Preoperative nutrition intervention in patients undergoing resection for upper gastrointestinal cancer: Results from the multi-centre nourish point prevalence study:Results from the Multi-Centre NOURISH Point Prevalence Study

Background: Preoperative nutrition intervention is recommended prior to upper gastrointestinal (UGI) cancer resection; however, there is limited understanding of interventions received in current clinical practice. This study investigated type and frequency of preoperative dietetics intervention and nutrition support received and clinical and demographic factors associated with receipt of intervention. Associations between intervention and preoperative weight loss, surgical length of stay (LOS), and complications were also investigated. Methods: The NOURISH Point Prevalence Study was conducted between September 2019 and May 2020 across 27 Australian tertiary centres. Subjective global assessment and weight were performed within 7 days of admission. Patients reported on preoperative dietetics and nutrition intervention, and surgical LOS and complications were recorded. Results: Two-hundred patients participated (59% male, mean (standard deviation) age 67 (10)). Sixty percent had seen a dietitian preoperatively, whilst 50% were receiving nutrition support (92% oral nutrition support (ONS)). Patients undergoing pancreatic surgery were less likely to receive dietetics intervention and nutrition support than oesophageal or gastric surgeries (p 2 weeks had lower mean (SD) percentage weight loss than those who did not (1.2 (1.8) vs. 2.9 (3.4), p = 0.001). In malnourished patients, total dietetics appointments ≥3 was independently associated with reduced surgical complications (odds ratio 0.2, 95% confidence interval (CI) 0.1, 0.9, p = 0.04), and ONS >2 weeks was associated with reduced LOS (regression coefficient −7.3, 95% CI −14.3, −0.3, p = 0.04). Conclusions: Despite recommendations, there are low rates of preoperative dietetics consultation and nutrition support in this population, which are associated with increased preoperative weight loss and risk of increased LOS and complications in malnourished patients. The results of this study provide insights into evidence–practice gaps for improvement and data to support further research regarding optimal methods of preoperative nutrition support

Transition from localized to extended eigenstates in the ensemble of power-law random banded matrices

We study statistical properties of the ensemble of large $N\times N$ random matrices whose entries $H_{ij}$ decrease in a power-law fashion $H_{ij}\sim|i-j|^{-\alpha}$. Mapping the problem onto a nonlinear $\sigma-$model with non-local interaction, we find a transition from localized to extended states at $\alpha=1$. At this critical value of $\alpha$ the system exhibits multifractality and spectral statistics intermediate between the Wigner-Dyson and Poisson one. These features are reminiscent of those typical for the mobility edge of disordered conductors. We find a continuous set of critical theories at $\alpha=1$, parametrized by the value of the coupling constant of the $\sigma-$model. At $\alpha>1$ all states are expected to be localized with integrable power-law tails. At the same time, for $1<\alpha<3/2$ the wave packet spreading at short time scale is superdiffusive: $\langle |r|\rangle\sim t^{\frac{1}{2\alpha-1}}$, which leads to a modification of the Altshuler-Shklovskii behavior of the spectral correlation function. At $1/2<\alpha<1$ the statistical properties of eigenstates are similar to those in a metallic sample in $d=(\alpha-1/2)^{-1}$ dimensions. Finally, the region $\alpha<1/2$ is equivalent to the corresponding Gaussian ensemble of random matrices $(\alpha=0)$. The theoretical predictions are compared with results of numerical simulations.Comment: 19 pages REVTEX, 4 figure

Negative impacts of invasive predators used as biological control agents against the pest snail Lissachatina fulica: the snail Euglandina ‘rosea’ and the flatworm Platydemus manokwari

