Low-carbon energy technologies (renewable energy and energy efficiency) are considered essential to achieve climate change mitigation goals, so a rapid deployment is needed. However there is a ...significant financing gap and many policymakers are concerned that investment for the large-scale deployment of low-carbon technologies will not materialise quickly enough. State investment banks (SIBs) can play a key role in closing this finance gap and leverage additional private finance. Based on 52 interviews, this paper presents empirical evidence on the role of three SIBs in addressing the barriers to financing low-carbon energy projects; the Clean Energy Finance Corporation (CEFC) in Australia, the Kreditanstalt fuer Wiederaufbau (KfW) in Germany and the Green Investment Bank (GIB) in the UK. We investigate the activities and financial instruments offered by SIBs and compare these to the need for such from low-carbon developers when sourcing finance. Findings show that aside from capital provision and de-risking, SIBs take a much broader role in catalysing private investments into low-carbon investments, including enabling financial sector learning, creating trust for projects and taking a first or early mover role to help projects gain a track record.
•The role of State Investment Banks (SIBs) is assessed.•Australia's CEFC, Germany's KfW and the UK's GIB are investigated.•SIBs take a broader role than capital provision and de-risking to mobilise finance.•SIBs take an educational role to enable financial sector learning.•SIBs signal trust and produce track records to crowd-in private finance.
•Integrates finance into multi-level perspective, building on evolutionary economics.•We argue finance is a regime by itself, interacting with all other regimes.•Financial policy interventions can ...fit and conform the technology niche.•Financial policy interventions can stretch and transform the financial regime.•Fitting-and-conforming niche can result in stretching-and-transforming regime.
Any major socio-technical transition requires a fundamental re-direction of financial capital from incumbent to new technologies and practices. While the transitions literature conceptually covers financial markets, the role of finance is marginalized and has scarcely been analysed empirically. To address this gap, here we build on the multi-level perspective (MLP), which considers financial markets as part of the existing regime. We argue that the role of finance is highly relevant for the niche-regime interaction: Redirecting finance towards new niche technologies requires that either the niche is fit for and conforms to the financial regime's expectations or the financial regime is stretched and transformed in order to accept and finance niche technologies. Based on 56 interviews, we identify factors that determine interactions between the financial regime and technology niches: these include acceptable risk and transaction size, an abundance of knowledge and heuristics in both the regime and niche, and an extensive, existing industry network. We further analyse how State Investment Bank (SIB) interventions in Germany, the UK and Australia, aimed to mobilise private finance into low-carbon project development, affect the interaction between the technology niche and financial regime, i.e. whether they resulted in fitting-and-conforming the technological niche for the financial regime or stretching-and-transforming the financial regime. Our results point to several important effects of SIB interventions, with most effects fitting the niche to the regime. However, we also detect effects that stretch and transform the financial regime – through evolutionary processes. Importantly, some effects occur as a consequence of the primary effects. Based on our findings we discuss policy implications on how to accelerate transitions through policies aiming at finance as well as theoretical insights gained through our analysis.
The possibility of using bioenergy as a climate change mitigation measure has sparked a discussion of whether and how bioenergy production contributes to sustainable development. We undertook a ...systematic review of the scientific literature to illuminate this relationship and found a limited scientific basis for policymaking. Our results indicate that knowledge on the sustainable development impacts of bioenergy production is concentrated in a few well‐studied countries, focuses on environmental and economic impacts, and mostly relates to dedicated agricultural biomass plantations. The scope and methodological approaches in studies differ widely and only a small share of the studies sufficiently reports on context and/or baseline conditions, which makes it difficult to get a general understanding of the attribution of impacts. Nevertheless, we identified regional patterns of positive or negative impacts for all categories – environmental, economic, institutional, social and technological. In general, economic and technological impacts were more frequently reported as positive, while social and environmental impacts were more frequently reported as negative (with the exception of impacts on direct substitution of GHG emission from fossil fuel). More focused and transparent research is needed to validate these patterns and develop a strong science underpinning for establishing policies and governance agreements that prevent/mitigate negative and promote positive impacts from bioenergy production.
Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide in adults. Pharmacological and non-pharmacological treatments are available; however, ...because of inadequate resources, antidepressants are used more frequently than psychological interventions. Prescription of these agents should be informed by the best available evidence. Therefore, we aimed to update and expand our previous work to compare and rank antidepressants for the acute treatment of adults with unipolar major depressive disorder.
