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Abstract Background Alzheimer’s disease (AD) is a neurodegenerative disorder that manifests sequential Aβ and tau brain pathology with age-dependent onset. Variants in the microglial immune receptor TREM2 are associated with enhanced risk of onset in sporadic Alzheimer’s disease (AD). While recent studies suggest TREM2 dysfunction can aggravate tau pathology, mechanisms underlying TREM2-dependent modulation of tau pathology remains elusive. Methods Here, we characterized differences in progressive tau spreading from the medial entorhinal cortex (MEC) to the hippocampus in wildtype (WT) and Trem2 knockout (KO) mice by injection of AAV-P301L tau into the MEC, and correlated changes in hippocampal tau histopathology with spatial and fear memory. We also compared effects of intraneuronal dispersion between cultured microglia and neurons using a microfluidic dispersion assay, analyzed differences in microglial tau trafficking following uptake, and quantified exosomal tau secretion and pathogenicity from purified WT and Trem2 KO exosomes. Results Trem2 deletion in mice (Trem2 KO) can enhance tau spreading from the medial entorhinal cortex (MEC) to the hippocampus, which coincides with impaired synaptic function and memory behavior. Trem2 deletion in microglia enhances intraneuronal dispersion of tau in vitro between neuronal layers cultured in a microfluidic chamber, and the presence of exosome inhibitors can significantly reduce tau in exosomes and extracellular media from tau-loaded microglia. Although microglial Trem2 deletion has no effect on tau uptake, Trem2 deletion enhances distribution to endosomal and cellular pre-exosomal compartments following internalization. Trem2 deletion has little effect on exosome size, however, proteomic analysis indicates that Trem2 deletion can modulate changes in the microglial proteomic landscape with tau and LPS/ATP treatment conditions associated with exosome induction. Furthermore, exosomes from Trem2 KO microglia show elevated tau levels, and feature enhanced tau-seeding capacity in a tau FRET reporter line compared to exosomes from WT microglia. Conclusion Together, our results reveal a role for Trem2 in suppressing exosomal tau pathogenicity, and demonstrates that Trem2 deletion can enhance tau trafficking, distribution and seeding through microglial exosomes. Graphical abstract

Medical interventions are often guided by optical tracking systems and optical coherence tomography has shown promising results for markerless tracking of soft tissue. The high spatial resolution and subsurface information contain valuable information about the underlying tissue structure and tracking of certain target structures is in principle possible. However, the small field-of-view complicates the selection of suitable regions-of-interest for tracking. Therefore, we extend an experimental setup and perform volumetric surface scanning of target structures to enlarge the field-of-view. We show that the setup allows for data acquisition and that precise merging of the volumes is possible with mean absolute errors from 0.041mm to 0.097mm.

Up to 20% of patients after total knee arthroplasty (TKA) are not satisfied with the result. Several designs of new implants try to rebuild natural knee kinematics. We hypothesized that an innovative implant design leads to better results concerning femoral rollback compared to an established implant design. For this pilot study, 21 patients were examined during TKA, receiving either an innovative (ATTUNETM Knee System (DePuy Inc.), n = 10) or an established (PFCTM (DePuy Inc.), n = 11) knee system. All patients underwent computer navigation. Knee kinematics was assessed after implantation. Outcome measure was anterior–posterior translation between femur and tibia. We were able to demonstrate a significantly higher femoral rollback in the innovative implant group (p < 0.001). The mean rollback of the innovative system was 11.00 mm (95%-confidence interval [CI], 10.77–11.24), of the established system 8.12 mm (95%-CI, 7.84–8.42). This study revealed a significantly increased lateral as well as medial femoral rollback of knees with the innovative prosthesis design. Our intraoperative finding needs to be confirmed using fluoroscopic or radiographic three-dimensional matching under full-weight-bearing conditions after complete recovery from surgery.

Glyn Burtt,1 Cassandra Springate,2 Alison Martin,2 Emily Woodward,3 Paul Zantek,1 Feras Al Jaafari,4 Gordon Muir,5 Vincent Misrai6 1Boston Scientific, Natick, MA, USA; 2Reviews Department, Crystallise Ltd, Essex, UK; 3Boston Scientific AG, Solothurn, Switzerland; 4Urology Department, NHS Fife, Scotland, UK; 5King’s College Hospital NHS Trust, London, UK; 6Clinique Pasteur, Toulouse, FranceCorrespondence: Alison Martin, Director and Head of Reviews, Crystallise Ltd, 17 High Street, Stanford-le-Hope, Essex, SS17 0HD, United Kingdom, Tel +44 1268 543470, Email alison.martin@crystallise.comObjective: To compare efficacy and safety outcomes of GreenLight, Holmium and Thulium laser techniques with standard monopolar and bipolar transurethral resection of the prostate (TURP) in high-risk patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO).Methods: We conducted a systematic literature review of studies in patients undergoing BPO surgeries who may be considered high-risk for standard TURP, with higher risk defined as follows: large prostates (≥ 80 mL) and/or taking antithrombotic agents and/or urinary retention and/or age > 80 years and/or significant comorbidity. Outcomes summarised included bleeding complications, re-intervention rates, hospital length of stay, and standard measures of disease and symptom severity for all available timepoints.Results: A total of 276 studies of 32,722 patients reported relevant data. Studies were heterogeneous in methodology, population and outcomes reported. IPSS reduction, Qmax improvement and PVR were similar across all interventions. Mean values at baseline and after 12 months across interventions were 13.2− 29 falling to 2.3− 10.8 for IPSS, 0− 19 mL/s increasing to 7.5− 34.1 mL/s for Qmax and 41.4− 954 mL falling to 5.1− 138.3 mL for PVR. Laser treatments show some advantages compared with monopolar and bipolar TURP for some adverse events and safety parameters such as bleeding complications. Duration of hospital stay, reinterventions and recatheterisations were lower with GreenLight, HoLEP, Thulium lasers, and bipolar enucleation than TURP.Conclusions: Laser therapies are effective and well-tolerated treatment options in high-risk patients with BPO compared with monopolar or bipolar TURP. The advantageous safety profile of laser treatments means that patients with a higher bleeding risk should be offered laser surgery preferentially to mTURP or bTURP.Keywords: benign prostatic hyperplasia, high-risk, GreenLight, Holmium laser enucleation of the prostate, HoLEP, Laser, transurethral resection of the prostate, TURP

