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Introduction/Aims: Heterogeneous nuclear ribonucleoprotein A1 is involved in nucleic acid homeostatic functions. The encoding gene HNRNPA1 has been associated with several neuromuscular disorders including an amyotrophic lateral sclerosis‐like phenotype, distal hereditary motor neuropathy, multisystem proteinopathy, and various myopathies. We report two unrelated individuals with monoallelic stop loss variants affecting the same codon of HNRNPA1. Methods: Two individuals with unsolved juvenile‐onset myopathy were enrolled under approved institutional protocols. Phenotype data were collected and genetic analyses were performed, including whole‐exome sequencing (WES). Results: The two probands (MNOT002‐01 and K1440‐01) showed a similar onset of slowly progressive extremity and facial weakness in early adolescence. K1440‐01 presented with facial weakness, winged scapula, elevated serum creatine kinase (CK) levels, and mild neck weakness. MNOT002‐01 also exhibited elevated CK levels along with facial weakness, cardiomyopathy, respiratory dysfunction, pectus excavatum, a mildly rigid spine, and loss of ambulation. On quadriceps muscle biopsy, K1440‐01 displayed rounded myofibers, mild variation in fiber diameter, and type 2 fiber hypertrophy, while MNOT002‐01 displayed rimmed vacuoles. Monoallelic stop‐loss variants in HNRNPA1 were identified for both probands: c.1119A>C p.*373Tyrext*6 (K1440‐01) and c.1118A>C p.*373Serext*6 (MNOT002‐01) affect the same codon and are both predicted to lead to the addition of six amino acids before termination at an alternative stop codon. Discussion: Both stop‐loss variants in our probands are likely pathogenic. Our findings contribute to the disease characterization of pathogenic variants in HNRNPA1. This gene should be screened in clinical diagnostic testing of unsolved cases of sporadic or dominant juvenile‐onset myopathy. [ABSTRACT FROM AUTHOR]

In the Coast Mountains of western British Columbia, an anomalous seismicity concentration exists near the intersection of the Coast Shear Zone, a major northwest–southeast trending Eocene-age shear zone that accommodated deformation between the Pacific and North America plates, with the Anahim Volcanic Belt, an east-northeast–west-northwest trending zone of volcanic features that decrease in age to the east. To better characterize seismicity in the Coast Mountains, we augment the existing Natural Resources Canada seismicity catalogue by applying an automatic detection and location algorithm to both permanent Canadian National Seismic Network stations and temporary stations from the 2005–2006 BATHOLITHS deployment, resulting in 837 relocated events with at least three paired P- and S-phase picks. Double-difference relocation reveals several small-scale linear strands subparallel to the Coast Shear Zone and within the Anahim Volcanic Belt and three clusters of events striking at a high angle to the Coast Shear Zone that occurred as swarms in 2015 and 2017. First-motion focal mechanisms exhibit extensional and strike-slip faulting. Our observations indicate that most of these events are not associated with surficial processes such as landslides, but rather, we hypothesize that the interaction of the Anahim Volcanic Belt and Coast Shear Zone has weakened the lithosphere in this region, leading to current-day strain localization and high heat flow that manifest seismicity, including swarm-like activity. [ABSTRACT FROM AUTHOR]

Herpesviruses are enveloped and have an amorphous protein layer surrounding the capsid, which is termed the tegument. Tegument proteins perform critical functions throughout the viral life cycle. This review provides a comprehensive and comparative analysis of the roles of specific tegument proteins in capsid transport and virion morphogenesis of selected, well-studied prototypes of each of the three subfamilies of Herpesviridae i.e., human herpesvirus-1/herpes simplex virus-1 (Alphaherpesvirinae), human herpesvirus-5/cytomegalovirus (Betaherpesvirinae) and human herpesvirus -8/Kaposi's sarcomavirus (Gammaherpesvirinae). Most of the current knowledge is based on alpha herpesviruses, in particular HSV-1. While some tegument proteins are released into the cytoplasm after virus entry, several tegument proteins remain associated with the capsid and are responsible for transport to and docking at the nucleus. After replication and capsid formation, the capsid is enveloped at the nuclear membrane, which is referred to as primary envelopment, followed by de-envelopment and release into the cytoplasm. This requires involvement of at least three tegument proteins. Subsequently, multiple interactions between tegument proteins and capsid proteins, other tegument proteins and glycoproteins are required for assembly of the virus particles and envelopment at the Golgi, with certain tegument proteins acting as the central hub for these interactions. Some redundancy in these interactions ensures appropriate morphogenesis. [ABSTRACT FROM AUTHOR]

We are a student–educator writing collective that have come together outside the formal classroom to experiment with 'writing differently', imbued with a desire to enact collective resistance against 'unnoticed' and intentionally hidden aspects of the business school curriculum that condone, normalize and reproduce social injustice and inequalities. As students and educator located in the Department of Organizational Psychology at a UK-based business school, we see our non-traditional writing and inquiry through collective writing as a form of resistance against hegemonic scientific norms of knowledge production that dominate our discipline. We evoked Freire's problem-posing education through a collective enactment of 'responsibility learning-in-action' by participating in regular 'writing as resistance' sessions, where we wrote around our lived experiences of the 'unnoticed' and intentionally hidden curriculum and responsibility learning in the same virtual space and time and then read aloud to one another. Our coming together through this practice (re)claims relationality and solidarity in the student–educator relationship, which is in itself a contribution to the topic of the intersections between responsibility learning and the hidden curriculum at business schools. [ABSTRACT FROM AUTHOR]

