Numerous publications have stated that metastases are responsible for 90% of cancer deaths, but data underlying this assertion has been lacking. Our objective was to determine what proportions of ...cancer deaths are caused by metastases. Population‐based data from the Cancer Registry of Norway for the years 2005‐2015 was analyzed. We compared all deaths in the Norwegian population where a cancer diagnosis was registered as cause of death. Deaths caused by cancer, with and without metastases, were analyzed, by sex and tumor group. For solid tumors, 66.7% of cancer deaths were registered with metastases as a contributing cause. Proportions varied substantially between tumor groups. Our data support the idea that the majority of deaths from solid tumors are caused by metastases. Thus, a better understanding of the biology of metastases and identification of druggable targets involved in growth at the metastatic site is a promising strategy to reduce cancer mortality.
In publications on cancer research, a common statement is that 90% of cancer deaths are caused by metastases, data underlying this assertion has been lacking. Using the nation‐wide, population based Norwegian Cancer Registry, we found that two of three of the deaths from solid tumors were registered with metastases as contributing cause of death, with substantial variation between tumor groups.
•Mindfulness-Based Resilience Training (MBRT) is feasible and acceptable to law enforcement officers.•Relative to no intervention control (NIC), MBRT participants endorsed reduced aggression and ...health risk outcomes.•MBRT participants had lower cortisol levels on day 3 post-training compared to NIC participants.•Psychological and physiological improvements at post-training were not maintained at 3-month follow-up.•Follow-up training or “booster” sessions may be needed to maintain training gains.
The primary objective of this study was to assess feasibility and gather preliminary outcome data on Mindfulness-Based Resilience Training (MBRT) for law enforcement officers. Participants (n = 61) were randomized to either an 8-week MBRT course or a no intervention control group. Self-report and physiological data were collected at baseline, post-training, and three months following intervention completion. Attendance, adherence, post-training participant feedback, and interventionist fidelity to protocol all demonstrated feasibility of MBRT for law enforcement officers. Compared to no intervention controls, MBRT participants experienced greater reductions in salivary cortisol, self-reported aggression, organizational stress, burnout, sleep disturbance, and reported increases in psychological flexibility and non-reactivity at post-training; however, group differences were not maintained at three-month follow-up. This initial randomized trial suggests MBRT is a feasible intervention. Outcome data suggest MBRT targets key physiological, psychological, and health risk factors in law enforcement officers, consistent with the potential to improve officer health and public safety. However, follow-up training or “booster” sessions may be needed to maintain training gains. A fully powered longitudinal randomized trial is warranted.
Before the COVID-19 pandemic, coronaviruses caused two noteworthy outbreaks: severe acute respiratory syndrome (SARS), starting in 2002, and Middle East respiratory syndrome (MERS), starting in 2012. ...We aimed to assess the psychiatric and neuropsychiatric presentations of SARS, MERS, and COVID-19.
In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases (from their inception until March 18, 2020), and medRxiv, bioRxiv, and PsyArXiv (between Jan 1, 2020, and April 10, 2020) were searched by two independent researchers for all English-language studies or preprints reporting data on the psychiatric and neuropsychiatric presentations of individuals with suspected or laboratory-confirmed coronavirus infection (SARS coronavirus, MERS coronavirus, or SARS coronavirus 2). We excluded studies limited to neurological complications without specified neuropsychiatric presentations and those investigating the indirect effects of coronavirus infections on the mental health of people who are not infected, such as those mediated through physical distancing measures such as self-isolation or quarantine. Outcomes were psychiatric signs or symptoms; symptom severity; diagnoses based on ICD-10, DSM-IV, or the Chinese Classification of Mental Disorders (third edition) or psychometric scales; quality of life; and employment. Both the systematic review and the meta-analysis stratified outcomes across illness stages (acute vs post-illness) for SARS and MERS. We used a random-effects model for the meta-analysis, and the meta-analytical effect size was prevalence for relevant outcomes, I2 statistics, and assessment of study quality.
