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Abstract Background Endometrial cancer (EC) is a major gynecological cancer with increasing incidence. It comprises four molecular subtypes with differing etiology, prognoses, and responses to chemotherapy. In the future, clinical trials testing new single agents or combination therapies will be targeted to the molecular subtype most likely to respond. As pre-clinical models that faithfully represent the molecular subtypes of EC are urgently needed, we sought to develop and characterize a panel of novel EC patient-derived xenograft (PDX) models. Methods Here, we report whole exome or whole genome sequencing of 11 PDX models and their matched primary tumor. Analysis of multiple PDX lineages and passages was performed to study tumor heterogeneity across lineages and/or passages. Based on recent reports of frequent defects in the homologous recombination (HR) pathway in EC, we assessed mutational signatures and HR deficiency scores and correlated these with in vivo responses to the PARP inhibitor (PARPi) talazoparib in six PDXs representing the copy number high/p53-mutant and mismatch-repair deficient molecular subtypes of EC. Results PDX models were successfully generated from grade 2/3 tumors, including three uterine carcinosarcomas. The models showed similar histomorphology to the primary tumors and represented all four molecular subtypes of EC, including five mismatch-repair deficient models. The different PDX lineages showed a wide range of inter-tumor and intra-tumor heterogeneity. However, for most PDX models, one arm recapitulated the molecular landscape of the primary tumor without major genomic drift. An in vivo response to talazoparib was detected in four copy number high models. Two models (carcinosarcomas) showed a response consistent with stable disease and two models (one copy number high serous EC and another carcinosarcoma) showed significant tumor growth inhibition, albeit one consistent with progressive disease; however, all lacked the HR deficiency genomic signature. Conclusions EC PDX models represent the four molecular subtypes of disease and can capture intra-tumor heterogeneity of the original primary tumor. PDXs of the copy number high molecular subtype showed sensitivity to PARPi; however, deeper and more durable responses will likely require combination of PARPi with other agents.

This research was carried out to evaluate the pedigree data of the Debrecen White rabbit breed. Pedigree information was supplied by the Debrecen White Rabbit Breeder Association. The final dataset contained all available information on animals registered by the breeding association up to 2023. The reference population was the active breeding stock in 2023. The estimated complete generation equivalent was 7.8, while the mean of maximum generations was 16.29 for the present stock. All individuals within the current population were inbred, with a 5.37% mean inbreeding coefficient. The division of the inbreeding coefficient showed that homozygosity is increasing in the current population. The genetic conservation index (GCI) was higher than 30 for 10.11% for the total population, and was above 38.69% for the current population.

Abstract This article examines the effects of different storage conditions on selected physicochemical properties of three types of agro-biomass pellets: sunflower husks, wheat straw and hemp hurds, and wood pellets. The tests were carried out in a climatic chamber, which allows simulation of real storage conditions, i.e. conditions with high air humidity and variable (±) ambient air temperatures. The results showed higher degradability of agro-biomass pellets compared to woody biomass. The pellets degraded to a less extent at varying ± temperatures than at high humidity (90% RH). After complete moisture saturation, durability decreases for agro-pellets by an average of 9%, while after freezing and defreezing for sunflower husk pellets and woody pellets durability decreases by 2%, and for hemp hurd pellets by 11%. In contrast, strength-by-dropping index for agro-pellets decreased by 20% after being in the environment (30 °C and 90%RH) and 15% under varying temperature conditions. No change in the energy parameters of all pellets in the dry matter was noted. On the other hand, an increase in the moisture content of pellets when they are stored under different environmental conditions results in a decrease in calorific value.

Abstract Coupling surface plasmon resonance (SPR) sensing with electrochemistry (EC) is a promising analytical strategy to obtain information about interfacial phenomena in heterogeneous reactions. Typical EC‐SPR sensors utilize a metal film both as the plasmonic material and as the working electrode. In this configuration, the eigenmodulation of the plasmonic properties of the metal film under applied potential results in a background signal, which hampers the unambiguous interpretation of the sensor response due to redox reactions. Here, a new strategy is presented to overcome this disadvantage by using a van der Waals heterostructure (vdW‐HS) as the working electrode. The vdW‐HS comprises of a graphene / hexagonal boron nitride (hBN) stack on a gold film of a standard SPR sensor. It is shown here that the background signal is completely suppressed enabling the unambiguous analysis of SPR sensor response due to electrochemical reactions. It is further observed that the potential dependent plasmonic signals are not just a reproduction of the electrochemical current and subtle differences can be traced back to the diffusive nature of the redox active species. Finally, it is demonstrated that EC‐SPR can be used as a complementary method to distinguish if the electrochemical response is mainly surface‐bound or due to diffusion.