The Queen Charlotte triple junction/Explorer microplate region offshore British Columbia, Canada, is marked by poorly understood and rapidly evolving microplate tectonics. Although the region hosts abundant seismicity, it has received relatively scant attention in recent years due to its remote, offshore location. We use the Regressive ESTimator (REST) algorithm to generate a new catalog of automatically detected earthquakes from 1995 to 2021, which, when merged with the existing Geological Survey of Canada catalog, yields the most extensive seismicity data set offshore British Columbia to date. We apply double‐difference relocation to these events and perform stress inversions using moment tensors for subregions within the study area. Our results confirm and extend previous models of microplate deformation processes. We suggest the Revere‐Dellwood‐Queen Charlotte fault system has evolved as a NW‐migrating, pull‐apart system between Haida Gwaii and the Explorer ridge that obeys global length/width scaling and whose bathymetric expression is influenced by volcanism plausibly induced by interaction with the Kodiak‐Bowie hotspot. Seismicity within the Explorer microplate is dominated by prominent, northeast‐trending lineations that emanate from the Sovanco fracture zone and parallel the Nootka fault zone. Alignment of these features with spreading structures that bound the microplate suggests that its breakup is controlled primarily by a strength fabric inherited at spreading ridges. Stress inversions are dominated by near‐vertical intermediate compressive stress reflecting the dominance of strike‐slip faulting. Stress varies systematically between transpression to the north along southern Haida Gwaii and seafloor spreading to the south along the Juan de Fuca ridge. Plain Language Summary: Offshore British Columbia, the Pacific, North America, and Juan de Fuca tectonic plates meet in a broad zone called a triple junction. As the plates adjust to changing relative plate motions, their present‐day deformation is recorded by seismicity. We expand the existing catalog of earthquakes offshore with an automatic earthquake detection algorithm and estimate their locations. We also analyze dominant stress patterns to provide insight into how the triple junction and Explorer plate are changing and moving. Extension between overlapping faults under prevailing compression gives rise to the observed volcanism and seismicity patterns. The length of overlap relative to the width follows a well established scaling. Along the Revere‐Dellwood fault, the seismicity pattern transitions from concentrated earthquakes along the fault with some compression at the continental margin, to more distributed seismicity and associated volcanism in the overlap region between it and the Queen Charlotte fault. Structures generated at the oceanic spreading ridges may control deformation as evidenced by our earthquake locations. Within the Explorer plate, the locations reveal NE‐trending lineations aligned with ridges generated by seafloor spreading. Seismicity provides a means to analyze deformation in the Explorer plate where the seafloor is obscured by heavy sedimentation. Key Points: Merged manual and automatic catalogs yield 18,441 double‐difference‐relocated earthquakes in the triple junction and Explorer regionsSeismicity distribution explained by migrating pull‐apart mechanism that yields insights into triple junction evolutionAlignment of seismicity in Explorer microplate with bordering ridges suggests breakup controlled by ocean‐spreading fabric [ABSTRACT FROM AUTHOR]

This paper compares different low-cost sensors that can measure (5G) RF-EMF exposure. The sensors are either commercially available (off-the-shelf Software Defined Radio (SDR) Adalm Pluto) or constructed by a research institution (i.e., imec-WAVES, Ghent University and Smart Sensor Systems research group (S³R), The Hague University of Applied Sciences). Both in-lab (GTEM cell) and in-situ measurements have been performed for this comparison. The in-lab measurements tested the linearity and sensitivity, which can then be used to calibrate the sensors. The in-situ testing confirmed that the low-cost hardware sensors and SDR can be used to assess the RF-EMF radiation. The variability between the sensors was 1.78 dB on average, with a maximum deviation of 5.26 dB. Values between 0.09 V/m and 2.44 V/m were obtained at a distance of about 50 m from the base station. These devices can be used to provide the general public and governments with temporal and spatial 5G electromagnetic field values. [ABSTRACT FROM AUTHOR]

Background: To evaluate the effects of a shared decision making (SDM) intervention for older adults with multiple chronic conditions (MCCs). Methods: A pragmatic trial evaluated the effects of the SDMMCC intervention, existing of SDM training for nine geriatricians in two hospitals and a preparatory tool for patients. A prospective pre-intervention post-intervention multi-center clinical study was conducted in which an usual care group of older patients with MCC and their informal caregivers was included before the implementation of the intervention and a new cohort of patients and informal caregivers after the implementation of the intervention. SDM was observed using the OPTIONMCC during video-recorded consultations. Patient- and caregivers reported outcomes regarding their role in SDM, involvement, perceived SDM and decisional conflict were measured. The differences between groups regarding the level of observed SDM (OPTIONMCC) were analyzed with a mixed model analysis. Dichotomous patient-reported outcomes were analyzed with a logistic mixed model. Results: From two outpatient geriatric clinics 216 patients with MCCs participated. The mean age was 77.3 years, and 56.3% of patients were female. No significant difference was found in the overall level of SDM as measured with the OPTIONMCC or in patient-reported outcomes. However, at item level the items discussing 'goals', 'options', and 'decision making' significantly improved after the intervention. The items discussing 'partnership' and 'evaluating the decision-making process' showed a significant decrease. Fifty-two percent of the patients completed the preparatory tool, but the results were only discussed in 12% of the consultations. Conclusion: This study provides scope for improvement of SDM in geriatrics. Engaging older adults with MCCs and informal caregivers in the decision making process should be an essential part of SDM training for geriatricians, beyond the SDM steps of explaining options, benefits and harms. More attention should be paid to the integration of preparatory work in the consultation. [ABSTRACT FROM AUTHOR]

In the framework of the French–Egyptian Imhotep Project, two spring gravimeters have been installed in the area of Lake Nasser (Egypt) with the aim to establish a first reliable gravity tide model for the region. The two tidal gravity stations are located in Aswan, on the northern edge of the lake and in Abu Simbel in the south, respectively. This study was mainly aimed to obtain a reliable model of the crustal response to tidal forces and, consequently, to increase the accuracy of the geodetic observations, to be used in future geophysical studies in this region as well as to investigate the effect of the Lake level variations on the crustal deformation and related gravity changes. Nearly 3 years of gravity records (from May 2018 to April 2021) were collected. Since no scale factor was available for the two gravimeters, the first step of this study was to achieve a reliable calibration for each of the two collected gravity signals. After removing the instrumental drift, spikes, steps and tares, both gravimeters have been calibrated by fitting the output signal against a synthetic reference signal based on the body tidal gravity response due to Wahr-Dehant Earth model and FES2014 ocean tidal loading model. The calibrated signals have been analyzed with ET34-X-V80 software for tidal analyses. This enabled us to retrieve a set of frequency-dependent gravity factors (amplitude and phase) for the main tidal waves, as well as to obtain gravity residuals. It turns out that the accuracy of the amplitude estimates for the main tidal waves is 0.2 ÷ 1% for LCR_ET16 in Aswan and 1 ÷ 10% for the LCR_D-218 in Abu Simbel. To improve the tidal model at Abu Simbel, LCR_ET16 was stopped in Aswan and relocated there. The first 90 days of gravity recordings from ET16 at Abu Simbel provide promising results, with an accuracy of the order of 0.1% for the main tidal waves, even better than the results obtained in Aswan. The residual gravity signal after tidal subtraction at Aswan is in the range of ± 50 µGal. Further analyses of the instrumental contribution are however needed before to be able to interpret this gravity signal in terms of surface loading (i.e. changes in the water level of Lake Nasser) or underground hydrology. [ABSTRACT FROM AUTHOR]

