Leveraging gains from African Center for Integrated Laboratory Training to combat HIV epidemic in sub-Saharan Africa.

BACKGROUND: In sub-Saharan Africa, there is dearth of trained laboratorians and strengthened laboratory systems to provide adequate and quality laboratory services for enhanced HIV control. In response to this challenge, in 2007, the African Centre for Integrated Laboratory Training (ACILT) was established in South Africa with a mission to train staffs from countries with high burdens of diseases in skills needed to strengthen sustainable laboratory systems. This study was undertaken to assess the transference of newly gained knowledge and skills to other laboratory staff, and to identify enabling and obstructive factors to their implementation. METHODS: We used Kirkpatrick model to determine training effectiveness by assessing the transference of newly gained knowledge and skills to participant's work environment, along with measuring enabling and obstructive factors. In addition to regular course evaluations at ACILT (pre and post training), in 2015 we sent e-questionnaires to 867 participants in 43 countries for course participation between 2008 and 2014. Diagnostics courses included Viral Load, and systems strengthening included strategic planning and Biosafety and Biosecurity. SAS v9.44 and Excel were used to analyze retrospective de-identified data collected at six months pre and post-training. RESULTS: Of the 867 participants, 203 (23.4%) responded and reported average improvements in accuracy and timeliness in Viral Load programs and to systems strengthening. For Viral Load testing, frequency of corrective action for unsatisfactory proficiency scores improved from 57 to 91%, testing error rates reduced from 12.9% to 4.9%; 88% responders contributed to the first national strategic plan development and 91% developed strategies to mitigate biosafety risks in their institutions. Key enabling factors were team and management support, and key obstructive factors included insufficient resources and staff's resistance to change. CONCLUSIONS: Training at ACILT had a documented positive impact on strengthening the laboratory capacity and laboratory workforce and substantial cost savings. ACILT's investment produced a multiplier effect whereby national laboratory systems, personnel and leadership reaped training benefits. This laboratory training centre with a global clientele contributed to improve existing laboratory services, systems and networks for the HIV epidemic and is now being leveraged for COVID-19 testing that has infected 41,332,899 people globally.

Coupled European and Greenland last glacial dust activity driven by North Atlantic climate.

Centennial-scale mineral dust peaks in last glacial Greenland ice cores match the timing of lowest Greenland temperatures, yet little is known of equivalent changes in dust-emitting regions, limiting our understanding of dust-climate interaction. Here, we present the most detailed and precise age model for European loess dust deposits to date, based on 125 accelerator mass spectrometry 14C ages from Dunaszekcso, Hungary. The record shows that variations in glacial dust deposition variability on centennial-millennial timescales in east central Europe and Greenland were synchronous within uncertainty. We suggest that precipitation and atmospheric circulation changes were likely the major influences on European glacial dust activity and propose that European dust emissions were modulated by dominant phases of the North Atlantic Oscillation, which had a major influence on vegetation and local climate of European dust source regions.

Fluvial landscapes of the Harappan civilization.

The collapse of the Bronze Age Harappan, one of the earliest urban civilizations, remains an enigma. Urbanism flourished in the western region of the Indo-Gangetic Plain for approximately 600 y, but since approximately 3,900 y ago, the total settled area and settlement sizes declined, many sites were abandoned, and a significant shift in site numbers and density towards the east is recorded. We report morphologic and chronologic evidence indicating that fluvial landscapes in Harappan territory became remarkably stable during the late Holocene as aridification intensified in the region after approximately 5,000 BP. Upstream on the alluvial plain, the large Himalayan rivers in Punjab stopped incising, while downstream, sedimentation slowed on the distinctive mega-fluvial ridge, which the Indus built in Sindh. This fluvial quiescence suggests a gradual decrease in flood intensity that probably stimulated intensive agriculture initially and encouraged urbanization around 4,500 BP. However, further decline in monsoon precipitation led to conditions adverse to both inundation- and rain-based farming. Contrary to earlier assumptions that a large glacier-fed Himalayan river, identified by some with the mythical Sarasvati, watered the Harappan heartland on the interfluve between the Indus and Ganges basins, we show that only monsoonal-fed rivers were active there during the Holocene. As the monsoon weakened, monsoonal rivers gradually dried or became seasonal, affecting habitability along their courses. Hydroclimatic stress increased the vulnerability of agricultural production supporting Harappan urbanism, leading to settlement downsizing, diversification of crops, and a drastic increase in settlements in the moister monsoon regions of the upper Punjab, Haryana, and Uttar Pradesh.

