Background: Disentangling adverse drug reactions from confounders remains a major challenge to assess causality and severity in neonates. Vancomycin and amikacin are perceived as nephrotoxic and often prescribed in neonates. We selected these compounds to assess their impact on creatinine dynamics as sensitive tool to detect a renal impairment signal. Methods: A recently developed dynamical model that characterized serum creatinine concentrations of 217 ELBW neonates (4036 serum creatinine observations) was enhanced with data on individual administration of vancomycin and/or amikacin to identify a potential effect of antibiotic exposure by nonlinear mixed-effects modelling analysis. Results: Of our ELBW patients, 77% were exposed to either vancomycin or amikacin. Antibiotic exposure resulted in transient lower overall creatinine clearance and a modest increase in serum creatinine. Dependency on gestational age was observed in the difference in serum creatinine when exposed to antibiotics during the third week after birth (difference in creatinine for a neonate at 24 weeks gestation decreased with 56% for a 32-week-old neonate). Conclusions: A previously described model on creatinine dynamics was used to explore and quantify the impact amikacin or vancomycin exposure on creatinine dynamics. Such tools can be used to explore minor changes, or compare minor differences between treatment modalities.

Wind energy in Europe is aimed to grow at a steady, high pace, but opposition from residents to local wind farm plans is one of the obstacles to further growth. A large body of evidence shows that local populations want to be involved and respected for their concerns, but in practice this is a complex process that cannot be solved with simple measures such as financial compensation. The visual presence and the acoustic impact of a wind farm is an important concern for residents. Generally environmental noise management aims to reduce the exposure of the population, usually based on acoustics and restricted to a limited number of sources (such as transportation or industry) and sound descriptors (such as Lden). Individual perceptions are taken into account only at an aggregate, statistical level (such as percentage of exposed, annoyed or sleep-disturbed persons in the population). Individual perceptions and reactions to sound vary in intensity and over different dimensions (such as pleasure/fear or distraction). Sound level is in fact a weak predictor of the perceived health effects of sound. The positive or negative perception of and attitude to the source of the sound is a better predictor of its effects. This article aims to show how the two perspectives (based on acoustics and on perception) can lead to a combined approach in the management of a wind farm aimed to reduce annoyance, not primarily of sound level. An important aspect in this approach is what the sound means to people: is it associated with the experience of having no say in plans, does it lead to anxiety or worry, is it appropriate? The available knowledge will be applied to wind farm management: planning as well as operation.

Important policy developments in dementia and palliative care in nursing homes between 2010 and 2015 in Flanders, Belgium might have influenced which people die in nursing homes and how they die. We aimed to examine differences between 2010 and 2015 in the prevalence and characteristics of residents with dementia in nursing homes in Flanders, and their palliative care service use and comfort in the last week of life. We used two retrospective epidemiological studies, including 198 residents in 2010 and 183 in 2015, who died with dementia in representative samples of nursing homes in Flanders. We found a 23%-point increase in dementia prevalence (P-value<0.001), with a total of 11%-point decrease in severe to very severe cognitive impairment (P=0.04). Controlling for this difference in resident characteristics, in the last week of life, there were increases in the use of pain assessment (+20%-point; P<0.001) and assistance with eating and drinking (+10%-point; P=0.02) but no change in total comfort. The higher prevalence of dementia in nursing homes with no improvement in residents’ total comfort while dying emphasize an urgent need to better support nursing homes in improving their capacities to provide timely and high-quality palliative care services to more residents dying with dementia.

Satellite-based broad-scale (i.e., global and continental) human settlement data offer foundational information for diverse applications spanning climate hazard mitigation, sustainable development monitoring, spatial epidemiology, and demographic modeling. While many human settlement products report exceptional detection accuracies above 85%, there is a substantial blind spot in that product validation is typically centered on large urban areas rather than rural, small-scale settlements that are home to 3.4 billion people. In this study, we make use of a data-rich collection of 30 refugee settlements in Uganda to produce a targeted assessment of small-scale settlement detection by four broad-scale human settlement products: Global Human Settlements Built-Up Sentinel-2 (GHS-BUILT-S2), World Settlement Footprint (WSF), High Resolution Settlement Layer (HRSL), and Geo-Referenced Infrastructure and Demographic Data for Development (GRID3). We measured each product’s areal coverage within refugee settlements, assessed product detection accuracies in comparison to an independent dataset of 317,416 refugee settlement building footprints, and examined agreement between products. For refugee settlements established before 2016, the human settlement products had a low median F1-Score (F1) of 0.24, a high median false alarm rate of 0.59, and tended to only agree at locations of highest building density. Individually, WSF entirely overlooked 8 of the 30 study refugee settlements (median F1=0.17); GHS-BUILT-S2 underestimated the building footprint area by a median 50% (F1=0.15); GRID3 overestimated the building footprint area by a median 280% (F1=0.38); and HRSL underestimated the median area by 7% (F1=0.34). All products suffer from low detection accuracy and high false alarm rates, but GRID3 and HRSL, based on 0.5 meter resolution imagery, offer better detection accuracy than GHS-BUILT S2 and WSF, which are based on 10-30 meter resolution imagery. These results show that human settlement products have far to go in providing an accurate depiction of small-scale refugee settlements and would benefit from incorporating refugee settlements in training and validation of broad-scale human settlement detection.

Battery electric vehicles provide an opportunity to balance supply and demand in future power systems with high shares of fluctuating renewable energy. Compared to other storage systems such as pumped-storage hydroelectricity, electric vehicle energy demand is highly dependent on charging and connection choices of vehicle users. We present a model framework of a utility-based stock and flow model, a utility-based microsimulation of charging decisions, and an energy system model including respective interfaces to assess how the representation of battery electric vehicle charging affects energy system optimization results. We then apply the framework to a scenario study for controlled charging of nine million electric vehicles in Germany in 2030. Assuming a respective fleet power demand of 27 TWh, we analyze the difference between power-system-based and vehicle user-based charging decisions in two respective scenarios. Our results show that taking into account vehicle users’ charging and connection decisions significantly decreases the load shifting potential of controlled charging. The analysis of marginal values of equations and variables of the optimization problem yields valuable insights on the importance of specific constraints and optimization variables. In particular, state-of-charge assumptions and representing fast charging drive curtailment of renewable energy feed-in and required gas power plant flexibility. A detailed representation of fleet charge connection is less important. Peak load can be significantly reduced by 5% and 3% in both scenarios, respectively. Shifted load is very robust across sensitivity analyses while other model results such as curtailment are more sensitive to factors such as underlying data years. Analyzing the importance of increased BEV fleet battery availability for power systems with different weather and electricity demand characteristics should be further scrutinized.

With the emergence of COVID-19 we are confronted with a new clinical picture of acute respiratory distress syndrome in the intensive care unit. In the majority of patients, the respiratory mechanics are very different from the “normal” ARDS patient. We measured transpulmonary pressure and dead space ventilation to assess the effects of high and low PEEP levels on lung compliance and ventilation-perfusion mismatching. Advanced respiratory mechanics were assessed in 14 patients. Compared to ARDS patients, lung compliance was relatively high (61 ± 5 mL/cmH₂O). COVID-19 patients had high dead space ventilation and gas exchange impairment (Bohr 52 ± 3%; Enghoff modification 67 ± 2%; ventilatory ratio 2.24 ± 0.23). we show that higher PEEP levels decrease lung compliance and in most cases increase dead space ventilation, indicating that high PEEP levels probably cause hyperinflation in patients with COVID-19. We suggest using prone position for an extended period of time, and apply lower PEEP levels as much as possible.

Reelin depletion and stress seem to affect similar pathways including GABAergic and glutamatergic signaling and both are implicated in psychiatric disorders in late adolescence/early adulthood. The interaction between reelin depletion and stress, however, remains unclear. To investigate this, male and female heterozygous reelin mice (HRM) and wildtype (WT) controls were treated with the stress hormone, corticosterone (CORT), during late adolescence to simulate chronic stress. Glucocorticoid receptors (GR), N-methyl-D-aspartate receptor (NMDAr) subunits, glutamic acid decarboxylase (GAD67) and parvalbumin (PV) were measured in the hippocampus and the prefrontal cortex (PFC) in adulthood. While no changes were seen in male mice, female HRM showed a significant reduction in GR expression in the dorsal hippocampus. In addition, CORT reduced GR levels as well as GluN2B and GluN2C subunits of NMDAr in the dorsal hippocampus in female mice only. CORT furthermore reduced GluN1 levels in the PFC of female mice. The combined effect of HRM and CORT treatment appeared to be additive in terms of GR expression in the dorsal hippocampus. Female-specific CORT-induced changes were associated with overall higher circulating CORT levels in female compared to male mice. This study shows differential effects of reelin depletion and CORT treatment on GR and NMDAr protein expression in male and female mice, suggesting that females are more susceptible to reelin haploinsufficiency as well as late-adolescent stress. These findings shed more light on female-specific vulnerability to stress and have implications for stress-associated mental illnesses with a female bias including anxiety and major depression.

Vitamin D is a nutrient with anti-inflammatory properties whose role is currently being evaluated in COVID-19. Although studies are conflicting, they seem to suggest a role for vitamin D in reducing disease susceptibility but not in improving clinical outcome. In order to understand why vitamin D does not seem to have much effect on decreasing disease severity, it is essential to appreciate pulmonary vitamin D metabolism. To reach the pulmonary compartment, vascular endothelial cells would need to take up vitamin D from the blood stream, but they lack vitamin D receptor (VDR) and the activating enzyme CYP27B1. Endothelialitis – an important disease manifestation of COVID-19 – is therefore not expected to be directly affected by vitamin D. Bronchial epithelial cells are usually among the first to be infected with SARS-CoV-2. They do express both VDR and CYP27B1, but circulating vitamin D may not reach bronchial epithelial cells without transportation from the blood stream through the blood vessel wall. Inhalation therapy with vitamin D has therefore been suggested as an alternative for oral administration to bypass endothelial cells and efficaciously target bronchial epithelium. In conclusion, based on the principles of pulmonary vitamin D metabolism, it is not expected that vitamin D administration has a significant effect on COVID-19 severity. Vitamin D is more likely to reduce SARS-CoV-2 susceptibility, but reaching the airways with oral supplementation will be difficult and vitamin D inhalation therapy should be considered.

Organ-on-Chip is a game-changing technology born from the convergence of tissue engineering and microfluidic technology. Organ-on-Chip devices (OoCs) are expected to offer effective solutions to persisting problems in drug development and personalized disease treatments. This opinion paper surveys the current landscape in research, development, application and market opportunities for OoCs to help establishing a global and multi-stakeholder OoC ecosystem. Based on a bibliometric study, a market analysis, expert interviews, and panel discussions held at the ORCHID Vision Workshop (Stuttgart, 23 May 2018), we outline presently unmet needs, key challenges, barriers and perspectives of the field, and finally propose recommendations towards the definition of a comprehensive roadmap that could render OoCs realistic models of human (patho)physiology in the near future.

Abstract Universities have the potential, and the responsibility, to take on more ecological and relational approaches to facilitating learning-based change in times of interconnected socio-ecological crises. Signs for a transition towards these more regenerative approaches of higher education (RHE) that include more place-based, ecological, and relational, ways of educating can already be found in niches across Europe (see for example the proliferation of education-based living labs, field labs, challenge labs). In this paper, the results of a podcast-based inquiry into the design practices and barriers of enacting such forms of RHE are shown. This study revealed seven educational practices that occurred across the innovation niches. It is important to note these practices are enacted in different ways, or are locally nested in unique expressions, For example, while the ‘practice’ of Cultivating Personal Transformations was represented across the included cases, the way these transformations were cultivated were unique expressions of each context. These RHE-design practices are derived from twenty-six narrative-based podcasts as interviews recorded in the April through June 2021 period. The resulting podcast (The Regenerative Education Podcast) was published on all major streaming platforms from October 2021 and included 21 participants active in Dutch Universities, 1 in Sweden, 1 in Germany, 1 in France, and 3 primarily online. Each episode engages with a leading practitioner, professor, teacher, and/or activist that is trying to connect their educational practice to making the world a more equitable, sustainable, and regenerative place. The episodes ranged from 30 to 70 minutes in total length and included both English (14) and Dutch (12) interviews. These episodes were analyzed through transition mapping a method based on story analysis and transition design. The results include seven design practices such as Cultivating Personal Transformations, Nurturing Ecosystems of Support, and Tackling Relevant and Urgent Transition Challenges, as well as a preliminary design tool that educational teams can use together with students and local agents in (re)designing their own RHE to connect their educational praxis with transition challenges.

Vaccine uptake is one of the indicators that has been used to guide immunization programs. This study aimed to evaluate whether the measles vaccine uptake is predicted by measles vaccine hesitancy. A community-based cross-sectional study was conducted in urban districts in Khartoum state in February 2019. Measles vaccine uptake among children was measured as either fully vaccinated or partially/not vaccinated. The Parents Attitude about Childhood Vaccination (PACV) scale was used to measure measles vaccine hesitancy. Multivariate logistic regression was run to identify the predictors of measles vaccination uptake controlling for sociodemographic variables and the adjusted odds ratios (aORs) with 95% CI were calculated. The receiver operator characteristic (ROC) curve was performed, besides area under the curve (AUC) for the PACV was computed. Data was collected from 495 participants. We found that measles vaccine hesitancy (PACV scores) predicted the uptake of measles vaccine after controlling other potential social confounders such as mother’s age and the number of children (aOR 1.055, 95% CI 1.028-1.028). Additionally, the ROC for the PACV yielded area under the curve (AUC 0.686 (95% CI 0.620-0.751, P <0.001). Our findings show that measles vaccine hesitancy in Sudan directly influences the uptake of the measles vaccine. Addressing the determinants of vaccine hesitancy through communication strategies will improve vaccine uptake.