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VP8, the most abundant tegument protein of bovine herpesvirus-1 (BoHV-1), plays an important role in viral replication. According to our previous studies, VP8 localizes to the Golgi apparatus of BoHV-1-infected cells where it can be packaged into the virus; however, Golgi localization of VP8 does not occur outside of the context of infection. The goal of this study was to identify the viral factor(s) involved in the tropism of VP8 towards the Golgi. VP8 was found to interact with glycoprotein M (gM), and the VP8 and gM domains that are essential for this interaction were identified. VP8 and gM colocalized to the Golgi apparatus in BoHV-1-infected cells. In cells co-transfected with VP8- and gM-encoding plasmids, VP8 was also found to be localized to the Golgi, suggesting gM to be sufficient. The localization of VP8 to the Golgi was lost in cells infected with a gM deletion mutant, and the amount of VP8 incorporated into mature virus was significantly reduced. However, with the restoration of gM in a revertant virus, the localization to the Golgi and the amount of VP8 incorporated in the virions were restored. These results indicate that gM plays a critical role in VP8 subcellular localization to the Golgi and packaging into mature virions. [ABSTRACT FROM AUTHOR]

Many individuals with muscular dystrophies remain genetically undiagnosed despite clinical diagnostic testing, including exome sequencing. Some may harbor previously undetected structural variants (SVs) or cryptic splice sites. We enrolled 10 unrelated families: nine had muscular dystrophy but lacked complete genetic diagnoses and one had an asymptomatic DMD duplication. Nanopore genomic long‐read sequencing identified previously undetected pathogenic variants in four individuals: an SV in DMD, an SV in LAMA2, and two single nucleotide variants in DMD that alter splicing. The DMD duplication in the asymptomatic individual was in tandem. Nanopore sequencing may help streamline genetic diagnostic approaches for muscular dystrophy. [ABSTRACT FROM AUTHOR]

This study is a metrological investigation of eight superconducting gravimeters that have operated in the Strasbourg gravimetric Observatory. These superconducting gravimeters include an older compact C026 model, a new observatory type iOSG23 and six iGravs (6, 15, 29, 30, 31, 32). We first compare the amplitude calibration of the meters using measurements from FG5 #206 absolute gravimeter (AG). In a next step we compute the amplitude calibration of all the meters by time regression with respect to iOSG23 itself carefully calibrated by numerous AG experiments. The relative calibration values are much more precise than absolute calibration for each instrument and strongly reduce any tidal residual signal. We also compare the time lags of the various instruments with respect to iOSG23, either by time cross-correlation or tidal analysis for the longest records (about 1 year). The instrumental drift behavior of the iGravs and iOSG23 is then investigated and we examine the relationships observed between gravity and body temperature measurements. Finally, we compare the noise levels of all the instruments. A three-channel correlation analysis is used to separate the incoherent (instrumental) noise from the coherent (ambient) noise. The self-noise is then compared to a model of thermal noise (Brownian motion) using the known instrumental parameters of the damped harmonic oscillator. The self-noise of iGrav instruments is well-explained by the thermal noise model at seismic frequencies (between 10–3 and 10–2 Hz). As expected, the self-noise of iOSG23 with a heavier sphere is also lower than that of iGravs at such frequencies. [ABSTRACT FROM AUTHOR]

Objective: To provide insight into professionals' perceptions of and experiences with shared decision-making (SDM) in the treatment of symptomatic patients with severe aortic stenosis (AS).Methods: A semistructured interview study was performed in the heart centres of academic and large teaching hospitals in the Netherlands between June and December 2020. Cardiothoracic surgeons, interventional cardiologists, nurse practitioners and physician assistants (n=21) involved in the decision-making process for treatment of severe AS were interviewed. An inductive thematic analysis was used to identify, analyse and report patterns in the data.Results: Four primary themes were generated: (1) the concept of SDM, (2) knowledge, (3) communication and interaction, and (4) implementation of SDM. Not all respondents considered patient participation as an element of SDM. They experienced a discrepancy between patients' wishes and treatment options. Respondents explained that not knowing patient preferences for health improvement hinders SDM and complicating patient characteristics for patient participation were perceived. A shared responsibility for improving SDM was suggested for patients and all professionals involved in the decision-making process for severe AS.Conclusions: Professionals struggle to make highly complex treatment decisions part of SDM and to embed patients' expectations of treatment and patients' preferences. Additionally, organisational constraints complicate the SDM process. To ensure sustainable high-quality care, professionals should increase their awareness of patient participation in SDM, and collaboration in the pathway for decision-making in severe AS is required to support the documentation and availability of information according to the principles of SDM. [ABSTRACT FROM AUTHOR]

