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Background Working in partnership with the Cambodian Ministry of Health, the Safe Surgery 2020 initiative (SS2020) supports the prioritization of surgery and mobilization of resources to target limited workforce capacity. An evaluation study was conducted to assess the impact of SS2020 on intervention hospitals in Cambodia. Objective To understand the impact of the SS2020 program on intervention hospitals in Cambodia by assessing the changes in key surgical performance indicators before and after the intervention, identifying key barriers and facilitators to adoption of learnings, and discovering lessons on the uptake and diffusion of this initiative in Cambodia and other similar contexts. Methods This study is a convergent mixed-methods evaluation of a one-year multicomponent SS2020 intervention. Surgical observations were conducted in 8 intervention hospitals at baseline and endline to evaluate pre and post adherence to 20 safety, teamwork, and communication items. Fifteen focus groups were conducted in all intervention sites at endline to assess key facilitators and barriers to positive impact. Results There was significant improvement in 19 of 20 indicators assessed during surgical observations. Among the highest performing indicators were safety items; among the lowest were communication items. Participants self-reported improved knowledge and positive behavior change after the intervention. Institutional change and direct patient impact were not widely reported. Most participants had favorable views of the mentorship model and were eager for the program to continue implementation. Conclusions The results provide evidence that change in surgical ecosystems can be achieved on a short timeline with limited resources. The hub-and-spoke mentorship model can be successful in improving knowledge and changing behavior in surgical safety. Workforce development is important to improving surgical systems, but greater financial and human resources are needed. Ministry support in adopting, leading, and scaling is crucial to the continued success of safe surgery interventions in Cambodia.

Enterprise budgets are effective planning tools for growers in search of help with forecasting, resource coordination, and better production decisions. In essence, enterprise budgets can help producers determine what to produce, how many acres to produce, the cost of production, and the necessary price to be profitable. This 5-page fact sheet written by Tara Wade, Barbara Hyman, Eugene McAvoy, and John VanSickle and published by the UF/IFAS Food and Resource Economics Department describes the process used to create the 2017/18 enterprise budget for tomatoes in southwest Florida and includes resources for producers interested in creating enterprise budgets for their own operations. https://edis.ifas.ufl.edu/fe1087

The complement system comprises the frontline of the innate immune system. Triggered by pathogenic surface patterns in different pathways, the cascade concludes with the formation of a membrane attack complex (MAC; complement components C5b to C9) and C5a, a potent anaphylatoxin that elicits various inflammatory signals through binding to C5a receptor 1 (C5aR1). Despite its important role in pathogen elimination, priming and recruitment of myeloid cells from the immune system, as well as crosstalk with other physiological systems, inadvertent activation of the complement system can result in self-attack and overreaction in autoinflammatory diseases. Consequently, it constitutes an interesting target for specialized therapies. The paradigm of safe and efficacious terminal complement pathway inhibition has been demonstrated by the approval of eculizumab in paroxysmal nocturnal hematuria. In addition, complement contribution in rare kidney diseases, such as lupus nephritis, IgA nephropathy, atypical hemolytic uremic syndrome, C3 glomerulopathy, or antineutrophil cytoplasmic antibody-associated vasculitis has been demonstrated. This review summarizes the involvement of the terminal effector agents of the complement system in these diseases and provides an overview of inhibitors for complement components C5, C5a, C5aR1, and MAC that are currently in clinical development. Furthermore, a link between increased complement activity and lung damage in severe COVID-19 patients is discussed and the potential for use of complement inhibitors in COVID-19 is presented.

Biochar has been made by carbonization of spent coffee grounds without further activation and has been characterized by several techniques revealing a material with a satisfactory balance of microporosity with meso and macroporosity. The material was fairly pure with 96% of its mass made of carbon and oxygen, 2.2% of K and the rest of unidentified minerals. This biochar was used to make a supercapacitor electrode combined with a photocatalytic fuel cell as an electric power source. It has been shown that the present biochar does apply as material to make a supercapacitor with specific capacitance mounting up to 200 Fg−1. Its combination with a photocatalytic fuel cell can be designed into a very simple system which provides several functions in one single device: solar energy conversion, photocatalytic degradation of an organic substance and storing of electric energy in a supercapacitor.

