Enhancing the Capabilities of Fluid Bed Granulation through Process Automation and Digitalisation

This paper describes a PAT-enabled, digitalised, and automated fluid bed granulation system. A multichannel Near-Infrared (NIR) spectrophotometer and a direct imaging particle size and shape analyser in constant dialogue with the SmartX no-code/low-code platform provide a ground-breaking process automation toolset now located at the Bernal Institute in the University of Limerick. Two sets of results are presented for this study, from two iterations of the Advance Dynamic Process Control (ADPC) controller application. The results demonstrate the direct measurement and control of the product’s critical quality attributes through digitality enabled feedback control of processing setpoints and parameters. The platform controlled the particle size more tightly compared to non-automated control and a more accurate measurement-driven process endpoint for moisture content was achieved. Implementing a digitally enabled control approach can significantly reduce batch to batch variation and greatly improve process performance and product consistency

Quantum chemistry simulation of ground- and excited-state properties of the sulfonium cation on a superconducting quantum processor

The computational description of correlated electronic structure, and particularly of excited states of many-electron systems, is an anticipated application for quantum devices. An important ramification is to determine the dominant molecular fragmentation pathways in photo-dissociation experiments of light-sensitive compounds, like sulfonium-based photo-acid generators used in photolithography. Here we simulate the static and dynamical electronic structure of the H$_3$S$^+$ molecule, taken as a minimal model of a triply-bonded sulfur cation, on a superconducting quantum processor of the IBM Falcon architecture. To this end, we combine a qubit reduction technique with variational and diagonalization quantum algorithms, and use a sequence of error-mitigation techniques. We compute dipole structure factors and partial atomic charges along ground- and excited-state potential energy curves, revealing the occurrence of homo- and heterolytic fragmentation. To the best of our knowledge, this is the first simulation of a photo-dissociation reaction on a superconducting quantum device, and an important step towards the computational description of photo-dissociation by quantum computing algorithms.Comment: 12 pages, 7 figure

Ion-Pairing Limits Crystal Growth in Metal-Oxygen Batteries

Aprotic alkali metal-oxygen batteries are widely considered to be promising high specific energy alternatives to Li-ion batteries. The growth and dissolution of alkali metal oxides such as Li2O2 in Li-O2 batteries and NaO2 and KO2 in Na- and K-O2 batteries, respectively, is central to the discharge and charge processes in these batteries. However, crystal growth and dissolution of the discharge products, especially in aprotic electrolytes, is poorly understood. In this work, we chose the growth of NaO2 in Na-O2 batteries as a model system and show that there is a strong correlation between the electrolyte salt concentration and the NaO2 crystal size. With a combination of experiments and theory, we argue that the correlation is a direct manifestation of the strong cation-anion interactions leading to decreased crystal growth rate at high salt concentrations. Further, we propose and experimentally demonstrate that cation-coordinating crown molecules are suitable electrochemically stable electrolyte additives that weaken ion-pairing and enhance discharge capacities in metal-oxygen batteries while not negatively affecting their rechargeability.Comment: 13 Pages, 4 Figures, 14 pages of Supplementary Informatio

In vitro influence of stem surface finish and mantle conformity on pressure generation in cemented hip arthroplasty

Background and purpose Under physiological loads, debonded cemented femoral stems have been shown to move within their cement mantle and generate a fluid pump that may facilitate peri-prosthetic osteolysis by pressurizing fluid and circulating wear debris. The long-term physiological loading of rough and polished tapered stems in vitro has shown differences in performance, with greater interface pressures generated by the rough stems. In this study we investigated the individual effects of stem surface finish, degree of mantle wear, and mode of loading on the stem pump mechanism

Oral rehydration versus intravenous therapy for treating dehydration due to gastroenteritis in children: a meta-analysis of randomised controlled trials