Tracing sources of inorganic suspended particulate matter in the Great Barrier Reef lagoon, Australia.

Water clarity on the inshore Great Barrier Reef (GBR) is greatly influenced by terrestrial runoff of suspended particulate matter (SPM). Catchment sediment tracing studies often do not extend into the marine environment, preventing the analysis of preferential marine transport. This study employs novel collection and sediment tracing techniques to examine the transport of the terrigenous 'mineral' component of plume SPM within the GBR lagoon for two flood events. Utilising geochemical, radionuclide and clay mineral analysis, we trace terrigenous mineral sediments > 100 km from the river mouth. We show that the SPM geochemistry is highly influenced by particle-size fractionation, desorption, and dilution within the plume, rendering traditional tracing methods unviable. However, the ratios of rare earth elements (REE) to thorium (Th) provide stable tracers of mineral SPM transported across the catchment to marine continuum and allow the identification of discrete catchment sources for each flood event. Plume sediment radionuclides are also stable and consistent with sub-surface erosion sources.

Activating p53 abolishes self-renewal of quiescent leukaemic stem cells in residual CML disease.

Whilst it is recognised that targeting self-renewal is an effective way to functionally impair the quiescent leukaemic stem cells (LSC) that persist as residual disease in chronic myeloid leukaemia (CML), developing therapeutic strategies to achieve this have proved challenging. We demonstrate that the regulatory programmes of quiescent LSC in chronic phase CML are similar to that of embryonic stem cells, pointing to a role for wild type p53 in LSC self-renewal. In support of this, increasing p53 activity in primitive CML cells using an MDM2 inhibitor in combination with a tyrosine kinase inhibitor resulted in reduced CFC outputs and engraftment potential, followed by loss of multilineage priming potential and LSC exhaustion when combination treatment was discontinued. Our work provides evidence that targeting LSC self-renewal is exploitable in the clinic to irreversibly impair quiescent LSC function in CML residual disease - with the potential to enable more CML patients to discontinue therapy and remain in therapy-free remission.

Comparison of HIV prevalence, incidence, and viral load suppression in Zambia population-based HIV impact assessments from 2016 and 2021.

BACKGROUND: The Zambian government has implemented a public health response to control the HIV epidemic in the country. Zambia conducted a population-based HIV impact assessment (ZAMPHIA) survey in 2021 to assess the status of the HIV epidemic to guide its public health programs. METHODS: ZAMPHIA 2021 was a cross-sectional two-stage cluster sample household survey among persons aged ≥15 years conducted in Zambia across all 10 provinces. Consenting participants were administered a standardized questionnaire and whole blood was tested for HIV according to national guidelines. HIV-1 viral load (VL), recent HIV infection, and antiretroviral medications were tested for in HIV-seropositive samples. Viral load suppression (VLS) was defined as <1000 copies/ml. ZAMPHIA 2021 results were compared to ZAMPHIA 2016 for persons aged 15-59 years (i.e., the overlapping age ranges). All estimates were weighted to account for nonresponse and survey design. RESULTS: During ZAMPHIA 2021, of 25 483 eligible persons aged ≥15 years, 18 804 (73.8%) were interviewed and tested for HIV. HIV prevalence was 11.0% and VLS prevalence was 86.2% overall, but was <80% among people living with HIV aged 15-24 years and in certain provinces. Among persons aged 15-59 years, from 2016 to 2021, HIV incidence declined from 0.6% to 0.3% ( P -value: 0.07) and VLS prevalence increased from 59.2% to 85.7% ( P -value: <0.01). DISCUSSION: Zambia has made substantial progress toward controlling the HIV epidemic from 2016 to 2021. Continued implementation of a test-and-treat strategy, with attention to groups with lower VLS in the ZAMPHIA 2021, could support reductions in HIV incidence and improve overall VLS in Zambia.

Defining paleoclimatic routes and opportunities for hominin dispersals across Iran.