Background: Although several National Data Registries for Congenital Heart Disease (CHD) exist, few are comprehensive and contemporary. A National Australian CHD Registry has been developed that aims to redress this by creating the first comprehensive data collection for CHD children and adults, initially across Australia. Methods: We defined and collected a minimum dataset of demographics, diagnoses, and procedures from people with CHD presenting at participating quaternary CHD services Australia-wide. Data were collected from a range of clinical data sources. Diagnoses and procedures were standardised to the European Paediatric Congenital Code – Short List. Methodological limitations were carefully documented. Results: From 8 participating institutions, an initial 359,084 patient records were assessed for eligibility and 68,234 unique individuals with structural CHD have been included in the current dataset. There were 20,395 (30 %) people with mild CHD, 25,157 (37 %) with moderate CHD, and 13,530 (20 %) with severe CHD (6 % unknown complexity). The most common diagnoses were Ventricular Septal Defect (16,781, 25 %), Atrial Septal Defect (6,607, 10 %), Aortic Valve Disorders (5516 8 %), Coarctation of the Aorta (5,321, 8 %), Tetralogy of Fallot (4,489, 7 %), Transposition of the Great Arteries (4,009, 6 %). Conclusion: The data presented here represents the most comprehensive cohort collected for the Australian CHD population thus far and is comparable with the largest contemporary CHD registries around the world. This Registry represents a key resource for improved understanding of the CHD population and will drive better care and outcomes for people living with CHD.

Background To characterize global and health‐related quality of life (QOL) among adults with Fontan physiology enrolled in the Australian and New Zealand Fontan Registry (ANZFR), and identify sociodemographic, clinical, psychological, and relational factors associated with outcomes. Methods and Results Using a cross‐sectional survey design, 66 adults with Fontan physiology (58% women; mean age, 29.6±7.7 years; range, 18–50 years) completed validated self‐report measures. Health‐related QOL was assessed using the Pediatric Quality of Life Inventory, and global QOL was assessed using a visual analog scale (0–10). Participants reported lower total health‐related QOL (P

IntroductionSurveillance, screening, and evaluation for neurodevelopmental delays is a pivotal component of post-surgical care for children with congenital heart disease (CHD). However, challenges exist in implementing such neurodevelopmental follow-up care in international practice. This study aimed to characterise key barriers, enablers, and opportunities for implementing and delivering outpatient cardiac neurodevelopmental follow-up care in Australia.Methodsan exploratory descriptive qualitative study was conducted with healthcare professionals across Australia who had lived experience of designing, implementing, or delivering neurodevelopmental care for children with CHD. Online semi-structured interviews were conducted using a guide informed by the Consolidated Framework for Implementation Research to explore contextual influences. Interview transcripts were analysed using a rapid qualitative approach including templated summaries and hybrid deductive-inductive matrix analysis.Resultsfifty-two participants were interviewed. Perceived barriers and enablers were organised into six higher-order themes: factors in the broader environmental, economic, and political context; healthcare system factors; organisational-level factors; provider factors; patient and family factors; and care model factors. The largest number of barriers occurred at the healthcare system level (service accessibility, fragmentation, funding, workforce), while service providers demonstrated the most enabling factors (interprofessional relationships, skilled teams, personal characteristics). Strategies to improve practice included building partnerships; generating evidence; increasing funding; adapting for family-centred care; and integrating systems and data.DiscussionAustralia shares many similar barriers and enablers to cardiac neurodevelopmental care with other international contexts. However, due to unique geographical and health-system factors, care models and implementation strategies will require adaption to the local context to improve service provision.

Summary: Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

Abstract In the framework of the Laser Lightning Rod project, whose aim is to show that laser-induced filaments can guide lightning discharges over considerable distances, we study over a distance of 140 m the filaments created by a laser system with J-range pulses of 1 ps duration at 1 kHz repetition rate. We investigate the spatial evolution of the multiple filamentation regime using the fundamental beam at 1030 nm or using combination with the second and third harmonics. The measurements were made using both a collimated beam and a loosely focused beam.

Realistic modeling of ecological population dynamics requires spatially explicit descriptions that can take into account spatial heterogeneity as well as long-distance dispersal. Here, we present Monte Carlo simulations and numerical renormalization group results for the paradigmatic model, the contact process, in the combined presence of these factors in both one and two-dimensional systems. Our results confirm our analytic arguments stating that the density vanishes smoothly at the extinction threshold, in a way characteristic of infinite-order transitions. This extremely smooth vanishing of the global density entails an enhanced exposure of the population to extinction events. At the same time, a reverse order parameter, the local persistence displays a discontinuity characteristic of mixed-order transitions, as it approaches a non-universal critical value algebraically with an exponent $\beta_p'

Teknologi membran digunakan dalam industri untuk proses pemisahan maupun pemurnian. Salah satu jenis polimer yang sering digunakan untuk membuat membran adalah selulosa asetat yang diperoleh dari Nata de coco. Tujuan dari penelitian ini untuk melihat pengaruh penambahan zat aditif polyethylene glycol terhadap karakterisasi dan kinerja membran selulosa asetat. Penambahan zat aditif polyethylene glycol, 10%, 17%, dan 28% dengan pelarut diklorometana 50% dan selulosa asetat 18%. Membran yang didapatkan dilakukan pengujian morfologi dan uji fluks membran. Hasil morfologi membran yang memenuhi syarat ultrafiltrasi adalah membran A didapatkan ukuran pori 0,618 µm, dan membran B sebesar 0,972 µm. hasil uji fluks rata-rata didapatkan 15,494 L/m2.jam untuk penambahan zat aditif 10%, 17,764 L/m2.jam untuk penambahan zat aditif 17% dan 19,455 L/m2.jam untuk penambahan zat aditif 28%. Hasil yang diperoleh menunjukkan bahwa pengaruh zat aditif pada membran selulosa asetat yaitu semakin banyak komposisi zat aditif maka semakin besar nilai fluks dan ukuran pori membran.

Carbon dioxide (CO2) emissions are a type of greenhouse gas emission which is the main factor in the emergence of the global warming phenomenon. Based on the total CO2 emissions released, there are 3 components that most influence high CO2 emissions, namely the electricity sector (42%), transportation (23%) and housing (6%). The trend of increasing CO2 will continue if no preventive measures are taken globally. One of these preventive efforts is to convert carbon dioxide (CO2) into methane (CH4), or known as the methanation process of carbon dioxide. In the field of fuel, the conversion of carbon dioxide into methane gas has more advantages in terms of thermodynamics. One of the factors that determine the methanation process is the activity of the catalyst. The catalyst used in this study was the Ni/Al2O3 catalyst. Ni/Al2O3 catalyst is a catalyst that has good performance in the methane formation process. However, the Ni/Al2O3 catalyst has disadvantages, one of which is that it is susceptible to carbon deposition and sintering on the catalyst. One way to improve catalyst stability performance is by adding a promoter. This research was carried out by varying the temperature, the amount of Ni/Al2O3 catalyst and adding a promoter to give structural changes to the catalyst. The results showed that the temperature and the amount of catalyst affect the amount of CH4 formed, and the addition of manganese (Mn) initiator can affect the pore structure of the catalyst.

Carbon dioxide (CO2) is one of the most critical greenhouse effect causes. One method that can reduce the problem of global warming is by converting CO2 and utilizing it into a CO2 hydrogenation reaction into methane. This research aims to obtain methane gas from CO2 gas using a Fixed Bed Reactor for the CO2 methanation process. This research uses Ni/Al2O3 catalyst as support and Fe metal as a promoter with in situ method by varying the amount of Fe metal promoter up to 1gr - 5gr and time variation of 30 minutes, 45 minutes and 60 minutes. The highest methane gas yield was obtained in sample 15 with more Fe metal promoter 5 gr (variation 1-5 gr) for 60 minutes (variation 30, 45, and 60 minutes), which amounted to 12.54%. The amount of Fe metal promoter and the length of time used is directly proportional to the methane gas (CH4) produced. This is because the addition of Fe as a promoter can increase catalyst activity and catalyst stability, so that the catalyst can work well in converting CO2 into methane thermal gas. Keywords: Carbon Dioxide, CO2 Methanation, Catalyst Ni/Al2O3, Promoter Fe, Methane (CH4).

Substitusi minyak bumi dengan nabati sebagai bahan pelumas dilakukan untuk menghasilkan minyak pelumas yang ramah lingkungan. Palm Fatty Acid Distillate (PFAD) menjadi salah satu produk turunan minyak kelapa sawit yang dapat dimanfaatkan sebagai bahan pembuatan grease. Grease adalah bahan semi padatan campuran antara minyak base oil dengan bahan pengentalnya (Thickening Agent) yang berfungsi mengurangi gesekan dan keausan antara dua bidang yang saling bergesekan. penelitian ini bertujuan untuk mendapatkan karakteristik grease menurut SNI dan mendapatkan tingkat NLGI terbaik. Penelitian ini dilakukan dengan komposisi antara base oil dan thickening agent dan zat aditif. Grease terbaik yang diperoleh termasuk dalam spesifikasi grease dan parameter kinerja untuk tingkat kualitas NLGI grade A dengan formulasi base oil : thickening agent 80:20 dengan penambahan zat aditif 3,5 ml, densitas 0,9057 gr/ml dan dropping point 98°C yang telah sesuai dengan SNI dengan penetrasi 241 mm yang mengindikasikan grease ke dalam kelas NLGI 3Â

Objective: To determine the incidence, outcomes, and evaluate diagnostic modalities for postoperative vocal cord dysfunction (VCD) following cardiothoracic surgery in children. Methods: A prospective mixed-methods study using principles of implementation science was completed. All patients undergoing surgery involving the aortic arch, ductus, or ligamentum arteriosum and vascular rings from September 2019 to December 2020 were enrolled. Patients underwent speech pathology assessment, laryngeal ultrasound, and flexible direct laryngoscopy. Results: Ninety-five patients were eligible for inclusion. The incidence of VCD ranged from 18% to 56% and varied according to procedure group. VCD occurred in 42% of neonates. Repair of hypoplastic aortic arch was associated with increased risk of VCD (57%; P = .002). There was no significant difference in duration of intubation, pediatric intensive care unit stay, or hospital stay. Forty percent children were able to achieve full oral feeding. Children with VCD were more likely to require nasogastric supplementary feeding at discharge (60% vs 36%; P = .044). Sixty-eight percent of patients demonstrated complete resolution of VCD at a median of 97 days postoperatively. Laryngeal ultrasound and speech pathology assessment combined had a sensitivity of 91% in comparison to flexible direct laryngoscopy. Conclusions: VCD occurred in one-third and resolved in two-thirds of patients at a median of 3 months following cardiac surgery. Aortic arch repair carried the highest risk of VCD. VCD adversely influenced feeding. Forty percent of patients achieved full oral feeding before discharge. VCD did not delay intensive care unit or hospital discharge. Speech pathology assessment and laryngeal ultrasound combined was reliable for diagnosis in most patients and was more patient friendly than flexible direct laryngoscopy.

Saat ini di Indonesia, terjadi penurunan pasokan sumber energi dan kelangkaan bahan bakar minyak. Oleh karena itu, kebutuhan akan sumber energi alternatif bernilai ekonomis serta ramah lingkungan semakin penting. Biogas merupakan solusi energi alternatif yang andal yang dapat dihasilkan dari bahan organik seperti kotoran ternak, daun kering, sampah organik dari pasar, air limbah domestik, industri makanan, dan lainnya. Jenis biomassa atau limbah yang berbeda menghasilkan jumlah biogas yang beragam. Dalam penelitian ini, bahan baku biogas terdiri dari campuran limbah cair industri tahu dan kotoran sapi. Komposisi utama dari biogas, yaitu (CH4) metana (50 – 70%), (CO2) karbon dioksida (25 – 45%), sejumlah kecil (H2) hidrogen, (N2) nitrogen, dan (H2S) hidrogen sulfida. Pemanfaatan biogas masih belum optimal karena masih mengandung gas pengotor seperti CO2 dan H2S yang dapat menyebabkan berkurangnya nilai kalor, korosif, dan beracun. Untuk mengatasi masalah ini, dapat dilakukan dengan melakukan pemurnian pada biogas. Pemurnian biogas dilakukan melalui metode absorpsi dengan menggunakan absorber MEA pada kolom isian. Variabel yang diamati pada penelitian ini adalah pengaruh konsentrasi MEA dan laju alir biogas terhadap peningkatan kandungan CH4. Hasil penelitian paling optimal dicapai pada konsentrasi MEA sebesar 2,5M dengan laju alir sebesar 0,6 liter/menit, menghasilkan kandungan CH4 sebesar 87,94%.

The aim of the paper was to analyse the possibility to use waste material which is created during the production of mineral-asphalt mixes as a side effect of the process of drying and dedusting diabase aggregate in high temperature. Experimental studies included the analysis of the influence of the addition of diabase dust on the improvement of the properties of cement concrete destined for the construction of local roads. The mineral additive in the form of diabase dust, which constitutes natural waste, was inserted into the concrete mix as a mineral additive substituting a part of the aggregate with the constant amount of cement and water, and additionally as the substitute for cement. The performed studies resulted in the conclusion that adding diabase dust significantly increased the tightness and density of concrete, which impacts the increase of compressive strength by 7, 21 and 28% in reference to model concrete. The insertion of the waste diabase dust into the concrete mix significantly improved the freeze-thaw resistance of concrete after 150 cycles of testing and reduced the water absorption by 6, 15 and 21%. Using diabase dust as a substitute in the following amount: 50, 100 and 150 kg/m3 did not cause significant changes in the scope of density and water absorption, whereas the reduction of the compressive strength was from 8, 23 and 33% in reference to the model concrete. The application of dust as the substitute for cement resulted in the reduction of the costs of concrete by 6, 12 and 18% and resulted in the possibility to fully apply waste material, which confirms the justness of undertaking implementation research. Concrete with the use of waste rock dusts may be qualified as concrete that is environmentally friendly and compliant with the sustainable development of modern construction materials.

Motivated by long-range dispersal in ecological systems, we formulate and apply a general strong-disorder renormalization group (SDRG) framework to describe one-dimensional disordered contact processes with heavy-tailed (such as power law, stretched exponential, and log-normal) dispersal kernels, widely used in ecology. The focus is on the close-to-critical scaling of the order parameters, including the commonly used density, as well as the less known persistence, which is nonzero in the inactive phase. Our analytic and numerical results obtained by SDRG schemes at different levels of approximation reveal that the more slowly decaying dispersal kernels lead to faster-vanishing densities as the critical point is approached. The persistence, however, shows an opposite tendency: the broadening of the dispersal makes its decline sharper at the critical point, becoming discontinuous for the extreme case of power-law dispersal. The SDRG schemes presented here also describe the quantum phase transition of random transverse-field Ising chains with ferromagnetic long-range interactions, the density corresponding to the magnetization of that model.

Background. Implementation of emergency endovascular aortic repair provides an attractive opportunity in the treatment of complicated acute aortic syndromes involving descending aorta. Aim. The aim of this study was to analyze the effectiveness of thoracic endovascular aortic repair (TEVAR) for the treatment of acute surgical emergencies involving the descending thoracic aorta. Methods. A retrospective review of the medical records of all patients undergoing TEVAR in a single center since 2007 was undertaken. Patients with the aortic disease treated on emergency inclusion criteria were complicated spontaneous acute aortic syndrome (csAAS), traumatic aortic acute injuries (TAIs), and other indications requiring emergent intervention. Technical and clinical success with patient mortality, survival, and reoperation rate was evaluated according to Society for Vascular Surgery reporting standards for thoracic endovascular aortic repair (TEVAR). Results The emergency interventions were necessary in 74 cases (51.0%), including patients with the complicated spontaneous acute aortic syndrome (csAAS) (64.8%; n = 48) and traumatic aortic acute injuries (TAIs) (31.1%). In addition, in one case aortic iatrogenic dissection (AID) and in 2 other fistulas after the previous stent graft, implantations were diagnosed. All procedures were done through surgically exposed femoral arteries while 2 hybrid procedures required additional approaches. The primary technical success rate was 95.9%, in 3 cases endoleak was reported. The primary clinical success occurred in 94.5%. All patients survived the endovascular interventions, whereas during in-hospital stay one of them died due to multiorgan failure (early mortality 1.3%). During the follow-up period, lasting 6 through 164 months (median 67), 11 patients died. Annual, five- and ten-year probability of survival was 86.4 ± 0.04%, 80.0 ± 0.05%, and 76.6 ± 0.06%, respectively. However, the rate of 5-year survivors was significantly higher after TAI (95.2%) than scAAS (63.4%) (p=0.008). Early after the procedure, one individual developed transient paraparesis (1.3%). No other serious stent-graft-related adverse events were noted within the postdischarge follow-up period. Conclusions. Descending aortic pathologies requiring emergent interventions can be treated by endovascular techniques with optimal results and low morbidity and mortality in an experienced and dedicated team.