Positive Health (PH) has been described as a promising transformative innovation to address the challenges of promoting well-being and reducing the burden of disease. The aim of this study is to review the current state of knowledge about PH as introduced by Huber et al. (2016) within the available scientific literature. A rapid review of the literature following the Cochrane Rapid Review recommendations. Three databases were searched (PubMed, Google Scholar, and CINAHL). Data were extracted and synthesized using a narrative approach. A total of 55 articles were included. Initial evaluation studies reveal promising results both at individual and collective levels. However, a need is expressed in several articles for further refinement of the conceptualization of PH and ways to make the effects of the PH approach more measurable. Professionals also expressed a desire for a more informed application and elaboration of the PH method across various settings and populations to enhance its effectiveness in practice. This rapid review highlights the transformative potential of PH in shifting from a disease-focused to a health-oriented paradigm of healthcare. It underscores the need for continued research regarding further development of the concept and its practical method, along with the necessity for methodological innovation.

Beta-glucan-stimulated mammalian macrophages show an increased responsiveness to secondary stimulation in a nonspecific manner. This phenomenon is known as trained innate immunity. Our study aimed to explore training of primary chicken monocytes. We hypothesized that primary chicken monocytes, similar to their mammalian counterparts, can be trained with β-glucan resulting in increased responses of these cells to a secondary stimulus. Primary blood monocytes of white leghorn chickens were primary stimulated with β-glucan microparticulates (M-βG), LPS, recombinant chicken interleukin-4 (IL-4) or combinations of these components for 48 h. On day 6, the primary stimulated cells were secondary stimulated with LPS. Nitric oxide (NO) production levels were measured as an indicator of pro-inflammatory activity. In addition, the cells were analysed by flow cytometry to characterize the population of trained cells and to investigate the expression of surface markers associated with activation. After the secondary LPS stimulation, surface expression of CSF1R and the activation markers CD40 and MHC-II was higher on macrophages that were trained with a combination of M-βG and IL-4 compared to unstimulated cells. This increased expression was paralleled by enhanced NO production. In conclusion, this study showed that trained innate immunity can be induced in primary chicken monocytes with β-glucan, which is in line with previous experiments in mammalian species. Innate immune training may have potential to improve health and vaccination strategies within the poultry sector.

Persistence of symptoms beyond three months after COVID-19 infection, often referred to as post-COVID-19 condition (PCC), is commonly experienced. It is hypothesized that PCC results from autonomic dysfunction with decreased vagal nerve activity, which can be indexed by low heart rate variability (HRV). The aim of this study was to assess the association of HRV upon admission with pulmonary function impairment and number of reported symptoms beyond three months after initial hospitalization for COVID-19 between February and December 2020. Follow-up took place three to five months after discharge and included pulmonary function tests and the assessment of persistent symptoms. HRV analysis was performed on one 10s electrocardiogram obtained upon admission. Analyses were performed using multivariable and multinomial logistic regression models. Among 171 patients who received follow-up, and with an electrocardiogram at admission, decreased diffusion capacity of the lung for carbon monoxide (DLCO) (41%) was most frequently found. After a median of 119 days (IQR 101-141), 81% of the participants reported at least one symptom. HRV was not associated with pulmonary function impairment or persistent symptoms three to five months after hospitalization for COVID-19.

Coronaviruses cause infections in humans and diverse species of animals and birds with a global distribution. Bovine coronavirus (BCoV) produces predominantly two forms of disease in cattle, a respiratory form, and a gastrointestinal form. All age groups of cattle are affected by the respiratory form of coronavirus whereas the gastroenteric form causes neonatal diarrhea or calf scour in young cattle and winter dysentery in adult cattle. The tremendous impacts of bovine respiratory disease and the associated losses are well-documented and underscores the importance of this pathogen. Beyond this, studies have demonstrated significant impacts on milk production associated with outbreaks of winter dysentery, with up to a 30% decrease in milk yield. Research data so far have shown that the viral structure or strain is not a determinant of tissue tropism and clinical form of the disease. In North America, BCoV was identified for the first time in 1972, and it continues to be a significant economic concern for the cattle industry. The virus is classified under Coronaviridae family, Betacoronavirus genus and Betacorovirus 1 species. A number of conventional and molecular diagnostic assays are available for the detection of BCoV from clinical samples. Conventional assays for BCoV detection include virus isolation, which is challenging from clinical samples, electron microscopy, fluorescent antibody assays, and various immunoassays. Molecular tests are mainly based on nucleic acid detection and predominantly include conventional and real-time polymerase chain reaction (PCR) assays. Isothermal amplification assays and genome sequencing have also been used increasingly in recent years for the detection and identification of BCoV. Loop-mediated isothermal amplification, helicase-dependent amplification, recombinase polymerase amplification, and multienzyme isothermal rapid amplification are some examples of the isothermal amplification assays for used BCoV. Point-of-care testing has gained some popularity recently as they can offer user-friendly testing on the farm (barn-side). The present study reviewed literature on coronavirus infections in cattle from the last three and a half decades and presents information mainly on the current and advancing diagnostics in addition to epidemiology, clinical presentations, and the impact of the disease on the cattle industry.

The sound power LW of wind turbines (WTs) over the past decades has developed in relation to their electric power P as LW ∝ logP. The spectral distribution of the sound did not change significantly over time. This applies to the average performance of wind turbines, with differences between individual WT types. Because of the expected growth of onshore wind energy, a greater number of people will be living close to wind farms. This sustains the need for sound reduction. Sound reduction measures, such as serrations, reduced tip speed and low noise modes, may counteract the development of higher sound power from ever bigger WTs. To investigate this, the sound production of WT types over the last decades is analysed in relation to their size and electric power and the application of sound reduction measures. The analysis includes the broad band A-weighted and low frequency sound power levels as well as more detailed spectral distributions. Results show that the sound power level of wind turbines above 3 MW on average increases less with size than smaller turbines did. This is due to a lower blade tip speed and the use of sound reducing serrations. The spectral content of wind turbine sound, including the lower frequencies, has not changed significantly.

With the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in coronavirus disease 2019 (COVID-19), corporate entities, federal, state, county and city governments, universities, school districts, places of worship, prisons, health care facilities, assisted living organizations, daycares, homeowners, and other building owners and occupants have an opportunity to reduce the potential for transmission through built environment (BE) mediated pathways. Over the last decade, substantial research into the presence, abundance, diversity, function, and transmission of microbes in the BE has taken place and revealed common pathogen exchange pathways and mechanisms. In this paper, we synthesize this microbiology of the BE research and the known information about SARS-CoV-2 to provide actionable and achievable guidance to BE decision makers, building operators, and all indoor occupants attempting to minimize infectious disease transmission through environmentally mediated pathways. We believe this information is useful to corporate and public administrators and individuals responsible for building operations and environmental services in their decision-making process about the degree and duration of social-distancing measures during viral epidemics and pandemics.

Digital microfluidics (DMF) holds great potential for the alleviation of laboratory procedures in assisted reproductive technologies (ARTs). Electrowetting on dielectric (EWOD) provides dynamic culture conditions in vitro that may better mimic the natural embryo microenvironment. Thus far, EWOD microdevices have been proposed for in vitro gamete and embryo handling in mice and for analyzing the human embryo secretome. This article presents the development of the first microfluidic chip utilizing EWOD technology designed for the manipulation of bovine embryos in vitro. The prototype sustains the cell cycles of embryos manipulated individually on the chips during in vitro culture (IVC). Challenges related to the chip fabrication as well as to its application during bovine embryo IVC in accordance with the adapted on-chip protocol are thoroughly discussed, and future directions for DMF in ARTs are indicated.

ω-Transaminases have been immobilized on macrocellular silica monoliths and used as heterogeneous biocatalysts in a continuous flow mode enantioselective transamination reaction. The support was prepared by a sol-gel method based on emulsion templating. The enzyme was immobilized on the structured silica monoliths both by adsorption, and by covalent grafting using amino-functionalized silica monoliths and glutaraldehyde as a coupling agent. A simple reactor set-up based on the use of a heat-shrinkable Teflon tube is presented and successfully used for the continuous flow kinetic resolution of a chiral amine, 4-bromo-α-methylbenzylamine. The porous structure of the supports ensures effective mass transfer and the reactor works in the plug flow regime without preferential flow paths. When immobilized in the monolith and used in the flow reactor, transaminases retain their activity and their enantioselectivity. The solid biocatalyst is also shown to be stable both on stream and during storage. These essential features pave the way to the successful development of an environmentally friendly process for chiral amines production.

Dysregulation of high-frequency neuronal oscillations has been implicated in the pathophysiology of schizophrenia. Chronic methamphetamine (METH) use can induce psychosis similar to paranoid schizophrenia. The current study in mice aimed to determine the effect of chronic METH treatment on ongoing and evoked neuronal oscillations. C57BL/6 mice were treated with METH or vehicle control for three weeks and implanted with extradural recording electrodes. Two weeks after the last METH injection, mice underwent three EEG recording sessions to measure ongoing and auditory-evoked gamma and beta oscillatory power in response to an acute challenge with METH (2mg/kg), the NMDA receptor antagonist MK-801 (0.3mg/kg), or saline control. A separate group of mice pretreated with METH showed significantly greater locomotor hyperactivity to an acute METH challenge, confirming long-term sensitisation. Chronic METH did not affect ongoing or evoked gamma or beta power. Acute MK-801 challenge reduced ongoing beta power whereas acute METH challenge significantly increased ongoing gamma power. Both MK-801 and METH challenge suppressed evoked gamma power. Chronic METH treatment did not modulate these acute drug effects. There were minor effects of chronic METH and acute METH and MK-801 on selected components of event-related potential (ERP) waves. In conclusion, chronic METH treatment did not exert neuroplastic effects on the regulation of cortical gamma oscillations in a manner consistent with schizophrenia, despite causing behavioural sensitisation.

Background: The prognostic and predictive role of stromal tumor-infiltrating lymphocytes (sTILs) is undetermined in pleomorphic invasive lobular cancer (pILC). The same applies for the expression of PD-1/PD-L1 in this rare breast cancer subtype. Here, we aimed to investigate the expression of sTILs, and analyze the PD-L1 expression levels in pILC. Methods: Archival tissues from sixty-six patients with pILC were collected. The sTIL density was scored as a percentage of tumor area, using the following cut-offs: 0%; <5%; 5-9%; and 10-50%. PD-L1 expression was analyzed using IHC on formalin-fixed, paraffin-embedded tissue sections, using the SP142 and 22C3 antibodies. Results: 82% of the sixty-six patients were hormone receptor-positive; 8% of cases were triple negative (TN), while 10% showed human epidermal growth factor receptor 2 (HER2) amplification. sTILs were present in 64% (1%) of the study population. Using the SP142 antibody, 36% of tumors demonstrated a positive PD-L1 score of 1%, and 28% had a positive PD-L1 score of 1 using the 22C3 antibody. There was no correlation of sTILs or PD-L1 expression with tumor size, tumor grade, nodal status, expression of estrogen receptor (ER) or amplification of HER2. Our data did not show any difference in survival between the three molecular subtypes of pILC with respect to sTILs and PD-L1 expression. Conclusion: This study shows that pILCs show some degree of sTILs and PD-L1 expression, however this was not associated with survival benefit. Additional large trials are needed to understand the immune infiltration in lobular cancer, even more in the pleomorphic subtype.

Background and Objectives: The aim of this study was to determine the job-related and individual features that influence BS and depression levels among dentists working in faculties, oral and dental health centres (ODHC) and private clinics. Materials and Methods: This prospective, cross sectional study was carried out on dentists working in different regions of Turkey. Data were collected using an on-line questionnaire created using Google Forms. The questionnaire consisted of demographic data, Maslach BS Inventory (MBI) and Beck Depression Inventory (BDI) sections. Demographics were age, height, weight, marital status, blood type, gender, monthly income, income satisfaction and having enough free time. The dentists were divided into 3 groups as faculty, private clinic and ODHC according to the institutions in which they worked. Results: Of the total 290 dentists enrolled in the study, there were 172 males and 118 females with a mean age of 36.98±5.6 years. 128 of the dentists worked in faculties, 72 in private clinics and 90 in ODHCs. It was observed that women's EE scores were higher than men's (P&lt;0.05). No statistically significant difference was found between the groups when comparing BS and depression scores according to marital status and blood group (P&gt;0.05). There was no significant relationship between emotional exhaustion (EE), depersonalisation (DP), personal accomplishment (PA) and depression scores according to age, BMI and work experience, age, work experience and BMI (P&lt;0.05). It was found that the EE scores of the dentists working in the faculty and private clinic were lower than those of the dentists working in the ODHC (P&lt;0.05). Monthly income was associated with depression (r = -0.35). Conclusions: This study showed that dentists working in ODHCs had more EE. These findings suggest that there is a need for improvement in the working conditions of dentists, particularly in ODHCs.

The worldwide spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has ubiquitously impacted many aspects of life. As vaccines continue to be manufactured and administered, limiting the spread of SARS-CoV-2 will rely more heavily on the early identification of contagious individuals occupying reopened and increasingly populated indoor environments. In this study, we investigated the utility of an impaction-based aerosol sampling system with multiple nucleic acid collection media. Heat-inactivated SARS-CoV-2 was utilized to perform bench-scale, short-range aerosol, and room-scale aerosol experiments. Through bench-scale experiments, AerosolSense Capture Media (ACM) and nylon flocked swabs were identified as the highest utility media. In room-scale aerosol experiments, consistent detection of aerosol SARS-CoV-2 was achieved at a concentration equal to or greater than 0.089 genome copies per liter of room air (gc/L) when air was sampled for eight hours or more at less than one air change per hour (ACH). Shorter sampling periods (~75 minutes) yielded consistent detection at ~31.8 gc/L of room air and intermittent detection down to ~0.318 gc/L at (1 and 6+ ACH respectively). These results support further exploration in real-world testing scenarios and suggest the utility of indoor aerosol surveillance as an effective risk mitigation strategy in occupied buildings.

