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Nanostructured titanium plays an important role in biomedical applications, especially in dentistry, as the nanostructured surface promotes bone cell growth and simultaneously prevents bacterial colonization. Nanostructured microstructures can be obtained through Severe Plastic Deformation processes. In this paper, thermomechanical processing via Equal Channel Angular Swaging for the continuous production of nanocrystalline Ti–13Nb–13Zr (TNZ) is investigated with respect to applications in dental implantology. TNZ is a second-generation β-rich (α + β) medical alloy which can consist of the three phases α- and β-phase as well as αʺ-martensite. The αʺ-martensite has a very low Young’s modulus and a comparably low strength with high ductility allowing metal forming even at low temperatures. By adjusting different phase volume fractions, a wide range of mechanical properties can be realized, especially Young’s modulus between 50 and 90 GPa at a yield strength exceeding 950 MPa making it an ideal material for dental implants and abutments. Graphical abstract

A series of epidemiological studies have shown the limited life expectancy of patients suffering from idiopathic normal pressure hydrocephalus (iNPH). In most cases, comorbid medical conditions are the cause of death, rather than iNPH. Though it has also been shown that shunting improves both life quality and lifetime. We sought to investigate the utility of the Charlson comorbidity index (CCI) for improved preoperative risk–benefit assessment of shunt surgery in individual iNPH cases. 208 shunted iNPH cases were prospectively investigated. Two in-person follow up visits at 3 and 12 months assessed postoperative clinical status. The correlation of the age adjusted CCI with survival was investigated over the median observation time of 2.37 years (IQR 1.16–4.15). Kaplan Meier statistics revealed that patients with a CCI score of 0–5 have a 5-year survival rate of 87%, compared to only 55% in patients with CCI > 5. Cox multivariate statistics revealed that the CCI was an independent predictor of survival, while common preoperative iNPH scores (modified Rankin Scale (mRS), gait score, and continence score) are not. As expected, mRS, gait, and continence scores improved during the postoperative follow up period, though relative improvement on any of these was not predicted by baseline CCI. The CCI is an easily applicable preoperative predictor of survival time in shunted iNPH patients. The lack of a correlation between the CCI and functional outcome means that even patients with multiple comorbidities and limited remaining lifetime may appreciate benefit from shunt surgery.

Trends for increased vegetation greenness based on satellite-derived data have been repeatedly published for the temperate grassland biome (including forest steppes) of eastern Inner Asia since 1982. Although this greening trend has been attenuated or partially reversed by drought in the early twenty-first century, linear increases in the Normalized Difference Vegetation Index (NDVI) or other parameters of vegetation greenness are nevertheless evident when the period since 1982 is regarded. However, the question arises whether these trends are part of a long-term trend driven by climate change, as simultaneously forests in the region show widespread drought-induced growth reductions and mortality outbreaks. Therefore, we hypothesized that the post-1982 greening trend was neither part of a long-term trend nor unprecedented. To test this hypothesis, we analyzed monthly maximum NDVI data from AVHRR time series and correlated these data with standardized tree-ring data of Larix sibirica from two regions of western Mongolia. We used linear regression to model the NDVI from tree-ring anomalies and to reconstruct the NDVI since 1940. These reconstructions show that the availability of satellite-based NDVI data coincidentally began during a dry period of low vegetation greenness in the early 1980s and was followed by a wet phase in the 1990s, producing the linear greening trend. No positive long-term trend in the reconstructed NDVI was observed from 1940 to 2010. This result rules out a recent climate change-driven greening trend for the grasslands and forest steppes of western Mongolia and calls into question its existence for all of eastern Inner Asia.

Since the introduction of transcutaneous-transcricoidal needle approaches, electromyography (EMG) of the posterior cricoarytenoid muscle (PCA) became easier to perform and teach. Among the Neurolaryngology working group of the European Laryngological Society, several centers have adopted PCA EMG as part of their routine EMG workup in vocal fold immobility collectively gathering long-term experience. The purpose is to give an update and an extension to already existing guidelines on laryngeal EMG with specific regard to PCA EMG.Consensus of all co-authors is based on continuous exchange of ideas and on joint laryngeal EMG workshop experiences over at least 7 years. A Delphi method of consensus development was used, i.e., the manuscript was circulated among the co-authors until full agreement was achieved.Step-by-step instructions on how to perform and interpret PCA EMG are provided.Further research should include the establishment of normal values for PCA and thyroarytenoid muscle (TA) EMG as well as studies on the nature of some unusual activation pattern commonly seen in chronically lesioned PCA.