Carolyn A Brown,1 Ajit A Londhe,1 Fang He,1 Alvan Cheng,1 Junjie Ma,1 Jie Zhang,1 Corinne G Brooks,1 J Michael Sprafka,1,2 Kimberly A Roehl,1 Katherine B Carlson,1,3 John H Page1 1Center for Observational Research, Amgen, Inc., Thousand Oaks, CA, USA; 2Woodford Research Associates, Thousand Oaks, CA, USA; 3Now with R&D Strategy, Moderna Inc., Cambridge, MA, USACorrespondence: Carolyn A Brown; John H Page, Center for Observational Research, Amgen, Inc., 1 Amgen Center Drive, B38-4B, Thousand Oaks, CA, 91320, USA, Tel +1-818-482-9477 ; +1-805-490-5527, Email cbrown14@amgen.com; Jopage@amgen.comIntroduction: In order to identify and evaluate candidate algorithms to detect COVID-19 cases in an electronic health record (EHR) database, this study examined and compared the utilization of acute respiratory disease codes from February to August 2020 versus the corresponding time period in the 3 years preceding.Methods: De-identified EHR data were used to identify codes of interest for candidate algorithms to identify COVID-19 patients. The number and proportion of patients who received a SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) within ± 10 days of the occurrence of the diagnosis code and patients who tested positive among those with a test result were calculated, resulting in 11 candidate algorithms. Sensitivity, specificity, and likelihood ratios assessed the candidate algorithms by clinical setting and time period. We adjusted for potential verification bias by weighting by the reciprocal of the estimated probability of verification.Results: From January to March 2020, the most commonly used diagnosis codes related to COVID-19 diagnosis were R06 (dyspnea) and R05 (cough). On or after April 1, 2020, the code with highest sensitivity for COVID-19, U07.1, had near perfect adjusted sensitivity (1.00 [95% CI 1.00, 1.00]) but low adjusted specificity (0.32 [95% CI 0.31, 0.33]) in hospitalized patients.Discussion: Algorithms based on the U07.1 code had high sensitivity among hospitalized patients, but low specificity, especially after April 2020. None of the combinations of ICD-10-CM codes assessed performed with a satisfactory combination of high sensitivity and high specificity when using the SARS-CoV-2 RT-PCR as the reference standard.Keywords: COVID-19, SARS-CoV-2, epidemiology, verification bias, validation

Determining the energy consumption level is one of the stages of energy efficiency monitoring facilities. The aim of the article is to adapt the energy baseline to the operating conditions of the facility in accordance with the ISO 50000 Standards requirements. The methodology for deter-mining the energy baseline was proposed to achieve the goal. The three-stage procedure for forming a set of relevant variables of the energy baseline, which allows taking into account the significance of variables, the possibility of their measurement, controllability and control, and the procedure for constructing a multifactorial model of the optimal structure for determining the energy baseline are the main scientific results. This methodology was applied to a boiler house of a district heating system. Relevant variables were formed using a three-stage selection of fac-tors that influence the gas consumption efficiency of the boiler house. Combinatorial algorithm of the group method of data handling was used for gas consumption simulation. The search for models of optimal complexity was performed in six classes of basic functions. The selection of better structures of the mathematical model was realized based on the criteria for its appropriate-ness (regularity, unbiasedness criterion, Schwartz, determination coefficient) and accuracy of the forecast using the morphological criterion. As a result, a multifactor mathematical model of optimal structure was obtained. The percent forecasting error did not exceed 1%. The signifi-cance of the results lies in the fact that the proposed methodology can be applied to any facility.

Maud Koopman,1– 3 Frits ME Franssen,1– 3 Swetlana Gaffron,4 Henrik Watz,5 Thierry Troosters,6,7 Judith Garcia-Aymerich,8– 10 Pierluigi Paggiaro,11 Eduard Molins,12 Miguel Moya,12 Lindy van Burk,13 Dieter Maier,14 Esther Garcia Gil,12 Emiel FM Wouters,1,3,15 Lowie EGW Vanfleteren,16 Martijn A Spruit1– 3 1Department of Research and Development, CIRO+, Center of Expertise for Chronic Organ Failure, Horn, the Netherlands; 2NUTRIM, School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht, the Netherlands; 3Department of Respiratory Medicine, Maastricht University Medical Center (MUMC+), Maastricht, the Netherlands; 4Viscovery Software GmbH, Vienna, Austria; 5Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany; 6Department of Rehabilitation Sciences, KU Leuven – University of Leuven, Leuven, Belgium; 7Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium; 8Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain; 9Universitat Pompeu Fabra (UPF), Barcelona, Spain; 10CIBER Epidemiología y Salud Publica (CIBERESP), Madrid, Spain; 11Department of Surgery, Medicine, Molecular Biology and Critical Care, University of Pisa, Pisa, Italy; 12AstraZeneca, Barcelona, Spain; 13AstraZeneca, Den Haag, the Netherlands; 14Biomax Informatics AB, Planegg, 82152, Germany; 15Ludwig Boltzmann Institute for Lung Health, Vienna, Austria; 16COPD Center, Sahlgrenska University Hospital, Institute of Medicine, University of Gothenburg, Gothenburg, SwedenCorrespondence: Maud Koopman, CIRO+, Center of Expertise for Chronic Organ Failure, Hornerheide 1, Horn, 6085 NM, the Netherlands, Email maudkoopman@gmail.comRationale: It is difficult to predict the effects of long-acting bronchodilators (LABD) on lung function, exercise capacity and physical activity in patients with chronic obstructive pulmonary disease (COPD). Therefore, the multidimensional response to LABD was profiled in COPD patients participating in the ACTIVATE study and randomized to LABD.Methods: In the ACTIVATE study, patients were randomized to aclidinium bromide/formoterol fumarate (AB/FF) or placebo for four weeks. The primary outcomes included (1) lung function as measured by functional residual capacity (FRC), residual volume (RV), and spirometric outcomes; (2) exercise performance as measured by a constant work rate cycle ergometry test (CWRT); and (3) physical activity (PA) using an activity monitor. Self-organizing maps (SOMs) were used to create an ordered representation of the patients who were randomly assigned to four weeks of AB/FF and cluster them into different outcome groups.Results: A total of 250 patients were randomized to AB/FF (n = 126) or placebo (n = 124). Patients in the AB/FF group (39.6% women) had moderate-to-severe COPD, static hyperinflation (FRC: 151.4 (27.7)% predicted) and preserved exercise capacity. Six clusters with differential outcomes were identified. Patients in clusters 1 and 2 had significant improvements in lung function compared to the remaining AB/FF-treated patients. Patients in clusters 1 and 3 had significant improvements in CWRT time, and patients in clusters 2, 3 and 6 had significant improvements in PA compared to the remaining AB/FF-treated patients.Conclusion: Individual responses to 4 weeks of AB/FF-treatment in COPD are differential and the degree of change differs across domains of lung function, exercise capacity and PA. These results indicate that clinical response to LABD therapy is difficult to predict and is non-linear, and show doctors that it is important to look at multiple outcomes simultaneously when evaluating the clinical response to LABD therapy.Clinical Trial Registration: The original ACTIVATE study was registered on ClinicalTrials.gov, registration number NCT02424344.Keywords: COPD, hyperinflation, physical activity

The security culture and security of the person need to be amplified in the context of the European integration process of the Republic of Moldova, especially in the conditions of the current COVID-19 pandemic. The most important political document concluded by Chisinau diplomacy with the European Union – the Agreement of Association of RM with the EU, signed on June 27, 2014, involves the establishment of a high level of protection of fundamental human rights and freedoms, including through the establishment of several mechanisms for strengthen the security culture and the ability of citizens to protect themselves against a wide diversity of security risks. A new dimension was acquired by this desideratum stipulated in the RM-EU Association Agreement in the conditions of the current pandemic of COVID-19, when the entire security system has been put to the test, undermining the foundations of a good functioning of human society both at the World scale, as well as in the Republic of Moldova.

