Random networks of core-shell-like Cu-Cu2O/CuO nanowires as surface plasmon resonance-enhanced sensors

The rapid oxide formation on pristine unprotected copper surfaces limits the direct application of Cu nanomaterials in electronics and sensor assemblies with physical contacts. However, it is not clear whether the growing cuprous (Cu2O) and cupric oxides (CuO) and the formation of core-shell-like Cu-Cu2O/CuO nanowires would cause any compromise for non-contact optical measurements, where light absorption and subsequent charge oscillation and separation take place such as those in surface plasmon-assisted and photocatalytic processes, respectively. Therefore, we analyze how the surface potential of hydrothermally synthetized copper nanowires changes as a function of time in ambient conditions using Kelvin probe force microscopy in dark and under light illumination to reveal charge accumulation on the nanowires and on the supporting gold substrate. Further, we perform finite element modeling of the optical absorption to predict plasmonic behavior of the nanostructures. The results suggest that the core-shell-like Cu-Cu2O/CuO nanowires may be useful both in photocatalytic and in surface plasmon-enhanced processes. Here, by exploiting the latter, we show that regardless of the native surface oxide formation, random networks of the nanowires on gold substrates work as excellent amplification media for surface-enhanced Raman spectroscopy as demonstrated in sensing of Rhodamine 6G dye molecules

Aggression subtypes relate to distinct resting state functional connectivity in children and adolescents with disruptive behavior

There is increasing evidence for altered brain resting state functional connectivity in adolescents with disruptive behavior. While a considerable body of behavioral research points to differences between reactive and proactive aggression, it remains unknown whether these two subtypes have dissociable effects on connectivity. Additionally, callous-unemotional traits are important specifiers in subtyping aggressive behavior along the affective dimension. Accordingly, we examined associations between two aggression subtypes along with callous-unemotional traits using a seed-to-voxel approach. Six functionally relevant seeds were selected to probe the salience and the default mode network, based on their presumed role in aggression. The resting state sequence was acquired from 207 children and adolescents of both sexes [mean age (standard deviation) = 13.30 (2.60); range = 8.02-18.35] as part of a Europe-based multi-center study. One hundred eighteen individuals exhibiting disruptive behavior (conduct disorder/oppositional defiant disorder) with varying comorbid attention-deficit/hyperactivity disorder (ADHD) symptoms were studied, together with 89 healthy controls. Proactive aggression was associated with increased left amygdala-precuneus coupling, while reactive aggression related to hyper-connectivities of the posterior cingulate cortex (PCC) to the parahippocampus, the left amygdala to the precuneus and to hypo-connectivity between the right anterior insula and the nucleus caudate. Callous-unemotional traits were linked to distinct hyper-connectivities to frontal, parietal, and cingulate areas. Additionally, compared to controls, cases demonstrated reduced connectivity of the PCC and left anterior insula to left frontal areas, the latter only when controlling for ADHD scores. Taken together, this study revealed aggression-subtype-specific patterns involving areas associated with emotion, empathy, morality, and cognitive control

Different Whole-Brain Functional Connectivity Correlates of Reactive-Proactive Aggression and Callous-Unemotional Traits in Disruptive Children and Adolescents

BackgroundDisruptive behavior in children and adolescents can manifest itself in reactive (RA) and proactive (PA) aggression and is modulated by callous-unemotional (CU) traits and comorbidity. Research on aggression subtype-specific neural correlates is limited and the role of comorbid symptoms largely neglected.MethodsThe current multi-center study extended previous efforts by investigating unrestricted resting state functional connectivity (rsFC) alterations. The large sample (n = 207) of children and adolescents aged 8 – 18 years (mean age = 13.30 ± 2.60 years) included 118 cases with disruptive behavior (80 diagnosed with Oppositional Defiant Disorder and/or Conduct Disorder) and 89 controls. Attention-deficit/hyperactivity disorder (ADHD) and anxiety symptoms were added as covariates. We measured changes in global and local voxel-to-voxel rsFC using functional magnetic resonance imaging at 3T (mean acquisition time = 8 min 25 sec).ResultsCompared to controls, cases demonstrated altered rsFC including frontal areas when anxiety but not ADHD symptoms were considered. Within cases, RA and PA scores related to changes in global and local rsFC in central gyrus and precuneus previously linked to aggression-related impairments. CU trait severity correlated with global rsFC alterations including inferior and middle temporal gyrus implicated in empathy, emotion, and reward-related activity. Importantly, most observed aggression subtype-specific patterns could only be identified when ADHD and anxiety problems were also accounted for.ConclusionsThe current study clarifies that distinct though overlapping brain connectivity measures can disentangle differing manifestations of aggressive behavior. Moreover, our results highlight the importance of considering comorbid symptoms for detecting aggression-related rsFC alterations.</jats:sec