Background: Schizophrenia is a severe psychiatric disorder that has a large impact on patients’ lives. In addition to Western medicine, the use of additional treatments, such as acupuncture, in treating the positive, negative, and cognitive symptoms is increasing. Methods: We conducted a systematic review on the use of acupuncture as an add-on treatment for patients with schizophrenia that are in regular care, with a special focus on the treatment of the often accompanying co-morbid sleep disorders. In this study, we searched the Medline, ScienceDirect, Cochrane Library, Scopus, and ERIC databases with a cut-off date of December 31, 2017, thereby following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol. Results: Our search resulted in 26 eligible studies. Most studies showed limited evidence for the use of acupuncture as add-on therapy in the treatment of clinical symptoms, but beneficial effects have been reported in the treatment of co-morbid sleep disorders. Conclusions: Limited evidence was found for the use of acupuncture as add-on therapy in the treatment of patients with schizophrenia; however, positive results were found in the treatment of sleep disorders, but this result needs to be confirmed in large, randomized, controlled trials.

The aim of this study was to compare the effect of using L-PRF in patients undergoing impacted lower third molar surgery with either primary or secondary closure techniques. Methods: This prospective, randomised, double-blind, split-mouth clinical trial was conducted in patients with bilateral lower impacted third molars of similar position. Primary closure was performed in group 1 and secondary closure in group 2. Group 1 closure technique was applied to one side of the patients and group 2 closure technique was applied to the other side at different times. Nine pa-tients were excluded from the study due to alveolitis and failure to attend regular control visits out of the 45 patients evaluated. Results: Of the 36 patients included in the study, 23 were female and 13 were male and the mean age was 22.42±3.36 years. The secondary closure group had lower VAS scores at hour 6 (p

The aim of this study was to evaluate the effect of two different insertion speeds at 8 different insertion torque values ranging from 25-60 during implantation in a dense polyurethane D1 bone model on the placement status and removal torque of dental implants. In this study, 50 pcf single layer polyurethane plates were used. In the study, a total of 320 implant sockets were divided into 2 groups as Group 1 (30 rpm) and Group 2 (50 rpm) in terms of insertion speed. Group 1 and Group 2 were divided into 8 subgroups as 25, 30, 35, 40, 45, 50, 55 and 60 torques. There were 20 implant sockets in each subgroup. During the implantations, implant placement status and removal torque values were assessed. There was a statistically significant difference between the 30 and 50 RPM groups in terms of overall implant placement status (p&lt;0.01). It was found that the removal torque values at 50 RPM were statistically significantly higher than those at 30 RPM (p&lt;0.01). This study showed that in dense D1 bone, the minimum parameters at which all implants could be placed at bone level were 50 torque at 30 rpm and 40 torque at 50 rpm.

Van Wyk Grumbach syndrome refers to the development of peripheral precocious puberty, long-standing hypothyroidism, and gonadal masses; when not diagnosed, an unnecessary gonadectomy may be done; Here we present a case of a 10-year-old girl with Down syndrome, short stature, and vitiligo presented with vaginal bleeding, and a pelvic mass, in whom bilateral gonadectomy was performed. Most cases of Van Wyk Grumbach syndrome present in women, and classic hypothyroidism symptoms always precede the diagnosis; 11% of patients have Down Syndrome, sometimes tumor markers get elevated, and some develop severe symptoms (myopathy, short stature, mental delay, ascites, pericardial effusion, Cullen sign, pituitary hyperplasia, and severe anemia), that respond to levothyroxine treatment; Conclusions: Children with peripheral precocious puberty and gonadal masses, must be studied for hypothyroidism before any radical decision is made. Keywords: Puberty, Precocious; Ovarian Cysts, gonadectomy, Van Wyk Grumbach Syndrome

Introduction: Clinicians have been struggling with the optimal diagnostic approach of patients with suspected COVID-19. We evaluated the added value of chest CT over RT-PCR alone. Methods: Consecutive adult patients with suspected COVID-19 presenting to the emergency department (Academic Medical Center, Amsterdam University Medical Centers, the Netherlands) from March 16^th to April 16^th were retrospectively included if they required hospital admission and underwent chest CT and RT-PCR testing for SARS-CoV-2 infection. The CO-RADS classification was used to assess the radiological probability of COVID-19, where a score of 1-2 was considered as negative, 3 as indeterminate, and 4-5 as positive. CT results were stratified by initial RT-PCR results. For patients with a negative RT-PCR but a positive CT, serology or multidisciplinary discussion after clinical follow-up constituted the final diagnosis. Results: 258 patients with suspected COVID-19 were admitted, of which 239 were included because they had both CT and RT-PCR testing upon admission. Overall, 112 patients (46.9%) had a positive initial RT-PCR, and 14 (5.9%) had a positive repeat RT-PCR. Of 127 patients with a negative or indeterminate initial RT-PCR, 38 (29.9% [95%CI 21.3-39.3%]) had a positive CT. Of these, 13 had a positive RT-PCR upon repeat testing, and 5 had positive serology. The remaining 20 patients were assessed in a multidisciplinary consensus meeting, and for 13 it was concluded that COVID-19 was ‘very likely’. Of 112 patients with a positive initial RT-PCR result, CT was positive in 104 (92.9% [95%CI 89.3-97.5%]). Conclusion: In a high-prevalence emergency department setting, chest CT showed high probability of COVID-19 (CO-RADS 4-5) in 29.9% of patients with a negative or indeterminate initial RT-PCR result. As the majority of these patients had proven or ‘very likely’ COVID-19 after follow-up, we believe that CT helps in the identification of patients who should be admitted in isolation.

An increasingly frail population in nursing homes accentuates the need for high quality care at the end of life and better access to palliative care in this context. Implementation of palliative care and its outcomes can be monitored by using quality indicators. Therefore, we developed a quality indicator set for palliative care in nursing homes and a tailored measurement procedure using a mixed-methods design. We developed the instrument in three phases: 1) literature search, 2) interviews with experts and 3) indicator and measurement selection by expert consensus (RAND/UCLA). Second, we pilot tested and evaluated the instrument in nine nursing homes in Flanders, Belgium. After identifying 26 indicators in the literature and expert interviews, 19 of them were selected through expert consensus. Setting-specific themes were advance care planning, autonomy and communication with family. The quantitative and qualitative analyses showed the indicators were measurable, had good preliminary face validity and discriminative power and were considered useful in terms of quality monitoring according to the caregivers. The quality indicators can be used in a large implementation study and process evaluation in order to achieve continuous monitoring of the access to palliative care for all residents in nursing homes.

Background: According to EWGSOP2, the diagnosis of sarcopenia is confirmed when in addition to low muscle strength, low muscle quantity or quality is present. Echo intensity (EI) determined by muscle ultrasound (US) has been proposed as an efficient method for the assessment of muscle quality. The effect of changing various US parameter settings on EI remains unclear. Therefore, the aim of this study was to assess the differences between EI values obtained by adjusting parameter settings over their entire range in a sample of middle-aged healthy subjects. Methods: Thirty-two repeated US scans of rectus femoris (RF) and rectus abdominis (RA) muscles were taken in eight men and three women with a portable Mindray M7 premium US machine, working in an Extended field-of-view, B-Mode setup, equipped with a linear 5.0-10.0 MHz transducer. The following US parameters and settings were fixed: gain 60dB, depth 6.5cm, and frequency 10 MHz. Readily adjustable parameters were dynamic range (DR), gray map (GM), line density, persistence, and IClear. A default setting DR65 was chosen as the reference setting. For each of the parameters, the settings of one single parameter of interest was changed over its entire range following a standardized protocol. The EI values were calculated using the open-source software ImageJ. Repeated measures analyses were performed to evaluate the effect of parameter settings on EI. Linear interpolation was used to determine non-significant ranges across a given parameter. Results: For the RF muscle, the EI values were significantly different across DR (p<0.001), GM (p<0.001), and IClear (p<0.001). Post hoc analysis confirmed the differences within these three settings. Echo intensity values within the range of DR55 to DR80 were not significantly different. For the RA muscle, the EI values were significantly different across DR (p=0.004) and GM (p=0.030). Post hoc pairwise comparisons revealed no significant difference with the default setting, except for DR150 (p=0.042). Conclusion: We showed that EI values differ across the DR and GM range, especially in the RF. We suggest using a DR setting within its midrange to minimize the effect of machine setting-dependent factors on EI values. These findings reconfirm the need for standardization of ultrasound echo intensity settings when applied for diagnostic purposes of muscle quality.

Intending to analyze the role of nuclear power in an integrated energy system, we used the IESA-Opt-N cost minimization model focusing on four key themes: system-wide impacts of nuclear power, uncertain technological costs, flexible generation, and cross-border electricity trade. We demonstrate that the Levelized Cost of Energy (LCOE) alone should not be used to demonstrate the economic feasibility of a power generation technology. For instance, under the default techno-economic assumptions, particularly the 5% discount rate and exogenous electricity trade potentials, it is cost-optimal for the Netherlands to invest in 9.6 GWe nuclear capacity by 2050. However, its LCOE is 34 €/MWh higher than offshore wind. Moreover, we found that nuclear power investments can reduce demand for variable renewable energy sources in the short term and higher energy independence (i.e., lower imports of natural gas, biomass, and electricity) in the long term. Furthermore, investing in nuclear power can reduce the mitigation costs of the Dutch energy system by 1.6% and 6.2% in 2040 and 2050, and 25% lower national CO₂ prices by 2050. However, this cost reduction is not significant given the odds of higher nuclear financing costs and longer construction times. In addition, this study has shown that lower financing costs (e.g., EU taxonomy support) considerably reduce the relevance of nuclear cost uncertainties on its investments. Furthermore, we demonstrate that the economic feasibility of national nuclear power investments can vary considerably depending on the cross-border electricity trade assumptions. Additionally, we found that lowering the cost of small modular reactors has more impact on their economic feasibility than increasing their generation flexibility. In conclusion, under the specific assumptions of this study, nuclear power can play a complementary role (in parallel to the wind and solar power) in supporting the Dutch energy transition from the sole techno-economic point of view.

Landsat and Sentinel-2 acquisitions are among the most widely used medium-resolution optical data adopted for terrestrial vegetation applications, such as land cover and land use mapping, vegetation condition and phenology monitoring, and disturbance and change mapping. When combined, both data archives provide over 40 years, and counting, of continuous and consistent observations. Although the spatio-temporal availability of both data archives is well-known at the scene level, information on the actual availability of cloud-, snow-, and shade-free observations at the pixel level is lacking and should be explored individually for each study to correctly parametrize subsequent analyses. However, data exploration is time and resource consuming, thus is rarely performed a-priori. Consequently, the spatio-temporal heterogeneity of usable data is often inadequately accounted for in the analysis design, risking ill-advised selection of algorithms and hypotheses, and thus inferior quality of final results. Here we present precomputed data on the daily 1982‑2023 availability of usable Landsat and Sentinel-2 acquisitions across the globe, sampled at a pixel-level in a regular 0.18°-point grid. The dataset comprises separate Landsat- and Sentinel‑2‑specific data records, and is accompanied by a pixel-specific growing season information to facilitate data exploration. The dataset was derived based on freely available 1982-2023 Landsat surface reflectance (Collection 2) and Sentinel-2 top-of-the-atmosphere reflectance (pre‑Collection-1 and Collection-1) scenes from 2015 through 2023, following the methodology developed in the recent study on data availability over Europe [1]. Growing season information was derived based on 2001‑2019 time series of the yearly 500 m MODIS land cover dynamics product (MCD12Q2; Collection 6) [1]. As such, the dataset presents a unique overview of the spatio-temporal availability of usable daily Landsat and Sentinel-2 data at the global scale, hence offering much needed a-priori information aiding identification of appropriate methods and challenges for terrestrial vegetation analyses at local to global scale.

The article concerns a relatively small but important fragment of John Paul II's pastoral activity, namely his pilgrimages to Poland: the nature of these pilgrimages, their historical background and teaching - especially to the extent that went beyond the immediate and Polish context. The text is the result not only of reading papal statements, but also of personal observation of the political and social atmosphere. The first two parts contain a concise description of the Pope's eight pilgrimages to Poland (before and after the political transformation). The third highlights out the main universal themes raised by the Pope: the dignity of the person, truth and freedom. During consecutive pilgrimages to Poland, he deepened and expanded the themes of his teaching. This collection of his sermons and speeches to Poles constitutes a comprehensive (devoid of redundant repetitions and omissions) treatment of important social, philosophical and theological issues. John Paul II, when speaking to Poles and about Poles, did not lose his universal perspective; he appealed both to Christians and to all people of good will. Papal pilgrimages to Poland are a significant part of modern Polish history, and their message is a valuable intellectual and spiritual gift.

In order to develop novel botanical insecticides, the joint action of Ligusticum chuanxiong oil (LCO) and lemongrass oil (LO) against Aphis citricola van der Goot was determined systematically indoors and outdoors. The chemical profiles of LCO and LO as determined by gas chromatography- mass spectrometry analysis revealed that main compounds from LCO were Z-Ligustilide (44.58%) and Senkyunolide A (26.92%), and that of LO were geranial (42.16%) and neral (32.58%), respectively. The mixture of LCO and LO showed significant synergy against A. citricola, with a common-toxicity coefficient (CTC) value of 221.46 at the optimal ratio of LCO to LO (4: 1, w/w). Based on the results of solvents and emulsifiers screening, L. Chuanxiong oil · Lemongrass oil 20% emulsifiable concentrate (20% LCO · LO EC) was developed, which was confirmed to meet the requirements of a commercial pesticide by quality test. Field trials indicated that the insecticidal activity of the diluted 20% LCO · LO EC (1000 fold dilution) was comparable to conventional pesticide (20% imidacloprid EC) on A. citricola 7 days after application. Thus, the mixture of LCO and LO has the potential to be further developed as a botanical pesticide.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an effective and widely used tool in the treatment of Parkinson’s disease (PD). STN-DBS has varied effects on speech. Clinical speech ratings suggest worsening following STN-DBS, but quantitative intelligibility, perceptual, and acoustic studies have produced mixed and inconsistent results. Improvements in phonation and declines in articulation have frequently been reported during different speech tasks under different stimulation conditions. Questions remain about preferred STN-DBS stimulation settings. Seven right-handed, native speakers of English with PD treated with bilateral STN-DBS were studied off medication at three stimulation conditions: stimulators off, 60 Hz (low frequency stimulation - LFS), and the typical clinical setting of 185 Hz (High frequency - HFS). Spontaneous speech was recorded in each condition and excerpts were prepared for transcription (intelligibility) and difficulty judgements. Separate excerpts were prepared for listeners to rate abnormalities in voice, articulation, fluency, and rate. Intelligibility for spontaneous speech was reduced at both HFS and LFS when compared to STN-DBS off. Speech produced at HFS was more intelligible than that produced at LFS, but HFS made the intelligibility task (transcription) subjectively more difficult. Both voice quality and articulation were judged to be more abnormal with STN-DBS on. STN-DBS reduced the intelligibility of spontaneous speech at both LFS and HFS but lowering the frequency did not improve intelligibility. Voice quality ratings with STN-DBS were correlated with the ratings made without stimulation. This was not true for articulation ratings. STN-DBS exacerbated an existing voice disorder and may have introduced new articulatory abnormalities.

The purpose of this study was to report data analysis results from the International Health Regulations (2005) Ship Sanitation Certificates (SSC), recorded in the European Information System (EIS). International sea trade and population movements by ships can contribute to the global spread of diseases. SSC are issued to ensure the implementation of control measures if public health risk exists on board. EIS designed according to the World Health Organization (WHO) “Handbook for Inspection of Ships and Issuance of SSC”. Inspection data were recorded and SSC issued by inspectors working at European ports were analysed. From July 2011-February 2017, 107 inspectors working at 54 ports in 11 countries inspected 5579 ships. Of these, there were 29 types under 85 flags (including 19 EU flags). As per IHR (2005) 10,281 Ship Sanitation Control Exception Certificates (SSCEC) and 296 Ship Sanitation Control Certificates (SSCC) were issued, 74 extensions to existing SSC were given, 7565 inspection findings were recorded, and 47 inspections were recorded without issuing an SSC. The most frequent inspection findings were the lack of potable water quality monitoring reports (23%). Ships aged ≥12 years (Odds Ratio, OR = 1.77, 95%Confidence Intervals, CI = 1.37–2.29) with an absence of cargo at time of inspection (OR = 3.36, 95%CI = 2.51–4.50) had a higher probability of receiving an SSCC, while ships under the EU flag had a lower probability of having inspection findings (OR = 0.72, 95%CI = 0.66–0.79). Risk factors to prioritise the inspections according to IHR were identified by using the EIS. A global information system, or connection of national or regional information systems and data exchange, could help to better implement SSC using common standards and procedures.

Background: Commensal Neisseria species are part of the oropharyngeal microbiome and important for health, but also serve as a reservoir for antimicrobial resistance. Little is known about the prevalence of these species in the general population, how this varies by age and how antimicrobial susceptibility varies between species. Methods: We assessed the prevalence and antimicrobial susceptibility of commensal Neisseria species in the parents (n=38) and children (n=50) of 35 families in Belgium.Results: Various commensal Neisseria (n=5) could be isolated from the participants. Most abundant were N. subflava and N. mucosa. N. subflava was detected in 77 of 88 (87.5%) individuals and N. mucosa in 64 of 88 (72.7%). N. mucosa was more prevalent in children (41/50 [82%]) than parents (23/38 [60.5%]; P<0.05), while N. bacilliformis was more prevalent in parents (7/36 [19.4%]) than children (2/50 [4%]; P<0.05). N. bacilliformis showed high ceftriaxone minimum inhibitory concentrations (MICs; median MIC 0.5mg/L; IQR 0.38-0.75) and these high MICs explained the higher ceftriaxone MICs of all Neisseria isolates from the parents than the children. The median azithromycin MIC of all Neisseria isolates per individual was positively correlated with the median family MIC (rho=0.24; P=0.033). The same association was found for the analysis limited to N. subflava (rho=0.36; P=0.004) and N. mucosa (rho=0.30; P=0.027). Interpretation: The most abundant commensal Neisseria species found in this population were N. subflava and N. mucosa, of which the prevalence of N. mucosa varied by age. The prevalence of N. bacilliformis also varied by age and showed concerningly high ceftriaxone MICs which warrant further investigation. We found evidence of clustering of azithromycin, but not ceftriaxone, MIC by family.

Leigh Van Valen was an American evolutionary biologist who made major contributions to evolutionary theory and is particularly remembered by his groundbreaking paper "A New Evolutionary Law" (1973) where he provided evidence from fossil record data that this law maintains that the probability of extinction within any group remains es­sentially constant through time. In order to explain such unexpected result, Van Valen formulated a very influential idea that he dubbed the "Red Queen hypothesis". It states that the constant decay must be a consequence of evolutionary interactions among connected species within ecological networks. In Van Valen's picture, species do not merely evolve: they also coevolve with other species. As a consequence, when thinking in adaptation to an external environment, the other species must be considered as part (may be a major part) of such external world. Van Valen's law provided the first complex systems theory of coevolutionary dynamics and inspired a whole range of theoretical and experimental developments and scholars from very diverse fields, from economics to physics. In that respect, Leigh Van Valen's contribution percolated far beyond its original formulation. Red Queen arms races are nowadays considered a widespread feature of complex adaptive systems.

Fanconi anemia (FA) develops due to a mutation in one of the FANC genes that are involved in repair of interstrand crosslinks (ICLs). FANCG, a member of the FA core complex, is essential for ICL repair. Previous FANCG-deficient mouse models were generated with drug-based selection cassettes in mixed mice backgrounds, leading to a disparity in interpretation of genotype-related phenotype. To exclude these confounders, we created a Fancg-KO (KO) mouse model using CRISPR/Cas9. The entire Fancg locus was targeted and maintained on the immunological well-characterized C57BL/6J background. Intercrossing of heterozygous mice resulted in sub-Mendelian numbers of homozygous mice, suggesting loss of FANCG can be embryonic lethal. KO mice displayed infertility, hypogonadism but no other developmental problems. Bone marrow analysis revealed a defect in various hematopoietic stem and progenitor subsets with a bias towards myelopoiesis. Cell lines derived from Fancg-KO mice were hypersensitive to crosslinking agents-cisplatin and Mitomycin C, and Fancg-KO mouse embryonic fibroblasts (MEFs) displayed increased γ-H2AX upon cisplatin treatment. Reconstitution of these MEFs with Fancg cDNA corrected for the ICL hypersensitivity. Collectively, this project provides a new, genetically and immunologically well-defined Fancg-KO mouse model for further in vivo and in vitro studies on FANCG and ICL repair.

An exploratory Life Cycle Assessment was carried out to provide insight into the environmental impacts of using the green seaweed Ulva spp. as a feedstock for production of bioplastic. The study focused on the production of lactic acid as a precursor of polylactic acid. The studied production process consists of (1) the cultivation of Ulva spp. in Integrated Multitrophic Aquaculture, (2) the processing of the biomass for solubilisation of sugars, (3) the fermentation of the sugars to lactic acid and (4) isolation of lactic acid from the fermentation broth. The study identifies environmental hotspots and compares the experimental seaweed production chain with conventional feedstock. The main hotspot identified is electricity consumption during seaweed cultivation. This impact of electricity consumption can be lowered by reducing energy use and sourcing renewable energy, and by improving the material efficiency in the product chain. To improve understanding of the environmental impacts of the production process, future studies can broaden the system boundaries and broaden the scope of sustainability issues included in the environmental assessment.

We show that the van der Waals gas does not exhibit just the celebrated liquid-gas 1 transition but also a quantum-classical one. We study the issue with reference to the LMC statistical 2 complexity and in relation to the order-disorder contrast.

The aim of this study was to evaluate the use of a flexible synthetic polymer bone graft to provide implant stability in the absence of implant stability during implant placement in a dense cortical bone model. Sockets were prepared on polyurethane blocks according to the standard implant socket drilling protocol in the control group, both oversizing and deepening in group 2, and oversizing only in group 3. In groups 2 and 3, flexible synthetic polymer bone grafts were placed in the sockets prior to implant placement. The implants were placed at bone level in all groups. The highest torque value obtained was recorded as the insertion torque. 75 implant sites in 3 groups were included in the study. The torque values of the implants in the control group were significantly higher than those of the implants with the oversized and deepened sockets and the oversized-only sockets (p&lt;0.05; p&lt;0.01).The torque values of the implants with the oversized and deepened sockets were significantly higher than those of the implants with the oversized-only sockets (p&lt;0.01). In this study, flexible synthetic polymer bone graft was shown to be effective in achieving implant stability in the management of implants with loss of primary stability.

This study explores the impact of the ‘pre-intervention effects’ of a community-based interventions. This refers to participatory research processes and parallel publicity in the media on changes in alcohol use and relevant mechanisms (rules and norms about alcohol, accessibility of alcohol in a formal setting) among adolescents before any intervention is implemented. In a quasi-experimental study, adolescent data were collected twice by means of self-report among adolescents living in two municipalities (control and experimental condition). Regression analysis showed pre-intervention main effects on adolescents’ perceived accessibility of alcohol in a formal setting. Moreover, among adolescents aged 15 years and older, the normative decline in strictness of rules and norms was less steep in the experimental condition compared to the control condition. Also, adolescents aged 14 years and younger in the experimental condition reported more weekly drinking compared to their peers in the control condition. No differential effects across gender were found. To conclude, applying a co-creational approach in the development of an intervention, not only contributes to more effective interventions in the end, but involvement of and discussions in the community at the start of intervention planning are contributing to changes in targeted factors. This implies that public discussions about the development of intervention strategies should be considered as an essential feature of co-creation in community-based interventions.

In this short paper we study some properties of the lines associated with van Aubel’s theorem in the special case when squares are replaced with equilateral triangles constructed on the sides of an arbitrary quadrilateral.

Background: Quality of life (QoL) in IC/BPS patients is an evidence gap in guidelines, because studies are limited and outdated. Therefore, guidelines might not reflect the current situation accurately, and no possible improvements in QoL of these patients. Secondly, guidelines suggest multimodal approach in therapy, however unknown is how the efficacy of these therapies are perceived by the patient themselves. The aim of this study is to investigate the perception of IC/BPS patients on their QoL and to determine which treatments they received and how they evaluate the efficacy of these various (alternative) therapies.Methods: Quantitative retrospective database study in IC/BPS patients, compiled of existing patient survey data (n=217) from July 2021. Results: The QoL of patients is affected significantly by IC/BPS. This is evident from the substantial self-reported impact by patients, the various affected domains on EQ-5D 5L. The QoL was not negatively affected by delayed diagnosis, but there were differences between female and males. Secondly, there was the wide array of (alternative) treatments utilized, although some have doubtful results and high dropout rates. Conclusion: QoL is considerably impaired in IC/BPS patients. Coagulation therapy and intravesical GAG therapy were most appreciated treatments. The diverse responses and adherence to various treatments warrant a personalized approach (phenotype-oriented therapy). To achieve improvement in the QoL, it is important to incorporate the patient’s perspective in treatment guidelines.

South Africa is a water stressed country experiencing mass urbanisation especially towards coastal cities. The country is already enduring the impacts of global warming and climate change with risk of water scarcity in many areas. The risk was evident with Cape Town near encounter with ‘Day Zero’ i.e., the day when water supplies would have been switched off and residents required to queue for daily water rations. The drought exposed the inadequa-cies of the existing water supply system. Paradoxically, in the same drought period, vast amounts of unutilized stormwater that could have augmented water supply run unabated into the ocean through rivers around the city. The study determined that the problem was not necessarily water shortage but lack of adequate water storage. This study investigated the suitability of coastal reservoirs for stormwater harvesting on the over 3000 km South African coastline. The objective was to identify suitable locations for coastal reservoirs. The study un-dertook a systematic process of selecting several candidate locations and eliminating unsuita-ble sites based on international best practice i.e., coastal topography, climate, hydrology, fluvi-al environment, catchment size and river water quality. Nine candidate sites were identified and ranked based on suitability and associated benefits. The identified locations in order of ranking include Knysna River, Berg River, Buffalo River, Kowie River, Thukela River, Orange River, Port of Richards Bay, Port of Durban, and Lourens River. The Knysna site, with a mean annual precipitation of 600 - 800 mm/annum and mean annual runoff of 100 - 500 Mm3/annum, was determined to be the most optimal location.

(1) Background: The Gárdos channel (KCNN4) and Piezo1 are the best-known ion channels in the red blood cell (RBC) membrane. Nevertheless, the quantitative electrophysiological behavior of RBCs and its heterogeneity are still not completely understood.; (2) Methods: Here we use state-of-the-art biochemical methods to probe for the abundance of the channels in RBCs. Furthermore, we utilize automated patch-clamp, based on planar chips, to compare the activity of the two channels in reticulocytes and mature RBCs. Besides this characterization, we performed membrane potential measurements to demonstrate the effect of channel activity and interplay on the RBC properties.; (3) Results: Both, Gárdos channel and Piezo1, albeit their average copy number of activatable channels per cell is in the single digit range, can be detected by transcriptome analysis of reticulocytes. Proteomics analysis of RBCs could only detect Piezo1 but not the Gárdos channel. Furthermore, they can be reliably measured in the whole-cell configuration of the patch-clamp method. While for the Gárdos channel the activity is higher in reticulocytes compared to mature RBCs, for Piezo1 the tendency is the opposite. While the interplay between Piezo1 and Gárdos channel cannot be followed using the patch-clamp measurements, it could be proved based on membrane potential measurements in populations of intact RBCs.; (4) Conclusions: We discuss the Gárdos channel and Piezo1 abundance, interdependencies and interactions in the context of their proposed physiological and pathophysiological functions, which are the passing of small constrictions, e.g., in the spleen, and their active participation in blood clot formation and thrombosis.

