We submit that the safe operating space of the planetary boundary of novel entities is exceeded since annual production and releases are increasing at a pace that outstrips the global capacity for ...assessment and monitoring. The novel entities boundary in the planetary boundaries framework refers to entities that are novel in a geological sense and that could have large-scale impacts that threaten the integrity of Earth system processes. We review the scientific literature relevant to quantifying the boundary for novel entities and highlight plastic pollution as a particular aspect of high concern. An impact pathway from production of novel entities to impacts on Earth system processes is presented. We define and apply three criteria for assessment of the suitability of control variables for the boundary: feasibility, relevance, and comprehensiveness. We propose several complementary control variables to capture the complexity of this boundary, while acknowledging major data limitations. We conclude that humanity is currently operating outside the planetary boundary based on the weight-of-evidence for several of these control variables. The increasing rate of production and releases of larger volumes and higher numbers of novel entities with diverse risk potentials exceed societies’ ability to conduct safety related assessments and monitoring. We recommend taking urgent action to reduce the harm associated with exceeding the boundary by reducing the production and releases of novel entities, noting that even so, the persistence of many novel entities and/or their associated effects will continue to pose a threat.
We use a mass complete (log( ) ) sample of galaxies with accurate photometric redshifts in the COSMOS field to construct the density field and the cosmic web to z = 1.2. The comic web extraction ...relies on the density field Hessian matrix and breaks the density field into clusters, filaments, and the field. We provide the density field and cosmic web measures to the community. We show that at z 0.8, the median star formation rate (SFR) in the cosmic web gradually declines from the field to clusters and this decline is especially sharp for satellites (∼1 dex versus ∼0.5 dex for centrals). However, at z 0.8, the trend flattens out for the overall galaxy population and satellites. For star-forming (SF) galaxies only, the median SFR is constant at z 0.5 but declines by ∼0.3-0.4 dex from the field to clusters for satellites and centrals at z 0.5. We argue that for satellites, the main role of the cosmic web environment is to control their SF fraction, whereas for centrals, it is mainly to control their overall SFR at z 0.5 and to set their fraction at z 0.5. We suggest that most satellites experience a rapid quenching mechanism as they fall from the field into clusters through filaments, whereas centrals mostly undergo a slow environmental quenching at z 0.5 and a fast mechanism at higher redshifts. Our preliminary results highlight the importance of the large-scale cosmic web on galaxy evolution.
A new synthetic route, to prepare an alkylated indacenodithieno3,2‐bthiophene‐based nonfullerene acceptor (C8‐ITIC), is reported. Compared to the reported ITIC with phenylalkyl side chains, the new ...acceptor C8‐ITIC exhibits a reduction in the optical band gap, higher absorptivity, and an increased propensity to crystallize. Accordingly, blends with the donor polymer PBDB‐T exhibit a power conversion efficiency (PCE) up to 12.4%. Further improvements in efficiency are found upon backbone fluorination of the donor polymer to afford the novel material PFBDB‐T. The resulting blend with C8‐ITIC shows an impressive PCE up to 13.2% as a result of the higher open‐circuit voltage. Electroluminescence studies demonstrate that backbone fluorination reduces the energy loss of the blends, with PFBDB‐T/C8‐ITIC‐based cells exhibiting a small energy loss of 0.6 eV combined with a high JSC of 19.6 mA cm−2.
The synthesis of a novel alkylated indacenodithioeno3,2‐bthiophene (C8‐IDTT) based nonfullerene acceptor (C8‐ITIC), is reported. Compared to ITIC with phenylalkyl side chains, the acceptor exhibits a redshifted absorption with increased absorptivity. Solar cell power conversion efficiencies (PCEs) of up to 13.2 % are achieved, with the high PCE attributed to the broad absorption, high crystallinity of C8‐ITIC and low voltage loss.
Abiraterone acetate received licencing for use in only “high-risk” metastatic hormone-naïve prostate cancer (mHNPC) following the LATITUDE trial findings. However, a “risk”-related effect was not ...seen in the STAMPEDE trial. There remains uncertainty as to whether men with LATITUDE “low-risk” M1 disease benefit from androgen deprivation therapy (ADT) combined with abiraterone acetate and prednisolone (AAP).
Evaluation of heterogeneity of effect between LATITUDE high- and low-risk M1 prostate cancer patients receiving ADT + AAP in the STAMPEDE trial.