Influence of Different Container Closure Systems and Capping Process Parameters on Product Quality and Container Closure Integrity (CCI) in GMP Drug Product Manufacturing

Capping equipment used in good manufacturing practice manufacturing features different designs and a variety of adjustable process parameters. The overall capping result is a complex interplay of the different capping process parameters and is insufficiently described in literature. It remains poorly studied how the different capping equipment designs and capping equipment process parameters (e.g., pre-compression force, capping plate height, turntable rotating speed) contribute to the final residual seal force of a sealed container closure system and its relation to container closure integrity and other drug product quality parameters. Stopper compression measured by computer tomography correlated to residual seal force measurements.In our studies, we used different container closure system configurations from different good manufacturing practice drug product fill & finish facilities to investigate the influence of differences in primary packaging, that is, vial size and rubber stopper design on the capping process and the capped drug product. In addition, we compared two large-scale good manufacturing practice manufacturing capping equipment and different capping equipment settings and their impact on product quality and integrity, as determined by residual seal force.The capping plate to plunger distance had a major influence on the obtained residual seal force values of a sealed vial, whereas the capping pre-compression force and the turntable rotation speed showed only a minor influence on the residual seal force of a sealed vial. Capping process parameters could not easily be transferred from capping equipment of different manufacturers. However, the residual seal force tester did provide a valuable tool to compare capping performance of different capping equipment. No vial showed any leakage greater than 10(-8)mbar L/s as measured by a helium mass spectrometry system, suggesting that container closure integrity was warranted in the residual seal force range tested for the tested container closure systems. LAY ABSTRACT: Capping equipment used in good manufacturing practice manufacturing features different designs and a variety of adjustable process parameters. The overall capping result is a complex interplay of the different capping process parameters and is insufficiently described in the literature. It remains poorly studied how the different capping equipment designs and capping equipment process parameters contribute to the final capping result.In this study, we used different container closure system configurations from different good manufacturing process drug product fill & finish facilities to investigate the influence of the vial size and the rubber stopper design on the capping process. In addition, we compared two examples of large-scale good manufacturing process capping equipment and different capping equipment settings and their impact on product quality and integrity, as determined by residual seal force

Random networks of core-shell-like Cu-Cu₂O/CuO nanowires as surface plasmon resonance-enhanced sensors

Abstract The rapid oxide formation on pristine unprotected copper surfaces limits the direct application of Cu nanomaterials in electronics and sensor assemblies with physical contacts. However, it is not clear whether the growing cuprous (Cu2O) and cupric oxides (CuO) and the formation of core-shell-like Cu-Cu2O/CuO nanowires would cause any compromise for non-contact optical measurements, where light absorption and subsequent charge oscillation and separation take place such as those in surface plasmon-assisted and photocatalytic processes, respectively. Therefore, we analyze how the surface potential of hydrothermally synthetized copper nanowires changes as a function of time in ambient conditions using Kelvin probe force microscopy in dark and under light illumination to reveal charge accumulation on the nanowires and on the supporting gold substrate. Further, we perform finite element modeling of the optical absorption to predict plasmonic behavior of the nanostructures. The results suggest that the core-shell-like Cu-Cu2O/CuO nanowires may be useful both in photocatalytic and in surface plasmon-enhanced processes. Here, by exploiting the latter, we show that regardless of the native surface oxide formation, random networks of the nanowires on gold substrates work as excellent amplification media for surface-enhanced Raman spectroscopy as demonstrated in sensing of Rhodamine 6G dye molecules

