The end-Ordovician extinction consisted of two discrete pulses, both linked, in various ways, to glaciation at the South Pole. The first phase, starting just below the Normalograptus extraordinarius ...Zone, particularly affected nektonic and planktonic species, while the second pulse, associated with the Normalograptus persculptus Zone, was less selective. Glacially induced cooling and oxygenation are two of many suggested kill mechanisms for the end-Ordovician extinction, but a general consensus is lacking. We have used geochemical redox indicators, such as iron speciation, molybdenum concentrations, pyrite framboid size distribution and sulfur isotopes to analyze the geochemistry in three key Hirnantian sections. These indicators reveal that reducing conditions were occasionally present at all three sites before the first pulse of the end-Ordovician extinction, and that these conditions expanded towards the second pulse. Even though the N. extraordinarius Zone appears to have been a time of oxygenated deposition, pyrite is significantly enriched in 34S in our sections as well as in sections reported from South China. This suggests a widespread reduction in marine sulfate concentrations, which we attribute to an increase in pyrite burial during the early Hirnantian. The S-isotope excursion coincides with a major positive carbon isotope excursion indicating elevated rates of organic carbon burial as well. We argue that euxinic conditions prevailed and intensified in the early Hirnantian oceans, and that a concomitant global sea level lowering pushed the chemocline deeper than the depositional setting of our sites. In the N. persculptus Zone, an interval associated with a major sea level rise, our redox indicators suggests that euxinic conditions, and ferruginous in some places, encroached onto the continental shelves. In our model, the expansion of euxinic conditions during the N. extraordinarius Zone was generated by a reorganization of nutrient cycling during sea level fall, and we argue, overall, that these dynamics in ocean chemistry played an important role for the end-Ordovician mass extinction. During the first pulse of the extinction, euxinia and a steepened oxygen gradient in the water column caused habitat loss for deep-water benthic and nektonic organisms. During the second pulse, the transgression of anoxic water onto the continental shelves caused extinction in shallower habitats.
► A sulfur isotope excursion shows widespread euxinia in the ‘oxic’ early Hirnantian. ► The nutrient-driven event was forced by sea level fall in a low-oxygen world. ► Euxinic conditions are also observed in the pre- and late Hirnantian. ► Anoxia, not cooling or oxygenation, was a likely kill-mechanism in the end-Ordovician mass extinction particularly in deeper-water faunas.
Studies in shift workers and model organisms link circadian disruption to breast cancer. However, molecular circadian rhythms in noncancerous and cancerous human breast tissues and their clinical ...relevance are largely unknown. We reconstructed rhythms informatically, integrating locally collected, time-stamped biopsies with public datasets. For noncancerous breast tissue, inflammatory, epithelial-mesenchymal transition (EMT), and estrogen responsiveness pathways show circadian modulation. Among tumors, clock correlation analysis demonstrates subtype-specific changes in circadian organization. Luminal A organoids and informatic ordering of luminal A samples exhibit continued, albeit dampened and reprogrammed rhythms. However, CYCLOPS magnitude, a measure of global rhythm strength, varied widely among luminal A samples. Cycling of EMT pathway genes was markedly increased in high-magnitude luminal A tumors. Surprisingly, patients with high-magnitude tumors had reduced 5-y survival. Correspondingly, 3D luminal A cultures show reduced invasion following molecular clock disruption. This study links subtype-specific circadian disruption in breast cancer to EMT, metastatic potential, and prognosis.
The early Cambrian Sirius Passet fauna of northernmost Greenland (Cambrian Series 2, Stage 3) contains exceptionally preserved soft tissues that provide an important window to early animal evolution, ...while the surrounding sediment holds critical data on the palaeodepositional water‐column chemistry. The present study combines palaeontological data with a multiproxy geochemical approach based on samples collected in situ at high stratigraphic resolution from Sirius Passet. After careful consideration of chemical alterations during burial, our results demonstrate that fossil preservation and biodiversity show significant correlation with iron enrichments (FeHR/FeT), trace metal behaviour (V/Al), and changes in nitrogen cycling (δ15N). These data, together with Mo/Al and the preservation of organic carbon (TOC), are consistent with a water column that was transiently low in oxygen concentration, or even intermittently anoxic. When compared with the biogeochemical characteristics of modern oxygen minimum zones (OMZs), geochemical and palaeontological data collectively suggest that oxygen concentrations as low as 0.2–0.4 ml/L restricted bioturbation but not the development of a largely nektobenthic community of predators and scavengers. We envisage for the Sirius Passet biota a depositional setting where anoxic water column conditions developed and passed over the depositional site, possibly in association with sea‐level change, and where this early Cambrian biota was established in conditions with very low oxygen.