Historically, urban development has always been centered on coastal areas – with access to waterbodies – seas, rivers and canals being a significant advantage for movement and trade. With most of the world’s megapolises located on coasts, land reclamation offers a solution for the expansion of city centers which are otherwise restricted by the coastline. The current understanding of urban regeneration and development on reclaimed lands is defined in this study, answering the basic questions of what, why and how. This study aims to assess the urban regeneration on reclaimed coastal land based on the principles of sustainable development defined by existing studies. The literature review establishes a theoretical framework and defines performance-based benchmarks identifying the spatial indicators of urban development. Composite indicators namely open space coverage, land use mix, percentage of coast for people, accessibility to public transportation and amenities, availability of pedestrian paths and cycling tracks and adequate road networks are considered for this framework. The conclusions are drawn based on the results of the analysis of spatial layout using GIS as a tool to map and empirically measure each indicator. The framework is validated using a major land reclamation project, West Bay, in the coastal urban area of ​​the city of Doha. The results determine that West Bay has achieved a good level of sustainability, although there are areas that could be enhanced to further improve the overall sustainability of urban development. These findings can serve as a guide for policymakers and various stakeholders for sustainable urban planning on reclaimed coastal lands.

The Van der Pol oscillator is a chaotic non-linear system. Small perturbations in initial conditions may result in wildly different trajectories. Because of its chaotic nature, controlling, or forcing, the behavior of a Van der Pol oscillator is difficult to achieve through traditional adaptive control methods. Connecting two Van der Pol oscillators together where the output of one oscillator, the driver, drives the behavior of its partner, the responder, is a proven technique for controlling the Van der Pol oscillator. Deterministic AI (DAI) is an adaptive feedback control method that leverages the known physics of the Van der Pol system to learn optimal system parameters for the forcing function. We assessed the performance of DAI employing three different online parameter estimation algorithms. Our evaluation criteria include mean absolute error (MAE) between the target trajectory and the response oscillator trajectory over time. RLS with exponential forgetting (RLS-EF) had the lowest MAE overall, with a 2.46% reduction in error. However, another method was notable. Least Mean Squares with normalized gradient adaptation (LMS-NG) had worse initial error in the first 10% of the simulation, but after that point had consistently better performance. We found that over the last 90% of the simulation, DAI with LMS-NG had a 48.7% reduction in MAE compared to feedforward alone.

The Vu Gia - Thu Bon River Basin (VG-TB) is confronting numerous challenges related to water security (WS), particularly in the face of the impacts of climate change. These challenges manifest in salinity intrusion, altered rainfall patterns, and reduced water supply in downstream areas. To assess the current state of water security in the basin, the study employed statistical analysis methods, Process Analysis Method (PAM), SMART, and Analytic Hierarchy Process (AHP) to develop a comprehensive Assessment Framework for Water Security (AFWS) in the VG-TB. The AFWS encompasses five key dimensions, 17 indicators, and 28 variables, aligning with the UN-Water definition of water security and addressing the Sustainable Development Goal 6 (SDG6) criteria for global water sustainability. It also adheres to the Asian Development Bank's (ADB) approach to water security assessment as outlined in the Asian Water Development Outlook (AWDO) reports. This allows for the computation of a comprehensive Water Security Index (WSI) for specific regions, serving as a foundation for decision-making and policy formulation aimed at enhancing water security in the context of climate change and facilitating sustainable basin development in the future.

Stumbling during gait is commonly encountered in patients who suffer from mild to serious walking problems, e.g. after stroke, in osteoarthritis, or amputees using a lower leg prosthesis. Instead of self-reporting, an objective assessment of the amount of stumbles in daily life would inform clinicians more accurately and enable the evaluation of treatments that aim to achive a safer walking pattern. An easy to use wearable might fullfill this need. The goal of the present study was to investigate whether a single inertial measurement unit (IMU) placed at the shank and machine learning algorithms could be used to detect and classify stumbling events in a dataset comprising of a wide variety of daily movements. Ten healthy test subjects were deliberately tripped by an unexpected and unseen obstacle while walking on a treadmill. The subjects stumbled a total of 276 times, both using an elevating recovery strategy and a lowering recovery strategy. Subjects also performed multiple Activities of Daily Living. During data processing, an event-defined window segmentation technique was used to trace high peaks in acceleration which could potentially be stumbles. In the reduced dataset, time windows were labelled with the aid of video annotation. Subsequently, discriminative features were extracted and fed to train seven different types of machine learning algorithms. Trained machine learning algorithms were validated using leave-one-subject-out cross-validation. Support Vector Machine (SVM) algorithms were most succesful, and could detect and classify stumbles with 100% sensitivity, 100% specificity and, 96.7% accuracy, in the independent testing dataset. The SVM algorithms were implemented in a user-friendly, freely available, stumble detection app named Stumblemeter. This work shows that stumble detection and classification based on SVMs is accurate and ready to apply in clinical practise.

Aggregation of the protein α-Synuclein (αSyn) is a hallmark of Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple systems atrophy, and alleviating the extent of αSyn pathology is an attractive strategy against neurodegeneration. The engineered binding protein β-wrapin AS69 binds monomeric αSyn. AS69 reduces primary and secondary nucleation as well as fibril elongation in vitro. It also mitigates aSyn pathology in a mouse model based on intrastriatal injection of aSyn pre-formed fibrils (PFF). Since the PFF-based model does not represent all aspects of PD, we tested here whether AS69 can reduce neurodegeneration resulting from αSyn overexpression. Human A53T-αSyn was overexpressed in the mouse Substantia nigra (SN) by using recombinant adeno-associated viral vector (rAAV). AS69 was also expressed by rAAV transduction. Behavioral tests and immunofluorescence stainings were used as outcomes.Transduction with rAAV-αSyn resulted in αSyn pathology as reported by phospho-αSyn staining and caused degeneration of dopaminergic neurons in the SN. The co-expression of rAAV-AS69 did not reduce αSyn pathology or degeneration of dopaminergic neurons. We conclude that αSyn monomer binding by rAAV-AS69 was insufficient to protect from aSyn pathology resulting from αSyn overexpression.

As the EU is moving towards a low carbon economy and seeks to further develop its renewable energy policy, this paper quantitatively investigates the impact of plausible energy market reforms from the perspective of bio-renewables. Employing a state-of-the-art biobased variant of a computable general equilibrium model, this study assesses the perceived medium-term benefits, risks and trade-offs which arise from an advanced biofuels plan, two exploratory scenarios of a more 'sustainable' conventional biofuels plan and a 'no-mandate' scenario. Consistent with more recent studies, none of the scenarios considered present significant challenges to EU food-security or agricultural land usage. An illustrative advanced biofuels plan simulation requires non-trivial public support to implement whilst a degree of competition for biomass with (high-value) advanced biomass material industries is observed. On the other hand, it significantly alleviates land use pressures, whilst lignocellulose biomass prices are not expected to increase to unsustainable levels. Clearly, these observations are subject to assumptions on technological change, sustainable biomass limits, expected trends in fossil fuel prices and EU access to third-country trade. With these same caveats in mind, the switch to increased bioethanol production does not result in significant market tensions in biomass markets.

PrEP uptake in the Netherlands is growing but remains at suboptimal levels. Hence, the analysis of hurdles is paramount. Given the initial focus of PrEP provision among men-who-have-sex-with-men (MSM) via a demonstration project that was launched in June 2015, AmPrEP in Amsterdam, and pharmacies in the main urban areas (so called “Randstad”, entailing Amsterdam, Utrecht, Leiden, The Hague and Rotterdam), investigating regional differences is necessary. This study seeks to unravel regional differences jointly with psycho-social determinants of PrEP uptake. This cross-sectional study included 3,232 HIV-negative Dutch MSM recruited via the EMIS survey in late 2017. Prevalence and standardized prevalence ratio (SPR) of PrEP awareness, intention and uptake were measured on a regional level (Randstad vs. the rest of the country). Multilevel logistic modelling was conducted to identify the association of PrEP uptake with PrEP awareness and intention, sociodemographic, psycho-social determinants, and random effects from regional differences. MSM from the Randstad used more PrEP (SPR=1.4 vs. 0.7) compared to the rest of the country, but there were minor differences for awareness and intention. The regional distinction was estimated to explain 4.6% of the PrEP use variance. We observed a greater influence from PrEP intention (OR=4.5, 95%CI 2.0-10.1), while there was limited influence from the awareness of PrEP (OR=0.4, 95%CI 0.04-4.4). Lower education (OR=0.4, 95%CI 0.2-0.9) was negatively associated with PrEP uptake, however, no significant difference was found between middle and high education (OR=1.2, 95%CI 0.7-2.0). We showed that regional differences – MSM in non-urban regions – and other psycho-social determinants account for lower PrEP uptake. Based on these findings, more fine-tuned PrEP access with a focus on non-urban regions can be implemented, and tailored campaigns increasing intention/use can be conducted among target populations.

Recently, doubts were raised about the existence of the bilingual advantage in cognitive control. The aim of the present review was to investigate the bilingual advantage and its modulating factors. We searched the Medline, ScienceDirect, Scopus, and ERIC databases for all original data and reviewed studies on bilingualism and cognitive control, with a cut-off date of October 31, 2018, thereby following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol. The results of the 46 original studies show that, indeed, the majority, 54.3%, reported beneficial effects of bilingualism on cognitive control tasks; however, 28.3% found mixed results, and 17.4% found evidence against its existence. Methodological differences seem to explain these mixed results: particularly, the varying selection of the bilingual participants, the use of non-standardized tests, and the fact that individual differences were often neglected, and that longitudinal designs were rare. Therefore, a serious risk for bias exists in both directions (i.e., in favor of and against the bilingual advantage). To conclude, we found some evidence for a bilingual advantage in cognitive control; however, if significant progress is to be made, better study designs, bigger data, and more longitudinal studies are needed.

Leaf color mutants (LCMs) are important resources for studying diverse metabolic processes such as chloroplast biogenesis and differentiation, pigments’ biosynthesis and accumulation, and photosynthesis. However, in Dendrobium officinale, LCMs are yet to be fully studied and exploited due to the unavailability of reliable RGs (reference genes) for qRT-PCR (quantitative real-time reverse transcription PCR) normalization. Hence, this study took advantage of previously released transcriptome data to select and evaluate the suitability of ten candidate RGs, including Actin (Actin), polyubiquitin (UBQ), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), elongation factor 1-α (EF1α), β-tubulin (β-TUB), α-tubulin (α-TUB), 60S ribosomal protein L13-1 (RPL13AD), aquaporin PIP1-2 (PIP1-2), Intima protein (ALB3) and Cyclin (CYCB1-2) for normalizing leaf color-related genes’ expression levels via qRT-PCR. Stability rankings analysis via common software Best-Keeper, GeNorm, and NormFinder disclosed that both ten genes met the requirements of RGs. Of them, EF1α exhibited the highest stability and was selected as the most reliable. The reliability and accuracy of EF1α were confirmed through qRT-PCR analysis of fifteen chlorophyll pathway-related genes. The expression patterns of these genes via EF1α normalization were consistent with the results by RNA-Seq. Our results will pave the way for molecular dissection of leaf color mutations in D. officinale.

A correctly obtained Land-use/land-cover (LULC) prediction map is essential to under-standing and assessing future patterns. In the study, the LULC map of Urmia/Iran in 2030 was produced using two different prediction methods CA-Markov and Artificial Neural Network (ANN). In general, the study followed a methodology consisting of three steps. In the first steps, Landsat satellite images acquired in 2000, 2010 and 2020 were classified with maximum likelihood algorithm and LULC maps were prepared for each year. In the second stage, to investigate the LULC prediction methods' validation (CA-Markov and ANN) the LULC prediction map of 2020 was produced using the LULC map of 2000 and 2010; In this step, the predicted LULC map of 2020 and the actual LULC map of 2020 were evaluated by correctness, completeness and quality indexes. Finally, The LULC map for 2030 was prepared using all two algorithms and the change map was extracted. The results show that the area of soil and vegetation decreased, and built-up regions increased during the research period. The methods validation results show that the two algorithms are much closer to each other. Nevertheless, in general, ANN has the highest completeness (96.21%) and quality (93.8%) and CA-Markov the most correctness (96.47). This study shows that the CA-Markov algorithm is most successful in predicting the future that had larger areas and a higher percentage in the region (urban and vegetation cover) and the ANN algorithm in predicting phenomena that had smaller levels with fewer percentages (soil and rock).

Adaptive Sliceable-Bandwidth Variable Transceivers (S-BVTs) are key enabler for future optical networks. In particular, those based on Discrete MultiTone (DMT) modulation and Direct Detection (DD) can be considered a flexible solution suitable to address the cost efficiency requirement of optical metro networks. In this paper, we propose to use this cost-effective S-BVT option/implementation in optical metro networks adopting switching nodes based on Semiconductor Optical Amplifier (SOA) technology. Bit loading (BL) and power loading (PL) algorithms are applied to the Digital Signal Processing (DSP) modules, to maximize the performance and/or the capacity as well as enhance the flexibility and adaptability of the system. Our analysis considers switching nodes based on SOAs with and without filtering elements and fiber spans of 25 km. We present the results up to 100 km, with and without SOA-based nodes. Firstly, we analyze the adaptive BVT transmission using the Margin Adaptive (MA) BL/PL algorithm at a fixed bit rate of 28 Gb/s. The possibility of controlling the SOAs current is a key factor to face the transmission impairments due to the fiber and the filtering elements. We also analyze the system considering Rate Adaptive (RA) transmission at a fixed target BER of 3.8·10⁻³, showing that a maximum capacity above 34 Gb/s can be achieved for a single span of 25 km. Although the cascading of filtering elements still constitutes a limiting factor, we show that an improvement of the net bit rate performance can be obtained thanks to the combined use of S-BVT and SOA technology at the switching nodes, resulting in a promising approach for designing future optical metro networks.

