Increasing the reward value of behavioral goals can facilitate cognitive processes required for goal achievement. This facilitation may be accomplished by the dynamic and flexible engagement of ...cognitive control mechanisms operating in distributed brain regions. It is still not clear, however, what are the characteristics of individuals, situations, and neural activation dynamics that optimize motivation-linked cognitive enhancement. Here we show that highly reward-sensitive individuals exhibited greater improvement of working memory performance in rewarding contexts, but exclusively on trials that were not rewarded. This effect was mediated by a shift in the temporal dynamics of activation within right lateral prefrontal cortex, from a transient to predominantly tonic mode, with an additional anticipatory transient boost. In contexts with intermittent rewards, a strategy of proactive cognitive control may enable globally optimal performance to facilitate reward attainment. Reward-sensitive individuals appear preferentially motivated to adopt this resource-demanding strategy, resulting in paradoxical benefits selectively for nonrewarded events.
The zebrafish is a powerful experimental system for uncovering gene function in vertebrate organisms. Nevertheless, studies in the zebrafish have been limited by the approaches available for ...eliminating gene function. Here we present simple and efficient methods for inducing, detecting, and recovering mutations at virtually any locus in the zebrafish. Briefly, double-strand DNA breaks are induced at a locus of interest by synthetic nucleases, called TALENs. Subsequent host repair of the DNA lesions leads to the generation of insertion and deletion mutations at the targeted locus. To detect the induced DNA sequence alterations at targeted loci, genomes are examined using High Resolution Melt Analysis, an efficient and sensitive method for detecting the presence of newly arising sequence polymorphisms. As the DNA binding specificity of a TALEN is determined by a custom designed array of DNA recognition modules, each of which interacts with a single target nucleotide, TALENs with very high target sequence specificities can be easily generated. Using freely accessible reagents and Web-based software, and a very simple cloning strategy, a TALEN that uniquely recognizes a specific pre-determined locus in the zebrafish genome can be generated within days. Here we develop and test the activity of four TALENs directed at different target genes. Using the experimental approach described here, every embryo injected with RNA encoding a TALEN will acquire targeted mutations. Multiple independently arising mutations are produced in each growing embryo, and up to 50% of the host genomes may acquire a targeted mutation. Upon reaching adulthood, approximately 90% of these animals transmit targeted mutations to their progeny. Results presented here indicate the TALENs are highly sequence-specific and produce minimal off-target effects. In all, it takes about two weeks to create a target-specific TALEN and generate growing embryos that harbor an array of germ line mutations at a pre-specified locus.
A major challenge in research on executive control is to reveal its functional decomposition into underlying neural mechanisms. A typical assumption is that this decomposition occurs solely through ...anatomically based dissociations. Here we tested an alternative hypothesis that different cognitive control processes may be implemented within the same brain regions, with fractionation and dissociation occurring on the basis of temporal dynamics. Regions within lateral prefrontal cortex (PFC) were examined that, in a prior study, exhibited contrasting temporal dynamics between older and younger adults during performance of the AX-CPT cognitive control task. The temporal dynamics in younger adults fit a proactive control pattern (primarily cue-based activation), whereas in older adults a reactive control pattern was found (primarily probebased activation). In the current study, we found that following a period of task-strategy training, these older adults exhibited a proactive shift within a subset of the PFC regions, normalizing their activity dynamics toward young adult patterns. Conversely, under conditions of penalty-based monetary incentives, the younger adults exhibited a reactive shift some of the same regions, altering their temporal dynamics toward the older adult baseline pattern. These experimentally induced crossover patterns of temporal dynamics provide strong support for dual modes of cognitive control that can be flexibly shifted within PFC regions, via modulation of neural responses to changing task conditions or behavioral goals.
Cognitive control and working memory processes have been found to be influenced by changes in motivational state. Nevertheless, the impact of different motivational variables on behavior and brain ...activity remains unclear.
The current study examined the impact of incentive category by varying on a within-subjects basis whether performance during a working memory task was reinforced with either secondary (monetary) or primary (liquid) rewards. The temporal dynamics of motivation-cognition interactions were investigated by employing an experimental design that enabled isolation of sustained and transient effects. Performance was dramatically and equivalently enhanced in each incentive condition, whereas neural activity dynamics differed between incentive categories. The monetary reward condition was associated with a tonic activation increase in primarily right-lateralized cognitive control regions including anterior prefrontal cortex (PFC), dorsolateral PFC, and parietal cortex. In the liquid condition, the identical regions instead showed a shift in transient activation from a reactive control pattern (primary probe-based activation) during no-incentive trials to proactive control (primary cue-based activation) during rewarded trials. Additionally, liquid-specific tonic activation increases were found in subcortical regions (amygdala, dorsal striatum, nucleus accumbens), indicating an anatomical double dissociation in the locus of sustained activation.
