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Objective To examine interrelations between care-related burden on informal caregivers and their proxy assessments of outcomes in people without natural speech.Design A cross-sectional survey.Setting Data were collected in January 2019 from a postal survey of informal caregivers of people without natural speech who are insured by a large regional health insurance company in the German federal state of Lower Saxony.Participants n=714 informal caregivers of people without natural speech of all ages and with various underlying disabilities were identified and contacted via the health insurance company. Data from n=165 informal caregivers (26.4%) were obtained.Main outcome measures Caregiver burden (self-reported, Burden Scale for Family Caregivers), pragmatic communication skills of people without natural speech (proxy report, self-developed), health-related quality of life of people without natural speech (proxy report, DISABKIDS Chronic Generic Measure - DCGM-12) and functioning of people without natural speech (proxy report, WHO Disability Assessment Schedule 2.0).Results The analyses revealed significant associations between caregiver burden on the one hand and both proxy-reported health-related quality of life (b=−0.422; p≤0.001) and functioning (b=0.521; p≤0.001) on the other. Adding caregiver burden to the regression model leads to a substantial increase in explained variance in functioning (R² Model 1=0.349; R² Model 2=0.575) as well as in health-related quality of life (R² Model 1=0.292; R² Model 2=0.460).Conclusions Caregiver burden should be considered an important determinant when informal caregivers report outcomes on behalf of people without natural speech. Longitudinal studies are recommended to better understand the burdens experienced by caregivers when supporting people without natural speech.Trial registration number DRKS00013628.

An object-based method for automatic iceberg detection has been applied to Advanced Synthetic Aperture Radar images in the Amundsen Sea Embayment (ASE), Antarctica. The images were acquired between 1 January 2006 and 8 April 2012 under varying meteorological, oceanographic and sea-ice conditions. During this time period, the icebergs were counted (average 1370 ± 50) and their surface area was estimated (average 1537.5 km2). The average surface area was about 2.5 times larger than the annual calved area (620 km2), indicating that the average iceberg age in the ASE is about 2.5 years, which was confirmed by observed residence times based on drift tracks. Most of the ASE icebergs were less than 1500 m long, and almost 90% of them were smaller than 2 km2. The proportion of small- and medium-sized icebergs (84.4%) was significantly higher than in the open ocean, where large icebergs (>10 km2) account for nearly the whole iceberg surface area. The opposite was true for the freshly calved icebergs in the ASE. The data indicate that the creation of icebergs in the ASE is dominated by steady small- to medium-scale calving from ice shelves fringing the embayment. In addition, rare calving events of giant icebergs occur on a decadal timescale. There is also some import of icebergs from the Bellingshausen Sea further east along the coast, in particular after large calving events there.

I simulated selective harvest strategies of moose (Alces alces) using antler point restrictions and protection of cows with calves to assess the impact of these strategies on population age structure and potential harvest efficiency (proportion of allowed shooting opportunities). The post-hunt, adult bull:cow ratio was held constant throughout the simulations, but age structure of the bull cohort was allowed to vary. The simulation showed that protecting bulls with few antler points (

Abstract Background New and inexperienced emergency medical service (EMS) professionals lack important experience. To prevent medical errors and improve retention there is an urgent need to identify ways to support new professionals during their first year in the EMS. Methods A purposeful sample and snowball technique was used and generated a panel of 32 registered nurses with 12–48 months of EMS experience. A Delphi technique in four rounds was used. Telephone interviews were undertaken in round one to identify what desirable support professionals new to the EMS desire during their first year. Content analysis of the transcribed interviews yielded items which were developed into a questionnaire. The experts graded each item in terms of perceived importance on a 5-graded likert scale. Consensus level was set at 75%. Items which reached consensus were removed from questionnaires used in subsequent rounds. Results Desirable support was categorized into eight areas: Support from practical skills exercises, support from theoretical knowledge, support from experiences based knowledge, theoretical support, support from an introduction period, support from colleagues and work environment, support from management and organization and other support. The experts agree on the level of importance on 64 of a total of 70 items regarding desirable support. One item was considered not important, graded 1 or 2, 63 items were considered important, graded 4 or 5. Conclusion Even with extensive formal competence the EMS context poses challenges where a wide variety of desirable forms of support is needed. Support structures should address both personal and professional levels and be EMS context oriented.

Abstract Introduction Health disparities arise from biological‐environmental interactions. Neuroimaging cohorts are reaching sufficiently large sample sizes such that analyses could evaluate how the environment affects the brain. We present a practical guide for applying geospatial methods to a neuroimaging cohort. Methods We estimated brain age gap (BAG) from structural magnetic resonance imaging (MRI) from 239 city‐dwelling participants in St. Louis, Missouri. We compared these participants to population‐level estimates from the American Community Survey (ACS). We used geospatial analysis to identify neighborhoods associated with patterns of altered brain structure. We also evaluated the relationship between Area Deprivation Index (ADI) and BAG. Results We identify areas in St. Louis, Missouri that were significantly associated with higher BAG from a spatially representative cohort. We provide replication code. Conclusion We observe a relationship between neighborhoods and brain health, which suggests that neighborhood‐based interventions could be appropriate. We encourage other studies to geocode participant information to evaluate biological‐environmental interaction.

Summary: Neuronal hyperactivity induces memory deficits in Alzheimer’s disease. However, how hyperactivity disrupts memory is unclear. Using in vivo synaptic imaging in the mouse visual cortex, we show that structural excitatory-inhibitory synapse imbalance in the apical dendrites favors hyperactivity in early amyloidosis. Consistent with this, natural images elicit neuronal hyperactivity in these mice. Compensatory changes that maintain activity homeostasis disrupt functional connectivity and increase population sparseness such that a small fraction of neurons dominates population activity. These properties reduce the selectivity of neural response to natural images and render visual recognition memory vulnerable to interference. Deprivation of non-specific visual experiences improves the neural representation and behavioral expression of visual familiarity. In contrast, in non-pathological conditions, deprivation of non-specific visual experiences induces disinhibition, increases excitability, and disrupts visual familiarity. We show that disrupted familiarity occurs when the fraction of high-responsive neurons and the persistence of neural representation of a memory-associated stimulus are not constrained.

Medulloblastoma (MB) is the most common malignant pediatric brain tumor, however, the mechanisms underlying tumorigenesis in different MB subgroups remain incompletely understood. Although previous studies of MB predisposition have been conducted in tertiary referral centers primarily in Caucasian cohorts, it is not unclear clear whether there exist population-specific genetic alterations in MBs. In this study, we investigated the contribution of genomic and transcriptomic alterations to the risk of malignant MB in the Chinese population (designated as the Asian cohort). We analyze the genomic and transcriptomic alterations of the Asian MB cohort by using a combination of whole-exome sequencing (WES) and RNA-deep-sequencing. In addition, we integrate publicly available data with the Asian MB cohort and identify a subset of potential MB-driving genes specifically enriched in each of the MB subgroups. We further characterize a newly identified group-3-enriched transcriptional regulator, ZNF124, and demonstrate that ZNF124 is critical for the growth of the most aggressive group-3 MB cells. Together, our analyses indicate conserved yet distinct genetic alterations and gene expression patterns of MBs between different ethnic groups. Our studies further provide an important resource for identifying potential tumor-driving factors in MBs, enhancing our understanding of the disease process for developing ethnically targeted therapies in patients with MB.

