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Quantile mapping is a method often used for the bias adjustment of climate model data toward a reference, i.e. to construct a transformation of the model's distribution to that of the reference. The main moments of the distributions are typically well transformed by quantile mapping, but statistical uncertainty increases towards the extreme tails, making robust transformations challenging. Because of the limited data at the extreme tails, an empirical quantile mapping also needs to make some estimation or fit a parameterised function for data beyond the calibration data range. Here, the MIdAS bias adjustment platform is employed to explore different methods for handling the extreme tail; these approaches are evaluated using an indicator of extreme precipitation – the maximum daily precipitation amount per year. Different methodologies are evaluated for a large ensemble of regional climate model projections over Scandinavia. The sensitivity of the empirical quantile mapping to the tails of the distribution is demonstrated, and it is found that the behaviour is significantly different within and outside of the calibration period, causing severe issues with the temporal consistency of the time series. The sensitivity is identified to be due to differences in the activated features of the bias adjustment within the calibration period (where the empirical transfer function is applied) and outside of that period (where the extrapolation method is likely applied). This means that the bias adjustment method is, in a sense, different between different time periods. Furthermore, finding a robust parameterisation for the tail is not straightforward. We identify a two-step solution that works well for this problem: We refer to the first step as “Murder your darlings”. By excluding data from the tail data in the calibration period, the extrapolation feature is activated for all time periods, even the calibration period. In the second step, applying an outlier-insensitive method for linear regression works well for finding an extrapolation parameterisation for the tail.

Over the last two decades, an emerging body of research has demonstrated that non-human animals exhibit the ability to combine context-specific calls into larger sequences. These structures have frequently been compared with language’s syntax, whereby linguistic units are combined to form larger structures, and leveraged to argue that syntax might not be unique to language. Currently, however, the overwhelming majority of examples of call combinations are limited to simple sequences comprising just two calls which differ dramatically from the open-ended hierarchical structuring of the syntax found in language. We revisit this issue by taking a whole-repertoire approach to investigate combinatoriality in common marmosets (Callithrix jacchus). We use Markov chain models to quantify the vocal sequences produced by marmosets providing evidence for structures beyond the bigram, including three-call and even combinations of up to eight or nine calls. Our analyses of these longer vocal sequences are suggestive of potential further internal organization, including some amount of recombination, nestedness and non-adjacent dependencies. We argue that data-driven, whole-repertoire analyses are fundamental to uncovering the combinatorial complexity of non-human animals and will further facilitate meaningful comparisons with language’s combinatoriality.

Abstract Patient-derived xenograft (PDX) models are widely used in cancer research. To investigate the genomic fidelity of non-small cell lung cancer PDX models, we established 48 PDX models from 22 patients enrolled in the TRACERx study. Multi-region tumor sampling increased successful PDX engraftment and most models were histologically similar to their parent tumor. Whole-exome sequencing enabled comparison of tumors and PDX models and we provide an adapted mouse reference genome for improved removal of NOD scid gamma (NSG) mouse-derived reads from sequencing data. PDX model establishment caused a genomic bottleneck, with models often representing a single tumor subclone. While distinct tumor subclones were represented in independent models from the same tumor, individual PDX models did not fully recapitulate intratumor heterogeneity. On-going genomic evolution in mice contributed modestly to the genomic distance between tumors and PDX models. Our study highlights the importance of considering primary tumor heterogeneity when using PDX models and emphasizes the benefit of comprehensive tumor sampling.

Abstract Stress arousal reappraisal (SAR) and stress-is-enhancing (SIE) mindset interventions aim to promote a more adaptive stress response by educating individuals about the functionality of stress. As part of this framework, an adaptive stress response is coupled with improved performance on stressful tasks. The goal of this meta-analysis is to evaluate the effectiveness of these interventions on task performance. The literature search yielded 44 effect sizes, and a random-effects model with Knapp-Hartung adjustment was used to pool them. The results revealed an overall small significant improvement in task performance (d = 0.23, p

Abstract Gephyrin is the main scaffolding protein at inhibitory postsynaptic sites, and its clusters are the signaling hubs where several molecular pathways converge. Post-translational modifications (PTMs) of gephyrin alter GABAA receptor clustering at the synapse, but it is unclear how this affects neuronal activity at the circuit level. We assessed the contribution of gephyrin PTMs to microcircuit activity in the mouse barrel cortex by slice electrophysiology and in vivo two-photon calcium imaging of layer 2/3 (L2/3) pyramidal cells during single-whisker stimulation. Our results suggest that, depending on the type of gephyrin PTM, the neuronal activities of L2/3 pyramidal neurons can be differentially modulated, leading to changes in the size of the neuronal population responding to the single-whisker stimulation. Furthermore, we show that gephyrin PTMs have their preference for selecting synaptic GABAA receptor subunits. Our results identify an important role of gephyrin and GABAergic postsynaptic sites for cortical microcircuit function during sensory stimulation.