Matthias Gijsen,1,2 Omar Elkayal,1 Pieter Annaert,1,3 Ruth Van Daele,1,2 Philippe Meersseman,4 Yves Debaveye,4 Joost Wauters,4 Erwin Dreesen,1 Isabel Spriet1,2 1Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium; 2Pharmacy Department, University Hospitals Leuven, Leuven, Belgium; 3BioNotus, Niel, Belgium; 4Department of Cellular and Molecular Medicine, KU Leuven, Leuven, BelgiumCorrespondence: Matthias GijsenPharmacy Department, University Hospitals Leuven, Herestraat 49, Leuven, 3000, BelgiumTel +32 16 340087Fax +32 16 343080Email mathias.gijsen@uzleuven.bePurpose: Critically ill patients with preserved or increased renal function have been shown to be at risk of underexposure to meropenem. Although many meropenem population pharmacokinetic (PK) models have been published, there is no large prospective population PK study with rich sampling focusing on patients most at risk of suboptimal pharmacokinetic/pharmacodynamic (PK/PD) target attainment. Therefore, the aim of the present study was to evaluate PK/PD target attainment and to perform a thorough covariate screening using population PK modelling of meropenem in septic patients with preserved or increased renal function.Patients and Methods: A single-centre prospective observational PK study was performed in the intensive care unit (ICU) of the University Hospitals Leuven. Patients with severe sepsis or septic shock and treated with meropenem in the ICU were screened for inclusion. Patients were excluded if they received renal replacement therapy or had an estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology collaboration equation < 70 mL/min/1.73m2 on the day of PK sampling. Successful PK/PD target attainment was defined as an unbound meropenem trough concentration above 2 mg/L or 8 mg/L. Population PK modelling was performed with NONMEM7.4.Results: In total, 58 patients were included, contributing 345 plasma samples over 70 dosing intervals. The 2 mg/L and 8 mg/L targets were successfully attained in 46% and 11% of all dosing intervals, respectively. A two-compartment population PK model with linear elimination and interindividual variability on clearance best described meropenem PK. The estimated creatinine clearance according to the Cockcroft-Gault equation was the only covariate retained during population PK analysis.Conclusion: This study provided detailed insight into meropenem PK in critically ill patients with preserved or increased renal function. We observed poor PK/PD target attainment, for which renal function was the only significant covariate.Trial Registration: This study is registered at ClinicalTrials.gov (NCT03560557).Keywords: intensive care, PK/PD, exposure, dose optimization, augmented renal clearance

As President Biden's administration works towards a ‘fair and humane’ immigration overhaul, it becomes critical to examine the implications of immigration policies/laws under the Trump administration on the well-being of undocumented residents to inform equitable reformations. We investigate challenges faced by undocumented Latinx immigrants in accessing health care services in the sociopolitical climate under the Trump administration. This study, which follows a similar study among frontline service providers, presents key findings from 23 in-depth interviews with Latinx individuals. Understanding their experiences is necessary to advance access to health-promoting services and uphold the human right to health. Our study participants' narratives document multiple barriers to health care services, many notably exacerbated by increasingly restrictive immigration policies/laws and heightened punitive interior enforcement practices under the Trump administration. As the nation awaits equitable immigration reform, health care organizations should immediately incorporate, amplify, or alter programs/practices to facilitate access among their undocumented clients. Focused organizational changes have the potential to reduce unmet health needs, minimize financial burdens for families, and curtail potential public health threats, the latter a particularly imperative goal within the current COVID-19 pandemic. We also distill conclusions drawn from our interviews with clients and their convergence with and divergence from conclusions drawn from our related research with providers. While providers recognize the negative impact of sociopolitical factors on their clients' access to health care services, client experiences illuminate potential gaps in their understanding. Bridging understanding between providers and clients can improve access, utilization, and retention in health care services.

The insight that optical vortex beams carry orbital angular momentum (OAM), which emerged in Leiden about 30 years ago, has since led to an ever expanding range of applications and follow-up studies. This paper starts with a short personal account of how these concepts arose. This is followed by a description of some recent ideas where the coupling of transverse orbital and spin angular momentum (SAM) in tightly focused laser beams produces interesting new effects. The deflection of a focused light beam by an atom in the focus is reminiscent of the Magnus effect known from aerodynamics. Momentum conservation dictates an accompanying light force on the atom, transverse to the optical axis. As a consequence, an atom held in an optical tweezer will be trapped at a small distance of up to λ/2π away from the optical axis, which depends on the spin state of the atom and the magnetic field direction. This opens up new avenues to control the state of motion of atoms in optical tweezers as well as potential applications in quantum gates and interferometry.

Revathy Munuswamy,1,&ast; Jana De Brandt,2,&ast; Chris Burtin,2 Wim Derave,3 Joseph Aumann,4 Martijn A Spruit,5,6,&ast; Luc Michiels1,&ast; 1Faculty of Medicine and Life Sciences, Biomedical Research Institute BIOMED, Hasselt University, Hasselt, Belgium; 2Faculty of Rehabilitation Sciences, Rehabilitation Research Center REVAL, Biomedical Research Institute BIOMED, Hasselt University, Hasselt, Belgium; 3Department of Movement and Sports Sciences, Ghent University, Ghent, Belgium; 4Department of Pneumology, Jessa Hospital, Hasselt, Belgium; 5Department of Research and Development, CIRO, Horn, the Netherlands; 6Department of Respiratory Medicine, Maastricht University Medical Centre, Faculty of Health, Medicine and Life Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht, the Netherlands&ast;These authors contributed equally to this workCorrespondence: Luc Michiels Email luc.michiels@uhasselt.beAbstract: Chronic low-grade systemic inflammation is frequently observed in patients with chronic obstructive pulmonary disease (COPD), e.g., elevated pentameric CRP (pCRP). However, pCRP can dissociate to form monomeric CRP (mCRP) which exhibits a clear pro-inflammatory behaviour in contrast to the more anti-inflammatory properties of pCRP. Therefore, mCRP may be an informative biomarker to demonstrate chronic low-grade systemic inflammation. This was confirmed by analysing serum samples from 38 patients with COPD and 18 non-COPD control persons (NCCP). mCRP was significantly elevated in patients with COPD vs. NCCP, indicating that mCRP might be considered as a new sensitive marker of chronic low-grade systemic inflammation.Keywords: COPD, low-grade systemic inflammation, pCRP, mCRP

Social media is commonly used by the public during election campaigns to express their opinions regarding different issues. Among various social media channels, Twitter provides an efficient platform for researchers and politicians to explore public opinion regarding a wide range of topics such as the economy and foreign policy. Current literature mainly focuses on analyzing the content of tweets without considering the gender of users. This research collects and analyzes a large number of tweets and uses computational, human coding, and statistical analyses to identify topics in more than 300,000 tweets posted during the 2020 U.S. presidential election and to compare female and male users regarding the average weight of the discussed topics. Our findings are based upon a wide range of topics, such as tax, climate change, and the COVID-19 pandemic. Out of the topics, there exists a significant difference between female and male users for more than 70% of topics.

