Regressions and meta-regressions are widely used to estimate patterns and effect sizes in various disciplines. However, many biological and medical analyses use relatively low sample size (N), ...contributing to concerns on reproducibility. What is the minimum N to identify the most plausible data pattern using regressions? Statistical power analysis is often used to answer that question, but it has its own problems and logically should follow model selection to first identify the most plausible model. Here we make null, simple linear and quadratic data with different variances and effect sizes. We then sample and use information theoretic model selection to evaluate minimum N for regression models. We also evaluate the use of coefficient of determination (R2) for this purpose; it is widely used but not recommended. With very low variance, both false positives and false negatives occurred at N < 8, but data shape was always clearly identified at N ≥ 8. With high variance, accurate inference was stable at N ≥ 25. Those outcomes were consistent at different effect sizes. Akaike Information Criterion weights (AICc wi) were essential to clearly identify patterns (e.g., simple linear vs. null); R2 or adjusted R2 values were not useful. We conclude that a minimum N = 8 is informative given very little variance, but minimum N ≥ 25 is required for more variance. Alternative models are better compared using information theory indices such as AIC but not R2 or adjusted R2. Insufficient N and R2-based model selection apparently contribute to confusion and low reproducibility in various disciplines. To avoid those problems, we recommend that research based on regressions or meta-regressions use N ≥ 25.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The importance of the amygdala as a salience detector and in emotional learning is now well accepted. The mechanisms that regulate and inhibit the amygdala, however, are less well understood. This ...review provides evidence from imaging and lesion studies to support the role of the ventromedial prefrontal cortex (vmPFC) as a moderator and inhibitor of the amygdala. The
dual inhibition
model centres on the broadly defined ventromedial prefrontal cortex (vmPFC) and the distinct role of two of its subcomponents, the rostral anterior cingulate cortex and orbitofrontal cortex. The
dual inhibition model
posits that these two regions, along with their associated inhibitory pathways, must interact for adequate inhibitory control of the amygdala and emotional regulation. Following a description of the model’s experimental support, it is then proposed as a neuropsychological mechanism for post-traumatic stress disorder (PTSD).
Flashbacks,
as a defining feature of PTSD, are described in terms of a subcortical orienting network. Finally, there is a discussion of how a neuropsychological understanding of post-traumatic stress disorder (PTSD) might inform a clinician’s approach to treatment and how the dual inhibition model might have a more general application to understanding emotional dysregulation.
Fructose intake has increased substantially throughout the developed world and is associated with obesity, type 2 diabetes and non-alcoholic fatty liver disease. Currently, our understanding of the ...metabolic and mechanistic implications for immune cells, such as monocytes and macrophages, exposed to elevated levels of dietary fructose is limited. Here, we show that fructose reprograms cellular metabolic pathways to favour glutaminolysis and oxidative metabolism, which are required to support increased inflammatory cytokine production in both LPS-treated human monocytes and mouse macrophages. A fructose-dependent increase in mTORC1 activity drives translation of pro-inflammatory cytokines in response to LPS. LPS-stimulated monocytes treated with fructose rely heavily on oxidative metabolism and have reduced flexibility in response to both glycolytic and mitochondrial inhibition, suggesting glycolysis and oxidative metabolism are inextricably coupled in these cells. The physiological implications of fructose exposure are demonstrated in a model of LPS-induced systemic inflammation, with mice exposed to fructose having increased levels of circulating IL-1β after LPS challenge. Taken together, our work underpins a pro-inflammatory role for dietary fructose in LPS-stimulated mononuclear phagocytes which occurs at the expense of metabolic flexibility.
To update the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast ...cancer to improve the accuracy of HER2 testing and its utility as a predictive marker in invasive breast cancer.
ASCO/CAP convened an Update Committee that included coauthors of the 2007 guideline to conduct a systematic literature review and update recommendations for optimal HER2 testing.
The Update Committee identified criteria and areas requiring clarification to improve the accuracy of HER2 testing by immunohistochemistry (IHC) or in situ hybridization (ISH). The guideline was reviewed and approved by both organizations.