Objective: To determine how much people with late effects of polio are bothered by various impairments and their influence on everyday life. Design: A mixed-methods design. Subjects/patients: Seven ...women and 7 men (mean age 70 years) with late effects of poli. Methods: Self-reported Impairments in Persons with late effects of Polio (SIPP) scale and face-to-face interviews. In SIPP, the participants rated, from 1 (not at all) to 4 (extremely), how much they had been bothered by late effects of polio-related impairments. Qualitative data were analysed using systematic text condensation. Each quotation was deductively analysed based on its conceptual representation regarding perceived influence on everyday life. Results: Participants were most bothered by muscle and/or joint pain during physical activity, muscle weakness and general fatigue, which corresponded with the number of interview quotations. The impairments negatively influenced daily life, such as household chores, walking, riding a bicycle and social participation. Increased impairments and reduced functioning on the less-affected side also caused worry and distress. Conclusion: Common late effects of polio-related impairments greatly affected participants' activity and participation. By using both the SIPP scale and face-to-face interviews, an increased understanding of how late effects of polio-related impairments influence everyday life was achieved.
To describe the experiences of growing up after acute paralytic poliomyelitis and strategies used to adapt to the new situation.
Seven women and seven men (mean age 70 years, min-max 61-78 years) ...with late effects of polio, who had contracted paralytic polio in their childhood. Data were collected using semi-structured interviews, transcribed verbatim, and analyzed by systematic text condensation.
Memories of contracting acute paralytic poliomyelitis involved being immobilized and sent away from home for surgical and physiotherapeutic treatment. Growing up in a social context that was often tough and unfriendly resulted in the development of strategies, such as optimistic thinking, trying to blend in, trusting one's ability to manage, and to handle the preconceptions and expectations of others. At the onset of late effects of polio, some of these strategies were still functioning, whereas overachieving, disregarding pain, and weariness were not.
The challenges of growing up with a disability following paralytic polio led to the development of various psychological strategies for managing daily life. By understanding these experiences and strategies, knowledge may be gained in assisting rehabilitation professionals to better support persons with late effects of polio in adapting to the new situation.
Implications for rehabilitation
At the onset of late effects of polio, strategies developed earlier in life, such as overachieving, disregarding pain, and weariness, may not function anymore.
Understanding the experiences of growing up with poliomyelitis can support rehabilitation professionals to provide targeted interventions for people with late effects of polio and enable them to develop new adaptive strategies.
Developing new strategies, such as accepting increased symptoms, and augmenting self-esteem and self-efficacy, may improve daily functioning among people with late effects of polio.
To explore how persons with late effects of polio experience falls and what strategies they use to manage the consequences of falls.
A qualitative study with face-to-face interviews. Data were ...analysed by systematic text condensation.
Fourteen ambulatory persons (7 women; mean age 70 years) with late effects of polio.
Analysis resulted in one main theme, "Everyday life is a challenge to avoid the consequences of falls", and 3 categories with 7 subcategories. Participants perceived that falls were unpredictable and could occur anywhere. Even slightly uneven surfaces could cause a fall, and increased impairments following late effects of polio led to reduced movement control and an inability to adjust balance quickly. Physical injuries were described after the falls, as well as emotional and psychological reactions, such as embarrassment, frustration and fear of falling. Assistive devices, careful planning and strategic thinking were strategies to prevent falls, together with adaptation and social comparisons to mitigate the emotional reactions.
Experiences of falls greatly affect persons with late effects of polio in daily life. To reduce falls and fall-related consequences both problem-focused and emotion-focused strategies are used. In order to increase daily functioning, these findings should be included in a multifaceted falls management programme.
Falls are common among persons with late effects of polio (LEoP), which may lead to fear of falling and activity avoidance in everyday life. Here, we assessed the occurrence of fall-related activity ...avoidance among persons with LEoP and explored how these experiences influenced daily life. Fourteen ambulatory persons (seven women; mean age 70 years) with LEoP participated. They responded to the modified Survey of Activities and Fear of Falling in the Elderly (mSAFFE) and participated in individual interviews, which were analysed by systematic text condensation. Each quotation was deductively analysed from its representation with regard to mSAFFE. We found that many persons often avoided activities related to standing and walking, for example, taking a bath, performing household chores, walking outdoors, attending social events if there were stairs in the building and travelling by public transport, due to fear of falling, increased pain and fatigability. To facilitate the performance of daily activities participants expressed that strategic thinking and aids were important to use. In conclusion, fall-related activity avoidance is common in persons with LEoP, which negatively influence daily life and social participation. To increase daily functioning in this population, fall-related activity avoidance should be included in a multifaceted fall management program.
