Resource efficiency analysis through planetary boundary-based life cycle assessment: a case study of sugarcane in Pakistan.

Purpose: Extensive agriculture activities for crop production have led to increasing environmental impacts that threaten to exceed environmentally safe limits. The purpose of this study is to analyze resource efficiency of the agri-food industry, considering the case of sugarcane production in Pakistan. Methods: A holistic approach has been applied by determining the relevant impact categories and Sustainable Development Goals (SDGs), and linking them with Planetary Boundary-based Life Cycle Assessment (PB-LCA). Both the spatially generic and spatially resolved approaches were considered with application of different sharing principles. Results and discussion: Application of different sharing principles showed high variations in the assigned share of the safe operating space values. When taking a spatially generic approach, most of the impacts (except marine eutrophication and water consumption) were within the safe operating space for equal per capita, economic, caloric, and grandfathering sharing principles. However, all the impacts exceeded their limits considering the agri-land sharing and land use impact surpassed its budget considering the grandfathering sharing. In the spatially resolved approach, most of the impact values surpassed the available budgets. Furthermore, the failure to attain the pertinent SDG targets from a PB-LCA perspective is indicated by the exceeding of safe operating space for relevant impact categories. Conclusions: Overall, the production of sugarcane was found to be unsustainable, requiring urgent action to promote resource improvement and contain the impacts within safe limits. The developed framework enabled the evaluation of the SDGs using PB-LCA at the product level. The target-driven impact reduction values would help in achieving the targets and prioritizing the efforts by making informed decisions for reducing impacts within safe limits. Supplementary Information: The online version contains supplementary material available at 10.1007/s11367-023-02185-7.

Can Science-Based Targets Make the Private Sector Paris-Aligned? A Review of the Emerging Evidence.

Purpose of Review: Companies increasingly set science-based targets (SBTs) for reducing greenhouse gas emissions. We review literature on SBTs to understand their potential for aligning corporate emissions with the temperature goal of the Paris Agreement. Recent Findings: SBT adoption by larger, more visible companies in high-income countries has accelerated. These companies tend to have a good prior reputation for managing climate impacts and most appear on track for meeting their scope 1 and 2 SBTs. More research is needed to distinguish between substantive and symbolic target-setting and understand how companies plan to achieve established SBTs. There is no consensus on whether current target-setting methods appropriately allocate emissions to individual companies or how much freedom companies should have in setting SBTs. Current emission accounting practices, target-setting methods, SBT governance, and insufficient transparency may allow companies to report some emission reductions that are not real and may result in insufficient collective emission reductions. Lower rates of SBT diffusion in low- and middle-income countries, in certain emission-intensive sectors, and by small- and medium-sized enterprises pose potential barriers for mainstreaming SBTs. While voluntary SBTs cannot substitute for more ambitious climate policy, it is unclear whether they delay or encourage policy needed for Paris alignment. Summary: We find evidence that SBT adoption corresponds to increased climate action. However, there is a need for further research from a diversity of approaches to better understand how SBTs may facilitate or hinder a just transition to low-carbon societies.

Long-term mortality and health-related quality of life of lower versus higher oxygenation targets in ICU patients with severe hypoxaemia.

PURPOSE: We assessed outcomes after 1 year of lower versus higher oxygenation targets in intensive care unit (ICU) patients with severe hypoxaemia. METHODS: Pre-planned analyses evaluating 1-year mortality and health-related quality-of-life (HRQoL) outcomes in the previously published Handling Oxygenation Targets in the ICU trial which randomised 2928 adults with acute hypoxaemia to targets of arterial oxygen of 8 kPa or 12 kPa throughout the ICU stay up to 90 days. One-year all-cause mortality was assessed in the intention-to-treat population. HRQoL was assessed using EuroQol 5 dimensions 5 levels (EQ-5D-5L) questionnaire and EQ visual analogue scale score (EQ-VAS), and analyses were conducted in both survivors only and the intention-to-treat population with assignment of the worst scores to deceased patients. RESULTS: We obtained 1-year vital status for 2887/2928 (98.6%), and HRQoL for 2600/2928 (88.8%) of the trial population. One year after randomisation, 707/1442 patients (49%) in the lower oxygenation group vs. 704/1445 (48.7%) in the higher oxygenation group had died (adjusted risk ratio 1.00; 95% confidence interval 0.93-1.08, p = 0.92). In total, 1189/1476 (80.4%) 1-year survivors participated in HRQoL interviews: median EQ-VAS scores were 65 (interquartile range 50-80) in the lower oxygenation group versus 67 (50-80) in the higher oxygenation group (p = 0.98). None of the five EQ-5D-5L dimensions differed between groups. CONCLUSION: Among adult ICU patients with severe hypoxaemia, a lower oxygenation target (8 kPa) did not improve survival or HRQoL at 1 year as compared to a higher oxygenation target (12 kPa).