Fossil and archaeological evidence indicates that hominin dispersals into Southwest Asia occurred throughout the Pleistocene, including the expansion of Homo sapiens populations out of Africa. While there is evidence for hominin occupations in the Pleistocene in Iran, as evidenced by the presence of Lower to Upper Paleolithic archaeological sites, the extent to which humid periods facilitated population expansions into western Asia has remained unclear. To test the role of humid periods on hominin dispersals here we assess Paleolithic site distributions and paleoenvironmental records across Iran. We developed the first spatially comprehensive, high-resolution paleohydrological model for Iran in order to assess water availability and its influence on hominin dispersals. We highlight environmentally mediated routes which likely played a key role in Late Pleistocene hominin dispersals, including the expansion of H. sapiens and Neanderthals eastwards into Asia. Our combined analyses indicate that, during MIS 5, there were opportunities for hominins to traverse a northern route through the Alborz and Kopet Dagh Mountains and the Dasht-I Kavir desert owing to the presence of activated fresh water sources. We recognize a new southern route along the Zagros Mountains and extending eastwards towards Pakistan and Afghanistan. We find evidence for a potential northern route during MIS 3, which would have permitted hominin movements and species interactions in Southwest Asia. Between humid periods, these interconnections would have waned, isolating populations in the Zagros and Alborz Mountains, where hominins may have continued to have had access to water.

Measuring training effectiveness of laboratory biosafety program offered at African Center for Integrated Laboratory Training in 22 President's Emergency Plan for AIDS Relief supported countries (2008-2014).

INTRODUCTION: The African Center for Integrated Laboratory Training (ACILT) in Johannesburg, South Africa offered a laboratory biosafety program to improve laboratory biosafety practices in 22 President's Emergency Plan for AIDS Relief (PEPFAR) supported countries. This manuscript evaluates the transference of newly gained knowledge and skills to the participants' place of employment for HIV and TB diagnostic laboratory programs. It also serves as a follow-on to a previously published manuscript that measured training effectiveness for all courses offered at ACILT. METHODS: ACILT offered 20 Laboratory Biosafety and Infrastructure courses (2008-2014), also referred as biosafety course/course comprising of 14 core laboratory safety elements to 402 participants from 22 countries. In 2015, participants received 22 e-questions divided into four categories: (1) Safety Policies, (2) Management's Engagement, (3) Safety Programs and (4) Assessments of Safety Practices to determine retrospectively the training effectiveness of biosafety practices in their place of employment 6 months before and after attending their course. We used Kirkpatrick model to assess the transference of knowledge, skills and obstructive factors. RESULTS: 20% (81/402) of the participants completed the e-questionnaire. The overall percentage of positive responses indicating implementation of new safety practices increased from 50% to 84%. Improvement occurred in all four categories after attending the course, with the greatest increases in Safety Policies (67-94%) and Safety Programs (43-91%). Creating a safety committee, allocating resources, and establishing a facility safety policy were important drivers for implementing and maintaining laboratory safety practices. In addition, accredited laboratories and countries with national safety regulations or policies had a higher percentage of improvements. The most reported challenges were inadequate funding and lack of management enforcement. CONCLUSIONS: PEPFAR and other partners' investments in training institutions, such as ACILT, were effective in building sustainable country ownership to strengthen biosafety practices and were leveraged to combat zoonotic diseases and COVID-19. Although support continues at the national/regional level, a standardized, coordinated and continent-wide sustainable approach to offer a biosafety program-like ACILT is missing. Continuous offerings of biosafety programs similar to ACILT could contribute to sustainable strengthening of laboratory biosafety, QMS and pandemic preparedness.

Forest-based biomass supply in Massachusetts: how much is there and how much is available.

Forest owners in Massachusetts (U.S.) live in a densely populated state and near forestland that is under pressure of development and characterized by small parcel size. Forest-based biomass harvesting in Massachusetts is a renewable energy topic generating a great deal of discussion among all constituents. To provide perspective on these discussions, our analysis asks how much forested land in Massachusetts could be available for biomass supply. This analysis considers the level of bioenergy production that could be maintained on an annual basis given the amount of woody biomass that is likely to be supplied from private- and state-owned Massachusetts forests, which comprises nearly 90% of the state's forests. Applying the most recent information on forest ownership and owner attitudes in Massachusetts, we estimate that between 80,000 and 369,000 dry tons/year of available wood-based biomass from forest management practices on private- and state-owned forests, or between 1.4 trillion and 6.2 trillion BTUs/year. These estimates represent between 0.09% and 0.42% of all Massachusetts residential, commercial and industrial annual consumption. These estimates are well below Kelty et al.'s (2008) estimate of 891,000 dry tons/year; the largest factors in this reduction are the reduced contribution of biomass due to social constraints and the amount of state land considered to be open to active management. Conversations regarding the use of biomass and its impacts on forests, as well as the development of biomass-related policy, should consider the supply of biomass that is likely available. While overall forest inventory estimates suggest one degree of availability, our research suggests that this needs to be tempered with the reality of ownership size and owner attitudes.

