture of circulating restricted hemopoietic progenitor cells from patients with idiopathic myelofibrosis (IMF), polycythemia vera (PV), and essential thrombocytopenia (ET). We have found differences in circulating granulocyte-macrophage, erythroid, and megakaryocytic progenitors that appear to be specific for these chronic myeloproliferative disorders. In IMF, most affected were granulocyte-macrophage progenitor cells (CFU-C), which circulated in increased numbers and were heterogeneous in their sensitivity to the regulatory factor(s) present in phytohemagglutinin (PHA) stimulated T-lymphocyte conditioned medium (CM). Most CFU-C were either highly sensitive to, or independent from, stimulatory factors, while others showed normal sensitivity. In some IMF patients, circulating megakaryocytic progenitors (CFU-M) were present that were capable of giving rise to colonies in the absence of added CM or erythropoietin (EPO). In PV, we confirmed the presence of circulating erythroid progenitor cells that give rise to colonies in culture without the addition of EPO. The number of circulating CFU-C was normal and they responded normally to CM. In ET, failure to detect 7-day circulating restricted progenitor cells was a common observation; the level of other circulating restricted progenitors was in the low normal range. Thus, despite certain common features, including a primary lesion at the level of the pluripotential hemopoietic stem cell, the myeloproliferative disorders differ with respect to the behavior in culture of their circulating restricted progenitor cells. These results have led us to postulate a second regulatory lesion in the pluripotential stem cell that differs in these disorders and is expressed at the level of the respective restricted progenitor cells.

The treatment of chronic psychophysiological insomnia presents a challenge that has not been met using currently available pharmacotherapy. Low energy emission therapy (LEET) has been developed as a potential alternative therapy for this disorder. LEET consists of amplitude-modulated electromagnetic fields delivered intrabuccally by means of an electrically conducting mouthpiece in direct contact with the oral mucosa. The effect of LEET on chronic psychophysiological insomnia was assessed with polysomnography (PSG) and sleep rating forms on a total of 106 patients at two different centers. Active or inactive LEET was administered for 20 minutes in late afternoon three times a week for a total of 12 treatments. Primary efficacy endpoints evaluating the results were changes from baseline in PSG-assessed total sleep time (TST) and sleep latency (SL). Secondary endpoints were changes in sleep efficiency (SE), sleep stages, and reports by the subjects of SL and TST. There was a significant increase in TST as assessed by PSG between baseline and post-treatment values for the active treatment group (76.0 +/- 11.1 minutes, p = 0.0001). The increase for the inactive treatment group was not statistically significant. The TST improvement was significantly greater for the active group when compared to the inactive group (adjusted for baseline TST; p = 0.020. R1 = 0.20). There was a significant decrease in SL as assessed by PSG between baseline and post-treatment values for the active treatment group (-21.6 +/- 5.9 minutes, p = 0.0006), whereas the decrease noted for the inactive treatment group was not statistically significant. The difference in SL decrease between the two treatment groups was marginally significant (adjusted for baseline SL and center, p = 0.068, R2 = 0.60). The number of sleep cycles per night increased by 30% after active treatment (p = 0.0001) but was unchanged following inactive treatment. Subjects did not experience rebound insomnia, and there were no significant side effects. The data presented in this report indicate that LEET administered for 20 minutes three times a week increased TST and reduced SL in chronic psychophysiological insomnia. LEET is safe and well tolerated and it effectively improved the sleep of chronic insomniacs given 12 treatments over a 4-week period by increasing the number of sleep cycles without altering the percentage of the various sleep stages during the night. The therapeutic action of LEET differs from that of currently available drug therapies in that the sleep pattern noted in insomniacs following LEET treatment more closely resembles nocturnal physiological sleep. This novel treatment may offer an attractive alternative therapy for chronic insomnia.

The pathogenesis of the granulopoietic failure in three children with severe congenital neutropenia was studied. Mature neutrophils were absent from both peripheral blood and bone marrow. Assay of bone marrow granulocyte colony-forming cells (CFU-C) in a methylcellulose tissue culture system using colony-stimulating activity (CSA) from peripheral blood leukocytes demonstrated normal or increased concentrations of CFU- C compared to those from marrows of 60 age-matched controls. Colonies were of normal size and by light microscopy appeared to contain granulocytes in all stages of maturation including the mature polymorphonuclear neutrophil. CFU-C from peripheral blood of two patients were normal. Production and activity of CSA from the patients' peripheral blood leukocytes and urinary CSA excretion were normal. No serum inhibitors against CFU-C or CSA could be demonstrated using both control and autologous marrow. The defect did not appear to be due to a lack of granulocytic stem cells, a reduction of humoral stimulators of granulopoiesis, nor the presence of an inhibitor as measured by these techniques.