Whale mortality and strandings have increased in recent years, with deceased whales often brought to landfill. However, the disposal of whale remains offshore holds significant ecological importance and can be a culturally and ethically sensitive approach. Moreover, offshore disposal mitigates potential risks associated with onshore whale remains disposal, such as the spread of diseases and the logistical challenges of managing large carcasses. A challenge with offshore disposal is defining the best release location to avoid the remains drifting ashore or into shipping channels. Here we compared the drift model outputs using a drift forecast model (SARMAP) for a 14 m whale carcass that was moved offshore in southeast Queensland, Australia, and fitted with a satellite tracker over an observation period of 150 h until positioning signal ceased. The modelling was conducted using different ocean products (BLUElink, HYCOM, and Copernicus), which showed a good agreement with the tracked whale carcass, albeit with changing wind conditions and contrasting currents flowing northward along the coast and, further offshore, flowing south. This case study illustrated that wind was the foremost driver of carcass drift due to the surface area above the water surface. The drift forecast simulations allowed for a reliable prediction of the floating whale drift that can assist authorities with decision making. Offshore disposal of whale carcasses is a sustainable practice but requires good planning and scientific assessment.

Large bone defects after trauma demand for adequate bone substitutes. Bone void fillers should be antibacterial and pro-angiogenic. One viable option is the use of composite materials like the combination of PLGA and amorphous calcium phosphate (aCaP).Copper stimulates angiogenesis and has antibacterial qualities. Either copper oxide (CuO) nanoparticles (NPs) were therefore added to PLGA/aCaP/CuO in different concentrations (1, 5 and 10 w/w %) or copper-doped tricalcium phosphate NPs (TCP with 2% of copper) were electrospun into PLGA/CuTCP nanocomposites.Bi-layered nanocomposites of PLGA/aCaP with different copper NPs (CuO or TCP) and a second layer of pristine PLGA were fabricated. Two clinical bacterial isolates (Staphylococcus aureus and Staphylococcus epidermidis) were used to assess antibacterial properties of the copper-containing materials. For angiogenesis, the chorioallantoic membrane (CAM) assay of the chicken embryo was performed.The higher the CuO content, the higher were the antibacterial properties, with 10 % CuO reducing bacterial adhesion most effectively. Vessel and cell densities were highest in the 5 % CuO containing scaffolds, while tissue integration was more pronounced at lower CuO content. The PLGA/aCaP/CuO (1 % CuO) behaved similar like PLGA/CuTCP in all angiogenic and antibacterial readouts, based on the same copper fraction.We conclude that CuO NPs or CuTCP NPs are useful components to increase angiogenic properties of nanocomposites and at the same time exhibiting antibacterial characteristics.

BackgroundAtopic dermatitis (AD) is a chronic relapsing inflammatory skin disease in which patients are sensitized towards a plethora of allergens. The hosts fungal microbiota, the mycobiota, that is believed to be altered in patients suffering from AD acts as such an allergen. The correlation context of specific sensitization, changes in mycobiota and its impact on disease severity however remains poorly understood.ObjectivesWe aim to enhance the understanding of the specific sensitization towards the mycobiota in AD patients in relation to their fungal skin colonization.MethodsSensitization pattern towards the Malassezia spp. and Candida albicans of 16 AD patients and 14 healthy controls (HC) were analyzed with the newly developed multiplex-assay ALEX2® and the established singleplex-assay ImmunoCAP®. We compared these findings with the fungal skin colonization analyzed by DNA sequencing of the internal transcribed spacer region 1 (ITS1).ResultsSensitization in general and towards Malassezia spp. and C. albicans is increased in AD patients compared to HC with a quantitative difference in severe AD when compared to mild to moderate AD. Further we saw an association between sensitization towards and skin colonization with Candida spp. yet a negative correlation between sensitization towards and skin colonization with Malassezia spp.ConclusionWe conclude that AD in general and severe AD in particular is associated with increased sensitization towards the hosts own mycobiota. There is positive correlation in Candida spp. skin colonization and negative in Malassezia spp. skin colonization when compared to AD, AD severity as well as to specific sensitization patterns.