Following the publication of their last work on the “didactics of Relation”, the authors offer additional insight from the book by Jean-Luc Nancy, Être singulier pluriel. The aim of this article is to clarify the term “plural” which characterizes the didactics of “pluri”lingualism by extending it to the ontological question of “being plural”. The language-culture didactics is thus invited to make its “Copernican revolution” by explicitly subscribing to social approaches based on collaboration and reticulated mediations.

Emese Csipke,1 Aisha Shafayat,2 Kirsty Sprange,2 Lucy Bradshaw,2 Alan A Montgomery,2 Reuben Ogollah,2 Esme Moniz-Cook,3 Martin Orrell4 1Division of Psychiatry, University College London, London, UK; 2Nottingham Clinical Trials Unit, University of Nottingham, Nottingham, UK; 3Faculty of Health Sciences University of Hull, Hull, UK; 4Institute of Mental Health, University of Nottingham, Nottingham, UKCorrespondence: Emese CsipkeDivision of Psychiatry, University College London, 6th Floor, Maple House, 149 Tottenham Court Road, London, W1T 7NF, UKEmail e.csipke@ucl.ac.ukBackground: There is a need for interventions to foster and maintain independence for people with dementia to support community living, improve morale, and reduce stigma. We investigated a social intervention to promote living well and enhance independence for people with mild dementia.Methods: In this two arm parallel group, feasibility RCT at six sites in England, participants were randomized (1:1) to the PRIDE intervention (encompassing social, physical, and cognitive domains supported by a facilitator over three sessions) compared to usual care only. The main objective was to determine the feasibility of a main trial with respect to measures of recruitment, retention, and adherence to the intervention.Results: During a 7-month period, 402 people were invited to the trial, 148 were screened (37%, 95% confidence interval (CI)=32– 42%), 137 were eligible at pre-consent, 94 consented to the trial (69% of those eligible, 95% CI=60– 76%), and 92 were randomized (46 to each group). Of those allocated to the intervention, 42 (91%) received at least one of three intervention sessions. Outcome assessment follow-up visits were completed for 73 participants at 6 months (79%, 95% CI=70– 87%), and this was similar for both groups.Conclusion: A large multi-center trial of the PRIDE intervention in community-dwelling people with mild dementia is feasible using systematic recruitment strategies. The intervention was successfully delivered and well received by participants. Findings from this study will be used to refine the design and processes for a definitive RCT.Trial Registration: ISRCTN, ISRCTN11288961, registered on 23 October 2018.Keywords: dementia, feasibility trial, randomized controlled trial, psychosocial intervention

Kirsty Sprange,1 Jules Beresford-Dent,2 Gail Mountain,2 Ben Thomas,3 Jessica Wright,3 Clare Mason,2 Cindy L Cooper3 1Nottingham Clinical Trials Unit, Faculty of Medicine, University of Nottingham, Nottingham, NG7 2RD, UK; 2University of Bradford, Bradford West Yorkshire, BD7 1DP, UK; 3Clinical Trials Research Unit, ScHARR, University of Sheffield, Sheffield, S1 4DP, UKCorrespondence: Kirsty SprangeNottingham Clinical Trials Unit, Building 42, Room A05, University of Nottingham, University Park, Nottingham, NG7 2RD, UKTel +44 0115 82 31574Email Kirsty.sprange@nottingham.ac.ukObjective: To identify the barriers and facilitators to the implementation of a complex psychosocial intervention though a study exploring the experiences of participants, carers and interventionists during a trial.Methods: Individual semi-structured interviews were conducted with participants, their carers, and interventionists from a sample of recruiting sites that took part in the Journeying through Dementia randomized controlled trial (RCT). Interview data were transcribed and analysed using framework analysis. Co-researcher data analysis workshops were also conducted to explore researcher interpretations of the data through the lens of those with lived experience of dementia. Triangulation enabled comparison of findings from the interviews with findings from the co-researcher workshops.Results: Three main themes emerged from the interview data: being prepared; intervention engagement; and participation and outcomes from engagement. From these themes, a number of factors that can moderate delivery and receipt of the intervention as intended were identified. These were context and environment; readiness, training, skills and competencies of the workforce; identifying meaningful participation and relationships.Conclusion: This study highlighted that the observed benefit of the intervention was nuanced for each individual. Mechanisms of change were influenced by a range of individual, social and contextual factors. Future research should therefore consider how best to identify and measure the multifaceted interplay of mechanisms of change in complex interventions.Trial Registration: ISRCTN17993825.Keywords: psychosocial, self-management, dementia, wellbeing, occupational therapy, qualitative

Background/Aim. Cholesteatoma is characterized by progressive growth with the erosion of surrounding bone due to pressure effects, enzymatic activity and activation of osteoclasts. The aim of this study was to examine the expression levels of tumor necrosis factor (TNF)-alpha receptor 2 (TNF R2) and interleukin-1 (IL-1) in chronic otitis media (COM) with and without acquired cholesteatoma and correlate them with the degree of bone destruction. Methods. The study included 178 patients of both sexes, aged 5–75 years, who underwent microsurgical treatment for COM, with and without cholesteatoma at the Ear, Nose and Throat Department, University Clinical Center of Republika Srpska (UCC RS), Banja Luka from 2015 to 2018. Based on cholesteatoma presence, the patients with COM were divided into two groups: with cholesteatoma (CCOM) (n = 97) and without cholesteatoma (COMWC) (n = 81). Samples of cholesteatoma perimatrix in the CCOM group and tympanic cavity inflamed mucosa in the COMWC group were collected intraoperatively. Intraoperative exploration of the middle ear included the status of the ossicular chain, individual ossicles, osseous walls of the external auditory canal (EAC) and tympanic cavity. Expression levels of TNF R2 and IL-1 were investigated by immunohistochemical analysis of tissue samples obtained during ear surgery. Results. The correlation between the level of osteodestruction and the presence of cholesteatoma was significant (p < 0.01). Elevated expression levels of TNF R2 and IL-1 were most frequent in CCOM patients with osteodestruction. The probability of osteodestruction of EAC and tympanic cavity walls was significantly higher in patients with high TNF R2 expression (p < 0.05). With respect to IL-1 expression levels, no significant correlation with the described pathomorphological changes was observed. Correlation between TNF R2 and IL-1 expressions and ossicular chain destruction was significant (p < 0.01). Conclusion. Cholesteatoma presence and elevated expression levels of TNF R2 and IL-1 in COM patients are significantly correlated. Expression levels of TNF R2 and IL-1 in acquired cholesteatoma tissue have a potential clinical significance for the occurrence of bone destruction compared to expression levels in inflamed mucosa of the tympanic cavity.

