Anatomy and resilience of the global production ecosystem.

Much of the Earth's biosphere has been appropriated for the production of harvestable biomass in the form of food, fuel and fibre. Here we show that the simplification and intensification of these systems and their growing connection to international markets has yielded a global production ecosystem that is homogenous, highly connected and characterized by weakened internal feedbacks. We argue that these features converge to yield high and predictable supplies of biomass in the short term, but create conditions for novel and pervasive risks to emerge and interact in the longer term. Steering the global production ecosystem towards a sustainable trajectory will require the redirection of finance, increased transparency and traceability in supply chains, and the participation of a multitude of players, including integrated 'keystone actors' such as multinational corporations.

From resilience thinking to Resilience Planning: Lessons from practice.

Resilience thinking has frequently been proposed as an alternative to conventional natural resource management, but there are few studies of its applications in real-world settings. To address this gap, we synthesized experiences from practitioners that have applied a resilience thinking approach to strategic planning, called Resilience Planning, in regional natural resource management organizations in Australia. This case represents one of the most extensive and long-term applications of resilience thinking in the world today. We conducted semi-structured interviews with Resilience Planning practitioners from nine organizations and reviewed strategic planning documents to investigate: 1) the key contributions of the approach to their existing strategic planning, and 2) what enabled and hindered the practitioners in applying and embedding the new approach in their organizations. Our results reveal that Resilience Planning contributed to developing a social-ecological systems perspective, more adaptive and collaborative approaches to planning, and that it clarified management goals of desirable resource conditions. Applying Resilience Planning required translating resilience thinking to practice in each unique circumstance, while simultaneously creating support among staff, and engaging external actors. Embedding Resilience Planning within organizations implied starting and maintaining longer-term change processes that required sustained multi-level organizational support. We conclude by identifying four lessons for successfully applying and embedding resilience practice in an organization: 1) to connect internal "entrepreneurs" to "interpreters" and "networkers" who work across organizations, 2) to assess the opportunity context for resilience practice, 3) to ensure that resilience practice is a learning process that engages internal and external actors, and 4) to develop reflective strategies for managing complexity and uncertainty.

A framework for planning of sustainable water and sanitation systems in peri-urban areas.

There are billions of people around the world that lack access to safe water supply and basic sanitation, a situation which puts the affected in severe health conditions as well as economical and social despair. Many of those lacking adequate water supply and sanitation systems can be found at the fringe of the cities in so called peri-urban areas, especially in the developing world. Planning in these areas is highly complex due to challenging environmental and physical conditions, high population density and unclear institutional boundaries. This article presents a framework aiming to support the planning process for sustainable water and sanitation systems in peri-urban areas. The suggested framework is based on different available planning approaches from a review of literature and websites of organisations and companies. It consists of a recommendation of important steps in the planning process as well as supporting tools. Further, it incorporates a set of sustainability criteria important for the peri-urban context and allows for the development of site specific systems. The framework has the aim to be flexible for different planning situations, and for suiting planners with different perspectives and amount of resources.

Environmental assessment and cost estimation of drinking water and wastewater systems for transition areas in Sweden.

In the Stockholm region there are around 90,000 households with single systems. These households cause larger phosphorus flows to the Baltic Sea than the 1.8 million people connected to four advanced large-scale treatment plants in the same region. According to city plans, some of these areas with on-site systems in transition to permanent living shall be connected to central systems. The problem is however that this sewer system will take decades to complete. It is also not ensured whether or not all peripheral areas with on-site systems could be connected to the central systems. To help support environmental decisions for the selection of wastewater systems for these areas, an Excel-based model has been developed where the cost for the systems can be assessed and evaluated in relation to their environmental impact. The model deals with two types of environmental issues: substance flow analysis and energy analysis. The cost part considers investigations, investments, design, operation, maintenance and supervision, and calculates total annual cost for the water and wastewater system per person.

Isosorbide mononitrate induces increased cervical expression of cyclooxygenase-2, but not of cyclooxygenase-1, at term.

