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

Deep mining of oxysterols and cholestenoic acids in human plasma and cerebrospinal fluid: Quantification using isotope dilution mass spectrometry

Both plasma and cerebrospinal fluid (CSF) are rich in cholesterol and its metabolites. Here we describe in detail a methodology for the identification and quantification of multiple sterols including oxysterols and sterol-acids found in these fluids. The method is translatable to any laboratory with access to liquid chromatography – tandem mass spectrometry. The method exploits isotope-dilution mass spectrometry for absolute quantification of target metabolites. The method is applicable for semi-quantification of other sterols for which isotope labelled surrogates are not available and approximate quantification of partially identified sterols. Values are reported for non-esterified sterols in the absence of saponification and total sterols following saponification. In this way absolute quantification data is reported for 17 sterols in the NIST SRM 1950 plasma along with semi-quantitative data for 8 additional sterols and approximate quantification for one further sterol. In a pooled (CSF) sample used for internal quality control, absolute quantification was performed on 10 sterols, semi-quantification on 9 sterols and approximate quantification on a further three partially identified sterols. The value of the method is illustrated by confirming the sterol phenotype of a patient suffering from ACOX2 deficiency, a rare disorder of bile acid biosynthesis, and in a plasma sample from a patient suffering from cerebrotendinous xanthomatosis, where cholesterol 27-hydroxylase is deficient

First measurement of direct f0(980)f_0(980) photoproduction on the proton

We report on the results of the first measurement of exclusive $f_0(980)$ meson photoproduction on protons for $E_\gamma=3.0 - 3.8$ GeV and $-t = 0.4-1.0$ GeV$^2$. Data were collected with the CLAS detector at the Thomas Jefferson National Accelerator Facility. The resonance was detected via its decay in the $\pi^+ \pi^-$ channel by performing a partial wave analysis of the reaction $\gamma p \to p \pi^+ \pi^-$. Clear evidence of the $f_0(980)$ meson was found in the interference between $P$ and $S$ waves at $M_{\pi^+ \pi^-}\sim 1$ GeV. The $S$-wave differential cross section integrated in the mass range of the $f_0(980)$ was found to be a factor of 50 smaller than the cross section for the $\rho$ meson. This is the first time the $f_0(980)$ meson has been measured in a photoproduction experiment

Measurement of the Mass Splittings between the bbˉχb,J(1P)b\bar{b}\chi_{b,J}(1P) States

We present new measurements of photon energies and branching fractions for the radiative transitions: Upsilon(2S)->gamma+chi_b(J=0,1,2). The masses of the chi_b states are determined from the measured radiative photon energies. The ratio of mass splittings between the chi_b substates, r==(M[J=2]-M[J=1])/(M[J=1]-M[J=0]) with M the chi_b mass, provides information on the nature of the bbbar confining potential. We find r(1P)=0.54+/-0.02+/-0.02. This value is in conflict with the previous world average, but more consistent with the theoretical expectation that r(1P)<r(2P); i.e., that this mass splittings ratio is smaller for the chi_b(1P) triplet than for the chi_b(2P) triplet.Comment: 11 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

School-based prevention for adolescent Internet addiction: prevention is the key. A systematic literature review

Adolescents’ media use represents a normative need for information, communication, recreation and functionality, yet problematic Internet use has increased. Given the arguably alarming prevalence rates worldwide and the increasingly problematic use of gaming and social media, the need for an integration of prevention efforts appears to be timely. The aim of this systematic literature review is (i) to identify school-based prevention programmes or protocols for Internet Addiction targeting adolescents within the school context and to examine the programmes’ effectiveness, and (ii) to highlight strengths, limitations, and best practices to inform the design of new initiatives, by capitalizing on these studies’ recommendations. The findings of the reviewed studies to date presented mixed outcomes and are in need of further empirical evidence. The current review identified the following needs to be addressed in future designs to: (i) define the clinical status of Internet Addiction more precisely, (ii) use more current psychometrically robust assessment tools for the measurement of effectiveness (based on the most recent empirical developments), (iii) reconsider the main outcome of Internet time reduction as it appears to be problematic, (iv) build methodologically sound evidence-based prevention programmes, (v) focus on skill enhancement and the use of protective and harm-reducing factors, and (vi) include IA as one of the risk behaviours in multi-risk behaviour interventions. These appear to be crucial factors in addressing future research designs and the formulation of new prevention initiatives. Validated findings could then inform promising strategies for IA and gaming prevention in public policy and education

