A qualitative meta-analysis of carbon offset quality criteria.

Reaching climate neutrality and limiting the global average temperature increase to 1.5 °C, which are the main targets of the Paris Agreement, requires both mitigation measures and offsetting. Despite existing standards to ensure the credibility and effectiveness of carbon offsets, they face challenges associated with their quality. Incorrect replacement factors or baseline values used for the calculations can lead to credits being overestimated. The quality of carbon offsets and its assurance through offsetting standards are addressed in many publications that provide quality criteria that should be fulfilled. However, the abundance of studies and the unclear consistency of quality criteria for carbon offsets make it difficult to draw generalized conclusions. The fragmented understanding of offset quality and its contribution to climate neutrality requires a comprehensive analysis to identify prevailing consensus and areas needing further research. The paper aims to fill this gap by synthesizing existing criteria through a qualitative meta-analysis of the current literature. Consensus and discrepancies in the carbon offset quality criteria and the ratings of the offsetting programs were identified providing a holistic overview. While only the criteria 'additionality' and 'permanence' are consistently addressed in all publications, their definitions and associated aspects vary. Although consensus exists for the criterion 'ex-post', it only appears in 57% of the publications. Differences in definitions are not reflected in the program ratings. The analysis has several challenges, such as accommodating varying study scopes and methods. However, the results highlight the need for a common understanding and provide a baseline reference to enhance the quality assessment of offsets to effectively contribute to climate neutrality.

Offsetting environmental impacts beyond climate change: the Circular Ecosystem Compensation approach.

Since the Paris Agreement entered into force, climate neutrality and associated compensation schemes are even more on the agenda of politics and companies. Challenges of existing offsetting schemes include the rather theoretical saving scenario and the limited scope of considered impacts. To address some of these limitations, this paper proposes the Circular Ecosystem Compensation (CEC) approach based on monetization of LCA results and Ecosystem Valuation. CEC consists of six steps: i) carrying out a life cycle assessment, ii) reducing the environmental impacts, iii) determining environmental costs applying monetization methods, iv) deriving the environmental value based on restoration costs methods, v) implementing the ecological restoration of ecosystems and vi) monitoring of the renaturation measures. Thus, CEC allows to offset a broad set of environmental impacts beyond climate change (e.g., acidification, eutrophication, land use, water use) in a real ecosystem by renaturation of degraded ecosystems. Environmental burdens and environmental benefits are balanced on a monetary basis, as the renaturation measures are monetized and used to compensate the monetized LCA results, e.g., of a product, organization or individual. In a case study, the implementation of the approach is presented to show the practical implementation of the CEC. The challenges of CEC include the integration of further impact categories, the availability of up-to-date and reliable monetization methods, the asynchrony and time-lag of the compensation from an ecosystem and biodiversity perspective and the proof of cost-efficiency of the renaturation measures. It is further discussed, if CEC can be a step beyond "climate neutrality" towards "environmental neutrality". The proposed approach should be further tested and is intended to foster progress in more comprehensive and robust offsetting of environmental impacts beyond climate change.

Life-LCA: case study of the life cycle impacts of an infant.

Purpose: The recently published first Life-LCA case study of a human being (0-49 years) did not use primary data for the "childhood and youth stage" (0-17 years). Consumption was assumed to contribute 50% of the calculated 48th baseline year. This led to uncertainties as consumer behavior changes from birth to adulthood. Furthermore, transport emissions and environmental impacts before birth were neglected. Therefore, this paper analyzes the prenatal and infancy phase (0-3 years) to develop the Life-LCA method and database further and evaluate generic assumptions. Methods: The Life-LCA method sets the reporting unit to newly defined prenatal and infancy phases. The reporting flow describes the range of all consumed products attributable to an infant. Primary data was collected with a sample of three study objects-a pregnant mother, a newborn baby, and a 3-year-old infant-living in Germany. The following environmental impact assessment categories are considered: climate change (GWP), acidification (AP), eutrophication (EP), and photochemical ozone creation (POCP). Results and discussion: Prenatal and infancy phase burdens account for a GWP of 4,011 kg CO2-eq., an AP of 22.3 kg SO2-eq., an EP of 10.7 kg PO4-eq., and a POCP of 1.7 kg C2H4-eq. The share of the prenatal phase is around 15-20% for all impact categories. Transport is a hotspot for GWP (30-60%) and POCP (45-70%) in both phases. AP (50%) and EP (45-50%) are dominated by food products, mainly meat (45%) and dairy products (35%). For the prenatal phase, energy and water consumption at birth rank third in GWP (8%). Diapers account for 6% (GWP) of the environmental burden in the infancy phase. Assumptions made in the first Life-LCA study connect closely with the values calculated for the first three years of infancy. A remaining challenge is allocating the impacts between infants and parents and developing a methodology for assessing data quality. Conclusion: Focusing on two new life phases has led to the subdivision of the "childhood and youth stage" and an extension of the system boundaries. The results' uncertainty was reduced by developing a new set of specific datasets focusing on several study objects. The case study results show the importance of primary data collection for evaluating generic assumptions. Additional studies on childhood and adolescence from 3 to 17 years are suggested for a robust assessment of the complete "childhood and youth stage." Supplementary Information: The online version contains supplementary material available at 10.1007/s11367-022-02129-7.