One of the challenges faced by current CRISPR/Cas9 editing strategies is the difficulty in rapidly selecting clonal populations of biallelically edited cells. Here we present Surface engiNeered fluorEscence Assisted Kit with Protein Epitope Enhanced Capture (SNEAK PEEC), a platform that combines human genome editing with cell-surface display, which enables the direct identification of biallelically edited clones with minimal screening.

Transmission control protocol (TCP) is the widely and dominantly used protocol in today’s internet. A very recent implementation of congestion control algorithm is BBR by Google. Bottleneck bandwidth and round-trip time (BBR) is a congestion control algorithm which is created with the aim of increasing throughput and reducing delay. The congestion control protocols mentioned previously try to determine congestion limits by filling router queues. BBR drains the router queues at the bottleneck by sending exactly at the bottleneck link rate. This is done by the BBR through pacing rate which infers the delivery rate of the receiver and uses this as the estimated bottleneck bandwidth. But when the data rate is high, in the startup phase itself pipe becomes full and leads to some degradation in the Access Point of wireless environments by inducing losses specific to this environment. So the current pacing rate is not suitable for producing higher throughputs. Therefore, in the proposed system named R-BBR, this startup gain should be lower than the current startup gain which eventually would reduce pacing rate to reduce queue pressure in the sink node during the startup phase. The startup phase of BBR is modified to solve the problem of pipe full under high data rate. R-BBR has been evaluated over a wide range of wired as well as wireless networks by varying different factors like startup gain, congestion window, and pacing rate. It is inferred that R-BBR performs better than BBR with significant performance improvement.

As cardio metabolic disease manifestations tend to cluster in families there is a need to better understand the underlying mechanisms in order to further develop preventive strategies. In fact, genetic markers used in genetic risk scores, important as they are, will not be able alone to explain these family clusters. Therefore, the search goes on for the so called missing heritability to better explain these associations. Shared lifestyle and social conditions in families, but also early life influences may be of importance. Gene-environmental interactions should be explored. In recent years interest has grown for the role of diet-microbiota associations, as microbiota patterns may be shared by family members. In the Malmö Offspring Study that started in 2013, we have so far been able to examine about 4700 subjects (18–71 years) representing children and grandchildren of index subjects from the first generation, examined in the Malmö Diet Cancer Study during 1991 to 1996. This will provide rich data and opportunities to analyse family traits of chronic disease across three generations. We will provide extensive genotyping and phenotyping including cardiovascular and respiratory function, as well as markers of glucose metabolism. In addition, also cognitive function will be assessed. A 4-day online dietary recall will be conducted and gut as well as oral microbiota analysed. The ambition is to provide one of the first large-scale European family studies with individual data across three generations, which could deepen our knowledge about the role of family traits for chronic disease and its underlying mechanisms. Electronic supplementary material The online version of this article (10.1007/s10654-020-00695-4) contains supplementary material, which is available to authorized users.

Background: Groin hernia management has a significant worldwide diversity with multiple surgical techniques and variable outcomes. The International guidelines for groin hernia management serve to help in groin hernia management, but the acceptance among general surgeons remains unknown. The aim of our study was to gauge the degree of agreement with the guidelines among health care professionals worldwide. Methods: Forty-six key statements and recommendations of the International guidelines for groin hernia management were selected and presented at plenary consensus conferences at four international congresses in Europe, the America’s and Asia. Participants could cast their votes through live voting. Additionally, a web survey was sent out to all society members allowing online voting after each congress. Consensus was defined as > 70% agreement among all participants. Results: In total 822 surgeons cast their vote on the key statements and recommendations during the four plenary consensus meetings or via the web survey. Consensus was reached on 34 out of 39 (87%) recommendations, and on six out of seven (86%) statements. No consensus was reached on the use of light versus heavy-weight meshes (69%), superior cost-effectiveness of day-case laparo-endoscopic repair (69%), omitting prophylactic antibiotics in hernia repair, general or local versus regional anesthesia in elderly patients (55%) and re-operation in case of immediate postoperative pain (59%). Conclusion: Globally, there is 87% consensus regarding the diagnosis and management of groin hernias. This provides a solid basis for standardizing the care path of patients with groin hernias.