Background: In order to provide the best care, the perspective of older COVID-19 patients must be involved in the development of treatment protocols. This study describes the experiences of older adults affected by COVID-19 who recovered in the hospital or at home. Methods: Qualitative semi-structured interviews were conducted with 23 older adults affected by COVID-19. A content-based thematic analysis was conducted. Results: Nine categories were identified as recurring topics, which were grouped into three major themes. The first theme describes experiences in the first phase of the disease when older adults fell ill. The second theme includes experiences during the illness, ranging from illness severity to participation in decision-making, communication barriers and isolation effects. The final theme covers the recovery course, residual symptoms and social aspects. Conclusion: Older adults treated for COVID-19 experienced a feeling of being in a fast-paced whirlwind and lost total control over the situation. Extra attention should be paid to shared decision making, coordinated information provision and the instalment of a primary contract to the patient. The uncertainty of their situation, isolation measures and fears could result in psychological consequences and hinder rehabilitation in older adults. [ABSTRACT FROM AUTHOR]

In 1976, a small group of lesbian feminists in Amsterdam named themselves after Jill Johnston's Lesbian Nation: The Feminist Solution (1973) and imagined a separate lesbian society, free from heteropatriarchal oppression. Despite naming themselves after Johnston, Lesbian Nation's main aim was inspired by French feminist theorist Monique Wittig: to subvert the existing symbolic order, and create a new one in its wake. Based on archival research and interviews, this article shows how Lesbian Nation combined both lesbian separatist and cultural feminist tendencies, by experimenting with lesbian identity and creating a women's culture. Discussing the similarities and differences between Lesbian Nation and its predecessor, Paarse September, this article illustrates how lesbian organising evolved in the Netherlands. More broadly, this article adds to lesbian feminist historiography, showing how a small group shaped their own lesbian feminist ideology – and brought this into practice – on a local scale. [ABSTRACT FROM AUTHOR]

Background: In order to provide the best care, the perspective of older COVID-19 patients must be involved in the development of treatment protocols. This study describes the experiences of older adults affected by COVID-19 who recovered in the hospital or at home. Methods: Qualitative semi-structured interviews were conducted with 23 older adults affected by COVID-19. A contentbased thematic analysis was conducted. Results: Nine categories were identified as recurring topics, which were grouped into three major themes. The first theme describes experiences in the first phase of the disease when older adults fell ill. The second theme includes experiences during the illness, ranging from illness severity to participation in decision-making, communication barriers and isolation effects. The final theme covers the recovery course, residual symptoms and social aspects. Conclusion: Older adults treated for COVID-19 experienced a feeling of being in a fast-paced whirlwind and lost total control over the situation. Extra attention should be paid to shared decision making, coordinated information provision and the instalment of a primary contract to the patient. The uncertainty of their situation, isolation measures and fears could result in psychological consequences and hinder rehabilitation in older adults. [ABSTRACT FROM AUTHOR]

Teddie Littel discusses the health connections between the mouth and body. [ABSTRACT FROM AUTHOR]

The most appropriate strategies for managing secondary genomic findings (SF) in clinical research are being developed and evaluated. We surveyed patients at the National Institute of Allergy and Infectious Diseases (NIAID) to evaluate decisional conflict regarding enrolling in a study that returns SF. Responses were collected using a cross‐sectional survey after informed consent but before return of SF. Sixty‐six adults of 116 eligible participants responded. No participant explicitly declined because they did not want to possibly receive a SF. Sixty‐five of 66 (98%) participants thought it was appropriate to return SFs in research; one participant was unsure. Decisional conflict regarding enrolling in a study returning SF was low overall with 68% of participants reporting a score of less than 10 on a 100‐point decisional conflict scale, implying that they felt informed, clear on what they wanted, and supported. Lower genetic literacy was weakly associated with higher decisional conflict (Spearman's rho = −0.297, p =.015). Six participants reported confusion related to the choices about SFs. Our data suggest that participants in our study feel it is appropriate to receive SF and have little decisional conflict about potentially receiving such information; however, some participants may need further education and counseling. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to describe barriers and facilitators for shared decision making (SDM) as experienced by older patients with multiple chronic conditions (MCCs), informal caregivers and health professionals.Methods: A structured literature search was conducted with 5 databases. Two reviewers independently assessed studies for eligibility and performed a quality assessment. The results from the included studies were summarized using a predefined taxonomy.Results: Our search yielded 3838 articles. Twenty-eight studies, listing 149 perceived barriers and 67 perceived facilitators for SDM, were included. Due to poor health and cognitive and/or physical impairments, older patients with MCCs participate less in SDM. Poor interpersonal skills of health professionals are perceived as hampering SDM, as do organizational barriers, such as pressure for time and high turnover of patients. However, among older patients with MCCs, SDM could be facilitated when patients share information about personal values, priorities and preferences, as well as information about quality of life and functional status. Informal caregivers may facilitate SDM by assisting patients with decision support, although informal caregivers can also complicate the SDM process, for example, when they have different views on treatment or the patient's capability to be involved. Coordination of care when multiple health professionals are involved is perceived as important.Conclusions: Although poor health is perceived as a barrier to participate in SDM, the personal experience of living with MCCs is considered valuable input in SDM. An explicit invitation to participate in SDM is important to older adults. Health professionals need a supporting organizational context and good communication skills to devise an individualized approach for patient care. [ABSTRACT FROM AUTHOR]

Background: Shared decision making (SDM) contributes to personalized decisions that fit the personal preferences of patients when choosing a treatment for a condition. However, older adults frequently face multiple chronic conditions (MCC). Therefore, implementing SDM requires special features. The aim of this paper is to describe the development of an intervention to improve SDM in older adults with MCC.Methods: Following the Medical Research Council framework for developing complex interventions, the SDMMCC intervention was developed step-wise. Based on a literature review and empirical research in a co-creation process with end users, we developed training for geriatricians and a preparatory tool for older patients with MCC and informal caregivers. After assessing feasibility, the intervention was implemented in a pilot study (N = 108) in two outpatient geriatric clinics of an academic and a non-academic teaching hospital in Amsterdam, the Netherlands.Results: Key elements of the training for geriatricians include developing skills to involve older adults with MCC and informal caregivers in SDM and following the six-step 'Dynamic model for SDM with frail older patients', as well as learning how to explore personal goals related to quality of life and how to form a partnership with the patient and the informal caregiver. Key elements of the preparatory tool for patients include an explicit invitation to participate in SDM, nomination that the patient's own knowledge is valuable, invitation to form a partnership with the geriatrician, encouragement to share information about daily and social functioning and exploration of possible goals. Furthermore, the invitation of informal caregivers to share their concerns was also a key element.Conclusions: Through a process of co-creation, both training for geriatricians and a preparatory tool for older adults and their informal caregivers were developed, tailored to the needs of the end users and based on the 'Dynamic model of SDM with frail older patients'. [ABSTRACT FROM AUTHOR]