Robert Jütte, von 1990 bis 2020 Leiter des Instituts für Geschichte der Medizin der Robert Bosch Stiftung in Stuttgart, hat im Jahr 2000 das Buch "Geschichte der Sinne" veröffentlicht und gilt damit im deutschen Sprachraum als Pionier der historischen Sinnesforschung. Im Rahmen des Workshops „Sinnesräume. Sensory Studies and Spatial Concepts: Schall (aus)messen, Grenzen (er)tasten, Gerüche (ein)ordnen, Zeiten (ab)schmecken …“ an der Universität Innsbruck, 27./28. Mai 2021, hielt er die Keynote mit dem Titel „Der Krieg und die Sinne. Vom Ersten zum Zweiten Weltkrieg“. Am Rande des Workshops führten Ellinor Forster und Regina Thumser-Wöhs das Gespräch mit Robert Jütte, zu dessen Schwerpunkten neben Medizingeschichte auch Alltags- und Kulturgeschichte der Frühen Neuzeit sowie jüdische Geschichte gehören.

Abstract In the past, the potato plant microbiota and rhizosphere have been studied in detail to improve plant growth and fitness. However, less is known about the postharvest potato tuber microbiome and its role in storage stability. The storage stability of potatoes depends on genotype and storage conditions, but the soil in which tubers were grown could also play a role. To understand the ecology and functional role of the postharvest potato microbiota, we planted four potato varieties in five soil types and monitored them until the tubers started sprouting. During storage, the bacterial community of tubers was analysed by next-generation sequencing of the 16S rRNA gene amplicons. The potato tubers exhibited soil-dependent differences in sprouting behaviour. The statistical analysis revealed a strong shift of the tuber-associated bacterial community from harvest to dormancy break. By combining indicator species analysis and a correlation matrix, we predicted associations between members of the bacterial community and tuber sprouting behaviour. Based on this, we identified Flavobacterium sp. isolates, which were able to influence sprouting behaviour by inhibiting potato bud outgrowth.

Abstract Percolation theory dictates an intuitive picture depicting correlated regions in complex systems as densely connected clusters. While this picture might be adequate at small scales and apart from criticality, we show that highly correlated sites in complex systems can be inherently disconnected. This finding indicates a counter-intuitive organization of dynamical correlations, where functional similarity decouples from physical connectivity. We illustrate the phenomenon on the example of the disordered contact process (DCP) of infection spreading in heterogeneous systems. We apply numerical simulations and an asymptotically exact renormalization group technique (SDRG) in 1, 2 and 3 dimensional systems as well as in two-dimensional lattices with long-ranged interactions. We conclude that the critical dynamics is well captured by mostly one, highly correlated, but spatially disconnected cluster. Our findings indicate that at criticality the relevant, simultaneously infected sites typically do not directly interact with each other. Due to the similarity of the SDRG equations, our results hold also for the critical behavior of the disordered quantum Ising model, leading to quantum correlated, yet spatially disconnected, magnetic domains.

An extraordinarily high intraspecific chemical diversity, i.e. chemodiversity, has been found in several plant species, of which some are of major ecological or economic relevance. Moreover, even within an individual plant there is substantial chemodiversity among tissues and across seasons. This chemodiversity likely has pronounced ecological effects on plant mutualists and antagonists, associated foodwebs and, ultimately, biodiversity. Surprisingly, studies on interactions between plants and their herbivores or pollinators often neglect plant chemistry as a level of diversity and phenotypic variation. The main aim of this Research Unit (RU) is to understand the emergence and maintenance of intraspecific chemodiversity in plants. We address the following central questions:1) How does plant chemodiversity vary across levels, i.e., within individuals, among individuals within populations, and among populations?2) What are the ecological consequences of intraspecific plant chemodiversity?3) How is plant chemodiversity genetically determined and maintained?By combining field and laboratory studies with metabolomics, transcriptomics, genetic tools, statistical data analysis and modelling, we aim to understand causes and consequences of plant chemodiversity and elucidate its impacts on the interactions of plants with their biotic environment. Furthermore, we want to identify general principles, which hold across different species, and develop meaningful measures to describe the fascinating diversity of defence chemicals in plants. These tasks require integrated scientific collaboration of experts in experimental and theoretical ecology, including chemical and molecular ecology, (bio)chemistry and evolution.