In 2015 Schiefer and Winfree introduced the chemical reaction network-controlled tile assembly model (CRN-TAM), a variant of the abstract tile assembly model (aTAM), where tile reactions are mediated via non-local chemical signals. In this paper, we introduce ALCH, an imperative programming language for specifying CRN-TAM programs. ALCH contains common features like Boolean variables, conditionals, and loops. It also supports CRN-TAM-specific features such as adding and removing tiles. A unique feature of the language is the branch statement, a nondeterministic control structure that allows us to query the current state of tile assemblies. We also developed a compiler that translates ALCH to the CRN-TAM, and a simulator that simulates and visualizes the self-assembly of a CRN-TAM program. Using this language, we show that the discrete Sierpinski triangle can be strictly self-assembled in the CRN-TAM. This solves an open problem that the CRN-TAM is capable of self-assembling infinite shapes at scale one that the aTAM cannot. ALCH allows us to present this construction at a high level, abstracting species and reactions into C-like code that is simpler to understand. Our construction utilizes two new CRN-TAM techniques that allow us to tackle this open problem. First, it employs the branching feature of ALCH to probe the previously placed tiles of the assembly and detect the presence and absence of tiles. Second, it uses scaffolding tiles to precisely control tile placement by occluding any undesired binding sites.

The transition from hunting to herding transformed the cold, arid steppes of Mongolia and Eastern Eurasia into a key social and economic center of the ancient world, but a fragmentary archaeological record limits our understanding of the subsistence base for early pastoral societies in this key region. Organic material preserved in high mountain ice provides rare snapshots into the use of alpine and high altitude zones, which played a central role in the emergence of East Asian pastoralism. Here, we present the results of the first archaeological survey of melting ice margins in the Altai Mountains of western Mongolia, revealing a near-continuous record of more than 3500 years of human activity. Osteology, radiocarbon dating, and collagen fingerprinting analysis of wooden projectiles, animal bone, and other artifacts indicate that big-game hunting and exploitation of alpine ice played a significant role during the emergence of mobile pastoralism in the Altai, and remained a core element of pastoral adaptation into the modern era. Extensive ice melting and loss of wildlife in the study area over recent decades, driven by a warming climate, poaching, and poorly regulated hunting, presents an urgent threat to the future viability of herding lifeways and the archaeological record of hunting in montane zones. Introduction - Mountain zones and the emergence of herding economies in Eastern Eurasia Results - Remote sensing - Pedestrian and horseback survey - Radiocarbon dating and cultural patterns Discussion - Weapon manufacture - Hunting strategies and butchery - Ritual activity - Other cultural activities - Role of mountain zones in emerging pastoral societies - Implications of climate change and poaching Conclusion Methods

This paper studies biogas value chains and the effect from various economic support instruments on these value chains. This is done by comparing two European countries that are quite similar in size, income levels and environmental ambitions, but which are using very different instruments to support biogas development. Norway provides investment support combined with support for inputs, while Danish support is focused on the biogas output side. The aim of the comparison is to clarify whether the policies in use have affected the design of biogas value chains such that they are determined by national support and are not viable under alternative support structures. Based on the findings, possible modifications of national support and other biogas regulation policy are suggested. The comparative study assesses the costs and income of an exemplary Norwegian value chain and a Danish value chain. The cases are evaluated by assessing the economic consequences of implementing the Danish instruments for a Norwegian value chain and vice versa. We find that structural and regulatory conditions have a large impact on the configuration of the value chains. The Danish value chain in Norwegian settings results in a large deficit (− 12.7€/tonne), while it was profitable in Denmark (+ 4.9€/tonne). The same is observed for the Norwegian value chain, but to a lesser extent. The policy implication of end-use support in Denmark is large-scale plants, maximising the output through co-digestion of manure and high-yield substrates, while avoiding losses. Investment support in Norway has increased biogas production from organic waste with less emphasis on efficient gas usage, while input support regarding manure has led to an increase in the usage of manure as substrate.

Microsporidia are eukaryotic parasites that infect essentially all animal species, including many of agricultural importance(1–3), and are significant opportunistic parasites of humans(4). They are characterized by having a specialized infection apparatus, an obligate intracellular lifestyle(5), rudimentary mitochondria and the smallest known eukaryotic genomes(5–7). Extreme genome compaction led to minimal gene sizes affecting even conserved ancient complexes such as the ribosome(8–10). In the present study, the cryo-electron microscopy structure of the ribosome from the microsporidium Vairimorpha necatrix is presented, which illustrates how genome compaction has resulted in the smallest known eukaryotic cytoplasmic ribosome. Selection pressure led to the loss of two ribosomal proteins and removal of essentially all eukaryote-specific ribosomal RNA (rRNA) expansion segments, reducing the rRNA to a functionally conserved core. The structure highlights how one microsporidia-specific and several repurposed existing ribosomal proteins compensate for the extensive rRNA reduction. The microsporidian ribosome is kept in an inactive state by two previously uncharacterized dormancy factors that specifically target the functionally important E-site, P-site and polypeptide exit tunnel. The present study illustrates the distinct effects of evolutionary pressure on RNA and protein-coding genes, provides a mechanism for ribosome inhibition and can serve as a structural basis for the development of inhibitors against microsporidian parasites.

Purpose Laryngeal electromyography (LEMG) has been considered as gold standard in diagnostics of vocal fold movement impairment, but is still not commonly implemented in clinical routine. Since the signal interpretation of LEMG signals (LEMGs) is often a subjective and semi-quantitative matter, the goal of this study was to evaluate the inter-rater reliability of neurolaryngologists on LEMGs of volitional muscle activity. Methods For this study, 52 representative LEMGs of 371 LEMG datasets were selected from a multicenter registry for a blinded evaluation by 7 experienced members of the neurolaryngology working group of the European Laryngological Society (ELS). For the measurement of the observer agreement between two raters, Cohen’s Kappa statistic was calculated. For the interpretation of agreements of diagnoses among the seven examiners, we used the Fleiss’ Kappa statistic. Result When focusing on the categories “no activity”, “single fiber pattern”, and “strongly decreased recruitment pattern”, the inter-rater agreement varied from Cohen’s Kappa values between 0.48 and 0.84, indicating moderate to near-perfect agreement between the rater pairs. Calculating with Fleiss’ Kappa, a value of 0.61 showed good agreement among the seven raters. For the rating categories, the Fleiss’ Kappa value ranged from 0.52 to 0.74, which also showed a good agreement. Conclusion A good inter-rater agreement between the participating neurolaryngologists was achieved in the interpretation of LEMGs. More instructional courses should be offered to broadly implement LEMG as a reliable diagnostic tool in evaluating vocal fold movement disorders in clinical routine and to develop future algorithms for therapy and computer-assisted examination.

Constitutive Russellian panpsychism seems to combine the strengths of its rivals, physicalism and dualism, while avoiding their weaknesses: by acknowledging the irreducibility of phenomenal properties yet grounding macro- in microphenomenality (phenomenal constitution), the view can avoid both anti-physicalist arguments and the causal exclusion problem for dualism. However, two severe objections have been raised: the combination problem for phenomenal constitution, and the structural exclusion problem for the position’s account of microphenomenal causation. It is currently hotly debated whether the combination problem can be overcome. If not, panpsychists are forced to view macrophenomenality as emergent. Yet emergent panpsychism is subject to the causal exclusion problem, thereby sacrificing panpsychism’s advantage over dualism. With regard to the structural exclusion problem, Morch (forthcoming) provides a solution in terms of microphenomenal powers. I argue that Morch’s view is not tenable. This notwithstanding, I develop a modification of her view which can solve the structural exclusion problem. Moreover, the emergentist version of this approach can avoid the causal exclusion problem. Thus, I aim to provide both a satisfying account of microphenomenal causation in panpsychism and a viable version of emergent panpsychism in case the combination problem turns out to be unsolvable.

In the past 25 years, genetic and biochemical analyses of ribosome assembly in yeast have identified most of the factors that participate in this complex pathway and have generated models for the mechanisms driving the assembly. More recently, the publication of numerous cryo-electron microscopy structures of yeast ribosome assembly intermediates has provided near-atomic resolution snapshots of ribosome precursor particles. Satisfyingly, these structural data support the genetic and biochemical models and provide additional mechanistic insight into ribosome assembly. In this Review, we discuss the mechanisms of assembly of the yeast small ribosomal subunit and large ribosomal subunit in the nucleolus, nucleus and cytoplasm. Particular emphasis is placed on concepts such as the mechanisms of RNA compaction, the functions of molecular switches and molecular mimicry, the irreversibility of assembly checkpoints and the roles of structural and functional proofreading of pre-ribosomal particles.

