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Background The largest West African monkeypox outbreak began September 2017, in Nigeria. Four individuals traveling from Nigeria to the United Kingdom (n = 2), Israel (n = 1), and Singapore (n = 1) became the first human monkeypox cases exported from Africa, and a related nosocomial transmission event in the United Kingdom became the first confirmed human-to-human monkeypox transmission event outside of Africa. Methods Epidemiological and molecular data for exported and Nigerian cases were analyzed jointly to better understand the exportations in the temporal and geographic context of the outbreak. Results Isolates from all travelers and a Bayelsa case shared a most recent common ancestor and traveled to Bayelsa, Delta, or Rivers states. Genetic variation for this cluster was lower than would be expected from a random sampling of genomes from this outbreak, but data did not support direct links between travelers. Conclusions Monophyly of exportation cases and the Bayelsa sample, along with the intermediate levels of genetic variation, suggest a small pool of related isolates is the likely source for the exported infections. This may be the result of the level of genetic variation present in monkeypox isolates circulating within the contiguous region of Bayelsa, Delta, and Rivers states, or another more restricted, yet unidentified source pool.

Freezing-thawing events contribute to the unique aroma profile of icewines. Differences in key odor-active volatile compounds between ‘Beibinghong’ (Vitis amurensis × V. vinifera) icewines and dry wines were investigated by gas chromatography-olfactometry and gas chromatography-mass spectrometry. Acceptable agreement between the olfactometric and quantitative results was obtained. ‘Beibinghong’ icewine was characterized by high concentrations of volatile phenols, lactones, (E)-β-damascenone, and phenylacetaldehyde, which were associated with on-vine freezing-thawing events in grape. Low concentrations of higher alcohol acetates and ethyl esters of fatty acids were attributed to hyperosmotic stress during fermentation. The overall aroma of icewine could be mimicked by reconstitution containing 44 identified volatiles. Partial least squares regression analysis demonstrated that the concentrations of these volatile compounds determined the distinct sensory profiles of icewines, which have higher intensities of honey/sweet, smoky, caramel, dried fruit, apricot/peach, and floral aromas, and lower intensities of fresh fruity and herbaceous notes in comparison with dry wines.

Monkeypox, caused by a zoonotic orthopoxvirus, is endemic in Central and West Africa. Monkeypox has been sporadically reported in the Republic of the Congo. During March 22–April 5, 2017, we investigated 43 suspected human monkeypox cases. We interviewed suspected case-patients and collected dried blood strips and vesicular and crust specimens (active lesions), which we tested for orthopoxvirus antibodies by ELISA and monkeypox virus and varicella zoster virus DNA by PCR. An ecologic investigation was conducted around Manfouété, and specimens from 105 small mammals were tested for anti-orthopoxvirus antibodies or DNA. Among the suspected human cases, 22 met the confirmed, probable, and possible case definitions. Only 18 patients had available dried blood strips; 100% were IgG positive, and 88.9% (16/18) were IgM positive. Among animals, only specimens from Cricetomys giant pouched rats showed presence of orthopoxvirus antibodies, adding evidence to this species’ involvement in the transmission and maintenance of monkeypox virus in nature.

Background This phase 1 dose-escalation trial studied MM-302, a novel HER2-targeted PEGylated antibody–liposomal doxorubicin conjugate, in HER2-positive locally advanced/metastatic breast cancer. Methods Patients were enrolled in four cohorts: MM-302 monotherapy (8, 16, 30, 40, and 50 mg/m2 every 4 weeks [q4w]); MM-302 (30 or 40 mg/m2 q4w) plus trastuzumab (4 mg/kg q2w); MM-302 (30 mg/m2) plus trastuzumab (6 mg/kg) q3w; MM-302 (30 mg/m2) plus trastuzumab (6 mg/kg) and cyclophosphamide (450 mg/m2) q3w. Results Sixty-nine patients were treated. The most common adverse events (AEs) were fatigue and nausea. Grade 3/4 AEs of special interest included neutropenia, fatigue, mucosal inflammation, anemia, thrombocytopenia, febrile neutropenia, and palmar-plantar erythrodysesthesia. The MTD was not reached. With MM-302 ≥ 30 mg/m2, overall response rate (ORR) was 13% and median progression-free survival (mPFS) 7.4 months (95% CI: 3·5–10·9) in all arms. In 25 anthracycline-naïve patients, ORR was 28·0% and mPFS 10·9 months (95% CI: 1·8–15·3). Imaging with 64Cu-labeled MM-302 visualized tumor-drug penetrance in tumors throughout the body, including the brain. Conclusion MM-302 monotherapy, in combination with trastuzumab, or trastuzumab plus cyclophosphamide, was well tolerated and showed promising efficacy. The selected phase 2 MM-302 dose was 30 mg/m2 plus 6 mg/kg trastuzumab q3w.

