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The collapse of ice shelves could expose tall ice cliffs at ice sheet margins. The marine ice cliff instability (MICI) is a hypothesis that predicts that, if these cliffs are tall enough, ice may fail structurally leading to self-sustained retreat. To date, projections that include MICI have been performed with a single model based on a simple parameterization. Here, we implement a physically motivated parameterization in three ice sheet models and simulate the response of the Amundsen Sea Embayment after a hypothetical collapse of floating ice. All models show that Thwaites Glacier would not retreat further in the 21st century. In another set of simulations, we force the grounding line to retreat into Thwaites' deeper basin to expose a taller cliff. In these simulations, rapid thinning and velocity increase reduce the calving rate, stabilizing the cliff. These experiments show that Thwaites may be less vulnerable to MICI than previously thought, and model projections that include this process should be re-evaluated.
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A decline in forced expiratory volume (FEV1) is a hallmark of obstructive respiratory diseases, an important cause of morbidity among the elderly. While some data exist on biomarkers that are related to FEV1, we sought to do a systematic analysis of causal relations of biomarkers with FEV1. Data from the general population-based AGES-Reykjavik study were used. Proteomic measurements were done using 4,782 DNA aptamers (SOMAmers). Data from 1,648 participants with spirometric data were used to assess the association of SOMAmer measurements with FEV1 using linear regression. Bi-directional Mendelian randomisation (MR) analyses were done to assess causal relations of observationally associated SOMAmers with FEV1, using genotype and SOMAmer data from 5,368 AGES-Reykjavik participants and genetic associations with FEV1 from a publicly available GWAS (n = 400,102). In observational analyses, 473 SOMAmers were associated with FEV1 after multiple testing adjustment. The most significant were R-Spondin 4, Alkaline Phosphatase, Placental Like 2 and Retinoic Acid Receptor Responder 2. Of the 235 SOMAmers with genetic data, eight were associated with FEV1 in MR analyses. Three were directionally consistent with the observational estimate, Thrombospondin 2 (THBS2), Endoplasmic Reticulum Oxidoreductase 1 Beta and Apolipoprotein M. THBS2 was further supported by a colocalization analysis. Analyses in the reverse direction, testing whether changes in SOMAmer levels were caused by changes in FEV1, were performed but no significant associations were found after multiple testing adjustments. In summary, this large scale proteogenomic analyses of FEV1 reveals protein markers of FEV1, as well as several proteins with potential causality to lung function.
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The East Antarctic Ice Sheet (EAIS) is currently surrounded by relatively cool water, but climatic shifts have the potential to increase basal melting via intrusions of warm modified Circumpolar Deep Water (mCDW) onto the continental shelf. Here we use an ice sheet model to show that under the current ocean regime, with only limited intrusions of mCDW, the EAIS will likely gain mass over the next 200 years due to the increased precipitation from a warming atmosphere outweighing increased ice discharge due to ice-shelf melting. However, if the ocean regime were to become dominated by greater mCDW intrusions, the EAIS would have a negative mass balance, contributing up to 48 mm of SLE over this time period. Our modelling finds George V Land to be particularly at risk to increased ocean induced melting. With warmer oceans, we also find that a mid range RCP4.5 emissions scenario is likely to result in a more negative mass balance than a high RCP8.5 emissions scenario, as the relative difference between increased precipitation due to a warming atmosphere and increased ice discharge due to a warming ocean is more negative in the mid range RCP4.5 emission scenario.