We did a systematic review and network meta-analysis. We searched Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, PsycINFO, the websites of regulatory agencies, and international registers for published and unpublished, double-blind, randomised controlled trials from their inception to Jan 8, 2016. We included placebo-controlled and head-to-head trials of 21 antidepressants used for the acute treatment of adults (≥18 years old and of both sexes) with major depressive disorder diagnosed according to standard operationalised criteria. We excluded quasi-randomised trials and trials that were incomplete or included 20% or more of participants with bipolar disorder, psychotic depression, or treatment-resistant depression; or patients with a serious concomitant medical illness. We extracted data following a predefined hierarchy. In network meta-analysis, we used group-level data. We assessed the studies' risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions, and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. Primary outcomes were efficacy (response rate) and acceptability (treatment discontinuations due to any cause). We estimated summary odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with PROSPERO, number CRD42012002291.
We identified 28 552 citations and of these included 522 trials comprising 116 477 participants. In terms of efficacy, all antidepressants were more effective than placebo, with ORs ranging between 2·13 (95% credible interval CrI 1·89–2·41) for amitriptyline and 1·37 (1·16–1·63) for reboxetine. For acceptability, only agomelatine (OR 0·84, 95% CrI 0·72–0·97) and fluoxetine (0·88, 0·80–0·96) were associated with fewer dropouts than placebo, whereas clomipramine was worse than placebo (1·30, 1·01–1·68). When all trials were considered, differences in ORs between antidepressants ranged from 1·15 to 1·55 for efficacy and from 0·64 to 0·83 for acceptability, with wide CrIs on most of the comparative analyses. In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19–1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51–0·84). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43–0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates (1·30–2·32). 46 (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low; and the certainty of evidence was moderate to very low.
All antidepressants were more efficacious than placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the analysis, whereas there was more variability in efficacy and acceptability in head-to-head trials. These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants.
National Institute for Health Research Oxford Health Biomedical Research Centre and the Japan Society for the Promotion of Science.
Antipsychotic drug efficacy may have decreased over recent decades. The authors present a meta-analysis of all placebo-controlled trials in patients with acute exacerbations of schizophrenia, and ...they investigate which trial characteristics have changed over the years and which are moderators of drug-placebo efficacy differences.
The search included multiple electronic databases. The outcomes were overall efficacy (primary outcome); responder and dropout rates; positive, negative, and depressive symptoms; quality of life; functioning; and major side effects. Potential moderators of efficacy were analyzed by meta-regression.
The analysis included 167 double-blind randomized controlled trials with 28,102 mainly chronic participants. The standardized mean difference (SMD) for overall efficacy was 0.47 (95% credible interval 0.42, 0.51), but accounting for small-trial effects and publication bias reduced the SMD to 0.38. At least a "minimal" response occurred in 51% of the antipsychotic group versus 30% in the placebo group, and 23% versus 14% had a "good" response. Positive symptoms (SMD 0.45) improved more than negative symptoms (SMD 0.35) and depression (SMD 0.27). Quality of life (SMD 0.35) and functioning (SMD 0.34) improved even in the short term. Antipsychotics differed substantially in side effects. Of the response predictors analyzed, 16 trial characteristics changed over the decades. However, in a multivariable meta-regression, only industry sponsorship and increasing placebo response were significant moderators of effect sizes. Drug response remained stable over time.
Approximately twice as many patients improved with antipsychotics as with placebo, but only a minority experienced a good response. Effect sizes were reduced by industry sponsorship and increasing placebo response, not decreasing drug response. Drug development may benefit from smaller samples but better-selected patients.
