The Challenge of Die Filling in Rotary Presses: A Systematic Study of Material Properties and Process Parameters

For the efficient and safe production of pharmaceutical tablets, a deep process understanding is of high importance. An essential process step during tableting is the die filling, as it is responsible for a consistent tablet weight and drug content. Furthermore, it affects the results of subsequent process steps, compaction and ejection, and thus critical quality attributes. This study focuses on understanding the influences of process parameters and material properties on die filling on a rotary tablet press. By the systematic variation in process parameters as the turret and paddle speeds as well as the fill and dosing depths, five formulations with differing properties are processed. Analysis of the normalized tablet weight, called filling yield, revealed different limitation mechanisms of the filling process, i.e., incomplete filled dies for certain parameter settings. Kinetic limitations occur due to a short residence time under the feed frame (filling time) caused by high turret speeds, which additionally induce high tablet weight variation coefficients. Characteristic maximum turret speeds at certain paddle speeds can be found to still achieve complete filling. At low turret speeds, densification of the powder inside the dies takes place, induced by two mechanisms: either high paddle speeds or high overfill ratios, or a combination of both. The challenge to fill the dies completely as well as avoid densification is dependent on material properties as the flowability. The mass discharge rate from an orifice was found to be in a linear correlation to the filling results of different formulations below complete filling

Parameter-based evaluation of attentional impairments in schizophrenia and their modulation by prefrontal transcranial direct current stimulation

Background: Attentional dysfunctions constitute core cognitive symptoms in schizophrenia, but the precise underlying neurocognitive mechanisms remain to be elucidated. Methods: In this randomized, double-blind, sham-controlled study, we applied, for the first time, a theoretically grounded modeling approach based on Bundesen’s Theory of Visual Attention (TVA) to (i) identify specific visual attentional parameters affected in schizophrenia and (ii) assess, as a proof of concept, the potential of single-dose anodal transcranial direct current stimulation (tDCS; 20 min, 2 mA) to the left dorsolateral prefrontal cortex to modulate these attentional parameters. To that end, attentional parameters were measured before (baseline), immediately after, and 24 h after the tDCS intervention in 20 schizophrenia patients and 20 healthy controls. Results: At baseline, analyses revealed significantly reduced visual processing speed and visual short-term memory storage capacity in schizophrenia. A significant stimulation condition × time point interaction in the schizophrenia patient group indicated improved processing speed at the follow-up session only in the sham condition (a practice effect), whereas performance remained stable across the three time points in patients receiving verum stimulation. In healthy controls, anodal tDCS did not result in a significant change in attentional performance. Conclusion: With regard to question (i) above, these findings are indicative of a processing speed and short-term memory deficit as primary sources of attentional deficits in schizophrenia. With regard to question (ii), the efficacy of single-dose anodal tDCS for improving (speed aspects of visual) cognition, it appears that prefrontal tDCS (at the settings used in the present study), rather than ameliorating the processing speed deficit in schizophrenia, actually may interfere with practice-dependent improvements in the rate of visual information uptake. Such potentially unexpected effects of tDCS ought to be taken into consideration when discussing its applicability in psychiatric populations. The study was registered at http://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00011665

Lower-Resolution Retrieval of Scenes in Older Adults With Subjective Cognitive Decline

Objective Scenes with more perceptual detail can help detect subtle memory deficits more than scenes with less detail. Here, we investigated whether older adults with subjective cognitive decline (SCD) show less brain activation and more memory deficits to scenes with more (vs. scenes with less) perceptual detail compared to controls (CON). Method In 37 healthy older adults (SCD: 16), we measured blood oxygenation level-dependent-functional magnetic resonance imaging during encoding and behavioral performance during retrieval. Results During encoding, higher activation to scenes with more (vs. less) perceptual detail in the parahippocampal place area predicted better memory performance in SCD and CON. During retrieval, superior performance for new scenes with more (vs. less) perceptual detail was significantly more pronounced in CON than in SCD. Conclusions Together, these results suggest a present, but attenuated benefit from perceptual detail for memory retrieval in SCD. Memory complaints in SCD might, thus, refer to a decreased availability of perceptual detail of previously encoded stimuli