Abstract A primary objective of synthetic biology is the construction of genetic circuits with behaviors that can be predicted based on the properties of the constituent genetic parts from which they are built. However a significant issue in the construction of synthetic genetic circuits is a phenomenon known as context dependence in which the behavior of a given part changes depending on the choice of adjacent or nearby parts. Interactions between parts compromise the modularity of the circuit, impeding the implementation of predictable genetic constructs. To address this issue, investigators have devised genetic insulators that prevent these unintended context-dependent interactions between neighboring parts. One of the most commonly used insulators in bacterial systems is the self-cleaving ribozyme RiboJ. Despite its utility as an insulator, there has been no systematic quantitative assessment of the effect of RiboJ on the expression level of downstream genetic parts. Here, we characterized the impact of insulation with RiboJ on expression of a reporter gene driven by a promoter from a library of 24 frequently employed constitutive promoters in an Escherichia coli model system. We show that, depending on the strength of the promoter, insulation with RiboJ increased protein abundance between twofold and tenfold and increased transcript abundance by an average of twofold. This result demonstrates that genetic insulators in E. coli can impact the expression of downstream genes, information that is essential for the design of predictable genetic circuits and constructs.

Ribonucleic acid (RNA) secondary structures and branching properties are important for determining functional ramifications in biology. While energy minimization of the Nearest Neighbor Thermodynamic Model (NNTM) is commonly used to identify such properties (number of hairpins, maximum ladder distance, etc.), it is difficult to know whether the resultant values fall within expected dispersion thresholds for a given energy function. The goal of this study was to construct a Markov chain capable of examining the dispersion of RNA secondary structures and branching properties obtained from NNTM energy function minimization independent of a specific nucleotide sequence. Plane trees are studied as a model for RNA secondary structure, with energy assigned to each tree based on the NNTM, and a corresponding Gibbs distribution is defined on the trees. Through a bijection between plane trees and 2-Motzkin paths, a Markov chain converging to the Gibbs distribution is constructed, and fast mixing time is established by estimating the spectral gap of the chain. The spectral gap estimate is obtained through a series of decompositions of the chain and also by building on known mixing time results for other chains on Dyck paths. The resulting algorithm can be used as a tool for exploring the branching structure of RNA, especially for long sequences, and to examine branching structure dependence on energy model parameters. Full exposition is provided for the mathematical techniques used with the expectation that these techniques will prove useful in bioinformatics, computational biology, and additional extended applications.

Abstract Background Monitoring elite athletes’ body composition (BC) is vital for health and optimizing performance in sports emphasizing leanness, such as athletics. This study aims to investigate and compare sex- and event-specific off-to in-season BC changes in endurance and power event athletics competitors. Methods Elite male and female endurance athletes (> 800 m runners; n = 21) and power event athletes (sprinters, jumpers; n = 32) underwent dual-energy X-ray absorptiometry (DXA) scans for whole and regional lean mass (LM), fat mass (FM), bone mineral content (BMC), and density (BMD) during off-season (September-October) and in-season (April-May). Linear mixed models tested between-group off-season differences in BC, within-group off-season to in-season changes, and between-group differences in change. To assess meaningful or least significant changes (LSC) in BC, DXA precision errors were determined from two consecutive total body scans in a subsample of athletes (n = 30). Results Male athletes (n = 26) gained significantly (p

ABSTRACTRationale The complex nature of student learning in clinical practice calls for a comprehensive pedagogical framework on how to create optimal learning affordances.Purpose The purpose of this study was to describe characteristics of conducted research regarding investigated research questions, distribution of different health care student groups, and employed methodological approaches.Methods A scoping review was chosen to capture the multifaceted characteristics in the field of learning in clinical practice. Funded local projects were analysed to provide significant core concepts for the literature search. A systematic search and review of articles published 2000–2019 in the Nordic countries was conducted according to PRISMA- ScR (23). The search was made in Medline (OVID), SveMed+ and CINAHL and resulted in 3126 articles. After screening of the titles and abstracts 988 articles were included for further review. The abstracts of all these articles were reviewed against established inclusion and exclusion criteria and 391 articles were included. Characteristics of purposes and research questions were analysed with a qualitative content approach resulting in identified subject areas including significant categories. Health care student groups and methodological approaches were also identified.Results Subjects predominating the research were organisation of clinical practice, supervision, and students’ experience followed by interprofessional learning and learning environment. Co-operation, university-clinical setting, and patients’ role were investigated to a small extent. Sparsely occurring subjects were also specific learning outcomes and evidence-based knowledge. Nursing students were involved in 74% of the studies, medical students in 20%, and other professions around 8%. Qualitative approaches were most common.Conclusion Health care students’ learning in clinical practice has been researched to a large extent within the Nordic countries and important subject areas are well represented. The research displays a great potential to extract and describe factors to create a pedagogical framework with significant meaning to support students’ learning.