We consider the Dirac field in polar formulation, showing that when torsion is taken in effective approximation the theory has the thermodynamic properties of a van der Waals gas, that when the limit of zero chiral angle is taken the theory reduces to that of a Weyssenhoff fluid, and that under the spinless condition it gives the Newtonian particle. This nesting of approximations will allow us to interpret the various objects pertaining to the spinor, with torsion providing a form of negative pressure, and the chiral angle being related to a type of internal dynamics.

The effect of atomic and molecular microfied dynamics on spectral line shapes is under consideration. This problem is treated in the framework of the Frequency Fluctuation Model (FFM). For the first time the FFM is tested for the broadening of a spectral line by neutral particles. The usage of the FFM allows one to derive simple analytical expressions and perform fast calculations of the intensity profile. The obtained results was compared with Chen and Takeo theory (CT), which is in a good agreement with experimental data. It was demonstrated that for moderate values of temperature and density the FFM successfully describes the effect of the microfield dynamics on a spectral line shape.

The Kwee van Woerden (KvW) method for the determination of eclipse minimum times has been a staple in eclipsing binary research for decades, due its simplicity and independence of external input parameters. However, its estimates of the timing error have been known to be of low reliability. During the analysis of very precise photometry of CM Draconis eclipses from TESS space mission data, KvW’s original equation for the timing error estimate produced numerical errors, which evidenced a fundamental problem in this equation. This contribution introduces an improved way to calculate the timing error with the KvW method. A code that implements this improved method, together with several further updates over the original method is presented as well. An example application on the CM Draconis light curves from TESS is given, where we show that its timing error estimates of about 1 second are in excellent agreement with error estimates obtained by other means.

This paper introduces the complex Rayleigh-van der Pol-Duffing oscillators (RVDOs), which are hyperchaotic and can be either autonomous or non-autonomous. The fundamental dynamics of the autonomous and nonautonomous complex RVDOs including dissipation, symmetry, fixed points and their stability are studied. These oscillators are found in various important fields of physics and engineering. The paper proposes a scheme to achieve phase synchronization (PS) and antiphase synchronization (APS) for different dimensional models. These kinds of synchronization are considered as generalization of several other types of synchronization. For this scheme we use the active control method based on Lyapunov stability theory. By analytically determining the control functions, the scheme achieved PS and APS. Our scheme is applied to study PS of hyperchaotic behaviours for two distinct hyperchaotic non-autonomous and autonomous complex RVDOs. Additionally, the scheme is employed to achieve APS of chaotic real non-autonomous RVDO and hyperchaotic complex autonomous RVDO, including those with different dimensions. Our work presents numerical results that plot the amplitudes and phases of these hyperchaotic behaviours, demonstrating the successful achievement of PS and APS.

The i-4-1-Health project is a One Health project on the prevalence and spread of antimicrobial resistance in the human and veterinary domain in the Dutch-Belgian cross-border region. This paper describes the main components of the laboratory protocol that was developed to standardise the microbiological methods used for the detection of intestinal carriage of highly-resistant microorganisms.

Presenting a case report about a 14-year-old female patient presenting with a history of weakness in all four limbs since the age of 5. The patient has a history of difficulty in walking, wearing footwear, climbing stairs, and performing fine motor tasks. During the neurological examination showed mild spasticity, muscle weakness, areflexia, ill-sustained clonus, and sensory deficits. Radiological examination, including a contrast-enhanced MRI of the brain was done which showed findings that are consistent with Megalencephalic leukoencephalopathy with subcortical cysts, also known as Van der Knaap disease.

The Covid-19 pandemic is a tragedy for those who have been hard hit worldwide. At the same time, it is also a test of concepts and practices of what good care is and requires, and how quality of care can be accounted for. In this paper, we present our Care-Ethical Model of Quality (CEMQ) and apply it to the case of residential care for older people in the Netherlands during the Covid-19 pandemic. Instead of thinking about care in healthcare and social welfare as a set of separate care acts, we think about care as a complex practice of relational caring, crossed by other practices. Instead of thinking about professional caregivers as functionaries obeying external rules, we think about them as practically wise professionals. Instead of thinking about developing external quality criteria and systems, we think about cultivating (self-)reflective quality awareness. Instead of abstracting from societal forces that make care possible but also limit it, we acknowledge them and find ways to deal with them. Based on these critical insights, the CEMQ model can be helpful to describe, interrogate, evaluate, and improve existing care practices. It has four entries: (i) the care receiver considered from their humanness, (ii) the caregiver considered from their solicitude, (iii) the care facility considered from its habitability and (iv) the societal, institutional and scholarly context considered from the perspective of the good life, justice and decency. The crux is enabling all these different entries with all their different aspects to be taken into account. In Corona times this turns out to be more crucial than ever.

The signature of chaotic systems can be characterized either by the sensitivity of the initial conditions or by the change of its parameters. This feature can be used for manufacturing high sensitivity sensors. Sensors based on chaotic circuits have already been used for measuring water salinity, inductive effects, and both noise and weak signals. This article investigates an impedance sensor based on the Van der Pol and Duffing damped oscillators. The calibration process is a key point and therefore the folding behavior of signal periods was also explored. A sensitivity of 0.15 kΩ/Period was estimated over a range from 89.5 to 91.6 kΩ. This range can be adjusted according to the application by varying the gain of the operational amplifier used in this implementation. The development of this type of sensor might be used in medical and biological engineering for skin impedance measurements, for example. This type of chaotic sensor has the advantage of sensing small disturbances and then detect small impedance changes within biological materials which, in turn, may not be possible with other detectors.

The use of sensors in monitoring of lateral accelerations in delivery van transport focuses on measuring lateral accelerations on routes with roundabouts and curves to increase road safety. Using microelectromechanical system (MEMS) sensors, it measures the lateral accelerations acting on the vehicle and the load being transported during the test drives to study vehicle dynamics for cargo securing. Using an accelerometer and position tracking, accelerations can be detected when traversing curves and roundabouts at selected locations on the vehicle. The level of accelerations on the roof of the vehicle was found to be like those occurring on a lashed load with limited movements, where regression analysis can be used to determine the relationship between lateral accelerations at different sensor positions. If we compare the mean values of the lateral accelerations of the individual events between the sensors, the sensor on the side of the vehicle body at the height of the sensor on the load had approximately 5% lower mean values than the sensor on the roof. The sensor on the load measured approximately 5% higher mean values than the sensor on the roof. Hence, the mean lateral accelerations of the individual events for the sensor on the load are 10% higher than for the sensor at the same height on the vehicle body. From the above testing, we can say that the values of the mean lateral accelerations of the van from the sensor on the roof of the vehicle, are closer to the values of the accelerations of the sensor on the load than to the values of the sensor on the body of the vehicle at the same height.

The turbulent Poiseuille flow between two parallel plates is one of the simplest possible physical situations, and it has been studied intensively. In this paper, we propose a modified Prandtl-van Driest mixing length that satisfies both boundary conditions and wall damping effects. With our new formulations, we numerically solve the problem and, moreover, propose an approximate analytical solution of mean velocity. As applications of our solution, an approximate analytical friction coefficient of turbulent Poiseuille flow is proposed.

Objective: This study aimed to demonstrate the availability of portable devices for nasal FeNO measurement, which could replace exhaled NO measurement based on the continuous aspiration of multiple flow measurement systems. Methods: A descriptive cross-sectional study. The healthy subjects without rhinosinusis disorders (control group) and those with diagnosed allergic rhinitis (AR group) were enrolled in the study. They underwent nasal and bronchial FeNO measurements by both fixed flow NObreath® connected to nasal mask and multiple flows HypAir FeNO®. Results: A total of 153 people were recruited including 63 healthy subjects and 90 subjects with AR. There were no statistically significant differences in anthropometric characteristics between the two groups (P > 0.05). There were a significant increase in FeNO values in the AR group compared to the control group; concentrations of nasal and bronchial FeNO mearsured by NObreath® were 76.0 ± 50.7 ppb (vs 36.0 ± 28.1 ppb, P < 0.01) and 32.3 ± 15.4 ppb (vs 9.2 ± 5.6 ppb, P < 0.001), and those mearsured by NObreath® Hypair FeNO® were 1796.9 ± 523.3 ppb (vs 400.2 ± 123.1 ppb, P < 0.001) and 37.3 ± 23.0 ppb (vs 17.4 ± 18.3 ppb, P < 0.01). A weak correlation between the values measured by NObreath® and Hypair FeNO® devices was observed (r = 0.023 and r = 0.089, respectively; p < 0.05). Conclusions: The handheld NObreath® device is effective in measuring FeNO concentrations in both normal subjects and AR patients. The advantages in price and size, creating a compact, low-cost device that is convenient for use and research.

Our aim was to compare the inter-rater agreement of Transvaginal ultrasonography (TVS) with Magnetic Resonance Imaging (MRI) regarding diagnosing adenomyosis and for various predefined imaging features of adenomyosis in the same set of women. MRIs were assessed by four experienced radiologists and 2D TVS videoclips and 3D ultrasound volumes were assessed by five experienced sonographers. Each rater subjectively evaluated the presence or absence of adenomyosis, assessed various imaging. Fleiss kappa (κ) was used to reflect inter-rater agreement for categorical data and the Intraclass correlation coefficient (ICC) to reflect the reliability of quantitative data. Agreement between raters for diagnosing adenomyosis was higher for TVS than for MRI (κ =0.42 vs.0.28). MRI had a higher inter-rater agreement in assessing wall asymmetry irregular Junctional Zone (JZ) presence of myometrial cysts, while TVU had a better agreement for globular shape. MRI showed a moderate-good reliability for measuring the JZ (ICC=0.57-0.82). For TVS, JZ was unmeasurable in &gt; 50% of cases and the remaining cases had a low reliability (ICC=-0.31-0.08). We found that Inter-rater agreement for diagnosing adenomyosis was higher for TVS than for MRI, despite that MRI showed a higher inter-rater agreement in most specific features. Measurements of JZ in the coronal plane with 3D TVS were unreliable and thus unlikely to be useful for diagnosing adenomyosis.

Objective: Infliximab (IFX) concentrations are a predictive factor (PF) of pharmacokinetic (PK) origin in the treatment of Crohn’s disease (CD). We evaluated clearance, another PF of PK origin, either alone or in combination with concentrations. Methods: PF of PK origin were evaluated from two cohorts, the first received standard dosing (n=37), and the second was designed to proactively target therapeutic IFX concentrations (n=108). Concentrations were measured using homogenous mobility shift assay. Clearance was estimated using nonlinear mixed effects methods with Bayesian priors. C-reactive protein based clinical remission (<3mg/L in the absence of symptoms) was used for the disease control outcome. Longitudinal changes in disease control due to factors including time, IFX concentration, and clearance were analyzed using repeated event analysis. Change in objective function value (∆OFV) was calculated to compare concentration and clearance. Results: Lower baseline clearance and proactive dosing associated with enhanced disease control during induction (p<0.01). Higher IFX concentrations and lower Clearance measured at the second, third and fourth infusion yielded improved disease control during maintenance (p<0.032). During maintenance, the association with disease control was better with clearance than with concentrations (∆OFV= -19.2; p<0.001), and the combination of both further minimized OFV (p<0.001) with markedly improved clinical yield in the presence of both PF of PK origin. Conclusion: PF of PK origin and lower clearance during induction and maintenance yielded enhanced disease control in pediatric CD treated with IFX. The combination of IFX concentration and clearance are better predictors of therapeutic outcome compared to either one alone.

Introduction: VULTO-VAN SILFHOUT-DE VRIES SYNDROME (VSVS;OMIM#615828) is an extremely rare hereditary disease associated with impaired intellectual development and speech, delayed psychomotor development and behavioral anomalies, including autistic behavioral traits and poor eye contact. To date, 27 patients with VSVS have been reported in the world literature. Materials and Methods: We describe a 23y.o. male patient with autism spectrum disorder (ASD) who was admitted to the gastroenterological hospital with signs of pseudomembranous colitis. ASD was first noted in the patient at the age of 2.5y.o. Later he developed epileptic seizers and prominent growth retardation. Prior to the hospitalization he was excluded chromosomal aberrations, Martin-Bell syndrome, aminoacidopathies/aminoacidurias associated with ASD. Whole genome sequencing was prescribed to the patient at 23y.o. Results: The patient appeared to be a heterozygous carrier of “de novo” variant c.662C>T (p.S221L) in ex 4 of the DEAF1 gene. c.662C> T had not been previously described in genomic databases. According to the ACMG criteria this missense variant was considered to be pathogenic. VSVS was diagnosed in the patient. Conclusions: The phenotype of the patient is very similar to the data presented in the world literature. However, growth retardation and cachexia, not previously described in the articles, are of interest.

The path towards decarbonization requires a progressive adaptation of all refrigeration systems, but only stationary ones have been intensely studied to improve their environmental performance. However, refrigerated transport is a vital piece of the cold chain, and it must be considered in the green transition. In this paper, we propose a model for a hybrid refrigerated van that includes photovoltaic panels and electric batteries to decrease total greenhouse gas emissions from the engine. Thermal, electrical, and battery sub-models are considered and integrated into the comprehensive hybrid solar-powered refrigerated van model. Different technologies are compared in economic terms, including Lithium and Lead-acid batteries and three different types of photovoltaic panels. The model was validated regarding van fuel consumption, showing a 4% deviation. Single and multiple delivery scenarios are considered to assess the energetic, economic, and environmental benefits. Monthly CO2,e emissions could be reduced to 20% compared to a standard refrigerated van. Despite the environmental benefits provided by this sustainable solution, the payback period is still too long (above 20 years) because of the necessary investment to adapt the vehicle and considering fuel and electricity prices currently.