Since 1955 snails of the Euglandina rosea species complex and Platydemus manokwari flatworms were widely introduced in attempted biological control of giant African snails (Lissachatina fulica) but have been implicated in the mass extinction of Pacific island snails. We review the histories of the 60 introductions and their impacts on L. fulica and native snails. Since 1993 there have been unofficial releases of Euglandina within island groups. Only three official P. manokwari releases took place, but new populations are being recorded at an increasing rate, probably because of accidental introduction. Claims that these predators controlled L. fulica cannot be substantiated; in some cases pest snail declines coincided with predator arrival but concomitant declines occurred elsewhere in the absence of the predator and the declines in some cases were only temporary. In the Hawaiian Islands, although there had been some earlier declines of native snails, the Euglandina impacts on native snails are clear with rapid decline of many endemic Hawaiian Achatinellinae following predator arrival. In the Society Islands, Partulidae tree snail populations remained stable until Euglandina introduction, when declines were extremely rapid with an exact correspondence between predator arrival and tree snail decline. Platydemus manokwari invasion coincides with native snail declines on some islands, notably the Ogasawara Islands of Japan, and its invasion of Florida has led to mass mortality of Liguus spp. tree snails. We conclude that Euglandina and P. manokwari are not effective biocontrol agents, but do have major negative effects on native snail faunas. These predatory snails and flatworms are generalist predators and as such are not suitable for biological control

Yeast Based Small Molecule Screen for Inhibitors of SARS-CoV

Severe acute respiratory coronavirus (SARS-CoV) emerged in 2002, resulting in roughly 8000 cases worldwide and 10% mortality. The animal reservoirs for SARS-CoV precursors still exist and the likelihood of future outbreaks in the human population is high. The SARS-CoV papain-like protease (PLP) is an attractive target for pharmaceutical development because it is essential for virus replication and is conserved among human coronaviruses. A yeast-based assay was established for PLP activity that relies on the ability of PLP to induce a pronounced slow-growth phenotype when expressed in S. cerevisiae. Induction of the slow-growth phenotype was shown to take place over a 60-hour time course, providing the basis for conducting a screen for small molecules that restore growth by inhibiting the function of PLP. Five chemical suppressors of the slow-growth phenotype were identified from the 2000 member NIH Diversity Set library. One of these, NSC158362, potently inhibited SARS-CoV replication in cell culture without toxic effects on cells, and it specifically inhibited SARS-CoV replication but not influenza virus replication. The effect of NSC158362 on PLP protease, deubiquitinase and anti-interferon activities was investigated but the compound did not alter these activities. Another suppressor, NSC158011, demonstrated the ability to inhibit PLP protease activity in a cell-based assay. The identification of these inhibitors demonstrated a strong functional connection between the PLP-based yeast assay, the inhibitory compounds, and SARS-CoV biology. Furthermore the data with NSC158362 suggest a novel mechanism for inhibition of SARS-CoV replication that may involve an unknown activity of PLP, or alternatively a direct effect on a cellular target that modifies or bypasses PLP function in yeast and mammalian cells

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

CD14 Signaling Restrains Chronic Inflammation through Induction of p38-MAPK/SOCS-Dependent Tolerance

Current thinking emphasizes the primacy of CD14 in facilitating recognition of microbes by certain TLRs to initiate pro-inflammatory signaling events and the importance of p38-MAPK in augmenting such responses. Herein, this paradigm is challenged by demonstrating that recognition of live Borrelia burgdorferi not only triggers an inflammatory response in the absence of CD14, but one that is, in part, a consequence of altered PI3K/AKT/p38-MAPK signaling and impaired negative regulation of TLR2. CD14 deficiency results in increased localization of PI3K to lipid rafts, hyperphosphorylation of AKT, and reduced activation of p38. Such aberrant signaling leads to decreased negative regulation by SOCS1, SOCS3, and CIS, thereby compromising the induction of tolerance in macrophages and engendering more severe and persistent inflammatory responses to B. burgdorferi. Importantly, these altered signaling events and the higher cytokine production observed can be mimicked through shRNA and pharmacological inhibition of p38 activity in CD14-expressing macrophages. Perturbation of this CD14/p38-MAPK-dependent immune regulation may underlie development of infectious chronic inflammatory syndromes

The United States COVID-19 Forecast Hub dataset

Academic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident cases, incident hospitalizations, incident deaths, and cumulative deaths due to COVID-19 at county, state, and national, levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages

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

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data