Introduction A surge in the use of paracetamol in neonates has resulted in growing concerns about its potential long-term adverse events. In this study, we conduct a systematic review of the long-term safety of prenatal and neonatal exposure to paracetamol in newborn infants.Methods and analysis We will follow the Joanna Briggs Institute Manual for Evidence Synthesis and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statements to conduct and report this review. We will conduct a systematic search of Embase, MEDLINE, Web of Science and Google Scholar for studies with data on long-term adverse events in neonates that were exposed to paracetamol in the prenatal and/or neonatal period. We will not apply language or design limitations. We will use standardised risk of bias assessment tools to perform a quality assessment of each included article.Ethics and dissemination This systematic review will only involve access to publicly available data, and therefore ethical approval will not be required. The results of this study will be communicated to the target audience through peer-reviewed publication as well as other knowledge exchange platforms, such as conferences, congresses or symposia.Trial registration The protocol for this systematic review is submitted for registration to international database of prospectively registered systematic reviews (PROSPERO, awaiting registration number).

Background Strengthening surgical services in resource-constrained settings is contingent on using high-quality data to inform decision making at clinical, facility, and policy levels. However, the evidence is sparse on gaps in paper-based medical record quality for surgical and obstetric patients in low-resource settings. Objective We aim to examine surgical and obstetric patient medical record data quality in health facilities as part of a surgical system strengthening initiative in northern Tanzania. Methods To measure the incidence of Surgical Site Infections (SSIs), sepsis and maternal sepsis surgical and obstetric inpatients were followed prospectively, over three months in ten primary, district, and regional health facilities in northern Tanzania. Between April 22nd to May 1st, 2018, we retrospectively reviewed paper-based medical records of surgical and obstetric patients diagnosed with SSIs, post-operative sepsis, and maternal sepsis in the three-month follow-up period. A data quality assessment tool with18 data elements related to documentation of SSIs and sepsis diagnosis, their respective symptoms and vital signs, inpatient daily monitoring indicators, and demographic information was developed and used to assess the completeness of patient medical records. Results Among the 157 patients diagnosed with SSI and sepsis, we found and reviewed 68% of all medical records. Among records reviewed, approximately one third (34%) and one quarter (23%) included documentation of SSI and sepsis diagnoses, respectively. 6% of reviewed records included documentation of all SSI and sepsis diagnoses, symptoms and vital signs, inpatient daily monitoring indicators, and demographic data. Conclusions Strengthening data quality and record-keeping is essential for surgical team communication, continuity of care, and patient safety, especially in low resource settings where paper-based records are the primary means of data collection. High-quality primary health information provides facilities with actionable data for improving surgical and obstetric care quality at the facility level.

BackgroundIn 2014, the government of Togo implemented a pilot unconditional cash transfer (UCT) program in rural villages that aimed at improving children's nutrition, health, and protection. It combined monthly UCTs (approximately US$8.40 /month) with a package of community activities (including behavior change communication [BCC] sessions, home visits, and integrated community case management of childhood illnesses and acute malnutrition [ICCM-Nut]) delivered to mother-child pairs during the first "1,000 days" of life. We primarily investigated program impact at population level on children's height-for-age z-scores (HAZs) and secondarily on stunting (HAZ < -2) and intermediary outcomes including household's food insecurity, mother-child pairs' diet and health, delivery in a health facility and low birth weight (LBW), women's knowledge, and physical intimate partner violence (IPV).Methods and findingsWe implemented a parallel-cluster-randomized controlled trial, in which 162 villages were randomized into either an intervention arm (UCTs + package of community activities, n = 82) or a control arm (package of community activities only, n = 80). Two different representative samples of children aged 6-29 months and their mothers were surveyed in each arm, one before the intervention in 2014 (control: n = 1,301, intervention: n = 1,357), the other 2 years afterwards in 2016 (control: n = 996, intervention: n = 1,035). Difference-in-differences (DD) estimates of impact were calculated, adjusting for clustering. Children's average age was 17.4 (± 0.24 SE) months in the control arm and 17.6 (± 0.19 SE) months in the intervention arm at baseline. UCTs had a protective effect on HAZ (DD = +0.25 z-scores, 95% confidence interval [CI]: 0.01-0.50, p = 0.039), which deteriorated in the control arm while remaining stable in the intervention arm, but had no impact on stunting (DD = -6.2 percentage points [pp], relative odds ratio [ROR]: 0.74, 95% CI: 0.51-1.06, p = 0.097). UCTs positively impacted both mothers' and children's (18-23 months) consumption of animal source foods (ASFs) (respectively, DD = +4.5 pp, ROR: 2.24, 95% CI: 1.09-4.61, p = 0.029 and DD = +9.1 pp, ROR: 2.65, 95% CI: 1.01-6.98, p = 0.048) and household food insecurity (DD = -10.7 pp, ROR: 0.63, 95% CI: 0.43-0.91, p = 0.016). UCTs did not impact on reported child morbidity 2 week's prior to report (DD = -3.5 pp, ROR: 0.80, 95% CI: 0.56-1.14, p = 0.214) but reduced the financial barrier to seeking healthcare for sick children (DD = -26.4 pp, ROR: 0.23, 95% CI: 0.08-0.66, p = 0.006). Women who received cash had higher odds of delivering in a health facility (DD = +10.6 pp, ROR: 1.53, 95% CI: 1.10-2.13, p = 0.012) and lower odds of giving birth to babies with birth weights (BWs) ConclusionsUCTs targeting the first "1,000 days" had a protective effect on child's linear growth in rural areas of Togo. Their simultaneous positive effects on various immediate, underlying, and basic causes of malnutrition certainly contributed to this ultimate impact. The positive impacts observed on pregnancy- and birth-related outcomes call for further attention to the conception period in nutrition-sensitive programs.Trial registrationISRCTN Registry ISRCTN83330970.

The use of additives in food products has become an important public health concern. In recent reports, dietary emulsifiers have been shown to affect the gut microbiota, contributing to a pro-inflammatory phenotype and metabolic syndrome. So far, it is not yet known whether similar microbiome shifts are observable for a more diverse set of emulsifier types and to what extent these effects vary with the unique features of an individual’s microbiome. To bridge this gap, we investigated the effect of five dietary emulsifiers on the fecal microbiota from 10 human individuals upon a 48 h exposure. Community structure was assessed with quantitative microbial profiling, functionality was evaluated by measuring fermentation metabolites, and pro-inflammatory properties were assessed with the phylogenetic prediction algorithm PICRUSt, together with a TLR5 reporter cell assay for flagellin. A comparison was made between two mainstream chemical emulsifiers (carboxymethylcellulose and P80), a natural extract (soy lecithin), and biotechnological emulsifiers (sophorolipids and rhamnolipids). While fecal microbiota responded in a donor-dependent manner to the different emulsifiers, profound differences between emulsifiers were observed. Rhamnolipids, sophorolipids, and soy lecithin eliminated 91 ± 0, 89 ± 1, and 87 ± 1% of the viable bacterial population after 48 h, yet they all selectively increased the proportional abundance of putative pathogens. Moreover, profound shifts in butyrate (−96 ± 6, −73 ± 24, and −34 ± 25%) and propionate (+13 ± 24, +88 ± 50, and +29 ± 16%) production were observed for these emulsifiers. Phylogenetic prediction indicated higher motility, which was, however, not confirmed by increased flagellin levels using the TLR5 reporter cell assay. We conclude that dietary emulsifiers can severely impact the gut microbiota, and this seems to be proportional to their emulsifying strength, rather than emulsifier type or origin. As biotechnological emulsifiers were especially more impactful than chemical emulsifiers, caution is warranted when considering them as more natural alternatives for clean label strategies.

Over the last few decades, nanotechnology has received a huge level of interest due to its extensive applications in various fields, including catalysis, electronics, optics, energy, and the environment [...]

Background and Objectives: Most studies based on self-reported data indicate that female patients more often than males have a same-gender preference for their primary care physician (PCP). Because self-reported preferences may not reflect true preferences, we analyzed objective data to investigate patients’ preferences for PCP gender. Methods: Analyses were performed on 2192 new patients seen within a university-based healthcare system by 13 PCPs (2 male, 11 female) during 2017. New patients were asked about their PCP gender preference when assigned a PCP. We compared the expected prevalence (proportion of males/females in overall patient population) and observed prevalence (gender distribution of patients for each PCP) by PCP gender. A mixed model with PCP as a random effect examined the odds of male and female patients being assigned a same-gender physician. Results: The expected prevalence of new patients was 65% female and 35% male. The observed prevalence (95% confidence interval [CI]) of male patients among male and female PCPs was, respectively, 59.7% (49.0%-69.5%) and 28.0% (24.0%-32.4%), with neither CI containing the expected prevalence of male patients (35%). Similarly, the observed prevalence of female patients among male and female PCPs was, respectively, 40.3% (95% CI 30.5%-51.0%) and 72.0% (95% CI 67.6%-76.0%), with neither CI containing the expected prevalence of female patients (65%). Conclusions: Both male and female patients often preferred to see a same-gender PCP with this preference more pronounced in males. Future research should seek to clarify the relationships between patients’ gender preferences, patient-physician gender concordance/discordance, patient satisfaction, and health outcomes.