In shared decision making, the exploration of preferred personal health outcomes is important. Patient-reported outcome measures (PROMs) provide input for discussions between patients and healthcare professionals. The Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS) PROM is a multidimensional questionnaire on the physical and mental health and wellbeing of older adults. This study investigates how the TOPICS-MDS could be used in individual healthcare conversations. We explored views of older adults regarding 1) whether the health domains they want to discuss are included in the TOPICS-MDS and 2) the comprehensibility of the TOPICS-MDS for healthcare conversations with older adults. A three-round Delphi study was conducted. A total of 57 older adults participated in the study, the mean (SD) age was 71.5 (8.5) years, and 78.9% of the participants were female. The participants were divided into four panels based on educational level and cultural background. We used online questionnaires and focus groups. Consensus was pre-defined to be the point when ≥75% of the participants agreed that a domain was important or very important (scored on a 5-point Likert scale). The inter-expert agreement was computed for Round 1 and 3 with Kendall's W. Round 2 was a focus-group. Qualitative data were analyzed by content analysis. Older adults considered 'functional limitations', 'emotional wellbeing', 'social functioning' and 'quality of life' to be important domains of the TOPICS-MDS to discuss in healthcare conversations. The participants added 'coping with stress', 'dealing with health conditions and the effects on life' as extra domains for healthcare conversations. Challenges regarding the comprehensibility of the TOPICS-MDS included difficult words and lengthy or sensitive questions. Questions that included multiple topics were difficult to understand. The TOPICS-MDS covers the domains of life that older adults value as important to discuss with healthcare professionals, and two additional domains were identified. For older adults with a low level of education or a culturally diverse background, the TOPICS-MDS needs to be adjusted for comprehensibility. [ABSTRACT FROM AUTHOR]

Introduction: Adjuvants form an integral component in most of the inactivated and subunit vaccine formulations. Careful and proper selection of adjuvants helps in promoting appropriate immune responses against target pathogens at both innate and adaptive levels such that protective immunity can be elicited. Areas covered: Herein, we describe the recent progress in our understanding of the mode of action of adjuvants that are licensed for use in human vaccines or in clinical or pre-clinical stages at both innate and adaptive levels. Different pathogens have distinct characteristics, which require the host to mount an appropriate immune response against them. Adjuvants can be selected to elicit a tailor-made immune response to specific pathogens based on their unique properties. Identification of biomarkers of adjuvanticity for several candidate vaccines using omics-based technologies can unravel the mechanism of action of modern and experimental adjuvants. Expert opinion: Adjuvant technology has been revolutionized over the last two decades. In-depth understanding of the role of adjuvants in activating the innate immune system, combined with systems vaccinology approaches, have led to the development of next-generation, novel adjuvants that can be used in vaccines against challenging pathogens and in specific target populations. [ABSTRACT FROM AUTHOR]

Tectonic tremor can be used to constrain seismic wave attenuation for use in ground motion prediction equations in regions where moderately sized earthquakes occur infrequently. Here we quantify seismic wave attenuation by inverting tremor ground motion amplitudes in different frequency bands of interest, to determine frequency dependence of and spatial variations in seismic wave attenuation in Cascadia. Due to the density of tremor data, we are able to resolve along‐strike variations in the attenuation parameter. We find that tectonic tremor exhibits the frequency dependence expected for attenuation, as determined from ground motion prediction equations developed from moderate‐to‐large magnitude earthquakes. This implies that attenuation along these paths is independent of the source mechanism. This study demonstrates that tectonic tremor can be used to provide insight into the physical factors responsible for attenuation and to refine estimates of attenuation for ground motion prediction, thus having important implications for hazard assessment and engineering seismology. Plain Language Summary: Earthquake ground motion models use estimates of seismic wave attenuation, that is, the decrease in amplitude of a seismic wave along its path from the earthquake source. Seismic wave attenuation is typically determined by analyzing ground motion from moderate‐to‐large earthquakes. Yet Cascadia also hosts tremor, a group of many small seismic signals accompanying slow sliding of the subducting plate. Because tremor occurs frequently when compared to regular earthquakes in Cascadia, it presents an opportunity to better refine attenuation parameters for use in ground motion models. We quantify seismic wave attenuation using tremor ground motion amplitudes to determine the extent of regional variations and frequency dependence of seismic wave attenuation in Cascadia. Incorporating spatial modifications and allowing for varying frequencies would increase the accuracy of the ground motion model. We are able to resolve spatial variations in the attenuation parameter along strike in Cascadia and observe the frequency dependence expected for attenuation, as seen in ground motion models developed from moderate‐to‐large magnitude earthquakes. Hence, we show that tectonic tremor can be used to provide insight into the physical factors responsible for attenuation and refine estimates of attenuation for ground motion models, thus having important implications for seismic hazard assessment. This is especially helpful in regions where moderate‐to‐large earthquakes are sparse, such as Cascadia. Key Points: Tectonic tremor can be used to constrain physical parameters for use in GMPEs where moderately sized earthquakes occur infrequentlyInversion of tectonic tremor data indicates that seismic wave attenuation varies along strike in CascadiaFrequency‐dependent attenuation from tectonic tremor is observed to be consistent with models developed using moderate‐to‐large earthquakes [ABSTRACT FROM AUTHOR]

