Early oncological outcomes of delayed radical prostatectomy: A prospective, international, follow-up analysis of the COVIDSurg-Cancer study.

Objectives: The objective of this study is to compare the early oncological outcomes of delayed (>90 days) versus scheduled (≤90 days) radical prostatectomy (RP).

Patients And Methods: Patients with prostate cancer due to undergo surgery between March 2020 and June 2020 who were enrolled in the COVIDSurg-Cancer international, observational study were prospectively followed up for 1 year. Time to surgery was defined as the difference between the operation date and the multi-disciplinary team decision to offer surgery.

Understanding the long-term impact of the COVID-19 pandemic on non-muscle-invasive bladder cancer outcomes: 12-Month follow-up data from the international, prospective COVIDSurg Cancer study.

Objective: The objective of this study was to report the 12-month oncological outcomes for patients with non-muscle-invasive bladder cancer (NMIBC) within the prospective, international COVIDSurg Cancer study.

Patients And Methods: Eligible patients were aged ≥18 years and scheduled for elective surgical management of NMIBC with curative intent (transurethral resection of bladder tumour [TURBT] or bladder biopsy) from 21 January to 14 April 2020. The primary outcome was disease recurrence within 12 months of previous elective TURBT/bladder biopsy.

Childbirth Acquired Perineal Trauma study (CHAPTER): a UK prospective cohort study protocol.

Introduction: Childbirth-related perineal trauma (CRPT) is the most common complication of childbirth affecting 80% of women overall after vaginal birth. There remains a lack of comprehensive evidence relating to the prevalence of subsequent health problems. Current evidence is related to short-term outcomes, for example, pain, but there is less known about longer-term outcomes such as infection, wound dehiscence, pelvic floor function and psychological outcomes.

Utility of severity assessment tools in COVID-19 pneumonia: a multicentre observational study.

Background: Severity scores in pneumonia and sepsis are being applied to SARS-CoV-2 infection. We aimed to assess whether these severity scores are accurate predictors of early adverse outcomes in COVID-19.

Methods: We conducted a multicentre observational study of hospitalised SARS-CoV-2 infection.

Emergent properties in the responses of tropical corals to recurrent climate extremes.

The frequency, intensity, and spatial scale of climate extremes are changing rapidly due to anthropogenic global warming. A growing research challenge is to understand how multiple climate-driven disturbances interact with each other over multi-decadal time frames, generating combined effects that cannot be predicted from single events alone. Here we examine the emergent dynamics of five coral bleaching events along the 2,300 km length of the Great Barrier Reef that affected >98% of the Reef between 1998 and 2020.

The spatial footprint and patchiness of large-scale disturbances on coral reefs.

Ecosystems have always been shaped by disturbances, but many of these events are becoming larger, more severe and more frequent. The recovery capacity of depleted populations depends on the frequency of disturbances, the spatial distribution of mortality and the scale of dispersal. Here, we show that four mass coral bleaching events on the Great Barrier Reef (in 1998, 2002, 2016 and 2017) each had markedly larger disturbance footprints and were less patchy than a severe category 5 tropical cyclone (Cyclone Yasi, 2011).

The population sizes and global extinction risk of reef-building coral species at biogeographic scales.

Knowledge of a species' abundance is critically important for assessing its risk of extinction, but for the vast majority of wild animal and plant species such data are scarce at biogeographic scales. Here, we estimate the total number of reef-building corals and the population sizes of more than 300 individual species on reefs spanning the Pacific Ocean biodiversity gradient, from Indonesia to French Polynesia. Our analysis suggests that approximately half a trillion corals (0.

Corridors of Clarity: Four Principles to Overcome Uncertainty Paralysis in the Anthropocene.

Global environmental change challenges humanity because of its broad scale, long-lasting, and potentially irreversible consequences. Key to an effective response is to use an appropriate scientific lens to peer through the mist of uncertainty that threatens timely and appropriate decisions surrounding these complex issues. Identifying such corridors of clarity could help understanding critical phenomena or causal pathways sufficiently well to justify taking policy action.

Long-term shifts in the colony size structure of coral populations along the Great Barrier Reef.

The age or size structure of a population has a marked influence on its demography and reproductive capacity. While declines in coral cover are well documented, concomitant shifts in the size-frequency distribution of coral colonies are rarely measured at large spatial scales. Here, we document major shifts in the colony size structure of coral populations along the 2300 km length of the Great Barrier Reef relative to historical baselines (1995/1996).

Correction to Identification of Quinoline-Based RIP2 Kinase Inhibitors with an Improved Therapeutic Index to the hERG Ion Channel.

[This corrects the article DOI: 10.1021/acsmedchemlett.8b00344.

Rebuilding marine life.