BACKGROUND: Despite treatment recommendations from various organizations, oral rehydration therapy (ORT) continues to be underused, particularly by physicians in high-income countries. We conducted a systematic review of randomised controlled trials (RCTs) to compare ORT and intravenous therapy (IVT) for the treatment of dehydration secondary to acute gastroenteritis in children. METHODS: RCTs were identified through MEDLINE, EMBASE, CENTRAL, authors and references of included trials, pharmaceutical companies, and relevant organizations. Screening and inclusion were performed independently by two reviewers in order to identify randomised or quasi-randomised controlled trials comparing ORT and IVT in children with acute diarrhea and dehydration. Two reviewers independently assessed study quality using the Jadad scale and allocation concealment. Data were extracted by one reviewer and checked by a second. The primary outcome measure was failure of rehydration. We analyzed data using standard meta-analytic techniques. RESULTS: The quality of the 14 included trials ranged from 0 to 3 (Jadad score); allocation concealment was unclear in all but one study. Using a random effects model, there was no significant difference in treatment failures (risk difference [RD] 3%; 95% confidence intervals [CI]: 0, 6). The Mantel-Haenzsel fixed effects model gave a significant difference between treatment groups (RD 4%; 95% CI: 2, 5) favoring IVT. Based on the four studies that reported deaths, there were six in the IVT groups and two in ORT. There were no significant differences in total fluid intake at six and 24 hours, weight gain, duration of diarrhea, or hypo/hypernatremia. Length of stay was significantly shorter for the ORT group (weighted mean difference [WMD] -1.2 days; 95% CI: -2.4,-0.02). Phlebitis occurred significantly more often with IVT (number needed to treat [NNT] 33; 95% CI: 25,100); paralytic ileus occurred more often with ORT (NNT 33; 95% CI: 20,100). These results may not be generalizable to children with persistent vomiting. CONCLUSION: There were no clinically important differences between ORT and IVT in terms of efficacy and safety. For every 25 children (95% CI: 20, 50) treated with ORT, one would fail and require IVT. The results support existing practice guidelines recommending ORT as the first course of treatment in appropriate children with dehydration secondary to gastroenteritis

Alpha-band rhythms in visual task performance: phase-locking by rhythmic sensory stimulation

Oscillations are an important aspect of neuronal activity. Interestingly, oscillatory patterns are also observed in behaviour, such as in visual performance measures after the presentation of a brief sensory event in the visual or another modality. These oscillations in visual performance cycle at the typical frequencies of brain rhythms, suggesting that perception may be closely linked to brain oscillations. We here investigated this link for a prominent rhythm of the visual system (the alpha-rhythm, 8-12 Hz) by applying rhythmic visual stimulation at alpha-frequency (10.6 Hz), known to lead to a resonance response in visual areas, and testing its effects on subsequent visual target discrimination. Our data show that rhythmic visual stimulation at 10.6 Hz: 1) has specific behavioral consequences, relative to stimulation at control frequencies (3.9 Hz, 7.1 Hz, 14.2 Hz), and 2) leads to alpha-band oscillations in visual performance measures, that 3) correlate in precise frequency across individuals with resting alpha-rhythms recorded over parieto-occipital areas. The most parsimonious explanation for these three findings is entrainment (phase-locking) of ongoing perceptually relevant alpha-band brain oscillations by rhythmic sensory events. These findings are in line with occipital alpha-oscillations underlying periodicity in visual performance, and suggest that rhythmic stimulation at frequencies of intrinsic brain-rhythms can be used to reveal influences of these rhythms on task performance to study their functional roles

Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family

An updated report on the incidence and epidemiological trends of keratinocyte cancers in the United Kingdom 2013-2018

Introduction: The most common cancers in the UK are keratinocyte cancers (KCs): the combined term for basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (cSCCs). Registration of KC is challenging due to high numbers and multiplicity of tumours per person. Methods: We provide an updated report on the descriptive epidemiology of trends in KC incidence for the resident populations of UK countries (England, Northern Ireland, Scotland and Wales) using population-based cancer registry and pathology report data, 2013-18. Results: Substantial increases in cSCC incidence in England, Scotland and Northern Ireland can be detected for the period of 2013-18, and the incidence of cSCC also increased in Wales from 2016 to 2018. In contrast, however, the pattern of annual change in the incidence of BCC across the nations differs. In England, the incidence of BCC declined slightly from 2016 to 2018, however, the overall trend across 2013-18 is not statistically significant. In Scotland, the incidence of BCC shows some variability, declining in 2017 before increasing in 2018, and the overall trend across 2013-18 was also not statistically significant. In Northern Ireland, the incidence of BCC increased significantly over the study period, and in Wales, the incidence of BCC increased from 2016 to 2018. One in five people will develop non-melanoma skin cancers (NMSC) in their lifetime in England. This estimate is much higher than the lifetime risk of melanoma (1 in 36 males and 1 in 47 females born after 1960 in the UK), which further highlights the burden of the disease and importance of early prevention strategies. Conclusions: We highlight how common these tumours are by publishing the first ever lifetime incidence of NMSC. Additionally, the first time reporting of the age standardised incidence of KC in Wales further confirms the scale of the disease burden posed by these cancers in the UK. With approximately one in five people developing NMSC in their lifetime, optimisation of skin cancer prevention, management and research are essential