Summary: The concept of dendritic cell (DC) maturation generally refers to the changes in morphology and function of DCs. Conventionally, DC maturity is based on three criteria: loss of endocytic ability, gain of high‐level capacity to present antigens and induce proliferation of T cells, and mobility of DCs toward high concentrations of CCL19. Impairment of DC maturation has been suggested as the main reason for infectivity or chronicity of several infectious agents. In the case of hepatitis C virus, this has been a matter of controversy for the last two decades. However, insufficient attention has been paid to the method of ex vivo maturation as the possible source of such controversies. We previously reported striking differences between DCs matured with different methods, so we propose the use of a standard quantitative index to determine the level of maturity in DCs as an approach to compare results from different studies. We designed and formulated a mathematically calculated index to numerically define the level of maturity based on experimental data from ex vivo assays. This introduces a standard maturation index (SMI) and weighted maturation index (WMI) based on strictly standardized mean differences between different methods of generating mature DCs. By calculating an SMI and a WMI, numerical values were assigned to the level of maturity achieved by DCs matured with different methods. SMI and WMI could be used as a standard tool to compare diversely generated mature DCs and so better interpret outcomes of ex vivo and in vivo studies with mature DCs. [ABSTRACT FROM AUTHOR]

Background: Eye movement desensitization and reprocessing (EMDR) is an effective psychological treatment for posttraumatic stress disorder. Recalling a memory while simultaneously making eye movements (EM) decreases a memory’s vividness and/or emotionality. It has been argued that non-specific factors, such as treatment expectancy and experimental demand, may contribute to the EMDR’s effectiveness. Objective: The present study was designed to test whether expectations about the working mechanism of EMDR would alter the memory attenuating effects of EM. Two experiments were conducted. In Experiment 1, we examined the effects of pre-existing (non-manipulated) knowledge of EMDR in participants with and without prior knowledge. In Experiment 2, we experimentally manipulated prior knowledge by providing participants without prior knowledge with correct or incorrect information about EMDR’s working mechanism. Method: Participants in both experiments recalled two aversive, autobiographical memories during brief sets of EM (Recall+EM) or keeping eyes stationary (Recall Only). Before and after the intervention, participants scored their memories on vividness and emotionality. A Bayesian approach was used to compare two competing hypotheses on the effects of (existing/given) prior knowledge: (1) Prior (correct) knowledge increases the effects of Recall+EM vs. Recall Only, vs. (2) prior knowledge does not affect the effects of Recall+EM. Results: Recall+EM caused greater reductions in memory vividness and emotionality than Recall Only in all groups, including the incorrect information group. In Experiment 1, both hypotheses were supported by the data: prior knowledge boosted the effects of EM, but only modestly. In Experiment 2, the second hypothesis was clearly supported over the first: providing knowledge of the underlying mechanism of EMDR did not alter the effects of EM. Conclusions: Recall+EM appears to be quite robust against the effects of prior expectations. As Recall+EM is the core component of EMDR, expectancy effects probably contribute little to the effectiveness of EMDR treatment. [ABSTRACT FROM AUTHOR]

WHIM syndrome is an autosomal dominant immunodeficiency disease caused by mutations affecting the carboxy-terminus of CXCR4. To characterize novel genetic causes of the syndrome, we recruited a pediatric patient with possible WHIM syndrome, performed CXCR4 gene sequencing and compared his clinical phenotype and CXCR4 tail amino acid sequences with other patients with WHIM syndrome carrying CXCR4 mutations. We identified and biochemically characterized a heterozygous 5 base pair deletion (nucleotides 986-990) located in the portion of the open reading frame (ORF) of CXCR4 that encodes the carboxy-terminal domain of the receptor. This CXCR4 mutation causes a frame-shift at codon 329 resulting in replacement of the final 24 predicted amino acids of the receptor with 12 missense amino acids. Like previously reported WHIM mutations, this frame-shift mutation CXCR4 decreased receptor downregulation in response to the CXCR4 agonist CXCL12 in patient PBMCs as well as in transfected K562 and HEK 293 cells, but increased calcium flux responses in K562 cells to CXCL12 stimulation. Thus, CXCR4 appears to be a de novo autosomal dominant frame-shift gain-of-function mutation that like other carboxy-terminus mutations causes WHIM syndrome. The same CXCR4 frame-shift variant has been reported to occur in tumor cells from a patient with Waldenström's Macroglobulemia (WM), but is caused by a distinct genetic mechanism: insertion of a single nucleotide in the L329 codon, providing additional evidence that the carboxy-terminus of CXCR4 is a genetic hotspot for mutation. [ABSTRACT FROM AUTHOR]

The article discusses the use of a lentiviral gene therapy approach for the treatment of X-linked severe combined immunodeficiency (SCID-X1) patients with persistent immune dysfunction despite haploidentical hematopoietic stem cell (HSC) transplant in infancy. The achievement of similar gene-marking levels in three younger patients is explored. The capability of the therapy to restore humoral immune function to posthaploidentical transplant older patients with SCID-X1 is also tackled.

Eye movement desensitization and reprocessing (EMDR) is an effective treatment for posttraumatic stress disorder. During this treatment, patients recall traumatic memories while making horizontal eye movements (EM). Studies have shown that EM not only desensitize negative memories but also positive memories and imagined events. Substance use behavior and craving are maintained by maladaptive memory associations and visual imagery. Preliminary findings have indicated that these mental images can be desensitized by EMDR techniques. We conducted two proof-of-principle studies to investigate whether EM can reduce the sensory richness of substance-related mental representations and accompanying craving levels. We investigated the effects of EM on (1) vividness of food-related mental imagery and food craving in dieting and non-dieting students and (2) vividness of recent smoking-related memories and cigarette craving in daily smokers. In both experiments, participants recalled the images while making EM or keeping eyes stationary. Image vividness and emotionality, image-specific craving and general craving were measured before and after the intervention. As a behavioral outcome measure, participants in study 1 were offered a snack choice at the end of the experiment. Results of both experiments showed that image vividness and craving increased in the control condition but remained stable or decreased after the EM intervention. EM additionally reduced image emotionality (experiment 2) and affected behavior (experiment 1): participants in the EM condition were more inclined to choose healthy over unhealthy snack options. In conclusion, these data suggest that EM can be used to reduce intensity of substance-related imagery and craving. Although long-term effects are yet to be demonstrated, the current studies suggest that EM might be a useful technique in addiction treatment. [ABSTRACT FROM AUTHOR]

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Dendritic cells (DCs) play an important role in the induction of the primary immune response to infection. DCs may express the tryptophan-catabolizing enzyme indolamine2,3-dioxygenase (IDO), which is an inducer of immune tolerance. Because there is evidence that chronic hepatitis C virus (HCV) infection leads to functional impairment of certain DC populations, we analysed IDO expression in DCs and monocytes from chronically infected and recovered HCV patients. The IDO1 and -2 expression was increased significantly in the monocytes of chronic HCV patients but, interestingly, not in those from recovered patients. The myeloid DCs from chronically infected HCV patients also showed enhanced IDO1 expression, while no change in either IDO1 or -2 was found for plasmacytoid DCs. Up-regulation of IDO1 gene expression was confirmed by the presence of enhanced kynurenine/tryptophan ratios in the plasma from chronic HCV patients. Increased IDO1 and -2 expression was also observed in monocytes from healthy donors infected with an adapted mutant of the HCV JFH-1 strain ex vivo, confirming a direct effect of HCV infection. These changes in IDO expression could be prevented by treatment with the IDO inhibitor 1-methyl tryptophan (1-mT). Furthermore, maturation of monocyte-derived DCs from chronically infected HCV patients, as well as well as monocyte-derived DCs infected ex vivo with HCV, was impaired, but this was reversed by 1-mT treatment. This suggests that IDO inhibitors may be used to treat chronic HCV patients in vivo, in conjunction with current therapies, or to activate DCs from patients ex vivo, such that they can be administered back as a DC-based therapeutic vaccine. [ABSTRACT FROM AUTHOR]

Eye movement desensitization and reprocessing (EMDR) is an efficacious treatment for post-traumatic stress disorder. In EMDR, patients recall a distressing memory and simultaneously make eye movements (EM). Both tasks are considered to require limited working memory (WM) resources. Because this leaves fewer resources available for memory retrieval, the memory should become less vivid and less emotional during future recall. In EMDR analogue studies, a standardized procedure has been used, in which participants receive the same dual task manipulation of 1 EM cycle per second (1 Hz). From a WM perspective, the WM taxation of the dual task might be titrated to the WM taxation of the memory image. We hypothesized that highly vivid images are more affected by high WM taxation and less vivid images are more affected by low WM taxation. In study 1, 34 participants performed a reaction time task, and rated image vividness, and difficulty of retrieving an image, during five speeds of EM and no EM. Both a high WM taxing frequency (fast EM; 1.2 Hz) and a low WM taxing frequency (slow EM; 0.8 Hz) were selected. In study 2, 72 participants recalled three highly vivid aversive autobiographical memory images (nD36) or three less vivid images (nD36) under each of three conditions: recall + fast EM, recall + slow EM, or recall only. Multi-level modeling revealed a consistent pattern for all outcome measures: recall + fast EM led to less emotional, less vivid and more difficult to retrieve images than recall + slow EM and recall only, and the effects of recall + slow EM felt consistently in between the effects of recall + fast EM and recall only, but only differed significantly from recall + fast EM. Crucially, image vividness did not interact with condition on the decrease of emotionality over time, which was inconsistent with the prediction. Implications for understanding the mechanisms of action in memory modification and directions for future research are discussed. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are multifunctional cells that are pivotal in immune defense. As such they have been explored as vaccine carriers, largely in cancer immunotherapy and against some infectious diseases including HIV and viral hepatitis. However, while the use of DCs as vaccine carrier has shown some promise in cancer immunotherapy, this approach is laborious and is subject to strict quality control, which makes it expensive. Furthermore, in some individuals chronically infected with HIV, HCV and/or HBV the numbers of circulating DCs are reduced and/or their functions impaired. In vivo expansion and mobilization of DCs with Flt3L in combination with antigen and/or adjuvant targeting to critical DC receptors may be a more effective approach to control viral replication in chronically infected HIV, HBV and/or HCV patients than current DC immunotherapy approaches. [ABSTRACT FROM AUTHOR]

Memories that are recalled while working memory (WM) is taxed, e.g., by making eye movements (EM), become blurred during the recall + EM and later recall, without EM. This may help to explain the effects of Eye Movement and Desensitisation and Reprocessing (EMDR) in the treatment of post-traumatic stress disorder (PTSD) in which patients make EM during trauma recall. Earlier experimental studies on recall + EM have focused on emotional memories. WM theory suggests that recall + EM is superior to recall only but is silent about effects of memory emotionality. Based on the emotion and memory literature, we examined whether recall + EM has superior effects in blurring emotional memories relative to neutral memories. Healthy volunteers recalled negative or neutral memories, matched for vividness, while visually tracking a dot that moved horizontally (“recall + EM”) or remained stationary (“recall only”). Compared to a pre-test, a post-test (without concentrating on the dot) replicated earlier findings: negative memories are rated as less vivid after “recall + EM” but not after “recall only”. This was not found for neutral memories. Emotional memories are more taxing than neutral memories, which may explain the findings. Alternatively, transient arousal induced by recall of aversive memories may promote reconsolidation of the blurred memory image that is provoked by EM. [ABSTRACT FROM PUBLISHER]

