Identifying leverage points for strengthening adaptive capacity to climate change

Leverage points from systems research are increasingly important to understand how to support transformations towards sustainability, but few studies have considered leverage points in strengthening adaptive capacity to climate change. The existing literature mainly considers strengthening adaptive capacity as a steady and linear process. This article explores possibilities to fast track positive adaptive capacity trajectories of small-scale farmers in the Northern Region of Ghana. Leverage points were identified by triangulating data from semi-structured interviews with farmers (n=72), key informant interviews (n=7) and focus group discussions (FG1 n=17; FG2 n=20). The results present two ways to approach adaptation planning: 1) using four generic leverage points (gender equality, social learning, information and knowledge, and access to finance) or 2) combining the adaptive capacity and leverage point frameworks, thereby creating 15 associations. The generic points provide a set of topics as a starting point for policy and intervention planning activities, while the 15 associations support the identification of place-specific leverage points. Four benefits of using leverage points for adaptive capacity in adaptation planning were identified: guidance on where to intervene in a system, ability to deal with complex systems, inclusion of both causal and teleological decision-making, and a possibility to target deep, transformative change. © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.Peer reviewe

Place based transformative learning: a framework to explore consciousness in sustainability initiatives

Based on a critical literature review, the article argues that transformative learning (TL) that fosters a shift in consciousness towards a more ecological approach is an inherently place-based phenomenon. In this article we build a place-based approach to TL based on a literature review. Our theoretical framework is grounded in three key themes which emerge from the literature: (re-) connection, (self-)compassion and creativity. (Re-)connection involves all processes that evoke an experience of the interconnected nature of all life. (Self-)compassion, acting to alleviate suffering or doing the least harm, naturally follows a sense of interconnection. Creativity is the materialisation of a sense of interconnection and compassion or the means through which these can be experienced. This theoretical framework can be used empirically to research the extent to which people involved in place-based sustainability initiatives develop an ecological consciousness. Empirical research can then be used to further develop and anchor this framework, and seek the kind of practices that can evoke experiences of connection, cultivate the human ability for compassion and give space for creative living.</p

Missing-in-metastasis and IRSp53 deform PI(4,5)P-2-rich membranes by an inverse BAR domain-like mechanism

The actin cytoskeleton plays a fundamental role in various motile and morphogenetic processes involving membrane dynamics. We show that actin-binding proteins MIM (missing-in-metastasis) and IRSp53 directly bind PI(4,5)P-2-rich membranes and deform them into tubular structures. This activity resides in the N-terminal IRSp53/MIM domain (IMD) of these proteins, which is structurally related to membrane-tubulating BAR (Bin/amphiphysin/Rvs) domains. We found that because of a difference in the geometry of the PI(4,5)P-2-binding site, IMDs induce a membrane curvature opposite that of BAR domains and deform membranes by binding to the interior of the tubule. This explains why IMD proteins induce plasma membrane protrusions rather than invaginations. We also provide evidence that the membrane-deforming activity of IMDs, instead of the previously proposed F-actin - bundling or GTPase-binding activities, is critical for the induction of the filopodia/microspikes in cultured mammalian cells. Together, these data reveal that interplay between actin dynamics and a novel membrane-deformation activity promotes cell motility and morphogenesis

Keuhkovaltimoiden pallolaajennus - uusi hoito krooniseen tromboemboliseen pulmonaalihypertensioon

• Krooninen tromboembolinen pulmonaalihypertensio huonontaa merkittävästi elämänlaatua. Hoitamattomana se voi johtaa ennenaikaiseen kuolemaan.• Taudin vakiintunut hoitomuoto on kirurginen keuhkovaltimoiden endarterektomia. Lähes puolelle potilaista seei sovi tai tulos jää huonoksi.• Keuhkovaltimoiden pallolaajennus on uusi tehokas hoito osalle potilaista.• TYKS:n Sydänkeskuksessa on tehty keuhkovaltimoiden pallolaajennuksia vuodesta 2016 ja tulokset ovat olleet rohkaisevia.</p

Specific autoantibody profiles and disease subgroups correlate with circulating micro-RNA in systemic sclerosis.