Abstract Objective Due to communication barriers, people without natural speech who use augmentative and alternative communication (AAC) are rarely interviewed about their healthcare needs, expectations, and experiences. This qualitative interview study aims to investigate how AAC users evaluate a new service delivery (nSD) in AAC care in Germany. Results We conducted 8 semi-structured qualitative interviews with 8 AAC users. The results of the performed qualitative content analysis show a positive evaluation of the nSD among AAC users. Contextual factors were identified that seem to hinder the achievement of the intervention goals. These include caregivers' prejudice and inexperience with AAC and an unfavourable environment in which AAC is used.

Abstract Background People with disabilities and without natural speech often rely on care provided by informal caregivers. The caregiving situation of these informal caregivers has been poorly researched. The objectives of the study are 1) to identify stressors, resources, and coping strategies among informal caregivers of people without natural speech and 2) to examine whether a complex intervention in augmentative and alternative communication (AAC) that is not primarily tailored to the needs of informal caregivers can reduce care-related burden. Methods The main components of the AAC intervention were (1) initial counselling session, (2) 4 AAC training sessions, (3) 20 AAC therapy sessions and (4) accompanying case management. The control group received only the initial counselling session. Within a quasi-experimental intervention study, survey data on self-perceived burden (Burden Scale for Family Caregivers, BSFC-s) from n = 154 informal caregivers of people without natural speech were collected at three time points between June 2018 and April 2021 from a postal survey. Qualitative interviews with n = 16 informal caregivers were conducted. Results Caregivers reported various stressors such as limited communication with the cared-for person and concerns about the living situation in adulthood. Diverse resources and effective coping strategies, which the caregivers refer to when dealing with stressors, could also be identified. Burden was significantly reduced in the intervention group compared to the control group. According to the results of the qualitative study, AAC use led to better communication skills and a reduction in behavioural problems and thus a decreased burden. Conclusions The AAC intervention seems to have a positive impact on self-perceived burden. Linkages between intervention components and burden reduction as well as stressors and coping strategies could be identified and provide an evidence-based foundation for developing future holistic interventions for families with individuals without natural speech. Trial registration German Clinical Trials Register (DRKS); ID: DRKS00013628 (registered on 05/02/2018).

Introduction: Cutibacterium acnes is the most common cause of postoperative infections in orthopaedic shoulder surgery and is hard to eradicate with current measures. Newer strategies focus on reducing bacterial load on the skin before surgery. Several previous studies have used a large number of both described and undescribed sampling techniques. The purpose of this study was to compare three previously described swab techniques to obtain bacterial cultures: Levine's (L) technique, the Z technique and the pencil eraser swab (PES) technique. Methods: Three consecutive skin swabs were collected from the right shoulder, on 15 healthy male volunteers, using Levine's technique, Z technique and PES technique from each participant. To determine the number of living bacteria, serial dilutions were made, and after culturing for 5 d, viable count (VC) was expressed as CFU/mL (with CFU representing colony-forming unit). Results: The PES technique yielded significantly higher VC than the two others. PES: median 3700 CFU/mL, L: 200 CFU/mL and Z: 220 CFU/mL (p=0.003). There was no significant difference between the methods regarding the number of positive cultures. PES: 14/15, L: 11/15 and Z: 12/15. Conclusions: There is a need to harmonise sampling techniques of C. acnes in order to compare the efficacy of different measures to reduce the bacterial load on the skin before and during surgery. Of the three tested methods, the PES technique is simple and produces the highest bacterial counts.