Beam Spin Asymmetries in DVCS with CLAS at 4 .8 GeV

We report measurements of the beam spin asymmetry in Deeply Virtual Compton Scattering (DVCS) at an electron beam energy of 4.8 GeV using the CLAS detector at the Thomas Jefferson National Accelerator Facility. The DVCS beam spin asymmetry has been measured in a wide range of kinematics, 1(GeV/c)$^2$ $<Q^2<2.8$(GeV/c)$^2$, $0.12<x_B<0.48$, and 0.1 (GeV/c)$^2$ $<-t<0.8$(GeV/c)$^2$, using the reaction \pEpX. The number of H$(e,e^{\prime}\gamma p)$ and H$(e,e^{\prime}\pi^0 p)$ events are separated in each $(Q^2,x_B,t)$ bin by a fit to the line shape of the H$(e,e^{\prime}p)X$ $M_x^2$ distribution. The validity of the method was studied in detail using experimental and simulated data. It was shown, that with the achieved missing mass squared resolution and the available statistics, the separation of DVCS-BH and $\pi^0$ events can reliably be done with less than 5% uncertainty. The $Q^2$- and $t$-dependences of the $\sin\phi$ moments of the asymmetry are extracted and compared with theoretical calculations

Phase II randomised discontinuation trial of brivanib in patients with advanced solid tumours

Background: Brivanib is a selective inhibitor of vascular endothelial growth factor and fibroblast growth factor (FGF) signalling. We performed a phase II randomised discontinuation trial of brivanib in 7 tumour types (soft-tissue sarcomas [STS], ovarian cancer, breast cancer, pancreatic cancer, non-small-cell lung cancer [NSCLC], gastric/esophageal cancer and transitional cell carcinoma [TCC]). Patients and methods: During a 12-week open-label lead-in period, patients received brivanib 800 mg daily and were evaluated for FGF2 status by immunohistochemistry. Patients with stable disease at week 12 were randomised to brivanib or placebo. A study steering committee evaluated week 12 response to determine if enrolment in a tumour type would continue. The primary objective was progression-free survival (PFS) for brivanib versus placebo in patients with FGF2-positive tumours. Results: A total of 595 patients were treated, and stable disease was observed at the week 12 randomisation point in all tumour types. Closure decisions were made for breast cancer, pancreatic cancer, NSCLC, gastric cancer and TCC. Criteria for expansion were met for STS and ovarian cancer. In 53 randomised patients with STS and FGF2-positive tumours, the median PFS was 2.8 months for brivanib and 1.4 months for placebo (hazard ratio [HR]: 0.58, p = 0.08). For all randomised patients with sarcomas, the median PFS was 2.8 months (95% confidence interval [CI]: 1.4–4.0) for those treated with brivanib compared with 1.4 months (95% CI: 1.3–1.6) for placebo (HR = 0.64, 95% CI: 0.38–1.07; p = 0.09). In the 36 randomised patients with ovarian cancer and FGF2-positive tumours, the median PFS was 4.0 (95% CI: 2.6–4.2) months for brivanib and 2.0 months (95% CI: 1.2–2.7) for placebo (HR: 0.56, 95% CI: 0.26–1.22). For all randomised patients with ovarian cancer, the median PFS in those randomised to brivanib was 4.0 months (95% CI: 2.6–4.2) and was 2.0 months (95% CI: 1.2–2.7) in those randomised to placebo (HR = 0.54, 95% CI: 0.25–1.17; p = 0.11). Conclusion: Brivanib demonstrated activity in STS and ovarian cancer with an acceptable safety profile. FGF2 expression, as defined in the protocol, is not a predictive biomarker of the efficacy of brivanib

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele