Showing papers by "University of Melbourne published in 2016"

Observation of Gravitational Waves from a Binary Black Hole Merger

Abstract: On September 14, 2015 at 09:50:45 UTC the two detectors of the Laser Interferometer Gravitational-Wave Observatory simultaneously observed a transient gravitational-wave signal. The signal sweeps upwards in frequency from 35 to 250 Hz with a peak gravitational-wave strain of $1.0 \times 10^{-21}$. It matches the waveform predicted by general relativity for the inspiral and merger of a pair of black holes and the ringdown of the resulting single black hole. The signal was observed with a matched-filter signal-to-noise ratio of 24 and a false alarm rate estimated to be less than 1 event per 203 000 years, equivalent to a significance greater than 5.1 {\sigma}. The source lies at a luminosity distance of $410^{+160}_{-180}$ Mpc corresponding to a redshift $z = 0.09^{+0.03}_{-0.04}$. In the source frame, the initial black hole masses are $36^{+5}_{-4} M_\odot$ and $29^{+4}_{-4} M_\odot$, and the final black hole mass is $62^{+4}_{-4} M_\odot$, with $3.0^{+0.5}_{-0.5} M_\odot c^2$ radiated in gravitational waves. All uncertainties define 90% credible intervals.These observations demonstrate the existence of binary stellar-mass black hole systems. This is the first direct detection of gravitational waves and the first observation of a binary black hole merger.

ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions.

Abstract: Non-randomised studies of the effects of interventions are critical to many areas of healthcare evaluation, but their results may be biased. It is therefore important to understand and appraise their strengths and weaknesses. We developed ROBINS-I (“Risk Of Bias In Non-randomised Studies - of Interventions”), a new tool for evaluating risk of bias in estimates of the comparative effectiveness (harm or benefit) of interventions from studies that did not use randomisation to allocate units (individuals or clusters of individuals) to comparison groups. The tool will be particularly useful to those undertaking systematic reviews that include non-randomised studies.

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

GW151226: observation of gravitational waves from a 22-solar-mass binary black hole coalescence

Abstract: We report the observation of a gravitational-wave signal produced by the coalescence of two stellar-mass black holes. The signal, GW151226, was observed by the twin detectors of the Laser Interferometer Gravitational-Wave Observatory (LIGO) on December 26, 2015 at 03:38:53 UTC. The signal was initially identified within 70 s by an online matched-filter search targeting binary coalescences. Subsequent off-line analyses recovered GW151226 with a network signal-to-noise ratio of 13 and a significance greater than 5 σ. The signal persisted in the LIGO frequency band for approximately 1 s, increasing in frequency and amplitude over about 55 cycles from 35 to 450 Hz, and reached a peak gravitational strain of 3.4+0.7−0.9×10−22. The inferred source-frame initial black hole masses are 14.2+8.3−3.7M⊙ and 7.5+2.3−2.3M⊙ and the final black hole mass is 20.8+6.1−1.7M⊙. We find that at least one of the component black holes has spin greater than 0.2. This source is located at a luminosity distance of 440+180−190 Mpc corresponding to a redshift 0.09+0.03−0.04. All uncertainties define a 90 % credible interval. This second gravitational-wave observation provides improved constraints on stellar populations and on deviations from general relativity.

Genomic analyses identify molecular subtypes of pancreatic cancer

Abstract: Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

Paris Agreement climate proposals need a boost to keep warming well below 2 °C

Abstract: The Paris climate agreement aims at holding global warming to well below 2 degrees Celsius and to "pursue efforts" to limit it to 1.5 degrees Celsius. To accomplish this, countries have submitted Intended Nationally Determined Contributions (INDCs) outlining their post-2020 climate action. Here we assess the effect of current INDCs on reducing aggregate greenhouse gas emissions, its implications for achieving the temperature objective of the Paris climate agreement, and potential options for overachievement. The INDCs collectively lower greenhouse gas emissions compared to where current policies stand, but still imply a median warming of 2.6-3.1 degrees Celsius by 2100. More can be achieved, because the agreement stipulates that targets for reducing greenhouse gas emissions are strengthened over time, both in ambition and scope. Substantial enhancement or over-delivery on current INDCs by additional national, sub-national and non-state actions is required to maintain a reasonable chance of meeting the target of keeping warming well below 2 degrees Celsius.

Unicycler: resolving bacterial genome assemblies from short and long sequencing reads

Abstract: The Illumina DNA sequencing platform generates accurate but short reads, which can be used to produce accurate but fragmented genome assemblies. Pacific Biosciences and Oxford Nanopore Technologies DNA sequencing platforms generate long reads that can produce more complete genome assemblies, but the sequencing is more expensive and error prone. There is significant interest in combining data from these complementary sequencing technologies to generate more accurate "hybrid" assemblies. However, few tools exist that truly leverage the benefits of both types of data, namely the accuracy of short reads and the structural resolving power of long reads. Here we present Unicycler, a new tool for assembling bacterial genomes from a combination of short and long reads, which produces assemblies that are accurate, complete and cost-effective. Unicycler builds an initial assembly graph from short reads using the de novo assembler SPAdes and then simplifies the graph using information from short and long reads. Unicycler utilises a novel semi-global aligner, which is used to align long reads to the assembly graph. Tests on both synthetic and real reads show Unicycler can assemble larger contigs with fewer misassemblies than other hybrid assemblers, even when long read depth and accuracy are low. Unicycler is open source (GPLv3) and available at github.com/rrwick/Unicycler.

Statistical tests, P values, confidence intervals, and power: a guide to misinterpretations

Abstract: Misinterpretation and abuse of statistical tests, confidence intervals, and statistical power have been decried for decades, yet remain rampant A key problem is that there are no interpretations of these concepts that are at once simple, intuitive, correct, and foolproof Instead, correct use and interpretation of these statistics requires an attention to detail which seems to tax the patience of working scientists This high cognitive demand has led to an epidemic of shortcut definitions and interpretations that are simply wrong, sometimes disastrously so-and yet these misinterpretations dominate much of the scientific literature In light of this problem, we provide definitions and a discussion of basic statistics that are more general and critical than typically found in traditional introductory expositions Our goal is to provide a resource for instructors, researchers, and consumers of statistics whose knowledge of statistical theory and technique may be limited but who wish to avoid and spot misinterpretations We emphasize how violation of often unstated analysis protocols (such as selecting analyses for presentation based on the P values they produce) can lead to small P values even if the declared test hypothesis is correct, and can lead to large P values even if that hypothesis is incorrect We then provide an explanatory list of 25 misinterpretations of P values, confidence intervals, and power We conclude with guidelines for improving statistical interpretation and reporting

Time to Treatment With Endovascular Thrombectomy and Outcomes From Ischemic Stroke: A Meta-analysis

Abstract: Importance Endovascular thrombectomy with second-generation devices is beneficial for patients with ischemic stroke due to intracranial large-vessel occlusions. Delineation of the association of treatment time with outcomes would help to guide implementation. Objective To characterize the period in which endovascular thrombectomy is associated with benefit, and the extent to which treatment delay is related to functional outcomes, mortality, and symptomatic intracranial hemorrhage. Design, Setting, and Patients Demographic, clinical, and brain imaging data as well as functional and radiologic outcomes were pooled from randomized phase 3 trials involving stent retrievers or other second-generation devices in a peer-reviewed publication (by July 1, 2016). The identified 5 trials enrolled patients at 89 international sites. Exposures Endovascular thrombectomy plus medical therapy vs medical therapy alone; time to treatment. Main Outcomes and Measures The primary outcome was degree of disability (mRS range, 0-6; lower scores indicating less disability) at 3 months, analyzed with the common odds ratio (cOR) to detect ordinal shift in the distribution of disability over the range of the mRS; secondary outcomes included functional independence at 3 months, mortality by 3 months, and symptomatic hemorrhagic transformation. Results Among all 1287 patients (endovascular thrombectomy + medical therapy [n = 634]; medical therapy alone [n = 653]) enrolled in the 5 trials (mean age, 66.5 years [SD, 13.1]; women, 47.0%), time from symptom onset to randomization was 196 minutes (IQR, 142 to 267). Among the endovascular group, symptom onset to arterial puncture was 238 minutes (IQR, 180 to 302) and symptom onset to reperfusion was 286 minutes (IQR, 215 to 363). At 90 days, the mean mRS score was 2.9 (95% CI, 2.7 to 3.1) in the endovascular group and 3.6 (95% CI, 3.5 to 3.8) in the medical therapy group. The odds of better disability outcomes at 90 days (mRS scale distribution) with the endovascular group declined with longer time from symptom onset to arterial puncture: cOR at 3 hours, 2.79 (95% CI, 1.96 to 3.98), absolute risk difference (ARD) for lower disability scores, 39.2%; cOR at 6 hours, 1.98 (95% CI, 1.30 to 3.00), ARD, 30.2%; cOR at 8 hours,1.57 (95% CI, 0.86 to 2.88), ARD, 15.7%; retaining statistical significance through 7 hours and 18 minutes. Among 390 patients who achieved substantial reperfusion with endovascular thrombectomy, each 1-hour delay to reperfusion was associated with a less favorable degree of disability (cOR, 0.84 [95% CI, 0.76 to 0.93]; ARD, −6.7%) and less functional independence (OR, 0.81 [95% CI, 0.71 to 0.92], ARD, −5.2% [95% CI, −8.3% to −2.1%]), but no change in mortality (OR, 1.12 [95% CI, 0.93 to 1.34]; ARD, 1.5% [95% CI, −0.9% to 4.2%]). Conclusions and Relevance In this individual patient data meta-analysis of patients with large-vessel ischemic stroke, earlier treatment with endovascular thrombectomy + medical therapy compared with medical therapy alone was associated with lower degrees of disability at 3 months. Benefit became nonsignificant after 7.3 hours.

Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets

Abstract: Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with human complex traits. However, the genes or functional DNA elements through which these variants exert their effects on the traits are often unknown. We propose a method (called SMR) that integrates summary-level data from GWAS with data from expression quantitative trait locus (eQTL) studies to identify genes whose expression levels are associated with a complex trait because of pleiotropy. We apply the method to five human complex traits using GWAS data on up to 339,224 individuals and eQTL data on 5,311 individuals, and we prioritize 126 genes (for example, TRAF1 and ANKRD55 for rheumatoid arthritis and SNX19 and NMRAL1 for schizophrenia), of which 25 genes are new candidates; 77 genes are not the nearest annotated gene to the top associated GWAS SNP. These genes provide important leads to design future functional studies to understand the mechanism whereby DNA variation leads to complex trait variation.

Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia

Abstract: BACKGROUND New treatments have improved outcomes for patients with relapsed chronic lymphocytic leukemia (CLL), but complete remissions remain uncommon. Venetoclax has a distinct mechanism of action; it targets BCL2, a protein central to the survival of CLL cells. METHODS We conducted a phase 1 dose-escalation study of daily oral venetoclax in patients with relapsed or refractory CLL or small lymphocytic lymphoma (SLL) to assess safety, pharmacokinetic profile, and efficacy. In the dose-escalation phase, 56 patients received active treatment in one of eight dose groups that ranged from 150 to 1200 mg per day. In an expansion cohort, 60 additional patients were treated with a weekly stepwise ramp-up in doses as high as 400 mg per day. RESULTS The majority of the study patients had received multiple previous treatments, and 89% had poor prognostic clinical or genetic features. Venetoclax was active at all dose levels. Clinical tumor lysis syndrome occurred in 3 of 56 patients in the dose-escalation cohort, with one death. After adjustments to the dose-escalation schedule, clinical tumor lysis syndrome did not occur in any of the 60 patients in the expansion cohort. Other toxic effects in cluded mild diarrhea (in 52% of the patients), upper respiratory tract infection (in 48%), nausea (in 47%), and grade 3 or 4 neutropenia (in 41%). A maximum tolerated dose was not identified. Among the 116 patients who received venetoclax, 92 (79%) had a response. Response rates ranged from 71 to 79% among patients in subgroups with an adverse prognosis, including those with resistance to fludarabine, those with chromosome 17p deletions (deletion 17p CLL), and those with unmutated IGHV. Complete remissions occurred in 20% of the patients, including 5% who had no minimal residual disease on flow cytometry. The 15-month progression-free survival estimate for the 400-mg dose groups was 69%. CONCLUSIONS Selective targeting of BCL2 with venetoclax had a manageable safety profile and induced substantial responses in patients with relapsed CLL or SLL, including those with poor prognostic features. (Funded by AbbVie and Genentech; ClinicalTrials.gov number, NCT01328626.)

Tests of general relativity with GW150914

Abstract: The LIGO detection of GW150914 provides an unprecedented opportunity to study the two-body motion of a compact-object binary in the large-velocity, highly nonlinear regime, and to witness the final merger of the binary and the excitation of uniquely relativistic modes of the gravitational field. We carry out several investigations to determine whether GW150914 is consistent with a binary black-hole merger in general relativity. We find that the final remnant’s mass and spin, as determined from the low-frequency (inspiral) and high-frequency (postinspiral) phases of the signal, are mutually consistent with the binary black-hole solution in general relativity. Furthermore, the data following the peak of GW150914 are consistent with the least-damped quasinormal mode inferred from the mass and spin of the remnant black hole. By using waveform models that allow for parametrized general-relativity violations during the inspiral and merger phases, we perform quantitative tests on the gravitational-wave phase in the dynamical regime and we determine the first empirical bounds on several high-order post-Newtonian coefficients. We constrain the graviton Compton wavelength, assuming that gravitons are dispersed in vacuum in the same way as particles with mass, obtaining a 90%-confidence lower bound of 1013 km. In conclusion, within our statistical uncertainties, we find no evidence for violations of general relativity in the genuinely strong-field regime of gravity.

