Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world’s rivers, representing the environmental influence of 471.4 million people across 137 geographic regions. Samples were obtained from 1,052 locations in 104 countries (representing all continents and 36 countries not previously studied for API contamination) and analyzed for 61 APIs. Highest cumulative API concentrations were observed in sub-Saharan Africa, south Asia, and South America. The most contaminated sites were in low- to middle-income countries and were associated with areas with poor wastewater and waste management infrastructure and pharmaceutical manufacturing. The most frequently detected APIs were carbamazepine, metformin, and caffeine (a compound also arising from lifestyle use), which were detected at over half of the sites monitored. Concentrations of at least one API at 25.7% of the sampling sites were greater than concentrations considered safe for aquatic organisms, or which are of concern in terms of selection for antimicrobial resistance. Therefore, pharmaceutical pollution poses a global threat to environmental and human health, as well as to delivery of the United Nations Sustainable Development Goals.

Preexploitation shark baselines and the history of human impact on coral reef–associated shark communities in the Caribbean are tpoorly understood. We recovered shark dermal denticles from mid-Holocene (∼7 ky ago) and modern reef sediments in Bocas del Toro, Caribbean Panama, to reconstruct an empirical shark baseline before major human impact and to quantify how much the modern shark community in the region had shifted from this historical reference point. We found that denticle accumulation rates, a proxy for shark abundance, declined by 71% since the mid-Holocene. All denticle morphotypes, which reflect shark community composition, experienced significant losses, but those morphotypes found on fast-swimming, pelagic sharks (e.g., families Carcharhinidae and Sphyrnidae) declined the most. An analysis of historical records suggested that the steepest decline in shark abundance occurred in the late 20th century, coinciding with the advent of a targeted shark fishery in Panama. Although the disproportionate loss of denticles characterizing pelagic sharks was consistent with overfishing, the large reduction in denticles characterizing demersal species with low commercial value (i.e., the nurse shark Ginglymostoma cirratum) indicated that other stressors could have exacerbated these declines. We demonstrate that the denticle record can reveal changes in shark communities over long ecological timescales, helping to contextualize contemporary abundances and inform shark management and ecology.

23There is a consensus that Caribbean coral reefs are a pale shadow of what they once were, 24 yet a reef's pre-human state is typically assumed or estimated using space-for-time 25 substitution approaches. These approaches may fail to account for past variation before 26 human impact which could mislead conservation priorities and actions. In this study we use 27 a suite of fossilised mid-Holocene (7.2-5.6 ka) fringing reefs in Caribbean Panama to define 28 the Historical Range of Variation (HRV) in coral community structure before human-impact 29 to provide context for the states of modern reefs in the same area. Using the abundances of 30 coral taxa to quantify communities, we found that most of the modern coral communities 31 exist in novel ecosystem states with no fossil precedence. We do however identify one 32 modern reef that is indistinguishable in coral community structure from the mid-Holocene 33 reefs. Reef-matrix cores show that the community on this reef has remained in a stable 34 state for over 760 years, suggesting long-term resistance to the region-wide shift to novel 35 states. Without historical context this robust and stable reef would be overlooked since it 36 does not fulfil expectations of what a "pristine" coral reef should look like. This example 37 illustrates how defining past variation using the fossil record can place modern degradation 38 in historical context and improve conservation recommendations. 39 40 41 Introduction 42Caribbean coral reefs started to deteriorate long before most were first surveyed [1][2][3][4][5][6][7]. 43Consequently, modern benchmarks used to inform and evaluate the success of conservation 44 actions often rely on space-for-time substitution, which assume that spatial patterns across 45 modern gradients are a suitable proxy for temporal patterns. The approach is a mainstay of 46 conservation ecology, and has proved beneficial in coral reef ecology [e.g. 8], but relies on 47 7 and 10.02% in modern samples (electronic supplementary material, Table S2), suggesting no 131 substantial difference in preservation between the two ages. Relative weights of coral taxa 132 in each sample were square-root transformed to reduce the influence of dominant taxa 133 prior to analysis. To calculate Bray-Curtis dissimilarities of samples we used the function 134 vegdist of the software package vegan [41] in R. The NMDS (Kruskal's Non-metric 135 Multidimensional Scaling) was computed using isoMDS function of the software package 136 MASS [42] in R which was then plotted using ggplot [43] in R [44]. The function adonis 137