Human milk (HM) appetite hormones and macronutrients may mediate satiety in breastfed infants. This study investigated associations between maternal adiposity and concentrations of HM leptin, ...adiponectin, protein and lactose, and whether these concentrations and the relationship between body mass index and percentage fat mass (%FM) in a breastfeeding population change over the first year of lactation. Lactating women (
= 59) provided milk samples (
= 283) at the 2nd, 5th, 9th and/or 12th month of lactation. Concentrations of leptin, adiponectin, total protein and lactose were measured. Maternal %FM was measured using bioimpedance spectroscopy. Higher maternal %FM was associated with higher leptin concentrations in both whole (0.006 ± 0.002 ng/mL,
= 0.008) and skim HM (0.005 ± 0.002 ng/mL,
= 0.007), and protein (0.16 ± 0.07 g/L,
= 0.028) concentrations. Adiponectin and lactose concentrations were not associated with %FM (0.01 ± 0.06 ng/mL,
= 0.81; 0.08 ± 0.11 g/L,
= 0.48, respectively). Whole milk concentrations of adiponectin and leptin did not differ significantly over the first year of lactation. These findings suggest that the level of maternal adiposity during lactation may influence the early appetite programming of breastfed infants by modulating concentrations of HM components.
All psychiatric disorders have suffered from a dearth of truly novel pharmacological interventions. In bipolar disorder, lithium remains a mainstay of treatment, six decades since its effects were ...serendipitously discovered. The lack of progress reflects several factors, including ignorance of the disorder's pathophysiology and the complexities of the clinical phenotype. After reviewing the current status, we discuss some ways forward. First, we highlight the need for a richer characterization of the clinical profile, facilitated by novel devices and new forms of data capture and analysis; such data are already promoting a reevaluation of the phenotype, with an emphasis on mood instability rather than on discrete clinical episodes. Second, experimental medicine can provide early indications of target engagement and therapeutic response, reducing the time, cost, and risk involved in evaluating potential mood stabilizers. Third, genomic data can inform target identification and validation, such as the increasing evidence for involvement of calcium channel genes in bipolar disorder. Finally, new methods and models relevant to bipolar disorder, including stem cells and genetically modified mice, are being used to study key pathways and drug effects. A combination of these approaches has real potential to break the impasse and deliver genuinely new treatments.
Breastfeeding has been implicated in the establishment of infant appetite regulation, feeding patterns and body composition (BC). A holistic approach is required to elucidate relationships between ...infant and maternal BC and contributing factors, such as breastfeeding parameters. Associations between maternal and breastfed term infant BC (
= 20) and feeding parameters during first 12 months of lactation were investigated. BC was measured at 2, 5, 9 and/or 12 months postpartum with ultrasound skinfolds (US; infants only) and bioimpedance spectroscopy (infants and mothers). 24-h milk intake (MI) and feeding frequency (FFQ) were measured. Higher FFQ was associated with larger 24-h MI (
≤ 0.003). Higher 24-h MI was associated with larger infant fat mass (FM) (US:
≤ 0.002), greater percentage FM (US:
≤ 0.008), greater FM index (FMI) (US:
≤ 0.001) and lower fat-free mass index (FFMI) (US:
0.015). Lower FFQ was associated with both larger FFM (US:
≤ 0.001) and FFMI (US:
< 0.001). Greater maternal adiposity was associated with smaller infant FFM measured with US (BMI:
< 0.010; %FM:
= 0.004; FMI:
< 0.011). Maternal BC was not associated with FFQ or 24-h MI. These results reinforce that early life is a critical window for infant programming and that breastfeeding may influence risk of later disease via modulation of BC.
Infants rely on their innate immune systems to protect them from infection. Human milk (HM) contains fatty acids (FAs) and monoacylglycerols that are known to exhibit antiviral and antibacterial ...properties in vitro. The specific fat content of HM may potentially affect the efficacy of this antimicrobial activity. This preliminary study investigates whether the proportions of FA in HM change in response to infections, leading to cold-like symptoms in the mother or infant. Milk samples were obtained from mothers (
= 26) when they and their infants were healthy, and when mother, infant, or both suffered cold-like symptoms. The milk was hydrolysed and FA proportions were measured using gas chromatography. Fifteen FAs were recorded, of which eight were detected in sufficient quantities for statistical analysis. The proportions of capric (C10:0) and lauric acids (C12:0) in HM were significantly lower, and palmitic acid (C16:0) was higher when mothers and infants were ill compared to healthy samples. Palmitoleic (C16:1, n-7) and stearic acid (C18:0) proportions were higher in HM when the infant was unwell, but were not related to maternal health. Whilst the differences detected were small (less than 0.5%), the effects may be additive and potentially have a protective function. The value of further studies is certainly indicated.
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