Yaws affects children in tropical regions, while syphilis primarily affects sexually active adults worldwide. Despite various campaigns towards the eradication of yaws and elimination of syphilis, these two diseases are still present in Ghana. The aetiological agents of both diseases, two Treponema pallidum subspecies, are genetically similar. This study aimed to assess the prevalence of these treponematoses and the occurrence of pathogens causing similar skin lesions in the Ashanti region of Ghana. A point-of-care test was used to determine the seroprevalence of the treponematoses. Both yaws and syphilis were identified in the Ashanti region of Ghana. Multiplex PCR was used to identify treponemes and other pathogens that cause similar skin lesions. The results indicated that the seroprevalences of T. pallidum in individuals with yaws-like and syphilis-like lesions were 17.2% and 10.8%, respectively. Multiplex PCR results showed that 9.1%, 1.8% and 0.9% of yaws-like lesions were positive for Haemophilus ducreyi, herpes simplex virus-1 (HSV-1) and T. pallidum respectively. Among syphilis-like lesions, 28.3% were positive for herpes simplex virus -2 (HSV-2) by PCR. To our knowledge, this is the first time HSV-I and HSV-2 have been reported from yaws-like and syphilis-like lesions, respectively, in Ghana. The presence of other organisms apart from T. pallidum in yaws-like and syphilis-like lesions could impede the total healing of these lesions and the full recovery of patients. This may complicate efforts to achieve yaws eradication by 2030 and the elimination of syphilis and warrants updated empirical treatment guidelines for skin ulcer diseases.

Abstract Background Breaking bad news (BBN; e.g., delivering a cancer diagnosis) is perceived as one of the most demanding communication tasks in the medical field and associated with high levels of stress. Physicians’ increased stress in BBN encounters can negatively impact their communication performance, and in the long term, patient-related health outcomes. Although a growing body of literature acknowledges the stressful nature of BBN, little has been done to address this issue. Therefore, there is a need for appropriate tools to help physicians cope with their stress response, so that they can perform BBN at their best. In the present study, we implement the biopsychosocial model of challenge and threat as theoretical framework. According to this model, the balance between perceived situational demands and perceived coping resources determines whether a stressful performance situation, such as BBN, is experienced as challenge (resources > demands) or threat (resources

Coupled glacio-hydrological models have recently become a valuable method for predicting the hydrological response of catchments in mountainous regions under a changing climate. While hydrological models focus mostly on processes of the non-glacierized part of the catchment with a relatively simple glacier representation, the latest generation of standalone (global) glacier models tend to describe glacier processes more accurately by using new global datasets and explicitly modeling ice-flow dynamics. Yet, to the authors' knowledge, existing catchment-scale coupled glacio-hydrological models either do not include these most recent advances in glacier modeling or are simply not available to other users. By making use of the capabilities of the free, distributed, physically-based Water Flow and Balance Simulation Model (WaSiM) and the Open Global Glacier Model (OGGM), a coupling scheme is developed to bridge the gap between global glacier representation and local catchment hydrology. The WaSiM-OGGM coupling scheme is used to further assess the impacts under future climates on the glaciological and hydrological processes in the Gepatschalm catchment (Austria), by considering a combination of three climate projections under the Representative Concentration Pathways (RCP) 2.6, 4.5, and 8.5. Additionally, the results are compared to the original WaSiM model with the integrated Volume-Area (VA) scaling approach for modeling glaciers. Although both models (WaSiM with VA scaling and WaSiM-OGGM coupling scheme) perform very similar during the historical simulations (1971–2010), large discrepancies arise when looking into the future (2011–2100). In terms of runoff, the VA scaling model suggests a reduction of the mean monthly peak between 10–19%, whereas a reduction of 26–41% is computed by the coupling scheme. Similarly, results suggest that glaciers will continuously retreat until 2100. By the end of the century, between 20–43% of the 2010 glacier area will remain according to the VA scaling model, but only 1–23% is expected to remain with the coupling scheme. The results from the WaSiM-OGGM coupling scheme raises awareness of including more sophisticated glacier evolution models when performing hydrological simulations at the catchment scale in the future. As the WaSiM-OGGM coupling scheme is released as open-source software, it is accessible to any interested modeler with limited or even no glacier knowledge.