Screening of BRCA1/2 deep intronic regions by targeted gene sequencing identifies the first germline BRCA1 variant causing pseudoexon activation in a patient with breast/ovarian cancer.

BACKGROUND: Genetic analysis of BRCA1 and BRCA2 for the diagnosis of hereditary breast and ovarian cancer (HBOC) is commonly restricted to coding regions and exon-intron boundaries. Although germline pathogenic variants in these regions explain about ~20% of HBOC cases, there is still an important fraction that remains undiagnosed. We have screened BRCA1/2 deep intronic regions to identify potential spliceogenic variants that could explain part of the missing HBOC susceptibility. METHODS: We analysed BRCA1/2 deep intronic regions by targeted gene sequencing in 192 high-risk HBOC families testing negative for BRCA1/2 during conventional analysis. Rare variants (MAF <0.005) predicted to create/activate splice sites were selected for further characterisation in patient RNA. The splicing outcome was analysed by RT-PCR and Sanger sequencing, and allelic imbalance was also determined when heterozygous exonic loci were present. RESULTS: A novel transcript was detected in BRCA1 c.4185+4105C>T variant carrier. This variant promotes the inclusion of a pseudoexon in mature mRNA, generating an aberrant transcript predicted to encode for a non-functional protein. Quantitative and allele-specific assays determined haploinsufficiency in the variant carrier, supporting a pathogenic effect for this variant. Genotyping of 1030 HBOC cases and 327 controls did not identify additional carriers in Spanish population. CONCLUSION: Screening of BRCA1/2 intronic regions has identified the first BRCA1 deep intronic variant associated with HBOC by pseudoexon activation. Although the frequency of deleterious variants in these regions appears to be low, our study highlights the importance of studying non-coding regions and performing comprehensive RNA assays to complement genetic diagnosis.

Enhancing the Water Accounting and Vulnerability Evaluation Model: WAVE.

Due to the increasing relevance of analyzing water consumption along product life cycles, the water accounting and vulnerability evaluation model (WAVE) has been updated and methodologically enhanced. Recent data from the atmospheric moisture tracking model WAM2-layers is used to update the basin internal evaporation recycling (BIER) ratio, which denotes atmospheric moisture recycling within drainage basins. Potential local impacts resulting from water consumption are quantified by means of the water deprivation index (WDI). Based on the hydrological model WaterGAP3, WDI is updated and methodologically refined to express a basin's vulnerability to freshwater deprivation resulting from the relative scarcity and absolute shortage of water. Compared to the predecessor version, BIER and WDI are provided on an increased spatial and temporal (monthly) resolution. Differences compared to annual averages are relevant in semiarid and arid basins characterized by a high seasonal variation of water consumption and availability. In order to support applicability in water footprinting and life cycle assessment, BIER and WDI are combined to an integrated WAVE+ factor, which is provided on different temporal and spatial resolutions. The applicability of the WAVE+ method is proven in a case study on sugar cane, and results are compared to those obtained by other impact assessment methods.

Alternative effector-function profiling identifies broad HIV-specific T-cell responses in highly HIV-exposed individuals who remain uninfected.