1963 studies and 87 preprints were identified by the systematic search, of which 65 peer-reviewed studies and seven preprints met inclusion criteria. The number of coronavirus cases of the included studies was 3559, ranging from 1 to 997, and the mean age of participants in studies ranged from 12·2 years (SD 4·1) to 68·0 years (single case report). Studies were from China, Hong Kong, South Korea, Canada, Saudi Arabia, France, Japan, Singapore, the UK, and the USA. Follow-up time for the post-illness studies varied between 60 days and 12 years. The systematic review revealed that during the acute illness, common symptoms among patients admitted to hospital for SARS or MERS included confusion (36 27·9%; 95% CI 20·5–36·0 of 129 patients), depressed mood (42 32·6%; 24·7–40·9 of 129), anxiety (46 35·7%; 27·6–44·2 of 129), impaired memory (44 34·1%; 26·2–42·5 of 129), and insomnia (54 41·9%; 22·5–50·5 of 129). Steroid-induced mania and psychosis were reported in 13 (0·7%) of 1744 patients with SARS in the acute stage in one study. In the post-illness stage, depressed mood (35 10·5%; 95% CI 7·5–14·1 of 332 patients), insomnia (34 12·1%; 8·6–16·3 of 280), anxiety (21 12·3%; 7·7–17·7 of 171), irritability (28 12·8%; 8·7–17·6 of 218), memory impairment (44 18·9%; 14·1–24·2 of 233), fatigue (61 19·3%; 15·1–23·9 of 316), and in one study traumatic memories (55 30·4%; 23·9–37·3 of 181) and sleep disorder (14 100·0%; 88·0–100·0 of 14) were frequently reported. The meta-analysis indicated that in the post-illness stage the point prevalence of post-traumatic stress disorder was 32·2% (95% CI 23·7–42·0; 121 of 402 cases from four studies), that of depression was 14·9% (12·1–18·2; 77 of 517 cases from five studies), and that of anxiety disorders was 14·8% (11·1–19·4; 42 of 284 cases from three studies). 446 (76·9%; 95% CI 68·1–84·6) of 580 patients from six studies had returned to work at a mean follow-up time of 35·3 months (SD 40·1). When data for patients with COVID-19 were examined (including preprint data), there was evidence for delirium (confusion in 26 65% of 40 intensive care unit patients and agitation in 40 69% of 58 intensive care unit patients in one study, and altered consciousness in 17 21% of 82 patients who subsequently died in another study). At discharge, 15 (33%) of 45 patients with COVID-19 who were assessed had a dysexecutive syndrome in one study. At the time of writing, there were two reports of hypoxic encephalopathy and one report of encephalitis. 68 (94%) of the 72 studies were of either low or medium quality.
If infection with SARS-CoV-2 follows a similar course to that with SARS-CoV or MERS-CoV, most patients should recover without experiencing mental illness. SARS-CoV-2 might cause delirium in a significant proportion of patients in the acute stage. Clinicians should be aware of the possibility of depression, anxiety, fatigue, post-traumatic stress disorder, and rarer neuropsychiatric syndromes in the longer term.
Wellcome Trust, UK National Institute for Health Research (NIHR), UK Medical Research Council, NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London.
One of the most pervasive themes in ecology is that biological diversity stabilizes ecosystem processes and the services they provide to society, a concept that has become a common argument for ...biodiversity conservation. Species-rich communities are thought to produce more temporally stable ecosystem services because of the complementary or independent dynamics among species that perform similar ecosystem functions. Such variance dampening within communities is referred to as a portfolio effect and is analogous to the effects of asset diversity on the stability of financial portfolios. In ecology, these arguments have focused on the effects of species diversity on ecosystem stability but have not considered the importance of biologically relevant diversity within individual species. Current rates of population extirpation are probably at least three orders of magnitude higher than species extinction rates, so there is a pressing need to clarify how population and life history diversity affect the performance of individual species in providing important ecosystem services. Here we use five decades of data from Oncorhynchus nerka (sockeye salmon) in Bristol Bay, Alaska, to provide the first quantification of portfolio effects that derive from population and life history diversity in an important and heavily exploited species. Variability in annual Bristol Bay salmon returns is 2.2 times lower than it would be if the system consisted of a single homogenous population rather than the several hundred discrete populations it currently consists of. Furthermore, if it were a single homogeneous population, such increased variability would lead to ten times more frequent fisheries closures. Portfolio effects are also evident in watershed food webs, where they stabilize and extend predator access to salmon resources. Our results demonstrate the critical importance of maintaining population diversity for stabilizing ecosystem services and securing the economies and livelihoods that depend on them. The reliability of ecosystem services will erode faster than indicated by species loss alone.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The development and deployment of several SARS-CoV-2 vaccines in a little over a year is an unprecedented achievement of modern medicine. The high levels of efficacy against transmission for some of ...these vaccines makes it feasible to use them to suppress SARS-CoV-2 altogether in regions with high vaccine acceptance. However, viral variants with reduced susceptibility to vaccinal and natural immunity threaten the utility of vaccines, particularly in scenarios where a return to pre-pandemic conditions occurs before the suppression of SARS-CoV-2 transmission. In this work we model the situation in the United States in May-June 2021, to demonstrate how pre-existing variants of SARS-CoV-2 may cause a rebound wave of COVID-19 in a matter of months under a certain set of conditions. A high burden of morbidity (and likely mortality) remains possible, even if the vaccines are partially effective against new variants and widely accepted. Our modeling suggests that variants that are already present within the population may be capable of quickly defeating the vaccines as a public health intervention, a serious potential limitation for strategies that emphasize rapid reopening before achieving control of SARS-CoV-2.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Toll-like receptors (TLRs) sense pathogen-associated molecular patterns to activate the production of inflammatory mediators. TLR4 recognizes lipopolysaccharide (LPS) and drives the secretion of ...inflammatory cytokines, often contributing to sepsis. We report that transient receptor potential melastatin-like 7 (TRPM7), a non-selective but Ca2+-conducting ion channel, mediates the cytosolic Ca2+ elevations essential for LPS-induced macrophage activation. LPS triggered TRPM7-dependent Ca2+ elevations essential for TLR4 endocytosis and the subsequent activation of the transcription factor IRF3. In a parallel pathway, the Ca2+ signaling initiated by TRPM7 was also essential for the nuclear translocation of NFκB. Consequently, TRPM7-deficient macrophages exhibited major deficits in the LPS-induced transcriptional programs in that they failed to produce IL-1β and other key pro-inflammatory cytokines. In accord with these defects, mice with myeloid-specific deletion of Trpm7 are protected from LPS-induced peritonitis. Our study highlights the importance of Ca2+ signaling in macrophage activation and identifies the ion channel TRPM7 as a central component of TLR4 signaling.