AIMS OF THE STUDY: We previously reported a re-emergence of syphilis from 2006 to 2009 with detection of congenital syphilis in Switzerland. This study aimed to reassess the incidence of children exposed to maternal syphilis during pregnancy and congenital syphilis in a following 10-year period in the canton of Zurich, the most populous canton in Switzerland with the highest incidences of syphilis. METHODS: Children were identified both by reviewing medical records at the four major neonatal and paediatric hospitals providing acute care in the canton of Zurich and by the serological database of the syphilis reference laboratory. Inclusion criteria for children were (a) date of birth in the period 2010–2019, (b) place of birth in the canton of Zurich, (c) evaluation for syphilis due to positive syphilis pregnancy screening and (d) age

Whilst radio, podcasts, and music streaming are considered unique audio formats that offer brands different opportunities, limited research has explored this notion. This current study analyses how the brain responds to these formats and suggests that they offer different branding opportunities. Participants’ engagement, attitude, attention, memory, and physiological arousal were measured while each audio format was consumed. The results revealed that music streaming elicited more positive attitudes, higher attention, greater levels of memory encoding, and increased physiological arousal compared to either radio or podcasts. This study emphasises the importance for brands of utilising diverse audio channels for unique branding and marketing opportunities.

To meet the European Union's 2050 climate neutrality target, future electricity generation is expected to largely rely on variable renewable energy (VRE). VRE supply, being dependant on weather, is susceptible to changing climate conditions. Based on spatiotemporally explicit climate data under a Paris-proof climate scenario and a comprehensive energy conversion model, this study assesses the projected changes of European VRE supply from the perspective of average production, production variability, spatiotemporal complementarity, and risk of concurrent renewable energy droughts.For the period 2045–2055, we find a minor reduction in average wind and solar production for most of Europe compared to the period 1990–2010. At the country level, the impact of climate change on average VRE production is rather limited in magnitude (within ±3% for wind and ±2% for solar). The projected mid-term changes in other aspects of VRE supply are also relatively small. This suggests climate-related impacts on European VRE supply are less of a concern if the Paris-proof emission reduction pathway is strictly followed.Based on spectral analysis, we identify strong seasonal wind-solar complementarities (with an anticorrelation between -0.6 and -0.9) at the cross-regional level. This reduces the demand for seasonal storage but requires coordinated cross-border efforts to develop a pan-European transmission infrastructure.The risk of concurrent renewable energy droughts between a country and the rest of Europe remains non-negligible, even under the copperplate assumption. Central Western European countries and Poland are most vulnerable to such risk, suggesting the need for the planning of adequate flexibility resources.

To determine the utilization rate of a home-based rehabilitation program after an inpatient rehabilitation stay, and to investigate the profile of users. Observational study. Inpatient rehabilitation facility in a tertiary hospital. Older patients (N=1913) discharged home between June 2018 and May 2021, after an inpatient rehabilitation stay. Not applicable. Discharge to home-based rehabilitation. Over the study period, 296 (15.5%) patients were discharged to home-based rehabilitation. Compared with the others, home-based rehabilitation patients were more frequently women (69.6% vs 61.5%; P =.008), and admitted after orthopedic surgery (elective or for fracture) (30.1% vs 16.1%; P <.001). They had worse functional performance at admission (mean Functional Independence Measure self-care score: 27.8±7.3 vs 30.8±6.7; P <.001), but greater gain in self-care during their inpatient stay (5.0±4.8 vs 4.4±4.7; P =.038). In multivariable analysis, being a woman (adjusted odds ratio [adjOR], 1.36; 95% confidence interval [CI], 1.01-1.82; P =.040), being admitted after orthopedic surgery (adjOR, 2.32; 95% CI, 1.64-3.27; P <.001), being admitted for gait disorders or falls (adjOR, 1.38; 95% CI, 1.01-1.88; P =.039), and showing greater gain in mobility during the inpatient stay (adjOR, 1.12; 95% CI, 1.07-1.17; P <.001) remained associated with discharge to home-based rehabilitation. In contrast, higher mobility at discharge decreased the odds of discharge to home-based rehabilitation (adjOR, 0.87; 95% CI, 0.83-0.91; P <.001). One in 6 patients benefited from home-based rehabilitation after their inpatient stay. Although these patients had poorer functional performance at admission and discharge, they showed greater mobility improvement during their inpatient stay, suggesting that their good recovery potential was a key determinant of their orientation toward home-based rehabilitation. [ABSTRACT FROM AUTHOR]