Esters are important flavor and fragrance compounds that are present in many food and beverage products. Many of these esters are produced by yeasts and bacteria during fermentation. While ester production in yeasts through the alcohol acyl transferase reaction has been thoroughly investigated, ester production through alcoholysis has been completely neglected. Here, we further analyze the catalytic capacity of the yeast Eat1 enzyme and demonstrate that it also has alcoholysis and thiolysis activities. Eat1 can perform alcoholysis in an aqueous environment in vitro, accepting a wide range of alcohols (C2–C10) but only a small range of acyl donors (C2–C4). We show that alcoholysis occurs in vivo in several Crabtree negative yeast species but also in engineered Saccharomyces cerevisiae strains that overexpress Eat1 homologs. The alcoholysis activity of Eat1 was also used to upgrade ethyl esters to butyl esters in vivo by overexpressing Eat1 in Clostridium beijerinckii. Approximately 17 mM of butyl acetate and 0.3 mM of butyl butyrate could be produced following our approach. Remarkably, the in vitro alcoholysis activity is 445 times higher than the previously described alcohol acyl transferase activity. Thus, alcoholysis is likely to affect the ester generation, both quantitatively and qualitatively, in food and beverage production processes. Moreover, mastering the alcoholysis activity of Eat1 may give rise to the production of novel food and beverage products.

Carbapenem-resistant enterobacteriaceae (CRE) bloodstream infections have been rapidly spreading worldwide with a high mortality and pose a challenge to therapeutic decision-making, especially in premature neonates because insufficient empirical antimicrobial therapy is independently associated with high mortality. This case reported that a premature infant with CRE bloodstream infection was treated successfully with high-dose meropenem treatment with model-based therapeutic drug monitoring (TDM). In clinical settings, treatment target attainment of meropenem can be improved by increasing the frequency of administration, prolonging the infusion time, and using a high dose. This case report shows a successful regimen for CRE infection in a premature neonate and emphasizes the utility of model-based TDM of high-dose meropenem treatment. The adequate antimicrobial benefit provided by innovative techniques could ensure the efficacy and safety of high-dose meropenem therapy for CRE infection.

SpoIIE is a phosphatase involved in the activation of the first sigma factor of the forespore, σF, during sporulation. A ΔspoIIE mutant of Clostridium beijerinckii NCIMB 8052, previously generated by CRISPR-Cas9, did not sporulate but still produced granulose and solvents. Microscopy analysis also showed that the cells of the ΔspoIIE mutant are elongated with the presence of multiple septa. This observation suggests that in C. beijerinckii, SpoIIE is necessary for the completion of the sporulation process, as seen in Bacillus and Clostridium acetobutylicum. Moreover, when grown in reactors, the spoIIE mutant produced higher levels of solvents than the wild type strain. The impact of the spoIIE inactivation on gene transcription was assessed by comparative transcriptome analysis at three time points (4 h, 11 h and 23 h). Approximately 5% of the genes were differentially expressed in the mutant compared to the wild type strain at all time points. Out of those only 12% were known sporulation genes. As expected, the genes belonging to the regulon of the sporulation specific transcription factors (σF, σE, σG, σK) were strongly down-regulated in the mutant. Inactivation of spoIIE also caused differential expression of genes involved in various cell processes at each time point. Moreover, at 23 h, genes involved in butanol formation and tolerance, as well as in cell motility, were up-regulated in the mutant. In contrast, several genes involved in cell wall composition, oxidative stress and amino acid transport were down-regulated. These results indicate an intricate interdependence of sporulation and stationary phase cellular events in C. beijerinckii.

There are two interrelated issues that seem to be emerging as central to the understanding of ecological systems more generally, particularly relevant to agroecosystems. First is the key insights of Alan Turing in which spatial pattern emerges from a system in which there is a reaction between two objects, both of which are diffusing in space, a pest and its natural enemy, for example. Secondly, as small-scale farmers make complex decisions about their farm's ecosystem management, they are forced to contemplate market forces as much as the background ecology. This necessity automatically involves a time lag in that remuneration for produce is realized substantially after the decision to plant is made. Here, behavioral economics intersects with non-linear ecological dynamics to produce an expectation of chaotic patterns. It is suggested that these two core ideas, spatial dynamics (e.g., Turing's dynamic instability in space) and chaos (e.g., Simon's constrained rationality in farm decisions) form a qualitative theoretical foundation for understanding the ecology of agroecosystems.

Renal precision medicine in neonates is useful to support decision making on pharmacotherapy, signal detection of adverse (drug) events, and individual prediction of short- and long-term prognosis. To estimate kidney function or glomerular filtration rate (GFR), the most commonly measured and readily accessible biomarker is serum creatinine (Scr). However, there is extensive variability in Scr observations and GFR estimates within the neonatal population, because of developmental physiology and superimposed pathology. Furthermore, assay related differences still matter for Scr, but also exist for Cystatin C. Observations in extreme low birth weight (ELBW) and term asphyxiated neonates will illustrate how renal precision medicine contributes to neonatal precision medicine. When the Kidney Disease Improving Global Outcome (KDIGO) definition of acute kidney injury (AKI) is used, this results in an incidence up to 50% in ELBW neonates, associated with increased mortality and morbidity. However, urine output criteria needed adaptations to broader time intervals or weight trends, while Scr and its trends do not provide sufficient detail on kidney function between ELBW neonates. Instead, we suggest to use assay-specific centile Scr values to better describe postnatal trends and have illustrated its relevance by quantifying an adverse drug event (ibuprofen) and by explaining individual amikacin clearance. Term asphyxiated neonates also commonly display AKI. While oliguria is a specific AKI indicator, the majority of term asphyxiated cases are non-oliguric. Asphyxia results in a clinical significant—commonly transient—mean GFR decrease (−50%) with a lower renal drug elimination. But there is still major (unexplained) inter-individual variability in GFR and subsequent renal drug elimination between these asphyxiated neonates. Recently, the Baby-NINJA (nephrotoxic injury negated by just-in-time action) study provided evidence on the concept that a focus on nephrotoxic injury negation has a significant impact on AKI incidence and severity. It is hereby important to realize that follow-up should not be discontinued at discharge, as there are concerns about long-term renal outcome. These illustrations suggest that integration of renal (patho)physiology into neonatal precision medicine are an important tool to improve contemporary neonatal care, not only for the short-term but also with a positive health impact throughout life.

The structure of terrestrial landscapes is commonly viewed as a problem of statistical description defined by the number, size and distance between habitat patches. Yet, for organisms living in that landscape, structure may be perceived very differently depending on the dispersal capacity of the organism of concern—large animals may perceive a highly fragmented forest as a single patch if adjacent forest patches are sufficiently close, while small animals may be less likely to disperse across degraded habitat and therefore experience a much different patch structure. This is particularly relevant for fragmented landscapes like cities. Urban gardens are reputed to support a diversity of native and non-native urban species found in urban landscapes. Yet we know little about the long-term persistence of organisms associated with urban gardens. Here we utilize Taylor's law, a universal scaling law denoting a power law relationship between population size and variance to indicate the synchrony of arthropod populations sampled across time in a fragmented urban landscape. Our results indicate that the utility of urban gardens as habitat is strongly dependent on sampling month, spatial scale and taxon. Constrained dispersal across the landscape may limit the potential of urban gardens to conserve natural enemies including ladybird beetles and parasitoid wasps. In contrast, aphid pests are moving much more freely in the landscape as exhibited through synchrony in abundances sampled across local and landscape scales. We find that regardless of the fragmentation pattern existing in the landscape, short-ranged arthropods are isolated to small, independent garden habitat patches (metapopulation-like) with abundances that oscillate out of sync, while long-ranged species traverse greater distances, synchronizing abundances across large, shared spaces (source sink-like). These results suggest an inherent link between Taylor's temporal law and metapopulation theory, providing a potential mechanism to explain species-specific slopes of Taylor's law as arising from the ability of organisms to differentially experience fragmented space along the continuum between metapopulation and source-sink.

Subclinical Ruminal Acidosis (SARA) and Subclinical Ketosis (SCK) are two of the most prevalent metabolic diseases of dairy cows, with impacts on reproductive performance. There is scarce literature about these diseases in dairy regions in Colombia. In 29 randomly selected herds in Pasto, Colombia, 249 dairy cows were followed weekly for two months postpartum to determine: 1) incidence risk of SARA and SCK; and 2) effects of SARA and SCK on the occurrence of postpartum anestrus (PA) at two months. Samples from ruminal liquor and blood were obtained one time per cow during the first week postpartum to determine presence of SARA (pH < 5.6) and SCK (1.0–2.9 mmol/L of blood Beta-Hydroxy-Butyrate), respectively. PA diagnosis was determined with ultrasound. Pregnancy risks at 30 and 60 days post-breeding (and assumed embryo losses between these days) were determined. Risk factors associated with PA were estimated through a mixed multi-level multivariable logistic regression model, adjusting for clustering of cows within herds. The incidence risks of SARA and SCK were 23.3% and 46.2%, respectively. Simultaneous occurrence of SCK and SARA (SCASCK) was present in 5.2% of the cows. In the final multivariable model, the occurrence of SARA (Odds Ratio: OR = 39.4), SCK (OR = 47.4) and SCASCK (OR = 68.5) was associated with increased odds of PA. Feeding a transition period diet was associated with reduced odds of PA (OR = 0.15). Second parity cows had significantly lower odds of PA than first parity cows (OR = 0.21). In conclusion, inadequate pre-partum and postpartum nutritional management of the herds increased the occurrence of SARA and SCK, which had adverse effects on reproductive performance.

We report the case of a 61-year-old man from northern Australia with concurrent community-onset Acinetobacter baumannii complex and Burkholderia pseudomallei bacteremia presenting as severe tropical pneumonia requiring intensive care unit support. The pneumonia was complicated by L3/4 discitis and vertebral osteomyelitis presumed to be due to melioidosis. His risk factors included chronic lung disease and immunosuppression with etanercept. This case of concurrent infection highlights the similar risk factors, presentation and epidemiology of both infections, emphasises the importance of accurate microbiologic identification and reinforces the current Australian empiric antimicrobial treatment recommendations for severe tropical pneumonia.

With the advent of highly sensitive technologies such as tandem mass spectrometry and next-generation sequencing, recombinant antibodies are now routinely analyzed for the presence of low-level sequence variants including amino acid misincorporations. During mAb cell culture process development, we found that proline was replaced with the non-canonical amino acid, hydroxyproline, in the protein sequence. We investigated the relationship between proline content in the cell culture media and proline sequence variants and found that the proline concentration was inversely correlated with the amount of sequence variants detected in the protein sequence. Hydroxyproline incorporation has been previously reported in recombinant proteins produced in mammalian expression systems as a post-translational modification. Given the dependency on proline levels, the mechanism was then investigated. To address the possibility of co-translational misincorporation of hydroxyproline, we used tandem mass spectrometry to measure incorporation of stable-isotope labelled hydroxyproline added to the feed of a production bioreactor. We discovered co-translational misincorporation of labelled hydroxyproline in the recombinant antibody. These findings are significant, since they underscore the need to track non-canonical amino acid incorporation as a co-translational event in CHO cells. Understanding the mechanism of hydroxyproline incorporation is crucial in developing an appropriate control strategy during biologics production.

Miniaturized fluorescence microscopes (miniscopes) have been instrumental to monitor neural signals during unrestrained behavior and their open-source versions have made them affordable. Often, the footprint and weight of open-source miniscopes is sacrificed for added functionality. Here, we present NINscope: a light-weight miniscope with a small footprint that integrates a high-sensitivity image sensor, an inertial measurement unit and an LED driver for an external optogenetic probe. We use it to perform the first concurrent cellular resolution recordings from cerebellum and cerebral cortex in unrestrained mice, demonstrate its optogenetic stimulation capabilities to examine cerebello-cerebral or cortico-striatal connectivity, and replicate findings of action encoding in dorsal striatum. In combination with cross-platform acquisition and control software, our miniscope is a versatile addition to the expanding tool chest of open-source miniscopes that will increase access to multi-region circuit investigations during unrestrained behavior.

