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Background. Encephalitis continues to result in substantial morbidity and mortality worldwide. Advances in diagnosis and management have been limited, in part, by a lack of consensus on case definitions, standardized diagnostic approaches, and priorities for research. Methods. In March 2012, the International Encephalitis Consortium, a committee begun in 2010 with members worldwide, held a meeting in Atlanta to discuss recent advances in encephalitis and to set priorities for future study. Results. We present a consensus document that proposes a standardized case definition and diagnostic guidelines for evaluation of adults and children with suspected encephalitis. In addition, areas of research priority, including host genetics and selected emerging infections, are discussed. Conclusions. We anticipate that this document, representing a synthesis of our discussions and supported by literature, will serve as a practical aid to clinicians evaluating patients with suspected encephalitis and will identify key areas and approaches to advance our knowledge of encephalitis.

Current models on solute transport often fail to reproduce discharge‐dependent behavior of solute transport in stream reaches because they rely on the assumption of well‐mixed conditions and fail to account for the complex coupling between in‐stream and subsurface flow. StorAge Selection (SAS) functions describe outflow as a mixture of waters of different ages, providing a framework to overcome the well‐mixed assumption in “traditional” transport models. In this study, we applied SAS functions to model solute transport from 13 slug tracer experiments conducted under varying hydrological conditions in a headwater stream reach. Using SAS function parameters (expressed in units of volume) together with measurements of groundwater (GW) levels and streambed microtopography, we partitioned the total water storage within the study reach into distinct components: advective storage, in‐stream transient storage, tracer‐derived hyporheic storage, and GW level‐derived hyporheic storage. This partitioning assumes that transport processes and subsurface water flow in stream reaches are associated with different storage volumes. We found positive linear relationships between discharge and age‐ranked, advective, and tracer‐derived hyporheic storage. In‐stream transient storage increased with discharge up to 17 L s−1, corresponding to the discharge threshold above which streambed sediments became completely submerged, and declined at higher flows. This pattern likely reflects the contribution of eddies at lower discharge levels and highlights the importance of in‐stream transient storage for solute transport. Our results demonstrate that partitioning the total water storage in a reach–enabled only through applying SAS functions–is essential for understanding and modeling solute transport under varying hydrological conditions.

Background. Encephalitis is a complex syndrome, and its etiology is often not identified. The California Encephalitis Project was initiated in 1998 to identify the causes and further describe the clinical and epidemiologic characteristics of encephalitis. Methods.A standardized report form was used to collect demographic and clinical data. Serum, cerebrospinal fluid, and respiratory specimens were obtained prospectively and were tested for the presence of herpesviruses, arboviruses, enteroviruses, measles, respiratory viruses, Chlamydia species, and Mycoplasma pneumoniae. The association between an identified infection and encephalitis was defined using predetermined, organism-specific criteria for confirmed, probable, or possible causes. Results. From 1998 through 2005, a total of 1570 patients were enrolled. Given the large number of patients, subgroups of patients with similar clinical characteristics and laboratory findings were identified. Ten clinical profiles were described. A confirmed or probable etiologic agent was identified for 16% of cases of encephalitis: 69% of these agents were viral; 20%, bacterial; 7%, prion; 3%, parasitic; and 1%, fungal. An additional 13% of cases had a possible etiology identified. Many of the agents classified as possible causes are suspected but have not yet been definitively demonstrated to cause encephalitis; these agents include M. pneumoniae (n = 96), influenza virus (n = 22), adenovirus (n = 14), Chlamydia species (n = 10), and human metapneumovirus (n = 4). A noninfectious etiology was identified for 8% of cases, and no etiology was found for 63% of cases. Conclusions. Although the etiology of encephalitis remains unknown in most cases, the recognition of discrete clinical profiles among patients with encephalitis should help focus our efforts toward understanding the etiology, pathogenesis, course, and management of this complex syndrome.

