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Experimental paradigms used in affective and clinical science often use stimuli such as images, scenarios, videos, or words to elicit emotional responses in study participants. Choosing appropriate stimuli that are highly evocative is essential to the study of emotional processes in both healthy and clinical populations. Selecting one set of stimuli that will be relevant for all subjects can be challenging because not every person responds the same way to a given stimulus. Machine learning can facilitate the personalization of such stimuli. The current study applied a novel statistical approach called a recommender algorithm to the selection of highly threatening words for a trauma-exposed population (N?=?837). Participants rated 513 threatening words, and we trained a user–user collaborative filtering recommender algorithm. The algorithm uses similarities between individuals to predict ratings for unrated words. We compared threat ratings for algorithm-based word selection to a random word set, a word set previously used in research, and trauma-specific word sets. Algorithm-selected personalized words were more threatening compared to non-personalized words with large effects (ds?=?2.10–2.92). Recommender algorithms can automate the personalization of stimuli from a large pool of possible stimuli to maximize emotional reactivity in research paradigms. These methods also hold potential for the personalization of behavioral treatments administered remotely where a provider is not available to tailor an intervention to the individual. The word personalization algorithm is available for use online (https://threat-word-predictor.herokuapp.com/).  相似文献   
64.

Objective

To assess the feasibility of measuring ventilatory threshold (VT) in higher-level motor-complete spinal cord injury (SCI) using 4 different analysis methods based on noninvasive gas exchange.

Design

Observational.

Setting

Laboratory testing.

Participants

Individuals with C4-T6 motor-complete SCI (16 paraplegia, 22 tetraplegia; American Spinal Injury Association Impairment Scale A/B; 42±10 years old).

Interventions

Not applicable.

Main Outcome

VT from a graded arm cycling test to volitional exhaustion using 4 methods: ventilatory equivalents, excess CO2, V-slope, and combined method.

Results

VT could be identified in all individuals with paraplegia, but in only 68% of individuals with tetraplegia. Individuals without observable VT completed the graded exercise test with lower ventilatory rate, peak power output, and peak oxygen consumption (Vo2peak) (all P<.05), compared to those with a detectable VT. Bland-Altman plots indicate minimal bias between methods (range: 0.01-0.03 L/min), with 95% limits of agreement of the difference within 0.25 L/min. Absolute V.o2 at VT with individual methods were all correlated to peak power output (r>0.74; P<.01) and Vo2peak (r>0.91; P<.01), with negligible differences between methods.

Conclusions

The assessment of VT is a feasible alternative to peak exercise testing for aerobic fitness in individuals with higher-level, motor-complete SCI, although care should be taken when interpreting VT in individuals with tetraplegia who have lower cardiorespiratory fitness and lower peak power outputs.  相似文献   
65.

Background and Purpose

Calcium/calmodulin-dependent protein kinase IIδ (CaMKIIδ) is an important regulator of cardiac contractile function and dysfunction and may be an unwanted secondary target for anti-cancer drugs such as sunitinib and imatinib that have been reported to alter cardiac performance. This study aimed to determine whether anti-cancer kinase inhibitors may affect CaMKII activity and expression when administered in vivo.

Experimental Approach

Cardiovascular haemodynamics in response to acute and chronic sunitinib treatment, and chronic imatinib treatment, were assessed in guinea pigs and the effects compared with those of the known positive and negative inotropes, isoprenaline and verapamil. Parallel studies from the same animals assessed CaMKIIδ expression and CaMKII activity following drug treatments.

Key Results

Acute administration of sunitinib decreased left ventricular (LV) dP/dtmax. Acute administration of isoprenaline increased LVdP/dtmax dose-dependently, while LVdP/dtmax was decreased by verapamil. CaMKII activity was decreased by acute administration of sunitinib and was increased by acute administration of isoprenaline, and decreased by acute administration of verapamil. CaMKIIδ expression following all acute treatments remained unchanged. Chronic imatinib and sunitinib treatments did not alter fractional shortening; however, both CaMKIIδ expression and CaMKII activity were significantly increased. Chronic administration of isoprenaline and verapamil decreased LV fractional shortening with parallel increases in CaMKIIδ expression and CaMKII activity.

Conclusions and Implications

Chronic sunitinib and imatinib treatment increased CaMKIIδ expression and CaMKII activity. As these compounds are associated with cardiac dysfunction, increased CaMKII expression could be an early indication of cellular cardiotoxicity marking potential progression of cardiac contractile dysfunction.Table of Links
TARGETS
Enzymesa
CaMKIIδ, calmodulin-dependent kinase II
Ion Channelsb
RyR, ryanodine receptor
Open in a separate window
LIGANDS
Imatinib
Isoprenaline
Sunitinib
Verapamil
Open in a separate windowThese Tables list key protein targets and ligands in this article which are hyperlinked to corresponding entries in http://www.guidetopharmacology.org, the common portal for data from the IUPHAR/BPS Guide to PHARMACOLOGY (Pawson et al., 2014) and are permanently archived in the Concise Guide to PHARMACOLOGY 2013/14a,bAlexander et al., 2013a,b,).  相似文献   
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67.