A post hoc subgroup analysis of the 2017 STAMPEDE “abiraterone comparison”. Staging scans for M1 patients contemporaneously randomised to ADT or ADT + AAP within the STAMPEDE trial were evaluated centrally and blind to treatment assignment. Stratification was by risk according to the criteria set out in the LATITUDE trial. Exploratory subgroup stratification incorporated the CHAARTED criteria.
The primary outcome measure was overall survival (OS) and the secondary outcome measure was failure-free survival (FFS). Further exploratory analysis evaluated clinical skeletal-related events, progression-free survival (PFS), and prostate cancer-specific death. Standard Cox-regression and Kaplan-Meier survival estimates were employed for analysis.
A total of 901 M1 STAMPEDE patients were evaluated after exclusions. Of the patients, 428 (48%) were identified as having a low risk and 473 (52%) a high risk. Patients receiving ADT + AAP had significantly improved OS (low-risk hazard ratio HR: 0.66, 95% confidence interval or CI 0.44–0.98) and FFS (low-risk HR: 0.24, 95% CI 0.17–0.33) compared with ADT alone. Heterogeneity of effect was not seen between low- and high-risk groups for OS or FFS. For OS benefit in low risk, the number needed to treat was four times greater than that for high risk. However, this was not observed for the other measured endpoints.
Men with mHNPC gain treatment benefit from ADT + AAP irrespective of risk stratification for “risk” or “volume”.
Coadministration of abiraterone acetate and prednisolone with androgen deprivation therapy (ADT) is associated with prolonged overall survival and disease control, compared with ADT alone, in all men with metastatic disease starting hormone therapy for the first time.
A significant treatment benefit is observed in men with metastatic hormone-naïve prostate cancer treated with androgen deprivation therapy combined with abiraterone acetate and prednisolone, irrespective of being designated as having a “low” or a “high” risk by the current treatment criteria. This consistent result applies to all efficacy outcome measures.
Based on previous findings, we hypothesised that radiotherapy to the prostate would improve overall survival in men with metastatic prostate cancer, and that the benefit would be greatest in patients ...with a low metastatic burden. We aimed to compare standard of care for metastatic prostate cancer, with and without radiotherapy.
We did a randomised controlled phase 3 trial at 117 hospitals in Switzerland and the UK. Eligible patients had newly diagnosed metastatic prostate cancer. We randomly allocated patients open-label in a 1:1 ratio to standard of care (control group) or standard of care and radiotherapy (radiotherapy group). Randomisation was stratified by hospital, age at randomisation, nodal involvement, WHO performance status, planned androgen deprivation therapy, planned docetaxel use (from December, 2015), and regular aspirin or non-steroidal anti-inflammatory drug use. Standard of care was lifelong androgen deprivation therapy, with up-front docetaxel permitted from December, 2015. Men allocated radiotherapy received either a daily (55 Gy in 20 fractions over 4 weeks) or weekly (36 Gy in six fractions over 6 weeks) schedule that was nominated before randomisation. The primary outcome was overall survival, measured as the number of deaths; this analysis had 90% power with a one-sided α of 2·5% for a hazard ratio (HR) of 0·75. Secondary outcomes were failure-free survival, progression-free survival, metastatic progression-free survival, prostate cancer-specific survival, and symptomatic local event-free survival. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. The primary outcome analysis was by intention to treat. Two prespecified subgroup analyses tested the effects of prostate radiotherapy by baseline metastatic burden and radiotherapy schedule. This trial is registered with ClinicalTrials.gov, number NCT00268476.
Between Jan 22, 2013, and Sept 2, 2016, 2061 men underwent randomisation, 1029 were allocated the control and 1032 radiotherapy. Allocated groups were balanced, with a median age of 68 years (IQR 63–73) and median amount of prostate-specific antigen of 97 ng/mL (33–315). 367 (18%) patients received early docetaxel. 1082 (52%) participants nominated the daily radiotherapy schedule before randomisation and 979 (48%) the weekly schedule. 819 (40%) men had a low metastatic burden, 1120 (54%) had a high metastatic burden, and the metastatic burden was unknown for 122 (6%). Radiotherapy improved failure-free survival (HR 0·76, 95% CI 0·68–0·84; p<0·0001) but not overall survival (0·92, 0·80–1·06; p=0·266). Radiotherapy was well tolerated, with 48 (5%) adverse events (Radiation Therapy Oncology Group grade 3–4) reported during radiotherapy and 37 (4%) after radiotherapy. The proportion reporting at least one severe adverse event (Common Terminology Criteria for Adverse Events grade 3 or worse) was similar by treatment group in the safety population (398 38% with control and 380 39% with radiotherapy).