OBJECTIVE: Prostaglandin and nitric oxide (NO) are both known to be involved in cervical ripening at term. The aim of the study was to investigate if NO has an effect on cervical expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), the two main isoenzymes involved in prostaglandin synthesis, and to localize these enzymes within the cervix. STUDY DESIGN: Women with an unripe cervix scheduled for elective caesarean section at term were randomly selected to receive vaginally either the NO donor isosorbide mononitrate (IMN) or placebo 4h before surgery. At the operating theatre, cervical tissue specimens were obtained for immunoblotting and immunohistochemistry. RESULTS: Increased expression of COX-2 was found in specimens exposed to IMN compared to specimens obtained from women in the placebo group. There was no difference in the expression of COX-1. Immunohistochemistry revealed similar localization of the two enzymes in treated and untreated women. CONCLUSIONS: Vaginal administration of IMN induces increased cervical expression of COX-2, but not of COX-1. This pathway may be of importance in the process of cervical ripening at term.

Removal of micro-organisms in a small-scale hydroponics wastewater treatment system.

AIMS: To measure the microbial removal capacity of a small-scale hydroponics wastewater treatment plant. METHODS AND RESULTS: Paired samples were taken from untreated, partly-treated and treated wastewater and analysed for faecal microbial indicators, i.e. coliforms, Escherichia coli, enterococci, Clostridium perfringens spores and somatic coliphages, by culture based methods. Escherichia coli was never detected in effluent water after >5.8-log removal. Enterococci, coliforms, spores and coliphages were removed by 4.5, 4.1, 2.3 and 2.5 log respectively. Most of the removal (60-87%) took place in the latter part of the system because of settling, normal inactivation (retention time 12.7 d) and sand filtration. Time-dependent log-linear removal was shown for spores (k = -0.17 log d(-1), r(2) = 0.99). CONCLUSIONS: Hydroponics wastewater treatment removed micro-organisms satisfactorily. SIGNIFICANCE AND IMPACT OF THE STUDY: Investigations on the microbial removal capacity of hydroponics have only been performed for bacterial indicators. In this study it has been shown that virus and (oo)cyst process indicators were removed and that hydroponics can be an alternative to conventional wastewater treatment.

Involvement of a nitric oxide-cyclic guanosine monophosphate pathway in control of fallopian tube contractility.

Fallopian tube smooth muscle contractions are physiologically related to transport of the ovum within the oviduct. Nitric oxide (NO) has proved to be a mediator of tubal contractility. The main pathway by which NO exerts its relaxing effect on tubal contractions has not been fully elucidated. NO-mediated effects may be cyclic guanosine monophosphate (cGMP)-dependent or cGMP-independent. The objective of the present study was to investigate whether a NO-cGMP pathway is present in the Fallopian tube and, if present, to examine whether this pathway is involved in tubal contractility. Tubal smooth muscle strips were mounted in organ baths for measurement of tissue cGMP and for isometric recording of contractile activity. Following administration of the NO donor spermine NONOate a more than three-fold increase in tissue levels of cGMP was measured. Pretreatment with inhibitors of cGMP production prior to administration of spermine NONOate resulted in similar levels of cGMP as found in strips exposed to only plain buffer solution. Administration of spermine NONOate to muscle baths resulted in a significant inhibition of contractile activity, while pretreatment with inhibitors of cGMP production almost eliminated the relaxing effect of the NO donor. This study showed that a NO-cGMP pathway is present in the Fallopian tube and that the pathway is involved in Fallopian tube contractility.

Gemeprost versus misoprostol for cervical priming before first-trimester abortion: a randomized controlled trial.

OBJECTIVE: To compare the efficacy of 400 microg of misoprostol with that of 1 mg of gemeprost as cervical priming agents when administered vaginally 3 to 4 hours before first-trimester vacuum aspiration abortion. METHODS: In a prospective controlled trial 90 nulliparous women who requested termination of pregnancy before 12 weeks' gestation were randomized to receive vaginally either misoprostol or gemeprost for cervical priming. The force to dilate the cervix was measured by the use of a cervical tonometer connected to Hegar dilators from 3 to 10 mm. The main outcome measures were baseline cervical dilation; the peak force to dilate the cervix at 8, 9, and 10 mm; and the cumulative force to dilate the cervix to 10 mm. RESULTS: Baseline cervical dilation did not differ significantly between the women who received misoprostol and those who were treated with gemeprost. Neither the peak force required to dilate the cervix at 8, 9, and 10 mm nor the cumulative force to dilate the cervix to 10 mm showed any significant difference between the two groups. CONCLUSION: Vaginally administered misoprostol (400 microg) is as effective as gemeprost (1 mg) for cervical priming 3 to 4 hours before surgical termination of first-trimester pregnancies.

A small scale hydroponics wastewater treatment system under Swedish conditions.

A treatment plant using conventional biological treatment combined with hydroponics and microalgae is constructed in a greenhouse in the area of Stockholm, Sweden. The treatment plant is built for research purposes and presently treats 0.559 m3 of domestic wastewater from the surrounding area per day. The system uses anoxic pre-denitrification followed by aerobic tanks for nitrification and plant growth. A microalgal step further reduces phosphorus, and a final sand filter polishes the water. During a three week period in July 2002 the treatment capacity of this system was evaluated with respect to removal of organic matter, phosphorus and nitrogen. 90% COD removal was obtained early in the system. Nitrification and denitrification was well established with total nitrogen reduction of 72%. Phosphorus was removed by 47% in the process. However, higher phosphorus removal values are expected as the microalgal step will be further developed. The results show that acceptable treatment can be achieved using this kind of system. Further optimisation of the system will lead to clean water as well as valuable plants to be harvested from the nutrient rich wastewater.

Nitric oxide induced cervical ripening in the human: Involvement of cyclic guanosine monophosphate, prostaglandin F(2 alpha), and prostaglandin E(2).

OBJECTIVE: The purpose of the study was to investigate possible mechanisms and morphologic changes involved in nitric oxide-induced cervical ripening. STUDY DESIGN: Women scheduled for surgical termination of first trimester pregnancy were randomized to 1 of 3 groups: isosorbide 5-mononitrate 40 mg 4 hours or 10 hours before the operation or no preoperative treatment. Cervical specimens were obtained for the analysis of tissue levels of cyclic guanosine monophosphate, cyclic adenosine monophosphate, cyclo-oxygenase 1, cyclo-oxygenase 2, prostaglandin F(2 alpha), and prostaglandin E(2) or were fixed in glutaraldehyde for microscopy. RESULTS: Increased levels of cyclic guanosine monophosphate, cyclo-oxygenase 2, prostaglandin F(2 alpha), and prostaglandin E(2) were found in samples that were exposed to isosorbide 5-mononitrate compared with control samples. Electron microscopy revealed stromal edema and collagen disorganization after isosorbide 5-mononitrate treatment. CONCLUSION: Cyclic guanosine monophosphate, prostaglandin F(2 alpha), and prostaglandin E(2) are involved in nitric oxide-induced cervical ripening. Nitric oxide causes morphologic changes similar to those changes seen during spontaneous cervical ripening.

Plasma concentrations of nitrate during the menstrual cycle, ovarian stimulation and ovarian hyperstimulation syndrome.

BACKGROUND: Nitric oxide (NO) is predominantly a locally acting mediator, affecting several functions in the human female reproductive tract. In vivo, it is quickly metabolized to its stable end product nitrate, which is cleared by the kidney. METHODS AND RESULTS: The aim of the present study was to evaluate possible fluctuations of plasma nitrate concentrations during the menstrual cycle, ovarian stimulation as well as ovarian hyperstimulation syndrome (OHSS). During the menstrual cycle (n = 19 women) the mean nitrate concentrations were between 26.7 and 29.5 micromol/l at all stages except for the day of ovulation, when the concentrations were significantly (P < 0.001) increased (mean 37.2 micromol/l +/- 2.0). Significantly lower concentrations of plasma nitrate (P < 0.01) were measured at the end of gonadotrophin-releasing hormone (GnRH) down-regulation (24.6 micromol/l +/- 1.4) compared with the concentrations found at day 8 of follicle-stimulating hormone (FSH) stimulation (34.9 micromol/l +/- 2.6) and at the day of human chorionic gonadotrophin (HCG) (35.6 micromol/l +/- 3.3). The concentrations of nitrate (33.4 micromol/l +/- 3.4) in women with OHSS (n = 13) were similar to those seen 5 days after embryo transfer (33.2 micromol/l +/- 2.3). CONCLUSIONS: The results indicate that NO synthesis is increased at the time of spontaneous ovulation. GnRH treatment inhibits NO synthesis, while NO production is not increased in women with OHSS.