Background: Despite developments in surgical techniques and medical care, people with a Fontan circulation still experience long-term complications; non-invasive therapies to optimize the circulation have not been established. Exercise intolerance affects the majority of the population and is associated with worse prognosis. Historically, people living with a Fontan circulation were advised to avoid physical activity, but a small number of heterogenous, predominantly uncontrolled studies have shown that exercise training is safe—and for unique reasons, may even be of heightened importance in the setting of Fontan physiology. The mechanisms underlying improvements in aerobic exercise capacity and the effects of exercise training on circulatory and end-organ function remain incompletely understood. Furthermore, the optimal methods of exercise prescription are poorly characterized. This highlights the need for large, well-designed, multi-center, randomized, controlled trials.Aims and Methods: The Fontan Fitness Intervention Trial (F-FIT)—a phase III clinical trial—aims to optimize exercise prescription and delivery in people with a Fontan circulation. In this multi-center, randomized, controlled study, eligible Fontan participants will be randomized to either a 4-month supervised aerobic and resistance exercise training program of moderate-to-vigorous intensity followed by an 8-month maintenance phase; or usual care (control group). Adolescent and adult (≥16 years) Fontan participants will be randomized to either traditional face-to-face exercise training, telehealth exercise training, or usual care in a three-arm trial with an allocation of 2:2:1 (traditional:telehealth:control). Children (

The environmental considerations need to be taken into account in any road resurfacing and upgrading project, for example, by reusing asphalt rubble for production of new pavement courses. Mixtures containing larger amounts of recycled asphalt pavement are improved by adding rejuvenator additives. The tests performed on the recycled asphalt mixtures containing lard imidazoline confirm the suitability of this agent for paving applications. Lard imidazoline was found to improve the stiffness modulus, fatigue performance and resistance to the action of water and freezing temperatures. The parameters obtained at the optimum content of additive complied with the criteria defined for virgin asphalt concrete and other mixtures of that kind.

Background: People with a Fontan circulation usually have moderately impaired exercise performance, although a subset have high physical performance (“Super-Fontan”), which may represent a low-risk phenotype.Methods: People with a “Super-Fontan” phenotype were defined as achieving normal exercise performance [≥80% predicted peak oxygen uptake (VO2) and work rate] during cardiopulmonary exercise testing (CPET) and were identified from the Australian and New Zealand Fontan Registry. A Fontan control group that included people with impaired exercise performance (

OBJECTIVES:. We sought to validate prognostic scores in coronavirus disease 2019 including National Early Warning Score, Modified Early Warning Score, and age-based modifications, and define their performance characteristics. DESIGN:. We analyzed prospectively collected data from the Adaptive COVID-19 Treatment Trial. National Early Warning Score was collected daily during the trial, Modified Early Warning Score was calculated, and age applied to both scores. We assessed prognostic value for the end points of recovery, mechanical ventilation, and death for score at enrollment, average, and slope of score over the first 48 hours. SETTING:. A multisite international inpatient trial. PATIENTS:. A total of 1,062 adult nonpregnant inpatients with severe coronavirus disease 2019 pneumonia. INTERVENTIONS:. Adaptive COVID-19 Treatment Trial 1 randomized participants to receive remdesivir or placebo. The prognostic value of predictive scores was evaluated in both groups separately to assess for differential performance in the setting of remdesivir treatment. MEASUREMENTS AND MAIN RESULTS:. For mortality, baseline National Early Warning Score and Modified Early Warning Score were weakly to moderately prognostic (c-index, 0.60–0.68), and improved with addition of age (c-index, 0.66–0.74). For recovery, baseline National Early Warning Score and Modified Early Warning Score demonstrated somewhat better prognostic ability (c-index, 0.65–0.69); however, National Early Warning Score+age and Modified Early Warning Score+age further improved performance (c-index, 0.68–0.71). For deterioration, baseline National Early Warning Score and Modified Early Warning Score were weakly to moderately prognostic (c-index, 0.59–0.69) and improved with addition of age (c-index, 0.63–0.70). All prognostic performance improvements due to addition of age were significant (p < 0.05). CONCLUSIONS:. In the Adaptive COVID-19 Treatment Trial 1 cohort, National Early Warning Score and Modified Early Warning Score demonstrated moderate prognostic performance in patients with severe coronavirus disease 2019, with improvement in predictive ability for National Early Warning Score+age and Modified Early Warning Score+age. Area under receiver operating curve for National Early Warning Score and Modified Early Warning Score improved in patients receiving remdesivir versus placebo early in the pandemic for recovery and mortality. Although these scores are simple and readily obtainable in myriad settings, in our data set, they were insufficiently predictive to completely replace clinical judgment in coronavirus disease 2019 and may serve best as an adjunct to triage, disposition, and resourcing decisions.