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BACKGROUND: Increasing evidence shows that lifestyle interventions can improve the symptoms, quality of life (QoL), and even overall survival of patients with cancer. Digital therapeutics (DTx) can help implement behavioral modifications and empower patients through education, lifestyle support, and remote symptom monitoring. OBJECTIVE: We aimed to test the feasibility of a DTx program for patients with cancer, as measured by engagement, retention, and acceptability. In addition, we explored the effects of the program on cancer-related QoL. METHODS: We conducted a 4-week single-arm trial in Iceland, where DTx was delivered through a smartphone app. The intervention consisted of patient education about mindfulness, sleep, stress, and nutrition; lifestyle coaching; and the completion of daily missions for tracking physical activity and exercise, reporting patient-reported outcomes (PROs), practicing mindfulness, and logging healthy food intake. Information on program engagement and retention, step goal attainment, as well as PROs were collected throughout the study. QoL was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 at baseline and follow-up. RESULTS: In total, 30 patients with cancer undergoing active therapy were enrolled, and 29 registered in the app (23 female, 18 with breast cancer; mean age 52.6, SD 11.5 years). Overall, 97% (28/29) of participants were active in 3 of the 4 weeks and completed the pre- and postprogram questionnaires. The weekly active days (median) were 6.8 (IQR 5.8-6.8), and 72% (21/29) of participants were active at least 5 days a week. Users interacted with the app on average 7.7 (SD 1.9) times per day. On week 1, all 29 participants used the step counter and logged an average of 20,306 steps; 21 (72%) participants reached their step goals of at least 3000 steps per day. On week 4, of the 28 active users, 27 (96%) were still logging their steps, with 19 (68%) reaching their step goals. Of the 28 participants who completed the satisfaction questionnaire, 25 (89%) were likely to recommend the program, 23 (82%) said the program helped them deal with the disease, and 24 (86%) said it helped them remember their medication. QoL assessment showed that the average global health status, functioning, and symptom burden remained stable from baseline to follow-up. In all, 50% (14/28) of participants reported less pain, and the average pain score decreased from 31 (SD 20.1) to 22.6 (SD 23.2; P=.16). There was no significant change in PROs on the quality of sleep, energy, and stress levels from the first to the last week. CONCLUSIONS: The high retention, engagement, and acceptability found in this study demonstrate that multidisciplinary DTx is feasible for patients with cancer. A longer, full-scale randomized controlled trial is currently being planned to evaluate the efficacy of the intervention.
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Antarctica's contribution to global mean sea level rise has been driven by an increase in ice discharge into the oceans. The rate of change and the mechanisms that drive variability in ice discharge are therefore important to consider in the context of projected future warming. Here, we report observations of both decadal trends and inter-annual variability in ice discharge across the Antarctic Ice Sheet at a variety of spatial scales that range from large drainage basins to individual outlet glacier catchments. Overall, we find a 37 ± 11 Gt year-1 increase in discharge between 1999 and 2010, but a much smaller increase of 4 ± 8 Gt year-1 between 2010 and 2018. Furthermore, comparisons reveal that neighbouring outlet glaciers can behave synchronously, but others show opposing trends, despite their close proximity. We link this spatial and temporal variability to changes in ice shelf buttressing and the modulating effect of local glacier geometry.
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INTRODUCTION: Five-year survival of people diagnosed with cancer has increased in past decades. Knowledge of the long-term effects of cancer treatment on fitness, body composition and health related quality of life (HR-QoL) is important for cancer patients. The study aimed to evaluate body composition, HR-QoL and personality D of people post cancer treatment in the last 10 years; and to observe whether fitness was correlated with body composition and HR-QoL amongst them. MATERIAL AND METHODS: Eighty participants 25 - 77 y/o of both genders in remission from cancer answered questionnaires on HR-QoL (SF-36v2 and EQ-5D-3L), personality D (DS14), general health, lifestyle and cancer treatment. Participants had their blood pressure measured, conducted the 6-minute walk test (6MWT) and had their body composition meas-ured: body mass index, body fat percentage, waist and hip circumferences. SPSS was used for statistical analysis. RESULTS: Approximately 2/3 of the participants had body composition over recommended values. Over half were overweight or obese. 66.3% had waist circumference over recommended values and 45.0% had waist/hip ratio over recommended values. 6MWT average distance was 634 m +/- 83 m. Significant correlation (p<0.05) was found between 6MWT and body composition and most categories of HR-QoL. -Increased fitness correlated with better body composition and higher HR-QoL. Only 13.8% of participants showed personality D. CONCLUSION: Cancer survivor's body composition is generally not at its best. It is important that people diagnosed with cancer are informed on the importance of healthy body composition. Fitness is an indicator for HR-QoL and body composition of cancer survivors.