Radiotherapy to the prostate did not improve overall survival for unselected patients with newly diagnosed metastatic prostate cancer.
Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Astellas, Clovis Oncology, Janssen, Novartis, Pfizer, and Sanofi-Aventis.
Anthropogenic emissions and land use changes have modified atmospheric aerosol concentrations and size distributions over time. Understanding preindustrial conditions and changes in organic aerosol ...due to anthropogenic activities is important because these features (1) influence estimates of aerosol radiative forcing and (2) can confound estimates of the historical response of climate to increases in greenhouse gases. Secondary organic aerosol (SOA), formed in the atmosphere by oxidation of organic gases, represents a major fraction of global submicron‐sized atmospheric organic aerosol. Over the past decade, significant advances in understanding SOA properties and formation mechanisms have occurred through measurements, yet current climate models typically do not comprehensively include all important processes. This review summarizes some of the important developments during the past decade in understanding SOA formation. We highlight the importance of some processes that influence the growth of SOA particles to sizes relevant for clouds and radiative forcing, including formation of extremely low volatility organics in the gas phase, acid‐catalyzed multiphase chemistry of isoprene epoxydiols, particle‐phase oligomerization, and physical properties such as volatility and viscosity. Several SOA processes highlighted in this review are complex and interdependent and have nonlinear effects on the properties, formation, and evolution of SOA. Current global models neglect this complexity and nonlinearity and thus are less likely to accurately predict the climate forcing of SOA and project future climate sensitivity to greenhouse gases. Efforts are also needed to rank the most influential processes and nonlinear process‐related interactions, so that these processes can be accurately represented in atmospheric chemistry‐climate models.
Plain Language Summary
Secondary organic aerosol (SOA), formed in the atmosphere by oxidation of organic gases, often represents a major fraction of global submicron‐sized atmospheric organic aerosol. Myriad processes affect SOA formation, several of which relate to interactions between natural biogenic emissions and predominantly anthropogenic species such as SO2, NOx, sulfate, nitrate, and ammonium. Many of these key processes are nonlinear and can be synergistic or act to compensate each other in terms of climate forcing. Current atmospheric chemistry‐climate models mostly do not treat these processes. We highlight a number of process‐level mechanisms related to the interactions between anthropogenic and biogenic SOA precursors, for which the corresponding impacts on the radiative effects of SOA need to be investigated in atmospheric chemistry‐climate models. Ultimately, climate models need to capture enough important features of the chemical and dynamic evolution of SOA, in terms of both aerosol number and aerosol mass, as a function of atmospheric variables and anthropogenic perturbations to reasonably predict the spatial and temporal distributions of SOA. A better understanding of SOA formation mechanisms and physical properties is needed to improve estimates of the extent to which anthropogenic emissions and land use changes have modified global aerosol concentrations and size distributions since preindustrial times.
Key Points
We review some important developments in secondary organic aerosol (SOA) that could impact aerosol radiative forcing and response of climate to greenhouse gases
We highlight some of the important processes that involve interactions between natural biogenic emissions and anthropogenic emissions
We discuss fundamental SOA properties volatility and viscosity and their relation to evolution of aerosol mass and number concentrations in the atmosphere
•Human–nature connections are receiving increasing attention in sustainability science.•Relevant insights have been obtained in diverse disciplines, but integration is lacking.•‘Nature’ is often ...undefined and the focus is on the individual.•Groups of papers characterised by cognitive psychology, nature experience and place attachment.•Integrating, expanding, and focusing on transformation are key steps forward.
In sustainability science calls are increasing for humanity to (re-)connect with nature, yet no systematic synthesis of the empirical literature on human–nature connection (HNC) exists. We reviewed 475 publications on HNC and found that most research has concentrated on individuals at local scales, often leaving ‘nature’ undefined. Cluster analysis identified three subgroups of publications: first, HNC as mind, dominated by the use of psychometric scales, second, HNC as experience, characterised by observation and qualitative analysis; and third, HNC as place, emphasising place attachment and reserve visitation. To address the challenge of connecting humanity with nature, future HNC scholarship must pursue cross-fertilization of methods and approaches, extend research beyond individuals, local scales, and Western societies, and increase guidance for sustainability transformations.