The characterization of host immune responses to human immunodeficiency virus (HIV) in HIV controllers and individuals with high exposure but seronegativity to HIV (HESN) is needed to guide the development of effective preventive and therapeutic vaccine candidates. However, several technical hurdles severely limit the definition of an effective virus-specific T-cell response. By using a toggle-peptide approach, which takes HIV sequence diversity into account, and a novel, boosted cytokine staining/flow cytometry strategy, we here describe new patterns of T-cell responses to HIV that would be missed by standard assays. Importantly, this approach also allows detection of broad and strong virus-specific T-cell responses in HESN individuals that are characterized by a T-helper type 1 cytokine-like effector profile and produce cytokines that have been associated with potential control of HIV infection, including interleukin 10, interleukin 13, and interleukin 22. These results establish a novel approach to improve the current understanding of HIV-specific T-cell immunity and identify cellular immune responses and individual cytokines as potential markers of relative HIV resistance. As such, the findings also help develop similar strategies for more-comprehensive assessments of host immune responses to other human infections and immune-mediated disorders.

Water accounting and vulnerability evaluation (WAVE): considering atmospheric evaporation recycling and the risk of freshwater depletion in water footprinting.

Aiming to enhance the analysis of water consumption and resulting consequences along the supply chain of products, the water accounting and vulnerability evaluation (WAVE) model is introduced. On the accounting level, atmospheric evaporation recycling within drainage basins is considered for the first time, which can reduce water consumption volumes by up to 32%. Rather than predicting impacts, WAVE analyzes the vulnerability of basins to freshwater depletion. Based on local blue water scarcity, the water depletion index (WDI) denotes the risk that water consumption can lead to depletion of freshwater resources. Water scarcity is determined by relating annual water consumption to availability in more than 11,000 basins. Additionally, WDI accounts for the presence of lakes and aquifers which have been neglected in water scarcity assessments so far. By setting WDI to the highest value in (semi)arid basins, absolute freshwater shortage is taken into account in addition to relative scarcity. This avoids mathematical artifacts of previous indicators which turn zero in deserts if consumption is zero. As illustrated in a case study of biofuels, WAVE can help to interpret volumetric water footprint figures and, thus, promotes a sustainable use of global freshwater resources.

Water footprint of European cars: potential impacts of water consumption along automobile life cycles.

Due to global increase of freshwater scarcity, knowledge about water consumption in product life cycles is important. This study analyzes water consumption and the resulting impacts of Volkswagen's car models Polo, Golf, and Passat and represents the first application of impact-oriented water footprint methods on complex industrial products. Freshwater consumption throughout the cars' life cycles is allocated to material groups and assigned to countries according to import mix shares or location of production sites. Based on these regionalized water inventories, consequences for human health, ecosystems, and resources are determined by using recently developed impact assessment methods. Water consumption along the life cycles of the three cars ranges from 52 to 83 m(3)/car, of which more than 95% is consumed in the production phase, mainly resulting from producing iron, steel, precious metals, and polymers. Results show that water consumption takes place in 43 countries worldwide and that only 10% is consumed directly at Volkswagen's production sites. Although impacts on health tend to be dominated by water consumption in South Africa and Mozambique, resulting from the production of precious metals and aluminum, consequences for ecosystems and resources are mainly caused by water consumption of material production in Europe.

Definition of the viral targets of protective HIV-1-specific T cell responses.

BACKGROUND: The efficacy of the CTL component of a future HIV-1 vaccine will depend on the induction of responses with the most potent antiviral activity and broad HLA class I restriction. However, current HIV vaccine designs are largely based on viral sequence alignments only, not incorporating experimental data on T cell function and specificity. METHODS: Here, 950 untreated HIV-1 clade B or -C infected individuals were tested for responses to sets of 410 overlapping peptides (OLP) spanning the entire HIV-1 proteome. For each OLP, a "protective ratio" (PR) was calculated as the ratio of median viral loads (VL) between OLP non-responders and responders. RESULTS: For both clades, there was a negative relationship between the PR and the entropy of the OLP sequence. There was also a significant additive effect of multiple responses to beneficial OLP. Responses to beneficial OLP were of significantly higher functional avidity than responses to non-beneficial OLP. They also had superior in-vitro antiviral activities and, importantly, were at least as predictive of individuals' viral loads than their HLA class I genotypes. CONCLUSIONS: The data thus identify immunogen sequence candidates for HIV and provide an approach for T cell immunogen design applicable to other viral infections.