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Composição Corporal , Sobreviventes de Câncer/psicologia , Neoplasias/terapia , Aptidão Física , Qualidade de Vida , Adiposidade , Adulto , Idoso , Feminino , Estado Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Personalidade Tipo D , Circunferência da CinturaRESUMO
Stearns and van der Veen (Reports, 20 July 2018, p. 273) conclude that fast glacier sliding is independent of basal drag (friction), even where drag balances most of the driving stress. This conclusion raises fundamental physical issues, the most striking of which is that sliding velocity would be independent of stresses imparted through the ice column, including gravitational driving stress.
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Idiopathic pulmonary fibrosis (IPF) is a fatal progressive lung disease occurring in adults. In the last decade, the results of a number of clinical trials based on the updated disease classification have been published. The registration of pirfenidone and nintedanib, the first two pharmacological treatment options approved for IPF, marks a new chapter in the management of patients with this disease. Other nonpharmacological treatments such as lung transplantation, rehabilitation and palliation have also been shown to be beneficial for these patients. In this review, past and present management is discussed based on a comprehensive literature search. A treatment algorithm is presented based on available evidence and our overall clinical experience. In addition, unmet needs with regard to treatment are highlighted and discussed. We describe the development of various treatment options for IPF from the first consensus to recent guidelines based on evidence from large-scale, multinational, randomized clinical trials, which have led to registration of the first drugs for IPF.
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Fibrose Pulmonar Idiopática/terapia , Algoritmos , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Humanos , Fibrose Pulmonar Idiopática/complicações , Indóis/efeitos adversos , Indóis/uso terapêutico , Piridonas/efeitos adversos , Piridonas/uso terapêuticoRESUMO
A new concept for treatment of infections is induction of our own antimicrobial peptides and the presented novel class of inducer, aroylated phenylenediamines (APDs), gives up to 20 to 30-fold induction of the human antimicrobial peptide LL-37, in vitro. In addition, oral administration of an APD in a rabbit model of Shigellosis resulted in recovery from the infection in a few days implying that APD's are promising candidates for treatment of infections.
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Peptídeos Catiônicos Antimicrobianos/metabolismo , Disenteria Bacilar/tratamento farmacológico , Fenilenodiaminas/farmacologia , Administração Oral , Animais , Linhagem Celular , Feminino , Humanos , Masculino , Fenilenodiaminas/síntese química , Fenilenodiaminas/química , Coelhos , CatelicidinasRESUMO
SETTING: The clinical differences between cryptogenic organising pneumonia (COP) and secondary organising pneumonia (OP) have not been studied well. OBJECTIVE: To compare clinical features in COP and secondary OP. DESIGN: Causes, clinical features, treatment, radiographic studies and pathology were studied. RESULTS: After re-evaluation, 104 patients fulfilled the diagnostic criteria, 58 for COP and 46 for secondary OP. The mean age was 68 years. Most of the patients were smokers (79/104). Infections were the most common causes of secondary OP (21/46). Cough was the most common symptom and crackles the most common sign. Crackles were more common in patients with secondary OP (P = 0.02). Transbronchial biopsy was the diagnostic test in 81/104 cases. Most patients had lowered partial oxygen pressure (PO(2)) and mildly restrictive spirometry, with no differences between the two groups. Radiographic features were similar. Corticosteroids were the treatment in 70% of the patients, but 27% received no pharmacological treatment. The average initial dose of steroids was 42 mg prednisolone, and was similar for both groups. Relapses were seen in 20% of cases, with no difference between the two groups. CONCLUSION: There were no major differences in clinical features of COP and secondary OP, except that crackles were more common in secondary OP.
