20,177 research outputs found

    An iterative warping and clustering algorithm to estimate multiple wave-shape functions from a nonstationary oscillatory signal

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    Nonsinusoidal oscillatory signals are everywhere. In practice, the nonsinusoidal oscillatory pattern, modeled as a 1-periodic wave-shape function (WSF), might vary from cycle to cycle. When there are finite different WSFs, s1,…,sKs_1,\ldots,s_K, so that the WSF jumps from one to another suddenly, the different WSFs and jumps encode useful information. We present an iterative warping and clustering algorithm to estimate s1,…,sKs_1,\ldots,s_K from a nonstationary oscillatory signal with time-varying amplitude and frequency, and hence the change points of the WSFs. The algorithm is a novel combination of time-frequency analysis, singular value decomposition entropy and vector spectral clustering. We demonstrate the efficiency of the proposed algorithm with simulated and real signals, including the voice signal, arterial blood pressure, electrocardiogram and accelerometer signal. Moreover, we provide a mathematical justification of the algorithm under the assumption that the amplitude and frequency of the signal are slowly time-varying and there are finite change points that model sudden changes from one wave-shape function to another one.Comment: 39 pages, 11 figure

    Phasing out coal for 2 \ub0C target requires worldwide replication of most ambitious national plans despite security and fairness concerns

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    Ending the use of unabated coal power is a key climate change mitigation measure. However, we do not know how fast it is feasible to phase-out coal on the global scale. Historical experience of individual countries indicates feasible coal phase-out rates, but can these be upscaled to the global level and accelerated by deliberate action? To answer this question, we analyse 72 national coal power phase-out pledges and show that these pledges have diffused to more challenging socio-economic contexts and now cover 17% of the global coal power fleet, but their impact on emissions (up to 4.8 Gt CO2 avoided by 2050) remains small compared to what is needed for achieving Paris climate targets. We also show that the ambition of pledges is similar across countries and broadly in line with historical precedents of coal power decline. While some pledges strengthen over time, up to 10% have been weakened by the energy crisis caused by the Russo-Ukrainian war. We construct scenarios of coal power decline based on empirically-grounded assumptions about future diffusion and ambition of coal phase-out policies. We show that under these assumptions unabated coal power generation in 2022-2050 would be between the median generation in 2 \ub0C-consistent IPCC AR6 pathways and the third quartile in 2.5 \ub0C-consistent pathways. More ambitious coal phase-out scenarios require much stronger effort in Asia than in OECD countries, which raises fairness and equity concerns. The majority of the 1.5 \ub0C- and 2 \ub0C-consistent IPCC pathways envision even more unequal distribution of effort and faster coal power decline in India and China than has ever been historically observed in individual countries or pledged by climate leaders

    A High-resolution Optical Survey of Upper Sco: Evidence for Coevolution of Accretion and Disk Winds

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    Magnetohydrodynamic (MHD) and photoevaporative winds are thought to play an important role in the evolution and dispersal of planet-forming disks. Here, we analyze high-resolution (Δv∼\Delta v \sim 7 kms−1^{-1}) optical spectra from a sample of 115 T Tauri stars in the ∼5−10\sim 5-10 Myr Upper Sco association and focus on the [O I]λ\lambda6300 and Hα\alpha lines to trace disk winds and accretion, respectively. Our sample covers a large range in spectral type and we divide it into Warm (G0-M3) and Cool (later than M3) to facilitate comparison with younger regions. We detect the [O I]λ\lambda6300 line in 45 out of 87 upper sco sources with protoplanetary disks and 32 out of 45 are accreting based on Hα\alpha profiles and equivalent widths. All [O I] λ\lambda6300 Upper Sco profiles have a low-velocity (centroid <−30< -30 kms−1^{-1}, LVC) emission and most (36/45) can be fit by a single Gaussian (SC). The SC distribution of centroid velocities and FWHMs is consistent with MHD disk winds. We also find that the Upper Sco sample follows the same accretion luminosity−-LVC [O I]λ\lambda6300 luminosity relation and the same anti-correlation between SC FWHM and WISE W3-W4 spectral index as the younger samples. These results indicate that accretion and disk winds coevolve and that, as inner disks clear out, wind emission arises further away from the star. Finally, our large spectral range coverage reveals that Cool stars have larger FWHMs normalized by stellar mass than Warm stars indicating that [O I]λ\lambda6300 emission arises closer in towards lower mass/lower luminosity stars.Comment: 47 pages, 32 figures; ApJ accepte