New or increased impairments may develop several decades after an acute poliomyelitis infection. These new symptoms, commonly referred to as late effects of polio (LEoP), are characterised by ...muscular weakness and fatigue, generalised fatigue, pain at rest or during activities and cold intolerance. Growing older with LEoP may lead to increased activity limitations and participation restrictions, but there is limited knowledge of how these persons perceive the practical and psychological consequences of ageing with LEoP and what strategies they use in daily life. The aim of this qualitative study was therefore to explore how ageing people with LEoP perceive the their situation and what strategies they use for managing daily life.
Seven women and seven men (mean age 70 years) were interviewed. They all had a confirmed history of acute poliomyelitis and new impairments after a stable period of at least 15 years. Data were transcribed verbatim and analysed using systematic text condensation.
The latent analysis resulted in three categories 'Various consequences of ageing with LEoP', 'Limitations in everyday activities and participation restrictions', and 'Strategies for managing daily life when ageing with LEoP' and 12 subcategories. The new impairments led to decreased physical and mental health. The participants perceived difficulties in performing everyday activities such as managing work, doing chores, partaking in recreational activities and participating in social events, thereby experiencing emotional and psychological distress. They managed to find strategies that mitigated their worries and upheld their self-confidence, for example finding practical solutions, making social comparisons, minimising, and avoidance.
Ageing with LEoP affected daily life to a great extent. The participants experienced considerable impact of the new and increased impairments on their life situation. Consequently, their ability to participate in various social activities also became restricted. Social comparisons and practical solutions are strategies that facilitate adaptation and acceptance of the new situation due to LEoP. This emphasises the need to design rehabilitation interventions that focus on coping, empowerment and self-management for people ageing with LEoP.
Reduced walking ability is common in persons with late effects of polio (LEoP). Here, we explored how many walking limitations persons with LEoP perceive, and how these limitations influence daily ...life, by using a mixed-methods design. Fourteen persons (mean age 70 years, whereof 7 women) with LEoP responded to the Walking Impact Scale (Walk-12), and were interviewed individually. Qualitative data were analysed by systematic text condensation, and each quotation was deductively analysed in relation to the items in Walk-12. Running was perceived as most limited, whereas walking indoors without using support was perceived as least limited. A majority (>70%) were moderately to extremely limited in standing or walking, in walking speed and distance, which affected concentration and effort, as well as gait quality aspects. The limited walking ability intruded on many everyday activities, both indoors and outdoors, which affected social participation negatively. To increase safety when walking and reduce the fall risk, various strategies were adopted such as using aids, walking carefully, and avoiding risky activities. In conclusion, LEoP-related walking limitations influence participants’ activity and participation greatly. By using both the Walk-12 scale and face-to-face interviews, an increased understanding of how walking limitations influence everyday life was achieved.
Background:
As the patents of originator biologics are expiring, biosimilar versions are becoming available for the treatment of inflammatory bowel disease (IBD). However, published switch studies of ...the first infliximab biosimilar, CT-P13, have delivered ambiguous results that could be interpreted as showing a trend towards inferior effectiveness in Crohn’s disease (CD) compared with ulcerative colitis (UC). The aim of this study was to investigate the effectiveness and safety of switching IBD patients from treatment with Remicade to CT-P13.
Methods:
In this prospective observational cohort study, all adult IBD patients on Remicade treatment, at four hospitals, were switched to CT-P13. The primary endpoint was change in clinical disease activity at 2, 6, and 12 months after the switch. Secondary endpoints were subgroup analyses of patients with and without concomitant immunomodulators; changes in biomarkers, quality of life, drug trough levels and anti-drug antibodies (ADAbs); and adverse events.
Results:
A total of 313 IBD patients were switched (195 CD; 118 UC). There were no significant changes in clinical disease activity, quality of life, biomarkers (except a small but significant increase in albumin in CD) including F-calprotectin, drug trough levels, or proportion of patients in remission. Disease worsening rates were 14.0% for CD and 13.8% for UC; and 2.7% developed ADAbs and 2.2% developed serious adverse events.
Conclusions:
This is the largest study of switched IBD patients published to date, and it demonstrates that switching from Remicade to CT-P13 may be done with preserved therapeutic effectiveness and safety in both CD and UC.
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