Saito et al. utilizing a very large data-set of over 1,000 oral samples, have uncovered relevant differences between salivary and tooth-associated plaque microbial communities. They also showed that microbial diversity and abundance of Treponema and Selenomonas were increased as periodontal disease progresses and describe novel bacterial interactions during disease.In recent years, our current understanding of the interplay between the oral microbiome and the host immune response has expanded considerably, becoming increasingly complex. Significant progress has been made towards studying how host microbial interactions can shape the clinical outcomes in health and disease. We now appreciate that these microbes are also taking part of diverse microbial assemblies inhabiting the oral cavity. One of the critical factors that has contributed to this knowledge is the wide utilization of next-generation sequencing techniques, which have allowed to unravel the complexity of oral microbial communities from a more ecological perspective. For instance, the study by Jia et al. examined the effect of cigarette smoking on the oral microbiota in a Chinese cohort of 316 healthy subjects. The results showed that smokers had significantly higher diversity and select bacterial species were associated with cigarette smoking. Further analyses showed increased levels of Actinomyces and Veillonella and expression of acid production-related pathways in smokers. The study concluded that cigarette smoking may affect oral health by creating an acidic environment that alters bacterial abundance and metabolic function.The influence of environmental factors on the oral microbiome has been a critical question in the field that continues to be interrogated. The study by Huang et al. presented relevant data of the salivary microbiome of 293 patients with progressive histological stages of gastric carcinogenesis. Patients with gastric cancer had increased pro-inflammatory bacteria; whereas the genera Haemophilus and Neisseria were decreased, which may lead to accumulation of carcinogens. Their findings suggest that oral bacteria may be involved in the pathogenesis of gastric carcinogenesis and propose potential diagnostic bacterial biomarkers for gastric cancer. Examining other systemic condition, He et al. showed how the oral microbial dysbiosis was associated with the pathogenesis of Immunoglobin A Nephropathy (IgAN), the most common type of glomerulonephritis. Data include the profile of the most abundant oral microbiota species in diseased patients versus controls indicating the shared and specific species between the two groups. The authors also showed correlative studies between oral microbiota and clinical sub-phenotypes of the disease defining predictive functional profiles that may be more associated with IgAN.We have also gained a much broader view of the importance of the oral microbiome and how its dysbiosis may play a crucial role in the pathogenesis of not only local diseases but in several systemic conditions. Bordagaray et al. the authors reported the potential dissemination of bacteria associated with apical periodontitis to the bloodstream. Porphyromonas spp. were frequently detected in tissues and root canals exudates from apical lesions. Total bacteria and P. endodontalis, but not P. gingivalis, were detected in peripheral blood mononuclear cells (PBMCs) from patients, suggesting that P. endodontalis may disseminate from the apical lesion to the systemic bloodstream by PBMCs. On a related topic, the relationship of oral bacteria and the overall bone metabolism is starting to be explored. Hirohashi et al. addressed a technical issue in their study, regarding the possibility to use tetracycline as a fluorescent dye to evaluate bone loss caused by the tetracycline-sensitive oral bacteria, Streptococcus mutans. Their findings revealed that tetracycline can be utilized in the measurement of bone loss induced by drug-sensitive bacteria, and that S. mutans triggers a reduction of bone mass possibly by reducing bone formation activity.Translocation of oral microorganisms to distant sites is also another critical aspect that may constitute a direct mechanism by which select oral bacteria impact systemic health. In the study by Porphyromonas gingivalis is a prominent example, and the study by Elsayed et al. assessed the role of this organism in the vulnerability to senescence in human primary isolated gingival keratinocytes and bone marrow-derived dendritic cells (DCs) from young (yDCs) and old (oDCs) mice. The authors found increased senescence, impaired maturation of DCs and proliferation of CD4+ T cells upon oDCs or yDCs+Pg stimulation. A characterization of exosomes of DCs (control and DCs+Pg) revealed a differential regulation of miRNAs in the Pg challenged group alongside an enrichment of the fimbrial adhesin protein mfa1 and pro-inflammatory cytokines. The study concluded that P. gingivalis can induce premature senescence through direct cellular invasion and by stimulating secretion of exosomes that promote paracrine immune senescence in bystander cells. Focusing on another periodontal organism, Treponema denticola, the study by Malone et al. evaluated the influence of this bacterium on the actin filaments of periodontal ligament (PDL) cells. The authors elegantly described mechanistic interactions between T. denticola and human PDL cells, showing that this periodontopathogen drives a pathological response characterized by upregulation of RASA4, depolymerization of actin filaments, and a subsequent increase in MMP-2 activity. Authors speculate that these contributions shed light on new potential targets for T. denticola-PDL interactions that may influence periodontal tissue homeostasis. The study of Li et al. examined the interplay of another periodontal bacteria, Fusobacterium nucleatum in combination with a recognized respiratory pathogen, Pseudomonas aeruginosa, and analyzed how these two organisms interacted with pulmonary epithelial cells. Co-infection of both organisms or pre-treatment with F. nucleatum resulted in increased bacterial invasion and inflammatory cytotoxicity of pulmonary epithelial cells. These findings provide novel insights on the mechanisms behind the deterioration of lung function associated to these two organisms.The study of host-microbial interactions between oral microorganisms and stromal or immune cells is at the center of the mechanistic understanding of how select oral pathobionts play a role in the pathogenesis of oral and systemic conditions. Oral bacteria associated with periodontal diseases have been the most thoroughly characterized in a variety of pathological settings. We would like to thank all authors in this collection for their valuable contributions. We hope this Research Topic continues to stimulate the generation of new knowledge dedicated to unravel influence of the oral microbiome on systemic health.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.This work was funded in part by ANID/Chilean National Fund for Scientific and Technologic Development (FONDECYT), grant #11180505 (to LA), and grants R01DE025037 and R01DE027374 from the National Institute of Dental and Craniofacial Research/National Institutes of Health (to SES).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The intestinal microbiota has gained increased attention from researchers within the swine industry due to its role in promoting intestinal maturation, immune system modulation, and consequently the enhancement of the health and growth performance of the host. This review aimed to provide updated scientific information on the interaction among intestinal microbiota, dietary components, and intestinal health of pigs. The small intestine is a key site to evaluate the interaction of the microbiota, diet, and host because it is the main site for digestion and absorption of nutrients and plays an important role within the immune system. The diet and its associated components such as feed additives are the main factors affecting the microbial composition and is central in stimulating a beneficial population of microbiota. The microbiota–host interaction modulates the immune system, and, concurrently, the immune system helps to modulate the microbiota composition. The direct interaction between the microbiota and the host is an indication that the mucosa-associated microbiota can be more effective in evaluating its effect on health parameters. It was demonstrated that the mucosa-associated microbiota should be evaluated when analyzing the interaction among diets, microbiota, and health. In addition, supplementation of feed additives aimed to promote the intestinal health of pigs should consider their roles in the modulation of mucosa-associated microbiota as biomarkers to predict the response of growth performance to dietary interventions. ModulatThe intestine of pigs is colonized by a dense, dynamic, and highly complex community of microorganisms composed mainly of bacteria . Along tMucosa-associated microbiota act as the frontline defenders against pathogens by competitive exclusion and immune status modulation . ProductTherefore, this review is focused on the role of mucosa-associated microbiota in the intestinal health of pigs and the interaction among the diets, microbiota, and immune system in the intestine of pigs.2Early establishment of the intestinal microbiota is extremely important for the maturation of the intestinal immune system, barrier function, and consequently the health and growth of pigs . In addi2.1Whether the intestine is first exposed to microbials in the uterus or during birth is still controversial . The pos2.2At birth, piglets face with a substantial load of microorganisms from the birth canal and the sow's feces . In commBacteroides, and Ruminococcaceae and lower proportions of Actinobacillus porcinus and Lactobacillus amylovorus compared with lighter piglets. The authors suggested that the quantity of milk ingested during lactation may potentially affect the health and performance of the host through modulation of the intestinal microbiota. The nutritional components of maternal milk include oligosaccharides that contribute greatly to the development of the intestinal microbiota , the ileal lumen had increased Lachnospiraceae and reduced Actinobacillus, whereas the ileal mucosa showed increased Megasphaera and Streptococcus, and reduced Candidatus arthromitus and Helicobacter. These different observations of microbiota responses can be attributed to physicochemical characteristics in the lumen and mucosa including oxygen and nutrient availability  are the major microbial metabolites produced from carbohydrates and the carbon chain of amino acids (AA) . BacteriBesides the contribution to energetic metabolism, SCFA can exert beneficial effects on the intestinal immune system . The SCFF. prausnitzii possess anti-inflammatory effects that can block nuclear factor-κβ (NF-κβ) activation and IL-8 production , ammonia, amines, hydrogen sulfide, phenols, and indoles . These coduction .4.3Receptors located on intestinal cells can identify the cell wall structures of mucosa-associated and activate the immune response . LipopolEscherichia coli (ETEC) (.Some bacteria possess cell membrane adhesins that have been shown to directly promote the immune response of the host . Before i (ETEC)  as showni (ETEC) .5The composition and the abundance of both luminal and mucosa-associated microbiota are largely affected by dietary factors. Intestinal immune system would be influenced by dietary factor directly or indirectly related to the composition and the abundance of intestinal microbiota. Influence of major nutrients and feed additives to intestinal microbiota and immune systems is reviewed in this section.5.1Klebsitella spp., E. coli, Streptococcus spp., Succinivibrio dextrinosolvens, Mitsuokella spp., and Anaerovibrio lipolytica , reducing the dietary crude protein from 18% to 15% decreased the abundance of harmful bacteria including Streptococcus and increased those considered beneficial, Lactobacillus and Bifidobacterium, in ileal digesta of growing pigs. Besides the modulation of the microbiota, the CP level can affect the profile of metabolites produced during fermentation  which are ligands for the aryl hydrocarbon receptor (AHR). Aryl hydrocarbon receptor induces the expression of interleukin 22 (IL-22) by the intestinal immune cells , further5.2Bifidobacterium longum, Prevotella copri, Bacteroides plebeius, and Bacteroides sp. primarily utilize soluble arabinoxylan producing oligosaccharides and SCFA, and lactate. Whereas Subdoligranulum sp., and Blautia obeum mostly utilize oligosaccharides.Dietary fiber is one of the dietary compounds most related to intestinal microbiota. After weaning the fiber content in the diet is one important antinutritional factor (ANF) affecting the health of pigs. The ANF effect of fiber is greater in nursery pigs due to the immature intestine being unable to handle the fiber properly. Pigs do not endogenously produce enzymes capable of degrading non-starch polysaccharide (NSP), however, the intestinal microbiota have a broad range of various enzymes related to NSP hydrolysis . The solFiber can be utilized by the intestinal microbiota in cross-feeding or a cell-dependent action. This may indicate that supplementation of a single enzyme may affect those bacteria utilizing the target subtract and the oligosaccharides released . Moreove5.3Selected feed additives directly or indirectly influence the composition and the abundance of both luminal and mucosa-associated microbiota, which in turn influence intestinal immune system. The effects of dietary intervention on the modulation of intestinal microbiota and health of pigs are summarized in 5.3.1Probiotics has been largely used in the swine industry to promote the healthy growth of pigs. The roles of probiotics are intrinsic and related to the host microbiota including competition for nutrients, adhesion sites on the intestinal mucosa, production of lactic acid, SCFA, and anti-microbial compounds . As consBacillus spp., Lactobacillus, Bifidobacterium, and Enterococcus are lactic acid-producing bacteria commonly used in probiotic mixtures due to their characteristics , downregulated the expression of genes related to immune system and enhanced the epithelial layers in the ileum  upregulating the goblet cells proliferation in the ileum. The greater number of goblet cells increased mucin 2 (MUC2) production preserving the intestinal barrier function. These results indicate that the balance of the intestinal microbiota should be considered when evaluating the probiotic effects on the health of the host. In addition, the changes on the fecal microbiota may not be correlated with the immune modulation on the small intestine  are non-digestive carbohydrates comprised of a mannose chain. Most feed additives containing MOS are derived from revisiae . A proporevisiae . Fouhse ned pigs , 2018. Aoli K88+ .Bifidobacterium and Lactobacillus proliferation in vitro. According to Bifidobacterium and Lactobacillus at species level depends on the degree of polymerization of the XOS. Moreover, the authors reported that XOS was not utilized as an energy source by Staphylococcus, E. coli, and most Clostridium species. The microbial ability to ferment XOS varies with the source of XOS , a functional carbohydrate derived from the hydrolysis of xylan, has been demonstrated to modulate the intestinal microbiota and the immune system of the host. Xylo-oligosaccharide has been shown to selectively stimulate the proliferation of bacteria generally associated to promote health benefits to the host . Mäkeläie of XOS . Pan et  digesta . AdditioIn addition to the effect of dietary XOS on the anti-inflammatory response mediated by the intestinal microbiota, XOS can directly affect the immune system . Nabarla5.3.3Lactobacillus casei increased the transcription of TLR. The production of TLR drives both T and B cells response leading to IgA production  are extracts derived from plants that have been used as phytobiotics to promote the health and growth performance of livestock due to their properties including antimicrobial capacity . The procrobiota . Pigletsin feces .Lactobacillus kitasatonis.Cardol and anacardic acid from cashew nutshell have shown antimicrobial activity against both Gram-positive and Gram-negative bacteria . Cardol Collectively, the effect of the numerous feed additives promoting health and growth response in pigs can be associated with the changes in the intestinal microbiota. Considering the microbiota modulation, the properties of the feed additives can be characterized by antimicrobial activity and by feeding selected microbiota. Therefore, the use of feed additives to modulate the microbiota at a specific level should consider the existing microbial community before nutritional interventions are put in place in order to promote a more precise response.6Prevotella, Lactobacillus, and Bifidobacterium have great abundance in the mucosa and are associated with health benefits. Whereas, Campylobacter, Clostridium, Veillonella, and Helicobacter are potentially harmful or associated with intestinal dysbiosis. These bacteria could be used as a biomarker to predict responsiveness to dietary interventions and more specific nutritional intervention depending on genetics, on-farm management, and current nutritional management. Therefore, understanding the roles of intestinal microbiota and their interaction with the host is essential in feed formulation and dietary supplementation in the swine industry.Modulation of intestinal microbiota toward a more beneficial microbial community can be a key factor in enhancing intestinal health and therefore increasing the growth performance of nursery pigs. The intestinal microbiota in the lumen and mucosa play an important role along the entire length of the intestine. The role of the microbiota in the lumen is more related to the digestive function, producing metabolites that further can interact with the host. Whereas, the mucosa-associated microbiota directly interacts with the epithelial cells in the intestine by using the adherence system and by producing metabolites directly secreted on the intestinal cells. The mucosa-associated microbiota also regulates the mucus production, a physical barrier against pathogenic adherence. Marcos EliasDuarte: Methodology; Resources; Software; Validation; Visualization; Roles/Writing – review & editing; Sung WooKim: Conceptualization; Data curation; Funding acquisition; Investigation; Methodology; Project administration; Resources; Software; Supervision; Validation; Roles/Writing – original draft; Writing – review & editing.We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper.