Modern conustructions of pedestrian bridges must satisfy functional and increasingly complex architectural requirements. In order to achieve the attractive design of pedestrian bridges, modern constructions generally differ from older, conventional solutions. The vibration problem of such structures shows that the dynamic response of the structure is governing for the design. This paper presents the comparative analysis of several dynamic models of pedestrian loads, described in various standards, guidelines, and recommendations. On the example of an arched pedestrian bridge, comparative analysis of the structure behavior due to the effect of pedestrian load was performed using numerical simulations in the SOFISTIK software, with the results obtained by analytical calculation procedures.

Families of color living in historically disinvested neighborhoods face a multitude of health disparities which have been exacerbated by COVID-19 and the resulting strategies to mitigate its transmission. School closure, which occurred with little warning and few, if any, resources for preparation, disrupted multiple aspects of families’ lives; these disruptions are anticipated to adversely impact mental health and well-being. The current study aims to advance understanding of the experiences of families of young children of color during the pandemic by utilizing a natural experiment design to test impact on child and parent mental health and sleep in the context of COVID-19 related school closure among families in historically disinvested neighborhoods. Data from this study come from an ongoing study of 281 families of color enrolled in 41 pre-kindergarten (pre-K) programs in neighborhoods across New York City (NYC). In NYC, school closure occurred on March 16, 2020, during a data collection period involving phone surveys with parents; the quasi-experimental design allows for comparison of the 198 families who had completed the survey prior to March 16, and the 83 families who completed the survey after March 16, using identical protocols and procedures. Results demonstrate poorer mental health among parents surveyed after school closure as compared to before school closure. No differences were found for parent sleep, child mental health, or child sleep. Implications of this work highlight the need for structural and systemic supports for families faced with compounding stressors as a result of the COVID-19 pandemic and related school closure.

Brandon T Goldenberg,1 Lucca Lacheta,1,2 Travis J Dekker,3 James D Spratt,1 Philip C Nolte,1 Peter J Millett1,4 1Steadman-Philippon Research Institute, Vail, CO 81657, USA; 2Center for Musculoskeletal Surgery, Charitè Universitaetsmedizin Berlin, Berlin, Germany; 3Department of Orthopaedic Surgery, Eglin Air Force Base, Elgin, FL, USA; 4The Steadman Clinic, Vail, CO 81657, USACorrespondence: Peter J Millett 181 West Meadow Drive Suite 1000, Vail, CO 81657, USATel +19704795876Fax +19704799753Email drmillett@thesteadmanclinic.comAbstract: Large and massive rotator cuff tears have the highest risk of retear. Common biologic modalities that can potentially reduce the retear rate and improve healing include platelet-rich plasma (PRP), scaffolds, and mesenchymal stem cells (MSCs). PRP has been studied for its role in improving rotator cuff healing and results of randomized controlled trials and meta-analyses show mixed results. Most studies in large and massivge tears show that PRP decreases the retear rate, but the connection between structural integrity and clinical outcomes is still unknown. Extracellular matrix (ECM) and synthetic scaffolds can increase healing in augmentation and bridging repair. Acellular dermal allografts have shown better healing rates and outcomes than xenografts in meta-analyses. Synthetic scaffolds augmented with bone marrow-derived stem cells have only been studied in vitro but are promising for the combination of mechanical stability and induction of a biological response. Superior capsule reconstruction is an exciting type of interposition graft reconstruction that has shown favorable early clinical outcomes for large and massive tears. Bone marrow-derived stem cells and adipose-derived stem cells improve the biomechanical characteristics of tendon repair and enhance the histological findings of the healing process in animal studies. However, evidence from human studies is lacking, especially in patients with large and massive tears. In summary, there are many biological options to augment rotator cuff repair in patients with large and massive tears. Due to mixed results and a lack of standardization in high-quality studies, we cannot recommend PRP at this time as an adjunct to rotator cuff repair. Both ECM and synthetic scaffolds, as well as SCR, can be used, especially in situations where native tendon is compromised, and additional mechanical augmentation is needed. Stem cells have been the least studied to date, so it is difficult to give recommendations for or against their use at this time.Keywords: biologics, large rotator cuff tears, massive rotator cuff tears, platelet-rich plasma, scaffolds, mesenchymal stem cells

Abstract Background Most hookah use studies have not included racial and ethnic minorities which limits our understanding of its use among these growing populations. This study aimed to investigate the individual characteristics of hookah use patterns and associated risk behaviors among an ethnically diverse sample of college students. Methods A cross-sectional survey of 2460 students (aged 18–25) was conducted in 2015, and data was analyzed in 2017. Descriptive statistics were used to present the sociodemographic characteristics, hookah use-related behavior, and binge drinking and marijuana use according to the current hookah use group, including never, exclusive, dual/poly hookah use. Multivariate logistic regression was conducted to examine how hookah related behavior and other risk behaviors varied by sociodemographics and hookah use patterns. Results Among current hookah users (n = 312), 70% were exclusive hookah users and 30% were dual/poly hookah users. There were no statistically significant differences in sociodemographic characteristics except for race/ethnicity (p

Dana Shalmon,1 Joel L Cohen,2 Marina Landau,3 Ines Verner,4 Eli Sprecher,1,5 Ofir Artzi1 1Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; 2AboutSkin Dermatology and AboutSkin Research, Greenwood and Lone Tree, CO, USA; 3Private Practice, Herzliya, Israel; 4Verner Clinic Tel Aviv, University of Rome “Guglielmo Marconi”, Israel, Italy; 5Department of Human Molecular Genetics & Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelCorrespondence: Ofir Artzi Email ofira@tlvmc.gov.ilBackground: Over the past few decades, soft tissue augmentation is ever-increasing, specifically hyaluronic acid (HA)-based filler injections. As the number of these procedures have risen, so have the adverse reactions. Delayed-type inflammatory reactions (DIRs) secondary to tissue fillers are typically classified according to the time of appearance post-procedure and have various presentations including nodules, abscesses, edema, and discoloration. Currently, the treatment of these complications varies among physicians.Objective: The aim of this study was to assess the knowledge and experience of practitioners in Israel who inject HA-based tissue fillers with respect to the management of late-onset procedural complications.Materials and Methods: A survey regarding management and treatment of late-onset inflammatory reactions was sent to 1120 physicians and dentists in Israel who practice tissue filler injections.Results: Three hundred thirty-four out of the 1120 practitioners replied to the questionnaire. The majority of respondents were dentists (group A) comprising 31% of all respondents. Group B accounted for 31% of injectors and consisted of dermatologists (19%) and plastic surgeons (12%), and group C (38%) accounted for all other practitioners; 48.2% of all injectors indicated that they have not previously encountered a DIR, whereas 11.4% responded that they have encountered more than 5 DIRs. In order to assess treatment management, we presented the injectors with a simulatory case of a woman with a late-onset complication. Most injectors referred the patient to the emergency department. When asked to establish a treatment plan, the majority of practitioners prescribed short-term oral steroids, ie, prednisone (35.3%). A limited number of patients were treated with intra-lesional hyaluronidase (31.4%) injection as only 34% of injectors kept hyaluronidase at their clinic.Conclusion: The varied approach regarding the management of delayed type reactions to HA-based filler injections, reflected in our study, illustrates the existing ambivalence in the current literature regarding the management and therapy of late-onset complications.Keywords: cosmetic techniques, dermal fillers/adverse effects, hyaluronic acid/adverse effects, delayed reaction, nodules, filler, hypersensitivity