MAP2K1-Mutated Melanocytic Neoplasms With a SPARK-Like Morphology.

ABSTRACT: Specific alterations involving MAPK genes (MAP3K8 fusions, MAP3K3 fusions) have been recently detected in a subgroup of spitzoid neoplasms that seem to constitute a distinctive clinicopathologic group, occur mostly in younger patients (median age 18 years) and present with atypical histologic features associated with frequent homozygous deletion of CDKN2A, qualifying a high proportion of them as Spitz melanoma (malignant Spitz tumor). Apart from lesions with spitzoid morphology harboring MAP3K8 or MAP3K3 fusion, a single case with MAP2K1 deletion has been identified. The authors report herein 4 melanocytic lesions with a MAP2K1 mutation, all showing similar microscopic appearances, including spitzoid cytology and dysplastic architectural features, resembling so-called SPARK nevus, suggesting that these lesions may represent another distinctive group.

A comprehensive planetary boundary-based method for the nitrogen cycle in life cycle assessment: Development and application to a tomato production case study.

Existing methods that apply the planetary boundary for the nitrogen cycle in life cycle assessment are spatially generic and use an indicator with limited environmental relevance. Here, we develop a spatially resolved method that can quantify the impact of nitrogen emissions to air, soil, freshwater or coastal water on "safe operating space" (SOS) for natural soil, freshwater and coastal water. The method can be used to identify potential "planetary boundary hotspots" in the life cycle of products and to inform appropriate interventions. The method is based on a coupling of existing environmental models and the identification of threshold and reference values in natural soil, freshwater and coastal water. The method is demonstrated for a case study on nitrogen emissions from open-field tomato production in 27 farming areas based on data for 199 farms in the year 2014. Nitrogen emissions were modelled from farm-level data on fertilizer application, fuel consumption and climate- and soil conditions. Two sharing principles, "status quo" and "gross value added", were tested for the assignment of SOS to 1 t of tomatoes. The coupling of models and identification of threshold and reference values resulted in spatially resolved characterization factors applicable to any nitrogen emission and estimations of SOS for each environmental compartment. In the case study, tomato production was found to range from not transgressing to transgressing its assigned SOS in each of the 27 farming areas, depending on the receiving compartment and sharing principle. A high nitrogen use efficiency scenario had the potential to reverse transgressions of assigned SOS for up to three farming locations. Despite of several sources of uncertainty, the developed method may be used in decision-support by stakeholders, ranging from individual producers to global governance institutions. To avoid sub-optimization, it should be applied with methods covering the other planetary boundaries.

Pre- and postnatal growth failure with microcephaly due to two novel heterozygous IGF1R mutations and response to growth hormone treatment.

AIM: To explore the phenotype and response to growth hormone in patients with heterozygous mutations in the insulin-like growth factor I receptor gene (IGF1R). METHODS: Children with short stature, microcephaly, born SGA combined with biochemical sign of IGF-I insensitivity were analysed for IGF1R mutations or deletions using Sanger sequencing and Multiple ligation-dependent probe amplification analysis. RESULTS: In two families, a novel heterozygous non-synonymous missense IGF1R variant was identified. In family 1, c.3364G > T, p.(Gly1122Cys) was found in the proband and co-segregated perfectly with the phenotype in three generations. In family 2, a de novo variant c.3530G > A, p.(Arg1177His) was detected. Both variants were rare, not present in the GnomAD database. Three individuals carrying IGF1R mutations have received rhGH treatment. The average gain in height SDS during treatment was 0.42 (range: 0.26-0.60) and 0.64 (range: 0.32-0.86) after 1 and 2 years of treatment, respectively. CONCLUSION: Our study presents two heterozygous IGF1R mutations causing pre- and postnatal growth failure and microcephaly and also indicates that individuals with heterozygous IGF1R mutations can respond to rhGH treatment. The findings highlight that sequencing of the IGF1R should be considered in children with microcephaly and short stature due to pre- and postnatal growth failure.

