Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Aeroacoustic near-field measurement with micrometer resolution

For the investigation of sound-flow interaction in near-fields, like aeroacoustic damping or acoustic streaming, measurements of the acoustic particle velocity (APV) and the flow velocity field with a micrometer resolution are required. In addition, a high working distance is needed for contactless measurement. For this task, the laser Doppler velocity profile sensor is shown to be a predestined tool. First, the APV measurement is successfully validated in an aeroacoustic duct using a microphone-based measurement method as a reference. Here, a minimum APV amplitude of 4 mm/s was resolved in agreement with the reference measurements. Then, the profile sensor was applied for measurements at a perforated acoustic liner with bias flow. Acoustically induced flow vortex structures were resolved with a spatial resolution of 10μm with a minimum distance of 350μm to the liner perforation. A comparison to frequency modulated Doppler global velocimetry (FM-DGV) demonstrated the advantage of the profile sensor for spatially resolved measurements of small scale structures. In contrast, FM-DGV is beneficial due to its high measurement rate which enables the spectral analysis of the velocity in order to better understand the energy transfer from sound to flow

Aeroacoustic near-field measurements with microscale resolution

In order to analyse aeroacoustic phenomena at near-fields, e.g. the sound–flow interaction at aircraft engine liners, measurements of the flow velocity and the acoustic particle velocity (APV) with microscale resolution are required. To this end, the APV measurement with a high spatial resolution of 10 μm was conducted by means of a laser Doppler velocity profile sensor. For validation of the APV measurements using the profile sensor in a superposed flow, a good agreement with indirect microphone measurements as a reference was achieved, up to a maximum Mach number of 0.25. Aeroacoustic measurements at a minimum distance of 350 μm to the perforation of a bias flow liner were performed using the profile sensor. As a result, acoustically induced velocity oscillations near the rim of the orifice were detected with microscale resolution. The phase-resolved oscillation field indicates vortex shedding from the perforation, which is initiated by the sound–flow interaction. Thus, it is demonstrated that the profile sensor is a valuable tool for analysing aeroacoustic phenomena at near-fields, down to the Kolmogorov scale

Variation on the Dopamine D2 Receptor gene (DRD2) is associated with basal ganglia-to-frontal structural connectivity

Dopaminergic neurotransmission in the mesocortical system is crucial for higher order cognition. Common variation on the dopamine D2 receptor (DRD2) gene has been linked to individual differences in dopaminergic signaling and was also repeatedly associated to cognitive markers. The relationship between dopaminergic genetic variants and neurostructural properties of the mesocortical system, however, has received little attention so far. Recently, the direction of a dopaminergic manipulation was predicted from the integrity of fiber tracts between subcortical areas and the frontal lobes. Fiber tract integrity was therefore proposed as an indicator of baseline dopamine activity. This raises the question whether DRD2 variants that relate to dopamine turnaround are also linked to fiber tract integrity. In the present study we assessed associations between the DRD2 rs6277 polymorphism and subcortical connections from connectome maps derived from diffusion weighted imaging in n = 105 healthy volunteers (43 males and 62 females). Carriers of the CC genotype who are characterized by elevated striatal dopamine turnaround showed higher integrity in terms of fractional anisotropy on fiber tracts between the basal ganglia and frontal regions compared to carriers of the CT and TT variant. Our results indicate that structural connectivity could serve as a conceptual link between genetically determined individual differences in dopaminergic activity and effects of dopamine challenges on executive functioning

Variation on the Dopamine D2 Receptor gene (DRD2) is associated with basal ganglia-to-frontal structural connectivity

Dopaminergic neurotransmission in the mesocortical system is crucial for higher order cognition. Common variation on the dopamine D2 receptor (DRD2) gene has been linked to individual differences in dopaminergic signaling and was also repeatedly associated to cognitive markers. The relationship between dopaminergic genetic variants and neurostructural properties of the mesocortical system, however, has received little attention so far. Recently, the direction of a dopaminergic manipulation was predicted from the integrity of fiber tracts between subcortical areas and the frontal lobes. Fiber tract integrity was therefore proposed as an indicator of baseline dopamine activity. This raises the question whether DRD2 variants that relate to dopamine turnaround are also linked to fiber tract integrity. In the present study we assessed associations between the DRD2 rs6277 polymorphism and subcortical connections from connectome maps derived from diffusion weighted imaging in n = 105 healthy volunteers (43 males and 62 females). Carriers of the CC genotype who are characterized by elevated striatal dopamine turnaround showed higher integrity in terms of fractional anisotropy on fiber tracts between the basal ganglia and frontal regions compared to carriers of the CT and TT variant. Our results indicate that structural connectivity could serve as a conceptual link between genetically determined individual differences in dopaminergic activity and effects of dopamine challenges on executive functioning

Serotonin and the Brain's Rich Club-Association Between Molecular Genetic Variation on the TPH2 Gene and the Structural Connectome

The rich club comprises a densely mutually connected set of hub regions in the brain, thought to serve as a processing and integration core. We assessed the impact of normal variation of the tryptophane hydroxylase 2 gene's promotor region (TPH2 rs4570625) on structural connectivity of the rich club pathways by means of a candidate gene association design. Tryptophane hydroxylase 2 (TPH2) is a rate-limiting enzyme in the biosynthesis of serotonin and is known to inhibit, in addition to its role as a trans-synaptic messenger, axonal and dendritic growth. The TPH2 T-variant has been associated with reduced mRNA expression and reduced serotonin levels, which may particularly influence the development of macroscale anatomical connectivity. Here, we show larger mean connectivity in the rich club in carriers of the T-variant, suggesting potential effects of upregulation of neural connectivity growth in this central core system. In addition, by edge-removal statistics, we show that the TPH2-associated higher levels of rich club connectivity are of importance for the functioning of the total structural network. The observed association is speculated to result from an effect of serotonin levels on brain development, potentially leading to stronger structural connectivity in heavily interconnected hubs

Swirl–nozzle interaction experiment: quasi-steady model-based analysis

Measurements of sound due to swirl–nozzle interaction are presented. In the experiment a swirl structure was generated by means of unsteady tangential injection into a steady swirl-free flow upstream from a choked convergent–divergent nozzle. Ingestion of swirl by the choked nozzle caused a mass-flow rate change, which resulted in a downstream-measured acoustic response. The downstream acoustic pressure was found to remain negative as long as the swirl is maintained and reflections from the open downstream pipe termination do not interfere. The amplitude of this initial acoustic response was found to be proportional to the square of the tangential mass-flow rate used to generate swirl. When the tangential injection valve was closed, the mass-flow rate through the nozzle increased, resulting in an increase of the downstream acoustic pressure. This increase in signal was compared to the prediction of an empirical quasi-steady model, constructed from steady-state flow measurements. As the opening time of the valve was varied, the signal due to swirl evacuation showed an initial overshoot with respect to quasi-steady behavior, after which it gradually decayed to quasi-steady behavior for tangential injection times long compared to the convection time in the pipe upstream of the nozzle. This demonstrates that the acoustic signal can be used to obtain quantitative information concerning the time dependence of the swirl in the system. This could be useful for understanding the dynamics of flow in engines with swirl-stabilized combustion. Graphic abstract: [Figure not available: see fulltext.].Aerodynamic