Impact of Vial Capping on Residual Seal Force and Container Closure Integrity

The vial capping process is a critical unit operation during drug product manufacturing, as it could possibly generate cosmetic defects or even affect container closure integrity. Yet there is significant variability in capping equipment and processes, and their relation to potential defects or container closure integrity has not been thoroughly studied. In this study we applied several methods-residual seal force tester, a self-developed system of a piezo force sensor measurement, and computed tomography-to characterize different container closure system combinations that had been sealed using different capping process parameter settings. Additionally, container closure integrity of these samples was measured using helium leakage (physical container closure integrity) and compared to characterization data. The different capping equipment settings lead to residual seal force values from 7 to 115 N. High residual seal force values were achieved with high capping pre-compression force and a short distance between the capping plate and plunge. The choice of container closure system influenced the obtained residual seal force values. The residual seal force tester and piezoelectric measurements showed similar trends. All vials passed physical container closure integrity testing, and no stopper rupture was seen with any of the settings applied, suggesting that container closure integrity was warranted for the studied container closure system with the chosen capping setting ranges

Aggression Subtypes Relate to Distinct Resting State Functional Connectivity in Disruptive Children and Adolescents

Objective There is increasing evidence for altered resting state functional connectivity (rsFC) in adolescents with disruptive behavior. Despite considerable ongoing behavioral research suggesting also important differences relating to reactive and proactive aggression, the corresponding rsFC correlates have not been studied to date. We therefore examined associations between these aggression subtypes along with subdimensions of callous-unemotional (CU) traits and rsFC using predefined seeds in aggression-related salience network (SN) and default mode network (DMN). Method Aggression subtype-specific whole-brain rsFC of SN and DMN seeds was investigated in a resting state sequence (mean acquisition time = 8 min 25 sec) acquired from 207 children and adolescents of both sexes aged 8 - 18 years (mean age (SD) = 13.30 (2.60) years; range = 8.02 – 18.35) in a multi-center study. One hundred eighteen individuals exhibited disruptive behavior (conduct disorder/oppositional defiant disorder) with different levels of comorbid ADHD symptoms, 89 were healthy. Results Compared to healthy controls, cases demonstrated reduced DMN and – after controlling for ADHD scores – SN seed-based rsFC with left hemispheric frontal clusters. We found increased and distinct aggression-subtype specific rsFC patterns. Specifically, reactive and proactive aggression correlated with distinct SN and DMN seed-based rsFC patterns. CU dimensions led to different DMN and SN rsFC with clusters including frontal, parietal, and cingulate areas. Conclusions This first study investigating reactive and proactive aggression along with CU dimensions reveals new subtype-specific whole-brain rsFC patterns in brain regions linked to processes like emotion, empathy, moral, and cognitive control

The pharmaceutical vial capping process; Container closure systems, capping equipment, regulatory framework, and seal quality tests

Parenteral drug products are protected by appropriate primary packaging to protect against environmental factors, including potential microbial contamination during shelf life duration. The most commonly used CCS configuration for parenteral drug products is the glass vial, sealed with a rubber stopper and an aluminum crimp cap. In combination with an adequately designed and controlled aseptic fill/finish processes, a well-designed and characterized capping process is indispensable to ensure product quality and integrity and to minimize rejections during the manufacturing process. In this review, the health authority requirements and expectations related to container closure system quality and container closure integrity are summarized. The pharmaceutical vial, the rubber stopper, and the crimp cap are described. Different capping techniques are critically compared: The most common capping equipment with a rotating capping plate produces the lowest amount of particle. The strength and challenges of methods to control the capping process are discussed. The residual seal force method can characterize the capping process independent of the used capping equipment or CCS. We analyze the root causes of several cosmetic defects associated with the vial capping process