Dataset of dust mass accumulation rates for the loess-palaeosol sequences from the Carpathian Basin.

In this article, a dataset of age-depth modelling data, sedimentation rates and dust mass accumulation rates (MAR) from four loess-palaeosol sequences from the Carpathian Basin is presented. The dataset is related to the article "Detailed luminescence dating of dust mass accumulation rates over the last two glacial-interglacial cycles from the Irig loess-palaeosol sequence, Carpathian Basin", published in the journal Global and Planetary Change by Peric et al. [1]. In the dataset, luminescence ages from the loess sites Irig, Nosak, Stari Slankamen and Crvenka were modeled using the r.bacon software after which the dust mass accumulation rates were calculated. For a more realistic representation the MARs were subsequently smoothed using the SigmaPlot software. For all sites, minimum, maximum, median and mean values for the modelled ages and accumulation rates are calculated and presented.

Large-number detrital zircon U-Pb ages reveal global cooling caused the formation of the Chinese Loess Plateau during Late Miocene.

The formation and evolution of the landscape of the Chinese Loess Plateau (CLP) is debated because of uncertainties regarding dust provenance. We present a quantitative estimation of dust source contributions to the CLP, based on more than 37,100 detrital zircon U-Pb ages, combined with mineral assemblages and isotope analyses. Our results reveal that the CLP was stepwise formed by ~8 million years (Ma) and is mainly composed of material from the Northeastern Qinghai-Tibetan Plateau, with stepwise shifts in relative contributions of different eolian silt sources occurring at ~2.6 Ma and 1.5 to 1.2 Ma. We infer that these changes were driven by stepwise global cooling, which induced aridification and enhanced silt production in glaciated-cold climate dust source regions, as well as dust ablation in the expanded arid regions. We propose that global cooling, rather than regional tectonic deformation, was the main driver of the formation and evolution of the CLP during late Cenozoic.

Measuring sediment grain size across the catchment to reef continuum: Improved methods and environmental insights.

Sediments collected within freshwater, estuarine and marine habitats were used to trial various chemical and physical pre-treatments to develop a systematic protocol for grain-size analysis using laser diffraction. Application of this protocol mitigates the influence of bio-physical processes that may transform grain-size distributions, enabling the characterisation and quantification of 'primary' mineral sediments across the complex freshwater-marine continuum to be more reliably assessed. Application of the protocol to two Great Barrier Reef (Australia) river catchments and their estuaries reveals the ecologically relevant <20 µm fraction comprises a larger component of exported sediment than existing methods indicate. These findings are highly relevant when comparing measured data to grain-size-specific modelled sediment loads and water-quality targets. Finally, adoption of the protocol also improves the environmental interpretation of the influence of 'terrigenous sediment' in marine settings, including quantification of newly-delivered flood plume sediment.

Catchment to sea connection: Impacts of terrestrial run-off on benthic ecosystems in American Samoa.

Variation in water quality can directly affect the composition of benthic assemblages on coral reefs. Yet, few studies have directly quantified nutrient and suspended particulate matter (SPM) to examine their potential impacts on benthic community structure, especially around high oceanic islands. We assessed the spatio-temporal variation of nutrients and SPM across six sites in American Samoa over a 12-month period and used exploratory path analysis to relate dissolved inorganic nutrients, land use, and natural and anthropogenic drivers to benthic assemblages on adjacent shallow reefs. Multivariate analyses showed clear gradients in nutrient concentrations, sediment accumulation and composition, and benthic structure across watersheds. Instream nutrients and land uses positively influenced reef flat nutrient concentrations, while benthic assemblages were best predicted by wave exposure, runoff, stream phosphate and dissolved inorganic nitrogen loads. Identifying locality-specific drivers of water quality and benthic condition can support targeted management in American Samoa and in other high islands.

Prevalence of SARS-CoV-2 in six districts in Zambia in July, 2020: a cross-sectional cluster sample survey.

BACKGROUND: Between March and December, 2020, more than 20 000 laboratory-confirmed cases of SARS-CoV-2 infection were reported in Zambia. However, the number of SARS-CoV-2 infections is likely to be higher than the confirmed case counts because many infected people have mild or no symptoms, and limitations exist with regard to testing capacity and surveillance systems in Zambia. We aimed to estimate SARS-CoV-2 prevalence in six districts of Zambia in July, 2020, using a population-based household survey. METHODS: Between July 4 and July 27, 2020, we did a cross-sectional cluster-sample survey of households in six districts of Zambia. Within each district, 16 standardised enumeration areas were randomly selected as primary sampling units using probability proportional to size. 20 households from each standardised enumeration area were selected using simple random sampling. All members of selected households were eligible to participate. Consenting participants completed a questionnaire and were tested for SARS-CoV-2 infection using real-time PCR (rtPCR) and anti-SARS-CoV-2 antibodies using ELISA. Prevalence estimates, adjusted for the survey design, were calculated for each diagnostic test separately, and combined. We applied the prevalence estimates to census population projections for each district to derive the estimated number of SARS-CoV-2 infections. FINDINGS: Overall, 4258 people from 1866 households participated in the study. The median age of participants was 18·2 years (IQR 7·7-31·4) and 50·6% of participants were female. SARS-CoV-2 prevalence for the combined measure was 10·6% (95% CI 7·3-13·9). The rtPCR-positive prevalence was 7·6% (4·7-10·6) and ELISA-positive prevalence was 2·1% (1·1-3·1). An estimated 454 708 SARS-CoV-2 infections (95% CI 312 705-596 713) occurred in the six districts between March and July, 2020, compared with 4917 laboratory-confirmed cases reported in official statistics from the Zambia National Public Health Institute. INTERPRETATION: The estimated number of SARS-CoV-2 infections was much higher than the number of reported cases in six districts in Zambia. The high rtPCR-positive SARS-CoV-2 prevalence was consistent with observed community transmission during the study period. The low ELISA-positive SARS-CoV-2 prevalence might be associated with mitigation measures instituted after initial cases were reported in March, 2020. Zambia should monitor patterns of SARS-CoV-2 prevalence and promote measures that can reduce transmission. FUNDING: US Centers for Disease Control and Prevention.

Tracing the sources of sediment and associated particulate nitrogen from different land uses in the Johnstone River catchment, Wet Tropics, north-eastern Australia.

While the ecosystem of the Great Barrier Reef (GBR), north-eastern Australia, is being threatened by the elevated levels of sediments and nutrients discharged from adjacent coastal river systems, the source of these detrimental pollutants are not well understood. Here we used a combined isotopic (δ13C, δ15N) and geochemical (Zn, Pt and S) signatures and stable isotope analysis in R (SIAR) mixing model to estimate the contribution of different land uses to the sediment and associated particulate nitrogen delivered to the Johnstone River. Results showed that rainforest was the largest contributor of suspended and bed sediments in the river estuary (both 33.1%), followed by banana (26.7%, 20.4%), sugarcane (21.5%, 21.4%) and grazing (18.7%, 25.1%). However, bananas and sugarcane land uses had the highest contribution to sediments delivered to the coast per unit of area. This will help land managers to prioritise on-ground activities to improve water quality in the GBR lagoon.

Multiple virus lineages sharing recent common ancestry were associated with a Large Rift Valley fever outbreak among livestock in Kenya during 2006-2007.

Rift Valley fever (RVF) virus historically has caused widespread and extensive outbreaks of severe human and livestock disease throughout Africa, Madagascar, and the Arabian Peninsula. Following unusually heavy rainfall during the late autumn of 2006, reports of human and animal illness consistent with RVF virus infection emerged across semiarid regions of the Garissa District of northeastern Kenya and southern Somalia. Following initial RVF virus laboratory confirmation, a high-throughput RVF diagnostic facility was established at the Kenyan Central Veterinary Laboratories in Kabete, Kenya, to support the real-time identification of infected livestock and to facilitate outbreak response and control activities. A total of 3,250 specimens from a variety of animal species, including domesticated livestock (cattle, sheep, goats, and camels) and wildlife collected from a total of 55 of 71 Kenyan administrative districts, were tested by molecular and serologic assays. Evidence of RVF infection was found in 9.2% of animals tested and across 23 districts of Kenya, reflecting the large number of affected livestock and the geographic extent of the outbreak. The complete S, M, and/or L genome segment sequence was obtained from a total of 31 RVF virus specimens spanning the entire known outbreak period (December-May) and geographic areas affected by RVF virus activity. Extensive genomic analyses demonstrated the concurrent circulation of multiple virus lineages, gene segment reassortment, and the common ancestry of the 2006/2007 outbreak viruses with those from the 1997-1998 east African RVF outbreak. Evidence of recent increases in genomic diversity and effective population size 2 to 4 years prior to the 2006-2007 outbreak also was found, indicating ongoing RVF virus activity and evolution during the interepizootic/epidemic period. These findings have implications for further studies of basic RVF virus ecology and the design of future surveillance/diagnostic activities, and they highlight the critical need for safe and effective vaccines and antiviral compounds to combat this significant veterinary and public health threat.

