•Sustainable development beyond focus on GDP growth needs to be explored.•Alternative a-growth futures, that fulfil sustainability targets are developed.•The scenarios presented explore four ...different sustainability approaches.•Illustrating options beyond economic growth enables discussion of alternatives.
The idea of continued economic growth is increasingly questioned and critically analysed on the basis of its potential negative sustainability impact. Along with the critique, visions and strategies for alternative systems need also be brought onto the agenda. The aim of this paper is to present the qualitative content of scenarios that explore sustainability strategies for the Swedish society when economic growth is not seen as an end in itself, and instead the objective is other values/targets that society might wish to achieve. Multi-target backcasting scenarios are developed that illustrate future states in which four sustainability targets (climate, land use, participation, and resource security) are to be attained. The focus of these four scenarios is: 1) a Collaborative economy, 2) Local self-sufficiency, 3) Automation for quality of life, and 4) Circular economy in the welfare state. In the paper, we also present the process of the development of the scenarios, and feedback from stakeholders. Although the focus is on Sweden, the process and scenarios may also be relevant for other similar countries. The scenarios are discussed in terms of their relevance and their purpose, the fulfilment of the sustainability targets, and the multi-target approach.
There is a scarcity of data exploring early breast cancer (eBC) in very young patients. We assessed shared and intrinsic prognostic factors in a large cohort of patients aged ≤35, compared to a ...control group aged 36 to 50.
Patients ≤50 were retrospectively identified from a multicentric cohort of 23,134 eBC patients who underwent primary surgery between 1990 and 2014. Multivariate Cox analyses for DFS and OS were built. To assess the independent impact of age, 1 to 3 case-control analysis was performed by matching ≤35 and 36–50 years patients.
Of 6481 patients, 556 were aged ≤35, and 5925 from 36 to 50. Age ≤35 was associated with larger tumors, higher grade, ER-negativity, macroscopic lymph node involvement (pN + macro), lymphovascular invasion (LVI), mastectomy, and chemotherapy (CT) use. In multivariate analysis, age ≤35 was associated with worse DFS HR 1.56, 95% CI 1.32–1.84; p < 0.001, and OS HR 1.29, 95% CI 1.03–1.60; p = 0.025, as were high grade, large tumor, LVI, pN + macro, ER-negativity, period of diagnostic, and absence of ET or CT (for DFS). Adverse prognostic impact of age ≤35 was maintained in the case control-matched analysis for DFS HR 1.56, 95%CI 1.28–1.91, p < 0.001, and OS HR 1.33, 95%CI 1.02–1.73, p = 0.032. When only considering patients ≤35, ER, tumor size, nodal status, and LVI were independently associated with survival in this subgroup.
Age ≤35 is associated with less favorable presentation and more aggressive treatment strategies. Our results support the poor prognosis value of young age, which independently persisted when adjusting for other prognostic factors and treatments.
•Young age is an independent prognostic factor.•Age ≤35 is associated with more severe presentation and more aggressive treatments.•Triple-negative, HER2-positive, and luminal-B subtypes are more common.
Since 1998 the serious public health problem in South East Asia of counterfeit artesunate, containing no or subtherapeutic amounts of the active antimalarial ingredient, has led to deaths from ...untreated malaria, reduced confidence in this vital drug, large economic losses for the legitimate manufacturers, and concerns that artemisinin resistance might be engendered.
With evidence of a deteriorating situation, a group of police, criminal analysts, chemists, palynologists, and health workers collaborated to determine the source of these counterfeits under the auspices of the International Criminal Police Organization (INTERPOL) and the Western Pacific World Health Organization Regional Office. A total of 391 samples of genuine and counterfeit artesunate collected in Vietnam (75), Cambodia (48), Lao PDR (115), Myanmar (Burma) (137) and the Thai/Myanmar border (16), were available for analysis. Sixteen different fake hologram types were identified. High-performance liquid chromatography and/or mass spectrometry confirmed that all specimens thought to be counterfeit (195/391, 49.9%) on the basis of packaging contained no or small quantities of artesunate (up to 12 mg per tablet as opposed to approximately 50 mg per genuine tablet). Chemical analysis demonstrated a wide diversity of wrong active ingredients, including banned pharmaceuticals, such as metamizole, and safrole, a carcinogen, and raw material for manufacture of methylenedioxymethamphetamine ('ecstasy'). Evidence from chemical, mineralogical, biological, and packaging analysis suggested that at least some of the counterfeits were manufactured in southeast People's Republic of China. This evidence prompted the Chinese Government to act quickly against the criminal traders with arrests and seizures.
