Landscape-scale drivers of glacial ecosystem change in the montane forests of the eastern Andean flank, Ecuador

Understanding the impact of landscape-scale disturbance events during the last glacial period is vital in accu- rately reconstructing the ecosystem dynamics of montane environments. Here, a sedimentary succession from the tropical montane cloud forest of the eastern Andean flank of Ecuador provides evidence of the role of non- climate drivers of vegetation change (volcanic events, fire regime and herbivory) during the late-Pleistocene. Multiproxy analysis (pollen, non-pollen palynomorphs, charcoal, geochemistry and carbon content) of the se- diments, radiocarbon dated to ca. 45–42 ka, provide a snap shot of the depositional environment, vegetation community and non-climate drivers of ecosystem dynamics. The geomorphology of the Vinillos study area, along with the organic‐carbon content, and aquatic remains suggest deposition took place near a valley floor in a swamp or shallow water environment. The pollen assemblage initially composed primarily of herbaceous types (Poaceae-Asteraceae-Solanaceae) is replaced by assemblages characterised by Andean forest taxa, (first Melastomataceae-Weinmannia-Ilex, and later, Alnus-Hedyosmum-Myrica). The pollen assemblages have no modern analogues in the tropical montane cloud forest of Ecuador. High micro-charcoal and rare macro-charcoal abundances co-occur with volcanic tephra deposits suggesting transportation from extra-local regions and that volcanic eruptions were an important source of ignition in the wider glacial landscape. The presence of the coprophilous fungi Sporormiella reveals the occurrence of herbivores in the glacial montane forest landscape. Pollen analysis indicates a stable regional vegetation community, with changes in vegetation population co- varying with large volcanic tephra deposits suggesting that the structure of glacial vegetation at Vinillos was driven by volcanic activity

Ganciclovir therapeutic drug monitoring in transplant recipients

BACKGROUND: The use of (val)ganciclovir is complicated by toxicity, slow response to treatment and acquired resistance. OBJECTIVES: To evaluate a routine therapeutic drug monitoring (TDM) programme for ganciclovir in a transplant patient population. METHODS: An observational study was performed in transplant recipients from June 2018 to February 2020. Dose adjustments were advised by the TDM pharmacist as part of clinical care. For prophylaxis, a trough concentration (Cmin) of 1-2 mg/L and an AUC24h of >50 mg·h/L were aimed for. For treatment, a Cmin of 2-4 mg/L and an AUC24h of 80-120 mg·h/L were aimed for. RESULTS: Ninety-five solid organ and stem cell transplant patients were enrolled. Overall, 450 serum concentrations were measured; with a median of 3 (IQR = 2-6) per patient. The median Cmin and AUC24h in the treatment and prophylaxis groups were 2.0 mg/L and 90 mg·h/L and 0.9 mg/L and 67 mg·h/L, respectively. Significant intra- and inter-patient patient variability was observed. The majority of patients with an estimated glomerular filtration rate of more than 120 mL/min/1.73 m2 and patients on continuous veno-venous haemofiltration showed underexposure. The highest Cmin and AUC24h values were associated with the increase in liver function markers and decline in WBC count as compared with baseline. CONCLUSIONS: This study revealed that a standard weight and kidney function-based dosing regimen resulted in highly variable ganciclovir Cmin and under- and over-exposure were observed in patients on dialysis and in patients with increased renal function. Clearly there is a need to explore the impact of concentration-guided dose adjustments in a prospective study

Life beyond 30: Probing the-20 < M (UV) <-17 Luminosity Function at 8 < z < 13 with the NIRCam Parallel Field of the MIRI Deep Survey

We present the ultraviolet luminosity function and an estimate of the cosmic star formation rate density at 8 8 galaxy candidates based on their dropout nature in the F115W and/or F150W filters, a high probability for their photometric redshifts, estimated with three different codes, being at z > 8, good fits based on χ 2 calculations, and predominant solutions compared to z < 8 alternatives. We find mild evolution in the luminosity function from z ∼ 13 to z ∼ 8, i.e., only a small increase in the average number density of ∼0.2 dex, while the faint-end slope and absolute magnitude of the knee remain approximately constant, with values α = − 2.2 ± 0.1, and M * = − 20.8 ± 0.2 mag. Comparing our results with the predictions of state-of-the-art galaxy evolution models, we find two main results: (1) a slower increase with time in the cosmic star formation rate density compared to a steeper rise predicted by models; (2) nearly a factor of 10 higher star formation activity concentrated in scales around 2 kpc in galaxies with stellar masses ∼108 M ⊙ during the first 350 Myr of the universe, z ∼ 12, with models matching better the luminosity density observational estimations ∼150 Myr later, by z ∼ 9

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

State of the climate in 2018

In 2018, the dominant greenhouse gases released into Earth’s atmosphere—carbon dioxide, methane, and nitrous oxide—continued their increase. The annual global average carbon dioxide concentration at Earth’s surface was 407.4 ± 0.1 ppm, the highest in the modern instrumental record and in ice core records dating back 800 000 years. Combined, greenhouse gases and several halogenated gases contribute just over 3 W m−2 to radiative forcing and represent a nearly 43% increase since 1990. Carbon dioxide is responsible for about 65% of this radiative forcing. With a weak La Niña in early 2018 transitioning to a weak El Niño by the year’s end, the global surface (land and ocean) temperature was the fourth highest on record, with only 2015 through 2017 being warmer. Several European countries reported record high annual temperatures. There were also more high, and fewer low, temperature extremes than in nearly all of the 68-year extremes record. Madagascar recorded a record daily temperature of 40.5°C in Morondava in March, while South Korea set its record high of 41.0°C in August in Hongcheon. Nawabshah, Pakistan, recorded its highest temperature of 50.2°C, which may be a new daily world record for April. Globally, the annual lower troposphere temperature was third to seventh highest, depending on the dataset analyzed. The lower stratospheric temperature was approximately fifth lowest. The 2018 Arctic land surface temperature was 1.2°C above the 1981–2010 average, tying for third highest in the 118-year record, following 2016 and 2017. June’s Arctic snow cover extent was almost half of what it was 35 years ago. Across Greenland, however, regional summer temperatures were generally below or near average. Additionally, a satellite survey of 47 glaciers in Greenland indicated a net increase in area for the first time since records began in 1999. Increasing permafrost temperatures were reported at most observation sites in the Arctic, with the overall increase of 0.1°–0.2°C between 2017 and 2018 being comparable to the highest rate of warming ever observed in the region. On 17 March, Arctic sea ice extent marked the second smallest annual maximum in the 38-year record, larger than only 2017. The minimum extent in 2018 was reached on 19 September and again on 23 September, tying 2008 and 2010 for the sixth lowest extent on record. The 23 September date tied 1997 as the latest sea ice minimum date on record. First-year ice now dominates the ice cover, comprising 77% of the March 2018 ice pack compared to 55% during the 1980s. Because thinner, younger ice is more vulnerable to melting out in summer, this shift in sea ice age has contributed to the decreasing trend in minimum ice extent. Regionally, Bering Sea ice extent was at record lows for almost the entire 2017/18 ice season. For the Antarctic continent as a whole, 2018 was warmer than average. On the highest points of the Antarctic Plateau, the automatic weather station Relay (74°S) broke or tied six monthly temperature records throughout the year, with August breaking its record by nearly 8°C. However, cool conditions in the western Bellingshausen Sea and Amundsen Sea sector contributed to a low melt season overall for 2017/18. High SSTs contributed to low summer sea ice extent in the Ross and Weddell Seas in 2018, underpinning the second lowest Antarctic summer minimum sea ice extent on record. Despite conducive conditions for its formation, the ozone hole at its maximum extent in September was near the 2000–18 mean, likely due to an ongoing slow decline in stratospheric chlorine monoxide concentration. Across the oceans, globally averaged SST decreased slightly since the record El Niño year of 2016 but was still far above the climatological mean. On average, SST is increasing at a rate of 0.10° ± 0.01°C decade−1 since 1950. The warming appeared largest in the tropical Indian Ocean and smallest in the North Pacific. The deeper ocean continues to warm year after year. For the seventh consecutive year, global annual mean sea level became the highest in the 26-year record, rising to 81 mm above the 1993 average. As anticipated in a warming climate, the hydrological cycle over the ocean is accelerating: dry regions are becoming drier and wet regions rainier. Closer to the equator, 95 named tropical storms were observed during 2018, well above the 1981–2010 average of 82. Eleven tropical cyclones reached Saffir–Simpson scale Category 5 intensity. North Atlantic Major Hurricane Michael’s landfall intensity of 140 kt was the fourth strongest for any continental U.S. hurricane landfall in the 168-year record. Michael caused more than 30 fatalities and $25 billion (U.S. dollars) in damages. In the western North Pacific, Super Typhoon Mangkhut led to 160 fatalities and$6 billion (U.S. dollars) in damages across the Philippines, Hong Kong, Macau, mainland China, Guam, and the Northern Mariana Islands. Tropical Storm Son-Tinh was responsible for 170 fatalities in Vietnam and Laos. Nearly all the islands of Micronesia experienced at least moderate impacts from various tropical cyclones. Across land, many areas around the globe received copious precipitation, notable at different time scales. Rodrigues and Réunion Island near southern Africa each reported their third wettest year on record. In Hawaii, 1262 mm precipitation at Waipā Gardens (Kauai) on 14–15 April set a new U.S. record for 24-h precipitation. In Brazil, the city of Belo Horizonte received nearly 75 mm of rain in just 20 minutes, nearly half its monthly average. Globally, fire activity during 2018 was the lowest since the start of the record in 1997, with a combined burned area of about 500 million hectares. This reinforced the long-term downward trend in fire emissions driven by changes in land use in frequently burning savannas. However, wildfires burned 3.5 million hectares across the United States, well above the 2000–10 average of 2.7 million hectares. Combined, U.S. wildfire damages for the 2017 and 2018 wildfire seasons exceeded $40 billion (U.S. dollars)

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2

A comprehensive quantification of global nitrous oxide sources and sinks

Nitrous oxide (N2O), like carbon dioxide, is a long-lived greenhouse gas that accumulates in the atmosphere. Over the past 150 years, increasing atmospheric N2O concentrations have contributed to stratospheric ozone depletion1 and climate change2, with the current rate of increase estimated at 2 per cent per decade. Existing national inventories do not provide a full picture of N2O emissions, owing to their omission of natural sources and limitations in methodology for attributing anthropogenic sources. Here we present a global N2O inventory that incorporates both natural and anthropogenic sources and accounts for the interaction between nitrogen additions and the biochemical processes that control N2O emissions. We use bottom-up (inventory, statistical extrapolation of flux measurements, process-based land and ocean modelling) and top-down (atmospheric inversion) approaches to provide a comprehensive quantification of global N2O sources and sinks resulting from 21 natural and human sectors between 1980 and 2016. Global N2O emissions were 17.0 (minimum–maximum estimates: 12.2–23.5) teragrams of nitrogen per year (bottom-up) and 16.9 (15.9–17.7) teragrams of nitrogen per year (top-down) between 2007 and 2016. Global human-induced emissions, which are dominated by nitrogen additions to croplands, increased by 30% over the past four decades to 7.3 (4.2–11.4) teragrams of nitrogen per year. This increase was mainly responsible for the growth in the atmospheric burden. Our findings point to growing N2O emissions in emerging economies—particularly Brazil, China and India. Analysis of process-based model estimates reveals an emerging N2O–climate feedback resulting from interactions between nitrogen additions and climate change. The recent growth in N2O emissions exceeds some of the highest projected emission scenarios3,4, underscoring the urgency to mitigate N2O emissions

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Transformations of Nitrosoarenes and Alkynyl Enones : Selective Synthesis of Nitrogen-Containing Compounds

The nitrogen atom plays a unique role in organic chemistry. It is abundantly found in organic materials and is responsible for the activity of many biologically relevant compounds. In this thesis, nitrosoarenes and keto- and pyridyl-substituted enynes are used as convenient starting materials for the selective synthesis of nitrogen-containing compounds. Nitrosoarenes are versatile compounds that can undergo a broad range of reactions. The nature of the nitroso group is significantly different from that of related nitrogen-based functional groups and this can be used as an advantage in the development of new methodology. In the first part of this thesis, the para-selective halogenation of nitrosoarenes with copper(II) halides as halogenating reagents is explored. The one-pot transformation of the products to the corresponding nitroarenes and anilines is demonstrated. The use of nitrosoarenes for radical N-perfluoroalkylation is presented in the next chapters. N-Perfluoroalkylation is a relatively new field and only a limited number of reagents and substrates have been employed so far. In this thesis, the stable and convenient Langlois reagent was used to achieve selective N-trifluoromethylation of nitrosoarenes to obtain the corresponding hydroxylamines. Longer perfluoroalkyl chains were investigated as well, but the less stable products were defluorinated to form hydroxamic acid derivatives. These products could be reduced to yield perfluoroalkyl amides. Keto- and pyridyl-substituted enynes are starting materials designed to undergo cyclization reactions in the presence of a metal catalyst and a nucleophile. This offers the possibility to obtain a variety of more complex molecular structures in a single step. In the second half of the thesis, the reaction between these starting materials and enamines is explored. A range of cyclopenta[c]furans were synthesized in good yields and with high diastereoselectivities from alkynyl enones and enamines with InBr3 as the catalyst. The enamines were formed in situ in a multicomponent reaction. Pyridyl-substituted enynes are the pyridine analogues of alkynyl enones and were found to form polycyclic indolizines in the reaction with cyclic enamines with AgOTf as a catalyst. Good yields and high to excellent diastereoselectivities were obtained. When the reaction was performed with in situ-generated enamines, different indolizine derivatives were obtained.At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 5: Manuscript.</p

Para-Selective Halogenation of Nitrosoarenes with Copper(II) Halides

The para-selective direct bromination and chlorination of nitrosoarenes with copper(II) bromide and chloride is reported. Under mild reaction conditions, a rang of halogenated arylnitroso compounds are obtained in moderate to good yields with high regioselectivity. Additionally, the versatility of the method is demonstrated by the development of a One-pot procedure to obtain the corresponding para-halogenated aniline- and nitrobenzene derivatives