When designing a study, the planned sample size is often based on power analyses. One way to choose an effect size for power analyses is by relying on pilot data. A-priori power analyses are only ...accurate when the effect size estimate is accurate. In this paper we highlight two sources of bias when performing a-priori power analyses for between-subject designs based on pilot data. First, we examine how the choice of the effect size index (η2, ω2 and ε2) affects the sample size and power of the main study. Based on our observations, we recommend against the use of η2 in a-priori power analyses. Second, we examine how the maximum sample size researchers are willing to collect in a main study (e.g. due to time or financial constraints) leads to overestimated effect size estimates in the studies that are performed. Determining the required sample size exclusively based on the effect size estimates from pilot data, and following up on pilot studies only when the sample size estimate for the main study is considered feasible, creates what we term follow-up bias. We explain how follow-up bias leads to underpowered main studies.
Our simulations show that designing main studies based on effect sizes estimated from small pilot studies does not yield desired levels of power due to accuracy bias and follow-up bias, even when publication bias is not an issue. We urge researchers to consider alternative approaches to determining the sample size of their studies, and discuss several options.
Ziconotide (Prialt(®)) is a synthetic conopeptide analgesic that acts by selectively antagonizing N-type voltage-gated calcium channels. Intrathecal ziconotide is the only non-opioid intrathecal ...analgesic that is FDA-approved for use in patients with treatment-refractory, chronic pain. The efficacy of intrathecal ziconotide was demonstrated in randomized, double-blind, placebo-controlled trials in patients with treatment-refractory noncancer-related pain or cancer- or AIDS-related pain. Across trials, ziconotide recipients had significantly greater reductions in pain intensity during ziconotide treatment than those receiving placebo (primary endpoint). At the end of the titration period, approximately one-sixth to one-third of patients with noncancer chronic pain and one-half with cancer- or AIDS-related pain who received ziconotide reached a pain response threshold (≥30 % reduction in the pain intensity score). In ziconotide responders, analgesic effects were enduring, with some patients continuing treatment over extended periods. Across trials, the chief tolerability concerns in ziconotide recipients during the titration phase and during extended treatment were related to CNS adverse events. These were mostly of mild to moderate intensity, although serious adverse events were commonly attributed to ziconotide treatment, especially in trials with rapid ziconotide titration and that permitted higher dosages. In general, clinically important non-CNS adverse events were infrequent, and during the ziconotide titration phase, relatively few patients discontinued treatment because of adverse events. Ongoing research will assess various strategies for selecting patients for ziconotide treatment and for enhancing its efficacy and tolerability. At the present time, intrathecal ziconotide provides a treatment option for patients with severe, unremitting pain who have failed to respond to other intensive analgesic regimens.
The potential cardiovascular (CV) disease (CVD) benefits of Omega-3 Polyunsaturated Fatty Acids (OM3) have been intensely studied and debated for decades. Initial trials were performed in patients ...with low use of maximal medical therapy for CVD, and reported significant mortality benefits with the use of 1 g/day OM3 intervention following myocardial infarction (MI). More recent studies, including cohorts of patients receiving modern guideline directed medical therapy for CVD, have often not shown similar benefits with OM3 use. We conducted a literature review using PubMed, professional society guidelines, specific journal databases including New England Journal of Medicine and Journal of the American College of Cardiology from January 1, 2007 to December 31, 2017. References from selected articles were also reviewed, as well as key articles outside of the selected time-frame for their important findings or historical perspectives.
Currently, there are no Class I recommendations from the American Heart Association (AHA) for the use of OM3, however, considering the safety of this therapy and beneficial findings of some modern studies (including patients with current maximal medical therapy for CVD), the AHA has recently expanded their list of Class II recommendations, in which treatment with OM3 for CVD benefit is reasonable. This review discusses the current state of the evidence, summarizes current professional recommendations, and provides recommendations for future research.