Vaccine hesitancy is an important feature of every vaccination and COVID-19 vaccination is not an exception. During the COVID-19 pandemic, vaccine hesitancy has exhibited different phases and has shown both temporal and spatial variation in these phases. This has likely arisen due to varied socio-behavioural characteristics of humans and their response towards COVID 19 pandemic and its vaccination strategies. This commentary highlights that there are multiple phases of vaccine hesitancy: Vaccine Eagerness, Vaccine Ignorance, Vaccine Resistance, Vaccine Confidence, Vaccine Complacency and Vaccine Apathy. Though the phases seem to be sequential, they may co-exist at the same time in different regions and at different times in the same region. This may be attributed to several factors influencing the phases of vaccine hesitancy. The complexities of the societal reactions need to be understood in full to be addressed better. There is a dire need of different strategies of communication to deal with the various nuances of all of the phases. To address of vaccine hesitancy, an understanding of the societal reactions leading to various phases of vaccine hesitancy is of utmost importance. The deluge of COVID patients has overwhelmed healthcare systems all over the world. The only hope to controlCOVID-19 during the pandemic was earnest research on developing and producing vaccines against COVID-19.Whenever there is vaccine introduction, vaccine hesitancy also comes into play due to the complex interaction of vaccine related factors, vaccinees’ dynamics, and other external issues . The pheIn relation to the COVID-19 pandemic, the world has also faced the unprecedented public health crisis of an infodemic, too much information including false information; and this has negatively impacted good decisions pertaining to health . The sprSince the emergence of COVID 19 pandemic, there have been numerous studies on vaccine hesitancy related to COVID 19 vaccine –15. UndeIt has been observed that the nature of vaccine hesitancy changes over time in the same population; and it changes as people experience subsequent vaccination . In thisDuring the early stages of COVID pandemic, when there was great fear of mortality and morbidity due to SARS COV-2 virus amongst the general population, significant keenness towards vaccines amongst the public was observed , 20. MosIgnorance may seem like bliss; but sometimes ignorance can be deadly. The United States has a process for Emergency Use Authorization (EUA) of new drugs and biologics. It is faster than full licensure but considered temporary . The US Another aspect of hesitancy due to ignorance followed the lowering of preventive measures by vaccinated and even unvaccinated people under the misconception that the vaccine was the complete solution to COVID-19. People also were unaware of the fact that after partial or even a full course of vaccination, they may contract infection but the severity would be less. This was the phase when the concept of break-through infections was not common. These factors led to a rising incidence in infections due to increased transmission of COVID 19 virus in the community. This ignorance also fuelled vaccine hesitancy in the communities and gave antivaxxers material to propagate their agenda .Intertwining with the phase of vaccine ignorance, the phase of vaccine resistance also showed its presence during the COVID 19 pandemic. Amidst bizarre theories of staunch anti-vaxxers, reduction in number of severe cases and reporting of Adverse Events Following Immunization (AEFI) led to this phase of vaccine hesitancy. Though most of the AEFI were mild, a few rare ones were serious or severe. Arzarpaneh and colleagues associated 15 types of cognitive bias as possible contributors to vaccine hesitancy [In this phase, social media was rife with posts disparaging the vaccines . The theThis phase occurs when the morbidity and mortality due to an infection such as COVID-19 is primarily seen in unvaccinated individuals. It suggests to people that the vaccine is effective against the disease particularly in reducing hospitalizations and deaths . In thisVaccine complacency is a recurring impediment to vaccination . With reThere have been instances of vaccine complacency in the past against other vaccination drives . VaccineAlthough only a few experts describe vaccine apathy as different from vaccine hesitancy , we consVaccine apathy occurs across various socioeconomic groups. For some, vaccination may be low-priority due to loosening of COVID-19 restrictions and return of life back to normal; whereas some individuals may be overwhelmed with higher priority problems of daily earning and other social responsibilities. Determining the magnitude of the vaccine-apathetic population is challenging. It is difficult to predict, like voters’ turnout in polls. Another problem in determining the true magnitude of the vaccine-apathetic population is that people tend to want to present themselves in a manner they think is favourable, so-called social desirability bias . Hence aPersons with antivaccine positions differ from apathetic people. The former have strongly held and highly defended attitudes, whereas in comparison the latter have weakly negative attitudes toward vaccines. Therefore, effective communication strategies to influence these two groups differ markedly. In the apathy phase of vaccine hesitancy, vaccine promotion approaches specifically addressing the apathetic population may be a vital component in increasing the vaccination coverage and for achieving the national vaccination goals.Though the phases of vaccine hesitancy have been described in sequential manner in this article, various phases can co-exist at the same time in different regions or even in the same region. Several factors leading to various societal reactions can influence the phases of vaccine hesitancy with respect to stage of the pandemic and geographical location. Various solutions to the problem of vaccine hesitancy have been proposed, but the comprehension of its complexity and the origin, existence and spread of each of its types or phases is essential to address it more convincingly –38. HumaThe societal reaction to the vaccine inequity in regards to vaccine availability in different parts of world may also lead to vaccine hesitancy which has not been discussed here and is a limitation of this paper. In addition, COVID-19 vaccination has been primarily an issue of adult immunization. In low and middle income countries, adult immunization is in its infancy . Therefo


Interestingly, some findings suggest a possible role for the GI microbiome in alcohol addiction or withdrawal. Unfortunately, there is a significant gap in knowledge in this area. Here we describe differences in the GI microbiome of alcoholic and non-alcoholic individuals and discuss the possible impact of microbes on the gut-brain axis, which could impact alcohol related behaviors (i.e. addiction). Understanding the role of the GI microbiome in alcohol related disorders will potentially lead to the development of successful microbiome-targeted therapeutics to help mitigate these disorders.Since the mid 1980’s, the impact of gastrointestinal (GI) microbiome changes during alcohol use disorder has been an area of significant interest. This work has resulted in the identification of specific changes in the abundance of certain members of the GI microbiome and the role these changes play in a variety of alcohol related disorders ( Alcoholism contributes significantly to global morbidity and mortality as roughly 5.3% of annual deaths result from harmful consumption of alcohol . In younAlcoholism has been studied for many years, with most of the research focusing on its impacts on the brain. A less studied, important area of recent research has been the examination of gastrointestinal (GI) microbiome changes in alcoholic patients. The first observation was made by Bode et al., who reported that jejunal aspirates from alcoholic individuals more commonly contained gram-negative anaerobic bacteria compared to control individuals . Mutlu aFaecalibacterium. Plasma levels of tryptophan and KYNA were also shown to negatively correlate with depression and alcohol craving, respectively  in the alcoholic GI tract due to repeated consumption of ethanol and constant metabolism of the alcohol; ethanol metabolism generates ROS through various routes including Cytochrome P450-dependent mechanisms . The cha11 bacteria per gram of feces . The potential roles of these taxa in substance use disorders are not fully elucidated.Bacteria are not the only microbes known to impact the GBA. Colonization by the commensal fungus,  pathway . Many geLactobacillus rhamnosus improved anxiety-like and depression-related phenotypes through the vagus nerve  metabolism . Research in the Kumamoto lab was supported by grant R01 AI118898 from the National Institutes of Health (to CK).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The destruction of natural habitat for cropland and pasture represents a major threat to global biodiversity. Despite widespread societal concern about biodiversity loss associated with food production, consumer access to quantitative estimates of the impact of crop production on the world's species has been very limited compared to assessments of other environmental variables such as greenhouse gas emissions or water use. Here, we present a consistent dataset of the biodiversity footprints of pasture and 175 crops at the global and national level. The data were generated by combining maps of the global distribution of agricultural areas in the year 2000 with spatially explicit estimates of the biodiversity loss associated with the conversion of natural habitat to farmland. Estimates were derived for three common alternative measures of biodiversity – species richness, threatened species richness, and range rarity – of the world's mammals, birds, and amphibians. Our dataset provides important quantitative information for food consumers and policy makers, allowing them to take evidence-based decisions to reduce the biodiversity footprint of global food production. Our dataset fills this gap by providing global and country-level impact estimates based on three common biodiversity measures.•Our data provide important quantitative evidence to inform the decision-making of conservationists, policy makers, and food consumers, aiming to reduce food-related biodiversity impacts.•Our estimates can be combined with crop-specific nutrient level data to rank crops and producing countries according to how efficiently they produce nutrients relative to the biodiversity footprint. This can facilitate the development of biodiversity-related food labelling systems, enabling consumers to reduce personal impacts and encourage shifts towards a sustainable food production.•Our data also open the space for in-depth analyses of the heterogeneity in the local biodiversity footprint of specific crops within and across producing countries. A better understanding of these patterns will help inform where the future expansion of growing areas of specific crops should be prioritised in order to minimise biodiversity impacts.1Our dataset  containsAnalogous data are provided for the distributions of the ratio of local biodiversity footprints to local crop yields. These data are relevant, in particular, when linked to crop-specific nutritional data: multiplying them with by amount of a given nutrient in one unit of crop produce makes it possible to rank different crops according to how efficiently they provide the given nutrient relative to their biodiversity footprint.In addition to the distributional data, our dataset contains spatially aggregated measures of the total biodiversity footprint of each crop in each country. These data make it possible, for example, to compare the contribution of specific crops or countries to the global biodiversity footprint of agriculture cf. .https://figshare.com/s/0695ac6fa97892225687).The three types of data are available as .xlsx files on the Figshare repository  for the year 2000 In addition to estimating the distributions of local biodiversity footprints on agricultural areas, we used crop-specific global maps of fresh-weight yields  local biodiversity footprints across agricultural areas. In addition, we derived spatially aggregated estimates of the biodiversity footprints of crops and pastures at country level by integrating local footprints over the relevant areas. For pasture, we used the physical area (in ha) covered by pasture in a grid cell In the case of crops, we used the physical area (in ha) covered by cropland in a grid cell Analogous data at country level, denoted Robert Beyer: Conceptualisation, Methodology, Formal analysis, Writing - Original Draft; Andrea Manica: Conceptualisation, Methodology, Writing - Review & Editing.The authors declare no conflict of interest.