Genetic screening in sudden cardiac death in the young can save future lives.

BACKGROUND: Autopsy of sudden cardiac death (SCD) in the young shows a structurally and histologically normal heart in about one third of cases. Sudden death in these cases is believed to be attributed in a high percentage to inherited arrhythmogenic diseases. The purpose of this study was to investigate the value of performing post-mortem genetic analysis for autopsy-negative sudden unexplained death (SUD) in 1 to 35 year olds. METHODS AND RESULTS: From January 2009 to December 2011, samples from 15 cases suffering SUD were referred to the Department of Clinical Genetics, Umeå University Hospital, Sweden, for molecular genetic evaluation. PCR and bidirectional Sanger sequencing of genes important for long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome type 1 (BrS1), and catecholaminergic polymorphic ventricular tachycardia (CPVT) (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, and RYR2) was performed. Multiplex ligation-dependent probe amplification (MLPA) was used to detect large deletions or duplications in the LQTS genes. Six pathogenic sequence variants (four LQTS and two CPVT) were discovered in 15 SUD cases (40%). Ten first-degree family members were found to be mutation carriers (seven LQTS and three CPVT). CONCLUSION: Cardiac ion channel genetic testing in autopsy-negative sudden death victims has a high diagnostic yield, with identification of the disease in 40 of families. First-degree family members should be offered predictive testing, clinical evaluation, and treatment with the ultimate goal to prevent sudden death.

Non-sedation versus sedation with a daily wake-up trial in critically ill patients receiving mechanical ventilation (NONSEDA Trial): study protocol for a randomised controlled trial.

BACKGROUND: Through many years, the standard care has been to use continuous sedation of critically ill patients during mechanical ventilation. However, preliminary randomised clinical trials indicate that it is beneficial to reduce the sedation level. No randomised trial has been conducted comparing sedation with no sedation, a priori powered to have all-cause mortality as primary outcome.The objective is to assess the benefits and harms of non-sedation versus sedation with a daily wake-up trial in critically ill patients. METHODS/DESIGN: The non-sedation (NONSEDA) trial is an investigator-initiated, randomised, clinical, parallel-group, multinational trial designed to include 700 patients from at least six ICUs in Denmark, Norway and Sweden.Inclusion criteria are mechanically ventilated patients with expected duration of mechanical ventilation >24 hours.Exclusion criteria are non-intubated patients, patients with severe head trauma, coma at admission or status epilepticus, patients treated with therapeutic hypothermia, patients with PaO2/FiO2 < 9 where sedation might be necessary to ensure sufficient oxygenation or place the patient in prone position.Experimental intervention is non-sedation supplemented with pain management during mechanical ventilation.Control intervention is sedation with a daily wake-up trial.The primary outcome will be all cause mortality at 90 days after randomization. Secondary outcomes will be: days until death throughout the total observation period; coma- and delirium-free days; highest RIFLE score; days until discharge from the intensive care unit (within 28 days); days until the participant is without mechanical ventilation (within 28 days); and proportion of patients with a major cardiovascular outcome. Explorative outcomes will be: all cause mortality at 28 days after randomisation; days until discharge from the intensive care unit; days until the participant is without mechanical ventilation; days until discharge from the hospital; organ failure.Trial size: we will include 700 participants (2 × 350) in order to detect or reject 25% relative risk reduction in mortality with a type I error risk of 5% and a type II error risk of 20% (power at 80%). DISCUSSION: The trial investigates potential benefits of non-sedation. This might have large impact on the future treatment of mechanically ventilated critically ill patients. TRIAL REGISTER: ClinicalTrials.gov NCT0196768, 09.01.2014.

Chemical footprint method for improved communication of freshwater ecotoxicity impacts in the context of ecological limits.