    Small newborns in post-conflict Northern Uganda: Burden and interventions for improved outcomes

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    Introduction: A small newborn can be the result of either a low birthweight (LBW), or a preterm birth (PB), or both. LBW can be due to either a preterm appropriate-for gestational-age (preterm-AGA), or a term small-for-gestational age (term-SGA) or intrauterine growth restriction (IUGR). An IUGR is a limited in-utero foetal growth rates or foetal weight < 10th percentile. Small newborns have an increased risk of dying, particularly in low-resource settings. We set out to assess the burden, the modifiable risk factors and health outcomes of small newborns in the post-conflict Northern Ugandan district of Lira. In addition, we studied the use of video-debriefing when training health staff in Helping Babies Breathe. Subjects and methods: In 2018-19, we conducted a community-based cohort study on 1556 mother-infant dyads, nested within a cluster randomized trial. In our cohort study, we estimated the incidence and risk factors for LBW and PB and the association of LBW with severe outcomes. We explored the prevalence of and factors associated with neonatal hypoglycaemia, as well as any association between neonatal death and hypoglycaemia. In addition, we conducted a cluster randomized trial to compare Helping Babies Breathe (HBB) training in combination with video debriefing to the traditional HBB training alone on the attainment and retention of health worker neonatal resuscitation competency. Results: The incidence of LBW and PB in our cohort was lower than the global estimates, 7.3% and 5.0%, respectively. Intermittent preventive treatment for malaria was associated with a reduced risk of LBW. HIV infection was associated with an increased risk of both LBW and PB, while maternal formal education (schooling) of ≥7 years was associated with a reduced risk of LBW and PB. The proportions of neonatal deaths were many-folds higher among LBW infants compared to their non-LBW counterparts. The proportion of neonatal deaths among LBW was 103/1000 live births compared to 5/1000 among the non-LBW. The prevalence of neonatal hypoglycaemia in our cohort was 2.5%. LBW and PB each independently were associated with an increased risk of neonatal hypoglycaemia. Neonatal hypoglycaemia was associated with an increased risk of hospitalisation and severe outcomes. We demonstrated that neonatal resuscitation training with video debriefing, improved competence attainment and retention among health workers, compared to traditional HBB training alone. Conclusion: In northern Uganda, small infants still have a many-fold higher risk of dying compared to normal infants. In addition, small infants are also at more risk of neonatal hypoglycaemia compared to normal infants. Efforts are needed to secure essential newborn care, should we reach the target of Sustainable Development Goal number 3.2 of reducing infant mortality to less than 12/1000 live births by 2030

    Pollution-induced community tolerance in freshwater biofilms – from molecular mechanisms to loss of community functions