Biochar from spent malt rootlets was employed as the template to synthesize hybrid biochar-ceria materials through a wet impregnation method. The materials were tested for the activation of persulfate (SPS) and subsequent degradation of sulfamethoxazole (SMX), a representative antibiotic, in various matrices. Different calcination temperatures in the range 300–500 °C were employed and the resulting materials were characterized by means of N2 adsorption and potentiometric mass titration as well as TGA, XRD, SEM, FTIR, DRS, and Raman spectroscopy. Calcination temperature affects the biochar content and the physicochemical properties of the hybrid materials, which were tested for the degradation of 500 μg L−1 SMX with SPS (in the range 200–500 mg L−1) in various matrices including ultrapure water (UPW), bottled water, wastewater, and UPW spiked with bicarbonate, chloride, or humic acid. Materials calcined at 300–350 °C, with a surface area of ca. 120 m2 g−1, were the most active, yielding ca. 65% SMX degradation after 120 min of reaction in UPW; materials calcined at higher temperatures as well as bare biochar were less active. Degradation decreased with increasing matrix complexity due to the interactions amongst the surface, the contaminant, and the oxidant. Experiments in the presence of scavengers (i.e., methanol, t-butanol, and sodium azide) revealed that sulfate and hydroxyl radicals as well as singlet oxygen were the main oxidative species.

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease worldwide and is impacted by an unhealthy diet with excessive calories, although the role of sugars in NAFLD etiology remains largely unexplored. Rare sugars are natural sugars with alternative monomers and glycosidic bonds, which have attracted attention as sugar replacers due to developments in enzyme engineering and hence an increased availability. We studied the impact of (rare) sugars on energy production, liver cell physiology and gene expression in human intestinal colorectal adenocarcinoma (Caco-2) cells, hepatoma G2 (HepG2) liver cells and a coculture model with these cells. Fat accumulation was investigated in the presence of an oleic/palmitic acid mixture. Glucose, fructose and galactose, but not mannose, l-arabinose, xylose and ribose enhanced hepatic fat accumulation in a HepG2 monoculture. In the coculture model, there was a non-significant trend (p = 0.08) towards higher (20–55% increased) median fat accumulation with maltose, kojibiose and nigerose. In this coculture model, cellular energy production was increased by glucose, maltose, kojibiose and nigerose, but not by trehalose. Furthermore, glucose, fructose and l-arabinose affected gene expression in a sugar-specific way in coculture HepG2 cells. These findings indicate that sugars provide structure-specific effects on cellular energy production, hepatic fat accumulation and gene expression, suggesting a health potential for trehalose and l-arabinose, as well as a differential impact of sugars beyond the distinction of conventional and rare sugars.

From Feynman diagrams to tensor networks, diagrammatic representations of computations in quantum mechanics have catalyzed progress in physics. These diagrams represent the underlying mathematical operations and aid physical interpretation, but cannot generally be computed with directly. In this paper we introduce the ZXH-calculus, a graphical language based on the ZX-calculus, that we use to represent and reason about many-body states entirely graphically. As a demonstration, we express the one-dimensional (1D) AKLT-state, a symmetry protected topological state, in the ZXH-calculus by developing a representation of spins higher than 1/2 within the calculus. By exploiting the simplifying power of the ZXH-calculus rules we show how this representation straightforwardly recovers the AKLT matrix-product state representation, the existence of topologically protected edge states, and the nonvanishing of a string-order parameter. Extending beyond these known properties, our diagrammatic approach also allows us to analytically derive that the Berry phase of any finite-length 1D AKLT chain is π. In addition, we provide an alternative proof that the two-dimensional (2D) AKLT-state on a hexagonal lattice can be reduced to a graph state, demonstrating that it is a universal quantum-computing resource. Lastly, we build 2D higher-order topological phases diagrammatically, which we use to illustrate a symmetry-breaking phase transition. Our results show that the ZXH-calculus is a powerful language for representing and computing with physical states entirely graphically, paving the way to develop more efficient many-body algorithms and giving a novel diagrammatic perspective on quantum phase transitions.

Progressive diseases tend to be heterogeneous in their underlying aetiology mechanism, disease manifestation, and disease time course. Here, Young and colleagues devise a computational method to account for both phenotypic heterogeneity and temporal heterogeneity, and demonstrate it using two neurodegenerative disease cohorts.