Sustainable Development Goal 14 of the United Nations aims to "conserve and sustainably use the oceans, seas and marine resources for sustainable development". Achieving this goal will require rebuilding the marine life-support systems that deliver the many benefits that society receives from a healthy ocean. Here we document the recovery of marine populations, habitats and ecosystems following past conservation interventions.

Climate change, ecosystems and abrupt change: science priorities.

Ecologists have long studied patterns, directions and tempos of change, but there is a pressing need to extend current understanding to empirical observations of abrupt changes as climate warming accelerates. Abrupt changes in ecological systems (ACES)-changes that are fast in time or fast relative to their drivers-are ubiquitous and increasing in frequency. Powerful theoretical frameworks exist, yet applications in real-world landscapes to detect, explain and anticipate ACES have lagged.

Deficits in functional trait diversity following recovery on coral reefs.

The disturbance regimes of ecosystems are changing, and prospects for continued recovery remain unclear. New assemblages with altered species composition may be deficient in key functional traits. Alternatively, important traits may be sustained by species that replace those in decline (response diversity).

Discovery of Pyrazolocarboxamides as Potent and Selective Receptor Interacting Protein 2 (RIP2) Kinase Inhibitors.

Herein we report the discovery of pyrazolocarboxamides as novel, potent, and kinase selective inhibitors of receptor interacting protein 2 kinase (RIP2). Fragment based screening and design principles led to the identification of the inhibitor series, and X-ray crystallography was used to inform key structural changes. Through key substitutions about the N1 and C5 N positions on the pyrazole ring significant kinase selectivity and potency were achieved.

Refugia under threat: Mass bleaching of coral assemblages in high-latitude eastern Australia.

Environmental anomalies that trigger adverse physiological responses and mortality are occurring with increasing frequency due to climate change. At species' range peripheries, environmental anomalies are particularly concerning because species often exist at their environmental tolerance limits and may not be able to migrate to escape unfavourable conditions. Here, we investigated the bleaching response and mortality of 14 coral genera across high-latitude eastern Australia during a global heat stress event in 2016.

Global warming impairs stock-recruitment dynamics of corals.

Changes in disturbance regimes due to climate change are increasingly challenging the capacity of ecosystems to absorb recurrent shocks and reassemble afterwards, escalating the risk of widespread ecological collapse of current ecosystems and the emergence of novel assemblages. In marine systems, the production of larvae and recruitment of functionally important species are fundamental processes for rebuilding depleted adult populations, maintaining resilience and avoiding regime shifts in the face of rising environmental pressures. Here we document a regional-scale shift in stock-recruitment relationships of corals along the Great Barrier Reef-the world's largest coral reef system-following unprecedented back-to-back mass bleaching events caused by global warming.

Identification of Quinoline-Based RIP2 Kinase Inhibitors with an Improved Therapeutic Index to the hERG Ion Channel.

RIP2 kinase was recently identified as a therapeutic target for a variety of autoimmune diseases. We have reported previously a selective 4-aminoquinoline-based RIP2 inhibitor and demonstrated its effectiveness in blocking downstream NOD2 signaling in cellular models, rodent in vivo models, and human ex vivo disease models. While this tool compound was valuable in validating the biological pathway, it suffered from activity at the hERG ion channel and a poor PK/PD profile thereby limiting progression of this analog.

Donated chemical probes for open science.

Potent, selective and broadly characterized small molecule modulators of protein function (chemical probes) are powerful research reagents. The pharmaceutical industry has generated many high-quality chemical probes and several of these have been made available to academia. However, probe-associated data and control compounds, such as inactive structurally related molecules and their associated data, are generally not accessible.

Global warming transforms coral reef assemblages.

Global warming is rapidly emerging as a universal threat to ecological integrity and function, highlighting the urgent need for a better understanding of the impact of heat exposure on the resilience of ecosystems and the people who depend on them . Here we show that in the aftermath of the record-breaking marine heatwave on the Great Barrier Reef in 2016 , corals began to die immediately on reefs where the accumulated heat exposure exceeded a critical threshold of degree heating weeks, which was 3-4 °C-weeks. After eight months, an exposure of 6 °C-weeks or more drove an unprecedented, regional-scale shift in the composition of coral assemblages, reflecting markedly divergent responses to heat stress by different taxa.

Biogeographical disparity in the functional diversity and redundancy of corals.

Corals are major contributors to a range of key ecosystem functions on tropical reefs, including calcification, photosynthesis, nutrient cycling, and the provision of habitat structure. The abundance of corals is declining at multiple scales, and the species composition of assemblages is responding to escalating human pressures, including anthropogenic global warming. An urgent challenge is to understand the functional consequences of these shifts in abundance and composition in different biogeographical contexts.