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    Exposure to herbicides poses a threat to aquatic biofilms by affecting their community structure, physiology and function. These changes render biofilms to become more tolerant, but on the downside community tolerance has ecologic costs. A concept that addresses induced community tolerance to a pollutant (PICT) was introduced by Blanck and Wängberg (1988). The basic principle of the concept is that microbial communities undergo pollution-induced succession when exposed to a pollutant over a long period of time, which changes communities structurally and functionally and enhancing tolerance to the pollutant exposure. However, the mechanisms of tolerance and the ecologic consequences were hardly studied up to date. This thesis addresses the structural and functional changes in biofilm communities and applies modern molecular methods to unravel molecular tolerance mechanisms. Two different freshwater biofilm communities were cultivated for a period of five weeks, with one of the communities being contaminated with 4 μg L-1 diuron. Subsequently, the communities were characterized for structural and functional differences, especially focusing on their crucial role of photosynthesis. The community structure of the autotrophs was assessed using HPLC-based pigment analysis and their functional alterations were investigated using Imaging-PAM fluorometry to study photosynthesis and community oxygen profiling to determine net primary production. Then, the molecular fingerprints of the communities were measured with meta-transcriptomics (RNA-Seq) and GC-based community metabolomics approaches and analyzed with respect to changes in their molecular functions. The communities were acute exposed to diuron for one hour in a dose-response design, to reveal a potential PICT and uncover related adaptation to diuron exposure. The combination of apical and molecular methods in a dose-response design enabled the linkage of functional effects of diuron exposure and underlying molecular mechanisms based on a sensitivity analysis. Chronic exposure to diuron impaired freshwater biofilms in their biomass accrual. The contaminated communities particularly lost autotrophic biomass, reflected by the decrease in specific chlorophyll a content. This loss was associated with a change in the molecular fingerprint of the communities, which substantiates structural and physiological changes. The decline in autotrophic biomass could be due to a primary loss of sensitive autotrophic organisms caused by the selection of better adapted species in the course of chronic exposure. Related to this hypothesis, an increase in diuron tolerance has been detected in the contaminated communities and molecular mechanisms facilitating tolerance have been found. It was shown that genes of the photosystem, reductive-pentose phosphate cycle and arginine metabolism were differentially expressed among the communities and that an increased amount of potential antioxidant degradation products was found in the contaminated communities. This led to the hypothesis that contaminated communities may have adapted to oxidative stress, making them less sensitive to diuron exposure. Moreover, the photosynthetic light harvesting complex was altered and the photoprotective xanthophyll cycle was increased in the contaminated communities. Despite these adaptation strategies, the loss of autotrophic biomass has been shown to impair primary production. This impairment persisted even under repeated short-term exposure, so that the tolerance mechanisms cannot safeguard primary production as a key function in aquatic systems.:1. The effect of chemicals on organisms and their functions .............................. 1 1.1 Welcome to the anthropocene .......................................................................... 1 1.2 From cellular stress responses to ecosystem resilience ................................... 3 1.2.1 The individual pursuit for homeostasis ....................................................... 3 1.2.2 Stability from diversity ................................................................................. 5 1.3 Community ecotoxicology - a step forward in monitoring the effects of chemical pollution? ................................................................................................................. 6 1.4 Functional ecotoxicological assessment of microbial communities ................... 9 1.5 Molecular tools – the key to a mechanistic understanding of stressor effects from a functional perspective in microbial communities? ...................................... 12 2. Aims and Hypothesis ......................................................................................... 14 2.1 Research question .......................................................................................... 14 2.2 Hypothesis and outline .................................................................................... 15 2.3 Experimental approach & concept .................................................................. 16 2.3.1 Aquatic freshwater biofilms as model community ..................................... 16 2.3.2 Diuron as model herbicide ........................................................................ 17 2.3.3 Experimental design ................................................................................. 18 3. Structural and physiological changes in microbial communities after chronic exposure - PICT and altered functional capacity ................................................. 21 3.1 Introduction ..................................................................................................... 21 3.2 Methods .......................................................................................................... 23 3.2.1 Biofilm cultivation ...................................................................................... 