A synthetic model simulator for intracranial aneurysm clipping: validation of the UpSurgeOn AneurysmBox

Background and objectives: In recent decades, the rise of endovascular management of aneurysms has led to a significant decline in operative training for surgical aneurysm clipping. Simulation has the potential to bridge this gap and benchtop synthetic simulators aim to combine the best of both anatomical realism and haptic feedback. The aim of this study was to validate a synthetic benchtop simulator for aneurysm clipping (AneurysmBox, UpSurgeOn). Methods: Expert and novice surgeons from multiple neurosurgical centres were asked to clip a terminal internal carotid artery aneurysm using the AneurysmBox. Face and content validity were evaluated using Likert scales by asking experts to complete a post-task questionnaire. Construct validity was evaluated by comparing expert and novice performance using the modified Objective Structured Assessment of Technical Skills (mOSATS), developing a curriculum-derived assessment of Specific Technical Skills (STS), and measuring the forces exerted using a force-sensitive glove. Results: Ten experts and eighteen novices completed the task. Most experts agreed that the brain looked realistic (8/10), but far fewer agreed that the brain felt realistic (2/10). Half the expert participants (5/10) agreed that the aneurysm clip application task was realistic. When compared to novices, experts had a significantly higher median mOSATS (27 vs. 14.5; p < 0.01) and STS score (18 vs. 9; p < 0.01); the STS score was strongly correlated with the previously validated mOSATS score (p < 0.01). Overall, there was a trend towards experts exerting a lower median force than novices, however, these differences were not statistically significant (3.8 N vs. 4.0 N; p = 0.77). Suggested improvements for the model included reduced stiffness and the addition of cerebrospinal fluid (CSF) and arachnoid mater. Conclusion: At present, the AneurysmBox has equivocal face and content validity, and future versions may benefit from materials that allow for improved haptic feedback. Nonetheless, it has good construct validity, suggesting it is a promising adjunct to training

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Specific Roles of Akt iso Forms in Apoptosis and Axon Growth Regulation in Neurons

Akt is a member of the AGC kinase family and consists of three isoforms. As one of the major regulators of the class I PI3 kinase pathway, it has a key role in the control of cell metabolism, growth, and survival. Although it has been extensively studied in the nervous system, we have only a faint knowledge of the specific role of each isoform in differentiated neurons. Here, we have used both cortical and hippocampal neuronal cultures to analyse their function. We characterized the expression and function of Akt isoforms, and some of their substrates along different stages of neuronal development using a specific shRNA approach to elucidate the involvement of each isoform in neuron viability, axon development, and cell signalling. Our results suggest that three Akt isoforms show substantial compensation in many processes. However, the disruption of Akt2 and Akt3 significantly reduced neuron viability and axon length. These changes correlated with a tendency to increase in active caspase 3 and a decrease in the phosphorylation of some elements of the mTORC1 pathway. Indeed, the decrease of Akt2 and more evident the inhibition of Akt3 reduced the expression and phosphorylation of S6. All these data indicate that Akt2 and Akt3 specifically regulate some aspects of apoptosis and cell growth in cultured neurons and may contribute to the understanding of mechanisms of neuron death and pathologies that show deregulated growth

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

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Not AvailableStudies to evaluate the release threshold level of potassium in Vertisols (shrink-swell soils) in different agroecological regions of India and how that may help in K fertility interpretations are rare. Thus the objectives of this study were (i) to evaluate the K status of Vertisols through release threshold levels and (ii) to relate the findings with soil K release and fertilizer management. Three established soil series samples were collected from Vertisols of different agro-ecological regions of India. Release threshold level (RTL) was assessed after equilibrating soil with 0.01M CaCl2 solution having series of soil: solution ratio, after which the remaining amount of exchangeable K was extracted with 1 N NH4OAc (pH 7). Total amount of K extracted (KT=K desorbed in CaCl2 solution plus K extracted with 1 N NH4OAc) remained more or less constant with decreasing K-level up to a certain value (say threshold value) below which KT increased sharply indicating K release from non-labile form. The threshold value in terms of K concentrations (Release Threshold Concentration) of Panjari, Nagpur, Maharashtra (Typic Haplusterts, Sub-humid dry), Teligi, Bellary, Karnataka (Sodic Haplusterts, Semi-arid dry) and Kheri, Jabalpur, Madhya Pradesh (Typic Haplusterts, Sub-humid moist) soils were 0.044–0.049, 0.034–0.062 and 0.043–0.11 mm, respectively. The high release threshold K levels in terms of concentration and activity ratio (AR) were observed in soils of Teligi and Kheri series as compared to soils of Panjari series due to high content of trioctahedral mica in the former two soils. The relationships between clay minerals, release threshold level, exchangeable potassium and non-exchangeable potassium determined by 1 N HNO3 and sodium tetra-phenyl borate (NaBPh4) have been discussed.Not Availabl