These different activation patterns suggest that primary and secondary rewards may produce similar behavioral changes through distinct neural mechanisms of reinforcement. Further, our results provide new evidence for the flexibility of cognitive control, in terms of the temporal dynamics of activation.
Free-living adherence to high-intensity interval training (HIIT) has not been adequately tested. This randomized trial examined changes in cardiorespiratory fitness (CRF) and accelerometer-measured ...purposeful physical activity over 12 months of free-living HIIT versus moderate-intensity continuous training (MICT).
Ninety-nine previously low-active participants with overweight/obesity were randomly assigned to HIIT (n = 47) or MICT (n = 52). Both interventions were combined with evidence-based behaviour change counselling consisting of 7 sessions over 2 weeks. Individuals in HIIT were prescribed 10 X 1-min interval-based exercise 3 times per week (totalling 75 min) whereas individuals in MICT were prescribed 150 min of steady-state exercise per week (50 mins 3 times per week). Using a maximal cycling test to exhaustion with expired gas analyses, CRF was assessed at baseline and after 6 and 12 months of free-living exercise. Moderate-to-vigorous physical activity of 10+ minutes (MVPA10+) was assessed by 7-day accelerometry at baseline, 3, 6, 9, and 12 months. Intention to treat analyses were conducted using linear mixed models.
CRF was improved over the 12 months relative to baseline in both HIIT (+ 0.15 l/min, 95% CI 0.08 to 0.23) and MICT (+ 0.11 l/min, 95% CI 0.05 to 0.18). Both groups improved 12-month MVPA10+ above baseline (HIIT: + 36 min/week, 95% CI 17 to 54; MICT: + 69 min/week, 95% CI 49 to 89) with the increase being greater (by 33 min, 95% CI 6 to 60) in MICT (between group difference, P = 0.018).
Despite being prescribed twice as many minutes of exercise and accumulating significantly more purposeful exercise, CRF improvements were similar across 12 months of free-living HIIT and MICT in previously low-active individuals with overweight/obesity.
Abstract
Background
As healthcare systems strive for efficiency, hospital “length of stay outliers” have the potential to significantly impact a hospital’s overall utilization. There is a tendency to ...exclude such “outlier” stays in local quality improvement and data reporting due to their assumed rare occurrence and disproportionate ability to skew mean and other summary data. This study sought to assess the influence of length of stay (LOS) outliers on inpatient length of stay and hospital capacity over a 5-year period at a large urban academic medical center.
Methods
From January 2014 through December 2019, 169,645 consecutive inpatient cases were analyzed and assigned an expected LOS based on national academic center benchmarks. Cases in the top 1% of national sample LOS by diagnosis were flagged as length of stay outliers.
Results
From 2014 to 2019, mean outlier LOS increased (40.98 to 45.11 days), as did inpatient LOS with outliers excluded (5.63 to 6.19 days). Outlier cases increased both in number (from 297 to 412) and as a percent of total discharges (0.98 to 1.56%), and outlier patient days increased from 6.7 to 9.8% of total inpatient plus observation days over the study period.
Conclusions
Outlier cases utilize a disproportionate and increasing share of hospital resources and available beds. The current tendency to exclude such outlier stays in data reporting due to assumed rare occurrence may need to be revisited. Outlier stays require distinct and targeted interventions to appropriately reduce length of stay to both improve patient care and maintain hospital capacity.
The effects of fatigue loading frequency (f), sensitization, and crack length on corrosion fatigue crack growth rates (da/dN) were investigated for AA5456-H116 under full immersion in 3.5 wt% NaCl. ...Results from fracture mechanics-based experiments conducted at a constant stress-intensity range (ΔK) and load ratio (R) suggest that highly sensitized AA5456-H116 microstructures (ASTM G67 nitric acid mass loss tests NAMLT value of 24 mg/cm
2
and higher) exhibit increased da/dN over microstructures in the as-received condition (NAMLT 5 mg/cm
2
) and the onset of an inverse f-dependence. For a single, high level of sensitization (70 mg/cm
2
), da/dN increased 3.5× as f decreased from 10 Hz to 0.03 Hz. At a singular low loading f of 0.03 Hz, high sensitization levels (65 mg/cm
2
) accelerated da/dN fivefold over da/dN in the as-received condition. The da/dN of microstructures below a critical NAMLT value of 24 mg/cm
2
were f-independent. Specifically, in microstructures with a low sensitization level (ASTM G67 NAMLT value less than 24 mg/cm
2
), there was no increase in da/dN as f decreased from 1 Hz to 0.03 Hz. At any singular f, sensitization up to 24 mg/cm
2
did not accelerate da/dN over the rate in an as-received microstructure. Additional testing established that the inverse f-dependence of da/dN observed in highly sensitized microstructures cannot be attributed to crack length effects. Two hypotheses are discussed that may explain the observed inverse relationship between f and da/dN in microstructures at or above the critical NAMLT value of 24 mg/cm
2
.