We have studied the behavior in culture of circulating restricted hemopoietic progenitor cells from patients with idiopathic myelofibrosis (IMF), polycythemia vera (PV), and essential thrombocytopenia (ET). We have found differences in circulating granulocyte-macrophage, erythroid, and megakaryocytic progenitors that appear to be specific for these chronic myeloproliferative disorders. In IMF, most affected were granulocyte-macrophage progenitor cells (CFU- C), which circulated in increased numbers and were heterogeneous in their sensitivity to the regulatory factor(s) present in phytohemagglutinin (PHA) stimulated T-lymphocyte conditioned medium (CM). Most CFU-C were either highly sensitive to, or independent from, stimulatory factors, while others showed normal sensitivity. In some IMF patients, circulating megakaryocytic progenitors (CFU-M) were present that were capable of giving rise to colonies in the absence of added CM or erythropoietin (EPO). In PV, we confirmed the presence of circulating erythroid progenitor cells that give rise to colonies in culture without the addition of EPO. The number of circulating CFU-C was normal and they responded normally to CM. In ET, failure to detect 7-day circulating restricted progenitor cells was a common observation; the level of other circulating restricted progenitors was in the low normal range. Thus, despite certain common features, including a primary lesion at the level of the pluripotential hemopoietic stem cell, the myeloproliferative disorders differ with respect to the behavior in culture of their circulating restricted progenitor cells. These results have led us to postulate a second regulatory lesion in the pluripotential stem cell that differs in these disorders and is expressed at the level of the respective restricted progenitor cells.

Southeast Asian ovalocytosis (SAO) is a hereditary condition that is widespread in parts of Southeast Asia. The ovalocytic erythrocytes are rigid and resistant to invasion by various malarial parasites. We have previously found that the underlying defect in SAO involves band 3 protein, the major transmembrane protein, which has abnormal structure and function. We now report two linked mutations in the erythrocyte band 3 gene in SAO: (i) a deletion of codons 400-408 and (ii) a substitution, A----G, in the first base of codon 56 leading to substitution of Lys-56 by Glu-56. The first defect leads to a deletion of nine amino acids in the boundary of cytoplasmic and membrane domains of band 3. This defect has been detected in all 30 ovalocytic subjects from Malaysia, the Philippines, and two unrelated coastal regions of Papua New Guinea, whereas it was absent in all 30 controls from Southeast Asia and 20 subjects of different ethnic origin from the United States. The Lys-56----Glu substitution has likewise been found in all SAO subjects. However, it has also been detected in 5 of the 50 control subjects, suggesting that it represents a linked polymorphism. We conclude that the deletion of codons 400-408 in the band 3 gene constitutes the underlying molecular defect in SAO.

Abstract: Low energy emission therapy (LEET) is a novel approach to delivering low levels of amplitude-modulated electromagnetic fields to the human brain. The sleep electroencephalogram (EEG) effects of a 15-min LEET treatment were investigated in a double-find cross-over study to assess sleep induction. Fifty-two healthy volunteers were exposed to both active and inactive LEET treatment sessions, with a minimum interval of 1 week between the two sessions. Baseline EEGs were obtained, and 15-min posttreatment EEGs were recorded and analyzed according to the Loomis classification. A significant increase in the duration of stage B1 sleep (0.58�2.42 min [mean�SD],p=0.046), decreased latency to the first 10 sec epoch of sleep (−1.23�5.32 min,p=0.051) and decreased latency to sleep stage B2 (−1.21�5.25 min,p=0.052) were observed after active treatment. Additionally, establishment of slow waves with progression from stages B to C was significantly more pronounced after active LEET treatment (p=0.040). A combined analysis of these results with those of an identical study performed in Denver showed that LEET had a significant effect on afternoon sleep induction and maintenance with shorter sleep latencies (decreased latency to the first 10 sec epoch of sleep; −1.00�5.51 min,p=0.033; decreased latency to sleep stage B2; −1.49�5.40 min,p=0.003), an increased duration of stage B2 (0.67�2.50 min,p=0.003), an increase in the total duration of sleep (0.69�4.21 min,p=0.049), and a more prominent establishment of slow waves with progression to a deeper sleep stage (p=0.006). It is concluded that the intermittent 42.7 HZ amplitude modulation of 27.12-MHz electromagnetic fields results in EEG changes consistent with shorter sleep latencies, longer sleep duration, and deeper sleep in healthy subjects.

Cell suspensions from human and mouse bone marrow, heterogeneous with respect to size, were physically separated by a technique of velocity sedimentation at unit gravity. Fractions were collected, cell counts performed, and a sedimentation "profile" obtained. Fractions were assayed in culture for response to phytohemagglutinin and to allogeneic irradiated leukocytes. The peak activity in these assays occurred in fractions taken from the region of small, slowly sedimenting, nucleated cells, which in humans have an average sedimentation velocity at 4°C of approximately 3.5 mm/hr. The results suggest that velocity sedimentation can be used to separate human stem cells from cells that cause graft-vs.-host disease.

Cell suspensions from human and mouse bone marrow, heterogeneous with respect to size, were physically separated by a technique of velocity sedimentation at unit gravity. Fractions were collected, cell counts performed, and a sedimentation “profile” obtained. Fractions were assayed in culture for response to phytohemagglutinin and to allogeneic irradiated leukocytes. The peak activity in these assays occurred in fractions taken from the region of small, slowly sedimenting, nucleated cells, which in humans have an average sedimentation velocity at 4°C of approximately 3.5 mm/hr. The results suggest that velocity sedimentation can be used to separate human stem cells from cells that cause graft-vs- host disease.

A 48-year-old woman presented with chronic myeloid leukemia six years after beginning repeated radioiodine treatments for papillary carcinoma of the thyroid gland. The literature on the association of radioiodine and chronic myeloid leukemia is reviewed.