The Update Committee recommends that HER2 status (HER2 negative or positive) be determined in all patients with invasive (early stage or recurrence) breast cancer on the basis of one or more HER2 test results (negative, equivocal, or positive). Testing criteria define HER2-positive status when (on observing within an area of tumor that amounts to > 10% of contiguous and homogeneous tumor cells) there is evidence of protein overexpression (IHC) or gene amplification (HER2 copy number or HER2/CEP17 ratio by ISH based on counting at least 20 cells within the area). If results are equivocal (revised criteria), reflex testing should be performed using an alternative assay (IHC or ISH). Repeat testing should be considered if results seem discordant with other histopathologic findings. Laboratories should demonstrate high concordance with a validated HER2 test on a sufficiently large and representative set of specimens. Testing must be performed in a laboratory accredited by CAP or another accrediting entity. The Update Committee urges providers and health systems to cooperate to ensure the highest quality testing. This guideline was developed through a collaboration between the American Society of Clinical Oncology and the College of American Pathologists and has been published jointly by invitation and consent in both Journal of Clinical Oncology and the Archives of Pathology & Laboratory Medicine.
Comprehensive assessments of species' extinction risks have documented the extinction crisis
and underpinned strategies for reducing those risks
. Global assessments reveal that, among tetrapods, ...40.7% of amphibians, 25.4% of mammals and 13.6% of birds are threatened with extinction
. Because global assessments have been lacking, reptiles have been omitted from conservation-prioritization analyses that encompass other tetrapods
. Reptiles are unusually diverse in arid regions, suggesting that they may have different conservation needs
. Here we provide a comprehensive extinction-risk assessment of reptiles and show that at least 1,829 out of 10,196 species (21.1%) are threatened-confirming a previous extrapolation
and representing 15.6 billion years of phylogenetic diversity. Reptiles are threatened by the same major factors that threaten other tetrapods-agriculture, logging, urban development and invasive species-although the threat posed by climate change remains uncertain. Reptiles inhabiting forests, where these threats are strongest, are more threatened than those in arid habitats, contrary to our prediction. Birds, mammals and amphibians are unexpectedly good surrogates for the conservation of reptiles, although threatened reptiles with the smallest ranges tend to be isolated from other threatened tetrapods. Although some reptiles-including most species of crocodiles and turtles-require urgent, targeted action to prevent extinctions, efforts to protect other tetrapods, such as habitat preservation and control of trade and invasive species, will probably also benefit many reptiles.
Abstract Objectives To investigate the physical demands of professional rugby league match-play using microtechnology, and to compare these demands with typical training activities used to prepare ...players for competition. Design Prospective cohort study. Methods Thirty elite rugby league players participated in this study. Seven hundred and eighty-six. training data sets and 104 data sets from National Rugby League matches were collected over one playing season. Movement was recorded using a commercially available microtechnology unit (minimaxX, Catapult Innovations), which provided information on speeds, distances, accelerations, physical collisions and repeated high-intensity efforts. Results Mean distances covered during match-play by the hit-up forwards, wide-running forwards, adjustables, and outside backs were 3,569 m, 5,561 m, 6,411 m, and 6,819 m, respectively. Hit-up forwards and wide-running forwards were engaged in a greater number of moderate and heavy collisions than the adjustables and outside backs, and more repeated high-intensity effort bouts per minute of play (1 bout every 4.8–6.3 min). The physical demands of traditional conditioning, repeated high-intensity effort exercise, and skill training activities were all lower than the physical demands of competition. Conclusions These results demonstrate that absolute distances covered during professional rugby league matches are greater for outside backs, while the collision and repeated high-intensity effort demands are higher for hit-up forwards and wide-running forwards. The specific physical demands of competitive play, especially those demands associated with collisions and repeated high-intensity efforts, were not well matched by those observed in traditional conditioning, repeated high-intensity effort exercise, and skills training activities. Further research is required to investigate whether modifications need to be made to these training activities to better prepare players for the demands of National Rugby League competition.
Abstract
High intensity interval training (HIIT) has been shown to consistently elicit rapid and significant adaptations in a number of physiological systems, across many different healthy and ...clinical populations. In addition, there is increasing interest in how some acute, yet transient responses to high intensity exercise potentially reduce the risks of particular diseases. Recent work has shown that discrete, brief bouts of high intensity exercise (termed ‘exercise snacks’) can improve glucose control and vascular health and thus counter the negative cardiometabolic consequences of prolonged, uninterrupted periods of inactivity. In this brief review, we advance the case, using evidence available from pre‐clinical studies in the exercise oncology literature, that brief, frequently completed bouts of high intensity exercise embedded within an individual's overall daily and weekly physical activity schedule, may transiently impact the tumour microenvironment and improve the health outcomes for those who have been diagnosed and treated for cancer.