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Pneumonia em Organização Criptogênica , Corticosteroides/uso terapêutico , Idoso , Infecções Bacterianas/complicações , Tosse/etiologia , Pneumonia em Organização Criptogênica/complicações , Pneumonia em Organização Criptogênica/diagnóstico , Pneumonia em Organização Criptogênica/diagnóstico por imagem , Pneumonia em Organização Criptogênica/tratamento farmacológico , Pneumonia em Organização Criptogênica/epidemiologia , Pneumonia em Organização Criptogênica/etiologia , Diagnóstico Diferencial , Feminino , Humanos , Islândia/epidemiologia , Masculino , Pessoa de Meia-Idade , Vigilância da População , Radiografia , Recidiva , Testes de Função Respiratória , Sons Respiratórios/etiologia , Estudos Retrospectivos , Fatores de Risco , Fumar/efeitos adversos , Resultado do Tratamento , Viroses/complicaçõesRESUMO
BACKGROUND: Microsurgical discectomies are an established procedure in spinal surgery. This operating technique was first used in the Department of Neurosurgery in Iceland in 1981 and has become standard operative treatment for herniated lumbar discs. There is a great variability in outcome reports regarding recurrence rate and re-operation rate. Few articles are based on follow-up of more than 10 years. This article presents the results of a 20 years follow-up study. METHODS: A retrospective study of all patients undergoing microsurgical discectomy for herniated lumbar disc, from June 1, 1981 to December 31, 1984. Outcome, based on recurrence rate, return to work and patient satisfaction was determined by a self-evaluation questionnaire, phone interviews and patient medical records. FINDINGS: Of the 170 patients, 134 (78.8%) were included in the study (M:F, 58:42%). Preoperative symptoms: back pain with sciatica 108 (80.6%), sciatica 20 (14.9%), back pain 2 (1.5%). Mean follow-up time was 20.7 years (19.5-22.8). Recurrence rate was 12.7%. 19 patients (14.2%) underwent a subsequent lumbar operation at a different level or side. A majority of patients 108 (80.6%) returned to previous level of work, 26 (19.4%) lost some or all working capabilities. Patient satisfaction was high, 91.1% reporting excellent (68.7%) or good (22.4%) results. 5.2% of patients rated the outcome fair and 3.7% poor. Women reported worse outcome than men, excellent M:F 74.7:60.7%, and poor 7.1:1.3%. There was no significant difference in patient satisfaction in patients undergoing additional operations or those with recurrence of the herniated disc. CONCLUSIONS: Outcome was very good with 92.0% return to work and 91.1% patient satisfaction. The recurrence rate was 12.7% with a substantial number of cases occurring 10-20 years after operation. To conclude, microsurgical discectomies maintain a high success rate in the long-term.
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Discotomia , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares , Microcirurgia , Adolescente , Adulto , Emprego , Feminino , Seguimentos , Humanos , Islândia , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Recidiva , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Most of the ice lost from the Antarctic ice sheet passes through a few fast-flowing and highly dynamic ice streams. Quantifying temporal variations in flow in these ice streams, and understanding their causes, is a prerequisite for estimating the potential contribution of the Antarctic ice sheet to global sea-level change. Here I show that surface velocities on a major West Antarctic Ice Stream, Rutford Ice Stream, vary periodically by about 20 per cent every two weeks as a result of tidal forcing. Tidally induced motion on ice streams has previously been thought to be limited to diurnal or even shorter-term variations. The existence of strong fortnightly variations in flow demonstrates the potential pitfalls of using repeated velocity measurements over intervals of days to infer long-term change.
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Antimicrobial peptides or host defence peptides are endogenous peptide antibiotics, which have been confirmed as an essential part of the immune system. Apart from direct killing of bacteria, a role for the peptides in antiviral and immunomodulatory functions has recently been claimed. In this chapter we have focused on the host contact with microbes, where these host defence peptides are key players. The interplay with commensals and pathogens in relation to antimicrobial peptide expression is discussed, with specific emphasis on the respiratory and the alimentary systems. A possible novel difference in epithelial interactions between commensals and pathogens is considered in relation to disease.
