Switching of excited states in cyclometalated platinum complexes incorporating pyridyl-acetylide ligands (Pt-C[triple bond, length as m-dash]C-py): a combined experimental and theoretical study

International audienceThis article presents the design of cyclometalated platinum(II) complexes incorporating pyridyl-appended acetylide ligands of the form Pt-C[triple bond, length as m-dash]C-py, acting either as sites for protonation or methylation reactions or as a host receptor for binding metal cations. The complexes studied are Pt(t-Bu2phbpy)(-C[triple bond, length as m-dash]C-py), 2, which can undergo protonation at the pyridyl N; its cationic N-methylated derivative [Pt(t-Bu2phbpy)(-C[triple bond, length as m-dash]C-pyMe)]+, 4, which serves as a model of the N-protonated species; and a derivative in which the pyridyl ring is incorporated into a macrocyclic diamide-crown ether ligand (3). The co-ligand t-Bu2phbpy is a cyclometalated, N[caret]N[caret]C-coordinated phenylbipyridine ligand carrying tert-butyl groups at the 4-positions of the pyridyl rings. The photophysical properties of the neutral compounds 2 and 3 have been compared to those of the pyridinium, methyl-pyridinium or metal-complexed species (namely 2-H+, 4 and 3-Pb2+). Detailed TD-DFT calculations provide a theoretical basis to account for the experimentally-observed changes upon protonation/methylation/complexation. The joint TD-DFT and experimental studies provide evidence for an unprecedented molecular switch in the nature of the excited state (from mixed L′LCT/MLCT to ML′CT) in which the acceptor ligand in the CT process switches from being the N[caret]N[caret]C ligand to the pyridyl acetylide

GTWS-MLrec: global terrestrial water storage reconstruction by machine learning from 1940 to present

Terrestrial water storage (TWS) includes all forms of water stored on and below the land surface, and is a key determinant of global water and energy budgets. However, TWS data from measurements by the Gravity Recovery and Climate Experiment (GRACE) satellite mission are only available from 2002, limiting global and regional understanding of the long-term trends and variabilities in the terrestrial water cycle under climate change. This study presents long-term (i.e., 1940–2022) and relatively high-resolution (i.e., 0.25∘) monthly time series of TWS anomalies over the global land surface. The reconstruction is achieved by using a set of machine learning models with a large number of predictors, including climatic and hydrological variables, land use/land cover data, and vegetation indicators (e.g., leaf area index). The outcome, machine-learning-reconstructed TWS estimates (i.e., GTWS-MLrec), fits well with the GRACE/GRACE-FO measurements, showing high correlation coefficients and low biases in the GRACE era. We also evaluate GTWS-MLrec with other independent products such as the land–ocean mass budget, atmospheric and terrestrial water budget in 341 large river basins, and streamflow measurements at 10 168 gauges. The results show that our proposed GTWS-MLrec performs overall as well as, or is more reliable than, previous TWS datasets. Moreover, our reconstructions successfully reproduce the consequences of climate variability such as strong El Niño events. The GTWS-MLrec dataset consists of three reconstructions based on (a) mascons of the Jet Propulsion Laboratory of the California Institute of Technology, the Center for Space Research at the University of Texas at Austin, and the Goddard Space Flight Center of NASA; (b) three detrended and de-seasonalized reconstructions; and (c) six global average TWS series over land areas, both with and without Greenland and Antarctica. Along with its extensive attributes, GTWS_MLrec can support a wide range of geoscience applications such as better understanding the global water budget, constraining and evaluating hydrological models, climate-carbon coupling, and water resources management. GTWS-MLrec is available on Zenodo through https://doi.org/10.5281/zenodo.10040927 (Yin, 2023)

Observed long-term land cover vs climate impacts on the West African hydrological cycle: lessons for the future ? [P-3330-65]

West Africa has experienced a long lasting, severe drought as from 1970, which seems to be attenuating since 2000. It has induced major changes in living conditions and resources over the region. In the same period, marked changes of land use and land cover have been observed: land clearing for agriculture, driven by high demographic growth rates, and ecosystem evolutions driven by the rainfall deficit. Depending on the region, the combined effects of these climate and environmental changes have induced contrasted impacts on the hydrological cycle. In the Sahel, runoff and river discharges have increased despite the rainfall reduction (“less rain, more water”, the so-called "Sahelian paradox "). Soil crusting and erosion have increased the runoff capacity of the watersheds so that it outperformed the rainfall deficit. Conversely, in the more humid Guinean and Sudanian regions to the South, the opposite (and expected) “less rain, less water” behavior is observed, but the signature of land cover changes can hardly be detected in the hydrological records. These observations over the past 50 years suggest that the hydrological response to climate change can not be analyzed irrespective of other concurrent changes, and primarily ecosystem dynamics and land cover changes. There is no consensus on future rainfall trend over West Africa in IPCC projections, although a higher occurrence of extreme events (rainstorms, dry spells) is expected. An increase in the need for arable land and water resources is expected as well, driven by economic development and demographic growth. Based on past long-term observations on the AMMA-CATCH observatory, we explore in this work various future combinations of climate vs environmental drivers, and we infer the expected resulting trends on water resources, along the west African eco-climatic gradient. (Texte intégral

Elimination of Active Trachoma after Two Topical Mass Treatments with Azithromycin 1.5% Eye Drops

Trachoma is the leading cause of infectious blindness worldwide, accounting for 1.3 million cases of blindness. Although it has disappeared in many regions of the world, trachoma is still endemic in Africa, Eastern Mediterranean, Latin America, Asia, and Australia. The WHO has currently set a target of 2020 for controlling trachoma to a low enough level that resulting blindness will not be a major public health concern. Topical tetracycline was for a long time the recommended treatment for active trachoma, but compliance to the regimen is extremely poor. Azithromycin has properties that make it an ideal treatment for Chlamydia trachomatis: high efficacy, intracellular accumulation, and a long tissue half-life. There is now a new mass treatment of trachoma by azithromycin 1.5% eye drops which is as effective as the oral route. In the test health district of Kolofata, Cameroon, the prevalence of trachoma among children dramatically decreased from 31% to less than 5% after 2 treatments. A third treatment was performed in January 2010. An epidemiological surveillance is implemented to see if this removal will be permanent. It also avoids misuse of oral azithromycin and the eye drops are directly treating the site of the infection

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

Global prevalence and genotype distribution of hepatitis C virus infection in 2015 : A modelling study

Publisher Copyright: © 2017 Elsevier LtdBackground The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of—and expansion on—the 2014 analysis, which reported 80 million (95% CI 64–103) viraemic infections in 2013. Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data. Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insufficient data to create a model. The global prevalence of viraemic HCV is estimated to be 1·0% (95% uncertainty interval 0·8–1·1) in 2015, corresponding to 71·1 million (62·5–79·4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively). Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections. Funding John C Martin Foundation.publishersversionPeer reviewe

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

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

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries