Reduced-Dose Thrombolysis in Acute Pulmonary Embolism A Systematic Review.

Pulmonary embolism (PE) is the third-leading cause of cardiovascular mortality and the second-leading cause of death in cancer patients. The clinical efficacy of thrombolysis for acute PE has been proven, yet the therapeutic window seems narrow, and the optimal dosing for pharmaceutical reperfusion therapy has not been established. Higher doses of systemic thrombolysis inevitably associated with an incremental increase in major bleeding risk. To date, there is no high-quality evidence regarding dosing and infusion rates of thrombolytic agents to treat acute PE. Most clinical trials have focused on thrombolysis compared with anticoagulation alone, but dose-finding studies are lacking. Evidence is now emerging that lower-dose thrombolytic administered through a peripheral vein is efficacious in accelerating thrombolysis in the central pulmonary artery and preventing acute right heart failure, with reduced risk for major bleeding. The present review will systematically summarize the current evidence of low-dose thrombolysis in acute PE.

Distributed mathematical model for simulating temperature profile in landfill.

Elevated Landfill temperatures have an undesirable effect on landfill cover, stability, slope and leachate migration pattern. Thus, to predict the temperature profile in the landfill a distributed numerical model using MacCormack finite difference method is developed. The developed model considers stratification of the upper and lower layers of the waste as new and old waste by assigning different values of heat generation for aerobic and anaerobic processes. Further, as the new layers of the waste get accumulated over the older layers, the density, moisture content and hydraulic conductivity of the underlying waste layers get modified. The mathematical model utilizes a predictor-corrector approach with a Dirichlet boundary at the surface and no flow condition at the bottom. The developed model is applied to the Gazipur site located in Delhi in India. A correlation coefficient of 0.8 and 0.73 is obtained between the simulated and observed temperatures in calibration and validation respectively. The result shows that the temperature at all the depths and in all the seasons was found to be higher than the atmospheric temperature. The maximum difference of 333 °C was observed in December, and the minimum difference of 22 °Cs was observed in June. The temperature rise is higher in the upper waste layers as it undergoes aerobic degradation. The locus of the maximum temperature gets modified with moisture movement. Since the developed model shows a good agreement with the field observation, it can be used to predict the temperature variation within the landfill under different climatic conditions.

ST elevation myocardial infarction - national trend analysis with mortality differences in outcomes based on day of hospitalization.

BACKGROUND: Patientswho present with acute ST elevation myocardial infarction (STEMI) need emergent revascularization. Our study aims to investigate the outcomes in patients with STEMI admitted during weekends versus weekdays. METHODS: We conducted a retrospective analysis of the nationwide inpatient sample database. Patients with an admitting diagnosis of STEMI identified by the International Classification of Disease code for the year 2016 were analyzed. A weighted descriptive analysis was performed to generate national estimates. Patients admitted over the weekend were compared to those admitted over the weekday. Patients were stratified by demographic and clinical factors including the Elixhauser comorbidity index. The primary outcome was in-hospital mortality and secondary outcomes were percutaneous coronary intervention (PCI) utilization rate, rate of transfer-out, length of stay (LOS), and total hospital charges. Statistical analysis including linear and logistic regression was performed using STATA. RESULTS: A total of 163 715 adult patients were admitted with STEMI, of which 27.9% (45 635) were admitted over the weekend. There were 76.2% Caucasians, 9.3% African Americans, and 8.0% Hispanics. Mean age of the patients was 63.2 years (95% CI, 62.9-63.5) for the weekend group and 63.7 years (95% CI, 63.5-63.9) for weekday admissions. The majority of the patients in both groups had Medicare (43.7% and 45.8% on weekends and weekdays, respectively; P = 0.0047). After adjusting for age, sex, race, income, Elixhauser comorbidity index, PCI use, hospital location, teaching status, and bed size, mortality was not significantly different in weekend versus weekday admissions (odds ratios 1.04; P = 0.498; 95% CI, 0.93-1.16). There was no significant difference in mean total charge per admission during the weekend versus weekday admissions ($107 093 versus $106 869; P = 0.99.) Mean LOS was 4.1 days for both groups (P = 0.81). CONCLUSIONS: There were no significant differences in mortality, LOS, or total hospital charge in STEMI patients being admitted during the weekend versus weekdays.

Elevated levels of anthropogenic antibiotic resistance gene marker, sul1, linked with extreme fecal contamination and poor water quality in wastewater-receiving ponds.

In several low- and middle-income countries, such as India, the rapid construction of toilets to combat open defecation has not been matched with adequate wastewater treatment, resulting in extreme fecal contamination of the receiving environments. The sewage-receiving surface water bodies, typically close to the residences, are a potential hotspot for disease transmission and antibiotic resistance. Water, soil, and sediment samples from seven wastewater-receiving ponds (WRPs) were analyzed for water quality, chlorophyll-a, fecal contamination (yccT for Escherichia coli), 16S rRNA gene copies, and anthropogenic antibiotic resistance gene markers-sul1 and intI1. These WRPs were contrasted with two ponds that did not directly receive sewage. The water quality in the WRPs was comparable to raw sewage (BOD: 210-380 mg/L; COD: 350-630 mg/L; total-N: 100-190 mg/L; and total-P: 6-21 mg/L), and the relative levels of the DNA marker of E. coli were very high (yccT: 0.1% to ∼100% of total bacterial count) indicating extreme fecal contamination. The relative levels of sul1 and intI1 were 1-3 orders of magnitude higher in WRPs (sul1: 0.32%-10% of total bacterial count; and intI1: 0.2%-5% of total bacterial count) compared to the ponds that did not receive sewage directly. The relative levels of sul1 correlated with the DNA marker for the fecal indicator, E. coli (p-value < 0.05; r = 0.50; Spearman's rank correlation), and poor water quality.

Assessing efficiency and economic viability in treating leachates emanating from the municipal landfill site at Gazipur, India.

The leachates emanating from the landfills are high in organic loads and thus become potential sources of contamination for both surface and groundwater. As the landfill ages, the nature of leachate changes from acidic to alkaline. The change in pH level affects the chemical oxygen demand (COD)/biochemical oxygen demand (BOD) ratio and when it is less than 0.63, chemical treatments are more effective over the biological treatment methods such as upflow anaerobic sludge blankets (UASB). The existing literature suggests coagulation-flocculation and advanced oxidation process (Fenton) as effective methods for treating wastewater but no comparison of the two are available. Thus, the present study attempts to identify the most efficient coagulants out of ferric chloride (FeCl3), ferrous sulphate (FeSO4) and alum [Al2(SO4)3]. Ferric chloride leading to 99% colour removal, 98% COD removal, 99% decrease in total organic carbon, 94.3% removal in NH3-N and 91.4% removal in total Kjeldahl nitrogen is observed to be the most efficient coagulant and surprisingly, proves to be even better than Fenton. To understand the field applicability of the two treatment procedures, coagulation with FeCl3 and Fenton are compared with the UASB method which is currently employed at Gazipur landfill site, Delhi. With lesser operational cost than UASB, both FeCl3 and Fenton perform better on cost-efficiency scale. Switching from in-suit UASB method to the FeCl3 method of treatment may result in decreasing the operational cost by 71.9% and to conventional Fenton may result in decreasing the operational cost by 76.8%.

Hydrothermal and thermal-alkali pretreatments of wheat straw: Co-digestion, substrate solubilization, biogas yield and kinetic study.

Agro-waste having lignocellulosic biomass is considered most effective (heating value 16 MJ/kg) for energy production through anaerobic digestion (AD). However, recalcitrant lignocellulosic fraction in agro-waste obstructs its biotransformation and is a rate-limiting step of the process. This study investigated the effects of hydrothermal and thermal-alkaline pretreatment on anaerobic co-digestion of wheat straw (WS). The hydrothermal pretreatment of WS revealed that 60 min was the best pretreatment time to achieve the highest substrate solubilization. It was employed for thermal-alkali pretreatment at variable temperatures and NaOH doses. Thermal-alkali pretreatment at 125°C-7% NaOH shows the highest (34%) biogas yield of 662 mL/gVS, followed by 646 mL/gVS biogas yield at 150°C-1% NaOH assay (31% higher) over control. Although the 125°C-7% NaOH assay achieved the highest biogas yield, the 150°C-1% NaOH assay was found more feasible considering the cost of a 6% higher chemical used in the earlier assay. The thermal-alkali pretreatment was observed to reduce the formation of recalcitrant compounds (HMF, Furfural) and increase the buffering capacity of the slurry over hydrothermal pretreatment. Principal component analysis (PCA) of the various pretreatment and AD operational parameters was carried out to study their in-depth correlation. Moreover, a kinetic study of the experimental data was performed to observe the biodegradation trend and compare it with the Modified Gompertz (MG) and First Order (FO) models.

Thirty-day readmission in patients with heart failure with preserved ejection fraction: Insights from the nationwide readmission database.

BACKGROUND: There are rising numbers of patients who have heart failure with preserved ejection fraction (HFpEF). Poorly understood pathophysiology of heart failure with preserved and reduced ejection fraction and due to a sparsity of studies, the management of HFpEF is challenging. AIM: To determine the hospital readmission rate within 30 d of acute or acute on chronic heart failure with preserved ejection fraction and its effect on mortality and burden on health care in the United States. METHODS: We performed a retrospective study using the Agency for Health-care Research and Quality Health-care Cost and Utilization Project, Nationwide Readmissions Database for the year 2017. We collected data on hospital readmissions of 60514 adults hospitalized for acute or acute on chronic HFpEF. The primary outcome was the rate of all-cause readmission within 30 d of discharge. Secondary outcomes were cause of readmission, mortality rate in readmitted and index patients, length of stay, total hospitalization costs and charges. Independent risk factors for readmission were identified using Cox regression analysis. RESULTS: The thirty day readmission rate was 21%. Approximately 9.17% of readmissions were in the setting of acute on chronic diastolic heart failure. Hypertensive chronic kidney disease with heart failure (1245; 9.7%) was the most common readmission diagnosis. Readmitted patients had higher in-hospital mortality (7.9% vs 2.9%, P = 0.000). Our study showed that Medicaid insurance, higher Charlson co-morbidity score, patient admitted to a teaching hospital and longer hospital stay were significant variables associated with higher readmission rates. Lower readmission rate was found in residents of small metropolitan or micropolitan areas, older age, female gender, and private insurance or no insurance were associated with lower risk of readmission. CONCLUSION: We found that patients hospitalized for acute or acute on chronic HFpEF, the thirty day readmission rate was 21%. Readmission cases had a higher mortality rate and increased healthcare resource utilization. The most common cause of readmission was cardio-renal syndrome.

Numerical groundwater modelling for studying surface water-groundwater interaction and impact of reduced draft on groundwater resources in central Ganga basin.

Water resources in India's Indo-Gangetic plains are over-exploited and vulnerable to impacts of climate change. The unequal spatial and temporal variation of meteorological, hydrological and hydrogeological parameters has created additional challenges for field engineers and policy planners. The groundwater and surface water are extensively utilized in the middle Gangetic plain for agriculture. The primary purpose of this study is to understand the discharge and recharge processes of groundwater system using trend analysis, and surface water and groundwater interaction using groundwater modelling. A comprehensive hydrological, and hydrogeological data analysis was carried out and a numerical groundwater model was developed for Bhojpur district, Bihar, India covering 2395 km2 geographical area, located in central Ganga basin. The groundwater level data analyses for the year 2018 revealed that depth to water level varies from 3.0 to 9.0 meter below ground level (m bgl) in the study area. The M-K test showed no significant declining trend in the groundwater level in the study area. The groundwater modelling results revealed that groundwater head is higher in the southern part of the district and the groundwater flow direction is from south-west to north-east. The groundwater head fluctuation between the monsoon and the summer seasons was observed to be 2 m, it is also witnessed that groundwater is contributing more to rivers in the monsoon season in comparison with other seasons. Impact of reduction in pumping on groundwater heads was also investigated, considering a 10% reduction in groundwater withdrawal. The results indicated an overall head rise of 2 m in the southern part and 0.2-0.5 m in the middle and northern part of the district.

Critical insights into anaerobic co-digestion of wheat straw with food waste and cattle manure: Synergistic effects on biogas yield and kinetic modeling.

In this study, four batch assays were performed to ensure the synergic effects of co-digestion and find out the best inoculums to substrate ratio (ISR), carbon to nitrogen ratio (C:N), and total solid (TS) percentage in sequence. The co-digestion of three feedstocks had a 20% higher biogas yield (416 mL/gVS added) than mono-digestion with 21% volatile solids (VS) degradation. The ISR of 2 leads to the highest biogas yield (431 mL/gVS added) and VS removal (30.3%) over other ISRs (0.5, 1.0, 2.5) studied. The lower ISR (<2) tended to have lower pH due to insufficient anaerobes inside the digester. The C:N 35 (with ISR 2) yielded 17.4% higher biogas (443.5 mL/gVS added) than mono-digestion and was the highest among the C:N ratios studied with 36.6% VS removal. The VFA, alkalinity, and pH in C:N 35 assay were more stable than in other C:N assays. In the fourth batch assay, varying TS% (5, 7.5, 10, 12.5) were used with optimized ISR (2) and C:N (35). Higher TS% (10 and 12.5) had some lag phase but later achieved higher biogas production. The 12.5% TS assay achieved 80% higher biogas yield (679 mL/gVS added) over mono-digestion, i.e., highest among the TS% studied, with 48% VS removal. In conclusion, co-digestion of mixed feedstocks with ISR 2, C:N 35, and TS 12.5% could degrade almost half of the substrate available for biodegradation. Further biodegradation may require pretreatment of the recalcitrant WS. Modified Gompertz, first-order, transference, and logistic models were used for kinetic study and curve fitting of experimental data. For the optimized batch assays, the estimated specific rate constants were 0.08, 0.12, 0.083, and 0.084. The data fits well in all the models, with the coefficient of discrimination (R2) ranging from 0.882 to 0.999.

Acute Myopericarditis After First Dose of mRNA-1273 SARS-CoV-2 Vaccine in a Young Adult.

The coronavirus disease (COVID-19 or SARS-CoV-2) pandemic has brought the global community to a halt. A return to normalcy is dependent on effective reopening strategies that encourage herd immunity through the implementation of vaccines. Cardiopulmonary inflammation has been reported in SARS-CoV-2 infection, independent of the severity, mainly amongst the juvenile population. Cardiovascular involvement following SARS-CoV-2 infection is associated with higher mortality and morbidity. Cardiovascular complications following COVID-19 vaccination have been documented as less severe, with no link between cardiovascular injury and death. This case report describes the presentation of an otherwise healthy 18-year-old male who experienced retrosternal chest pain after receiving a first dose of the mRNA-1273 vaccine. The patient had a negative polymerase chain reaction (PCR) test for COVID-19 infection. An electrocardiogram revealed diffuse ST elevation and PR segment depression, with increased inflammatory markers consistent with pericarditis. Elevation of troponin (16 ng/mL), evidence of borderline reduced ejection fraction (50-55%), and global left ventricular hypokinesis were suggestive of myopericarditis. Infectious and autoimmune studies were negative. The patient was treated mainly with non-steroidal anti-inflammatory drugs and colchicine, which resulted in a significant improvement of clinical symptoms. As the administration of emergency COVID-19 vaccines continues worldwide, it is of paramount importance to be aware of possible adverse events, including those affecting the cardiovascular system.

Slither Into the Heart: Salmonella Endocarditis Following Rattlesnake Meat Ingestion.

Salmonellae foodborne infections are a well described and documented entity, however cardiac complications of Salmonellae foodborne infections including infective endocarditis (IE) are rare. Here we present a case of infective endocarditis as a result of bacteremia caused by multiple species of Salmonella. The patient initially presented with chest pain, fever and altered mental status. Troponin and ECG were unremarkable. The patient was started on empiric antibiotics. Blood cultures grew Salmonella species serotype O&H. Transesophageal echocardiogram (TEE) confirmed aortic valve vegetation. Regional cultural practices suggested possible contamination attributed to ingestion of rattlesnake meat, a practice that has been previously described and well-established in various Hispanic folk practices. Upon further history taking, the patient was found to be regularly consuming dried rattlesnake meat preparations, a rather common practice in Chihuahua desert region. Surgery was not indicated, and the patient was treated with six weeks of antibiotics. This case presents an opportunity to gain insight into such a unique manifestation of Salmonellae, offering a potential facet of information for clinicians to better understand its presentation, susceptibility, and potential adverse outcomes.

The Cardiovascular Effects of Electronic Cigarettes.

PURPOSE OF REVIEW: Electronic cigarettes (e-cigarettes) are gaining rapid popularity among all age groups, especially among youth. They have evolved into technologically advanced devices capable of delivering nicotine concentration and other substances. In addition to nicotine, e-cigarettes' constituents possess variety of toxic chemicals that have adverse effects on human body. RECENT FINDINGS: In recent years, steady downward trend in tobacco usage has been observed; however, e-cigarette use is on upward trend. E-cigarettes are advertised as "safer" alternatives to conventional smoking and as an aid to smoking cessation. Emerging studies have, however, shown that e-cigarettes have harmful effects on the cardiovascular system and that most of the e-cigarette users are dual users, concurrently using e-cigarettes and smoking conventional cigarettes. Despite a gap in clinical studies and randomized trials analyzing adverse cardiovascular effects of e-cigarette use, the existing literature supports that different constituents of e-cigarettes such as nicotine, carbonyls, and particulate matters carry potential risk for cardiovascular diseases (CVD) on its users.

Medical Therapy Versus Revascularization in Patients with Stable Ischemic Heart Disease and Advanced Chronic Kidney Disease.

PURPOSE OF REVIEW: This article reviews the evidence on optimal medical therapy (OMT) versus coronary revascularization in patients with stable ischemic heart disease (SIHD) and advanced chronic kidney disease (CKD). RECENT FINDINGS: A post hoc analysis of the COURAGE trial in patients with SIHD and CKD showed no difference in freedom from angina, death, and nonfatal myocardial infarction (MI) between OMT and percutaneous intervention plus OMT compared with patients without CKD. The ISCHEMIA-CKD trial of 777 patients with advanced CKD revealed no difference in cumulative incidence of death or nonfatal MI at 3 years between OMT and revascularization but the composite of death or new dialysis was higher in the invasive arm. Additionally, there were no significant or sustained benefits in related to angina-related health status in invasive versus conservative strategy. An initial revascularization strategy does not reduce mortality or MI or relieve angina symptoms in patients with SIHD and advanced CKD.

Advances in the management of atrial fibrillation with a special focus on non-pharmacological approaches to prevent thromboembolism: a review of current recommendations.

Atrial fibrillation (AFIB) is the most common heart rhythm abnormality and is associated with significant morbidity and mortality. While the treatment of AFIB involves strategies of rate with or without rhythm control, it is also essential to strategize appropriate therapies to prevent thromboembolic complications arising from AFIB. Previously, anticoagulation was the main treatment option which exposed patients to higher than usual risk of bleeding. However, with the advent of new technology, novel therapeutic options aimed at surgical or percutaneous exclusion or occlusion of the left atrial appendage in preventing thromboembolic complications from AFIB have evolved. This review evaluates recent advances and therapeutic options in treating AFIB with a special focus on both surgical and percutaneous interventions which can reduce and/or eliminate thromboembolic complications of AFIB.

Current Use and Trends in Unprotected Left Main Coronary Artery Percutaneous Intervention.

PURPOSE OF REVIEW: To review the clinical evidence on the use of percutaneous coronary intervention (PCI) revascularization options in left main (LM) disease in comparison with coronary artery bypass graft (CABG). Coronary artery disease (CAD) involving the LM is associated with high morbidity and mortality. Though CABG remains the gold standard for complex CAD involving the LM artery, recent trials have shown a trend towards non-inferiority of the LM PCI when compared with CABG in certain subset of patients. RECENT FINDINGS: Two recent major randomized trials compared the outcomes of PCI versus CABG in the LM and multi-vessel disease with LM involvement. The NOBLE trial included patients with all range of Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) scores and utilized biolimus drug-eluting stent (DES). The trial concluded that MACCE (major adverse cardiac and cerebrovascular event) was significantly higher with PCI (28%) when compared with CABG (18%) but overall stroke and motility were not different. EXCEL trial evaluated the same treatment option in low to intermediate SYNTAX score population with third-generation everolimus DES platform as PCI option. Results showed no significant differences in the composite primary endpoints of death, stroke, and myocardial infarction (MI) at the end of 30 days (22% versus 19.2%, p = 0.13), although repeat revascularization was higher in PCI group (16.9% versus 10%). Recent evidence suggests that PCI is an acceptable alternative to treat symptomatic LM stenosis in select group of patients. In low to medium SYNTAX score, particularly in patients without diabetes mellitus, PCI remains a viable option. Future trials focusing on evaluating subset of patients who would benefit from one particular revascularization option in comparison with other is warranted.

The Clinical Significance of Physiological Assessment of Residual Ischemia After Percutaneous Coronary Intervention.

PURPOSE OF REVIEW: Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) have emerged as the invasive diagnostic tools of choice for hemodynamic assessment of the severity of CAD (coronary artery disease). We sought to comprehensively review the evidence on the utility of hemodynamic assessment of the coronary stenoses after percutaneous coronary intervention (PCI) using FFR/iFR, mechanisms of positive post-PCI iFR/FFR, and the clinical impact of significant residual ischemia. RECENT FINDINGS: The evidence on the utility of the post-PCI hemodynamic assessment has accumulated over the last few years. The post hoc analysis from the FAME 1 and FAME 2 data shows that higher post-PCI FFR is associated with better symptomatic improvement and lower event rate with larger increase in delta FFR (∆ FFR: post-PCI FFR - pre-PCI FFR). Unlike pre-PCI FFR, a consensus has not been established on the optimal value of post-PCI FFR, though multiple studies point toward better clinical outcomes with higher post-PCI FFR and larger ∆ FFR. Visual assessment of adequate stent apposition by coronary angiography is insufficient in evaluating for residual ischemia. The hemodynamic evaluation of residual ischemia by post-PCI FFR/iFR yields clinically relevant data and allows for appropriate post PCI optimization.

Patent Foramen Ovale, the Role of Antiplatelet Therapy Alone or Anticoagulant Therapy Alone Versus Device Closure for Cryptogenic Stroke: A Review of the Literature and Current Recommendations.

Cryptogenic stroke and its relation to the Patent Foramen Ovale (PFO) is a long-debated topic. Recent clinical trials have unequivocally established the relationship between cryptogenic strokes and paradoxical embolism across the PFO. This slit-like communication exists in everyone before birth, but most often closes shortly after birth. PFO may persist as a narrow channel of communication between the right and left atria in approximately 25-27% of adults. In this review, we examine the clinical relevance of the PFO with analysis of the latest trials evaluating catheter-based closure of PFO's for cryptogenic stroke. We also review the current evidence examining the use of antiplatelet medications versus anticoagulants for stroke prevention in those patients with PFO who do not qualify for closure per current guidelines.

Single-year thermal regime and inferred permafrost occurrence in the upper Ganglass catchment of the cold-arid Himalaya, Ladakh, India.

Cold-arid regions of the trans-Himalaya in the Indian Himalayan Region (IHR) is suspected to have a significant area of permafrost. However, information on the ground thermal regime of these permafrost areas is so far not available. This study bridge this knowledge gap by analysing the sub-surface thermal regime of selected sites in the Ganglass catchment, Ladakh range. Near surface ground temperature data recorded during September 2016 to August 2017 using 24-miniature temperature data loggers distributed across 12 plots and covering an elevation range of 4700-5612 m a.s.l. are used in this study. Permafrost characteristics including plausible ranges of thermal offset, active-layer thickness and mean annual ground temperature at 10 m depth were estimated by driving a one-dimensional heat conduction model. Two statistical models were used to map first order estimates of permafrost area in this 15.4 km2 catchment. Study suggest permafrost occurrence at all sites above 4900 m a.s.l. with active-layer thickness ranging from 0.1 to 4.2 m and the mean annual ground surface temperature ranging from between -10.0 and -0.85 °C for these sites. MAAT at these sites range from -4.1 to -8.9 °C and the surface offsets vary from -1.1 to 3.9 °C. Estimated thermal offset range from -0.9 to 0 °C. Both statistical models show comparable results and suggest 95% mean permafrost cover in the catchment above 4727 m a.s.l. These results strongly indicate existence of significant permafrost areas across the high elevations of the cold-arid regions of IHR. So far, permafrost processes are not considered for assessing present and future estimates of water and regional climate and as a causative factor for disasters like debris flows and landslides in the region. This study highlight the need for greater research efforts on Himalayan permafrost to have a comprehensive understanding of Himalayan cryosphere.

Untangling the water-food-energy-environment nexus for global change adaptation in a complex Himalayan water resource system.

Holistic water management approaches are essential under future climate and socio-economic changes, especially while trying to achieve inter-disciplinary societal goals such as the Sustainable Development Goals (SDGs) of clean water, hunger eradication, clean energy and life on land. Assessing water resources within a water-food-energy-environment nexus approach enables the relationships between water-related sectors to be untangled while incorporating impacts of societal changes. We use a systems modelling approach to explore global change impacts on the nexus in the mid-21st century in a complex western Himalayan water resource system in India, considering a range of climate change and alternative socio-economic development scenarios. Results show that future socio-economic changes will have a much stronger impact on the nexus compared to climate change. Hydropower generation and environmental protection represent the major opportunities and limitations for adaptation in the studied system and should, thereby, be the focus for actions and systemic transformations in pursue of the SDGs. The emergence of scenario-specific synergies and trade-offs between nexus component indicators demonstrates the benefits that water resource systems models can make to designing better responses to the complex nexus challenges associated with future global change.