23 3.2.2 Dry weight and autotrophic index ............................................................. 23 3.2.4 Pigment analysis of periphyton ................................................................. 23 3.2.4.1 In-vivo pigment analysis for community characterization ....................... 24 3.2.4.2 In-vivo pigment analysis based on Imaging-PAM fluorometry ............... 24 3.2.4.3 In-vivo pigment fluorescence for tolerance detection ............................. 26 3.2.4.4 Ex-vivo pigment analysis by high-pressure liquid-chromatography ....... 27 3.2.5 Community oxygen metabolism measurements ....................................... 28 3.3 Results and discussion ................................................................................... 29 3.3.1 Comparison of the structural community parameters ............................... 29 3.3.2 Photosynthetic activity and primary production of the communities after selection phase ................................................................................................. 33 3.3.3 Acquisition of photosynthetic tolerance .................................................... 34 3.3.4 Primary production at exposure conditions ............................................... 36 3.3.5 Tolerance detection in primary production ................................................ 37 3.4 Summary and Conclusion ........................................................................... 40 4. Community gene expression analysis by meta-transcriptomics ................... 41 4.1 Introduction to meta-transcriptomics ............................................................... 41 4.2. Methods ......................................................................................................... 43 4.2.1 Sampling and RNA extraction................................................................... 43 4.2.2 RNA sequencing analysis ......................................................................... 44 4.2.3 Data assembly and processing................................................................. 45 4.2.4 Prioritization of contigs and annotation ..................................................... 47 4.2.5 Sensitivity analysis of biological processes .............................................. 48 4.3 Results and discussion ................................................................................... 48 4.3.1 Characterization of the meta-transcriptomic fingerprints .......................... 49 4.3.2 Insights into community stress response mechanisms using trend analysis (DRomic’s) ......................................................................................................... 51 4.3.3 Response pattern in the isoform PS genes .............................................. 63 4.5 Summary and conclusion ................................................................................ 65 5. Community metabolome analysis ..................................................................... 66 5.1 Introduction to community metabolomics ........................................................ 66 5.2 Methods .......................................................................................................... 68 5.2.1 Sampling, metabolite extraction and derivatisation................................... 68 5.2.2 GC-TOF-MS analysis ............................................................................... 69 5.2.3 Data processing and statistical analysis ................................................... 69 5.3 Results and discussion ................................................................................... 70 5.3.1 Characterization of the metabolic fingerprints .......................................... 70 5.3.2 Difference in the metabolic fingerprints .................................................... 71 5.3.3 Differential metabolic responses of the communities to short-term exposure of diuron ............................................................................................................ 73 5.4 Summary and conclusion ................................................................................ 78 6. Synthesis ............................................................................................................. 79 6.1 Approaches and challenges for linking molecular data to functional measurements ...................................................................................................... 79 6.2 Methods .......................................................................................................... 83 6.2.1 Summary on the data ............................................................................... 83 6.2.2 Aggregation of molecular data to index values (TELI and MELI) .............. 83 6.2.3 Functional annotation of contigs and metabolites using KEGG ................ 83 6.3 Results and discussion ................................................................................... 85 6.3.1 Results of aggregation techniques ........................................................... 85 6.3.2 Sensitivity analysis of the different molecular approaches and endpoints 86 6.3.3 Mechanistic view of the molecular stress responses based on KEGG functions ............................................................................................................ 89 6.4 Consolidation of the results – holistic interpretation and discussion ............... 93 6.4.1 Adaptation to chronic diuron exposure - from molecular changes to community effects.............................................................................................. 93 6.4.2 Assessment of the ecological costs of Pollution-induced community tolerance based on primary production ............................................................. 94 6.5 Outlook ............................................................................................................ 9