Loss of motion and stiffness after fracture of the digits are most commonly a result of soft tissue contracture and adhesions. However, stiffness can also have a bony etiology. We present a case of synostosis of the thumb interphalangeal joint after non-operative treatment of a closed fracture. Stiffness and loss of motion are common sequelae after fractures of the phalanges of the hand. Fibrosis and contracture of collateral ligaments, joint capsule, and/or adhesions of the flexor and extensor tendons are common causes of stiffness and can result in significant loss of function. Since a soft tissue etiology is most common, bony causes of post-traumatic stiffness may be overlooked. Although uncommon in the hand, synostosis may be a late cause of stiffness after injury. We present a case of synostosis of the thumb after closed fracture.The patient is a 48-year-old right-hand dominant male who injured his left hand reaching into a snow blower. The patient was taken in transfer from an outside hospital arriving with plain films from the facility’s emergency department. Physical exam and the plain films revealed closed injuries including a minimally displaced radial condylar fracture of the thumb proximal phalangeal head, minimally displaced supracondylar neck fracture of the index finger proximal phalanx, nondisplaced midshaft fracture of the middle phalanx of the middle finger and an open fracture dislocation through the distal interphalangeal (DIP) joint of the small finger with near complete amputation .There was a delay in transfer resulting in the patient presenting at almost 6 h post-injury. The patient was anxious to proceed with treatment. The patient’s injuries were identifiable from the plain films and due to the open nature of the small finger injury, repeat films were not obtained before surgery. The emergent issue was the open injury to the small finger and treatment options were discussed with the patient. Revision amputation was chosen as treatment for the small finger. Closed treatment without reduction was chosen for the index and middle fingers secondary to the stable nature of the fractures. The intra-articular nature of the thumb fracture was discussed with the patient, including the risk of post-traumatic arthritis. However, the patient declined surgical treatment. Therefore, closed treatment without reduction was chosen as definitive management.Revision amputation with disarticulation through the DIP joint and primary closure of the left small finger injury was performed. The patient began a course of hand therapy at 5 days post-injury. A hand-based thumb spica splint was fabricated including the interphalangeal (IP) joint of the thumb in neutral extension at metacarpophalangeal (MP) and IP joint. The index finger MP and proximal interphalangeal (PIP) joint were included in the splint in intrinsic plus position and the middle finger included the DIP joint, also in intrinsic plus position. Secondary to the stable nature of the index and middle finger fractures, we started active and active assistive motion to those digits. We allowed for unrestricted active and gentle passive motion to the ring and small fingers. As the thumb proximal phalangeal head fracture was intra-articular, it was decided to delay range of motion for 3 weeks until there was clinical union with no pain to palpation at the fracture site.Upon discontinuation of immobilization of the thumb at three weeks post-injury, the patient’s arc of motion at the IP joint actively and passively was 25°. Within the 3 and 8-week post-injury time period, the therapist reported worsening of active and passive motion. At 8-week follow up, the patient lacked active and passive motion at the IP joint; the joint was fixed at 20° of flexion. Range of motion had normalized in all other fingers. All fractures were healed radiographically; however, early heterotopic ossification (HO) was noted at the IP joint of the thumb . The calTo rule out flexor tendon discontinuity as a cause of loss of motion, an MRI scan was obtained which revealed an intact flexor tendon with no bony involvement of the tendon . The losExcision of the synostosis was performed through a volar approach . MobilizFractures of the tubular bones of the hand are common injuries with an incidence of 12.5 per 10,000 persons per year for the phalanges [Post-traumatic stiffness of the hand is typically a result of fibrosis and contracture of soft tissue structures including the collateral ligaments, volar plate, and tendon adhesions. Stiffness of the hand can occur as a result of heterotopic ossification and synostosis, but is rare. Heterotopic ossification (HO) is characterized by the presence of bone in soft tissue where bone normally does not exist. Synostosis represents the progression of HO resulting in the fusion of two bones. In our case, the initial calcification represented HO which progressed into synostosis once the IP joint was fused.HO and synostosis are often associated with closed head, spinal cord, and thermal injuries . In the HO has been described after open injuries to the hand, specifically lacerations. Barlaan et al. described a case of HO after traumatic laceration of the middle finger extensor tendon without bony injury . Lorio eHO in the hand has been reported without a history of trauma. Hamada et al. described the development of HO in the digital nerves . Kim et Orthopedists should be cognizant that persistent late stiffness may be a result of a bony etiology and not just soft tissue fibrosis and contracture. Impingement by heterotopic bone may result in some loss of motion; however, complete loss of passive motion may suggest synostosis. Intra-articular malunion or involvement of the retrocondylar space with mechanical impingement can also result in loss of active and passive motion. While there was joint incongruity in our example, the patient regained functional range of motion after removal of the bony bridge, indicating the stiffness was the result of the synostosis and not articular malunion or adhesions.Other etiology should be considered when confronted with radiographic heterotopic bone or periarticular calcification. Acute calcific periarthritis, gout and pseudo-gout can present with calcification on imaging studies, which is typically amorphous. These inflammatory arthropathies typically present as atraumatic and painful. Radiographic findings typically will resolve or improve in 2–3 weeks . Our patExperience with early excision of synostosis at the proximal radioulnar joint of the elbow suggests that waiting for radiographic maturity is not needed . Early eIndomethacin was prescribed postoperatively for prophylaxis against recurrence. While multiple studies have compared the efficacy of the use of indomethacin and radiation therapy for the prevention of HO, these studies predominantly focus on the hip . Multipl


Psychoeducation has the potential to support students experiencing distress and help meet the demand for support; however, there is a need to understand how these programs are experienced. Web-based diaries are a useful activity for psychoeducation because of their therapeutic benefits, ability to capture naturalistic data relevant to well-being, and appropriateness for text analysis methods.This study aims to examine how university students use electronic diaries within a psychoeducation program designed to enhance mental well-being.The Science of Happiness course was administered to 154 undergraduate students in a university setting (the United Kingdom). Diaries were collected from the students for 9 weeks. Baseline well-being data were collected using the Short Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS). The percentage of negative and positive emotion words used in diaries  and use of words from five life domains  were calculated using the Linguistic Inquiry and Word Count 2015 software. Random effects  regression models were estimated to examine whether time, diary characteristics, demographics, and baseline well-being predict the emotional tone of diaries.A total of 149 students participated in the diary study, producing 1124 individual diary entries. Compliance with the diary task peaked in week 1  and was at its lowest in week 3 . Compared with week 1, diaries were significantly more positive in their emotional tone during week 5  and week 6  when students were tasked with writing about gratitude and their strengths. Across weeks, moderate and high baseline SWEMWBS scores were associated with a higher percentage of positive emotion words used in diaries . At week 1, the diaries of students with the highest levels of baseline well-being  were more emotionally positive on average than the diaries of students with the lowest levels of baseline well-being . Diaries largely focused on the use of social words. The emotional tone of diary entries was positively related to the use of leisure  and social words , and inversely related to the use of health words .We found evidence for short-term task-specific spikes in the emotional positivity of web-based diary entries and recommend future studies examine the possibility of long-term impacts on the writing and well-being of students. With student well-being strategies in mind, universities should value and encourage leisure and social activities. There is mounting concern regarding increases in the number of young people aged 16-24 years) reporting long-standing mental health difficulties 4 years r. AlongsiThe mental health of university students has been a priority in the higher education sector for at least a century . In the Psychoeducation, which involves the provision of information, tips for self-management, and guidance for staying well , may be Diaries are a promising tool for integration into psychoeducation programs because of their potential for both therapeutic benefit and data collection . DiariesOne of the earliest diary studies examining well-being in university found that common worries included academic stress and common sources of happiness included friendships . PreviouThe availability and progression of technology has been critical in the ongoing advancement of diary-based research. In the field of diary analysis, researchers have used technology to identify prospective participants on the web , automatSignificant advancement has also been made in the analysis of open-text data contained within diaries. Natural language processing methods are being increasingly used to automate the analysis of diaries, as seen in a web-based eating disorder intervention . StatistThis study aims to examine how university students use electronic diaries within a psychoeducation program designed to develop mental well-being skills (Science of Happiness course). Longitudinal diary data enabled us to examine how the program was experienced and how the proportion of positive and negative emotion words  within diaries fluctuated over time. Automated text analysis methods were used to analyze the written content of the diaries. This study has 5 key research questions:How compliant are students to the web-based diary task across weeks?How does the proportion of positive and negative emotion words  within the diaries develop over time?How are time, sociodemographics, diary characteristics, and baseline self-reported well-being related to the emotional tone of diaries? (model 1)Is the trajectory of emotional tone within diaries dependent on baseline levels of well-being? (model 2)Which life domains do students discuss most in their diaries, and how do these topics relate to the emotional tone of diary entries? (model 3)Science of Happiness course was offered to students on 14 undergraduate courses in their first year of study (including study abroad programs) in exchange for academic credits. The course began in the first semester of the study (September 2019) and involved weekly lectures, weekly group tasks, and weekly diary entries (the focus of this research). The main evaluation examining the impact of the intervention is presented in a publication submitted separately [The sample consisted of 154 university undergraduate students at a university in the UK. The parately .Sociodemographic characteristics and well-being data were collected at baseline. Parallel to the intervention, linked anonymized diary entries were collected digitally on a weekly basis at 9 time points.Each student was assigned a study participant number, and no personally identifiable data were included in the research data set. Diary data were extracted from the web platform they were submitted to (Blackboard) and deposited in a Microsoft Excel spreadsheet stored on a secure server. Within the software, students were only able to submit one diary entry per week. The study obtained ethical approval from the University of Bristol Faculty Ethics Review Committee (reference: 27061987862).solicited, given that they were requested by us for this study, rather than being spontaneous [The diaries we collected were ntaneous . Studentntaneous .A brief sociodemographic survey was used to capture data on gender, age, nationality, and ethnicity. Mental well-being was measured using the 7-item Short Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS) . The oridictionary method approach to text analysis. This deductive approach involved automating the analysis of diary content based on a predetermined dictionary-based coding scheme [This study used a g scheme .All diaries were completed in the English language. Text data were stored in Microsoft Excel in a wide format (one participant per row and 1 week of diary entries per column). Typos were managed using guidance developed by the Language Use and Social Interaction lab . A manuaroominate were changed to ruminate to ensure the text analysis software was able to correctly identify the words used. Words such as kinda were not corrected because of the ability of text analysis software to recognize and correctly classify slang text-speech. In total, 892 words were manually corrected during the data cleaning process.All diaries were manually scanned for typos, and words such as Linguistic Inquiry and Word Count (LIWC) 2015 is a stand-alone piece of software that has been empirically validated to analyze the linguistic, social, and psychological content of text data . LIWC 20negative emotion section of LIWC’s internal dictionary and 5 of its words were found in the positive emotion section of LIWC’s internal dictionary, the positive emotion score would be 5, the negative emotion score would be 5, and the emotional tone score would be 50. Higher scores on the emotional tone variable indicate a greater ratio of positivity within the text of diary entries, with scores above 50 indicating a greater proportion of positive words and scores below 50, indicating a greater proportion of negative words.We also used the emotional tone variable generated by the LIWC software. This reflects the ratio of positive and negative emotion words. If a diary entry contained 100 words and 5 of its words were found in the Data were analyzed using STATA 16 (StataCorp LLC) . SociodeThe trajectory of emotional tone across weeks is displayed in line graphs. The trajectory of emotional tone seen in the whole data set  was compared with the trajectory seen for the subsample with full compliance to diary entry .We applied 4 models using random effects generalized least squares with an autoregressive disturbances regression approach . This meA summary of the sample characteristics is provided in From 855 diaries, the SWEMWBS scores were recoded by tertiles for the diaries of students with low well-being , moderate well-being , and high well-being .Compliance with the diary task by week is displayed in Participants were grouped by those who completed all 9 entries , 8 entries , 7 entries , or fewer than 6 entries . Descriptive statistics for the characteristics of participants across the 4 levels of diary compliance are presented in 0-103.5 word count length and 195/280, 69.6% for diaries of 265+ word count).There were no clear patterns in the age of respondents or emotional tone of diary entries based on the 4 word count categories . Longer The pattern of scores for the available-case analysis and the complete-case analysis followed an inverted U shape , with a P<.001) and 26.62 , respectively, in comparison with the emotional tone of diary entries in week 1. The mean emotional tone did not significantly differ from week 1 for the remaining 6 weeks. As the age of students increased by 1 year, the emotional tone of diary entries was higher, on average, by 1.98 . Students with both moderate  and high  levels of baseline well-being had diaries with significantly higher emotional tone compared with students with low baseline well-being. Gender and diary characteristics had no clear effects.The results from the random effects generalized least squares regression examining the role of week effects, sociodemographics, diary characteristics, and baseline levels of well-being in determining the emotional tone of diary entries are presented in P=.03), indicating a better fitting model. To examine how the pattern of emotional tone differed between students with the lowest and highest well-being across the weeks, we plotted the mean emotional tone for students with the highest and lowest levels of well-being  and time (weeks) improved the fit of the model . Adding The use of words from 5 life domains (mean percentage of words per diary entry) across the 9 weeks is presented in social words in diaries increased by 1, the emotional tone of diaries increased by an average of 0.74 . As the percentage of leisure words in diaries increased by 1, the emotional tone of diaries increased on average by 3.56 . Finally, as the percentage of health words in diaries increased by 1, the emotional tone of diaries was more negative by an average of 1.96 . The relationships between work- and money-related words and the emotional tone of diary entries were nonsignificant.Compliance with the diary task peaked in week 1  and the fewest diaries were completed in week 3 . Students with the most completed diaries had the highest diary word counts, highest levels of baseline well-being, and on average had diaries with the highest emotional tone. Compared with week 1, diaries were significantly more positive in their emotional tone during weeks 5 and 6 when diary tasks involved writing about gratitude and strengths, respectively. This improvement in emotional tone was not observed at the end of the course, indicating a short-term rather than a lasting improvement in the emotional tone of writing. Higher levels of baseline well-being were associated with more emotionally positive diary entries, and the pattern of emotional tone within diaries across the weeks seen for students with low, moderate, and high baseline well-being was distinct. Diaries predominantly focused on social topics throughout the weeks, and the emotional tone of diaries was positively related to the use of leisure and social words and negatively related to the use of health words.The dominant focus on social topics within well-being–oriented diaries reinforces findings from previous research, indicating that a lack of social connectedness predicted higher levels of related mental distress (anxiety and depression) in a cross-sectional study of UK university students . In thisThe analysis of word use across life domains highlights the importance of social factors and leisure in the lives of university students. As such, attempts to tackle student well-being concerns should continue to experiment with the utility of peer support networks, engaging familial support and responsible use of social media. In terms of the important role leisure plays in student well-being, universities are encouraged to ensure multiple options for leisure are readily available, and students are encouraged to select activities that are personally satisfying . The proThese findings also have implications for the ongoing development of the Science of Happiness course. We present evidence for students’ acceptance and willingness to engage in a reasonably rigorous schedule of weekly web-based written diary tasks. It is also noteworthy that one of the weeks with lower compliance to the diary entry task occurred when students were on a break from study (week 3), which provides us important insight into the level of engagement to expect when students are disengaged from university academic activities. This work also provides data-driven guidance as to which students may be more prone to disengage from the task .There are wider implications for how student data are used as technology develops. The text analysis methods described in this paper could readily be applied to routinely collected information from students, for example, in written requests for well-being support, to estimate levels of distress based on the use of emotional words. Any developments in this area should reflect on the ethical questions about privacy and student preferences raised by experts working in the area of learning analytics . StudentThis study has several limitations. Participants in this study were self-selected; therefore, the respondents in this study may not be representative of the wider student population. Available national data indicate that the UK university population is slightly more female and two-thirds of White ethnicity ; howeverIn this study of undergraduate students, diaries predominantly focused on social topics; however, future research could examine whether different patterns, such as a focus on money or health, are observed in nonstudent samples of young adults. This study could build on attempts to investigate how distinct the challenges experienced by students are to university populations ,46. SepaGiven the noticeable spike in emotional tone observed when students were tasked with writing diaries about gratitude, a future iteration of the course could focus solely on this subject . Future One explanation for why compliance with the diary task fell to 72.5% (108/149) in week 9 is that this time point marked the conclusion of the course. Exploring this phenomenon and broader motivations for participation in the course would expand our understanding of how the course is interpreted and experienced. In future research, it would be informative to examine the acceptability of automated digital prompts designed to encourage the use of the web-based diaries, especially for participants who are willing yet have simply forgotten to complete the task.This study demonstrated the informative power of web-based diaries, the flexibility of computerized text analysis methods, and differential experiences of students with varying levels of baseline well-being engaged in psychoeducation. Students used their diaries with a high level of compliance and wrote with the highest proportion of positive emotion words during weeks where diaries focused on gratitude and strengths. Further research is needed to explore the importance of leisure to well-being the longer-term impact of diaries on well-being, and suggestions are provided for how the science of happiness could be adapted in the future. We present support for previous studies highlighting the importance of social factors and leisure for student well-being, and echo recommendations that universities should ensure these activities are facilitated and encouraged.