•The effects of low water vapor, low temperature environments, on the FCGR of 2199 AA.•FCGR was found to decrease with decreasing water vapor pressure systematically.•Temperature was varied from 23C ...to −65 °C and only −30 °C and −50 °C effected FCGR.•The proposed reasoning for low temp changes in FCGR are H-dislocation interactions.
The objective of the study is to evaluate the fatigue crack growth of a third-generation Al-Li-Cu alloy (2199-T86) in environments relevant to high-altitude flight. Reduction of PH2O at 23 °C resulted in a general reduction of crack growth rates. A local minimum in growth rates were observed at intermediate ΔK and PH2O and was attributed to roughness induced impedance of water transport through the crack wake. Decreasing temperature had no effect on growth kinetics down to −15 °C, but decreased crack rates were observed at −30 °C and −50 °C.
Fatigue crack growth experiments were conducted on highly sensitized AA5456-H116 in laboratory air and 0.6 M NaCl at two applied potentials (−900 mVSCE and −1300 mVSCE; vs. saturated calomel ...electrode) using frequencies of 5 and 0.1 Hz. At 5 Hz, the fatigue crack growth rate (da/dN) was similar between −900 mVSCE and −1300 mVSCE (~1.5 × 10−4 mm/cycle), which were both approximately 10-fold faster than the da/dN measured in laboratory air. However, significant differences in da/dN were observed between −900 and −1300 mVSCE for testing at 0.1 Hz. Specifically, while a nominally similar da/dN to the 5 Hz data was observed for −900 mVSCE, a 1000-fold decrease in da/dN was noted for −1300 mVSCE at 0.1 Hz. Microscopy of the crack tip region on interrupted fatigue experiments conducted at −1300 mVSCE revealed significant blunting of the crack tip at 0.1 Hz, while the crack tip cycled at 5 Hz remained sharp. A stepped potential experiment demonstrated that the measured da/dN at −1100 mVSCE decreased by multiple orders of magnitude when this potential was approached from the cathodic versus the anodic direction. Collectively, these data suggest a salient role of corrosion-induced blunting on the measured da/dN for highly sensitized AA5xxx-series alloys immersed in marine environments at highly cathodic potentials and low loading frequency.
•Microstructures with low DoS exhibit f-independent corrosion fatigue kinetics.•High DoS microstructures increase CF da/dN 10× for every 10× decrease in f.•CF da/dN of high DoS microstructure is ...1000× higher than AR material at 0.01 Hz.
Corrosion fatigue crack growth rates (da/dN) of AA5083-H131 when loaded in 3.5 wt% NaCl increase as the level of sensitization increases and exhibit a strong inverse fatigue loading frequency dependence when heavily sensitized. High Mg 5xxx series Al alloys are known to exhibit decreased resistance to intergranular corrosion and intergranular stress corrosion cracking due to the formation of the active Al3Mg2-β phase on grain boundaries when exposed to slightly elevated temperatures for prolonged periods of time, a phenomenon known as sensitization. High resolution fracture mechanics based experiments conducted at constant ΔK and R-ratio under full immersion in 3.5 wt% NaCl show that da/dN in a heavily sensitized microstructure increases by an order of magnitude for each order of magnitude decrease in fatigue loading frequency, while da/dN for the as-received and unsensitized microstructure has little to no frequency dependence. Futhermore, for higher frequency loading at 1 Hz, da/dN for the highly sensitized microstructures is one order of magnitude higher than the as-received microstructure; while for the low frequency loading at 0.01 Hz, da/dN for the highly sensitized microstructure is three orders of magnitude higher than the as-received microstructure. The findings of this study suggest that typical higher frequency laboratory testing studies at 10 Hz may severely underestimate fatigue life under service relevant loading conditions.
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