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Pulmonary endarterectomy (PEA) is the gold standard treatment for operable chronic thromboembolic pulmonary hypertension (CTEPH). However, a proportion of patients with operable disease decline ...surgery. There are currently no published data on this patient group. The aim of this study was to identify outcomes and prognostic factors in a large cohort of consecutive patients with CTEPH.Data were collected for consecutive, treatment-naive CTEPH patients at the Pulmonary Vascular Disease Unit of the Royal Hallamshire Hospital (Sheffield, UK) between 2001 and 2014.Of 550 CTEPH patients (mean±sd age 63±15 years, follow-up 4±3 years), 49% underwent surgery, 32% had technically operable disease and did not undergo surgery (including patient choice n=72 and unfit for surgery n=63), and 19% had inoperable disease due to disease distribution. The 5-year survival was superior in patients undergoing PEA (83%)
technically operable disease who did not undergo surgery (53%) and inoperable due to disease distribution (59%) (p<0.001). Survival was superior in patients following PEA compared with those offered but declining surgery (55%) (p<0.001). In patients offered PEA, independent prognostic factors included mixed venous oxygen saturation, gas transfer and patient decision to proceed to surgery.Outcomes in CTEPH following PEA are excellent and superior to patients declining surgery, and strongly favour consideration of a surgical intervention in eligible patients.
As land is converted to agriculture (e.g., pastures), natural vegetation is repeatedly disturbed, creating various levels of habitat alteration in which flowering plants and pollinators (e.g., bees) ...interact. Community structure of flowering plants, bees, and flower-bee interactions may each respond to disturbance, but potentially in different ways or magnitudes. We studied flowering plants, bees, and their interactions across four mechanical disturbance levels in and near Archbold Biological Station, Florida (USA) for one year, using repeated sampling with standard techniques in replicated plots. Data were analyzed for community structure, flower-bee interactions and bipartite network structure. Over 7500 flowering plants (81 species) and almost 5000 bees (48 species) were sampled, representing >80% of estimated species richness. Disturbance altered available flower diversity and both shifted and simplified compositions of floral and bee communities. Importantly, the number of foraging bee species did not decrease with disturbance but fewer bee species interacted with flowers given greater disturbance, indicating that disturbance reduced successful foraging. Interaction networks became simpler with disturbance, and the non-native European honey bee (Apis mellifera) became more dominant as disturbance intensity increased. Flower-bee interactions were most sensitive to disturbance. For some native bees, anthropogenic disturbance may contribute to ecological trap conditions and drive long-term diversity patterns. Attention to interaction networks will help land managers identify plant species to conserve and restore flowering plants that are vital to native pollinator communities.
•Anthropogenic disturbance homogenizes plant and bee communities.•Multiple native bees forage unsuccessfully in disturbed areas.•Disturbed interaction networks are simpler and dominated by European honey bees.•Determining ideal interaction network structure is vital for conservation/restoration.•Planting native bee-preferred flowering plants may conserve network function.
To update the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast ...cancer to improve the accuracy of HER2 testing and its utility as a predictive marker in invasive breast cancer.
ASCO/CAP convened an Update Committee that included coauthors of the 2007 guideline to conduct a systematic literature review and update recommendations for optimal HER2 testing.
The Update Committee identified criteria and areas requiring clarification to improve the accuracy of HER2 testing by immunohistochemistry (IHC) or in situ hybridization (ISH). The guideline was reviewed and approved by both organizations.
The Update Committee recommends that HER2 status (HER2 negative or positive) be determined in all patients with invasive (early stage or recurrence) breast cancer on the basis of one or more HER2 test results (negative, equivocal, or positive). Testing criteria define HER2-positive status when (on observing within an area of tumor that amounts to >10% of contiguous and homogeneous tumor cells) there is evidence of protein overexpression (IHC) or gene amplification (HER2 copy number or HER2/CEP17 ratio by ISH based on counting at least 20 cells within the area). If results are equivocal (revised criteria), reflex testing should be performed using an alternative assay (IHC or ISH). Repeat testing should be considered if results seem discordant with other histopathologic findings. Laboratories should demonstrate high concordance with a validated HER2 test on a sufficiently large and representative set of specimens. Testing must be performed in a laboratory accredited by CAP or another accrediting entity. The Update Committee urges providers and health systems to cooperate to ensure the highest quality testing.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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