Background In 2015, Ethiopia designated rabies as a priority zoonotic disease. Challenges in rabies diagnostic capacity, including laboratory safety, were identified in 2016. As a pilot evaluation, the national rabies laboratory in Ethiopia (EPHI) was chosen to participate in an evaluation of necropsy laboratory facilities and procedures which was conducted over two years. This evaluation identified areas for improvement that strengthening would enhance safety in the laboratory environment. Process changes, specifically in cleaning procedures, will decrease the likelihood of cross contamination and improve precision of testing. Methods This evaluation consisted of two sections: a 38-question verbal interview and an observational evaluation of necropsy laboratory practice. In March 2018, we evaluated EPHI’s laboratory biosafety procedures, and the laboratory technicians’ knowledge, practices, and attitudes in the animal necropsy laboratory before CDC-led laboratory trainings (September and December 2018). A post-training evaluation was conducted in March 2019. # Results Safety compliance scores in 2019 were noticeably increased from 2018. Interview scores increased from 57% to 91% and laboratory observation scores increased from 74% to 91%. Conclusion This evaluation revealed that a necropsy laboratory assessment could be a valuable tool for understanding challenges faced by laboratories performing rabies diagnosis in Ethiopia. Assessment materials help to identify on-going challenges as well as areas of improvement in a systematic manner. In the future, this assessment could be used as a model for labs performing rabies diagnosis in a decentralized system. Additional rabies laboratories are anticipated to stand up throughout Ethiopia and laboratory assessments based on this methodology could provide valuable insights into how to mitigate risks.

Diabetes insipidus (DI) is an uncommon perioperative complication that can occur secondary to medications or surgical manipulation and can cause significant hypovolemia and electrolyte abnormalities. We reviewed and evaluated the current literature and identified 29 cases of DI related to medications commonly used in anesthesia such as propofol, dexmedetomidine, sevoflurane, ketamine, and opioids. This review summarizes the case reports and frequency of DI with each medication and presents possible pathophysiology. Medication-induced DI should be included in the differential diagnosis when intraoperative polyuria is identified. Early identification, removal of the agent, and treatment of intraoperative DI are critical to minimize complications.

Typesetting 2-dimensional mathematical notation can present challenges to users who rely upon WYSIWYG (what you see is what you get) word processing editors, which allow for direct manipulation of text. These editors use various models to represent 2-dimensional mathematical structure within the 1-dimensional word processing environment. The 2-dimensional nature of mathematical notations manifests itself in a variety of ways, and we hypothesize that two distinct models, structure-based (Microsoft Word Equation Editor) and free-form (MC\(^2\): Mathematics Classroom Collaborator) handle different types of mathematical structure with varying degrees of success. To test this hypothesis, an eye-tracking study was conducted to compare how these two models affect task efficiency for mathematical “expert” and “novice” users, as well as working memory interference, and cognitive load. The study required users to transcribe mathematical expressions containing three types of structure: linear (1-dimensional), exponential, and rational (fractions). Handwriting was used as a control. Results showed superior performance by the structure-based model for the transcription of fractions, while the free-form model displayed ameliorated performance for the transcription of exponents. Handwriting was found to be significantly more efficient, but cognitive effects were inconclusive. Few differences were found with respect to user mathematical experience level. These findings show evidence that neither of these models is superior for the typesetting of all mathematics, but rather that features of each model are better equipped to handle different mathematical structures. Therefore, word processing editors can improve the facility of typesetting 2-dimensional mathematics by incorporating elements of both tested models to improve the overall user experience. Such optimization will ultimately facilitate the digital learning and communication of mathematical content.