For this, a universal duality between the quench dynamics and the equilibrium topological phase of the spin model is obtained in the time dimension by extracting information from the field evolution dynamics in modulated ring systems in simulations. This work also shows that the photonic synthetic frequency dimension provides an efficient and powerful way to explore the topological nonequilibrium dynamics.The notion of topological phases extended to dynamical systems stimulates extensive studies, of which the characterization of nonequilibrium topological invariants is a central issue and usually necessitates the information of quantum dynamics in both the time and momentum dimensions. Here, we propose the topological holographic quench dynamics in synthetic dimension, and also show it provides a highly efficient scheme to characterize photonic topological phases. A pseudospin model is constructed with ring resonators in a synthetic lattice formed by frequencies of light, and the quench dynamics is induced by initializing a trivial state, which evolves under a topological Hamiltonian. Our key prediction is that the complete topological information of the Hamiltonian is encoded in quench dynamics solely in the time dimension, and is further mapped to lower-dimensional space, manifesting the holographic features of the dynamics. In particular, two fundamental time scales emerge in the dynamical evolution, with one mimicking the topological band on the momentum dimension and the other characterizing the  Topological holographic quench dynamics in a synthetic frequency dimension studied in modulated ring system shows the universal bulk-surface duality with complete topological information being encoded in the single time variable. In addition to the great progress made for equilibrium phases, the nonequilibrium quantum dynamics can exhibit exotic behaviors7, and the notion of topological phases has been extended to far-from-equilibrium dynamical systems, with novel topological physics being uncovered, such as the anomalous topological states in Floquet systems14 and dynamical topology emerging in quantum quenches29. In particular, a universal dynamical bulk-surface correspondence was predicted when quenching a system across topological transition32, showing that the bulk topology of an equilibrium topological phase has a one-to-one correspondence to quench-induced dynamical topological patterns emerging on the lower-dimensional momentum subspaces called band inversion surfaces (BISs). The dynamical bulk-surface correspondence connects the equilibrium topological phases with far-from-equilibrium quantum dynamics, which was further extended to correlated system33, high-order regimes35, and to generic nonadiabatic quenches36. This opens the way to characterize equilibrium topological phases by nonequilibrium quench dynamics, and inversely, to classify nonequilibrium quantum dynamics by topological theory, with the experimental studies having been widely reported recently44. The nonequilibrium topological invariants are typically defined via time dimension and momentum space, and their characterization naturally necessitates the information of quantum dynamics in both the time and spatial dimensions.The discovery of topological quantum phases has revolutionized the understanding of the fundamental phases of quantum matter and ignited extensive research in condensed matter physics over the past decades47 were proposed and opened an intriguing avenue towards the quantum simulation of exotic topological physics beyond physical dimensions50. Following the numerous theoretical proposals on synthetic dimensions using a different degree of freedoms such as the frequency or the orbital angular momentum of light54, and the hyperfine levels of atoms55, experiments have been recently performed to demonstrate the two-dimensional topological insulator56 and the Hall ladder57 in the synthetic space, where the effective magnetic field for photons is generated, and visualize the edge states59. Further, the high-dimensional physics can be studied in a photonic platform with lower dimensionality64. More recently, the experimental platforms for generating the synthetic dimension along the frequency axis have also been proposed and demonstrated using the ring resonator66, in which the photonic modes at equally spanned frequencies are coupled through the dynamic modulation. In this system, the band structure in the synthetic dimension can be measured in the static steady-state regime in the experiment65. On the other hand, with the synthetic dimensions the novel optical phenomena and applications have been proposed, including the realizations of unidirectional frequency translation67, pulse narrowing68, active photon storage69, and topological laser70. Therefore, synthetic dimensions in photonics not only provide a unique way to simulate quench dynamics but also can find many novel applications for light. In particular, the reciprocal dimension of the frequency axis of light is the time dimension, which naturally arises the question: how to understand the quench dynamics in the synthetic frequency dimension. Successful answering of this question can also trigger further studies of quench dynamics of the complicated model in higher dimensions on modulated ring systems.In order to go beyond the spatial degree of freedom and capture the extensive information of quantum dynamics, the synthetic dimensionsresidue time evolution after the quench. By extracting information of the field onto two time scales in simulations, we find the dynamical topological patterns obtained on BISs, which render an emergent dynamical bulk-surface duality and provide a holographic characterization of the topological spin model, with the complete information being encoded in the single variable, i.e., the time evolution, in sharp contrast to the conventional nonequilibrium topological states. The dynamical topology is robust against disorders and has high experimental feasibility. This work shows advantages in exploring the topological phases with holographic quench dynamics in the synthetic dimensions and provides an insight into classifying the far-from-equilibrium dynamics with nontrivial topology based on the synthetic photonic crystals.In this article, we combine the concepts of dynamical classification and synthetic dimension and propose a highly efficient scheme to characterize topological phases by holographic quench dynamics. The topological holographic quench dynamics refer to a procedure of the quench dynamics simulated by encoding the complete topological information of light fields in a time dimension, which is further mapped to a lower-dimensional subspace through the bulk-surface duality. We construct a one-dimensional pseudospin model in a photonic synthetic lattice in the frequency domain and investigate the quench dynamics by initializing a trivial phase, which evolves under a topological Hamiltonian. We show that the full dynamical evolution is featured by two fundamental time scales, with which the quench dynamics exhibit universal topological patterns. In particular, one time scale mimics the Bloch momenta of the topological band and the other  characterizes the 71. Ring B has shifted resonant modes at frequencies We start with illustrating our idea of using ring resonators under dynamic modulations to artificially engineer a tight-binding lattice of pseudospin states along the frequency axis of light. As shown in Fig. 72:The couplings between modes in the ring resonators are engineered by properly setting the phase modulators. We place one phase modulator [labeled as PM A(C) in Fig. Ea, Eb and output amplitudes The pseudospin-1/2 system is realized by modulating the resonator couplings. The field in ring A(C) is coupled with the field in ring B through the evanescent wave. The corresponding coupling equation is described by the coupling matrix between input electric field amplitudes Here, The coupling between resonant modes in rings A and C are mediated by ring B, as illustrated in Fig. entclass1pt{minima71. We choose modulation phases to be either 73. Such Hamiltonian of the system readsω0):We now turn to the effective model of the coupled ring system. The modulations including modulation phases inside rings have high tunability32. One notes that the Hamiltonian in Eq. 14) refleThe coupling in Eq.  between The coupling between fields in rings C and B is similarly described.71.In simulations, the four external waveguides coupling rings A and C, as shown in Fig. ilar Eq.  with theSupplementary InformationCartoon Movie


Ventricular assist devices (VADs) are used to provide mechanical circulatory support to patients with end-stage heart failure. The driveline connecting the external power source to the pump(s) of the intra-corporal VAD breaches the protective skin barrier and provides a track for microbes to invade the interior of the patient’s body. Driveline infection constitutes a major and potentially fatal vulnerability of VAD therapy. Driveline infection cannot traditionally be salvaged and requires the extraction of the entire VAD system. We report here the successful eradication of a VAD driveline infection with a taurolidine-containing antimicrobial solution used for preventing the infection of cardiac implantable electronic devices. If replicated in more cases, the novel treatment concept described here may provide a valuable alternative management strategy of salvage rather than explantation for VAD driveline infection. Ventricular assist devices (VADs) provide mechanical circulatory support to patients with end-stage heart failure, and may be used as either a bridge to cardiac transplantation or a destination therapy in their own right. VADs can be intra- or extra-corporal, depending on whether the pump(s) driving the circulation of blood are located inside or outside of the patient’s body. While technical advances have greatly improved the safety and reliability of these highly sophisticated electro-mechanical devices, the rates of certain complications  have remained steady. Infection of the driveline connecting the external power source to the pump(s) inside the patient’s body is the leading cause of hospital re-admission for intracorporeal VADs. Mortality is 5.6 times higher in patients with VAD-related infections and can exceed 35%. Microbes form biofilms on the driveline and can be resistant to antimicrobial agents commonly used during VAD revision ,2.TauroPace™  is an antimicrobial solution used for preventing infection from cardiac implantable electronic devices (CIEDs). The agent is versatile in its application and can be used for wiping the external surfaces of medical devices, flushing their inner surfaces (if they have lumens), or irrigating the surgical site. Its main active ingredient is Taurolidine, an amino acid compound that breaks