Abstract Background Trauma is the leading cause of morbidity and mortality in children in the United States. The antifibrinolytic drug tranexamic acid (TXA) improves survival in adults with traumatic hemorrhage, however, the drug has not been evaluated in a clinical trial in severely injured children. We designed the Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children (TIC-TOC) trial to evaluate the feasibility of conducting a confirmatory clinical trial that evaluates the effects of TXA in children with severe trauma and hemorrhagic injuries. Methods Children with severe trauma and evidence of hemorrhagic torso or brain injuries will be randomized to one of three arms: (1) TXA dose A (15 mg/kg bolus dose over 20 min, followed by 2 mg/kg/hr infusion over 8 h), (2) TXA dose B (30 mg/kg bolus dose over 20 min, followed by 4 mg/kg/hr infusion over 8 h), or (3) placebo. We will use permuted-block randomization by injury type: hemorrhagic brain injury, hemorrhagic torso injury, and combined hemorrhagic brain and torso injury. The trial will be conducted at four pediatric Level I trauma centers. We will collect the following outcome measures: global functioning as measured by the Pediatric Quality of Life (PedsQL) and Pediatric Glasgow Outcome Scale Extended (GOS-E Peds), working memory (digit span test), total amount of blood products transfused in the initial 48 h, intracranial hemorrhage progression at 24 h, coagulation biomarkers, and adverse events (specifically thromboembolic events and seizures). Discussion This multicenter trial will provide important preliminary data and assess the feasibility of conducting a confirmatory clinical trial that evaluates the benefits of TXA in children with severe trauma and hemorrhagic injuries to the torso and/or brain. Trial registration ClinicalTrials.gov registration number: NCT02840097. Registered on 14 July 2016.

The sustainability of infrastructure projects is becoming increasingly important issue in engineering practice. This means that in the future the construction materials will be selected on the basis of the contribution they can make to reach sustainability requirements. Geopolymers are materials based on by-products from industries. By using geopolymer concrete technology it is possible to reduce our waste and to produce concrete in the environmental-friendly way. An 80% or greater reduction of greenhouse gases compared with Ordinary Portland Cement (OPC) can be achieved through geopolymer technology. However, there are limited practical applications and experience. For a broad and large scale industrial application of geopolymer concrete, challenges still exist in the technological and engineering aspects. The main goal of GeoCon Bridge project was to develop a geopolymer concrete mixture and to upscale it to structural application. The outputs of projects provide input for development of recommendations for structural design of geopolymer based reinforced concrete elements. Through a combination of laboratory experiments on material and structural elements, structural design and finite element simulations, and based on previous experience with OPC concrete, knowledge generated in this project provides an important step towards a “cement free” construction. The project was performed jointly by three team members: Microlab and Group of Concrete Structures from Technical University of Delft and Technical University of Eindhoven.

Gliosis and fibrosis after spinal cord injury (SCI) lead to formation of a scar that is an impediment to axonal regeneration. Fibrotic scarring is characterized by the accumulation of fibronectin, collagen, and fibroblasts at the lesion site. The mechanisms regulating fibrotic scarring after SCI and its effects on axonal elongation and functional recovery are not well understood. In this study, we examined the effects of eliminating an isoform of fibronectin containing the Extra Domain A domain (FnEDA) on both fibrosis and on functional recovery after contusion SCI using male and female FnEDA-null mice. Eliminating FnEDA did not reduce the acute fibrotic response but markedly diminished chronic fibrotic scarring after SCI. Glial scarring was unchanged after SCI in FnEDA-null mice. We found that FnEDA was important for the long-term stability of the assembled fibronectin matrix during both the subacute and chronic phases of SCI. Motor functional recovery was significantly improved, and there were increased numbers of axons in the lesion site compared to wildtype mice, suggesting that the chronic fibrotic response is detrimental to recovery. Our data provide insight into the mechanisms of fibrosis after SCI and suggest that disruption of fibronectin matrix stability by targeting FnEDA represents a potential therapeutic strategy for promoting recovery after SCI.

In mainstream or strong university education, the teacher selects and transmits knowledge and skills that students are to acquire and reproduce. Many researchers of radical embodied cognitive science still adhere to this way of teaching, even though this prescriptive pedagogy deeply contrasts with the theoretical underpinnings of their science. In this paper, we search for alternative ways of teaching that are more aligned with the central non-prescriptive and non-representational tenets of radical embodied cognitive science. To this end, we discuss recent views on education by Tim Ingold and Gert Biesta, which are based on Dewey’s philosophy of pragmatism and Gibsons’ ecological approach. The paper starts by introducing radical embodied cognitive science, particularly as it relates to motor skill learning, one of our prime interests in research and teaching. Next, we provide a synopsis and critique of the still dominant prescriptive and explicating pedagogy of strong education. Following Ingold and Biesta, we search for a weak alternative through a careful consideration of the education of attention and the participating teacher. To illustrate our arguments, we use examples of the first author’s teaching about/of motor skill learning. The paper is concluded by briefly considering the implications of weak education for a radical embodied science of motor skill learning.