An international multi-disciplinary group obtained evidence that some of the counterfeit artesunate was manufactured in China, and this prompted a criminal investigation. International cross-disciplinary collaborations may be appropriate in the investigation of other serious counterfeit medicine public health problems elsewhere, but strengthening of international collaborations and forensic and drug regulatory authority capacity will be required.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hormone-activated proteolysis is a recurring theme of plant hormone signaling mechanisms. In strigolactone signaling, the enzyme receptor DWARF14 (D14) and an F-box protein, MORE AXILLARY GROWTH2 ...(MAX2), mark SUPPRESSOR OF MAX2 1-LIKE (SMXL) family proteins SMXL6, SMXL7, and SMXL8 for rapid degradation. Removal of these transcriptional corepressors initiates downstream growth responses. The homologous proteins SMXL3, SMXL4, and SMXL5, however, are resistant to MAX2-mediated degradation. We discovered that the smxl4 smxl5 mutant has enhanced responses to strigolactone. SMXL5 attenuates strigolactone signaling by interfering with AtD14–SMXL7 interactions. SMXL5 interacts with AtD14 and SMXL7, providing two possible ways to inhibit SMXL7 degradation. SMXL5 function is partially dependent on an ethylene-responsive-element binding-factor-associated amphiphilic repression (EAR) motif, which typically mediates interactions with the TOPLESS family of transcriptional corepressors. However, we found that loss of the EAR motif reduces SMXL5–SMXL7 interactions and the attenuation of strigolactone signaling by SMXL5. We hypothesize that integration of SMXL5 into heteromeric SMXL complexes reduces the susceptibility of SMXL6/7/8 proteins to strigolactone-activated degradation and that the EAR motif promotes the formation or stability of these complexes. This mechanism may provide a way to spatially or temporally fine-tune strigolactone signaling through the regulation of SMXL5 expression or translation.
Strigolactones are phytohormones that trigger proteolysis of a subset of growth-regulating proteins in the SMAX1-LIKE (SMXL) family. SMXL5, which is degradation resistant, attenuates strigolactone signaling by inhibiting degradation of strigolactone-targeted proteins. The stabilizing effect of SMXL5 putatively occurs through formation of heteromeric SMXL complexes and is highly dependent on an EAR motif that facilitates interactions with TOPLESS family transcriptional corepressors.
This paper presents the research protocol of the GoveRnance for Equity, EnviroNment and Health in the City (GREENH-City) project funded by the National Institute for Cancer (Subvention ...N°2017-003-INCA). In France, health inequities have tended to increase since the late 1980s. Numerous studies show the influence of social, economic, geographic and political determinants on health inequities across the life course. Exposure to environmental factors is uneven across the population and may impact on health and health inequities. In cities, green spaces contribute to creating healthy settings which may help tackle health inequities. Health in All Policies (HiAP) represents one of the key strategies for addressing social and environmental determinants of health inequities. The objective of this research is to identify the most promising interventions to operationalize the HiAP approaches at the city level to tackle health inequities through urban green spaces. It is a participatory interventional research to analyze public policy in real life setting (WHO Healthy Cities).
It is a mixed method systemic study with a quantitative approach for the 80 cities and a comparative qualitative multiple case-studies of 6 cities. The research combines 3 different lens: 1/a political analysis of how municipalities apply HiAP to reduce social inequities of health through green space policies and interventions 2/a geographical and topological characterization of green spaces and 3/ on-site observations of the use of green spaces by the inhabitants.
City profiles will be identified regarding their HiAP approaches and the extent to which these cities address social inequities in health as part of their green space policy action. The analysis of the transferability of the results will inform policy recommendations in the rest of the Health City Network and widely for the French municipalities.
The study will help identify factors enabling the implementation of the HiAP approach at a municipal level, promoting the development of green spaces policies in urban areas in order to tackle the social inequities in health.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Elderly breast cancer (BC) patients have been underrepresented in clinical trials whereas ~60% of deaths from BC occur in women aged 70 years and older. Only limited data are available on the ...prognostic impact of age according to treatment, especially in the triple-negative (TN) and Her2-positive because of the lower frequency of these subtypes in elderly patients. We report herein the results of a multicenter retrospective study analyzing the prognostic impact of age according to treatment delivered in TN and Her2-positive BC patients of 70 years or older, including comparison by age groups.
The medical records of 31,473 patients treated from January 1991 to December 2018 were retrieved from 13 French cancer centers for retrospective analysis. Our study population included all ≥70 patients with TN or Her2-positive BC treated by upfront surgery. Three age categories were determined: 70-74, 75-80, and > 80 years.