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Peptídeos Catiônicos Antimicrobianos/fisiologia , Defensinas/fisiologia , Imunidade Inata , Colo/imunologia , Fibrose Cística/imunologia , Sistema Digestório/imunologia , Humanos , Fatores Imunológicos/fisiologia , Intestino Delgado/imunologia , Boca/imunologia , Sistema Respiratório/imunologia , Pele/imunologia , Estômago/imunologia , CatelicidinasRESUMO
BACKGROUND: Cryptogenic organising pneumonia (COP) has also been called idiopathic bronchiolitis obliterans organising pneumonia. In secondary organising pneumonia (SOP) the causes can be identified or it occurs in a characteristic clinical context. The aim of this study was to determine the incidence and epidemiological features of COP and SOP nationwide in Iceland over an extended period. METHODS: A retrospective study of organising pneumonia (OP) in Iceland over 20 years was conducted and the epidemiology and survival were studied. All pathological reports of patients diagnosed with or suspected of having COP or SOP in the period 1984-2003 were identified and the pathology samples were re-evaluated using strict diagnostic criteria. RESULTS: After re-evaluation, 104 patients fulfilled the diagnostic criteria for OP (58 COP and 46 SOP). The mean annual incidence of OP was 1.97/100 000 population (1.10/100 000 for COP and 0.87/100 000 for SOP). The mean age at diagnosis was 67 years with a wide age range. The most common causes of death were lung diseases other than OP, and only one patient died from OP. Patients with OP had a lower rate of survival than the general population, but there was no statistical difference between COP and SOP. CONCLUSIONS: The incidence of OP is higher than previously reported, suggesting that OP needs to be considered as a diagnosis more often than has been done in the past.
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Pneumonia em Organização Criptogênica/epidemiologia , Adolescente , Adulto , Idoso , Pneumonia em Organização Criptogênica/mortalidade , Feminino , Humanos , Islândia/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de SobrevidaRESUMO
The human cathelicidin LL-37 has been shown to be involved in the barrier function of the innate immunity, being released from specific cells upon challenge and exerting immunomodulatory effects. We here demonstrate that LL-37 affects immature dendritic cells, derived from human peripheral blood monocytes (MDDC). LL-37 is internalized by MDDC with subsequent localization primarily in the cytoplasmic compartment. However, LL-37 could also be detected in the nuclei of MDDC, suggesting that LL-37 may be transported into the nucleus. The uptake of LL-37 is dose, time and energy dependent, indicating that the observed internalization process involves an endocytic pathway. Incubation of immature MDDC with LL-37 caused phenotypic changes, characterized by an increased expression of the antigen-presenting molecule HLA-DR, and the costimulatory molecule CD86. Taken together, these findings suggest that LL-37 released upon triggering of the innate immunity, may affect cellular adaptive immunity through an interaction with immature dendritic cells.
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Peptídeos Catiônicos Antimicrobianos/metabolismo , Diferenciação Celular/imunologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Imunofenotipagem , Sequência de Aminoácidos , Peptídeos Catiônicos Antimicrobianos/fisiologia , Células Cultivadas , Citocinas/biossíntese , Células Dendríticas/citologia , Humanos , Imunidade Celular , Líquido Intracelular/imunologia , Líquido Intracelular/metabolismo , Dados de Sequência Molecular , Monócitos/citologia , Monócitos/imunologia , Monócitos/metabolismo , CatelicidinasRESUMO
BACKGROUND: Atopic eczema (AE) is a multifactorial disease, which has increased in prevalence. The skin-colonizing yeast Malasezzia sympodialis can induce IgE- and T-cell reactivity in patients with AE. LL-37 is an endogenous peptide antibiotic belonging to the cathelicidin family. The aim of this study was to examine whether exposure to M. sympodialis would affect the expression of LL-37 in dendritic cells. METHODS: The presence of LL-37 was analyzed in monocyte-derived dendritic cells (MDDCs) generated from healthy individuals and patients with AE by Western blotting and the corresponding cDNA by real-time quantitative RT-PCR. Antibacterial activity was measured with an inhibition zone assay in fractions after reverse phase chromatography. RESULTS: For the first time we here present data, showing that LL-37 is produced by MDDCs. Notably, the secretion of LL-37 was substantially enhanced in M. sympodialis-exposed MDDCs generated from patients with a high degree of eczema, as measured by SCORAD, compared to healthy controls and patients with a low SCORAD. The relative expression of LL-37 transcript in MDDCs generated from patients was up-regulated after 1 h of exposure to M. sympodialis and declined gradually at the time points analyzed, whereas the transcription was unaffected in the MDDCs of healthy controls. CONCLUSIONS: Our results suggest that M. sympodialis can trigger the innate immune response differently in patients with AE and healthy individuals. The enhanced LL-37 secretion from the MDDCs in the patients with AE may reflect the severity of their inflammatory response to M. sympodialis.