The present study addresses the question of whether explicit, survey-type measures of attitude differ in sensitivity when compared to implicit, non-conscious measures of attitude in the context of attitude changes in response to evaluative conditioning (EC). In the frame of a pre-test, participants rated 300 brand names on a Likert-type scale, the results of which were then used to create personalised lists of neutral brands. After this initial online component, the participants were exposed to one, five, and ten rounds of EC (during three separate sessions), during which half of the brands were paired with pleasant audio excerpts (positive EC) and the remainder were paired with unpleasant audio excerpts (negative EC). Following each conditioning round, the participants rated the brand names again, whilst changes in the brain’s electrical activity in response to the brands were recorded via electroencephalography (EEG). After having rated the brand names, the participants also completed two implicit association tests (IAT; one for each of the neutral conditions). The results revealed that self-reported, explicit responses of brand names remained unchanged despite having been conditioned. Similarly, the IAT did not reveal any declines in reaction time. In contrast, the EEG data appeared to not only be sensitive to initial brand ratings, but also the conditioning effects of initially neutral brands. Respective neurophysiological effects were found at frontal electrode locations AF3 and AF4 for a 1 s-long time window starting at 400 ms after stimulus onset. Furthermore, the EEG revealed that changes in brand attitude are more susceptible to the effects of negative conditioning than positive conditioning. Given the rather small sample size, any generalizability seems vague, but the present results provide scientific evidence that EEG could indeed be a valuable additional method to investigate EC effects. The results of this study support the notion of utilising a multidimensional approach, inclusive of neuroscience, to understanding consumer attitudes instead of solely relying on self-report measures. In the end, the brain knows more than it admits to consciousness and language, which is why objective methods should always be included in any study.

Commitments to Forest and Landscape Restoration are rapidly growing and being implemented globally to tackle the climate and biodiversity crises. Restoration initiatives largely based on tree planting necessitate an increased supply of high-quality and suitably adapted tree planting material. We evaluated the native tree seed supply systems in Burkina Faso, Cameroon, Ghana, and Kenya, four countries with large commitments to increase tree cover. We applied an established indicator framework to assess the adequacy of any current tree seed system to meet national needs. The study aimed to analyse (i) how well-established the native tree seed supply systems are, (ii) how public and non-public actors differ regarding the perception of existing seed systems, and (iii) the main barriers to strengthening current seed systems. Our findings identified significant gaps in the native tree seed supply systems of the four countries, arising particularly from shortfalls in the enabling environment. We found a lack of involvement of local community members in the seed systems, with a crucial need for strengthening policy, capacity building and investment in seed systems. We propose a multi-stakeholder approach and the application of online tools to improve seed systems to meet the demand for high-quality native tree seeds.

Even though restoring missing teeth and oral tissue with dental implants is perceived by most patients as a positive experience, patients lack access to evidence-based information about different treatment options. In order to provide more accurate information for public dental education in Switzerland and to compare it worldwide, this descriptive cross-sectional survey-based study assessed pre-operative attitudes, awareness, and knowledge of patients. A total of 160 patients with indication for tooth extraction were selected randomly from clinical routine between August 2022 and February 2023. Statistical analysis was performed including the chi-square test based on a significance level of 0.05. The results confirm that most patients (78%) were aware of implants as a treatment option for replacing missing teeth and consider them a prioritized solution (79%). Their primary sources of information are dentists (59%), the Internet (50%), relatives and friends (40%). The majority of patients (84%) wanted the surgical procedure to be performed by a board-certified clinical specialist expecting high functional and aesthetic outcomes. Low levels of knowledge could be observed regarding postoperative care, functionality, and clinical performance of implants. This survey-based study revealed a positive attitude and an acceptable level of awareness and knowledge regarding the use of dental implants.

Abstract Background Recent experimental work has shown that the evolutionary dynamics of bacteria expanding across space can differ dramatically from what we expect under well-mixed conditions. During spatial expansion, deleterious mutations can accumulate due to inefficient selection on the expansion front, potentially interfering with and modifying adaptive evolutionary processes. Results We used whole genome sequencing to follow the genomic evolution of 10 mutator Escherichia coli lines during 39 days ( ~ 1650 generations) of a spatial expansion, which allowed us to gain a temporal perspective on the interaction of adaptive and non-adaptive evolutionary processes during range expansions. We used elastic net regression to infer the positive or negative effects of mutations on colony growth. The colony size, measured after three day of growth, decreased at the end of the experiment in all 10 lines, and mutations accumulated at a nearly constant rate over the whole experiment. We find evidence that beneficial mutations accumulate primarily at an early stage of the experiment, leading to a non-linear change of colony size over time. Indeed, the rate of colony size expansion remains almost constant at the beginning of the experiment and then decreases after ~ 12 days of evolution. We also find that beneficial mutations are enriched in genes encoding transport proteins, and genes coding for the membrane structure, whereas deleterious mutations show no enrichment for any biological process. Conclusions Our experiment shows that beneficial mutations target specific biological functions mostly involved in inter or extra membrane processes, whereas deleterious mutations are randomly distributed over the whole genome. It thus appears that the interaction between genetic drift and the availability or depletion of beneficial mutations determines the change in fitness of bacterial populations during range expansion.