The California Encephalitis Project (CEP), established in 1998 to explore encephalitic etiologies, has identified patients with N-methyl-D-aspartate receptor (NMDAR) antibodies, the likely etiology of their encephalitis. This study compares the presentation of such patients to those with viral encephalitis, so that infectious disease clinicians may identify individuals with this treatable disorder. Patients were physician-referred, and standardized forms were used to gather demographic, clinical, and laboratory data. Features of anti-NMDAR+ patients were compared with the viral encephalitides of enteroviral (EV), rabies, and herpes simplex-1 (HSV-1) origins. Sixteen cases with confirmed viral etiologies were all negative on NMDAR antibody testing. Ten anti-NMDAR+ patients were profiled with a median age of 18.5 years (range 11-31 years). None were Caucasian. They had a characteristic progression with prominent psychiatric symptoms, autonomic instability, significant neurologic abnormalities, and seizures. Two had a teratoma, and, of the remaining eight, four had serologic evidence of acute Mycoplasma infection. The clinical and imaging features of anti-NMDAR+ patients served to differentiate this autoimmune disorder from HSV-1, EV, and rabies. Unlike classic paraneoplastic encephalitis, anti-NMDAR encephalitis affects younger patients and is often treatable. The association of NMDAR antibodies in patients with possible Mycoplasma pneumoniae infection warrants further study.

NuRadioMC is a Monte Carlo framework designed to simulate ultra-high energy neutrino detectors that rely on the radio detection method. This method exploits the radio emission generated in the electromagnetic component of a particle shower following a neutrino interaction. NuRadioMC simulates everything from the neutrino interaction in a medium, the subsequent Askaryan radio emission, the propagation of the radio signal to the detector and finally the detector response. NuRadioMC is designed as a modern, modular Python-based framework, combining flexibility in detector design with user-friendliness. It includes a state-of-the-art event generator, an improved modelling of the radio emission, a revisited approach to signal propagation and increased flexibility and precision in the detector simulation. This paper focuses on the implemented physics processes and their implications for detector design. A variety of models and parameterizations for the radio emission of neutrino-induced showers are compared and reviewed. Comprehensive examples are used to discuss the capabilities of the code and different aspects of instrumental design decisions.

Purpose The posterior tibial slope has a huge influence on the kinematics of the knee. In several orthopedic interventions such as high tibial osteotomy and unicondylar or bicondylar knee replacement changing, the tibial slope can result in altered knee mechanics. Therefore, an exact preoperative measurement of the posterior tibial slope is mandatory. Several methods are used on conventional radiographs and CT scans, but until now there is no standard validated method. The aim of this study was to compare several methods and imaging techniques to measure the posterior tibial slope and to establish a standard and reliable measurement method by radiography. Methods Fourteen knees (seven cadavers) were scanned by a 64-slice CT, a 3T-MRI, and true lateral radiographs were performed. The anatomical references (TPAA = tibial proximal anatomical axis; ATC = anterior tibial cortex; PTC = posterior tibial cortex) and the new computed reference (MPA = mean of PTA and ATC) were compared by short as well as long radiographs, CT scan and MRI. The influence of a malrotation in radiographs of the knees was also analyzed. Results CT scan and MRI are suitable for the measurement of the medial and lateral posterior tibial slopes, the results of the radiographs varied depending on the method used. The new method (MPA) showed the best correlation to the CT scan ( r  = 0.997), even on short radiographs (10 cm distal the joint line). Conclusion The measurement of the posterior tibial slope on a short lateral radiograph using the MPA is a reliable method and should be established as a standard. Level of evidence Diagnostic study, Level II.