Aims

Older patients commonly suffer from multimorbidites and take multiple medications. As a result, these patients are more vulnerable to potentially inappropriate prescribing (PIP). PIP in older patients may result in adverse drug events (ADEs) and hospitalizations. However, little has been done to identify why PIP occurs. The objectives of this study were (i) to identify hospital doctors'' perceptions as to why PIP occurs, (ii) to identify the barriers to addressing the issues identified and (iii) to determine which intervention types would be best suited to improving prescribing.

Methods

Semi-structured interviews based on the Theoretical Domains Framework (TDF), a tool used to apply behaviour change theories, were conducted with 22 hospital doctors. Content analysis was conducted to identify domains of the TDF that could be targeted to improve prescribing for older people. These domains were then mapped to the behaviour change wheel to identify possible intervention types.

Results

Content analysis identified five of the 12 domains in the TDF as relevant: (i) environmental context and resources, (ii) knowledge, (iii) skills, (iv) social influences and (v) memory/attention and decision processes. Using the behaviour change wheel, the types of interventions deemed suitable were those based on training and environmental restructuring.

Conclusion

This study shows that doctors feel there is insufficient emphasis on geriatric pharmacotherapy in their undergraduate/postgraduate training. An intervention providing supplementary training, with particular emphasis on decision processes and dealing with social influences would be justified. This study has, however, uncovered many areas for potential intervention in the future.  相似文献   
68.
Inhibition of aldosterone biosynthesis by atriopeptins in rat adrenal cells   总被引:2,自引:0,他引:2  
The effect of synthetic atriopeptins on basal and stimulated aldosterone secretion was determined in isolated adrenal glomerulosa cells of the rat. Neither atriopeptin I (1-21) or III (1-24, i.e., the Phe-Arg-Tyr carboxy-terminal extension of atriopeptin I) altered basal aldosterone release. However, if the cells were prepared from adrenals of sodium-depleted rats, the basal aldosterone release was increased by 9-fold, compared with cells from normal rats. This elevated release was inhibited by 32% by atriopeptin I and atriopeptin III. Atriopeptin III was more potent than atriopeptin I. Angiotensin II and adrenocorticotropin stimulated the release of aldosterone in a concentration-related manner. Both atriopeptin I and atriopeptin III inhibited the stimulation by the peptides. Atriopeptin I inhibited angiotensin II- and adrenocorticotropin-induced aldosterone production by 50% at concentrations of 12 and 11 nM, respectively, and 0.5 and 0.2 nM, respectively, for atriopeptin III. Potassium-stimulated aldosterone production was also inhibited by atriopeptin I and atriopeptin III with 50% inhibition at concentrations of 10 and 0.4 nM, respectively. Shorter peptides (1-20, 1-19, and 3-19) were equipotent to atriopeptin I (1-21) as inhibitors of angiotensin II-induced steroidogenesis. To determine the site at which atriopeptins inhibit aldosterone synthesis, we used cyanoketone to inhibit 3 beta-hydroxy-dehydrogenase and dissociate the early and late pathways. Angiotensin II (2 nM) increased the synthesis of pregnenolone (early pathway), as well as the conversion of [3H]corticosterone to [3H]aldosterone (late pathway). Atriopeptin III inhibited basal pregnenolone synthesis by 36% and completely blocked angiotensin II-stimulated synthesis. The peptide similarly inhibited the late pathway.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   
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70.
Prevalence and vascular associations with migraine in older Australians   总被引:3,自引:0,他引:3  
Background: Migraine is a common disorder with recently described vascular associations, yet there are few Australian population-based data describing migraine prevalence.
Aims: To assess the prevalence and vascular associations with lifetime past history of typical migraine headache in a representative sample of older Australians.
Methods: The Blue Mountains Eye Study examined 3654 permanent residents aged 49 or older living in two postcode areas, west of Sydney (82.4% participation) during 1992–4. A structured interview was administered, including questions about past or present history of typical migraine. The diagnosis was consistent with International Headache Society criteria.
Results: A lifetime past history of typical migraine was given by 17% of participants, including 22% of women and 10% of men, a female:male ratio of 2.3:1. A marked trend for declining lifetime migraine frequency with increasing age was found for both sexes. Modest statistically significant associations were found with vascular disease history, after multivariate adjustment, which included vascular risk factors. These associations were stronger in men than in women. Among men, typical migraine was significantly associated with history of angina, odds ratio (OR) 2.0, acute myocardial infarction (OR 1.9) and stroke (OR 2.2). Among women, statistically significant associations were present only with history of myocardial infarct (OR 1.8).
Conclusions: These data indicate similar prevalence rates for lifetime typical migraine history in a representative sample of older Australians, compared to recent US and Canadian populations. Modest, statistically significant associations between typical migraine and past history of vascular disease were found, with the strongest associations found in men.  相似文献   
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