down by hydrolysis in vivo to release methylol groups. Methylol groups readily react with and denature the peptidoglycans in the bacterial cell wall, and the polysaccharide and lipopolysaccharide components of endotoxins and certain susceptible exotoxins. The results are the destruction of the bacterial cell, the inhibition of surface attachment biofilm formation, and the inactivation of endotoxins and some exotoxins. The active taurolidine compounds have a half-life of 1.56 h and 6 h in the presence of saccharides, peptides and glycans. The final products of taurolidine metabolism are the non-essential amino acid taurine, and water. Taurine degradation leads to an acidic environment in the surgical site, which increases the chemical activities of the Taurolidine compound, setting up a positive feedback loop for its biological effects . TaurineBoth minors were initially implanted with the Heart Ware™  left ventricular assist device (LVAD) in the paediatric cardio-thoracic department of the University Hospital Erlangen.The first patient received the LVAD as a destination therapy for terminal heart failure in dilated cardiomyopathy. The patient was not eligible for urgent heart transplantation due to a rare mitochondriopathy. The second patient received the LVAD as a bridge to cardiac transplantation. The underlying pathology was dilated cardiomyopathy secondary to chronic non-viral myocarditis, incidentally discovered when the patient was investigated for a thromboembolic stroke in the middle cerebral artery and bilateral pneumonia.Both patients displayed the skin appearance typical of driveline infection when admitted to our centre . EndocarVAD salvage procedure: The skin around the exit site and the fibrous tissues around the driveline were excised. The driveline was mobilised from the subcutaneous tissues and washed with the Taurolidine solution. The infected, partially necrotic wound bed was debrided until healthy uninfected tissues were seen. The driveline was brushed to remove any adherent debris. The entire surgical field from the exit site of the driveline to the mediastinum was thoroughly irrigated with the Taurolidine solution . The knitted Poly-ethylene-terephthalate velour cover surrounding the driveline was saturated with the Taurolidine solution, placed in the final position, and secured to the fascia rectus abdominis with Polyester sutures. The original skin exit site was reused and no new exit point for the driveline was fashioned. The subcutaneous space was closed with a Polyglactin suture. The skin edges were closed with interrupted non-absorbable monofilament sutures. Negative pressure therapy  was applied to the surgical wound for 7 days, with the sponge dressing changed every 3 days. Aseptic wound dressing was then applied and changed daily for the next 7 days. Parenteral antibiotic therapy was administered for a total of 14 days in the first case and 12 days in the second case. Inflammation had clinically disappeared from the driveline skin exit site 3 days after the revision procedure, which we had not experienced before the use of the Taurolidine solution. VAD driveline infection did not reoccur after the 10-month follow-up (December 2021) and both patients remained in excellent condition.Our surgical approach for managing driveline infection should be “standard of care” and performed in identical or similar fashions in centres with the appropriate expertise. The use of various antiseptics to irrigate the surgical field in the revision of driveline infection may also be common. The use of Taurolidine in this context is novel. The use of Taurolidine to treat surgical infection in the operation room was first described in some anecdotal reports in the 1980s. Subsequently, Taurolidine has been most commonly used in locking solutions to prevent catheter-related bloodstream infection in fragile patients ,5,6. As Despite the encouraging preliminary results with the use of the Taurolidine solution to treat driveline infection , further confirmation is needed before its widespread adoption can be recommended. There is extensive clinical experience with the use of the Taurolidine solution in CIED procedures, giving reassurance on the safety if, not the efficacy of the product.


Friction models are proposed for anisotropic and heterogeneous dry friction on boundaries of polymer solids. Unit vectors and oriented angles of sliding velocities, radii of curvature and unit normal vectors of sliding trajectories are taken as independent variables in constitutive equations of anisotropic and heterogeneous friction. Heterogeneous dry friction of a polymer pin in pin-on-disc tests is illustrated in the case of Archimedean spiral trajectory. Individual molecular chains composing polymer materials can move inside the material with a high degree of friction anisotropy. The resistance of macromolecule motion is considered with respect to micromechanical models of macromolecules, their kinematics, and friction laws. Two approaches are applied for modeling of anisotropic friction inside polymer materials: continuum-based models (anisotropic viscous friction) and micromechanical models (anisotropic dry friction). Examples of macromolecule dry friction are considered under conditions of spinning and sliding of a disc-like macromolecule and snake-like sliding of a long macromolecule. This study is an extension of the research presented at 14th World Congress on Computational Mechanics (WCCM) and European Community on Computational Methods in Applied Sciences (ECCOMAS) Congress 2020, virtual congress: 11–15 January 2021 [Polymers and polymer composites are materials of great importance in friction assemblies of machines and devices operating in unlubricated contact conditions (or in starved lubrication conditions) because of their self-lubricating character e.g., dry sliding bearings . PolymerThere are various reasons of friction anisotropy and heterogeneity on boundaries of polymer solids, e.g., in polymer composites, semicrystalline polymers, and self-assembled and self-lubricating polymers. In composites consisting of components of different materials, external boundaries have mosaic structures, since different components are exposed at different points on the boundaries ,5,6. PolFriction phenomena inside polymer materials are equally important as well as on external boundaries of polymer solids. Macromolecular polymers are repeated combinations of numerous simple chemical molecules (monomers) produced by a cyclic repetition in the fabrication process. Usually randomly distributed macromolecules do not have a specific orientation, but polymers are macromolecular materials with evolving properties. The evolution of polymer microstructure can be induced by action of large external loads  or high temperatures, and it has the following two forms: (a) unraveling of the molecular chains constituting the polymeric network, (b) relative motion of the unraveled chains or their segments through the surrounding moving macromolecules. In other words, large deformations initiate the orientation process of macromolecules ,16,17. TThe purpose of this study is to include microstructure evolution effects in friction equations for polymers on external boundaries of solids and inside materials. This is realized with the aid of anisotropic and nonhomogeneous friction models including useful additional independent variables. The paper is organized as follows: in a first step, friction on boundaries of solids is investigated ; in a seModels of friction on external boundaries of polymer solids describe friction of polymers rubbing against another or against boundaries of different materials. In the literature, the model of dry friction or its contemporary modifications are used ,13. The Macromolecular materials require specific constitutive relations for friction. Proposed in this study constitutive models of dry friction on boundaries of polymer solids are based on the phenomenological approach with additional variables that describe microstructural effects. The similar research methodology is used in advanced models of plasticity with internal (hidden) state variables . The folv of the sliding velocity Dependence of the friction force on the sliding direction is described with the aid of the unit vector city u˙t , i.e., and the sliding direction v . This is the so-called directionally asymmetric friction. The asymmetric friction description must include the sense of the sliding direction. Due to this we introduce the oriented angle  as the iection v . The friCi=Ci(αv)The friction tensors are assumed to be trigonometrical polynomials of the variable  followsCi(αv)=CiIf the parameters Equation  describen  gives tquation  is nonpositive.The friction constitutive functions are assumed to satisfy the dissipation inequality (25) for any sliding motion. The condition of the dissipated energy restricts constants (friction tensors) in the friction constitutive equations.Friction and wear of polytetrafluoroethylene (PTFE) and high density polyethylene (HDPE) are sensitive to the orientation of the molecular chains with respect to sliding directions ,29,30,31With the aid of a multidirectional tribometer of the type pin-on-disc , frictiom is the mass of the material point, x is the position vector of the material point with respect to the reference system F is the central force. The motion Equation  in a sliding base plane (the disc) with the given sliding trajectory. The motion of the point in the reference system Cxy  is descrCxy  and (20), we propose the following isotropic second-order tensor Let us consider the second-order formulation Equation  of the hIn the second-order formulation Equation , the hetThe coefficient of the dissipative friction force component The last term in Equation  defines The coefficient of the gyroscopic friction force component is given byThe coefficients dynamics ,24,25.The material parameters used in the friction equations can be determined directly from experiments, since proposed dry friction models on boundaries of polymer solids are based on the phenomenological approach.Usually two independent components describe the energy dissipation during sliding on the external boundaries of elastomer solids. So called two-component elastomer friction models include adhesion and hysteresis effects ,33,34. FVery high hysteresis of bulk deformations takes place in elastomers ,33,34. TPolymers are modeled as assemblies of great number of isolated individual micro-elements composing the materials. In the frame of micromechanics various models of the individual molecular chains are proposed in the literature, e.g., bead-spring, bead-rod, elastic dumbbell model, reptation type tube, rod-like macromolecule, disc-like macromolecule . In the Rouse model —the macrDe Gennes tube model —the indiPolymers in liquid crystal phase can form long