    Long-acting reversible contraception (LARC) after pregnancy and childbirth

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    Background and aims: Unmet need of contraception is a global challenge. The need of additional visits to initiate contraception is found to be a barrier for postpartum and postabortion contraceptive care. The IUDs and the implant are called long-acting reversible contraception (LARC). The LARC-method can be used for years without having to remember a contraceptive during sexual intercourse or, in case of hormonal contraception, every day, week or month. The overall aim of this thesis was to add knowledge to the field of long-acting reversible contraception after pregnancy in Sweden in our effort to improve the quality of contraceptive care after pregnancy and childbirth. Methods and main results: Study 1 was a retrospective cohort study including 11,066 women. Data was extracted from medical records regarding attendance to the postpartum visit and choice of contraception, breastfeeding, and abortion during 12-24 months after delivery. The primary outcome was the proportion of induced abortions during follow-up, with the outcome measure of abortion being a surrogate for unintended pregnancy. Among attendees to the follow up 2.1 % had an abortion compared to 3.6 % among nonattendants. A decision to use LARC was associated with a lower risk of abortion (OR 0.74; 95% CI 0.60-0.91; p = .005), as was exclusive breastfeeding (p < .001). Smoking and having had an earlier abortion were associated with a higher risk of abortion during the follow-up. Study II and III were open-label, prospective, randomised, controlled, multicenter studies. In study II, 101 women were either allocated to early placement (52/101) of a hormonal IUD within 48 hours after vaginal delivery or to standard placement (49/101) at 6-8 weeks postpartum. Follow-up was one year after IUD placement. Inclusion was prematurely stopped after an interim analysis due to high expulsion rate in the early placement group, and instead of 600 women only 101 were included. In the early placement group 23/52 (44.2 %) of devices were expelled within a year and 10 women had the hormonal device replaced. In the standard placement group there were no expulsions. The IUD continuation rate for the early group was 37/52 (71.2%), compared to 41/49 (83.7%, p = .13) for the standard placement group at study closure. In study III, 240 women seeking medical abortion up to 63 days´ gestation were randomised to either IUD placement within 48 hours (120/240) after completed abortion or to IUD placement at 2-4 weeks (120/240) after abortion. Follow-up was one year after abortion. The primary outcome was IUD use at 6 months postabortion. In the early placement group (intervention), 91/111 (82%) women used IUD at 6 months compared to 87/112 (77.7%) in the later placement (control) group (p= .51) Pain scores at IUD placement (measured by the visual analogue scale) were lower in the intervention group (p= .002). Women in the intervention group preferred the allocated time significantly more often compared to the control group (p= .03). There was no difference regarding expulsion. In study II and III there were no differences regarding safety profile between groups. Study IV was a qualitative study where 20 women who had undergone elective caesarean section (CS) were interviewed within 6 weeks of CS, to enable deeper understanding of women´s preferences and needs regarding contraceptive services at the time of pregnancy. Ten of the interviewees had chosen IUD placement during the latest CS. Three themes were identified; Receptivity to contraceptive counseling during pregnancy; Communication and decision-making of postpartum contraception during pregnancy and Needs to navigate in the Maternal Health Care System to receive contraceptive services before and after caesarean section. Women were generally positive to contraceptive counseling from about 25 gestational weeks and expressed positive attitudes about the concept of antenatal counseling. Feeling involved and informed was important, but few women had been involved in antenatal counseling. Women who had chosen IUD placement during CS were usually satisfied with the decision. Some interviewees expressed a need to navigate in the contraceptive services by themselves. The communication and coordinating units that should integrate around the woman have not sufficiently adapted to new evidence, needs and conditions. Conclusions: The choice of LARC postpartum is associated with lower risk for unintended pregnancy compared to the choice of other contraceptives or no choice at all. Attendance to the postpartum visit is a prerequisite to initiate LARC when provision of early/immediate LARC initiation postpartum is not part of the established contraceptive health care. Placement of a hormonal IUD within 48 hours after vaginal delivery seems safe, accepted by patients but associated with much higher expulsion rates compared to placement 6- 12 weeks postpartum. Early placement of an IUD within 48 hours after completed medical abortion does not lead to higher continuation rates at one year after abortion compared to standard placement 2-4 weeks after abortion when devices are provided free of charge. Early placement seems safe, preferred by patients, and associated with lower pain scores compared to standard IUD placement postabortion. Antenatal counseling for contraceptive method to use postpartum seems acceptable to women from around 25 gestational weeks. To have the opportunity to discuss contraception antenatally and enable placement during planned CS is generally considered valuable

    Complement mediated synapse elimination in schizophrenia

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    Schizophrenia (SCZ) is a devastating psychiatric disorder with a typically age of onset in late adolescence. The heritability is estimated to be in between 60-80% and large-scale genome-wide studies have revealed a prominent polygenic component to SCZ risk and identified more than three-hundred common risk variants. Despite a better understanding of which genetic risk variants that increases SCZ risk, it has been challenging to map out the pathophysiology of the disorder. This has stalled the development of target drugs and current treatment options display moderate efficacy and are prone to produce side-effects. SCZ is generally considered a neurodevelopmental disorder and it was proposed more than forty years ago that physiological removal of less active synapses in adolescence, i.e., synaptic pruning, is increased in SCZ and hereby causes the core symptoms of the disorder. This theory has then been supported by post-mortem brain tissue and imaging studies displaying decreased synapse density in SCZ. More recently, it was then shown that the most strongly associated risk loci can largely be explained by copy numbers of a gene coding for the complement factor 4A (C4A). As microglia prune synapses with the help of complement signalling, we therefore decided to use a recently developed human 2D in vitro assay to assess microglial uptake of synaptic structures in models based on cells from individuals with SCZ and healthy controls (study I). We observed excessive uptake of synaptic structures in SCZ models and by mixing synapses from healthy controls with microglia from SCZ patients, and vice versa, we showed the contribution of microglial and neuronal factors contributing to this excessive uptake of synaptic structures. We then developed an in vitro assay to study neuronal complement deposition dependent on copy numbers of C4A in the neuronal lines. Complement 3 (C3) deposition increased by C4A copy numbers but was independent of C4B copy numbers (also unrelated to SCZ risk). Similar C4A copy numbers correlated with the extent of microglial uptake of synapses. Microglial uptake of synaptic structures could also be inhibited by the tetracycline minocycline that also decreased risk of developing SCZ in an electronic health record cohort. In study II, we cerebrospinal fluid (CSF) from first-episode psychosis patients to measure protein levels of C4A. In two independent cohorts, we observed elevated C4A levels (although not C4B levels) in first-episode patients that later were to develop SCZ and could show correlations with markers of synapse density. However, elevated C4A levels could not fully be explained by more copy numbers of C4A in individuals with SCZ and in vitro experiments revealed that SCZ-associated cytokines can induce C4A mRNA expression while also correlating with C4A in patient-derived CSF. In study III, we set-up a 3D brain organoid models to more fully comprehensively capture processes in the developing human brain and then also included innately developing microglia. We display synaptic pruning within these models and use single cell RNA sequencing to validate them. In conclusion, this thesis uses patient-derived cellular modelling to uncover a disease mechanism in SCZ that link genetic risk variants with bona fide protein changes in living patients

    Targeted proteomics links virulence factor expression with clinical severity in staphylococcal pneumonia

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    IntroductionThe bacterial pathogen Staphylococcus aureus harbors numerous virulence factors that impact infection severity. Beyond virulence gene presence or absence, the expression level of virulence proteins is known to vary across S. aureus lineages and isolates. However, the impact of expression level on severity is poorly understood due to the lack of high-throughput quantification methods of virulence proteins.MethodsWe present a targeted proteomic approach able to monitor 42 staphylococcal proteins in a single experiment. Using this approach, we compared the quantitative virulomes of 136 S. aureus isolates from a nationwide cohort of French patients with severe community-acquired staphylococcal pneumonia, all requiring intensive care. We used multivariable regression models adjusted for patient baseline health (Charlson comorbidity score) to identify the virulence factors whose in vitro expression level predicted pneumonia severity markers, namely leukopenia and hemoptysis, as well as patient survival.ResultsWe found that leukopenia was predicted by higher expression of HlgB, Nuc, and Tsst-1 and lower expression of BlaI and HlgC, while hemoptysis was predicted by higher expression of BlaZ and HlgB and lower expression of HlgC. Strikingly, mortality was independently predicted in a dose-dependent fashion by a single phage-encoded virulence factor, the Panton-Valentine leucocidin (PVL), both in logistic (OR 1.28; 95%CI[1.02;1.60]) and survival (HR 1.15; 95%CI[1.02;1.30]) regression models.DiscussionThese findings demonstrate that the in vitro expression level of virulence factors can be correlated with infection severity using targeted proteomics, a method that may be adapted to other bacterial pathogens

    Microplastics in European sea salts – An example of exposure through consumer choice and of interstudy methodological discrepancies

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    Microplastics are contaminants of emerging concern, not least due to their global presence in marine surface waters. Unsurprisingly, microplastics have been reported in salts harvested from numerous locations. We extracted microplastics from 13 European sea salts through 30% H2O2 digestion and filtration over 5-µm filters. Filters were visually inspected at magnifications to x100. A subsample of potential microplastics was subjected to Raman spectroscopy. Particle mass was estimated, and human dose exposure calculated. After blank corrections, median concentrations were 466 ± 152 microplastics kg-1 ranging from 74 to 1155 items kg-1. Traditionally harvested salts contained fewer microplastics than most industrially harvested ones (t-test, p < 0.01). Approximately 14 µg of microplastics (< 12 particles) may be absorbed by the human body annually, of which a quarter may derive from a consumer choosing sea salt. We reviewed existing studies, showing that targeting different particle sizes and incomplete filtrations hinder interstudy comparison, indicating the importance of method harmonisation for future studies. Excess salt consumption is detrimental to human health; the hazardousness of ingesting microplastics on the other hand has yet to be shown. A portion of microplastics may enter sea salts through production processes rather than source materials
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