En este trabajo se presenta una guía conceptual y práctica para estimar la fiabilidad de consistencia interna de medidas obtenidas mediante suma o promedio de ítems con base en las aportaciones más ...recientes de la psicometría. El coeficiente de fiabilidad de consistencia interna se presenta como un subproducto del modelo de medida subyacente en las respuestas a los ítems y se propone su estimación mediante un procedimiento de análisis de los ítems en tres fases, a saber, análisis descriptivo, comprobación de los modelos de medida pertinentes y cálculo del coeficiente de consistencia interna y su intervalo de confianza. Se proporcionan las siguientes fórmulas: (a) los coeficientes alfa de Cronbach y omega para medidas unidimensionales con ítems cuantitativos (b) los coeficientes omega ordinal, alfa ordinal y de fiabilidad no lineal para ítems dicotómicos y ordinales, y (c) los coeficientes omega y omega jerárquico para medidas esencialmente unidimensionales con efectos de método. El procedimiento se generaliza al análisis de medidas obtenidas por suma ponderada, de escalas multidimensionales, de diseños complejos con datos multinivel y/o faltantes y también al desarrollo de escalas. Con fines ilustrativos se expone el análisis de cuatro ejemplos numéricos y se proporcionan los datos y la sintaxis en R.
We report on the first experimental measurements made at a magnetic confinement fusion device of the T + T → α + 2n reaction indicating the presence of the intermediate two-body resonant reaction T + ...T → ⁵He + n. During the second deuterium-tritium campaign (DTE2) at the Joint European Torus, measurements of fusion plasmas with high tritium concentrations, n_T/(n_T + n_D) ≈ 0.99, heated with T neutral beam injection (NBI), were performed using the neutron time-of-flight (TOF) spectrometer TOFOR. We detect a peak in the neutron emission TOF spectrum consistent with the two-body resonant reaction. The TT neutron emission energy spectrum is modeled using an R-matrix framework where the distributions of the most likely model parameters given our experimental TOF data are determined utilizing a Markov chain Monte Carlo approach. We compare our best estimate of the TT neutron emission energy spectrum with results obtained at inertial confinement fusion experiments at the OMEGA facility and find a spectral shape that is consistent with the energy dependency in the neutron spectrum observed at OMEGA.
PICO Question
In symptomatic cats with feline immunodeficiency virus (FIV), does high-dose subcutaneous recombinant feline interferon-omega (rFeIFN-ω) administration lead to reduced clinical signs ...compared to cats who were not administered rFeIFN-ω?
Clinical bottom line
Category of research
Treatment.
Number and type of study designs reviewed
Three studies were critically reviewed, including one randomised controlled trial, one non-randomised controlled trial, and one uncontrolled clinical trial.
Strength of evidence
Weak.
Outcomes reported
Each of the studies reported that rFeIFN-ω administration significantly reduced clinical signs in FIV infected cats. However, all three papers have limitations in their study design and statistical analysis which lower the strength of the evidence they provide.
Conclusion
There is only weak evidence demonstrating that rFeIFN-ω administration leads to reduced clinical signs in FIV positive cats. Currently, there is a lack of well-designed, double-blinded, randomised, placebo-controlled clinical trials which have an adequate sample size and specifically focus on FIV positive cats. As a result, more robust evidence is needed to prove the definitive therapeutic benefit of rFeIFN-ω in symptomatic FIV patients. Treatment with rFeIFN-ω may still be considered by clinicians for cats with clinical signs potentially associated with retroviral infection, such as oral lesions and stomatitis, particularly if they are not responding well to supportive therapy alone.
How to apply this evidence in practice
The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources.
Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.
Resolution of acute inflammation is governed, in part, by lipid mediator class switching from proin flammatory eicosanoids to specialized proresolving mediators, including a recently identified new ...pathway of mediators, termed maresin conjugates in tissue regeneration (MCTR), which includes MCTR1, MCTR2, and MCTR3. Here, we addressed whether each MCTR can impact the known vascular actions of cysteinyl leukotrienes. Leukotriene D4 (LTD4; 1.5 nmol/mouse) initiated vascular leakage in mouse cremaster vessels, which was reduced (>75%) by MCTR1 and MCTR2 (0.15 nmol each). With isolated Ciona intestinalis (sea squirt) primordial hearts, LTD4 (1–100 nM) induced negative inotropic action and lowered heartbeats 20–30%. Each MCTR (1–100 nM) prevented LTD4‐reduced heart rates. With human cysteinyl leukotriene receptor‐1 (CysLT1) expressed in CHO cells, each MCTR (10–100 nM) significantly reduced LTD4‐initiated signaling. To assess the contribution of CysLT1 in the proresolving actions of MCTR, we carried out human macrophage (MΦ) phagocytosis. Each MCTR (0.1–10 nM) stimulated human MΦ phagocytosis of live Escherichia coli, whereas LTD4 did not stimulate phagocytosis. MCTR‐activated phagocytosis was significantly blocked by a pharmacologic receptor antagonist (MK571). With both CHO‐CysLT1 and human MΦs, each MCTR competed for specific 3H‐LTD4 binding with apparent lower affinity than LTD4. Thus, each MCTR functionally interacts with human CysLT1 to pharmacologically counter‐regulate vascular responses and stimulate physiologic phagocytosis with MΦs.—Chiang, N., Riley, I. R., Dalli, J., Rodriguez, A. R., Spur, B. W., Serhan, C. N. New maresin conjugates in tissue regeneration pathway counters leukotriene D4‐ stimulated vascular responses. FASEB J. 32, 4043–4052 (2018). www.fasebj.org
Many consumer research and social science journals are increasingly urging behavioral researchers to submit effect sizes among their reported results. Yet most researchers are less familiar with ...effect sizes than with significance tests, even in choosing among them. This article clarifies the concepts, formulae, and appropriate usage of the “variance explained” effect size indices, eta‐squared, omega‐squared, and epsilon‐squared (η2,ω2,ε2), and their partial effect size variants (ηp2,ωp2,εp2). Equations are presented, explained, and illustrated. Software is provided to facilitate the calculation of the indices in SAS, SPSS, and R, and suggestions and updated guidance are offered to scholars regarding reporting practices. The primary contribution of this article is to clarify the role of variance explained effect sizes in behavioral research so that scholars can be confident in precisely understanding the content of these measures in their analysis and reporting.
Titanium alloy Ti-1Al-8V-5Fe (Ti-185) has essentially remained an experimental alloy since its invention because of the formation of iron-stabilized beta-flecks in conventional manufacturing. Laser ...directed energy deposition (L-DED) has the potential to avoid this issue while realizing in-situ ageing. This work investigates the L-DED fabrication of Ti-185 alloy. We show that the precipitate phases along the build height of the Ti-185 plate sample have a decisive influence on its tensile properties. Due to the formation of the embrittling isothermal omega-phase (ωiso), the top region of the Ti-185 plate sample exhibited zero plasticity, while the middle region, which is free of the omega-phase (ω), demonstrated significant tensile ductility (20 ± 2 %) and strength (1042 ± 13 MPa). The formation of each phase is elucidated using simulated temperature evolution profiles in the plate sample. Furthermore, we show that converting the isothermal omega-phase into the athermal omega-phase (ωath) through beta-annealing and water quenching restores tensile ductility.
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One of the most controversial areas of nutrition research relates to fats, particularly essential fatty acids, in the context of cardiovascular disease risk. A critical feature of dietary fatty acids ...is that they incorporate into the plasma membrane, modifying fluidity and key physiological functions. Importantly, they can reshape the bioavailability of eicosanoids and other lipid mediators, which direct cellular responses to external stimuli, such as inflammation and chronic stress conditions. This paper provides an overview of the most recent evidence, as well as historical controversies, linking fat consumption with human health and disease. We underscore current pitfalls in the area of fatty acid research and critically frame fatty acid intake in the larger context of diet and behavior. We conclude that fundamental research on fatty acids and lipids is appropriate in certain areas, but the rigor and reproducibility are lacking in others. The pros and cons are highlighted throughout the review, seeking to guide future research on the important area of nutrition, fat intake, and cardiovascular disease risk.
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