Criticality Assessment of the Life Cycle of Passenger Vehicles Produced in China.

China is globally the largest and a rapidly growing market for electric vehicles. The aim of the paper is to determine challenges related to criticality and environmental impacts of battery electric vehicles and internal combustion engine vehicles, focusing not only on a global but also the Chinese perspective, applying the ESSENZ method, which covers a unique approach to determine criticality aspects as well as integrating life cycle assessment results. Real industry data for vehicles and batteries produced in China was collected. Further, for the criticality assessment, Chinese import patterns are analyzed. The results show that the battery electric vehicle has similar and partly increased environmental impacts compared with the internal combustion engine vehicle. For both, the vehicle cycle contributes to a large proportion in all the environmental impact categories except for global warming. Further, battery electric vehicles show a higher criticality than internal combustion engine vehicles, with tantalum, lithium, and cobalt playing essential roles. In addition, the Chinese-specific results show a lower criticality compared to the global assessment for the considered categories trade barriers and political stability, while again tantalum crude oil and cobalt have high potential supply disruptions. Concluding, battery electric vehicles still face challenges regarding their environmental as well as criticality performance from the whole supply chain both in China and worldwide. One reason is the replacement of the lithium-ion power battery. By enhancing its quality and establishing battery recycling, the impacts of battery electric vehicle would decrease. Supplementary Information: The online version contains supplementary material available at 10.1007/s43615-021-00012-5.

BRCA1 and BRCA2 whole cDNA analysis in unsolved hereditary breast/ovarian cancer patients.

Germline pathogenic variants in BRCA1 and BRCA2 genes (BRCA1/2) explain an important fraction of hereditary breast/ovarian cancer (HBOC) cases. Genetic testing generally involves examining coding regions and exon/intron boundaries, thus the frequency of deleterious variants in non-coding regions is unknown. Here we analysed BRCA1/2 whole cDNA in a large cohort of 320 unsolved high-risk HBOC cases in order to identify potential splicing alterations explained by variants in BRCA1/2 deep intronic regions. Whole RNA splicing profiles were analysed by RT-PCR using Sanger sequencing or high-resolution electrophoresis in a QIAxcel instrument. Known predominant BRCA1/2 alternative splicing events were detected, together with two novel events BRCA1 ▼21 and BRCA2 Δ18q_27p. BRCA2 exon 3 skipping was detected in one patient (male) affected with breast cancer, caused by a known Portuguese founder mutation (c.156_157insAluYa5). An altered BRCA2 splicing pattern was detected in three patients, consisting in the up-regulation of ▼20A, Δ22 and ▼20A+Δ22 transcripts. In silico analysis and semi-quantitative data identified the polymorphism BRCA2 c.8755-66T>C as a potential modifier of Δ22 levels. Our findings suggest that mRNA alterations in BRCA1/2 caused by deep intronic variants are rare in Spanish population. However, RNA analysis complements DNA-based strategies allowing the identification of alterations that could go undetected by conventional testing.

Does the SLC40A1 gene modify HFE-related haemochromatosis phenotypes?

Most hereditary haemochromatosis patients are homozygous for the C282Y mutation of the HFE gene. However, the phenotypic expression and clinical aggressiveness of the disease differs considerably from patient to patient. The main objective of this work was to study the role of variants in the SLC40A1 gene in the severity of iron overload and his clinical consequences in 100 Spanish probands homozygous for the C282Y mutation of the HFE gene. We performed automated sequencing of the coding regions, including intron-exon junctions of the SLC40A1 gene. We studied the association between polymorphisms in the SLC40A1 gene and median values of iron removed, taking into account statistical corrections for multiple comparisons. No pathogenic mutations in the SLC40A1 were detected. Five known single nucleotide polymorphisms (SNPs) were identified, and two of them were associated with phenotypic characteristics. IVS1-24 C>G was associated with the amount of iron removed and presence of liver disease: Of the 83 patients finally studied for this SNP, the amount of iron removed was above the median in 36 of 56 (64.3%) for C/C, in nine of 23(39.1%) for C/G and in zero of four (0%) for G/G patients (P=0.01). Liver damage was observed in 34 of 56 patients (60.7%) for C/C, in eight of 23 (34.8%) for C/G and in zero of four (0%) for G/G (P=0.01). Both associations remained significant at multivariate analysis (P=0.011 and P=0.023, respectively). IVS1-24 C>G on the ferroportin gene seems to be a genetic modifier for clinical aggressiveness of HFE1 haemochromatosis.

