Loss and Damage in the mountain cryosphere

The mountain cryosphere, which includes glaciers, permafrost, and snow, is one of the Earth’s systems most strongly affected by climate change. In recent decades, changes in the cryosphere have been well documented in many high-mountain regions. While there are some benefits from snow and ice loss, the negative impacts, including from glacier lake outburst floods and variations in glacier runoff, are generally considered to far outweigh the positive impacts, particularly if cultural impacts are considered. In international climate policy, there has been growing momentum to address the negative impacts of climate change, or ‘Loss and Damage’ (L&D) from climate change. It is not clear exactly what can and should be done to tackle L&D, but researchers and practitioners are beginning to engage with policy discussions and develop potential frameworks and supporting information. Despite the strong impact of climate change on the mountain cryosphere, there has been limited interaction between cryosphere researchers and L&D. Therefore, little work has been done to consider how L&D in the mountain cryosphere might be conceptualized, categorized, and assessed. Here, we make a first attempt to analyze L&D in the mountain cryosphere by conducting a systematic literature review to extract L&D impacts and examples from existing literature. We find that L&D is a global phenomenon in the mountain cryosphere and has been more frequently documented in the developing world, both in relation with slow and sudden onset processes. We develop a categorization of L&D, making distinctions between physical and societal impacts, primary and secondary impacts, and identifying seven types of L&D (including L&D to culture, livelihoods, revenue, natural resources, life, and security). We hope this conceptual approach will support future work to understand and address L&D in the mountain cryosphere

Mitochondrial oxidative stress and nitrate tolerance – comparison of nitroglycerin and pentaerithrityl tetranitrate in Mn-SOD(+/- )mice

BACKGROUND: Chronic therapy with nitroglycerin (GTN) results in a rapid development of nitrate tolerance which is associated with an increased production of reactive oxygen species (ROS). According to recent studies, mitochondrial ROS formation and oxidative inactivation of the organic nitrate bioactivating enzyme mitochondrial aldehyde dehydrogenase (ALDH-2) play an important role for the development of nitrate and cross-tolerance. METHODS: Tolerance was induced by infusion of wild type (WT) and heterozygous manganese superoxide dismutase mice (Mn-SOD(+/-)) with ethanolic solution of GTN (12.5 μg/min/kg for 4 d). For comparison, the tolerance-free pentaerithrityl tetranitrate (PETN, 17.5 μg/min/kg for 4 d) was infused in DMSO. Vascular reactivity was measured by isometric tension studies of isolated aortic rings. ROS formation and aldehyde dehydrogenase (ALDH-2) activity was measured in isolated heart mitochondria. RESULTS: Chronic GTN infusion lead to impaired vascular responses to GTN and acetylcholine (ACh), increased the ROS formation in mitochondria and decreased ALDH-2 activity in Mn-SOD(+/- )mice. In contrast, PETN infusion did not increase mitochondrial ROS formation, did not decrease ALDH-2 activity and accordingly did not lead to tolerance and cross-tolerance in Mn-SOD(+/- )mice. PETN but not GTN increased heme oxygenase-1 mRNA in EA.hy 926 cells and bilirubin efficiently scavenged GTN-derived ROS. CONCLUSION: Chronic GTN infusion stimulates mitochondrial ROS production which is an important mechanism leading to tolerance and cross-tolerance. The tetranitrate PETN is devoid of mitochondrial oxidative stress induction and according to the present animal study as well as numerous previous clinical studies can be used without limitations due to tolerance and cross-tolerance

Integrated assessment and adaptation to climate change impacts in the Peruvian Andes

The Andes as mountain regions worldwide, provide fundamental resources, not only for the local population. Due to the topographic characteristics, the potential for natural hazards is higher than elsewhere. In these areas, assessments of climate change impacts and the development of adequate adaptation strategies therefore become particular important. The data basis, however, is often scarce. Moreover, perceptions of changes and needs are often divergent between national and local levels, which make the implementation of adaptation measures a challenge. Taking the Peruvian Andes as an example, this paper aims at initiating a discussion about scientific baseline and integrative concepts needed to deal with the adverse effects of climate change in mountain regions

Loss and damage in the mountain cryosphere

The mountain cryosphere, which includes glaciers, permafrost, and snow, is one of the Earth’s systems most strongly affected by climate change. In recent decades, changes in the cryosphere have been well documented in many high-mountain regions. While there are some benefits from snow and ice loss, the negative impacts, including from glacier lake outburst floods and variations in glacier runoff, are generally considered to far outweigh the positive impacts, particularly if cultural impacts are considered. In international climate policy, there has been growing momentum to address the negative impacts of climate change, or ‘Loss and Damage’ (L&D;) from climate change. It is not clear exactly what can and should be done to tackle L&D;, but researchers and practitioners are beginning to engage with policy discussions and develop potential frameworks and supporting information. Despite the strong impact of climate change on the mountain cryosphere, there has been limited interaction between cryosphere researchers and L&D.; Therefore, little work has been done to consider how L&D; in the mountain cryosphere might be conceptualized, categorized, and assessed. Here, we make a first attempt to analyze L&D; in the mountain cryosphere by conducting a systematic literature review to extract L&D; impacts and examples from existing literature. We find that L&D; is a global phenomenon in the mountain cryosphere and has been more frequently documented in the developing world, both in relation with slow and sudden onset processes. We develop a categorization of L&D;, making distinctions between physical and societal impacts, primary and secondary impacts, and identifying seven types of L&D; (including L&D; to culture, livelihoods, revenue, natural resources, life, and security). We hope this conceptual approach will support future work to understand and address L&D; in the mountain cryosphere

Perioperative Fluid Management in Colorectal Surgery: Institutional Approach to Standardized Practice.