Abstract Background OnabotulinumtoxinA (BOTOX®, Allergan plc, Dublin, Ireland) is approved for the preventive treatment of headaches in adult patients with chronic migraine (CM) in Australia by the country’s reimbursement mechanism for medicines, the Pharmaceutical Benefits Scheme (PBS). To our knowledge, this study represents the first focused report evaluating real-world evidence of onabotulinumtoxinA treatment via the PBS in Australian clinics. Methods This study reviewed the medical records of adults with inadequately controlled CM from 7 private neurology practices in Australia who, beginning in March 2014, received PBS-subsidized onabotulinumtoxinA per product labelling for the first time. The primary effectiveness measure was the percentage of patients achieving a response defined by 50% or greater reduction in headache days from baseline after 2 treatment cycles. Additional data were recorded in the case report form when available and included demographics, clinical characteristics, headache severity and frequency, Headache Impact Test (HIT-6) score, medication use, and days missed of work or study at baseline, after 2 treatment cycles, and at last follow-up. Differences in mean changes from baseline were evaluated with a 1-tailed t-test or Pearson’s chi-squared test (p

Abstract Background Onchocerciasis is a neglected tropical disease which is still of immense major public health concern in several areas of Africa and the Americas. The disease manifests either as ocular or as dermal onchocerciasis with several symptoms including itching, nodules, skin thickening, visual impairment and blindness. Ivermectin has been an efficient microfilaricide against the causative agent of the disease (Onchocerca volvulus) but reports from some areas in Africa suggest the development of resistance to this drug. The aim of this study was to determine the prevalence of onchocerciasis and associated clinical conditions frequently associated with the disease in three endemic communities in Ghana which have been subjected to 18 to 20 rounds of mass drug administration of ivermectin. This was to help determine whether or not onchocerciasis persists in these communities. Methods A cross-sectional study design was adopted. Three communities (Tanfiano, Senya and Kokompe) in the Nkoranza North District of Ghana where mass drug administration of ivermectin had been ongoing for more than two decades were selected for the study. The population was randomly sampled and 114 participants recruited for the study based on the eligibility criteria. The study participants were examined for the presence of parasites and clinical manifestations of onchocerciasis following established protocols. Results The study showed that the prevalence of microfilaria in the Tanfiano, Senya, Kokompe communities were 13.2, 2.4, and 2.9%, with nodule prevalence being 5.3, 4.9 and 14.3% respectively. Females in the study communities had a higher prevalence of microfilaria carriers (5.17%) relative to males (2.44%), but this difference was not statistically significant (p = 0.2800, unpaired t test). The most frequent clinical manifestation observed in this study among all participants was dermatitis (25.4%), followed by visual impairment & nodules (7.9% each) and then by blindness (4.4%). Conclusion The study showed that despite several years of mass drug administration with ivermectin, infection with onchocerciasis and the commonly associated clinical manifestations of the disease still persist in the study communities. This calls for a greater urgency for research and development aimed at discovering new or repurposed anti-filarial agents which will augment ivermectin if global onchocerciasis eradication targets are to be achieved.

Cerebral computed tomography angiography is a widely available imaging technique that helps in the diagnosis of vascular pathologies. Contrast administration is needed to accurately assess the arteries. On non-contrast computed tomography, arteries are hardly distinguishable from the brain tissue, therefore, radiologists do not consider this imaging modality appropriate for the evaluation of vascular pathologies. There are known contraindications to administering iodinated contrast media, and in these cases, the patient has to undergo another examination to visualize cerebral arteries, such as magnetic resonance angiography. Deep learning for image segmentation has proven to perform well on medical data for a variety of tasks. The aim of this research was to apply deep learning methods to segment cerebral arteries on non-contrast computed tomography scans and consequently, generate angiographies without the need for contrast administration. The dataset for this research included 131 patients who underwent brain non-contrast computed tomography directly followed by computed tomography with contrast administration. Then, the segmentations of arteries were generated and aligned with non-contrast computed tomography scans. A deep learning model based on the U-net architecture was trained to perform the segmentation of blood vessels on non-contrast computed tomography. An evaluation was performed on separate test data, as well as using cross-validation, reaching Dice coefficients of 0.638 and 0.673, respectively. This study proves that deep learning methods can be leveraged to quickly solve problems that are difficult and time-consuming for a human observer, therefore providing physicians with additional information on the patient. To encourage the further development of similar tools, all code used for this research is publicly available.

Intrathecal analgesia has increased over the last 30 years. In oncology, it is a real alternative for the treatment of refractory pain. The diversity of the molecules alone or in combination that can be used, the risk related to the route of administration, and the cost of certain molecules are all arguments in favor of centralized preparation within the pharmacy. The purposes of this work are first of all to explain the reasons for centralization of these preparations, and in a second time to describe the circuit developed within our establishment.