Lower visual processing speed relates to greater subjective cognitive complaints in community-dwelling healthy older adults

Introduction: Subjective cognitive complaints in older age may reflect subtle objective impairments in basic cognitive functions that might foreshadow broader cognitive problems. Such cognitive functions, however, are not captured by standard neuropsychological testing. Visual processing speed is a basic visual attention function that underlies the performance of cognitive tasks relying on visual stimuli. Here, we test the hypothesis that lower visual processing speed correlates with greater subjective cognitive complaints in healthy older adults from the community. Methods: To do so, we assessed a sample of 30 healthy, cognitively normal older adults (73.07 ± 7.73 years old; range: 60–82; 15 females) with respect to individual subjective cognitive complaints and visual processing speed. We quantified the degree of subjective cognitive complaints with two widely-used questionnaires: the Memory Functioning Questionnaire and the Everyday Cognition. We used verbal report tasks and the theory of visual attention to estimate a visual processing speed parameter independently from motor speed and other visual attention parameters, i.e., visual threshold, visual short-term memory storage capacity, top-down control, and spatial weighting. Results: We found that lower visual processing speed correlated with greater subjective complaints and that this relationship was not explained by age, education, or depressive symptoms. The association with subjective cognitive complaints was specific to visual processing speed, as it was not observed for other visual attention parameters. Discussion: These results indicate that subjective cognitive complaints reflect a reduction in visual processing speed in healthy older adults. Together, our results suggest that the combined assessment of subjective cognitive complaints and visual processing speed has the potential to identify individuals at risk for cognitive impairment before the standard tests show any abnormal results

Lower visual processing speed relates to greater subjective cognitive complaints in community-dwelling healthy older adults

Introduction: Subjective cognitive complaints in older age may reflect subtle objective impairments in basic cognitive functions that might foreshadow broader cognitive problems. Such cognitive functions, however, are not captured by standard neuropsychological testing. Visual processing speed is a basic visual attention function that underlies the performance of cognitive tasks relying on visual stimuli. Here, we test the hypothesis that lower visual processing speed correlates with greater subjective cognitive complaints in healthy older adults from the community. Methods: To do so, we assessed a sample of 30 healthy, cognitively normal older adults (73.07 ± 7.73 years old; range: 60–82; 15 females) with respect to individual subjective cognitive complaints and visual processing speed. We quantified the degree of subjective cognitive complaints with two widely-used questionnaires: the Memory Functioning Questionnaire and the Everyday Cognition. We used verbal report tasks and the theory of visual attention to estimate a visual processing speed parameter independently from motor speed and other visual attention parameters, i.e., visual threshold, visual short-term memory storage capacity, top-down control, and spatial weighting. Results: We found that lower visual processing speed correlated with greater subjective complaints and that this relationship was not explained by age, education, or depressive symptoms. The association with subjective cognitive complaints was specific to visual processing speed, as it was not observed for other visual attention parameters. Discussion: These results indicate that subjective cognitive complaints reflect a reduction in visual processing speed in healthy older adults. Together, our results suggest that the combined assessment of subjective cognitive complaints and visual processing speed has the potential to identify individuals at risk for cognitive impairment before the standard tests show any abnormal results

Human subsystems of medial temporal lobes extend locally to amygdala nuclei and globally to an allostatic-interoceptive system