Background Mesh implants are widely used to reinforce the abdominal wall, although the inevitable inflammatory foreign body reaction (FBR) at the interface leads to complications. Macrophages are suspected to regulate the subsequent scar formation, but it is still unclear whether adequate fibrous scar formation with collagen deposition depends mainly on the presence of M1 or M2 macrophages. Methods This study investigated the FBR to seven human polypropylene meshes, which were removed after a median incorporation time of 1 year due to the primary complaint of recurrence. Using immunofluorescence, the FBR was examined in six regional zones with increasing distance from the mesh fibers up to 350 µm, based on the cell densities, macrophage M1 (CD86) and M2 (CD163, CD206) phenotypes, deposition of collagen-I and -III, and expression of matrix metalloproteinase-2 (MMP-2) and -8 as indicator of collagen degradation. Results All mesh–tissue complexes demonstrated a decrease in cell density and macrophages with distance to the mesh fibers. Overall, about 60% of the macrophages presented an M2 phenotype, whereas only 6% an M1 phenotype. Over 70% of macrophages showed co-expression with collagen-I or -III and over 50% with MMP-2. Conclusions The chronic FBR to polypropylene meshes is associated with an M2 macrophage response, which is accompanied by collagen deposition and MMP-2 expression. These findings challenge the idea that mainly M1 macrophages are related to inflammation and highlights that iatrogenic attempts to polarize these cells towards the M2 phenotype may not be a solution to ameliorate the long-term foreign body reaction.

Cryo-electron microscopy structures of multiple states along the assembly pathway of the nucleolar pre-60S ribosomal subunit suggest that folding of the pre-ribosomal RNA and sequential binding of transient assembly factors are regulated by steric hindrance among these factors. Cryo-electron microscopy approaches provide unprecedented views of how large molecular complexes assemble in cells. Sebastian Klinge and colleagues used these techniques to analyse the formation of the large pre-60S ribosomal subunit at a resolution of 3.4 A. These analyses show that the concerted activity of several assembly factors is important for the stabilization and remodelling of intermediate structures of RNA and proteins while avoiding premature folding states. Progress through sequential steps of this assembly pathway is needed to achieve the correct conformation of the polypeptide exit tunnel of the ribosome. Early co-transcriptional events during eukaryotic ribosome assembly result in the formation of precursors of the small (40S) and large (60S) ribosomal subunits1. A multitude of transient assembly factors regulate and chaperone the systematic folding of pre-ribosomal RNA subdomains. However, owing to a lack of structural information, the role of these factors during early nucleolar 60S assembly is not fully understood. Here we report cryo-electron microscopy (cryo-EM) reconstructions of the nucleolar pre-60S ribosomal subunit in different conformational states at resolutions of up to 3.4 A. These reconstructions reveal how steric hindrance and molecular mimicry are used to prevent both premature folding states and binding of later factors. This is accomplished by the concerted activity of 21 ribosome assembly factors that stabilize and remodel pre-ribosomal RNA and ribosomal proteins. Among these factors, three Brix-domain proteins and their binding partners form a ring-like structure at ribosomal RNA (rRNA) domain boundaries to support the architecture of the maturing particle. The existence of mutually exclusive conformations of these pre-60S particles suggests that the formation of the polypeptide exit tunnel is achieved through different folding pathways during subsequent stages of ribosome assembly. These structures rationalize previous genetic and biochemical data and highlight the mechanisms that drive eukaryotic ribosome assembly in a unidirectional manner.

PURPOSE OF REVIEW: The treatment of pain in patients with cirrhosis is complicated by unpredictable hepatic drug metabolism and a higher risk of adverse drug reactions. We aimed to conduct a scoping review regarding pain management in cirrhosis. RECENT FINDINGS: Despite the high prevalence of pain in patients with cirrhosis, there is little literature to guide the management of pain in this population. Complex pain syndromes and disease-specific pain etiologies exist are common in patients with cirrhosis. There are numerous contraindications and limitations when considering pharmacotherapy for analgesia in cirrhosis, specifically with non-steroidal anti-inflammatory drugs (NSAIDS) and opioid medications. Non-pharmacologic therapies for pain have not been specifically assessed in this population. SUMMARY: As with other populations, a multi-dimensional treatment approach to pain with a focus on physical, behavioral, procedural and pharmacologic treatment is recommended when caring for patients with cirrhosis and pain. However, more research is needed to evaluate opioid-sparing and non-pharmacologic analgesia in this population.