The major fluvoxamine metabolite in urine is formed by CYP2D6.

OBJECTIVE: Previous studies have shown that fluvoxamine is metabolized by CYP1A2 and CYP2D6, but there is no information on the impact the various CYP enzymes have on the different metabolic pathways of fluvoxamine biotransformation. The present study was designed to investigate this issue. METHODS: The major fluvoxamine metabolite, the 5-demethoxylated carboxylic acid metabolite, was analyzed in urine from 50 healthy volunteers after intake of a single oral dose of 50 mg fluvoxamine, and the formation clearance for the metabolite (CLm) was calculated. Of the subjects, 28 were non-smoking CYP2D6 and CYP2C19 extensive metabolizers (EMs), 12 were smokers and were thus considered to have an induced CYP1A2 activity, 5 were CYP2D6 poor metabolizers (PMs), and 5 were CYP2C19 PMs. In 11 of the non-smoking EMs, 200 mg caffeine was given at another occasion in order to calculate oral caffeine clearance as a measure of CYP1A2 activity. In addition, CLm was calculated in ten other subjects given increasing doses of fluvoxamine for 4 weeks. RESULTS: Oral clearance of fluvoxamine was significantly higher in smokers, and significantly lower in CYP2D6 PMs than in non-smoking EMs. CLm was 78% lower in CYP2D6 PMs than in the EMs. Smoking and being a CYP2C19 PM did not influence CLm. There was no significant correlation between oral caffeine clearance and CLm. CLm decreased with increasing fluvoxamine dosage, but the decrease in oral clearance was even higher. CONCLUSION: These results indicate that CYP2D6 catalyzes the major metabolic pathway of fluvoxamine, whereas CYP1A2 seems to catalyze other less important pathways. Both the CYP2D6 and the CYP1A2 pathways seem to be saturated in parallel with increasing fluvoxamine dosage.

Nitric oxide synthases in the human cervix at term pregnancy and effects of nitric oxide on cervical smooth muscle contractility.

OBJECTIVE: The purpose of the study was to determine whether a nitric oxide-generating system exists in the uterine cervix at term pregnancy and to study the effects of nitric oxide on contracting cervical strips. STUDY DESIGN: Tissue specimens were obtained from the cervices of women after deliveries and at elective cesarean deliveries. Immunohistochemical techniques and immunoblotting were used to identify isoforms of nitric oxide synthase. The effects of nitric oxide on cervical contractility were examined by the addition of nitroglycerin or spermine NONOate [(Z)-1-(N -[3-aminopropyl]-N -[4-(3-aminopropyl-ammonio)butyl]-amino)-diazen-1-ium-1,2-++ +diolate] to organ baths. RESULTS: Immunohistochemical examination demonstrated positive staining for both endothelial and inducible nitric oxide synthase. Both isoforms of nitric oxide synthase were clearly detectable by immunoblotting. Significant inhibition of contractile activity (10(-7)-10(-5) mol/L) was observed when nitroglycerin or spermine NONOate was administered. CONCLUSION: An endogenous nitric oxide system is present in the uterine cervix at term, and this tissue is responsive to nitric oxide, which causes relaxation of the cervical muscle.

Localization of nitric oxide synthase and effects of nitric oxide donors on the human Fallopian tube.