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Peptídeos Catiônicos Antimicrobianos/biossíntese , Células Dendríticas/imunologia , Dermatite Atópica/imunologia , Malassezia/fisiologia , Adulto , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Células Dendríticas/metabolismo , Feminino , Humanos , Imunidade Inata , Masculino , Pessoa de Meia-Idade , CatelicidinasRESUMO
Vernix caseosa is a white cream-like substance that covers the skin of the foetus and the newborn baby. Recently, we discovered antimicrobial peptides/proteins such as LL-37 in vernix, suggesting host defence functions of vernix. In a proteomic approach, we have continued to characterize proteins in vernix and have identified 20 proteins, plus additional variant forms. The novel proteins identified, considered to be involved in host defence, are cystatin A, UGRP-1, and calgranulin A, B and C. These proteins add protective functions to vernix such as antifungal activity, opsonizing capacity, protease inhibition and parasite inactivation. The composition of the lipids in vernix has also been characterized and among these compounds the free fatty acids were found to exhibit antimicrobial activity. Interestingly, the vernix lipids enhance the antimicrobial activity of LL-37 in vitro, indicating interactions between lipids and antimicrobial peptides in vernix. In conclusion, vernix is a balanced cream of compounds involved in host defence, protecting the foetus and newborn against infection.
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Anti-Infecciosos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Lipídeos/farmacologia , Verniz Caseoso/química , Sequência de Aminoácidos , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/isolamento & purificação , Bactérias/efeitos dos fármacos , Clorexidina/análise , Humanos , Recém-Nascido , Lipídeos/química , Lipídeos/isolamento & purificação , Dados de Sequência Molecular , Proteômica , Verniz Caseoso/metabolismo , CatelicidinasRESUMO
The aim of the present study was to analyse the risk of rehospitalisation in patients with chronic obstructive pulmonary disease and associated risk factors. This prospective study included 416 patients from a university hospital in each of the five Nordic countries. Data included demographic information, spirometry, comorbidity and 12 month follow-up for 406 patients. The hospital anxiety and depression scale and St. George's Respiratory Questionnaire (SGRQ) were applied to all patients. The number of patients that had a re-admission within 12 months was 246 (60.6%). Patients that had a re-admission had lower lung function and health status. A low forced expiratory volume in one second (FEV1) and health status were independent predictors for re-admission. Hazard ratio (HR; 95% CI) was 0.82 (0.74-0.90) per 10% increase of the predicted FEV1 and 1.06 (1.02-1.10) per 4 units increase in total SGRQ score. The risk of rehospitalisation was also increased in subjects with anxiety (HR 1.76 (1.16-2.68)) and in subjects with low health status (total SGRQ score >60 units). When comparing the different subscales in the SGRQ, the closest relation between the risk of rehospitalisation was seen with the activity scale (HR 1.07 (1.03-1.11) per 4 unit increase). In patients with low health status, anxiety is an important risk factor for rehospitalisation. This may be important for patient treatment and warrants further studies.