Understanding the evolution of Tetraconata or Pancrustacea-the clade that includes crustaceans and insects-requires a well-resolved hypothesis regarding the relationships within and among its ...constituent taxa. Here, we assembled a taxon-rich phylogenomic dataset focusing on crustacean lineages based solely on genomes and new-generation Illumina-generated transcriptomes, including 89 representatives of Tetraconata. This constitutes, to our knowledge, the first phylogenomic study specifically addressing internal relationships of Malacostraca (with 26 species included) and Branchiopoda (36 species). Seven matrices comprising 81-684 orthogroups and 17 690-242 530 amino acid positions were assembled and analysed under five different analytical approaches. To maximize gene occupancy and to improve resolution, taxon-specific matrices were designed for Malacostraca and Branchiopoda. Key tetraconatan taxa (i.e. Oligostraca, Multicrustacea, Branchiopoda, Malacostraca, Thecostraca, Copepoda and Hexapoda) were monophyletic and well supported. Within Branchiopoda, Phyllopoda, Diplostraca, Cladoceromorpha and Cladocera were monophyletic. Within Malacostraca, the clades Eumalacostraca, Decapoda and Reptantia were well supported. Recovery of Caridoida or Peracarida was highly dependent on the analysis for the complete matrix, but it was consistently monophyletic in the malacostracan-specific matrices. From such examples, we demonstrate that taxon-specific matrices and particular evolutionary models and analytical methods, namely CAT-GTR and Dayhoff recoding, outperform other approaches in resolving certain recalcitrant nodes in phylogenomic analyses.
Summary Background The aim of this trial was to compare dose-escalated conformal radiotherapy with control-dose conformal radiotherapy in patients with localised prostate cancer. Preliminary findings ...reported after 5 years of follow-up showed that escalated-dose conformal radiotherapy improved biochemical progression-free survival. Based on the sample size calculation, we planned to analyse overall survival when 190 deaths occurred; this target has now been reached, after a median 10 years of follow-up. Methods RT01 was a phase 3, open-label, international, randomised controlled trial enrolling men with histologically confirmed T1b–T3a, N0, M0 prostate cancer with prostate specific antigen of less than 50 ng/mL. Patients were randomly assigned centrally in a 1:1 ratio, using a computer-based minimisation algorithm stratifying by risk of seminal vesicle invasion and centre to either the control group (64 Gy in 32 fractions, the standard dose at the time the trial was designed) or the escalated-dose group (74 Gy in 37 fractions). Neither patients nor investigators were masked to assignment. All patients received neoadjuvant androgen deprivation therapy for 3–6 months before the start of conformal radiotherapy, which continued until the end of conformal radiotherapy. The coprimary outcome measures were biochemical progression-free survival and overall survival. All analyses were done on an intention-to-treat basis. Treatment-related side-effects have been reported previously. This trial is registered, number ISRCTN47772397. Findings Between Jan 7, 1998, and Dec 20, 2001, 862 men were registered and 843 subsequently randomly assigned: 422 to the escalated-dose group and 421 to the control group. As of Aug 2, 2011, 236 deaths had occurred: 118 in each group. Median follow-up was 10·0 years (IQR 9·1–10·8). Overall survival at 10 years was 71% (95% CI 66–75) in each group (hazard ratio HR 0·99, 95% CI 0·77–1·28; p=0·96). Biochemical progression or progressive disease occurred in 391 patients (221 57% in the control group and 170 43% in the escalated-dose group). At 10 years, biochemical progression-free survival was 43% (95% CI 38–48) in the control group and 55% (50–61) in the escalated-dose group (HR 0·69, 95% CI 0·56–0·84; p=0·0003). Interpretation At a median follow-up of 10 years, escalated-dose conformal radiotherapy with neoadjuvant androgen deprivation therapy showed an advantage in biochemical progression-free survival, but this advantage did not translate into an improvement in overall survival. These efficacy data for escalated-dose treatment must be weighed against the increase in acute and late toxicities associated with the escalated dose and emphasise the importance of use of appropriate modern radiotherapy methods to reduce side-effects. Funding UK Medical Research Council.
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