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Abstract Background The COVID-19 pandemic engendered numerous societal and economic challenges in addition to health-related concerns. Maintenance of healthcare utilization assumed immense significance during this period. However, few studies have examined the association between loneliness and cancelled medical appointments during the COVID-19 pandemic. This study aimed to examine whether medical appointments are less likely to be cancelled with increased loneliness during a pandemic. We analyzed the association between loneliness and both patient- and provider-initiated appointment cancellations. Methods Cross-sectional data from the Hamburg City Health Study (HCHS) were collected during April 2020–November 2021. The analytical sample included 1,840 participants with an average age of 55.1 years (standard deviation: 6.5, range 45–76 years). Medical appointments cancelled by individuals—medical appointments in general, and GP, specialist, and dentist appointments—and appointments cancelled by healthcare providers served as outcome measures. Loneliness was quantified using a single item ranging from 0 to 10. Accordingly, we created empirical loneliness tertiles. Covariates were selected based on the Andersen model. Several penalized maximum likelihood logistic regressions were utilized to examine the association between loneliness and cancellation of medical appointments during the COVID-19 pandemic. Results The penalized maximum likelihood logistic regressions showed that, compared to individuals in the lowest loneliness tertiles, individuals in the other two tertiles reported a higher chance of medical appointments cancellation by individuals, particularly driven by cancelled GP appointments. Except for age and sex, none of the covariates were comparably associated with the outcomes. When appointments cancelled by healthcare providers served as outcomes, only a higher number of chronic conditions was significantly positively associated with it. Conclusions Individuals scoring higher in loneliness had a greater chance of cancelling medical (particularly GP) appointments. This may contribute to a potential cascade of loneliness and skipped medical appointments in the future, resulting in adverse health outcomes over the medium-to-long term. Future research should examine whether lonely people are more likely to lack the social motivation to visit the doctor.

Identifying functional biomarkers related to treatment success can aid in expediting therapy optimization, as well as contribute to a better understanding of the neural mechanisms of the treatment-resistant depression (TRD) and subcallosal cingulate deep brain stimulation (SCC-DBS).Magnetoencephalography data were obtained from 16 individuals with SCC-DBS for TRD and 25 healthy subjects. The first objective of the study was to identify region-specific oscillatory modulations that both (i) discriminate individuals with TRD (with SCC-DBS OFF) from healthy controls, and (ii) discriminate TRD treatment responders from non-responders (with SCC-DBS ON). The second objective of this work was to further explore the effects of stimulation intensity and frequency on oscillatory activity in the identified brain regions of interest.Oscillatory power analyses led to the identification of brain regions that differentiated responders from non-responders based on modulations of increased alpha (8–12 Hz) and decreased gamma (32–116 Hz) power within nodes of the default mode, central executive, and somatomotor networks, Broca's area, and lingual gyrus. Within these nodes, it was also found that low stimulation frequency had stronger effects on oscillatory modulation than increased stimulation intensity.The identified functional network biomarkers implicate modulation of TRD-related activity in brain regions involved in emotional control/processing, motor control, and the interaction between speech, vision, and memory, which have all been implicated in depression. These electrophysiological biomarkers have the potential to be used as functional proxies for therapy optimization. Additional stimulation parameter analyses revealed that oscillatory modulations can be strengthened by increasing stimulation intensity or reducing frequency, which may represent potential avenues of direction in non-responders.

Abstract High power solid-state Li batteries (SSLB) are hindered by the formation of dendrite-like structures at high current rates. Hence, new design principles are needed to overcome this limitation. By introducing dislocations, we aim to tailor mechanical properties in order to withstand the mechanical stress leading to Li penetration and resulting in a short circuit by a crack-opening mechanism. Such defect engineering, furthermore, appears to enable whisker-like Li metal electrodes for high-rate Li plating. To reach these goals, the challenge of introducing dislocations into ceramic electrolytes needs to be addressed which requires to establish fundamental understanding of the mechanics of dislocations in the particular ceramics. Here we evaluate uniaxial deformation at elevated temperatures as one possible approach to introduce dislocations. By using hot-pressed pellets and single crystals grown by Czochralski method of Li6.4La3Zr1.4Ta0.6O12 garnets as a model system the plastic deformation by more than 10% is demonstrated. While conclusions on the predominating deformation mechanism remain challenging, analysis of activation energy, activation volume, diffusion creep, and the defect structure potentially point to a deformation mechanism involving dislocations. These parameters allow identification of a process window and are a key step on the road of making dislocations available as a design element for SSLB.