Mutations in HAMP and HJV genes and their impact on expression of clinical hemochromatosis in a cohort of 100 Spanish patients homozygous for the C282Y mutation of HFE gene.

Most hereditary hemochromatosis (HH) patients are homozygous for the C282Y mutation of the HFE gene. Nevertheless, penetrance of the disease is very variable. In some patients, penetrance can be mediated by concomitant mutations in other iron master genes. We evaluated the clinical impact of hepcidin (HAMP) and hemojuvelin mutations in a cohort of 100 Spanish patients homozygous for the C282Y mutation of the HFE gene. HAMP and hemojuvelin mutations were evaluated in all patients by bidirectional direct cycle sequencing. Phenotype-genotype interactions were evaluated. A heterozygous mutation of the HAMP gene (G71D) was found in only one out of 100 cases. Following, we performed a study of several members of that family, and we observed several members had a digenic inheritance of the C282Y mutation of the HFE gene and the G71D mutation of the HAMP gene. This mutation in the HAMP gene did not modify the phenotype of the individuals who were homozygous for the C282Y mutation. One other patient presented a new polymorphism in the hemojuvelin gene, without consequences in iron load or clinical course of the disease. In conclusion, HAMP and hemojuvelin mutations are rare among Spanish HH patients, and their impact in this population is not significant.

Multigene panel testing beyond BRCA1/2 in breast/ovarian cancer Spanish families and clinical actionability of findings.

PURPOSE: Few and small studies have been reported about multigene testing usage by massively parallel sequencing in European cancer families. There is an open debate about what genes should be tested, and the actionability of some included genes is under research. METHODS: We investigated a panel of 34 known high/moderate-risk cancer genes, including 16 related to breast or ovarian cancer (BC/OC) genes, and 63 candidate genes to BC/OC in 192 clinically suspicious of hereditary breast/ovarian cancer (HBOC) Spanish families without pathogenic variants in BRCA1 or BRCA2 (BRCA1/2). RESULTS: We identified 16 patients who carried a high- or moderate-risk pathogenic variant in eight genes: 4 PALB2, 3 ATM, 2 RAD51D, 2 TP53, 2 APC, 1 BRIP1, 1 PTEN and 1 PMS2. These findings led to increased surveillance or prevention options in 12 patients and predictive testing in their family members. We detected 383 unique variants of uncertain significance in known cancer genes, of which 35 were prioritized in silico. Eighteen loss-of-function variants were detected in candidate BC/OC genes in 17 patients (1 BARD1, 1 ERCC3, 1 ERCC5, 2 FANCE, 1 FANCI, 2 FANCL, 1 FANCM, 1 MCPH1, 1 PPM1D, 2 RBBP8, 3 RECQL4 and 1 with SLX4 and XRCC2), three of which also carry pathogenic variants in known cancer genes. CONCLUSIONS: Eight percent of the BRCA1/2 negative patients carry pathogenic variants in other actionable genes. The multigene panel usage improves the diagnostic yield in HBOC testing and it is an effective tool to identify potentially new candidate genes.

Product environmental footprint in policy and market decisions: Applicability and impact assessment.

In April 2013, the European Commission published the Product and Organisation Environmental Footprint (PEF/OEF) methodology--a life cycle-based multicriteria measure of the environmental performance of products, services, and organizations. With its approach of "comparability over flexibility," the PEF/OEF methodology aims at harmonizing existing methods, while decreasing the flexibility provided by the International Organization for Standardization (ISO) standards regarding methodological choices. Currently, a 3-y pilot phase is running, aiming at testing the methodology and developing product category and organization sector rules (PEFCR/OEFSR). Although a harmonized method is in theory a good idea, the PEF/OEF methodology presents challenges, including a risk of confusion and limitations in applicability to practice. The paper discusses the main differences between the PEF and ISO methodologies and highlights challenges regarding PEF applicability, with a focus on impact assessment. Some methodological aspects of the PEF and PEFCR Guides are found to contradict the ISO 14044 (2006) and ISO 14025 (2006). Others, such as prohibition of inventory cutoffs, are impractical. The evaluation of the impact assessment methods proposed in the PEF/OEF Guide showed that the predefined methods for water consumption, land use, and abiotic resources are not adequate because of modeling artefacts, missing inventory data, or incomplete characterization factors. However, the methods for global warming and ozone depletion perform very well. The results of this study are relevant for the PEF (and OEF) pilot phase, which aims at testing the PEF (OEF) methodology (and potentially adapting it) as well as addressing challenges and coping with them.

