Predicting the dispersal of SARS-CoV-2 RNA from the wastewater treatment plant to the coast

Viral pathogens including SARS-CoV-2 RNA have been detected in wastewater treatment effluent, and untreated sewage overflows, that pose an exposure hazard to humans. We assessed whether SARS-CoV-2 RNA was likely to have been present in detectable quantities in UK rivers and estuaries during the first wave of the Covid-19 pandemic. We simulated realistic viral concentrations parameterised on the Camel and Conwy catchments (UK) and their populations, showing detectable SARS-CoV-2 RNA concentrations for untreated but not for treated loading, but also being contingent on viral decay, hydrology, catchment type/shape, and location. Under mean or low river flow conditions, viral RNA concentrated within the estuaries allowing for viral build-up and caused a lag by up to several weeks between the peak in community infections and the viral peak in the environment. There was an increased hazard posed by SARS-CoV-2 RNA with a T90 decay rate >24 h, as the estuarine build-up effect increased. High discharge events transported the viral RNA downstream and offshore, increasing the exposure risk to coastal bathing waters and shellfisheries – although dilution in this case reduced viral concentrations well below detectable levels. Our results highlight the sensitivity of exposure to viral pathogens downstream of wastewater treatment, across a range of viral loadings and catchment characteristics – with implications to environmental surveillance

ESPEN guideline: Clinical nutrition in surgery.

Early oral feeding is the preferred mode of nutrition for surgical patients. Avoidance of any nutritional therapy bears the risk of underfeeding during the postoperative course after major surgery. Considering that malnutrition and underfeeding are risk factors for postoperative complications, early enteral feeding is especially relevant for any surgical patient at nutritional risk, especially for those undergoing upper gastrointestinal surgery. The focus of this guideline is to cover nutritional aspects of the Enhanced Recovery After Surgery (ERAS) concept and the special nutritional needs of patients undergoing major surgery, e.g. for cancer, and of those developing severe complications despite best perioperative care. From a metabolic and nutritional point of view, the key aspects of perioperative care include: • integration of nutrition into the overall management of the patient • avoidance of long periods of preoperative fasting • re-establishment of oral feeding as early as possible after surgery • start of nutritional therapy early, as soon as a nutritional risk becomes apparent • metabolic control e.g. of blood glucose • reduction of factors which exacerbate stress-related catabolism or impair gastrointestinal function • minimized time on paralytic agents for ventilator management in the postoperative period • early mobilisation to facilitate protein synthesis and muscle function The guideline presents 37 recommendations for clinical practice

A comparison of precipitation and filtration-based SARS-CoV-2 recovery methods and the influence of temperature, turbidity, and surfactant load in urban wastewater

Wastewater-based epidemiology (WBE) has become a complimentary surveillance tool during the SARS-CoV-2 pandemic. Viral concentration methods from wastewater are still being optimised and compared, whilst viral recovery under different wastewater characteristics and storage temperatures remains poorly understood. Using urban wastewater samples, we tested three viral concentration methods; polyethylene glycol precipitation (PEG), ammonium sulphate precipitation (AS), and CP select™ InnovaPrep® (IP) ultrafiltration. We found no major difference in SARS-CoV-2 and faecal indicator virus (crAssphage) recovery from wastewater samples (n = 46) using these methods, PEG slightly (albeit non-significantly), outperformed AS and IP for SARS-CoV-2 detection, as a higher genome copies per litre (gc/l) was recorded for a larger proportion of samples. Next generation sequencing of 8 paired samples revealed non-significant differences in the quality of data between AS and IP, though IP data quality was slightly better and less variable. A controlled experiment assessed the impact of wastewater suspended solids (turbidity; 0–400 NTU), surfactant load (0–200 mg/l), and storage temperature (5–20 °C) on viral recovery using the AS and IP methods. SARS-CoV-2 recoveries were >20% with AS and  0.05), whilst surfactant and storage temperature combined were significant negative correlates (p < 0.001 and p < 0.05, respectively). In conclusion, our results show that choice of methodology had small effect on viral recovery of SARS-CoV-2 and crAssphage in wastewater samples within this study. In contrast, sample turbidity, storage temperature, and surfactant load did affect viral recovery, highlighting the need for careful consideration of the viral concentration methodology used when working with wastewater samples