Through social media like Instagram, users are constantly exposed to “perfect” lives and thin-ideal bodies. Research in this field has predominantly focused on the time youth spend on Instagram and the effects on their body image, oftentimes uncovering negative effects. Little research has been done on the root of the influence: the consumed content itself. Hence, this study aims to qualitatively uncover the types of content that trigger youths’ body image. Using a diary study, 28 youth ( M age  = 21.86; 79% female) reported 140 influential body image Instagram posts over five days, uncovering trigger points and providing their motivations, emotions, and impacts on body image. Based on these posts, four content categories were distinguished: Thin Ideal, Body Positivity, Fitness, and Lifestyle. These different content types seemed to trigger different emotions regarding body image, and gender distinctions in content could be noticed. The study increased youths’ awareness of Instagram’s influence on their mood and body perception. The findings imply that the discussion about the effects of social media on body image should be nuanced, taking into account different types of content and users. Using this information, future interventions could focus on the conscious use of social media rather than merely limiting its use.

Over the last 25 years, radiowave detection of neutrino-generated signals, using cold polar ice as the neutrino target, has emerged as perhaps the most promising technique for detection of extragalactic ultra-high energy neutrinos (corresponding to neutrino energies in excess of 0.01 Joules, or 1017 electron volts). During the summer of 2021 and in tandem with the initial deployment of the Radio Neutrino Observatory in Greenland (RNO-G), we conducted radioglaciological measurements at Summit Station, Greenland to refine our understanding of the ice target. We report the result of one such measurement, the radio-frequency electric field attenuation length $L_\\alpha$. We find an approximately linear dependence of $L_\\alpha$ on frequency with the best fit of the average field attenuation for the upper 1500 m of ice: $\\langle L_\\alpha \\rangle = ( ( 1154 \\pm 121) - ( 0.81 \\pm 0.14) \\, ( \\nu /{\\rm MHz}) ) \\,{\\rm m}$ for frequencies ν ∈ [145 − 350] MHz.

Since summer 2021, the Radio Neutrino Observatory in Greenland (RNO-G) is searching for astrophysical neutrinos at energies >10 PeV by detecting the radio emission from particle showers in the ice around Summit Station, Greenland. We present an extensive simulation study that shows how RNO-G will be able to measure the energy of such particle cascades, which will in turn be used to estimate the energy of the incoming neutrino that caused them. The location of the neutrino interaction is determined using the differences in arrival times between channels and the electric field of the radio signal is reconstructed using a novel approach based on Information Field Theory. Based on these properties, the shower energy can be estimated. We show that this method can achieve an uncertainty of 13% on the logarithm of the shower energy after modest quality cuts and estimate how this can constrain the energy of the neutrino. The method presented in this paper is applicable to all similar radio neutrino detectors, such as the proposed radio array of IceCube-Gen2.

Background:Approximately 50% of women of childbearing age with autoimmune diseases such as rheumatoid arthritis, psoriatic arthritis (PsA), plaque psoriasis, Crohn’s disease and axial spondylarthritis (axSpA) require therapeutic intervention.[1] However, there are limited data on the pharmacokinetics (PK) of treatments during pregnancy. Certolizumab pegol (CZP), a PEGylated Fc-free tumour necrosis factor inhibitor, may be used in adults for the treatment of the aforementioned autoimmune diseases. We report PK and safety results from the first longitudinal assessment of CZP PK during pregnancy.Objectives:To investigate the longitudinal PK and safety of the use of CZP during pregnancy and post-partum by measuring plasma CZP concentration and monitoring treatment-‍emergent adverse events (TEAEs).Methods:The CHERISH study (NCT04163016) was a multicentre, longitudinal, interventional, prospective, open-label phase 1B exploratory study evaluating the impact of pregnancy on the PK of CZP. The study consisted of a screening period, pregnancy period (up to 40 weeks), post-partum period (up to 13 weeks), and a safety follow-up contact (five weeks after final study visit). Patients (pts) were pregnant (≤10 weeks gestation at time of enrolment) and on stable, maintenance dose CZP treatment for ≥12 weeks prior to being enrolled in the study. Predose PK samples were collected ≤4 hours prior to dosing every 4 weeks (Q4W) starting with the first dose after enrolment. Postdose PK samples were taken 7 days after CZP dose administration every 8 weeks. One predose sample and one postdose sample were taken 11–14 weeks post-partum.The primary variable was predose and postdose plasma CZP concentrations adjusted for disease phenotype, gestational week, trimester and pre/postdose, assessed in pts receiving ≥1 dose of CZP after enrolment (pharmacokinetic per protocol set); safety was assessed in pts receiving CZP at screening (safety set). Adjusted mean differences and 95% confidence intervals were estimated for overall plasma CZP concentrations during pregnancy vs post-partum using a linear mixed effects model.Results:Of the 21 enrolled pts (CZP 200 mg every two weeks [Q2W], n=15; CZP 400 mg Q2W, n=1; CZP 400 mg Q4W, n=5), 16 (76.2%) completed the study. The mean age of pts was 32.2 (standard deviation: 4.6) years and the most common primary indication for CZP treatment reported was rheumatoid arthritis (n=9 [42.9%]). The range of plasma CZP concentrations observed (Figure 1) was within the range of plasma concentrations observed in CZP studies of non-pregnant pts with PsA, axSpA and rheumatoid arthritis (1.7–45.3 μg/mL).2,3,4Plasma CZP concentrations were lower during pregnancy relative to post-partum, though between trimesters there were no large variations in in CZP concentrations. Mean differences in overall plasma CZP concentrations during pregnancy vs post-partum were reduced when accounting for individual serum albumin and body mass index, but not C-‍reactive protein (Figure 2).The safety profile observed in this study was consistent with the known safety profile of CZP.5 17 (81.0%) pts had a TEAE; the most common maternal TEAE was infections and infestations (n=12 [57.1%]). No study pt deaths, infant illnesses, or other safety concerns were reported.Conclusion:PK data of CZP in pregnant pts were similar to non-pregnant pts and remained consistent throughout pregnancy, though pregnant pts had lower CZP plasma concentrations than post-partum.2,3,4 This suggests that pts may remain on their dosing regimen during pregnancy, particularly as CZP has been shown to minimally cross the placental barrier,1 to ensure stable plasma concentration throughout pregnancy.REFERENCES:[1] Mariette X et al, Ann Rheum Dis 2017;77:228–33. 2. European Medicines Agency, Cimzia Assessment Report 2013; 3. Gehin JE et al, Arthritis Res Ther 2019;21:256. 4. Paul S et al, Clin Transl Sci 2020;13(4):743–51. 5. Curtis JR et al, RMD Open 2019;5(1):e000942.Acknowledgements:Funded by UCB Pharma. Medical writing support provided by Costello Medical and funded by UCB Pharma.Disclosure of Interests:Megan E.B. Clowse UCB Pharma, GSK, Grant/research support from: UCB Pharma, GSK, Radboud J.E.M. Dolhain Speaking fees from UCB Pharma, Roche, Abbvie, Genzyme, Novartis, AstraZeneca, and Eli Lilly., Unrestricted research grants from Dutch Arthritis Association, ZonMw, UCB Pharma and Galapagos., Stephanie Finzel Speaker’s honoraria: Abbvie, Chugai, Galapagos, GSK, Novartis, UCB Pharma, Consultant for: Novartis, NovoNordisk, Grant/research support from: Novartis, Frauke Förger Speakers bureau from Mepha, Roche, UCB Pharma, MSD., Grant/research support from UCB Pharma., Cornelia Glaser Speaker’s honoraria from Galapagos, GSK, Pfizer and UCB Pharma., Andrea Pluma Sanjurjo: None declared, Laura Shaughnessy Employee of UCB Pharma., Jagdev Sidhu Employee of UCB Pharma., Jemma Greenin Employee of UCB Pharma., Kathy Rice Employee of UCB Pharma., Marie Teil Employee of UCB Pharma.