Of 528 patients included, 243 patients were 70-74 years old (46%), 172 were 75-80 years (32.6%) and 113 were >80 years (21.4%). Half the population (51.9%, 274 patients) were TN, 30.1% (159) Her2-positive/hormone receptors (HR)-positive, and, 18% (95) Her2-positive/endocrine receptors (ER)-negative BC. Advanced tumor stage was associated with older age but no other prognostic factors (tumor subtype, tumor grade, LVI). Adjuvant chemotherapy delivery was inversely proportional to age. With 49 months median follow-up, all patient outcomes (overall survival (OS), disease-free survival (DFS), breast cancer-specific survival (BCSS), and recurrence-free survival (RFS)) significantly decreased as age increased. In multivariate analysis, age >80, pT2-3 sizes, axillary macrometastases, lymphovascular involvement, and HR-negativity tumor negatively affected DFS and OS. Comparison between age >80 and <=80 years old showed worse RFS in patients aged > 80 (HR=1.771, p=0.031).
TN and Her2-positive subtypes occur at similar frequency in elderly patients. Older age is associated with more advanced tumor stage presentation. Chemotherapy use decreases with older age without worse other pejorative prognostic factors. Age >80, but not ≤80, independently affected DFS and OS.
Refinements in endoscopic instrumentation, the widespread popularization of endourology and the minimal invasiveness of endoscopic approaches have led to evolving interest in expanding applications ...for their use and now include incision of posterior urethral valves (PUV). We aimed to report our paediatric experience of PUV incision with Holmium:YAG laser updating of the endoscopic technique, how we set parameters for the laser energy and provide some tips and tricks to increase the likelihood of completing treatment.
A monocentric, prospective, continuous series of boys with PUV were treated endoscopically using a Holmium: YAG laser (1.2 J, 20 Hz, 800 μs). Feasibility was evaluated using operative time in minutes, spontaneous normal micturition after bladder catheter removal, and the duration of bladder catheterization in days in the absence of satisfactory micturition. Peri-operative complications were recorded. A VCUG was performed at 6 weeks postoperatively to exclude residual valves.
Since September 2018, 18 children with PUV were included. The median age at the time of endoscopic laser incision was 12 days (1 day-5 years). The median operative duration was 28 min (17–35). The urinary catheter was systematically removed on the first postoperative day. There were no intraoperative or anaesthesia-related complications. More specifically, no urethral injuries and no bleeding were recorded. No incomplete VUP incision was found on follow-up VCUG, and no endoscopic revision was necessary thus far, with a median follow-up of 44 months (6 months–60 months).
The use of the Holmium: YAG laser introduces new perspectives in the treatment of PUV. Its mechanism of action is considered a photothermic effect with a vapourization effect. The laser energy released by the Holmium: YAG source has a short tissue penetration distance and is strongly absorbed in an aqueous environment and therefore limits thermal tissue damage and favours early tissue re-epithelialization, reducing the risk of urethral stricture and decreasing postoperative oedema. The use of the laser in “incision” mode is the setting that most solicits the capacities of the laser (high energy, high frequency, and long pulse). The use of laser energy has the advantage of allowing tissue vapourization while ensuring maximal haemostasis and the possibility of introducing the laser fibre through the working channels of small, 6-Fr paediatric endoscopes.
In our experience, endoscopic PUV incision using the Holmium: YAG laser appears to be a safe and efficient technique.
Abstract Objective To compare the long-term efficacy of Young-Dees bladder neck reconstruction (YDBNR) alone versus YDBNR plus BNI in patients with urinary incontinence caused by urethral sphincter ...insufficiency. Patients and methods Between 1987 and 2006, we assessed the continence rates obtained with YDBNR and BNI as a supplementary treatment for persistent outlet insufficiency in patients with neurogenic bladder (group-1, n = 35) and bladder exstrophy (group-2, n = 20). Median postoperative follow-up was 16 years (range: 5–29). Results A total of 55 children (23 males and 32 females) underwent YDBNR at the median age of 7.6 years (range: 1.9–17.25). Only 10 patients (18%) were considered continent after the isolated YDBNR; 17% (n = 6/35) from group-1 and 20% (n = 4/20) from group-2 (p = 1). Because of unsatisfactory results after YDBNR, 81.8% (n = 45/55) received BNI. Fifteen patients (33%) became continent with an average of 2.29 injections (±1.1); 44.8% (n = 13/29) from group-1 and 12.5% (n = 2/16) from group-2. A significant difference was found on comparing the social continence rate attained with YDBNR plus BNI between patients from group-1 and group-2 (54% versus 30%, p = 0.04). The difference between males and females in terms of continence rates was not statistically significant. Conclusion Long-term results of YDBNR are modest. BNI does bolster up the results of YDBNR, especially in patients with neurogenic bladder.