Abstract This paper aims to evaluate the reliability indexes of reinforced concrete beams designed in accordance with brazilian code NBR-6118:2014 in relation to the ultimate limit state of flexure. The main statistics of the resistance model are obtained through Monte Carlo simulation using ANSYS software and its probabilistic design tool. The reliability indexes are evaluated by FORM, being performed a parametric study in order to assess the influence of the main design variables on the safety level reached. It can be noticed that the reliability indexes are shown unsatisfactory in the combinations which the live loads are predominant.

Bog pine is an endangered species in Europe as drainage of bogs permits colonisation by Norway spruce, resulting in severe bog pine habitat loss in marginal bog forests, and a habitat shift towards the bog centre where growing conditions are extreme. Thus, we investigated the physiological causes that limit bog pine regeneration at the bog margins and growth in the centre. We measured needle nitrogen concentration, chlorophyll content, photosynthetic capacity and the morphological traits of bog pine and spruce along transects from the centre to the margin of a bog in the Black Forest, Germany. Needle nitrogen and chlorophyll contents in the bog pine increased from the centre to the margin. However, photosynthesis was independent of chlorophyll content indicating that other factors, such as light rather than nutrients, may limit regeneration of bog pine. Vitality of bog pine was highest at the edge of the bog centre. This zone appears to be a compromise between nutrient limitation and shallow water levels on the one hand, and light limitation caused by spruce on the other. Therefore, in order to conserve bog pine, it is necessary to maintain wet and open bog forests that cannot be colonised by spruce.

Abstract Background Medically unexplained symptoms (MUS) and somatoform disorders are common in general practices, but there is evidence that general practitioners (GPs) rarely use these codes. Assuming that correct classification and coding of symptoms and diseases are important for adequate management and treatment, insights into these processes could reveal problematic areas and possible solutions. Our study aims at exploring general practitioners’ views on coding and reasons for not coding MUS/somatoform disorders. Methods We invited GPs to participate in six focus groups (N = 42). Patient vignettes and a semi-structured guideline were used by two moderators to facilitate the discussions. Recordings were transcribed verbatim. Two researchers analyzed the data using structuring content analysis with deductive and inductive category building. Results Three main categories turned out to be most relevant. For category a) “benefits of coding” GPs described that coding is seen as being done for reimbursement purposes and is not necessarily linked to the content of their reference files for a specific patient. Others reported to code specific diagnoses only if longer consultations to explore psychosomatic symptoms or psychotherapy are intended to be billed. Reasons for b) “restrained coding” were attempting to protect the patient from stigma through certain diagnoses and the preference for tentative diagnoses and functional coding. Some GPs admitted to c) “code inaccurately” attributing this to insufficient knowledge of ICD-10-criteria, time constraints or using “rules of thumb” for coding. Conclusions There seem to be challenges in the process of coding of MUS and somatoform disorders, but GPs appear not to contest the patients’ suffering and accept uncertainty (about diagnoses) as an elementary part of their work. From GPs’ points of view ICD-10-coding does not appear to be a necessary requirement for treating patients and coding might be avoided to protect the patients from stigma and other negative consequences. Our findings supply a possible explanation for the commonly seen difference between routine and epidemiological data. The recent developments in the DSM-5 and the upcoming ICD-11 will supposedly change acceptance and handling of these diagnoses for GPs and patients. Either way, consequences for GPs’ diagnosing and coding behavior are not yet foreseeable.

Abstract Introduction There is conflicting evidence whether high‐density lipoprotein cholesterol (HDL‐C) is a risk factor for Alzheimer's disease (AD) and dementia. Genetic variation in the cholesteryl ester transfer protein (CETP) locus is associated with altered HDL‐C. We aimed to assess AD risk by genetically predicted HDL‐C. Methods Ten single nucleotide polymorphisms within the CETP locus predicting HDL‐C were applied to the International Genomics of Alzheimer's Project (IGAP) exome chip stage 1 results in up 16,097 late onset AD cases and 18,077 cognitively normal elderly controls. We performed instrumental variables analysis using inverse variance weighting, weighted median, and MR‐Egger. Results Based on 10 single nucleotide polymorphisms distinctly predicting HDL‐C in the CETP locus, we found that HDL‐C was not associated with risk of AD (P > .7). Discussion Our study does not support the role of HDL‐C on risk of AD through HDL‐C altered by CETP. This study does not rule out other mechanisms by which HDL‐C affects risk of AD.

Abstract Background Patients from rural and urban regions should have equitable access to health care. In Germany, the physician-patient-ratio and the supply of medical services vary greatly between urban and rural areas. The aim of our study was to explore the regional variations of the perceived health care problems in ambulatory care from the perspective of affected professionals and laypersons i.e. general practitioners and their patients. Methods We conducted 27 focus groups with general practitioners (n = 65) and patients (n = 145) from urban areas, environs and rural areas in northern Germany. Discussions were facilitated by two researchers using a semi-structured guideline. The transcripts were content analyzed using deductive and inductive categories. Results General practitioners and patients reported problems due to demographic change and patient behaviour, through structural inequalities and the ambulatory reimbursement system as well as with specialist care and inpatient care. A high physician density, associated with high competition between general practitioners, a high fluctuation of patients and a low status of general practitioners were the main problems reported in urban areas. In contrast, participants from rural areas reported an insufficient physician density, a lack of young recruits in primary care and a resulting increased workload as problematic. All regions are concerned with subjectively inadequate general practitioners’ budgets, insufficiently compensated consultations and problems in the cooperation with specialists and inpatient care institutions. Most problems were mentioned by GPs and patients alike, but some (e.g. high competition rates in urban regions and problems with inpatient care) were only mentioned by GPs. Conclusions While many problems arise in urban regions as well as in rural regions, our results support the notion that there is an urgent need for action in rural areas. Possible measures include the support of telemedicine, delegation of medical services and reoccupation of vacant practices. The attractiveness of working in rural areas for general practitioners, specialists and clinicians must be increased by consolidating and expanding rural infrastructure (e.g. child care and cultural life). The above mentioned results also indicate that the ambulatory reimbursement system should be examined regarding the reported inequalities. Measures to further enhance the cooperation between general practitioners, specialists and inpatient care should be taken to solve supra-regionally reported problems. Problems showing regional variations indicate the need for measures to balance these variations between the regions. This is the first German study to analyze subjective views of the stakeholders concerned on regionally variating problems in ambulatory care. Further studies are needed to quantify the extent of the identified problems and differences. A corresponding survey is currently under way.

In recent years, advances in biomedicine have revealed an important role for post-transcriptional mechanisms of gene expression regulation in pathologic conditions. In cancer in general and leukaemia specifically, RNA binding proteins have emerged as important regulator of RNA homoeostasis that are often dysregulated in the disease state. Having established the importance of these pathogenetic mechanisms, there have been a number of efforts to target RNA binding proteins using oligonucleotide-based strategies, as well as with small organic molecules. The field is at an exciting inflection point with the convergence of biomedical knowledge, small molecule screening strategies and improved chemical methods for synthesis and construction of sophisticated small molecules. Here, we review the mechanisms of post-transcriptional gene regulation, specifically in leukaemia, current small-molecule based efforts to target RNA binding proteins, and future prospects.

Hardware and software of the universally applicable instrument - referred to as a 2D/3D total station – are described here, as well as its practical use. At its core it consists of a 3D camera – often also called a ToF camera, a pmd camera or a RIM-camera – combined with a common industrial 2D camera. The cameras are rigidly coupled with their optical axes in parallel. A new type of instrument was created mounting this 2D/3D system on a tripod in a specific way. Because of it sharing certain characteristics with a total station and a tacheometer, respectively, the new device was called a 2D/3D total station. It may effectively replace a common total station or a laser scanner in some respects. After a brief overview of the prototype's features this paper then focuses on the methodological characteristics for practical application. Its usability as a universally applicable stand-alone instrument is demonstrated for surveying, recording RGB-coloured point clouds as well as delivering images for documentation and visualisation. Because of its limited range (10m without reflector and 150 m to reflector prisms) and low range accuracy (ca. 2 cm to 3 cm) compared to present-day total stations and laser scanners, the practical usage of the 2D/3D total station is currently limited to acquisition of accidents, forensic purpuses, speleology or facility management, as well as architectural recordings with low requirements regarding accuracy. However, the author is convinced that in the near future advancements in 3D camera technology will allow this type of comparatively low cost instrument to replace the total station as well as the laser scanner in an increasing number of areas.