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•TRPM7 is essential for LPS-induced macrophage activation•TRPM7 mediates the Ca2+ influx necessary for TLR4 endocytosis•LPS-induced phosphorylation and translocation of NFκB p65 and IRF3 depend on TRPM7•Mice with a myeloid-specific Trpm7 deletion are resistant to LPS-induced peritonitis
Schappe et al. show that genetic deletion of Trpm7 in macrophages or pharmacological inhibition of TRPM7 channel prevents macrophage activation due to the loss of TRPM7-mediated Ca2+ influx in response to LPS. The study identifies TRPM7 as a Ca2+-entry pathway required for macrophage activation.
In the COVID-19 crisis, the science of learning has two different responsibilities: first, to offer guidance about how best to deal with the impact of the current situation, including lockdown and ...home-schooling; and second, to consider bigger questions about what this large-scale educational experiment might mean for the future. The first part of this Viewpoint summarises advice for parents on mental health, and on becoming stand-in-teachers. The second part, taking the longer view, considers the potential negative impact of the COVID-19 crisis in increasing inequality in education; but also the potential positive impact of driving innovations in technology use for educating children.
Abstract
The initiation of a rapid intensification (RI) event for a tropical cyclone (TC) at major hurricane intensity is a rare event in the North Atlantic basin. This study examined the ...environmental and vortex-scale processes related to such an RI event observed in Hurricane Irma (2017) using a combination of flight-level and airborne radar aircraft reconnaissance observations, microwave satellite observations, and model environmental analyses. The onset of RI was linked to an increase in sea surface temperatures and ocean heat content toward levels more commonly associated with North Atlantic RI episodes. Remarkably, Irma’s RI event comprised two rapidly evolving eyewall replacement cycle (ERC) episodes that each completed in less than 12 h. The two ERC events displayed different secondary eyewall formation (SEF) mechanisms and vortex evolutions. During the first SEF event, a secondary maximum in ascent and tangential wind was observed at the leading edge of a mesoscale descending inflow jet. During the ensuing ERC event, the primary eyewall weakened and ultimately collapsed, resulting in a brief period of weakening. The second SEF event displayed characteristics consistent with unbalanced boundary layer dynamics. Additionally, it is plausible that both SEF events were affected by the stagnation and axisymmeterization of outward-propagating vortex Rossby waves. During the second ERC event, the TC continued to rapidly intensify, which is a stark contrast to the ERC paradigm described in the literature. The differing ERC evolutions appear linked to the vortex response to changing environmental conditions. The results presented here underscore the utility of frequent aircraft reconnaissance observations for an improved understanding of TC dynamics.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Anthracycline-induced cardiotoxicity (ACT) is a serious adverse drug reaction limiting anthracycline use and causing substantial morbidity and mortality. Our aim was to identify genetic variants ...associated with ACT in patients treated for childhood cancer.
We carried out a study of 2,977 single-nucleotide polymorphisms (SNPs) in 220 key drug biotransformation genes in a discovery cohort of 156 anthracycline-treated children from British Columbia, with replication in a second cohort of 188 children from across Canada and further replication of the top SNP in a third cohort of 96 patients from Amsterdam, the Netherlands.
We identified a highly significant association of a synonymous coding variant rs7853758 (L461L) within the SLC28A3 gene with ACT (odds ratio, 0.35; P = 1.8 × 10(-5) for all cohorts combined). Additional associations (P < .01) with risk and protective variants in other genes including SLC28A1 and several adenosine triphosphate-binding cassette transporters (ABCB1, ABCB4, and ABCC1) were present. We further explored combining multiple variants into a single-prediction model together with clinical risk factors and classification of patients into three risk groups. In the high-risk group, 75% of patients were accurately predicted to develop ACT, with 36% developing this within the first year alone, whereas in the low-risk group, 96% of patients were accurately predicted not to develop ACT.
We have identified multiple genetic variants in SLC28A3 and other genes associated with ACT. Combined with clinical risk factors, genetic risk profiling might be used to identify high-risk patients who can then be provided with safer treatment options.
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