Purpose – This paper aims to examine how visual and haptic package design characteristics singularly and jointly affect consumers' brand impressions. Design/methodology/approach – Integrating and extending design perception with congruence and fluency theories, the paper presents three research propositions that are tested in three studies. Bottled water serves as an example category with data provided by professionals and consumers. Findings – Study 1 identifies key types of holistic bimodal designs (Modern, Big Grip, Prototypical-Small, Boxy Billboards, and Prototypical-Large) based on brand visual and haptic factors. Study 2 relates these types to unique single-modal brand impressions. Study 3 determines how consumers evaluate brands depending on the semantic congruence between haptics and visuals. Except for the excitement dimension, brand evaluations are more positive under conditions of high rather than low congruence. Research limitations/implications – The findings are obtained for a single category (bottled water) using experiments designed to highlight and focus consumer attention on the formation of impressions. The findings may thus not fully reflect consumer responses in actual retail purchase situations. Practical implications – The paper provides preliminary guidelines on how to utilize visual and haptic cues in the design of brand packages for stimulating desired consumer responses. Originality/value – The work presented in this paper contributes to the literature on design-based brand inferences and semantic congruence by integrating the visual with the haptic perspectives. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is the leading cause of infant bronchiolitis. The closely related pneumonia virus of mice (PVM) causes a similar immune-mediated disease in mice, which allows an analysis of host factors that lead to severe illness. This project was designed to compare the immune responses to lethal and sublethal doses of PVM strain 15 in Balb/c and C57Bl/6 mice. Balb/c mice responded to PVM infection with an earlier and stronger innate response that failed to control viral replication. Production of inflammatory cyto- and chemokines, as well as infiltration of neutrophils and IFN-γ secreting natural killer cells into the lungs, was more predominant in Balb/c mice. In contrast, C57Bl/6 mice were capable of suppressing both viral replication and innate inflammatory responses. After a sublethal infection, PVM-induced IFN-γ production by splenocytes was stronger early during infection and weaker at late time points in C57Bl/6 mice when compared to Balb/c mice. Furthermore, although the IgG levels were similar and the mucosal IgA titres lower, the virus neutralizing antibody titres were higher in C57Bl/6 mice than in Balb/c mice. Overall, the difference in susceptibility of these two strains appeared to be related not to an inherent T helper bias, but to the capacity of the C57Bl/6 mice to control both viral replication and the immune response elicited by PVM. [ABSTRACT FROM AUTHOR]

Excessive computer gaming has recently been proposed as a possible pathological illness. However, research on this topic is still in its infancy and underlying neurobiological mechanisms have not yet been identified. The determination of underlying mechanisms of excessive gaming might be useful for the identification of those at risk, a better understanding of the behavior and the development of interventions. Excessive gaming has been often compared with pathological gambling and substance use disorder. Both disorders are characterized by high levels of impulsivity, which incorporates deficits in error processing and response inhibition. The present study aimed to investigate error processing and response inhibition in excessive gamers and controls using a Go/ NoGo paradigm combined with event-related potential recordings. Results indicated that excessive gamers show reduced error-related negativity amplitudes in response to incorrect trials relative to correct trials, implying poor error processing in this population. Furthermore, excessive gamers display higher levels of self-reported impulsivity as well as more impulsive responding as reflected by less behavioral inhibition on the Go/ NoGo task. The present study indicates that excessive gaming partly parallels impulse control and substance use disorders regarding impulsivity measured on the self-reported, behavioral and electrophysiological level. Although the present study does not allow drawing firm conclusions on causality, it might be that trait impulsivity, poor error processing and diminished behavioral response inhibition underlie the excessive gaming patterns observed in certain individuals. They might be less sensitive to negative consequences of gaming and therefore continue their behavior despite adverse consequences. [ABSTRACT FROM AUTHOR]

Background: Classical conditioning has been suggested to play an important role in the development, maintenance, and relapse of tobacco smoking. Several studies have shown that initially neutral stimuli that are directly paired with smoking are able to elicit conditioned responses. However, there have been few human studies that demonstrate the contribution of higher-order conditioning to smoking addiction, although it is assumed that higher-order conditioning predominates learning in the outside world. In the present study a higherorder conditioning task was designed in which brain responses of smokers and non-smokers were conditioned by pairing smoking-related and neutral stimuli (CS1smoke and CS1neutral) with two geometrical figures (CS2smoke and CS2neutral). ERPs were recorded to all CSs. Results: Data showed that the geometrical figure that was paired with smoking stimuli elicited significantly larger P2 and P3 waves than the geometrical figure that was paired with neutral stimuli. During the first half of the experiment this effect was only present in smokers whereas non-smokers displayed no significant differences between both stimuli, indicating that neutral cues paired with motivationally relevant smoking-related stimuli gain more motivational significance even though they were never paired directly with smoking. These conclusions are underscored by self-reported evidence of enhanced second-order conditioning in smokers. Conclusions: It can be concluded that smokers show associative learning for higher-order smoking-related stimuli. The present study directly shows the contribution of higher-order conditioning to smoking addiction and is the first to reveal its electrophysiological correlates. Although results are preliminary, they may help in understanding the etiology of smoking addiction and its persistence. [ABSTRACT FROM AUTHOR]

The article examines the exposure of beef calves to bovine viral diarrhea virus (BVDV) and bovine herpes virus 1 (BHV-1) type 2. Respiratory illness caused by Mycoplasma bovis are found in most of the calves that are pre-exposed to BHV-1 type 2. The percentage of abnormal tissue is reduced through a reduction in the number of the bacteria administered to BHV-1 exposed animals. The severity of clinical signs is found not affected by such reduction.

Attentional bias is considered an important concept in addiction since it has been found to correlate with subjective craving and is strongly associated with relapse after periods of abstinence. Hence, investigating in ways to regulate attention for drug cues would be of major clinical relevance. The present study examined deliberate, cognitive modulation of motivated attention for smoking cues in smokers. The effects of three different reappraisal strategies on an electrophysiological measure of attentive processing were investigated. Early and late LPP components in response to passively viewed neutral and smoking pictures were compared with LPPs in response to smoking pictures that were reappraised with three different reappraisal strategies. Results show that when smokers actively imagine how pleasant it would be to smoke (pleasant condition), their early LPP in response to smoking cues increases, but when smokers actively focus on an alternative stimulus (distraction condition) or think of a rational, uninvolved interpretation of the situation (rational condition), smoking-related late LPP amplitude decreases to the processing level of neutral stimuli. Present results are the first to indicate that smoking cue-elicited LPP amplitudes can be modulated by cognitive strategies, suggesting that attentive processing of smoking cues can be intentionally regulated by smokers with various levels of dependence. Although cognitive strategies can lead to enhanced processing of smoking cues, it is not completely clear whether cognitive strategies are also successful in reducing smoking-related motivated attention. Although findings do point in this direction, present study is best considered preliminary and a starting point for other research on this topic. A focus on the distraction strategy is proposed, as there are indications that this strategy is more successful than the rational strategy in decreasing LPP amplitude. [ABSTRACT FROM AUTHOR]