Modern grassland management seeks to provide many ecosystem services and experimental studies in resource-poor grasslands have shown a positive relationship between plant species richness and a variety of ecosystem functions. Thus, increasing species richness might help to enhance multifunctionality in managed grasslands if the relationship between species richness and ecosystem functioning is equally valid in high-input grassland systems. We tested the relative effects of low-input to high-input management intensities and low to high plant species richness. Using a combination of mowing frequencies (1, 2 or 4 cuts per season) and fertilisation levels (0, 100 and 200 kg N ha−1 a−1), we studied the productivity of 78 experimental grassland communities of increasing plant species richness (1, 2, 4, 8 or 16 species with 1 to 4 functional groups) in two successive years. Our results showed that in both years higher diversity was more effective in increasing productivity than higher management intensity: the 16-species mixtures had a surplus of 449 g m−2 y−1 in 2006 and 492 g m−2 y−1 in 2007 over the monoculture yields whereas the high-input management resulted in only 315 g m−2 y−1 higher productivity in 2006 and 440 g m−2 y−1 in 2007 than the low-input management. In addition, high-diversity low-input grassland communities had similar productivity as low-diversity high-input communities. The slopes of the biodiversity – productivity relationships significantly increased with increasing levels of management intensity in both years. We conclude that the biological mechanisms leading to enhanced biomass production in diverse grassland communities are as effective for productivity as a combination of several agricultural measures. Our results demonstrate that high-diversity low-input grassland communities provide not only a high diversity of plants and other organisms, but also ensure high forage yields, thus granting the basis for multifunctional managed grasslands.

This paper presents an updated trend analysis of water vapour in the lower midlatitude stratosphere from the Boulder balloon-borne NOAA frostpoint hygrometer measurements and from the Halogen Occulation Experiment (HALOE). Two corrections for instrumental bias are applied to homogenise the frostpoint data series, and a quality assessment of all soundings after 1991 is presented. Linear trend estimates based on the corrected data for the period 1980–2000 are up to 40% lower than previously reported. Vertically resolved trends and variability are calculated with a multi regression analysis including the quasi-biennal oscillation and equivalent latitude as explanatory variables. In the range of 380 to 640 K potential temperature (≈14 to 25 km), the frostpoint data from 1981 to 2006 show positive linear trends between 0.3±0.3 and 0.7±0.1%/yr. The same dataset shows trends between −0.2±0.3 and 1.0±0.3%/yr for the period 1992 to 2005. HALOE data over the same time period suggest negative trends ranging from −1.1±0.2 to −0.1±0.1%/yr. In the lower stratosphere, a rapid drop of water vapour is observed in 2000/2001 with little change since. At higher altitudes, the transition is more gradual, with slowly decreasing concentrations between 2001 and 2007. This pattern is consistent with a change induced by a drop of water concentrations at entry into the stratosphere. Previously noted differences in trends and variability between frostpoint and HALOE remain for the homogenised data. Due to uncertainties in reanalysis temperatures and stratospheric transport combined with uncertainties in observations, no quantitative inference about changes of water entering the stratosphere in the tropics could be made with the mid latitude measurements analysed here.

Hand-written or printed manuscript data are an important source for paleo-climatological studies, but bringing them into a suitable format can be a time consuming adventure with uncertain success. Before digitising such data (e.g., in the context a specific research project), it is worthwhile spending a few thoughts on the characteristics of the data, the scientific requirements with respect to quality and coverage, the metadata, and technical aspects such as reproduction techniques, digitising techniques, and quality control strategies. Here we briefly discuss the most important considerations according to our own experience and describe different methods for digitising numeric or text data (optical character recognition, speech recognition, and key entry). We present a tentative guide that is intended to help others compiling the necessary information and making the right decisions.