We present accurate time delays for the quadruply imaged quasar HE 0435-1223. The delays were measured from 575 independent photometric points obtained in the R-band between January 2004 and March ...2010. With seven years of data, we clearly show that quasar image A is affected by strong microlensing variations and that the time delays are best expressed relative to quasar image B. We measured ΔtBC = 7.8 ± 0.8 days, ΔtBD = -6.5 ± 0.7 days and ΔtCD = -14.3 ± 0.8 days. We spacially deconvolved HST NICMOS2 F160W images to derive accurate astrometry of the quasar images and to infer the light profile of the lensing galaxy. We combined these images with a stellar population fitting of a deep VLT spectrum of the lensing galaxy to estimate the baryonic fraction, fb, in the Einstein radius. We measured fb = 0.65-0.10+0.13 if the lensing galaxy has a Salpeter IMF and fb = 0.45-0.07+0.04 if it has a Kroupa IMF. The spectrum also allowed us to estimate the velocity dispersion of the lensing galaxy, σap = 222 ± 34 km s-1. We used fb and σap to constrain an analytical model of the lensing galaxy composed of an Hernquist plus generalized NFW profile. We solved the Jeans equations numerically for the model and explored the parameter space under the additional requirement that the model must predict the correct astrometry for the quasar images. Given the current error bars on fb and σap, we did not constrain H0 yet with high accuracy, i.e., we found a broad range of models with χ2 < 1. However, narrowing this range is possible, provided a better velocity dispersion measurement becomes available. In addition, increasing the depth of the current HST imaging data of HE 0435-1223 will allow us to combine ourconstraints with lens reconstruction techniques that make use of the full Einstein ring that is visible in this object.
Based on observations made with the 1.2 m Euler Swiss Telescope, the 1.5 m telescope of Maidanak Observatory in Uzbekistan, and with the 1.2 m Mercator Telescope, operated on the island of La Palma by the Flemish Community, at the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofísica de Canarias. The NASA/ESA Hubble Space Telescope data was obtained from the data archive at the Space Telescope Science Institute, which is operated by AURA, the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS-5-26555.Light curves are only available at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/536/A53
A global systematic sampling scheme has been developed by the UN FAO and the EC TREES project to estimate rates of deforestation at global or continental levels at intervals of 5 to 10 years. This ...global scheme can be intensified to produce results at the national level. In this paper, using surrogate observations, we compare the deforestation estimates derived from these two levels of sampling intensities (one, the global, for the Brazilian Amazon the other, national, for French Guiana) to estimates derived from the official inventories. We also report the precisions that are achieved due to sampling errors and, in the case of French Guiana, compare such precision with the official inventory precision.
We extract nine sample data sets from the official wall-to-wall deforestation map derived from satellite interpretations produced for the Brazilian Amazon for the year 2002 to 2003. This global sampling scheme estimate gives 2.81 million ha of deforestation (mean from nine simulated replicates) with a standard error of 0.10 million ha. This compares with the full population estimate from the wall-to-wall interpretations of 2.73 million ha deforested, which is within one standard error of our sampling test estimate. The relative difference between the mean estimate from sampling approach and the full population estimate is 3.1%, and the standard error represents 4.0% of the full population estimate.
This global sampling is then intensified to a territorial level with a case study over French Guiana to estimate deforestation between the years 1990 and 2006. For the historical reference period, 1990, Landsat-5 Thematic Mapper data were used. A coverage of SPOT-HRV imagery at 20 m × 20 m resolution acquired at the Cayenne receiving station in French Guiana was used for year 2006.
Our estimates from the intensified global sampling scheme over French Guiana are compared with those produced by the national authority to report on deforestation rates under the Kyoto protocol rules for its overseas department. The latter estimates come from a sample of nearly 17,000 plots analyzed from same spatial imagery acquired between year 1990 and year 2006. This sampling scheme is derived from the traditional forest inventory methods carried out by IFN (Inventaire Forestier National). Our intensified global sampling scheme leads to an estimate of 96,650 ha deforested between 1990 and 2006, which is within the 95% confidence interval of the IFN sampling scheme, which gives an estimate of 91,722 ha, representing a relative difference from the IFN of 5.4%.
These results demonstrate that the intensification of the global sampling scheme can provide forest area change estimates close to those achieved by official forest inventories (<6%), with precisions of between 4% and 7%, although we only estimate errors from sampling, not from the use of surrogate data.
Such methods could be used by developing countries to demonstrate that they are fulfilling requirements for reducing emissions from deforestation in the framework of an REDD (Reducing Emissions from Deforestation in Developing Countries) mechanism under discussion within the United Nations Framework Convention on Climate Change (UNFCCC). Monitoring systems at national levels in tropical countries can also benefit from pan-tropical and regional observations, to ensure consistency between different national monitoring systems.
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