Shift of large-scale atmospheric systems over Europe during late MIS 3 and implications for Modern Human dispersal.

Understanding the past dynamics of large-scale atmospheric systems is crucial for our knowledge of the palaeoclimate conditions in Europe. Southeastern Europe currently lies at the border between Atlantic, Mediterranean, and continental climate zones. Past changes in the relative influence of associated atmospheric systems must have been recorded in the region's palaeoarchives. By comparing high-resolution grain-size, environmental magnetic and geochemical data from two loess-palaeosol sequences in the Lower Danube Basin with other Eurasian palaeorecords, we reconstructed past climatic patterns over Southeastern Europe and the related interaction of the prevailing large-scale circulation modes over Europe, especially during late Marine Isotope Stage 3 (40,000-27,000 years ago). We demonstrate that during this time interval, the intensification of the Siberian High had a crucial influence on European climate causing the more continental conditions over major parts of Europe, and a southwards shift of the Westerlies. Such a climatic and environmental change, combined with the Campanian Ignimbrite/Y-5 volcanic eruption, may have driven the Anatomically Modern Human dispersal towards Central and Western Europe, pointing to a corridor over the Eastern European Plain as an important pathway in their dispersal.

Complying with a corporate global noise health surveillance procedure--do the benefits outweigh the costs?

The purpose of this study was to determine whether the benefits of early identification of work-related noise-induced hearing loss outweigh the costs of complying with a Global Noise Medical Surveillance Procedure of a large corporation. Hearing is fundamental to language, communication, and socialization. Its loss is a common cause of disability, affecting an estimated 20 to 40 million individuals in the United States (Daniell et al., 1998). NIOSH reported that approximately 30 million U.S. workers are exposed to noise on the job and that noise-induced hearing loss is one of the most common occupational diseases. It is irreversible (NIOSH, 2004). The average cost of a noise-induced hearing loss is reported to range from dollars 4,726 to dollars 25,500. Corporate history indicates a range of dollars 44 to dollars 20,157 per case. During this 4-year study in one plant, the average annual cost of complying with the Global Noise Medical Surveillance Procedure was dollars 19,509 to screen an average of 390 employees, or dollars 50 per worker. The study identified 11 non-work-related standard threshold shifts. All cases were referred for appropriate early intervention. Given the results, this hearing health program is considered beneficial to the corporation for both work- and non-work-related reasons.

Loess Plateau storage of Northeastern Tibetan Plateau-derived Yellow River sediment.

Marine accumulations of terrigenous sediment are widely assumed to accurately record climatic- and tectonic-controlled mountain denudation and play an important role in understanding late Cenozoic mountain uplift and global cooling. Underpinning this is the assumption that the majority of sediment eroded from hinterland orogenic belts is transported to and ultimately stored in marine basins with little lag between erosion and deposition. Here we use a detailed and multi-technique sedimentary provenance dataset from the Yellow River to show that substantial amounts of sediment eroded from Northeast Tibet and carried by the river's upper reach are stored in the Chinese Loess Plateau and the western Mu Us desert. This finding revises our understanding of the origin of the Chinese Loess Plateau and provides a potential solution for mismatches between late Cenozoic terrestrial sedimentation and marine geochemistry records, as well as between global CO2 and erosion records.

Pacific freshening drives Pliocene cooling and Asian monsoon intensification.

The monsoon is a fundamental component of Earth's climate. The Pliocene warm period is characterized by long-term global cooling yet concurrent monsoon dynamics are poorly known. Here we present the first fully quantified and calibrated reconstructions of separate Pliocene air temperature and East Asian summer monsoon precipitation histories on the Chinese Loess Plateau through joint analysis of loess/red clay magnetic parameters with different sensitivities to air temperature and precipitation. East Asian summer monsoon precipitation shows an intensified trend, paradoxically at the same time that climate cooled. We propose a hitherto unrecognized feedback where persistently intensified East Asian summer monsoon during the late Pliocene, triggered by the gradual closure of the Panama Seaway, reinforced late Pliocene Pacific freshening, sea-ice development and ice volume increase, culminating in initiation of the extensive Northern Hemisphere glaciations of the Quaternary Ice Age. This feedback mechanism represents a fundamental reinterpretation of the origin of the Quaternary glaciations and the impact of the monsoon.