The ecological footprint method has been successful in communicating environmental impacts of anthropogenic activities in the context of ecological limits. We introduce a chemical footprint method that expresses ecotoxicity impacts from anthropogenic chemical emissions as the dilution needed to avoid freshwater ecosystem damage. The indicator is based on USEtox characterization factors with a modified toxicity reference point. Chemical footprint results can be compared to the actual dilution capacity within the geographic vicinity receiving the emissions to estimate whether its ecological limit has been exceeded and hence whether emissions can be expected to be environmentally sustainable. The footprint method was illustrated using two case studies. The first was all inventoried emissions from European countries and selected metropolitan areas in 2004, which indicated that the dilution capacity was likely exceeded for most European countries and all landlocked metropolitan areas. The second case study indicated that peak application of pesticides alone was likely to exceed Denmark's freshwater dilution capacity in 1999-2011. The uncertainty assessment showed that better spatially differentiated fate factors would be useful and pointed out other major sources of uncertainty and some opportunities to reduce these.

Numerical simulations of the pulsating flow of cerebrospinal fluid flow in the cervical spinal canal of a Chiari patient.

The flow of cerebrospinal fluid (CSF) in a patient-specific model of the subarachnoid space in a Chiari I patient was investigated using numerical simulations. The pulsating CSF flow was modeled using a time-varying velocity pulse based on peak velocity measurements (diastole and systole) derived from a selection of patients with Chiari I malformation. The present study introduces the general definition of the Reynolds number to provide a measure of CSF flow instability to give an estimate of the possibility of turbulence occurring in CSF flow. This was motivated by the fact that the combination of pulsating flow and the geometric complexity of the spinal canal may result in local Reynolds numbers that are significantly higher than the commonly used global measure such that flow instabilities may develop into turbulent flow in these regions. The local Reynolds number was used in combination with derived statistics to characterize the flow. The results revealed the existence of both local unstable regions and local regions with velocity fluctuations similar in magnitude to what is observed in fully turbulent flows. The results also indicated that the fluctuations were not self-sustained turbulence, but rather flow instabilities that may develop into turbulence. The case considered was therefore believed to represent a CSF flow close to transition.

Founder mutations characterise the mutation panorama in 200 Swedish index cases referred for Long QT syndrome genetic testing.

BACKGROUND: Long QT syndrome (LQTS) is an inherited arrhythmic disorder characterised by prolongation of the QT interval on ECG, presence of syncope and sudden death. The symptoms in LQTS patients are highly variable, and genotype influences the clinical course. This study aims to report the spectrum of LQTS mutations in a Swedish cohort. METHODS: Between March 2006 and October 2009, two hundred, unrelated index cases were referred to the Department of Clinical Genetics, Umeå University Hospital, Sweden, for LQTS genetic testing. We scanned five of the LQTS-susceptibility genes (KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2) for mutations by DHPLC and/or sequencing. We applied MLPA to detect large deletions or duplications in the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes. Furthermore, the gene RYR2 was screened in 36 selected LQTS genotype-negative patients to detect cases with the clinically overlapping disease catecholaminergic polymorphic ventricular tachycardia (CPVT). RESULTS: In total, a disease-causing mutation was identified in 103 of the 200 (52%) index cases. Of these, altered exon copy numbers in the KCNH2 gene accounted for 2% of the mutations, whereas a RYR2 mutation accounted for 3% of the mutations. The genotype-positive cases stemmed from 64 distinct mutations, of which 28% were novel to this cohort. The majority of the distinct mutations were found in a single case (80%), whereas 20% of the mutations were observed more than once. Two founder mutations, KCNQ1 p.Y111C and KCNQ1 p.R518*, accounted for 25% of the genotype-positive index cases. Genetic cascade screening of 481 relatives to the 103 index cases with an identified mutation revealed 41% mutation carriers who were at risk of cardiac events such as syncope or sudden unexpected death. CONCLUSION: In this cohort of Swedish index cases with suspected LQTS, a disease-causing mutation was identified in 52% of the referred patients. Copy number variations explained 2% of the mutations and 3 of 36 selected cases (8%) harboured a mutation in the RYR2 gene. The mutation panorama is characterised by founder mutations (25%), even so, this cohort increases the amount of known LQTS-associated mutations, as approximately one-third (28%) of the detected mutations were unique.

Direct numerical simulation of transitional flow in a patient-specific intracranial aneurysm.