We fabricate paper-supported semiconducting devices by rubbing a layered molybdenum disulfide (MoS₂) crystal onto a piece of paper, similarly to the action of drawing/writing with a pencil on paper. We show that the abrasion between the MoS₂ crystal and the paper substrate efficiently exfoliates the crystals, breaking the weak van der Waals interlayer bonds and leading to the deposition of a film of interconnected MoS₂ platelets. Employing this simple method, that can be easily extended to other 2D materials, we fabricate MoS₂-on-paper broadband photodectectors with spectral sensitivity from the ultraviolet (UV) to the near-infrared (NIR). We also used these paper-based photodetectors to acquire pictures of objects by mounting the photodetectors in a homebuilt single-pixel camera setup.

To assess the community health workers’ (CHWs) knowledge, attitude, and practices (KAP) in type-2 diabetes (T2D) and hypertension (HTN) management. We thus also sought to assess the potential health system barriers for incorporating CHWs in T2D and HTN management. Mixed-method study comprised (1) a survey among 153 active CHWs to assess their KAP of T2D and HTN, and (2) semi-structured interviews with key informants to understand challenges of the health system and proposed solutions in incorporating CHWs in T2D and HTN management. The majority of CHWs correctly answered general knowledge questions on NCDs, risk factors, and prevention; however, only one-quarter correctly answered questions on smoking, family history, or tobacco use as risk factors. Most respondents appeared to have positive attitudes and have been practicing some activities related to T2D and HTN. Both financial and non-financial resource constraints were cited as challenges of the health system; therefore, re-structuring the role definition of CHWs and task of responsibilities, and assessment the need and workload have been proposed as ways forwards to effectively incorporate CHWs in T2D and HTN care. CHWs in Cambodia have shown their potential in T2D and HTN management; however, a well-designed strategy including technical training, clearly defined roles and responsibilities, and strong supporting structure are important to maximize their potential in the health system.

Background: A significant proportion of SARS-CoV-2-infected patients develops respiratory failure. Thromboembolism is also prevalent in coronavirus disease 2019 (Covid-19). Vitamin K plays a role in coagulation and possibly also in lung diseases. We therefore hypothesized that vitamin K is implicated in Covid-19 pathogenesis. Methods: 134 Covid-19 patients and 184 controls were included. Inactive vitamin K-dependent matrix Gla protein (i.e.dp-ucMGP) and prothrombin (i.e. PIVKA-II) were measured, which are inversely related to respectively extrahepatic and hepatic vitamin K status. Desmosine was measured to quantify elastic fiber degradation. Lung involvement and arterial calcifications severity were assessed by computed tomography. Results Dp-ucMGP was elevated in Covid-19 patients compared to controls (P=0.001). Higher dp-ucMGP was found in Covid-19 patients with poor compared to better outcomes (P=0.002). PIVKA-II was normal in 81.8%, mildly elevated in 14.0% and moderately elevated in 4.1% of Covid-19 patients not using vitamin K antagonists. Dp-ucMGP in Covid-19 patients was correlated with desmosine (P<0.001), thoracic aortic calcification (P<0.001) but not with pneumonia severity. Conclusions: Extrahepatic vitamin K status was severely reduced in Covid-19 patients, as reflected by elevated inactive MGP, and related to poor outcome. Procoagulant prothrombin activity remained preserved in the majority of Covid-19 patients, which is compatible with the increased thrombogenicity that is frequently observed in severe Covid-19. Impaired MGP activation was linked to accelerated elastic fiber degradation and premorbid vascular calcifications. A trial should assess whether increasing MGP and protein S activity by vitamin K administration improves Covid-19 outcomes.

Background: Radiotherapy in the head-and-neck area is one of the main curative treatment options. However, this comes at the cost of varying levels of normal tissue toxicity, affecting up to 80% of patients. Mucositis can cause pain, weight loss and treatment delay leading to worse outcomes and decreased quality of life. Therefore, there is an urgent need for an approach to predict normal mucosa response in patients prior to treatment. Methods: We here describe an assay to detect irradiation response in patient healthy oral mucosa tissue. Mucosa specimens from the oral cavity were obtained after surgical resection, cut into thin slices, irradiated, and cultured for three days. Seven samples were irradiated with X-ray and three additional samples were irradiated with both X-ray and protons. Results: Healthy oral mucosa tissue slices maintained normal morphology and viability for three days. We measured a dose-dependent response to X-ray irradiation and compared X-ray and proton irradiation in the same mucosa sample, using standardized automated image analysis. Furthermore, increased levels of inflammation inducing factors - major drivers in mucositis development - could be detected after irradiation. Conclusion: This model can be utilized for investigating mechanistic aspects of mucositis development and can be developed into an assay to predict radiation-induced toxicity in normal mucosa.

Most striking observations in COVID-19 patients are the hints on pulmonary edema (also seen on CT scans as ground glass opacities), dry cough, fluid restrictions to prevent more severe hypoxia, the huge PEEP that is needed while lungs are compliant, and the fact that anti-inflammatory therapies are not powerful enough to counter the severity of the disease. We propose that the severity of the disease and many deaths are due to a local vascular problem due to activation of B1 receptors on endothelial cells in the lungs. SARS-CoV-2 enters the cell via ACE2, a cell membrane bound molecule with enzymatic activity that next to its role in RAS is needed to inactivate des-Arg⁹ bradykinin, the potent ligand of the bradykinin receptor type 1 (B1). In contrast to bradykinin receptor 2 (B2), the B1 receptor on endothelial cells is upregulated by proinflammatory cytokines. Without ACE2 acting as a guardian to inactivate the ligands of B1, the lung environment is prone for local vascular leakage leading to angioedema. Angioedema is likely a feature already early in disease, and might explain the typical CT scans and the feeling of people that they drown. In some patients, this is followed by a clinical worsening of disease around day 9 due to the formation antibodies directed against the spike (S)-antigen of the corona-virus that binds to ACE2 that could contribute to disease by enhancement of local immune cell influx and proinflammatory cytokines leading to damage. In parallel, inflammation induces more B1 expression, and possibly via antibody-dependent enhancement of viral infection leading to continued ACE2 dysfunction in the lung because of persistence of the virus. In this viewpoint we propose that a bradykinin-dependent local lung angioedema via B1 and B2 receptors is an important feature of COVID-19, resulting in a very high number of ICU admissions. We propose that blocking the B1 and B2 receptors might have an ameliorating effect on disease caused by COVID-19. This kinin-dependent pulmonary edema is resistant to corticosteroids or adrenaline and should be targeted as long as the virus is present. In addition, this pathway might indirectly be responsive to anti-inflammatory agents or neutralizing strategies for the anti-S-antibody induced effects, but by itself is likely to be insufficient to reverse all the pulmonary edema. Moreover, we provide a suggestion of how to ventilate in the ICU in the context of this hypothesis.

Rice, as a staple crop feeding billions, faces constant threats from various diseases jeopardizing global food security. Precise understanding of disease resistance mechanisms is crucial for developing resilient rice varieties. Traditional genetic mapping methods, such as QTL mapping, provide valuable insights into the genetic basis of diseases. However, the complex nature of rice diseases demands a holistic approach to gain accurate knowledge of it. Omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, enable a comprehensive analysis of biological molecules, uncovering intricate molecular interactions within the rice plant. Integration of various mapping techniques using multi-omics data has revolutionized our understanding of rice disease resistance. By overlaying genetic maps with high-throughput omics datasets, researchers can pinpoint specific genes, proteins, or metabolites associated with disease resistance. This integration enhances the precision of disease-related biomarkers with better understanding of their functional roles in disease resistance. Improvement of rice breeding for disease resistance through this integration represents a significant stride in agricultural science because better understanding of the molecular intricacies and interactions underlying disease resistance architecture leads to more precise and efficient development of resilient and productive rice varieties. In this review, we explore how the integration of mapping and omics data can give a transformative impact on rice breeding for enhancing disease resistance.

Homogeneous water dispersions of MWCNTs were prepared by ultrasonication in the presence of an amphiphilic polystyrene-block-poly(acrylic acid) (PS-b-PAA) copolymer. The ability of PS-b-PAA to disperse and stabilize MWCTNs was investigated by UV-vis, SEM and zeta potential. It is shown that the copolymer can disperse nanotubes directly by sonication in water. The results show that the addition of a styrene block to PAA enhances the dispersion efficiency compared to pure PAA, possibly due to the nanotube affinity with the polystyrene moiety. Notably, the dispersions show an evident pH-responsive behavior, being MWCNTs reaggregation promoted in basic environment. Furthermore, composites obtained by drop casting display electrical conductivity responsive to pH variations, showing the potential of such materials for sensing applications.

This study examined the efficacy of essential oil (EO) obtained from the Australian native plants, lemon myrtle (Backhousia citriodora) (LM) to inhibit Penicillium digitatum by in vitro agar diffusion and vapor assay, and in inoculated oranges. Gas chromatograph/mass spectrometry analysis revealed the main constituent of LM EO as citral. Pure citral was also included in the experiment for com-parison. LM EO at 1, 2, 3, 4 and 5 µL disc-1 in the in vitro tests significantly inhibited fungal growth compared to the non-treated control. Moreover, LM EO at 4 and 5 µL disc-1 in both the assays completely inhibited fungal growth similar to its main component of citral. Inoculated oranges dipped in 1000 μL L-1 LM EO solutions for 5, 10, 15 and 30 sec showed significantly lower fungal wounds compared to control. While higher dipping times generated slight rind injury, a 5 and 10 sec dip did not cause any injury to the fruit rind. The quality assessments and sensory evaluations also revealed that the addition of LM EO did not adversely affect the quality and taste of the oranges. These findings suggest LM EO as an alternative to synthetic fungicides to inhibit wastage in citrus during storage.

Lightning is responsible for most annually burned area by wildfires in the extratropical region of the Northern Hemisphere. Hence, predicting the occurrence of wildfires requires reliable forecasting of the chance of cloud-to-ground lightning strikes during storms. Here, we describe the development and verification of a probabilistic lightning-strike algorithm designed to run on a uniform 20-km grid over the Continental USA and Alaska. The algorithm consists of a large set of logistic equations parameterized via logistic regression using long-term data records of observed lightning strikes and meteorological reanalysis fields from NOAA. Principal Component Analysis was employed to extract 13 Principal Components (strong predictors) from a list of 611 potential predictors. Our statistical analysis revealed that the occurrence of cloud-to-ground lightning strikes primarily depends on three factors: horizontal temperature distribution by pressure levels, amount of low-level atmospheric moisture, and wind vectors. These physical variables impact the vertical separation of electric charges in the lower troposphere during storms causing the voltage potential between ground and the cloud deck to increase to a level that triggers electrical discharges. Results from a forecast verification using independent data showed excellent model skill, thus making this algorithm suitable for inclusion into software systems forecasting the chance of wildfire ignitions.

Grain quality, cooking quality and nutritional quality traits are some of the major attributes that enhance uptake and utilisation of improved cowpea varieties. Therefore, there is need for a better understanding of the genetic variation and inter-relationships among these quality traits in cowpea to integrate them in cowpea breeding programs. The study was conducted to determine genetic variability among 306 cowpea genotypes for grain quality, cooking quality and nutritional quality traits and to understand the interrelationships among these traits for exploitation in breeding programs. The results showed highly significant differences (P

Molecular dynamics(MD) simulations are carried out to characterize the mechanicalproperties and failure behavior of van der Waals heterostructures composed ofgraphene and hexagonal boron nitride(hBN) single layer sheets. The graphene–hBNand hBN–graphene–hBN heterostructures simulations are carried out under tensileand shear deformation. Accordingly, stress versus strain curves of each systemare plotted and various properties of heterostructures, namely elastic modulusand shear modulus as well as failure stress and failure strain, are evaluatedand compared with one another as well as with the pristine graphene and hBNsheets. Subsequently, the failure mechanism/characterization of each sheet in theheterostructures is described. Alternatively, the elastic and shear modulus of eachheterostructure are computed by means of rule of mixture(ROM) which are in goodagreement with results that are obtained from MD simulations.

Neurology is a quickly evolving specialty that requires clinicians to make precise and prompt diagnoses and clinical decisions based on the latest evidence-based medicine practices. In all Neurology subspecialties, Stroke and Epilepsy in particular, clinical decisions affecting patient outcomes depend on neurologists accurately assessing patient disability. Artificial intelligence (AI) can predict the expected neurological impairment from an AIS (Acute Ischemic Stroke), the possibility of ICH (IntraCranial Hemorrhage) expansion, and the clinical outcomes of comatose patients. This review article informs readers of artificial intelligence principles and methods. The article introduces the basic terminology of artificial intelligence before reviewing current and developing AI applications in neurology practice. AI holds promise as a tool to ease a neurologist’s daily workflow and supply unique diagnostic insights by analyzing data simultaneously from several sources, including neurological history and examination, blood and CSF laboratory testing, CNS electrophysiologic evaluations, and CNS imaging studies. AI-based methods are poised to complement the other tools neurologists use to make prompt and precise decisions that lead to favorable patient outcomes.

Damaged connective tissues between the bone and tendons or ligaments are common among adults regardless of activity level. Achilles tendinosis is one of the most common tissue defects and enthesopathies. The patient in this study is a 54-year-old female with chronic Achilles tendinosis from chronic enthesopathy at the Achilles tendon insertion with a retrocalcaneal exostosis for three years who has failed standard-of-care practices for over two years. The patient received extracorporeal pulsed-activated therapy (EPAT) before applying 2ml of CryoText, a Wharton’s jelly tissue allograft. The patient then received class IV laser therapy treatments twice weekly for three weeks. The patient started with a 10/10 VAS at the initial visit. At five weeks post-application, the patient’s score had improved by 80% at 2/10 VAS. By week 13, the patient rated her pain as 0/10 VAS. The improvement in patient-reported pain and functionality reported in this study after the application of Wharton’s Jelly, EPAT, and class IV laser therapy warrants future research studying the safety and efficacy of these patient care modalities together.