rigid macromolecules similar to rods and flat rigid macromolecules similar to discs. During motions of rod-like and disc-like macromolecules the energy dissipation takes part since the resistance to motion between these objects is present. Two particular cases of the resistance to motion (friction) can be considered: (a) friction of rod-like macromolecules under rolling with and without slipping, (b) friction of disc-like macromolecules under spinning and sliding. In both cases, friction forces and friction couples are present.From the mechanical point of view, polymers may have simultaneously viscous properties typical in fluids and elastic properties as in solids. In the literature, constitutive laws between stresses and strains in polymers are described with the aid of the following two approaches. (a) Phenomenological modeling. The models are extensions of the constitutive theories developed for metals and their alloys e.g., visco-elasiticity, visco-plasticity . Melted In this study, we use the similar research methodology and the motion resistance between molecular chains we describe: (a) in terms of an extension of constitutive ideas from bulk polymer materials, i.e., continuum-based models of friction, and (b) taking into account the micro-models and kinematics of the polymer chains, i.e., micromechanical models of friction. The resistance to motion of the macromolecules is described with the aid of friction laws ,19.The motion resistance of the moving molecular chains we consider with respect to the individual molecular model and kinematical properties of the chains. We assume that micromechanical models of polymer macromolecules are in contact with a hypothetical base plane in the presence of anisotropic dry friction . KinematIn the given conditions, the macromolecules in polymers are independent kinematical elements. Usually large external loads (or high temperatures) can initiate the movements of the molecular chains one with respect to other. The motion of the macromolecules consists of translations and rotations. Due to this the macromolecule models have translational and rotational degrees of freedom. Furthermore, the macromolecules can change shapes under large external loads. Individual polymer macromolecules meet the resistance to motion with very high degree of friction anisotropy .i-th bead  follows the Langevin equation:m is the mass of the bead, 1 is the unit tensor, The macromolecule motions are liquid-like and Brownian type. In stochastic dynamics, Langevin equation of motion describes Brownian movements using Newton motion equation with an additional term including external random excitations  ,38,39,40In computational mechanics various numerical techniques are used to predict the behavior of polymers as molecular systems when subject to applied loads: Molecular Dynamics (MD), Discrete Element Method (DEM), Finite Element Method (FEM). A precise friction constitutive model is a key factor in numerical calculations.Nanometer is the length scale of the polymer chain. Nanosecond is the time scale in dynamics of polymer chains. Due to this, trial-and-error method can be a way of identification of the material parameters used in the micromechanical models.In the literature, the models of anisotropic viscous friction are used as laws of the motion resistance of the polymer macromolecules due to interactions with the neighboring macromolecules ,40. In tThe anisotropic viscous friction in Equation  is descrp and the velocity The vectors of the friction force The representation matrix of the anisotropic viscous friction tensor Equation  has two This friction is orthotropic in the horizontal plane and isotropic in the transverse direction.In , rod-likSpinning is the angular motion about the normal axis to the disc and to the base plane. Spinning of the disc is described by the unit vector i = 1,2). The scalar function r describes arbitrary distribution of the normal pressure at the contact area F with arbitrary shape and dimensions. During spinning, the disc particles contacting with the base plane have translational velocities. The unit vector The axis of rotation is called the spin center or the spin pole or the center of gravity . Let theLet the friction force at point P of the unit contact area Equation , i.e., with isotropic friction, (b) with orthotropic friction, i.e.,F are constant during spinning. Then, the friction characteristics are defined by the following formulas for the contact with isotropic friction Equation H1=−For the contact with orthotropic friction Equation , the friF of the disc has the circular shape with the radius a, and it rotates about the center of the disc; then, the quantities We assume that the contact area The vectors of the friction forces and their moments for the contact of the disc and the base plane with isotropic friction Equation  are giveEquation  of the bv and spinning about the axis normal to the contact with velocity unit vector F is described by the resultant vector M of the friction force moments with respect to the center of the disc. In accordance with the friction models, the linear mapping L exists between the resultant vectors of the friction forces and the unit vectors of the translational and spinning velocities, i.e.,We consider coupled kinematics when the disc-like macromolecule participate simultaneously in sliding and spinning motions . TranslaL at the contact of the circular disc of the radius a and the constant normal pressure. In the case of isotropic friction Equation , positions on sliding trajectories (friction heterogeneity), specific models of individual macromolecules, and their kinematics inside the polymer materials.Main advantages of the proposed friction models are as follows: they are simple enough and they have a finite number of parameters (easy to determine in experiments), and they can be extended to other types of frictional anisotropy and nonhomogeneity important in polymers. Applied in this study, continuum mechanics principles are a powerful tool in the modeling of polymer friction.The friction models on external boundaries of solid polymers can be used to simulate, predict, and improve the frictional behavior of polymeric component parts of mechanical systems, e.g., dry sliding bearings, sliding seals, transmission belts, car tires, prostheses of human joints, etc.The friction models inside the polymer materials can be used in studies of macromolecule dynamics with friction effects, and they can have practical applications in simulation and optimization of properties of polymer melts, gels, solutions, and liquid crystals in fabrication processes of the chemical industry.


Temporal indentations are the most impacting craniofacial complication after coronal flap dissection. It is mainly due to a temporal fat pad or temporalis muscle dissection.Because of the great improvements achieved recently in CAD-CAM-aided surgery and the possibility of performing accurate pre-surgical virtual planning, it is now possible to correct it with a customised virtual approach. Furthermore, advancements in material science have allowed surgeons to rely on biocompatible materials like PEEK (showing a low complication and recurrence rate) for the manufacturing of patient-specific implants.We hereby describe our experience on a case of secondary and corrective surgery after a fronto-orbital remodelling, in which we used PEEK implants designed by CAD and optimized by finite element modelling. Temporal hollowing is one of the most frequent cosmetic complications after coronal incisions; although the aetiopathogenesis is still controversial, fat pad and temporalis muscle atrophy are thought to be the main causes.,Since it is frequently a reason for cosmetic dissatisfaction and psychological distress for patients, several surgical methods have been developed to prevent it or treat it,A wide range of secondary surgical solutions has been developed, ranging from autologous fat transfer to patient-specific implants (PSI) developed in biocompatible materials (polyether ether ketone (PEEK) and polymethylmethacrylate (PMMA)), because of the advent of technologies for CAD-CAM-aided surgery.We hereby present a case of temporal deformity due to previous fronto-orbital advancement remodelling (FOAR), where the patient (a 13-year-old boy) underwent a PEEK custom cranioplasty, planned by finite element modelling (FEM) prediction.The patient was admitted to the Craniofacial Unit at Great Ormond Hospital for Children in London to undergo FOAR in 2005 at the age of 1 year following a diagnosis of metopic craniosynostosis. Twelve years later (at the age of 13), the patient noted indentations at the temporal regions A-C.FigurA CT scan was performed for preoperative assessment of soft and bony tissue. The CT scans were imported into Mimics Innovation Suite  which was used to perform 3D soft and hard tissue reconstruction A-B. The To test the effect of implant insertion, FEM  was used. The upper face of the patient was discretized A and impThe simulations B were coThe implants were positioned in the theatre. The pre-existing coronal incision was re-opened after injection of tumescent solution. The coronal composite flap was then raised in the sub-pericranial plane. The temporalis muscles appeared to be contracted and attached more inferiorly than normal on the skull. Afterwards, implants were secured to the cranium with titanium mini-screws, and the temporalis muscles were resuspended by pre-designed drill holes in the implant with 3-0 PDS suture. The entire surgical procedure lasted for 90 minutes. The patient was discharged on the first post-operative day after an uneventful recovery. The preoperative CT A was quaPEEK patient-specific implants have been successfully used in craniofacial surgery for over 20 years.,The findings in the literature are controversial when it comes to the complication rates of PEEK implants, but a few have been reported relatively to the use in the case of cranioplasty.The numerical model used to design the implant is simplified and only includes soft and bony tissues, which were modelled as linear materials. This assumption may affect the accuracy of the simulation results in terms of stress analysis, but – as the aim of the simulation was to predict the soft tissue displacement – it bears no effect on the implant design pipeline hereby presented. This is also reflected in the good matching between the simulated tissue response and the actual surgical outcomes as shown in This case demonstrates the advantages of surgical planning of complex soft tissue augmentations using FEM to accurately design the shape and the position of the implants. Although PEEK is expensive, total expenditure was offset by the reduction in operating time and hospital stay. In our experience, PEEK PSIs have been a reliable technique to overcome the temporal hollowing.None