Administration of opioids significantly effects tidal volume, respiratory rate, and blunts CO2 responsiveness. The precise neural mechanisms that determine the respiratory depressant effects of ...opioids are controversial. One hypothesis is that mu‐opioid agonists hyperpolarize neurons located in the pons and this action prolongs inspiratory cycle duration. We tested the plausibility of this hypothesis by employing a neuromechanical model of the respiratory control system. We targeted medullary inspiratory neuron axon terminals that influence 4 neuronal populations within the pons that had an inspiratory component to their discharge (inspiratory (I), expiratory/inspiratory (EI), rostral inspiratory/expiratory (rIE), and caudal inspiratory/expiratory (cIE)) neurons). We systematically decreased the conductance of these synapses by 25, 50, 75 and 100 percent and monitored the effect on the respiratory motor pattern. Simulations revealed that decreasing the conductance of synapses from medullary inspiratory neurons to neuronal populations in the pons altered the breathing pattern. In general, a reduction in synaptic conductance from medullary inspiratory neurons to each of the 4 pontine neuron populations decreased their excitability. Decreasing the synaptic conductance from the medullary inspiratory decrementing (I‐Dec) population to the: 1) I pons population resulted in a decrease in phrenic burst frequency and a decrease in the Inspiratory‐Driver (I‐Driver) population excitability, 2) EI pons population resulted in a decrease in I pons excitability and phrenic neurogram magnitude, 3) rIE population did not reveal significant changes in the breathing pattern from control, and 4) cIE population resulted a decrease in I‐Driver population excitability, phrenic neurogram amplitude and phrenic burst frequency. Decreasing conductance of synapses from the inspiratory augmenting (I‐Aug) population to the I pons, cIE, or rIE populations resulted in decreases in phrenic neurogram magnitude. Our simulation data support the plausibility of presynaptic effects of opioids within the pontine respiratory group that induce respiratory depression. Further, these presynaptic effects can induce selective alterations in inspiratory drive and/or breathing cycle timing.
Administration of opioids can lead to respiratory depression and eventually death. Opioids can alter the frequency and magnitude of inspiratory motor drive by binding to mu‐opioid receptors on ...inspiratory neurons located in several areas of the brainstem. Lalley (Am J Physiol: Regul. 285:R1287‐1304, 2003) suggested that some of the effects of fentanyl on bulbospinal inspiratory neuron activity were presynaptic. We tested the feasibility of pre‐ vs post‐synaptic effects of opioids with an integrate‐and‐fire computational neural biomechanical model of the brainstem respiratory network. Our previous simulations utilizing this model involved separately reducing conductance at groups of synapses that excited inspiratory‐augmenting (I‐Aug) or inspiratory‐decrementing (I‐Dec) neuron populations to simulate opioid‐mediated decreases in the presynaptic excitability of excitatory axons to these neurons from inspiratory driver neurons (I‐driver). We found that the presynaptic hypothesis was best supported by a mechanism involving depression of the excitatory synapse between I‐driver and I‐decrementing neurons. The current modeling investigation extends that work by focusing on three inspiratory neuron populations: I‐Aug, I‐Dec, and late inspiratory (late‐I). We separately decreased the conductance of each excitatory synapse to examine how these changes would affect the respiratory pattern. Simulations revealed that systematically decreasing the conductance of synapses from the I‐Aug neuron population to late‐I and I‐ Aug bulbospinal populations by 50% resulted in a decrease in frequency, duration, and amplitude of inspiratory drive. Decreasing the conductance of excitatory synapses from I‐Dec neurons to I‐Aug, and late‐I populations had a limited effect on inspiratory activity. Similar results were observed when the conductance of excitatory synapses was reduced from the late‐I population to its I‐Dec and I‐Aug targets. Overall, these results indicate that a plausible mechanism for respiratory suppression by opioids could include depression of excitatory synaptic actions between selected medullary inspiratory neuron populations.
An iron(II)-based metal–organic framework featuring coordinatively unsaturated redox-active metal cation sites, Fe2(dobdc) (dobdc4– = 2,5-dioxido-1,4-benzenedicarboxylate), is shown to strongly bind ...nitric oxide at 298 K. Adsorption isotherms indicate an adsorption capacity greater than 16 wt %, corresponding to the adsorption of one NO molecule per iron center. Infrared, UV–vis, and Mössbauer spectroscopies, together with magnetic susceptibility data, confirm the strong binding is a result of electron transfer from the FeII sites to form FeIII–NO– adducts. Consistent with these results, powder neutron diffraction experiments indicate that NO is bound to the iron centers of the framework with an Fe–NO separation of 1.77(1) Å and an Fe–N–O angle of 150.9(5)°. The nitric oxide-containing material, Fe2(NO)2(dobdc), steadily releases bound NO under humid conditions over the course of more than 10 days, suggesting it, and potential future iron(II)-based metal–organic frameworks, are good candidates for certain biomedical applications.
A widespread form of bias has slipped under our cultural and academic radar. People who are single are targets of singlism: negative stereotypes and discrimination. Compared to married or coupled ...people, who are often described in very positive terms, singles are assumed to be immature, maladjusted, and self-centered. Although the perceived differences between people who have and have not married are large, the actual differences are not. Moreover, there is currently scant recognition that singlism exists, and when singlism is acknowledged, it is often accepted as legitimate.
The ThyroSeq v2 next-generation sequencing assay estimates the probability of malignancy in indeterminate thyroid nodules. Its diagnostic accuracy in different practice settings and patient ...populations is not well understood.
We analyzed 273 Bethesda III/IV indeterminate thyroid nodules evaluated with ThyroSeq at 4 institutions: 2 comprehensive cancer centers (n = 98 and 102), a multicenter health care system (n = 60), and an academic medical center (n = 13). The positive and negative predictive values of ThyroSeq and distribution of final pathologic diagnoses were analyzed and compared with values predicted by Bayes theorem.
Across 4 institutions, the positive predictive value was 35% (22%–43%) and negative predictive value was 93% (88%–100%). Predictive values correlated closely with Bayes theorem estimates (r2 = 0.84), although positive predictive values were lower than expected. RAS mutations were the most common molecular alteration. Among 84 RAS-mutated nodules, malignancy risk was variable (25%, range 10%–37%) and distribution of benign diagnoses differed across institutions (adenoma/hyperplasia 12%–85%, noninvasive follicular thyroid neoplasm with papillary-like nuclear features 5%–46%).
In a multi-institutional analysis, ThyroSeq positive predictive values were variable and lower than expected. This is attributable to differences in the prevalence of malignancy and variability in pathologist interpretations of noninvasive tumors. It is important that clinicians understand ThyroSeq performance in their practice setting when evaluating these results.
Investigating Variation in Replicability Klein, Richard A.; Ratliff, Kate A.; Vianello, Michelangelo ...
Social psychology (Göttingen, Germany),
01/2014, Letnik:
45, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Although replication is a central tenet of science, direct replications are rare
in psychology. This research tested variation in the replicability of 13 classic and
contemporary effects across 36 ...independent samples totaling 6,344 participants. In the
aggregate, 10 effects replicated consistently. One effect - imagined contact reducing
prejudice - showed weak support for replicability. And two effects - flag priming
influencing conservatism and currency priming influencing system justification - did not
replicate. We compared whether the conditions such as lab versus online or US versus
international sample predicted effect magnitudes. By and large they did not. The results of
this small sample of effects suggest that replicability is more dependent on the effect itself
than on the sample and setting used to investigate the effect.
Metal–organic frameworks (MOFs) are a rapidly growing class of materials that offer great promise in various applications. However, the synthesis remains challenging: for example, a range of crystal ...structures can often be accessed from the same building blocks, which complicates the phase selectivity. Likewise, the high sensitivity to slight changes in synthesis conditions may cause reproducibility issues. This is crucial, as it hampers the research and commercialization of affected MOFs. Here, it presents the first‐ever interlaboratory study of the synthetic reproducibility of two Zr–porphyrin MOFs, PCN‐222 and PCN‐224, to investigate the scope of this problem. For PCN‐222, only one sample out of ten was phase pure and of the correct symmetry, while for PCN‐224, three are phase pure, although none of these show the spatial linker order characteristic of PCN‐224. Instead, these samples resemble dPCN‐224 (disordered PCN‐224), which has recently been reported. The variability in thermal behavior, defect content, and surface area of the synthesised samples are also studied. The results have important ramifications for field of metal–organic frameworks and their crystallization, by highlighting the synthetic challenges associated with a multi‐variable synthesis space and flat energy landscapes characteristic of MOFs.
It performed an interlaboratory study of the synthesis of the metal‐organic frameworks (MOFs) PCN‐222 and PCN‐224. Ten participants independently synthesized the two MOFs and the products are analyzed, primarily by X‐ray diffraction. The success rates are low (one‐three samples corresponding to a pure sample of the correct phase), thus highlighting the problems with irreproducibility in MOF synthesis.
Abstract Objective One publication reported that lower body satisfaction and lower education were independent predictors of depression in polycystic ovary syndrome (PCOS) in women. This study ...replicates that analysis using different instruments, and adds androgen levels to the model. Methods Cross-sectional analysis of questionnaires (Quick Inventory of Depressive Symptomatology-Self-Report, Body Esteem Scale) and serum androgens from a community cohort with (n=94) and without (n=96) PCOS, matched by BMI category. Non-parametric tests, Spearman correlations, and negative binomial regression models were analyzed. Results Depression symptoms were common (40–60% in lean, overweight and obese BMI categories) in the PCOS cohort, albeit generally of mild severity. The PCOS women had similar depression symptom severity (P > .20) and similar body dissatisfaction (P ≥ .25) as the regularly cycling women in total and stratified by BMI category. In both the PCOS and non-PCOS cohorts, depression symptom severity was positively correlated with dissatisfaction with physical appearance and physical conditioning (P < .02). Body dissatisfaction (especially perception of physical conditioning) was strongly associated with more severe depression symptoms in non-obese PCOS women (BMI < 30, P < .04) before and after controlling for age, testosterone and free testosterone. In contrast, for obese women with PCOS, depression was unrelated to body dissatisfaction after controlling for age. Conclusions Among non-obese PCOS women, their subjective body image was strongly associated with the severity of their depression symptoms. Most of the obese PCOS cohort had low body satisfaction and depression symptoms, therefore individual differences in the body dissatisfaction scores were not helpful in identifying depression symptom severity. Neither testosterone nor free testosterone was associated with depression symptom severity in PCOS women after controlling for body dissatisfaction and age.
Objective. To describe parent/caregiver reasons for attrition from tertiary care weight management clinics/programs. Study design. A telephone survey was administered to 147 parents from weight ...management clinics/programs in the National Association of Children’s Hospitals and Related Institutions’ (now Children’s Hospital Association’s) FOCUS on a Fitter Future II collaborative. Results. Scheduling, barriers to recommendation implementation, and transportation issues were endorsed by more than half of parents as having a moderate to high influence on their decision not to return. Family motivation and mismatched expectations between families and clinic/program staff were mentioned as influential by more than one-third. Only mismatched expectations correlated with patient demographics and referral patterns. Conclusions. Although limited by small sample size, the study found that parents who left geographically diverse weight management clinics/programs reported similar reasons for attrition. Future efforts should include offering alternative visit times, more treatment options, and financial and transportation assistance and exploring family expectations.
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