This file includesSupplemental radiometric dating methods figures S1 to S4 Tables S1 and S2References for supplementary material 1 Supplemental radiometric dating methods U-Th dating was conducted on coral fragments using a Nu Plasma multi-collector inductively-coupled plasma mass spectrometer (MC-ICP-MS) in the Radiogenic Isotope Facility at the University of Queensland, following chemical treatment procedures and MC-ICP-MS analytical protocols described in Clark et al. [1] . For U-Th dating, each coral sample consisting of ~150 mg fine sand-size chips that were carefully fragmented, H 2 O 2 -treated and then hand-picked under a binocular microscope to remove any trace detritus or grains with discolouration was spiked with a mixed 229 Th-233 U tracer and then completely dissolved in double-distilled concentrated HNO 3 . After digestion, each sample was further treated with H 2 O 2 to decompose trace amounts of organic matter (if any) and to facilitate complete sample-tracer homogenization. U and Th were separated using conventional anion-exchange column chemistry using Bio-Rad AG 1-X8 resin. After stripping off the matrix from the column using double-distilled 7N HNO 3 as eluent, 4 N HNO 3 and 2%HNO 3 +0.03% HF mixture were used to elute U and Th into 3.5 ml pre-cleaned test tubes, respectively. After screening U and Th concentrations in the U and Th fractions using their 1:100 dilute solutions on a quadrupole ICP-MS, the U and Th separates for the samples were then re-mixed in 2% HNO 3 to make ~3 ml solution in a pre-cleaned 3.5 ml test tube. The mixed solution for each sample contained the entire Th fraction and a small percentage of the U fraction. The amount of U fraction to be added to the mixed solution was calculated based on the screening results and the MC-ICP-MS working sensitivity of the day, aiming to achieve ~5 volts of 238 U signal. The remixed U-Th solution was injected into the MC-ICP-MS through a DSN-100 desolvation nebulizer system with an uptake rate of ~0.06 ml/min. U-Th isotopic measurements were performed on the MC-ICP-MS using a detector configuration to allow simultaneous measurements of both U and Th isotopes. The 230 Th/ 238 U and 234 U/ 238 U activity ratios of the samples were calculated using the decay constants given in Cheng et al. [2] . 230 Th ages were calculated using the Isoplot 3.75 Program [3] . 230 Th ages were corrected for non-radiogenic 230 Th contributions using a modelled two-component-mixing non-radiogenic 230 Th/ 232 Th value based on the equation in Clark et al. [1] .

In Panama, shark fisheries were initially developed in the 1980s and progressively increased in production in the 1990s mainly due to the high demand for shark fins and meat from the international Asian market. Since then, and despite the exploitation rate (average 3,514 t year–1) and endangered status of some species, shark fisheries have seldom been studied, and official statistics are general or incomplete and not suitable for the development of appropriate conservation and management strategies. To understand the dynamics of shark fisheries in Panama, field surveys were conducted between 2007 and 2009 at several landing ports of small‐scale and industrial fisheries, at fish processing plants and on‐board fishing vessels in Pacific Panama, where most of the fishing vessels of the country operate. In general, it was found that the artisanal and industrial fisheries of the Pacific coast of Panama regularly exploit at least 18 species of sharks, which are also being exploited by neighbouring countries in the eastern Pacific, suggesting the importance of coordinated conservation initiatives across the multiple jurisdictions. A large number of the individuals caught were immature, implying a certain level of impact on recruitment rates. This pattern was particularly evident in species such as Sphyrna lewini, for which immature individuals represented at least 99% and 63% of the total catch by small‐scale and industrial fisheries, respectively. Catch per unit of effort analyses showed that Carcharhinus and Sphyrna species were the most exploited (representing ~80% of the catches) by industrial fisheries in Panama between 2006 and 2009, suggesting that fishery management should provide special attention to these groups. It is expected that the information presented here provides a baseline to develop new regulations, including the implementation of annual quotas and fishing seasons and the protection of nursery areas, for the long‐term sustainability and conservation of sharks in Panama.