The present review discusses restrictive perioperative fluid protocols within enhanced recovery after surgery (ERAS) pathways. Standardized definitions of a restrictive or liberal fluid regimen are lacking since they depend on conflicting evidence, institutional protocols, and personal preferences. Challenges related to restrictive fluid protocols are related to proper patient selection within standardized ERAS protocols. On the other hand, invasive goal-directed fluid therapy (GDFT) is reserved for more challenging disease presentations and polymorbid and frail patients. While the perfusion rate (mL/kg/h) appears less predictive for postoperative outcomes, the authors identified critical thresholds related to total intravenous fluids and weight gain. These thresholds are discussed within the available evidence. The authors aim to introduce their institutional approach to standardized practice

Residue-resolved stability of full-consensus ankyrin repeat proteins probed by NMR

We investigated the stability determinants and the unfolding characteristics of full-consensus Designed Ankyrin Repeat Proteins (DARPins) by NMR. Despite the repeating sequence motifs, the resonances could be fully assigned using 1H, 15N, 13C triple labeled proteins. To remove further ambiguities, paramagnetic spin labels were attached to either end of these elongated proteins which attenuate the resonances of the spatially closest residues. Deuterium exchange experiments of DARPins with 2 and 3 internal repeats between N- and C-terminal capping repeats (NI2C, NI3C) and NI3C_Mut5, where the C-cap had been reengineered, indicate that the stability of the full-consensus ankyrin repeat proteins is strongly dependent on the coupling between repeats, as the stabilized cap decreases the exchange rate throughout the whole protein. Some amide protons require more than a year to exchange at 37°C, highlighting the extraordinary stability of the proteins. Denaturant induced unfolding, followed by deuterium exchange, chemical shift change and heteronuclear nuclear Overhauser effects, is consistent with an Ising-type description of equilibrium folding for NI3C_Mut5, while for native state deuterium exchange, we postulate local fluctuations to dominate exchange as unfolding events are too slow in these very stable proteins. The location of extraordinarily slowly exchanging protons indicate a very stable core structure in the DARPins which combines hydrophobic shielding with favorable electrostatic interactions. These investigations help the understanding of repeat protein architecture and the further design of DARPins for biomedical applications where high stability is required

Enhanced recovery ERAS for elderly: a safe and beneficial pathway in colorectal surgery.

Enhanced recovery after surgery (ERAS) pathway includes recovery goals requiring active participation of the patients; this may be perceived as "aggressive" care in older patients. The aim of the present study was to assess whether ERAS was feasible and beneficial in older patients. Since June 2011, all consecutive colorectal patients were included in an ERAS pathway and documented in a dedicated prospective database. This retrospective analysis included 513 patients, 311 younger patients (<70 years) and 202 older patients (≥70 years). Outcomes were adherence to the ERAS pathway, functional recovery, postoperative complications, and hospital stay. Older patients had significantly more diabetes, malignancies, cardiac, and respiratory co-morbidities; both groups underwent similar surgical procedures. Overall adherence to the ERAS pathway was in median 78 % in younger and 74 % in older patients (P = 0.86). In older patients, urinary drains were kept longer (P = 0.001), and oral fluid intake was reduced from day 0 to day 3 (P < 0.001). There were no differences in mobilization and intake of nutritional supplements. Postoperative complications were similar for both comparative groups (51.5 vs. 46.6 %, P = 0.32). Median length of stay was 7 days (IQR 5-13) in older patients vs. 6 days (IQR 4-10) in the younger group (P = 0.001). Adherence to the ERAS pathway was equally high in older patients. Despite more co-morbidities, older patients did not experience more complications. Recovery was similar and hospital stay was only 1 day longer than in younger patients. ERAS pathway is of value for all patients and does not need any adaptation for the elderly

Compliance with enhanced recovery after surgery program in gynecology: are all items of equal importance?

Enhanced recovery after surgery (ERAS) guidelines in gynecologic surgery are a set of multiple recommendations based on the best available evidence. However, according to previous studies, maintaining high compliance is challenging in daily clinical practice. The aim of this study was to assess the impact of compliance to individual ERAS items on clinical outcomes. Retrospective cohort study of a prospectively maintained database of 446 consecutive women undergoing gynecologic oncology surgery (both open and minimally invasive) within an ERAS program from 1 October 2013 until 31 January 2017 in a tertiary academic center in Switzerland. Demographics, adherence, and outcomes were retrieved from a prospectively maintained database. Uni- and multivariate logistic regression was performed, with adjustment for confounding factors. Main outcomes were overall compliance, compliance to each individual ERAS item, and impact on post-operative complications according to Clavien classification. A total of 446 patients were included, 26.2 % (n=117) had at least one complication (Clavien I-V), and 11.4 % (n=51) had a prolonged length of hospital stay. The single independent risk factor for overall complications was intra-operative blood loss > 200 mL (OR 3.32; 95% CI 1.6 to 6.89, p=0.001). Overall compliance >70% with ERAS items (OR 0.15; 95% CI 0.03 to 0.66, p=0.12) showed a protective effect on complications. Increased compliance was also associated with a shorter length of hospital stay (OR 0.2; 95% CI 0.435 to 0.93, p=0.001). Compliance >70% with modifiable ERAS items was significantly associated with reduced overall complications. Best possible compliance with all ERAS items is the goal to achieve lower complication rates after gynecologic oncology surgery