Objective: Prevention of recurrent stroke in patients with embolic stroke of undetermined source (ESUS) is challenging. The advent of safer anticoagulation in the form of direct oral anticoagulants (DOACs) has prompted exploration of prophylactic anticoagulation for all ESUS patients, rather than anticoagulating just those with documented atrial fibrillation (AF). However, recent trials have failed to demonstrate a clinical benefit, while observing increased bleeding. We modeled the economic impact of anticoagulating ESUS patients without documented AF across multiple geographies. Methods: CRYSTAL-AF trial data were used to assess ischaemic stroke event rates in ESUS patients confirmed AF-free after long-term monitoring. Anticipated bleeding event rates (including both minor and major bleeds) with aspirin, dabigatran 150 mg, and rivaroxaban 20 mg were sourced from published meta-analyses, whilst a 30% ischaemic stroke reduction for both DOACs was assumed. Cost data for clinical events and pharmaceuticals were collected from the local payer perspective. Results: Compared with aspirin, dabigatran and rivaroxaban resulted in 17.9 and 29.9 additional bleeding events per 100 patients over a patient’s lifetime, respectively. Despite incorporating into our model the proposed 30% reduction in ischaemic stroke risk, both DOACs were cost-additive over patient lifetime, as the costs of bleeding events and pharmaceuticals outweighed cost savings associated with the reduction in ischaemic strokes. DOACs added £5953–£7018 per patient (UK), €6683–€7368 (Netherlands), €4933–€9378 (Spain), AUD$5353–6539 (Australia) and $26,768–$32,259 (US) of payer cost depending on the agent prescribed. Additionally, in the U.S. patient pharmacy co-payments ranged from $2468–$12,844 depending on agent and patient plan. In all settings, cost-savings could not be demonstrated even when the modelling assumed 100% protection from recurrent ischaemic strokes, due to the very low underlying risk of recurrent ischaemic stroke in this population (1.27 per 100 patient-years). Conclusions: Anticoagulation of non-AF patients may cause excess bleeds and add substantial costs for uncertain benefits, suggesting a personalised approach to anticoagulation in ESUS patients. © 2021, The Author(s).

In this project the use of Virtual World technology and Artificial Intelligence to produce a shared social landscape for the society of learners. The idea is to create a Virtual World in which learners can participate and interact. One that is parallel to the learning environment or classroom. This can be viewed as an online multi-user environment such as “Second-Life” where on-line learners can interact and construct their own spaces. Their ability to work in that space is governed by input from their robot mentor. Skills in the Virtual World are provided as a result of a student’s behavior in the learning environment. The Virtual World can persist after the learning session is concluded so it provided an incentive for learners to do well in the learning session so that they can acquire points that translate into skills in the corresponding Virtual World. That Virtual World can be shared by several learning sessions or classes to provide a more comprehensive learning environment.

Nitrite (NO2-) is a prevalent nitrogen oxyanion in environmental and industrial processes, but its behavior in solution, including ion pair formation, is complex. This solution phase complexity impacts industries such as nuclear waste treatment, where NO2- significantly affects the solubility of other constituents present in sodium hydroxide (NaOH)-rich nuclear waste. This work provides molecular scale information into sodium nitrite (NaNO2) and NaOH ion-pairing processes to provide a physical basis for later development of thermodynamic models. Solubility isotherms of NaNO2 in aqueous mixtures with NaOH and total alkalinity were also measured. Spectroscopic characterization of these solutions utilized high-field nuclear magnetic resonance spectroscopy (NMR) and Raman spectroscopy, with additional solution structure detailed by X-ray total scattering pairwise distribution function analysis (X-ray PDF). Despite the NO2- deformation Raman band's insensitivity to added NaOH in saturated NaNO2 solutions, 23Na and 15N NMR studies indicated the Na+ and NO2- chemical environments change likely due to ion pairing. The ion pairing correlates with a decrease in diffusion coefficient of solution species as measured by pulsed field gradient 23Na and 1H NMR. Two-dimensional correlation analyses of the 2800-4000 cm-1 Raman region and X-ray PDF indicated that saturated NaNO2 and NaOH mixtures disrupt the hydrogen network of water into a new structure where the length of the OO correlations is contracted relative to the typical H2O structure. Beyond describing the solubility of NaNO2 in a multicomponent electrolyte mixture, these results also indicate that nitrite exhibits greater ion pairing in mixtures of concentrated NaNO2 and NaOH than in comparable solutions with only NaNO2.