In experiments turbulence has previously been shown to occur in intracranial aneurysms. The effects of turbulence induced oscillatory wall stresses could be of great importance in understanding aneurysm rupture. To investigate the effects of turbulence on blood flow in an intracranial aneurysm, we performed a high resolution computational fluid dynamics (CFD) simulation in a patient specific middle cerebral artery (MCA) aneurysm using a realistic, pulsatile inflow velocity. The flow showed transition to turbulence just after peak systole, before relaminarization occurred during diastole. The turbulent structures greatly affected both the frequency of change of wall shear stress (WSS) direction and WSS magnitude, which reached a maximum value of 41.5Pa. The recorded frequencies were predominantly in the range of 1-500Hz. The current study confirms, through properly resolved CFD simulations that turbulence can occur in intracranial aneurysms.

Dispersion of Legionella-containing aerosols from a biological treatment plant, Norway.

Legionella was detected in aeration ponds (biological treatment plant) at Borregaard Ind. Ltd., Norway, and in air samples harvested directly above these ponds. Since 2005, three outbreaks of legionellosis occurred within a 10 km radius from this plant. This work addresses the dispersion patterns of Legionella-containing particles by characterizing the aerosol plume emitted from these ponds (outbreak source) less than 500 meters using wind-tunnel measurements, CFD simulations, and real-life measurements. The most abundant particles directly over the ponds were less than 6 and more than 15 microm. The results showed that the aerosol plume remained narrow; 180 meters wide at 350 meters downwind of the ponds, and that 2 and 18 microm aerosols were mainly deposited in the vicinity of the ponds ( 150 - 200 meters). Furthermore, the maximum aerosol concentration level appeared 5-10 meters above ground level and the maximum concentration 500 meters downwind was approximately 2 per cent of the concentration level directly above the ponds. Our study demonstrates the strength of combining modeling with real-life aerosol analyses increasing the understanding of dispersion of airborne (pathogenic) microorganisms.

A missense mutation in the aggrecan C-type lectin domain disrupts extracellular matrix interactions and causes dominant familial osteochondritis dissecans.

Osteochondritis dissecans is a disorder in which fragments of articular cartilage and subchondral bone dislodge from the joint surface. We analyzed a five-generation family in which affected members had autosomal-dominant familial osteochondritis dissecans. A genome-wide linkage analysis identified aggrecan (ACAN) as a prime candidate gene for the disorder. Sequence analysis of ACAN revealed heterozygosity for a missense mutation (c.6907G > A) in affected individuals, resulting in a p.V2303M amino acid substitution in the aggrecan G3 domain C-type lectin, which mediates interactions with other proteins in the cartilage extracellular matrix. Binding studies with recombinant mutated and wild-type G3 proteins showed loss of fibulin-1, fibulin-2, and tenascin-R interactions for the V2303M protein. Mass spectrometric analyses of aggrecan purified from patient cartilage verified that V2303M aggrecan is produced and present in the tissue. Our results provide a molecular mechanism for the etiology of familial osteochondritis dissecans and show the importance of the aggrecan C-type lectin interactions for cartilage function in vivo.

Tracking airborne Legionella and Legionella pneumophila at a biological treatment plant.

Biological treatment plants are frequently used to degrade organic substances in wastewater from wood refinement processes. Aeration ponds in such plants provide an optimal growth environment for many microorganisms, including Legionella species. To investigate whether legionellae could be dispersed as aerosols from the ponds and transported by the wind, the wetted-wall cyclone SASS 2000(PLUS) and the impactors MAS-100 and STA-204 were used to collect air samples directly above, upwind, and downwind of aeration ponds during a 4-month period. Computational fluid dynamics was used a priori to estimate the aerosol paths and to determine suitable air-sampling locations. Several Legionella species, including Legionella pneumophila, were identified in air samples at the biological treatment plant using microbiological and molecular methods. L. pneumophila was identified up to distances of 200 m downwind from the ponds, but, in general, not upwind nor outside the predicted aerosol paths. The highest concentration level of viable legionellae was identified directly above the aeration ponds (3300 CFU/m3). This level decreased as the distance from the aeration ponds increased. Molecular typing indicated that a single clone of L. pneumophila was dispersed from the ponds during the period of the study. Thus, our study demonstrated that aerosols generated at aeration ponds of biological treatment facilities may contain L. pneumophila, which then can be transported by the wind to the surroundings. The methods used in this study may be generically applied to trace biological aerosols that may pose a challenge to environmental occupational health.