HLA class I protective alleles in an HIV-1-infected subject homozygous for CCR5-Δ32/Δ32.

Homozygosity for a 32 bp deletion in CCR5 (CCR5-Δ32/Δ32) is associated with strong resistance against HIV-1 infection. Several HLA types have been associated to improved viral control and/or delayed progression to AIDS. We report a unique HIV-1 infected individual homozygous for CCR5-Δ32/Δ32 and carrier of HLA-A*2402 and HLA-B*5701. In comparison with earlier data and although a replication competent virus has been isolated, the patient presents better immune status, response to treatment and disease evolution, which may be related to the control exerted by HLA class I restricted T cell immunity. Importantly, the accumulation of protective factors does not warrant a complete protection to HIV infection and the subsequent life-long treatment.

Serum soluble transferrin receptor concentrations are increased in central obesity. Results from a screening programme for hereditary hemochromatosis in men with hyperferritinemia.

BACKGROUND: A decrease in the serum concentrations of the soluble transferrin receptor (sTfR) is considered a good index of tissue iron. Because obesity is associated with hyperferritinemia and this is considered a sign of iron overload, a decrease in sTfR would be expected for the obese. We evaluated whether obese men with hyperferritinemia, detected in a genetic screening programme for hereditary hemochromatosis (HH), have lower serum concentrations of sTfR than their non-obese counterparts. METHODS: 75 men (age: 55.4+/-12.4 years) with hyperferritinemia (serum ferritin--SF > 200 microg/L) and no known conditions of iron overload were evaluated for body mass index (BMI), waist circumference (WC), blood pressure, traditional indices of iron status, sTfR, fasting plasma glucose, lipid profile, insulin resistance (HOMA-IR), highly-sensitive C-reactive protein, hepatic enzymes and HFE gene mutations of HH. RESULTS: sTfR correlated with BMI (r=0.289; p=0.014) and with WC (r=0.420; p<0.001). Thirty-two subjects were obese (BM > or = 30 kg/m(2)) and had a significantly higher sTfR (2.95 (2.22-3.28) vs 2.28 (1.88-2.91) mg/L; p=0.013), hemoglobin (157+/-12 vs 152+/-11 gr/L; p=0.049) and HOMA-IR (1.38 (1.04-2.69) vs 1.02 (0.60-1.55) mg/L; p=0.009) than the non-obese. WC explained separately more variability of the sTfR than BMI (r(2)=0.177; p=0.002 and r=0.077; p=0.042, respectively), after adjusting for potential confounders. CONCLUSION: An increase in serum concentrations of sTfR is associated with central obesity in men with hyperferritinemia.

The relationship between iron overload and clinical characteristics in a Spanish cohort of 100 C282Y homozygous hemochromatosis patients.

We studied the relationship between iron removed by venesection, sex, age, and clinical characteristics in a group of 100 Spanish probands with hereditary hemochromatosis (HH), all C282Y homozygous in the HFE gene. Iron overload was higher in men than in women (P < 0.0001) and increased with age (P = 0.02). Forty-four patients presented with liver disease (28 had fibrosis-cirrhosis of the liver), 24 with diabetes, 18 with arthropathy, and 13/73 men with impotence. No clinical consequences of hemochromatosis were observed in 43 patients. The number of clinical complications was higher in men (P = 0.01) and increased with age (P = 0.006) and with the amount of iron removed (P < 0.0001). The amount of iron removed was significantly higher by univariate analysis in patients with liver disease (P < 0.0001), diabetes (P = 0.007), arthropathy (P = 0.006), and impotence (P = 0.003) than in patients without these complications. In the multivariant analysis, only liver disease maintained a significant relationship with the amount of iron removed (P < 0.0001). Diabetes and arthropathy were closely related with previous liver disease, and impotence appeared mainly in hemochromatosic men with diabetes and alcoholism.