In Computation intelligence algorithm performance is crucial especially when the complexity of the system increases and becomes chaotic (un-predictable). In Cultural Systems many algorithms are able to predict the system performance as the complexity is linear, or non-linear. However, when it is chaotic the prediction quality decreases dramatically. In this paper, we are show that Common Value Auctions are able to distribute sufficient information through the system in order to sustain the prediction rate even on the edge of chaos. This sustainability is expressed here in terms of increased resilience and robustness. Systems that rely on wisdom of the crowd based approaches are shown not to do as well when environmental change goes from linear to non-linear, and finally to chaotic.

Background Monkeypox is a poorly described emerging zoonosis endemic to Central and Western Africa. Methods Using surveillance data from Tshuapa Province, Democratic Republic of the Congo during 2011–2015, we evaluated differences in incidence, exposures, and clinical presentation of polymerase chain reaction–confirmed cases by sex and age. Results We report 1057 confirmed cases. The average annual incidence was 14.1 per 100 000 (95% confidence interval, 13.3–15.0). The incidence was higher in male patients (incidence rate ratio comparing males to females, 1.21; 95% confidence interval, 1.07–1.37), except among those 20–29 years old (0.70; .51–.95). Females aged 20–29 years also reported a high frequency of exposures (26.2%) to people with monkeypox-like symptoms.The highest incidence was among 10–19-year-old males, the cohort reporting the highest proportion of animal exposures (37.5%). The incidence was lower among those presumed to have received smallpox vaccination than among those presumed unvaccinated. No differences were observed by age group in lesion count or lesion severity score. Conclusions Monkeypox incidence was twice that reported during 1980–1985, an increase possibly linked to declining immunity provided by smallpox vaccination. The high proportion of cases attributed to human exposures suggests changing exposure patterns. Cases were distributed across age and sex, suggesting frequent exposures that follow sociocultural norms.

Insights into self-assembly enable the 3D printing of super-soft elastomers at room temperature without solvent., Super-soft elastomers derived from bottlebrush polymers show promise as advanced materials for biomimetic tissue and device applications, but current processing strategies are restricted to simple molding. Here, we introduce a design concept that enables the three-dimensional (3D) printing of super-soft and solvent-free bottlebrush elastomers at room temperature. The key advance is a class of inks comprising statistical bottlebrush polymers that self-assemble into well-ordered body-centered cubic sphere phases. These soft solids undergo sharp and reversible yielding at 20°C in response to shear with a yield stress that can be tuned by manipulating the length scale of microphase separation. The addition of a soluble photocrosslinker allows complete ultraviolet curing after extrusion to form super-soft elastomers with near-perfect recoverable elasticity well beyond the yield strain. These structure–property design rules create exciting opportunities to tailor the performance of 3D-printed elastomers in ways that are not possible with current materials and processes.

The role of oligomeric aluminate species in the precipitation of aluminum (Al) phases such as gibbsite (α-Al(OH)

This paper provides an overview of the DeepDive system and its use to uncover ancient submerged sites. While this paper focuses on one example, the system is designed to be generally applicable to other environments that are difficult to access and contain unknown components. The incorporated AI tool learns to identify systematic patterns in the environment of an ancient civilization resources and can also provide an opportunity to generate and test Anthropological and Archaeological theories. This paper demonstrates some of these basic capabilities and their potential to aid in the generic exploration of ancient sites and the civilizations that produced them.