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Not AvailableStudies to evaluate the release threshold level of potassium in Vertisols (shrink-swell soils) in different agro-ecological regions of India and how that may help in K fertility interpretations are rare. Thus the objectives of this study were (i) to evaluate the K status of Vertisols through release threshold levels and (ii) to relate the findings with soil K release and fertilizer management. Three established soil series samples were collected from Vertisols of different agro-ecological regions of India. Release threshold level (RTL) was assessed after equilibrating soil with 0.01M CaCl2 solution having series of soil: solution ratio, after which the remaining amount of exchangeable K was extracted with 1N NH4OAc (pH 7). Total amount of K extracted (KT = K desorbed in CaCl2 solution plus K extracted with 1 N NH4OAc) remained more or less constant with decreasing K-level up to a certain value ( say threshold value) below which KT increased sharply indicating K release from non-labile form. The threshold value in terms of K concentrations (Release Threshold Concentration) of Panjari, Nagpur, Maharashtra (TypicHaplusterts, Sub-humid dry), Teligi, Bellary, Karnataka (SodicHaplusterts, Semi-arid dry) and Kheri, Jabalpur, Madhya Pradesh (TypicHaplusterts, Sub-humid moist) soils were 0.044 – 0.049, 0.034 – 0.062 and 0.043 – 0.11 m M, respectively. The high release threshold K levels in terms of concentration and activity ratio (AR) were observed in soils of Teligi and Kheri series as compared to soils of Panjari series due to high content of trioctahedral mica in the former two soils. The relationships between clay minerals, release threshold level, exchangeable potassium and non-exchangeable potassium determined by 1 N HNO3 and sodium tetra-phenylborate (NaBPh4) have been discussed.Not Availabl

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Not AvailableStudies to evaluate the release threshold level of potassium in Vertisols (shrink-swell soils) in different agro-ecological regions of India and how that may help in K fertility interpretations are rare. Thus the objectives of this study were (i) to evaluate the K status of Vertisols through release threshold levels and (ii) to relate the findings with soil K release and fertilizer management. Three established soil series samples were collected from Vertisols of different agro-ecological regions of India. Release threshold level (RTL) was assessed after equilibrating soil with 0.01 M CaCl2 solution having series of soil: solution ratio, after which the remaining amount of exchangeable K was extracted with 1 N NH4OAc (pH 7). Total amount of K extracted (KT = K desorbed in CaCl2 solution plus K extracted with 1 N NH4OAc) remained more or less constant with decreasing K-level up to a certain value (say threshold value) below which KT increased sharply indicating K release from non-labile form. The threshold value in terms of K concentrations (Release Threshold Concentration) of Panjari, Nagpur, Maharashtra (Typic Haplusterts, Sub-humid dry), Teligi, Bellary, Karnataka (Sodic Haplusterts, Semi-arid dry) and Kheri, Jabalpur, Madhya Pradesh (Typic Haplusterts, Sub-humid moist) soils were 0.044–0.049, 0.034–0.062 and 0.043–0.11 mm, respectively. The high release threshold K levels in terms of concentration and activity ratio (AR) were observed in soils of Teligi and Kheri series as compared to soils of Panjari series due to high content of trioctahedral mica in the former two soils. The relationships between clay minerals, release threshold level, exchangeable potassium and non-exchangeable potassium determined by 1 N HNO3 and sodium tetra-phenyl borate (NaBPh4) have been discussed.Not Availabl