Pulmonary hypertension (PH) is a serious condition linked to immune-system dysfunction. Myositis-specific/associated antibodies (MSA/MAA) play a role in idiopathic inflammatory myopathy (IIM) and interstitial lung disease (ILD), but their significance in PH remains unclear. We believe the presence of these antibodies, may be underestimated. This study analyzed adult PH patients without pre-existing IIM for MSA/MAA prevalence using a line-blot assay. We compared PH patients with and without ILD signs to a cohort clinically suspected of IIM/ILD (n=558). Our PH cohort (n=121) showed a significantly higher prevalence of overall weak positive MSA/MAAs and positive overlap syndrome-associated MAAs than the suspected IIM/ILD group (p

The number of engineers who are transitioning into environmental sustainability careers is growing, though a gap still exists between supply and demand. This presents an opportunity for undergraduate engineering students to fulfill the demand as environmental sustainability professionals. This qualitative exploratory study investigated environmental sustainability learning experiences and future career interests in environmental sustainability. The social cognitive theory (SCCT) was utilized as a theoretical lens, exploring undergraduate students’ environmental sustainability interests, related learning experiences and their interest in pursuing a future career in environmental sustainability. Twenty-five undergraduate engineering students in various engineering disciplines were interviewed for this study. Data were analyzed to (1) identify students’ interest in pursuing a career in environmental sustainability, (2) determine if students’ interests have changed since they began their undergraduate studies, and (3) explore how learning experiences have impacted students’ future career choice. The findings posit that exposure to environmental sustainability learning experiences is impactful and plays an important role, impacting students' interests in pursuing careers in sustainability. Results reveal that elements such as personal beliefs and salary considerations inspire career choices. This research contributes to addressing the demand for additional working professionals who are prepared to tackle environmental sustainability issues, highlighting the role of learning experiences in shaping students' career interests.

This paper addresses the fate of extended space-time symmetries, in particular conformal symmetry and supersymmetry, in two-dimensional Rindler space-time appropriate to a uniformly accelerated non-inertial frame in flat 1+1-dimensional space-time. Generically, in addition to a conformal co-ordinate transformation, the transformation of fields from Minkowski to Rindler space is accompanied by local conformal and Lorentz transformations of the components, which also affect the Bogoliubov transformations between the associated Fock spaces. I construct these transformations for massless scalars and spinors, as well as for the ghost and super-ghost fields necessary in theories with local conformal and supersymmetries, as arising from coupling to 2-D gravity or supergravity. Cancellation of the anomalies in Minkowski and in Rindler space requires theories with the well-known critical spectrum of particles arising in string theory in the limit of infinite strings, and is relevant for the equivalence of Minkowski and Rindler frame theories.

When using computer-aided translation systems in a typical, professional translation workflow, there are several stages at which there is room for improvement. The SCATE (Smart Computer-Aided Translation Environment) project investigated several of these aspects, both from a human-computer interaction point of view, as well as from a purely technological side. This paper describes the SCATE research with respect to improved fuzzy matching, parallel treebanks, the integration of translation memories with machine translation, quality estimation, terminology extraction from comparable texts, the use of speech recognition in the translation process, and human computer interaction and interface design for the professional translation environment. For each of these topics, we describe the experiments we performed and the conclusions drawn, providing an overview of the highlights of the entire SCATE project.

Background: Bacteria can survive antibiotic exposure by mechanisms like tolerance without a shift in antimicrobial susceptibility. In this study, we investigated the presence of tolerance to three antimicrobials, ceftriaxone (CRO), azithromycin (AZM), and ciprofloxacin (CIP), in clinical isolates and WHO reference panel of N. gonorrhoeae and explored the prevalence between urogenital and anorectal infection sites. Methods: We examined 66 N. gonorrhoeae clinical isolates, evenly divided between anorectal and urogenital infection sites, using a modified tolerance disk (TD test) for three antibiotics. The isolates underwent a three-step incubation process wherein the isolates were exposed to an antibiotic disc for 20 hours of incubation (Step I), followed by the replacement of the antibiotic disc with a nutrient disc for overnight incubation (Step II) and additional overnight incubation with extra nutrients (Step III). Results: Four isolates were lost due to contamination. Of 62 clinical isolates, 7 exhibited tolerance to AZM, with 6 from anorectal and 1 from urogenital sites (p = 0.0496). Tolerance to CRO was observed in 11 isolates, which was significantly associated with the infection site, with 9 from the anorectum, and 2 from the urogenital site being tolerant (p = 0.02). Tolerance to CIP was found in 11 isolates, but was not significantly associated with the infection site. Tolerance was also detected in 8 (K, M, N, O, P, U, V, W) out of the 14 WHO (World Health Organization) reference strains, with varying patterns of tolerance to CRO (n=8), CIP (n=2) and AZM (n=1). Conclusion: This study identified CRO, AZM, and CIP tolerance in clinical Neisseria gonorrhoeae isolates. Significant variations in tolerance proportions between anorectal and urogenital infection sites, particularly for CRO, were observed. Additionally, tolerance was detected in WHO reference strains.

In the dynamic interplay between people and their physical environments, the Global South stands as a mosaic undergoing a multitude of transformative influences in architecture and urbanism where examining social sustainability becomes imperative. While prevailing attention remains on environmental and economic sustainability, this study addresses a persistent gap in the urban literature by focusing on the dynamic and manifold nature of social sustainability. Positioning itself within the context of sustainable development, the study links the pursuit of social aspects of sustainability with selected unique urban contexts from the Global South. Five cases that include Alexandria (Egypt), Tripoli (Libya), Basra (Iraq), Lilongwe (Malawi), and Accra (Ghana) are discussed through multi-layered investigations that involve attitude surveys, interviews, focus groups, participatory systematic observations, and behavioral mapping, engaging directly with inhabitants and stakeholders. Uncovering people-place narratives in the identified contexts, the cases are developed into five knowledge typologies that serve as practical tools for planning and design decision-making, policy formulation, and academic discourse. Discussions are conceived to demonstrate the transformative role people-place narratives play in fostering a more sustainable and equitable urban future. Conclusions are drawn to offer practical insights for stakeholders involved in various capacities in shaping the urban landscape of the Global South.

The Food Boost Challenge (FBC) was developed using a participatory action research approach to enhance healthy eating behaviors, here vegetable and fruit products (V&amp;F-products) among adolescents, particularly those with lower education levels. FBC is a quadruple helix innovation process, involving adolescents, (peer)researchers, and food system partners of non-governmental and commercial organizations. In 2021-2022, 34 partners provided both cash and in-kind contributions to join the FBC-community. Phase 1 involved 200 students identifying barriers and drivers for consumption of F&amp;V-products among 1000 pre-vocational adolescents, aged 12-20 years. In phase 2, student teams submitted innovative ideas, resulting in 25 concepts fitting into ≥1 of 4 routes: I) innovative technology for a healthy diet, II) new food products/concepts for adolescents, III) hotspots improving F&amp;V-product experience, and IV) new routes to market. In phase 3 consortia of adolescents, students and partners were formed to develop 10 selected concepts into prototypes, and phase 4 offered teams a national platform. Results show FBC resonates with all stakeholders, generating valuable insights to increase F&amp;V-intake. Prototypes in all 4 routes have been developed, with some already in the implementation stage. Additionally, other regions in the Netherlands have adopted the FBC approach. Overall, FBC is an approach that transforms ideas into actionable measures and shows potential to be adapted to promote various healthy eating behaviors among school students.

Astronauts are at risk of losing 1.0 to 1.5% of their bone mass for every month they spend in space despite their adherence to high impact exercise training programs and dietary regimens designed to preserve their musculoskeletal system. This loss is the result of microgravity-related impairment of osteocyte and osteoblast function and the consequent upregulation of osteoclast-mediated bone resorption. This review describes the ontogeny of osteoclast hematopoietic stem cells, the contributions of macrophage colony stimulating factor, activator of NFkB and the calcineurin pathways make in osteoclast differentiation, and provides details of bone formation, the osteoclast cytoskeleton, the immune regulation of osteoclasts, and osteoclast mechanotransduction on Earth, in the microgravity of space, and in conditions of simulated microgravity. The article discusses the need to better understand how osteoclasts are able to function in zero gravity and reviews current and prospective therapies that may be used to treat osteoclast-mediated bone disease.

Our study reviews the significance of archaeological parks in the tourism sector, with a specific focus on how digital presence and visitor feedback impact their cultural and touristic appeal. Utilizing statistical analyses such as regression and cluster analysis on data sourced from both Hungarian and Western European parks, the research scrutinizes TripAdvisor and Google ratings, alongside the volume of photographs and reviews. The findings highlight a modest correlation between digital visibility and overall visitor ratings, underscoring the complex relationship between online engagement and the quality of visitor experience. Notably, the cluster analysis identified two distinct groups, signifying diverse levels of visitor engagement and digital visibility across the parks. The conclusions drawn advocate for a comprehensive strategy to enhance visitor experiences, emphasizing the integration of digital engagement with the promotion of the parks cultural and historical values. By exploring the influence of digital presence on the appeal of archaeological parks, our study sheds light on the evolving interface between urban studies and digital heritage, highlighting how digital tools and online platforms are becoming increasingly integral in shaping the perceptions and experiences of urban cultural sites.

Most empirical work on sources of economic growth for different countries lack country-specific empirical evidence to guide policy choices in individual developing countries and previous studies of factor productivity tend to focus on the entire economy or a single sector. In this study, we use the recently developed growth accounting tools to explicitly determine the sources of economic growth at both national and sectoral levels in Zambia between 1970 and 2013. We use data from World Development Indicators and Zambia’s Central Statistical Office. On average, total factor productivity (TFP) contributes about 5.7% to economic growth. Sectoral analysis shows that agriculture contributes the least to GDP and that within each sector; factors that contribute to growth differ. Structural transformation has been slow and contributed to the observed inefficiency. We outline the implications of the observed growth and provide recommendations.

The production and secretion of very-low density lipoproteins (VLDL) by hepatocytes has a direct impact on liver fat content as well as the concentration of cholesterol and triglycerides in the circulation and thus affects liver and cardiovascular health, respectively. Importantly, excess caloric intake and lack of physical activity are associated with overproduction of VLDL, hepatic steatosis, and increased levels of atherogenic lipoproteins. Cholesterol as well as triglycerides in remnant particles after VLDL lipolysis are risk factors for atherosclerotic cardiovascular disease (ASCVD) and have garnered increasing attention over the last few decades. To date, however, increased risk of ASCVD is not the only concern when considering today’s cardiometabolic patients, as they often also suffer from hepatic steatosis. This notion highlights the importance of understanding the molecular regulation of VLDL biogenesis. Fortunately, there has been a resurgence of interest in the intracellular assembly, trafficking, degradation, and secretion of VLDL by hepatocytes, that has led to many exciting new molecular insights, the topic of this review. We think that increasing our understanding of the biology of this pathway will help improve the health of the cardiometabolic patient in the long term.

This study presents the development and pilot implementation of an assessment and shared deci-sion-making methodology called the Gezamenlijk Inschatten van Zorgbehoeften (GIZ), designed for youth (health) care professionals working with children and families. The three-phase approach included a needs assessment, development of the GIZ methodology, and pilot implementation in a preventive youth health care and youth care setting, involving parents, adolescents, and youth (health) care professionals. The needs assessment produced nine criteria that the GIZ methodology needed to meet. Based on these criteria, the GIZ methodology was developed and described using the Template for Intervention Description and Replication (TIDieR). The pilot implementation demonstrated high client engagement, satisfaction, and feasibility in daily practice. The GIZ ap-proach promotes appropriate support for families by improving the joint assessment and shared decision-making process in youth (health) care. This study supports the implementation of GIZ in youth (health) care practice and highlights the need for further focus on implementation and sus-tainability.

Mycobacterium avium ssp paratuberculosis (MAP) is the causative agent of Johne’s disease (JD) in animals and a suspected cause of Crohn’s disease (CD) in humans. Crohn’s Disease is a progressive, detrimental granulomatous enteritis of which common therapies are targeted to suppressing certain components of the immune system. The efficacy of these treatments can be variable and temporary with no clear process of selection for the individual patient. However, diagnosis of MAP has been elusive in patients with Crohn’s Disease. In animals it can be detected by several different techniques, including bacterial cell culture, polymerase chain reaction (PCR), and immunological targets. To move to an understanding of the possible pathogenicity of MAP and the sup-posed cause of CD in humans, it is necessary to demonstrate the presence of cell wall deficient mycobacterial (CWDM) forms of MAP in blood and tissue cultures from patients with CD. From this, more tailored and accurate therapies can be implemented and be developed to eradicate this infectious organism from humans. Current anti-mycobacterial antibiotics have limited efficacy as MAP is subtly different from tuberculosis. Newer methods, such as vaccination and gut microbiome remediation will be essential as part of combination therapies.

1). BACKGROUND: Cell wall deficient mycobacteria (CWDM) have seldom been isolated in bacterial culture from human subjects. particularly in clinical disease, such as Crohn’s disease. Techniques have focused on the use of polymerase chain reaction (PCR) for the detection of CWDM in association with inflammatory bowel disease. (IBD). This paper is a report of the development of methods to demonstrate the presence of CWDM using the Ziehl-Neelsen (ZN) stain. This is in addition to the detection of the growth of CWDM in fluid media. 2). METHODS: The use of the ZN stain is suitable for the demonstration of CWDM in clinical samples and cultures, when the staining methods that were common prior to the 1970’s, are adopted. Specific culture media are developed and tested in parallel. Alterations in the concentration of basic fuchsin, and changes in the decolourising solutions are necessary. Decolourising solutions such as 20% concentrated sulphuric acid in water are preferable for detection of CWDM in cultures. 3). RESULTS: CWDM can be readily demonstrated using the simple methods outlined in this report. The ability to visualise the presence of CWDM opens the door to the development of specific fluid media for the isolation of CWDM in culture. 4). CONCLUSION: The ZN stain methods optimised for the demonstration of Mycobacterium tuberculosis complex (MTBC) are not suitable for research into infectious causes of inflammatory bowel disease (IBD), as well as for the detection of CWDM in latent tuberculosis. Revisiting the techniques for the detection of CWDM may also refocus attention on inflammatory diseases considered to be idiopathic, but having hallmarks of an infectious process.