Physical Model for Plaque Action in the Tooth-Plaque-Saliva System

A physical model describing the interrelationships of demineralization, remineralization, plaque thickness, glucose levels, and plaque enzymatic activity was presented. Selection of constants and variations of the parameters were kept in the range of possible in vivo situations. The results of calculations were discussed and correlated with the results of in vivo studies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66483/2/10.1177_00220345700490013001.pd

Indications of Linkage and Association of Gilles de la Tourette Syndrome in Two Independent Family Samples: 17q25 Is a Putative Susceptibility Region

Gilles de la Tourette syndrome (GTS) is characterized by multiple motor and phonic tics and high comorbidity rates with other neurobehavioral disorders. It is hypothesized that frontal-subcortical pathways and a complex genetic background are involved in the etiopathogenesis of the disorder. The genetic basis of GTS remains elusive. However, several genomic regions have been implicated. Among them, 17q25 appears to be of special interest, as suggested by various independent investigators. In the present study, we explored the possibility that 17q25 contributes to the genetic component of GTS. The initial scan of chromosome 17 performed on two large pedigrees provided a nonparametric LOD score of 2.41 near D17S928. Fine mapping with 17 additional microsatellite markers increased the peak to 2.61 (P=.002). The original families, as well as two additional pedigrees, were genotyped for 25 single-nucleotide polymorphisms (SNPs), with a focus on three genes in the indicated region that could play a role in the development of GTS, on the basis of their function and expression profile. Multiple three-marker haplotypes spanning all three genes studied provided highly significant association results (P<.001). An independent sample of 96 small families with one or two children affected with GTS was also studied. Of the 25 SNPs, 3 were associated with GTS at a statistically significant level. The transmission/disequilibrium test for a three-site haplotype moving window again provided multiple positive results. The background linkage disequilibrium (LD) of the region was studied in eight populations of European origin. A complicated pattern was revealed, with the pairwise tests producing unexpectedly high LD values at the telomeric TBCD gene. In conclusion, our findings warrant the further investigation of 17q25 as a candidate susceptibility region for GTS

Early- Onset Stroke and Vasculopathy Associated with Mutations in ADA2

Adenosine deaminase 2 (ADA2) is an enzyme involved in purine metabolism and a growth factor that influences the development of endothelial cells and leukocytes. This study shows that defects in ADA2 cause recurrent fevers, vascular pathologic features, and mild immunodeficiency. Patients with autoinflammatory disease sometimes present with clinical findings that encompass multiple organ systems.(1) Three unrelated children presented to the National Institutes of Health (NIH) Clinical Center with intermittent fevers, recurrent lacunar strokes, elevated levels of acute-phase reactants, livedoid rash, hepatosplenomegaly, and hypogammaglobulinemia. Collectively, these findings do not easily fit with any of the known inherited autoinflammatory diseases. Hereditary or acquired vascular disorders can have protean manifestations yet be caused by mutations in a single gene. Diseases such as the Aicardi-Goutieres syndrome,(2),(3) polypoidal choroidal vasculopathy,(4) sickle cell anemia,(5) livedoid vasculopathy,(6) and the small-vessel vasculitides(7),(8) are examples of systemic ...</p

Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts

Background Genetic factors influence chronic obstructive pulmonary disease (COPD) risk, but the individual variants that have been identified have small effects. We hypothesised that a polygenic risk score using additional variants would predict COPD and associated phenotypes. Methods We constructed a polygenic risk score using a genome-wide association study of lung function (FEV1 and FEV1/forced vital capacity [FVC]) from the UK Biobank and SpiroMeta. We tested this polygenic risk score in nine cohorts of multiple ethnicities for an association with moderate-to-severe COPD (defined as FEV1/FVC <0·7 and FEV1 <80% of predicted). Associations were tested using logistic regression models, adjusting for age, sex, height, smoking pack-years, and principal components of genetic ancestry. We assessed predictive performance of models by area under the curve. In a subset of studies, we also studied quantitative and qualitative CT imaging phenotypes that reflect parenchymal and airway pathology, and patterns of reduced lung growth. Findings The polygenic risk score was associated with COPD in European (odds ratio [OR] per SD 1·81 [95% CI 1·74–1·88] and non-European (1·42 [1·34–1·51]) populations. Compared with the first decile, the tenth decile of the polygenic risk score was associated with COPD, with an OR of 7·99 (6·56–9·72) in European ancestry and 4·83 (3·45–6·77) in non-European ancestry cohorts. The polygenic risk score was superior to previously described genetic risk scores and, when combined with clinical risk factors (ie, age, sex, and smoking pack-years), showed improved prediction for COPD compared with a model comprising clinical risk factors alone (AUC 0·80 [0·79–0·81] vs 0·76 [0·75–0·76]). The polygenic risk score was associated with CT imaging phenotypes, including wall area percent, quantitative and qualitative measures of emphysema, local histogram emphysema patterns, and destructive emphysema subtypes. The polygenic risk score was associated with a reduced lung growth pattern. Interpretation A risk score comprised of genetic variants can identify a small subset of individuals at markedly increased risk for moderate-to-severe COPD, emphysema subtyp

Synaptic processes and immune-related pathways implicated in Tourette syndrome.

Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS

Exotic ρ±ρ0\rho^\pm\rho^0 state photoproduction

It is shown that the list of unusual mesons planned for a careful study in photoproduction can be extended by the exotic states $X^\pm(1600)$ with $I^G(J ^{PC})=2^+(2^{++})$ which should be looked for in the $\rho^\pm\rho^0$ decay channels in the reactions $\gamma N\to\rho^\pm\rho^0N$ and $\gamma N\to\rho^\pm \rho^0\Delta$. The full classification of the $\rho^\pm\rho^0$ states by their quantum numbers is presented. A simple model for the spin structure of the $\gamma p\to f_2(1270)p$, $\gamma p\to a^0_2(1320)p$, and $\gamma N\to X^\pm (N, \Delta)$ reaction amplitudes is formulated and the tentative estimates of the corresponding cross sections at the incident photon energy $E_\gamma\approx 6$ GeV are obtained: $\sigma(\gamma p\to f_2(1270)p)\approx0.12$ $\mu$b, $\sigma(\gamma p\to a^0_2(1320)p)\approx0.25$ $\mu$b, $\sigma(\gamma N\to X^\pm N\to\rho^\pm\rho^0N)\approx0.018$ $\mu$b, and $\sigma(\gamma p\to X^-\Delta^{++ }\to\rho^-\rho^0\Delta^{++})\approx0.031$ $\mu$b. The problem of the $X^\pm$ signal extraction from the natural background due to the other $\pi^\pm\pi^0 \pi^+\pi^-$ production channels is discussed. In particular the estimates are presented for the $\gamma p\to h_1(1170)\pi^+n$, $\gamma p\to\rho'^{+}n\to \pi^+\pi^0\pi^+\pi^-n$, and $\gamma p\to\omega\rho^0p$ reaction cross sections. Our main conclusion is that the search for the exotic $X^\pm(2^+(2^{++}))$ states is quite feasible at JEFLAB facility. The expected yield of the $\gamma N\to X^\pm N\to\rho^\pm\rho^0N$ events in a 30-day run at the 100% detection efficiency approximates $2.8\times10^6$ events.Comment: 19 pages, revtex, 1 figure in postscipt, some comments and references added, a few minor typos corrected, to be published in Phys. Rev.