To evaluate the expression profiles of cell-free plasma miRNAs in SSc and to characterize their correlation with disease subgroups (lcSSc and dcSSc) and with autoantibody profiles

Follow-Up of Cancer Patients Receiving Anti-PD-(L)1 Therapy Using an Electronic Patient-Reported Outcomes Tool (KISS): Prospective Feasibility Cohort Study

Background: Immune checkpoint inhibitors (ICIs) have become a standard of care for various tumor types. Their unique spectrum of side effects demands continuous and long-lasting assessment of symptoms. Electronic patient-reported outcome (ePRO) follow-up has been shown to improve survival and quality of life of cancer patients treated with chemotherapy.Objective: This study aimed to investigate whether ePRO follow-up of cancer patients treated with ICIs is feasible. The study analyzed (1) the variety of patient reported symptoms, (2) etiology of alerts, (3) symptom correlations, and (4) patient compliance.Methods: In this prospective, one-arm, multi-institutional study, we recruited adult cancer patients whose advanced cancer was treated with anti-programmed cell death protein 1 (PD)-ligand (L)1 agents in outpatient settings. The ePRO tool consisted of a weekly questionnaire evaluating the presence of typical side effects, with an algorithm assessing the severity of the symptom according to National Cancer Institute Common Terminology Criteria for Adverse Events and an urgency algorithm sending alerts to the care team. A patient experience survey was conducted monthly. The patients were followed up to 6 months or until disease progression.Results: A total of 889 symptom questionnaires was completed by 37 patients (lung cancer, n=15; melanoma, n=9; genitourinary cancer, n=9; head and neck cancer, n=4). Patients showed good adherence to ePRO follow-up. The most common grade 1 symptoms were fatigue (28%) and itching (13%), grade 2 symptoms were loss of appetite (12%) and nausea (12%), and grade 3-4 symptoms were cough (6%) and loss of appetite (4%). The most common reasons for alerts were loss of appetite and shortness of breath. In the treatment benefit analysis, positive correlations were seen between clinical benefit and itching as well as progressive disease and chest pain.Conclusions: According to the results, ePRO follow-up of cancer patients receiving ICIs is feasible. ePROs capture a wide range of symptoms. Some symptoms correlate to treatment benefit, suggesting that individual prediction models could be generated

NMD and microRNA expression profiling of the HPCX1 locus reveal MAGEC1 as a candidate prostate cancer predisposition gene

Conclusions: Further functional studies are needed to fully understand the possible contribution of these miRNAs and MAGEC1 start codon variant to PC

PseudoGeneQuest – Service for identification of different pseudogene types in the human genome

<p>Abstract</p> <p>Background</p> <p>Pseudogenes, nonfunctional copies of genes, evolve fast due the lack of evolutionary pressures and thus appear in several different forms. PseudoGeneQuest is an online tool to search the human genome for a given query sequence and to identify different types of pseudogenes as well as novel genes and gene fragments.</p> <p>Description</p> <p>The service can detect pseudogenes, that have arisen either by retrotransposition or segmental genome duplication, many of which are not listed in the public pseudogene databases. The service has a user-friendly web interface and uses a powerful computer cluster in order to perform parallel searches and provide relatively fast runtimes despite exhaustive database searches and analyses.</p> <p>Conclusion</p> <p>PseudoGeneQuest is a versatile tool for detecting novel pseudogene candidates from the human genome. The service searches human genome sequences for five types of pseudogenes and provides an output that allows easy further analysis of observations. In addition to the result file the system provides visualization of the results linked to Ensembl Genome Browser. PseudoGeneQuest service is freely available.</p

Impact of deep learning-determined smoking status on mortality of cancer patients: never too late to quit

BackgroundPersistent smoking after cancer diagnosis is associated with increased overall mortality (OM) and cancer mortality (CM). According to the 2020 Surgeon General's report, smoking cessation may reduce CM but supporting evidence is not wide. Use of deep learning-based modeling that enables universal natural language processing of medical narratives to acquire population-based real-life smoking data may help overcome the challenge. We assessed the effect of smoking status and within-1-year smoking cessation on CM by an in-house adapted freely available language processing algorithm.Materials and methodsThis cross-sectional real-world study included 29 823 patients diagnosed with cancer in 2009-2018 in Southwest Finland. The medical narrative, International Classification of Diseases-10th edition codes, histology, cancer treatment records, and death certificates were combined. Over 162 000 sentences describing tobacco smoking behavior were analyzed with ULMFiT and BERT algorithms.ResultsThe language model classified the smoking status of 23 031 patients. Recent quitters had reduced CM [hazard ratio (HR) 0.80 (0.74-0.87)] and OM [HR 0.78 (0.72-0.84)] compared to persistent smokers. Compared to never smokers, persistent smokers had increased CM in head and neck, gastro-esophageal, pancreatic, lung, prostate, and breast cancer and Hodgkin's lymphoma, irrespective of age, comorbidities, performance status, or presence of metastatic disease. Increased CM was also observed in smokers with colorectal cancer, men with melanoma or bladder cancer, and lymphoid and myeloid leukemia, but no longer independently of the abovementioned covariates. Specificity and sensitivity were 96%/96%, 98%/68%, and 88%/99% for never, former, and current smokers, respectively, being essentially the same with both models.ConclusionsDeep learning can be used to classify large amounts of smoking data from the medical narrative with good accuracy. The results highlight the detrimental effects of persistent smoking in oncologic patients and emphasize that smoking cessation should always be an essential element of patient counseling.</p