Ofir Artzi,1,2 Joel L Cohen,3 Jeffrey S Dover,4– 6 Atchima Suwanchinda,7,8 Tatjana Pavicic,9 Marina Landau,10 Greg J Goodman,11 Sahar Ghannam,12 Firas Al Niaimi,13 Jani AJ van Loghem,14 Kate Goldie,15 Sonja Sattler,16 Daniel Cassuto,17 Ting Song Lim,18 Rungsima Wanitphakdeedecha,19 Ines Verner,20,21 Tanja C Fischer,22,23 Vivian Bucay,24 Eli Sprecher,1,2,25 Dana Shalmon1,2 1Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3AboutSkin Dermatology and AboutSkin Research, , Greenwood Village and Lone Tree, CO, USA; 4SkinCare Physicians, Chestnut Hill, MA, USA; 5Dermatology, Yale University School of Medicine, New Haven, CT, USA; 6Dermatology, Brown Medical School, Rhode Island, USA; 7Department of Dermatology, School of Anti-Aging and Regenerative Medicine, Mae Fah Luang University, Bangkok, Thailand; 8Division of Dermatology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 9Private Practice for Dermatology and Aesthetics Dr. Tatjana Pavicic, Munich 80539, Germany; 10Dermatology, Private Practice, Herzliya, Israel; 11Monash University, Clayton, Victoria, Australia; 12Associate Prof. of Dermatology, Alexandria University, Alexandria, Egypt; 13 152, Harley street, London, UK; 14UMA Institute, Amsterdam 1017, TX, Netherlands; 15Medical Director European Medical Aesthetics Ltd, London W1G 8QN, UK; 16Rosenpark Klinik, Darmstadt, Germany; 17Private Practice, Milan, Italy; 18Clique Clinic, Kuala Lumpur, Malaysia; 19Department of Dermatology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; 20Verner Clinic, Tel Aviv, Israel; 21Department of Dermatology, University of Rome, Guglielmo Marconi, Italy; 22Skin and Laser Center, Potsdam, Germany; 23School of Medicine, University of Frankfurt, Germany; 24Bucay Center for Dermatology and Aesthetics, UTHSC, San Antonio, TX, USA; 25Department of Human Molecular Genetics & Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelCorrespondence: Ofir ArtziTel Aviv Sourasky Medical Center, Weizman 6, Tel Aviv, IsraelTel +972-54-5968961Fax +972-77-2001801Email ofira@tlvmc.gov.ilBackground and Objectives: There is a wide diversity of opinions regarding the management of delayed inflammatory reactions (DIRs) secondary to hyaluronic acid (HA)-based fillers. The plethora of approaches has led the authors to conduct a review regarding management and treatment of DIRs as well as establish therapeutic guidelines for this purpose.Materials and Methods: A review of the literature was performed through databases such as PubMed using keywords including HA-fillers and complications, delayed HA filler sequelae and therapy, soft tissue and dermal filler reactions and management. Additionally, a survey comprised of questions regarding the management and treatment of DIRs was sent to 18 physicians highly experienced with soft-tissue filler injections in 10 countries. Their answers and recommendations were analyzed and debated amongst these panelists.Results: Sixteen panelists favored antibiotic therapy as first-line treatment for DIRs, specifically dual antibiotic therapy consisting of a fluoroquinolone along with a tetracycline or macrolide for a period of 3– 6 weeks. The majority refrained from the use of intralesional (IL) or systemic steroids except in the case of disfiguring or recalcitrant reactions. IL hyaluronidase was recommended by 13 panelists; however, some preferred a watchful waiting approach for a period of 48 hours to 2 weeks prior to IL hyaluronidase, and in cases where antibiotics did not lead to improvement.Conclusion: A consensus was reached and summarized to propose a clear, easy-to-follow, stepwise algorithm for the treatment of DIRs.Keywords: cosmetic techniques, dermal fillers/adverse effects, hyaluronic acid/adverse effects

Gail Mountain,1 Kirsty Sprange,2 Robin Chatters1 1School of Health and Related Research, Faculty of Medicine, University of Sheffield, Sheffield, UK; 2Faculty of Medicine, University of Nottingham, Nottingham, UKCorrespondence: Gail MountainSchool of Health and Related Research, University of Sheffield, Regent Court, Regent Street, Sheffield S1 4DA, UKTel +44 75 4067 1442Email g.a.mountain@sheffield.ac.ukObjective: This qualitative study embedded within a randomized controlled trial was conducted to explore the acceptability, experiences of, and short-term impact of a preventive health intervention (Lifestyle Matters) from the perspectives of those who took part, and to uncover any evidence for the theorised mechanisms of action (improved participation and self efficacy) underpinning the intervention. It was also conducted to help explain the quantitative trial results.Methods: A purposive sample of 13 trial participants who had been randomized to receive the Lifestyle Matters intervention (approximately 10%) were individually qualitatively interviewed immediately following their involvement. All four intervention facilitators were also individually interviewed.Results: Evidence of the hypothesized behavioural changes could be identified within the interview data, demonstrating the potential of this intervention. However, lack of adherence to the overall intervention eroded receipt of benefit. This finding complements the quantitative trial results which found that the study had failed to recruit those who considered themselves to be at risk of age-related decline.Conclusion: This form of preventive health intervention requires proactive identification of those who recognise the need to make lifestyle changes. This is difficult if reactive health and social care systems are the main referral routes. The methodological approaches taken towards the study of complex interventions requires reconsideration if potential benefits are to be accurately assessed.Clinical Trial Registration: ISRCTN67209155Keywords: preventive health intervention, older people, qualitative study, randomized controlled trial

Background/Aim: An important period in becoming a young woman is studying at the University. It is a period of taking responsibility for yourself, your health and social relationships. The abilities formed during this period directly affect one's physical and mental health. The study was undertaken in order to determine anthropometric characteristics and to evaluate the health of female students aged 19 to 22. Methods: An analytical population study based on a survey using a standardised SF36 self-report health test and measurement using an objective bioimpedance method with Omron BF 511 estimated 408 female students of the University of Banja Luka aged 19 to 22, based on inclusion criteria. Results: The mean body mass index (BMI) ± standard deviation of female students was 22.1 ± 3.2 kg/m2 , with 31.80 ± 6.47 percent fat and 28.15 ± 2.81 percent muscle mass. The mean values ± standard deviation of the SF 36 for mental health (MH) questionnaires was 60.7 ± 24.95 and for physical health (FH) 72.21 ± 25.89. Conclusion: Female students have ideal BMI values. Physical health self-assessment reached higher values than the mental health self-assessment, which is probably related to mental distress and problems during studying.

