Protect or perish: Quantitative analysis of state-level species protection supports preservation of the Endangered Species Act

To combat biodiversity loss in the United States, imperiled species are protected under the federal Endangered Species Act (ESA), which is currently threatened by political initiatives seeking to weaken it and potentially transfer substantial authority to the states. To assess the conservation capacity of current state laws, we conducted a quantitative analysis of imperiled species protection within all 50 states by compiling data on all state-listed species, ESA-listed species, and IUCN Red List species in each state. We found that currently 16% of ESA-listed species and 52% of IUCN imperiled species are not protected by any state law, and if the ESA were repealed these numbers could increase to 73% of ESA-listed species and 81% of IUCN imperiled species unprotected. Although protection varies widely among states, our results suggest that revoking the ESA would be highly detrimental to imperiled species conservation and recovery in the United States

Attention bias to emotional faces varies by IQ and anxiety in Williams syndrome

Individuals with Williams syndrome (WS) often experience significant anxiety. A promising approach to anxiety intervention has emerged from cognitive studies of attention bias to threat. To investigate the utility of this intervention in WS, this study examined attention bias to happy and angry faces in individuals with WS (N=46). Results showed a significant difference in attention bias patterns as a function of IQ and anxiety. Individuals with higher IQ or higher anxiety showed a significant bias toward angry, but not happy faces, whereas individuals with lower IQ or lower anxiety showed the opposite pattern. These results suggest that attention bias interventions to modify a threat bias may be most effectively targeted to anxious individuals with WS with relatively high IQ

A connectome and analysis of the adult Drosophila central brain.

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets. We define cell types, refine computational compartments, and provide an exhaustive atlas of cell examples and types, many of them novel. We provide detailed circuits consisting of neurons and their chemical synapses for most of the central brain. We make the data public and simplify access, reducing the effort needed to answer circuit questions, and provide procedures linking the neurons defined by our analysis with genetic reagents. Biologically, we examine distributions of connection strengths, neural motifs on different scales, electrical consequences of compartmentalization, and evidence that maximizing packing density is an important criterion in the evolution of the fly's brain

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Phenotypic and Genotypic Heterogeneity in Autism Spectrum Disorder

Many genetic events can cause autism spectrum disorder (ASD). One specific genetic event involves deletion or duplication of approximately 50 genes, 22q11.2 Deletion/Duplication Syndrome, and leads to ASD in 10-40% of cases. Chapter 1 describes an effort to identify a critical region that confers ASD risk within those ~50 genes and reports that the Low Copy Repeat-A to B region shows the strongest association. Next, we explore ‘background genetics’ the remainder of the genome, almost entirely inherited from one’s parents - that interact with genetic events such as 22q11.2 deletions/duplications. Quantifying a heritable phenotype in one’s parents can indirectly quantify the phenotype encoded in one’s ‘background genetics.’ Heterogeneity among individuals with 22q11.2 Deletion/Duplication Syndrome, therefore, can be partially explained by heterogeneity among their parents’ phenotypes. An ideal heritable trait in which to explore this framework is one of the most studied and understood constructs in psychology: IQ. However, few studies measure parental IQ due to the prohibitive cost and inconvenience of current IQ assessments. Chapter 2 reports the optimal methods for using small sample sizes to develop and calibrate a large, computer adaptive item pool for a new IQ assessment. The method described can be used to develop an online IQ test to facilitate data collection from families and understanding of ‘background genetics.’ Chapter 3 tests whether ‘IQ’ holds the same meaning for children with autism when assessed with the Differential Ability Scales, 2nd Edition (DAS-II) compared to the normative, standardization sample and reports that while verbal and nonverbal reasoning scores do function similarly between groups, the spatial composite score does not. Taken together, these three chapters advance our understanding of IQ assessment in autism and provide one example of a genetics-first sample in which these insights can be applied. Given the importance of IQ for predicting outcomes and its heterogeneity within genetically homogenous samples, the rapidly evolving field of ASD behavioral genetics stands to benefit from an efficient, valid online IQ assessment of verbal and nonverbal reasoning, which hold the same meaning for individuals with autism and typical individuals on the commonly used DAS-II

Phenotypic and Genotypic Heterogeneity in Autism Spectrum Disorder

Many genetic events can cause autism spectrum disorder (ASD). One specific genetic event involves deletion or duplication of approximately 50 genes, 22q11.2 Deletion/Duplication Syndrome, and leads to ASD in 10-40% of cases. Chapter 1 describes an effort to identify a critical region that confers ASD risk within those ~50 genes and reports that the Low Copy Repeat-A to B region shows the strongest association. Next, we explore ‘background genetics’ the remainder of the genome, almost entirely inherited from one’s parents - that interact with genetic events such as 22q11.2 deletions/duplications. Quantifying a heritable phenotype in one’s parents can indirectly quantify the phenotype encoded in one’s ‘background genetics.’ Heterogeneity among individuals with 22q11.2 Deletion/Duplication Syndrome, therefore, can be partially explained by heterogeneity among their parents’ phenotypes. An ideal heritable trait in which to explore this framework is one of the most studied and understood constructs in psychology: IQ. However, few studies measure parental IQ due to the prohibitive cost and inconvenience of current IQ assessments. Chapter 2 reports the optimal methods for using small sample sizes to develop and calibrate a large, computer adaptive item pool for a new IQ assessment. The method described can be used to develop an online IQ test to facilitate data collection from families and understanding of ‘background genetics.’ Chapter 3 tests whether ‘IQ’ holds the same meaning for children with autism when assessed with the Differential Ability Scales, 2nd Edition (DAS-II) compared to the normative, standardization sample and reports that while verbal and nonverbal reasoning scores do function similarly between groups, the spatial composite score does not. Taken together, these three chapters advance our understanding of IQ assessment in autism and provide one example of a genetics-first sample in which these insights can be applied. Given the importance of IQ for predicting outcomes and its heterogeneity within genetically homogenous samples, the rapidly evolving field of ASD behavioral genetics stands to benefit from an efficient, valid online IQ assessment of verbal and nonverbal reasoning, which hold the same meaning for individuals with autism and typical individuals on the commonly used DAS-II