Statistical tests, P-values, confidence intervals, and power: a guide to misinterpretations

Abstract: Misinterpretation and abuse of statistical tests, confidence intervals, and statistical power have been decried for decades, yet remain rampant. A key problem is that there are no interpretations of these concepts that are at once simple, intuitive, correct, and foolproof. Instead, correct use and interpretation of these statistics requires an attention to detail which seems to tax the patience of working scientists. This high cognitive demand has led to an epidemic of shortcut definitions and interpretations that are simply wrong, sometimes disastrously so-and yet these misinterpretations dominate much of the scientific literature. In light of this problem, we provide definitions and a discussion of basic statistics that are more general and critical than typically found in traditional introductory expositions. Our goal is to provide a resource for instructors, researchers, and consumers of statistics whose knowledge of statistical theory and technique may be limited but who wish to avoid and spot misinterpretations. We emphasize how violation of often unstated analysis protocols (such as selecting analyses for presentation based on the P values they produce) can lead to small P values even if the declared test hypothesis is correct, and can lead to large P values even if that hypothesis is incorrect. We then provide an explanatory list of 25 misinterpretations of P values, confidence intervals, and power. We conclude with guidelines for improving statistical interpretation and reporting.

New tools for studying microglia in the mouse and human CNS.

Abstract: The specific function of microglia, the tissue resident macrophages of the brain and spinal cord, has been difficult to ascertain because of a lack of tools to distinguish microglia from other immune cells, thereby limiting specific immunostaining, purification, and manipulation. Because of their unique developmental origins and predicted functions, the distinction of microglia from other myeloid cells is critically important for understanding brain development and disease; better tools would greatly facilitate studies of microglia function in the developing, adult, and injured CNS. Here, we identify transmembrane protein 119 (Tmem119), a cell-surface protein of unknown function, as a highly expressed microglia-specific marker in both mouse and human. We developed monoclonal antibodies to its intracellular and extracellular domains that enable the immunostaining of microglia in histological sections in healthy and diseased brains, as well as isolation of pure nonactivated microglia by FACS. Using our antibodies, we provide, to our knowledge, the first RNAseq profiles of highly pure mouse microglia during development and after an immune challenge. We used these to demonstrate that mouse microglia mature by the second postnatal week and to predict novel microglial functions. Together, we anticipate these resources will be valuable for the future study and understanding of microglia in health and disease.

REVEL: An Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants

Abstract: The vast majority of coding variants are rare, and assessment of the contribution of rare variants to complex traits is hampered by low statistical power and limited functional data. Improved methods for predicting the pathogenicity of rare coding variants are needed to facilitate the discovery of disease variants from exome sequencing studies. We developed REVEL (rare exome variant ensemble learner), an ensemble method for predicting the pathogenicity of missense variants on the basis of individual tools: MutPred, FATHMM, VEST, PolyPhen, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP, SiPhy, phyloP, and phastCons. REVEL was trained with recently discovered pathogenic and rare neutral missense variants, excluding those previously used to train its constituent tools. When applied to two independent test sets, REVEL had the best overall performance (p −12 ) as compared to any individual tool and seven ensemble methods: MetaSVM, MetaLR, KGGSeq, Condel, CADD, DANN, and Eigen. Importantly, REVEL also had the best performance for distinguishing pathogenic from rare neutral variants with allele frequencies

Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria.

Abstract: During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this "silent" stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations.