In mammals, the hippocampus, entorhinal, perirhinal, and parahippocampal cortices (i.e., core regions of the human medial temporal lobes, MTL) are locally interlaced with the adjacent amygdala nuclei at the structural and functional levels. At the global brain level, the human MTL has been described as part of the default mode network whereas amygdala nuclei as parts of the salience network, with both networks forming collectively a large-scale brain system supporting allostatic-interoceptive functions. We hypothesized (i) that intrinsic functional connectivity of slow activity fluctuations would reveal human MTL subsystems locally extending to the amygdala; and (ii) that these extended local subsystems would be globally embedded in large-scale brain systems supporting allostatic-interoceptive functions. From the resting-state fMRI data of three independent samples of cognitively healthy adults (one main and two replication samples: Ns = 101, 61, and 29, respectively), we analyzed the functional connectivity of fluctuating ongoing BOLD-activity within and outside the amygdala-MTL in a data-driven way using masked independent component and dual-regression analyses. We found that at the local level MTL subsystems extend to the amygdala and are functionally organized along the longitudinal amygdala-MTL axis. These subsystems were characterized by a consistent involvement of amygdala, hippocampus, and entorhinal cortex, but a variable participation of perirhinal and parahippocampal regions. At the global level, amygdala-MTL subsystems selectively connected to salience, thalamic-brainstem, and default mode networks – the major cortical and subcortical parts of the allostatic-interoceptive system. These results provide evidence for integrated amygdala-MTL subsystems in humans, which are embedded within a larger allostatic-interoceptive system

Revisiting remote drivers of the 2014 drought in South-Eastern Brazil

South-Eastern Brazil experienced a devastating drought associated with significant agricultural losses in austral summer 2014. The drought was linked to the development of a quasi-stationary anticyclone in the South Atlantic in early 2014 that affected local precipitation patterns over South-East Brazil. Previous studies have suggested that the unusual blocking was triggered by tropical Pacific sea surface temperature (SST) anomalies and, more recently, by convection over the Indian Ocean related to the Madden-Julian Oscillation. Further investigation of the proposed teleconnections appears crucial for anticipating future economic impacts. In this study, we use numerical experiments with an idealized atmospheric general circulation model forced with the observed 2013/2014 SST anomalies in different ocean basins to understand the dominant mechanism that initiated the 2014 South Atlantic anticyclonic anomaly. We show that a forcing with global 2013/2014 SST anomalies enhances the chance for the occurrence of positive geopotential height anomalies in the South Atlantic. However, further sensitivity experiments with SST forcings in separate ocean basins suggest that neither the Indian Ocean nor tropical Pacific SST anomalies alone have contributed significantly to the anomalous atmospheric circulation that led to the 2014 South-East Brazil drought. The model study rather points to an important role of remote forcing from the South Pacific, local South Atlantic SSTs, and internal atmospheric variability in driving the persistent blocking over the South Atlantic

Dual Task Effects on Visual Attention Capacity in Normal Aging

Older adults show higher dual task performance decrements than younger adults. While this is assumed to be related to attentional capacity reductions, the precise affected functions are not specified. Such specification is, however, possible based on the "theory of visual attention" (TVA) which allows for modeling of distinct attentional capacity parameters. Furthermore, it is unclear whether older adults show qualitatively different attentional effects or whether they show the same effects as younger adults experience under more challenging conditions. By varying the complexity of the secondary task, it is possible to address this question. In our study, participants performed a verbal whole report of briefly presented letter arrays. TVA-based fitting of report performance delivered parameters of visual threshold to, processing speed C, and visual short-term memory (VSTM) storage capacity K. Furthermore, participants performed a concurrent motor task consisting of continuous tapping of a (simple or complex) sequence. Both TVA and tapping tasks were performed under single and dual task conditions. Two groups of 30 younger adults each performed either the simple or complex tapping, and a group of 30 older adults performed the simple tapping condition. In older participants, VSTM storage capacity declined under dual task conditions. While no such effect was found in younger subjects performing the simple tapping sequence under dual task conditions, the younger group performing the complex tapping task under dual task conditions also showed a significant VSTM capacity reduction. Generally, no significant effect on other TVA parameters or on tapping accuracy was found. Comparable goodness-of-fit measures were obtained for the TVA modeling data in single and dual tasks, indicating that tasks were executed in a qualitatively similar, continuous manner, although quantitatively less efficiently under dual- compared to single-task conditions. Taken together, our results show that the age-specific effects of motor-cognitive dual task interference are reflected by a stronger decline of VSTM storage capacity. They support an interpretation of VSTM as central attentional capacity, which is shared across visual uptake and concurrent motor performance. Capacity limits are reached earlier, and already under lower motor task complexity, in older compared to younger adults