Jolaade Kalinowski,1 Barbara C Wallace,2 Natasha J Williams,1 Tanya M Spruill1 1Department of Population Health, NYU School of Medicine, New York, NY, USA; 2Department of Health Education, Teachers College, Columbia University, New York, NY, USACorrespondence: Jolaade KalinowskiNYU School of Medicine, 180 Madison Avenue, 7-21A, New York, NY 10016, USATel +1 646 501-3437Email Jolaade.Kalinowski@nyumc.orgObjective: To elucidate women’s experiences with opioid medications and their perspectives on provider education regarding opioid use, risks and safety.Methods: Women with a self-reported history of pain who had been prescribed opioids were recruited in 2016 using a convenience sampling approach that included an online social media campaign. Participants (N=154) completed online surveys and open-ended questions regarding their experiences with pain and opioids, and their perspectives on the quality of education they received from their providers.Results: Participants reported receiving insufficient education about opioid-related side effects, as reflected in both ratings for the quantity and quality of education they received from their providers. Non-white participants reported lower quantity and poorer quality of provider education (p

Objective(s)To use machine learning (ML) to predict short-term requirements for invasive ventilation in patients with COVID-19 admitted to Australian intensive care units (ICUs).DesignA machine learning study within a national ICU COVID-19 registry in Australia.ParticipantsAdult patients who were spontaneously breathing and admitted to participating ICUs with laboratory-confirmed COVID-19 from 20 February 2020 to 7 March 2021. Patients intubated on day one of their ICU admission were excluded.Main outcome measuresSix machine learning models predicted the requirement for invasive ventilation by day three of ICU admission from variables recorded on the first calendar day of ICU admission; (1) random forest classifier (RF), (2) decision tree classifier (DT), (3) logistic regression (LR), (4) K neighbours classifier (KNN), (5) support vector machine (SVM), and (6) gradient boosted machine (GBM). Cross-validation was used to assess the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of machine learning models.Results300 ICU admissions collected from 53 ICUs across Australia were included. The median [IQR] age of patients was 59 [50-69] years, 109 (36%) were female and 60 (20%) required invasive ventilation on day two or three. Random forest and Gradient boosted machine were the best performing algorithms, achieving mean (SD) AUCs of 0.69 (0.06) and 0.68 (0.07), and mean sensitivities of 77 (19%) and 81 (17%), respectively.ConclusionMachine learning can be used to predict subsequent ventilation in patients with COVID-19 who were spontaneously breathing and admitted to Australian ICUs.

Habitat loss and fragmentation are two important drivers of biodiversity decline. Understanding how species respond to landscape composition and configuration in dynamic landscapes is of great importance for informing the conservation and management of grassland species. With limited conservation resources, prescribed management targeted at the appropriate landscape process is necessary for the effective management of species. We used pheasants (Phasianus colchicus) across South Dakota, USA as a model species to identify environmental factors driving spatiotemporal variation in population productivity. Using an emerging Hotspot analysis, we analyzed annual count data from 105 fixed pheasant brood routes over a 24-year period to identify high (HotSpot) and low (ColdSpot) pheasant population productivity areas. We then applied classification and regression tree modeling to evaluate landscape attributes associated with pheasant productivity among spatial scales (500 m and 1000 m). We found that the amount of grassland at a local spatial scale was the primary factor influencing an area being a HotSpot. Our results also demonstrated non-significant or weak effects of fragmentation per se on pheasant populations. These findings are in accordance with the habitat amount hypothesis highlighting the importance of habitat amount in the landscape for maintaining and increasing the pheasant population. We, therefore, recommend that managers should focus on increasing the total habitat area in the landscape and restoring degraded habitats. Our method of identifying areas of high productivity across the landscape can be applied to other species with count data.

Vadym Gnatkovsky,1 Alessandro Cattalini,1 Alessandro Antonini,2 Laura Spreafico,2 Matteo Saini,2 Francesco Noè,1 Camilla Alessi,1 Laura Librizzi,1 Laura Uva,1 Carlo Efisio Marras,3 Marco de Curtis,1 Sandro Ferrari2 1Unit of Epileptology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy; 2WISE Srl, Cologno Monzese, Milano, Italy; 3Neurosurgery Unit, Department of Neuroscience and Neurorehabilitation, IRCCS Bambino Gesù Children’s Hospital, Roma, ItalyCorrespondence: Vadym GnatkovskyUnit of Epileptology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Amadeo, 42, Milano 20133, ItalyTel +39 0223944518Email Vadym.Gnatkovsky@istituto-besta.itBackground: Multielectrodes are implanted in central and peripheral nervous systems for rehabilitation and diagnostic purposes. The physical resistance of intracranial devices to mechanical stress is critical and fractures or electrode displacement may occur. We describe here a new recording device with stretchable properties based on Supersonic Cluster Beam Implantation (SCBI) technology with high mechanical adaptability to displacement and movement.Results: The capability of SCBI-based multichannel electrodes to record brain electrical activity was compared to glass/silicon microelectrodes in acute in vitro experiments on the isolated guinea pig brain preparation. Field potentials and power frequency analysis demonstrated equal recording features for SCBI and standard electrodes. Chronic in vivo epidural implantation of the SCBI electrodes confirmed excellent long-term recording properties in comparison to standard EEG metal electrodes. Tissue biocompatibility was demonstrated by neuropathological evaluation of the brain tissue 2 months after the implantation of the devices in the subarachnoid space.Conclusion: We confirm the biocompatibility of novel SCBI-based stretchable electrode devices and demonstrate their suitability for recording electrical brain activity in pre-clinical settings.Keywords: brain, field potentials, recording electrodes, supersonic cluster beam implantation

The socio-political, economic, cultural, religious, ethical, mental or technological-communicative differences, with a major impact on the living standards, on the quality of life standards in human communities inhabiting the planet Earth, contribute to the strengthening of mankind’s potential to cope with the most violent and destructive effects and results of the multidimensional global crisis, through the diversity of chances and identities it generates. The central concern in the process of building security culture as a state policy is the strengthening of human security with its new aspects in the context of the security approach to the building of a knowledge-based society, of a morally refurbished society, rebuilt on noospheric and bioethical principles.