Binary Black Hole Mergers in the First Advanced LIGO Observing Run

Abstract: The first observational run of the Advanced LIGO detectors, from September 12, 2015 to January 19, 2016, saw the first detections of gravitational waves from binary black hole mergers. In this paper we present full results from a search for binary black hole merger signals with total masses up to 100M⊙ and detailed implications from our observations of these systems. Our search, based on general-relativistic models of gravitational wave signals from binary black hole systems, unambiguously identified two signals, GW150914 and GW151226, with a significance of greater than 5σ over the observing period. It also identified a third possible signal, LVT151012, with substantially lower significance, which has a 87% probability of being of astrophysical origin. We provide detailed estimates of the parameters of the observed systems. Both GW150914 and GW151226 provide an unprecedented opportunity to study the two-body motion of a compact-object binary in the large velocity, highly nonlinear regime. We do not observe any deviations from general relativity, and place improved empirical bounds on several high-order post-Newtonian coefficients. From our observations we infer stellar-mass binary black hole merger rates lying in the range 9−240Gpc−3yr−1. These observations are beginning to inform astrophysical predictions of binary black hole formation rates, and indicate that future observing runs of the Advanced detector network will yield many more gravitational wave detections.

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants

Abstract: Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.

Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer

Abstract: Stage II colon cancer, which has spread through the wall of the colon but has not metastasized to the lymph nodes, can present a therapeutic dilemma. On one hand, these tumors can usually be completely removed by surgery, and the majority does not recur even without chemotherapy. On the other hand, it is difficult to determine which of these tumors will recur and to identify patients who would benefit from adjuvant chemotherapy after surgery. Tie et al. show that the presence of circulating tumor DNA in a patient’s blood after surgery is a sign of persistent tumor and a greatly increased risk of relapse, suggesting that this group of patients may require chemotherapy to prevent recurrence.

Primary open-angle glaucoma.

Abstract: Glaucoma is an optic neuropathy that is characterized by the progressive degeneration of the optic nerve, leading to visual impairment. Glaucoma is the main cause of irreversible blindness worldwide, but typically remains asymptomatic until very severe. Open-angle glaucoma comprises the majority of cases in the United States and western Europe, of which, primary open-angle glaucoma (POAG) is the most common type. By contrast, in China and other Asian countries, angle-closure glaucoma is highly prevalent. These two types of glaucoma are characterized based on the anatomic configuration of the aqueous humour outflow pathway. The pathophysiology of POAG is not well understood, but it is an optic neuropathy that is thought to be associated with intraocular pressure (IOP)-related damage to the optic nerve head and resultant loss of retinal ganglion cells (RGCs). POAG is generally diagnosed during routine eye examination, which includes fundoscopic evaluation and visual field assessment (using perimetry). An increase in IOP, measured by tonometry, is not essential for diagnosis. Management of POAG includes topical drug therapies and surgery to reduce IOP, although new therapies targeting neuroprotection of RGCs and axonal regeneration are under development.

Google Scholar, Scopus and the Web of Science: a longitudinal and cross-disciplinary comparison

Abstract: This article aims to provide a systematic and comprehensive comparison of the coverage of the three major bibliometric databases: Google Scholar, Scopus and the Web of Science. Based on a sample of 146 senior academics in five broad disciplinary areas, we therefore provide both a longitudinal and a cross-disciplinary comparison of the three databases. Our longitudinal comparison of eight data points between 2013 and 2015 shows a consistent and reasonably stable quarterly growth for both publications and citations across the three databases. This suggests that all three databases provide sufficient stability of coverage to be used for more detailed cross-disciplinary comparisons. Our cross-disciplinary comparison of the three databases includes four key research metrics (publications, citations, h-index, and hI, annual, an annualised individual h-index) and five major disciplines (Humanities, Social Sciences, Engineering, Sciences and Life Sciences). We show that both the data source and the specific metrics used change the conclusions that can be drawn from cross-disciplinary comparisons.

Properties of the Binary Black Hole Merger GW150914

Abstract: On September 14, 2015, the Laser Interferometer Gravitational-wave Observatory (LIGO) detected a gravitational-wave transient (GW150914); we characterise the properties of the source and its parameters. The data around the time of the event were analysed coherently across the LIGO network using a suite of accurate waveform models that describe gravitational waves from a compact binary system in general relativity. GW150914 was produced by a nearly equal mass binary black hole of $36^{+5}_{-4} M_\odot$ and $29^{+4}_{-4} M_\odot$ (for each parameter we report the median value and the range of the 90% credible interval). The dimensionless spin magnitude of the more massive black hole is bound to be $0.7$ (at 90% probability). The luminosity distance to the source is $410^{+160}_{-180}$ Mpc, corresponding to a redshift $0.09^{+0.03}_{-0.04}$ assuming standard cosmology. The source location is constrained to an annulus section of $590$ deg$^2$, primarily in the southern hemisphere. The binary merges into a black hole of $62^{+4}_{-4} M_\odot$ and spin $0.67^{+0.05}_{-0.07}$. This black hole is significantly more massive than any other known in the stellar-mass regime.