Contemporary 'deep learning' (DL) models have proven to be effective in a wide variety of applications. However, the right network topology for the problem at hand may be complex and not immediately obvious. This has given rise to the secondary field of neural architecture search (NAS). This paper describes a NAS method based on graph evolution pioneered by Neuro-evolution of Augmenting Topologies (NEAT), but driven by the evolutionary mechanisms underlying Cultural Algorithms (CA). CA is a population-based, stochastic optimization system inspired by problem solving in human cultures, suited to solving problems such as NAS. We present CATNeuro a system for evolving DL models guided by CA metaheuristics called Knowledge Sources (KS). The KS store knowledge harvested from prior generations and use it to guide subsequent generations in the search space. A knowledge distribution mechanism, which assigns a KS to each individual in the population, is an instrumental part of this process. CATNeuro, is applied to find optimal network topologies to play a 2D fighting game called FightingICE (based on "The Rumble Fish" game). A policy-based, reinforcement learning method is used to create the training data for network optimization. CATNeuro is still evolving. In this primary foray into NAS, we contrast the performance of CATNeuro with two different knowledge distribution mechanisms - the stalwart Weighted Majority (WTD) - which represents "wisdom of the crowds" - and a new one based on the Stag-Hunt game from evolutionary game theory. We show that Stag-Hunt has a statistical edge over WTD in many areas and thus is a better candidate for future development with CATNeuro.

Recently it has been found that the earth’s oceans are warming at a pace that is 40% faster than predicted by a United Nations panel a few years ago. As a result, 2018 has become the warmest year on record for the earth’s oceans. That is because the oceans have acted as a buffer by absorbing 93% of the heat produced by the greenhouse gases [1]. The impact of the oceanic warming has already been felt in terms of the periodic warming of the Pacific Ocean as an effect of the ENSO process. The ENSO process is a cycle of warming and subsequent cooling of the Pacific Ocean that can last over a period of years. This cycle was first documented by Peruvian fishermen in the early 1600’s. So it has been part of the environmental challenges that have been presented to economic agents throughout the world since then. It has even been suggested that the cycle has increased in frequency over the years, perhaps in response to the overall issues related to global warming. [2] [3]In this paper Cultural Algorithms are used to develop a multiobjective agent-based model of artisanal (traditional offshore) fishing behavior in coastal Peru, Cerro Azul. The data used to produce this model comes from the observation of fishing behavior over a four year period, 1982-1986. During this period over 6000 individual fishing trips were documented. This observation period overlapped with one of the largest ENSO activities ever recorded. As a result, it was possible to observe the changes in fishing behavior that were the result of this process. While the data is several decades old, the ENSO process was first observed in Peru in 1502. Thus, this data can be considered to reflect the adaptations that have been made to the process in the ensuing centuries.The model was used to produce Pareto curves that reflected tradeoffs in terms of fish quality and trip effort during each of three phases on the ENSO process. A version of Cultural Algorithms, CAPSO, was then used to compute whether these curves were significantly different from each other. The results suggested that they each represented a different phased response to the local climate change. During the warming phase fisherman had to exert less effort to secure quality fish than in the subsequent cooling off period. In that period there were more types of catches but they were distributed over a wider area. The final, back to normal phase reflected a compromise between the two, where fewer types of catches of slightly lower quality, but with lesser effort than in the previous phases.

Cultural Algorithms have led to the development of many ways to distribute information within social networks. These mechanisms act by helping the system make decisions about how information is distributed through a population network, and thus are called distribution or decision mechanisms. Many distribution mechanisms have been developed using techniques from auction theory, game theory and various forms of voting construct. Here we discuss several methods of Knowledge distribution collectively called the auction distributions mechanisms and their performance is compared using dynamic complex real-valued functional landscapes. We perform this comparison with regards to robustness, how well the system finds solutions, and resilience, how well the system reacts to changes in the dynamics of the system. In this paper an additional Subcultured Distribution Mechanism is described that works to factor the knowledge distribution mechanism into subnetworks in order to support a “deep social learning” approach. The Subcultured Distribution Mechanism is compared with the results of each individual distribution mechanism without a subculture enhancement, when applied to a series of dynamic complex optimization problems of varying complexities. The results suggest that relatively simple mechanism such as Weighted Majority Wins and First Price Auction are sufficient for environments that exhibit low entropic levels of change such as in linear changing environments. For nonlinearly changing environments, First Price Multi-round and English Auctions are most of effective on their own. The Subcultured Distribution Mechanism extension of these mechanisms was found to be best suited for complexities where the two distribution mechanisms had similar performances, and in the most chaotic environments where having multiple distribution mechanisms to choose from was advantageous.