Zaira Khalid,1 Hasina Momotaz,2 Farren Briggs,3 Kristin A Cassidy,1,2 Naomi S Chaytor,4 Robert T Fraser,5 Mary R Janevic,6 Barbara Jobst,7 Erica K Johnson,8 Peter Scal,9 Tanya M Spruill,10 Betsy K Wilson,2 Martha Sajatovic1,2 1Department of Psychiatry, Case Western Reserve University School of Medicine, University Hospitals Cleveland Medical Center , Cleveland, OH, USA; 2Department of Neurology, Case Western Reserve University School of Medicine, Neurological and Behavioral Outcomes Center, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; 3Department of Population Health and Quantitative Science, School of Medicine, Case Western Reserve University, Cleveland, OH, USA; 4Department of Medical Education and Clinical Sciences, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA, USA; 5Department of Rehabilitation Medicine, University of Washington, Seattle, WA, USA; 6Center for Managing Chronic Disease, University of Michigan School of Public Health, Ann Arbor, MI, USA; 7Department of Neurology, Geisel School of Medicine at Dartmouth, Dartmouth College, Lebanon, NH, USA; 8Health Promotion Research Center, University of Washington, Seattle, WA, USA; 9Department of Pediatrics and Adolescent Health, University of Minnesota, Minneapolis, MN, USA; 10Department of Population Health, NYU School of Medicine, New York, NY, USACorrespondence: Martha SajatovicPrevention Research Center, Case Western Reserve University School of Medicine, University Hospitals Cleveland Medical Center, 10524 Euclid Avenue, Cleveland, OH 44106, USATel +1 216 844-2808Fax +1 216 844-2742Email Martha.sajatovic@uhhospitals.orgAim: There are limited data on psychological outcomes in older people with epilepsy (PWE). This analysis, from a large pooled dataset of clinical studies from the Managing Epilepsy Well (MEW) Network, examined clinical variables including depressive symptom severity, quality of life and epilepsy self-management competency among older (age 55+) vs younger (

Shaundra Eichstadt,1 Jean Y Tang,1 Daniel C Solis,1 Zurab Siprashvili,1 M Peter Marinkovich,1,2 Nedra Whitehead,3 Matthew Schu,3 Fang Fang,3 Stephen W Erickson,3 Mary E Ritchey,3 Max Colao,4 Kaye Spratt,4 Amir Shaygan,5 Mark J Ahn,5 Kavita Y Sarin1 1Stanford University School of Medicine, Department of Dermatology, Redwood City, CA 94063, USA; 2Veterans Affairs Medical Center, Palo Alto, CA, USA; 3RTI International, Research Triangle Park, NC, USA; 4Abeona Therapeutics, New York, NY, USA; 5Department of Engineering and Technology Management, Portland State University, Portland, OR, USACorrespondence: Mark J AhnDepartment of Engineering and Technology Management, Portland State University, 1900 SW 4th Avenue, Suite LL50-01, Portland, OR 97201, USATel +1503961-4466Email mahn@pdx.eduBackground: Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited genetic disorder characterized by recurrent and chronic open wounds with significant morbidity, impaired quality of life, and early mortality. RDEB patients demonstrate reduction or structural alteration type VII collagen (C7) owing to mutations in the gene COL7A1, the main component of anchoring fibrils (AF) necessary to maintain epidermal-dermal cohesion. While over 700 alterations in COL7A1 have been reported to cause dystrophic epidermolysis bullosa (DEB), which may be inherited in an autosomal dominant (DDEB) or autosomal recessive pattern (RDEB), the incidence and prevalence of RDEB is not well defined. To date, the widely estimated incidence (0.2–6.65 per million births) and prevalence (3.5–20.4 per million people) of RDEB has been primarily characterized by limited analyses of clinical databases or registries.Methods: Using a genetic modelling approach, we use whole exome and genome sequencing data to estimate the allele frequency of pathogenic variants. Through the ClinVar and NCBI database of human genome variants and phenotypes, DEB Register, and analyzing premature COL7A1 termination variants we built a model to predict the pathogenicity of previously unclassified variants. We applied the model to publicly available sequences from the Exome Aggregation Consortium (ExAC) and Genome Aggregation Database (gnomAD) and identified variants which were classified as pathogenic for RDEB from which we estimate disease incidence and prevalence.Results: Genetic modelling applied to the whole exome and genome sequencing data resulted in the identification of predicted RDEB pathogenic alleles, from which our estimate of the incidence of RDEB is 95 per million live births, 30 times the 3.05 per million live birth incidence estimated by the National Epidermolysis Bullosa Registry (NEBR). Using a simulation approach, we estimate a mean of approximately 3,850 patients in the US who may benefit from COL7A1-mediated treatments in the US.Conclusion: We conclude that genetic allele frequency estimation may enhance the underdiagnosis of rare genetic diseases generally, and RDEB specifically, which may improve incidence and prevalence estimates of patients who may benefit from treatment.Keywords: Dystrophic Epidermolysis Bullosa, genotype, phenotype, incidence, prevalence

An electrophysical wasteless technology is presented based on the electrochemical activation of the acid whey in a periodic regime. Under consideration are variations of such principal parameters as the electric current density, voltage, pH, oxidation-reduction potential, temperature, specific energy consumption, and the degree of isolation of whey proteins in the protein-mineral concentrates (PMCs). It is found that the isolation of whey proteins in the PMCs makes about 80% from the first minutes of the process and remains constant during the rest of it at the current density j=10 mA·cm-2 and the specific energy consumption by 2.5 times lower than during processing at j=20 mA·cm-2, in the latter case, the isolation of whey proteins in the PMCs makes about 73-75%, which allows for decreasing the energy consumption during processing. However, in the liquid phase (LP), the recovery of about 84%, which means that from the first minutes, there are intensively formed protein compounds with a high molecular weight thatwhich cannot be isolated as foam as a result of the ion flotation, remaining in the LP contained in the cathode cell. These investigations demonstrate an opportunity to properly control the processing of the acid whey, which depends on the processing regime (the electric current density) necessary for an optimal isolation of protein fractions in the PMCs, with a simultaneous decrease of the specific energy consumption per a unit of volume.

Cement composite long-term property assessment usually is limited to the compression strain state due to the difficulty of performing long-term tests in tension and 3-point bending. This paper shows the difference in long-term properties in compression, tension, and 3-point bending for plain ordinary Portland cement mortar (OPC). The obtained results were compared to reinforced specimen results to determine whether the PVA refibres improve the long-term properties of OPC mortar in various stress-strain conditions. Cylinders, compact tension specimens (CT), and beams – plates were prepared to evaluate material properties and the role of fibre reinforcement in these different stress states. Additionally, to conventional surface-attached strain gauges, 2D-DIC was employed to observe the creep strain of specimens in tension. This paper aim to determine long-term property differences in compression, tension and 3-point bending and, also, to see if low amount PVA fibre incorporation improve long-term properties in previously stated stress-strain states. It was determined that the usage of 1 % of PVA fibres increases creep strains in compression on average by 15 % and reduced by 7 % in tension. It reduces shrinkage strain by 18 % in compression and 8 % in tension. The long-term deflection for the PVA fibre-reinforced specimens are, on average by 55 % higher than for plain OPC mortar specimens in 3-point bending.