The objective of the study was to assess the plausible existence of a nitric oxide (NO) system within the human Fallopian tube and to examine the effects of NO on tubal contractility. Tissue was obtained from fertile women at operations due to non-tubal diseases. Production of NO and sites of nitric oxide synthase (NOS) activity were assessed by the use of NADPH diaphorase staining and by immunoblots as well as immunohistochemistry for the isoforms of NOS. Effects of NO on tubal contractility in vitro were examined by adding either of two NO donors (nitroglycerin, spermine NONOate) or an analogue of its second messenger (8-bromo cyclic GMP). The production of NO was indicated by positive NADPH diaphorase staining. In immunoblots, endothelial and inducible NOS were demonstrated in all samples analysed. By immunohistochemistry, moderate staining for endothelial NOS was demonstrated in the luminal epithelial cells and in the endothelial cells of blood vessels. Moderate staining for inducible NO synthase was seen in smooth muscle cells and weak staining in epithelial cells. Nitroglycerin, spermine NONOate and 8-bromo cGMP all resulted in a concentration-dependent inhibition of contractility with significant contractility inhibition at 10(-7) mol/l, 10(-6) mol/l and 10(-5) mol/l respectively. The study demonstrates the existence of an endogenous NO system, which may be of physiological importance in Fallopian tube function.

Nitric oxide-mediated effects on myometrial contractility at term during prelabor and labor.

OBJECTIVE: To assess the existence of a nitric oxide (NO) system in the human myometrium and the effects of mediators of this system on contractile activity in vitro. METHODS: Myometrial tissue was obtained before the onset of labor and during labor at term. Production of NO was assessed by the use of nicotinamide dinucleotide phosphate diaphorase staining and by immunoblots for NO. Effects of NO were examined by adding L-arginine (the substrate for NO synthesis); N(G)-nitro-L-arginine methyl ester (an inhibitor of NO synthase); two NO donors, sodium nitroprusside and spermine NONOate; as well as 8-bromo cyclic guanosine monophosphate (8-bromo cGMP) (a second messenger analogue) to organ baths. RESULTS: Myometrial NO production was indicated by positive nicotinamide adenine dinucleotide phosphate diaphorase staining. Immunoblots detected endothelial NO synthase, whereas only a weak signal for inducible NO synthase was seen. The addition of L-arginine (10(-4)-10(-3) mol/L) did not result in any change of contractility. N(G)-nitro-L-arginine methyl ester (10(-3) mol/L) caused a minor increase of contractility in half of the specimens. Sodium nitroprusside, spermine NONOate, and 8-bromo cGMP resulted in a concentration-dependent inhibition of contractility (10(-7)-10(-6) mol/L for sodium nitroprusside, 10(-6)-10(-5) mol/L for spermine NONOate, and 10(-5)-10(-3) mol/L for 8-bromo cGMP). However, at 10(-5)-10(-4) mol/L, sodium nitroprusside exhibited a dose-dependent increase in the frequency of contractions. Women in prelabor did not differ from those in active labor. CONCLUSION: The myometrium produces NO at term. Nitric oxide inhibits myometrial contractile activity. The responsiveness to NO is similar in nonlaboring and laboring women.

[3H]GBR 12935 binding in platelets from poor and extensive cytochrome P-4502D6 metabolizers.

Previous studies have indicated that part of the binding of [3H] [1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl) piperazine dihydrochloride] ([3H]GBR 12935) to human platelets is to a piperazine acceptor site, which might be associated with cytochrome P-450IID6 (CYP4502D6, debrisoquine-4-hydroxylase). Due to mutant CYP4502D6 alleles, 5-10% of Caucasians are poor metabolizers of CYP4502D6 substrates such as debrisoquine and dextromethorphan. In the present study, possible differences in binding characteristics of [3H]GBR 12935 in platelets from CYP4502D6 poor and extensive metabolizers were investigated. The most prominent finding was a gender difference, with males having significantly higher Kd values than females. There were no differences in Bmax. After correction for gender, there was a tendency towards higher Kd values in poor metabolizers than in extensive metabolizers, although the difference was not statistically significant. Whether this finding corresponds to reduced CYP4502D6 activity is a matter of further investigation.

Nitric oxide mediated inhibition of contractile activity in the human uterine cervix.

Nitric oxide (NO) is an important modulator of contractile activity in various tissues. The aim of the present study was to investigate the possible existence of an NO system within the human uterine cervix and to study the effects of NO on the cervix in early pregnancy. Cervical tissue specimens were obtained from 24 women in connection with first trimester legal abortion. NADPH diaphorase staining was used to identify nitric oxide synthase activity within the cervical tissue. Cylindrical tissue specimens were mounted in organ bath chambers for isometric registration of contractile activity. The presence of a functional NO system in the cervix was investigated by adding either sodium nitroprusside or spermine NONOate, two different NO donors, or 8-bromo cGMP, an analogue of the second messenger cyclic guanosine monophosphate (cGMP), to the organ baths. Positive NADPH diaphorase staining was clearly observed in the walls of blood vessels, in cervical smooth muscle cells, and cells scattered in the connective tissue. The NO donating drugs sodium nitroprusside and spermine NONOate both caused a dose-dependent inhibition of spontaneous contractile activity with significant inhibition at concentrations of 10(-5) and 10(-7) M respectively. Furthermore, the participation of NO in the regulation of cervical contractility was indicated by a significant concentration-dependent inhibition of spontaneous contractions when 8-bromo cGMP (10(-5)-10(-3) M) was added to the organ baths. The study indicates the existence of an NO system within the human uterine cervix and a role of NO in control of cervical function.

Excretion of citalopram in breast milk.

AIMS: The objective of this study was to measure to secretion of the selective serotonin uptake inhibitor citalopram in breast milk. METHODS: The excretion of citalopram in breast milk was studied at steady-state conditions in two patients with depression and in one healthy volunteer after ingestion of a single dose citalopram. RESULTS: Milk/serum concentration ratios based on single pairs of samples from the two patients ranged from 1.16 to 1.88. Based on milk concentration data from the patients, the absolute dose ingested by a suckling infant would be 4.3-17.6 micrograms kg-1 day-1, and the relative dose 0.7-5.9% of the weight-adjusted maternal dose. Based on area-under-the-time-concentration curves from the healthy volunteer, the milk/serum ratio was 1.00, the absolute dose to the infant during steady-state conditions would be 11.2 micrograms kg-1 day-1 and the relative dose 1.8% of the weight-adjusted maternal dose. CONCLUSION: The study shows that the relative dose to a suckling infant is close to that reported for fluoxetine, and higher than reported for fluvoxamine, paroxetine and sertraline.

Carcinoma of the uterine cervix in pregnancy. A study of the incidence and treatment in the western region of Sweden 1973 to 1992.

OBJECTIVE: To review the incidence, treatment and outcome of cervical cancer during pregnancy in the Western region of Sweden. METHODS: Population based data on cervical cancer during pregnancy were collected from 1973 to 1992. RESULTS: Cervical carcinoma was diagnosed in 33 women in association with pregnancy, giving an incidence of 11.1 cases per 100,000 deliveries and 7.5 cases per 100,000 pregnancies. Pregnancy complicated one of every 55 cases of invasive carcinoma. Twelve women were in the 3rd trimester and nine women were post partum. Abnormal bleeding was the symptom that led to examination and diagnosis in 54.5% of the women and 45.5% of the women were asymptomatic but had an abnormal cervico-vaginal cytological test (39.4%) or abnormal finding at vaginal examination (6.1%) in association with pregnancy. In the 1st-2nd trimester all but one woman and in the 3rd trimester all but two women, had a stage I carcinoma. Post partum five women were in stage I, three women were in stage II and one woman had a stage III carcinoma. Histology revealed squamous cell carcinoma in 29 women, adenocarcinoma in three women and adenosquamous carcinoma in one woman. During the follow up period 1/12 women in the 1st trimester, 4/12 in the 3rd trimester and 2/9 women post partum have died of disease. CONCLUSION: During the years of this study different modalities of treatment were used, with a change from primary radiation to primary surgery.