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Background: Patients with eye disease have an increased risk for developing neurodegenerative disease. Neurodegenerative proteins can be measured in the eye; however, correlations between biomarker levels in eye fluid and neuropathological diagnoses have not been established. Objective: This exploratory, retrospective study examined vitreous humor from 41 postmortem eyes and brain tissue with neuropathological diagnoses of Alzheimer’s disease (AD, n = 7), chronic traumatic encephalopathy (CTE, n = 15), both AD + CTE (n = 10), and without significant neuropathology (controls, n = 9). Methods: Protein biomarkers i.e., amyloid-β (Aβ 40,42), total tau (tTau), phosphorylated tau (pTau181,231), neurofilament light chain (NfL), and eotaxin-1 were quantitatively measured by immunoassay. Non-parametric tests were used to compare vitreous biomarker levels between groups. Spearman’s rank correlation tests were used to correlate biomarker levels in vitreous and cortical tissue. The level of significance was set to α= 0.10. Results: In pairwise comparisons, tTau levels were significantly increased in AD and CTE groups versus controls (p = 0.08 for both) as well as AD versus AD+CTE group and CTE versus AD+CTE group (p = 0.049 for both). Vitreous NfL levels were significantly increased in low CTE (Stage I/II) versus no CTE (p = 0.096) and in low CTE versus high CTE stage (p = 0.03). Vitreous and cortical tissue levels of pTau 231 (p = 0.02, r = 0.38) and t-Tau (p = 0.04, r = –0.34) were significantly correlated. Conclusion: The postmortem vitreous humor biomarker levels significantly correlate with AD and CTE pathology in corresponding brains, while vitreous NfL was correlated with the CTE staging. This exploratory study indicates that biomarkers in the vitreous humor may serve as a proxy for neuropathological disease.

OBJECTIVE Evaluate whether general practitioners’ formal small animal (canine and feline) nutrition instruction in veterinary school and the amount and type of continuing education engagement affect perceived self-reported confidence and frequency in discussing nutrition with clients. SAMPLE 403 small animal veterinarians who responded to an online survey distributed through the American Animal Hospital Association. PROCEDURES Veterinarians were surveyed regarding perceived amount of formal instruction received in veterinary school, interest, time committed to self-education, and confidence in both self and staff knowledge in small animal nutrition. RESULTS Of those veterinarians who responded to the survey, 57.1% (201/352) reported they received “none” or “very little” formal instruction in small animal nutrition, while 151 of 352 answered “some” or “a significant amount.” Veterinarians with more formal instruction and veterinarians who reported spending more time in self-education had increased confidence in their own nutritional knowledge (P < .01) and that of their staff (P < .01). CLINICAL RELEVANCE Veterinarians with self-reported significant formal instruction and veterinarians with higher continuing education engagement were more confident in their knowledge and their staff’s knowledge regarding therapeutic and nontherapeutic small animal nutrition. Therefore, it is important for the profession to address veterinary nutrition education gaps in order to increase the veterinary healthcare team’s engagement in nutritional discussions with their clients for both healthy and sick pets.

Over the last 17 years, there has been a remarkable increase in scientific research concerning chronic traumatic encephalopathy (CTE). Since the publication of NINDS–NIBIB criteria for the neuropathological diagnosis of CTE in 2016, and diagnostic refinements in 2021, hundreds of contact sport athletes and others have been diagnosed at postmortem examination with CTE. CTE has been reported in amateur and professional athletes, including a bull rider, boxers, wrestlers, and American, Canadian, and Australian rules football, rugby union, rugby league, soccer, and ice hockey players. The pathology of CTE is unique, characterized by a pathognomonic lesion consisting of a perivascular accumulation of neuronal phosphorylated tau (p-tau) variably alongside astrocytic aggregates at the depths of the cortical sulci, and a distinctive molecular structural configuration of p-tau fibrils that is unlike the changes observed with aging, Alzheimer’s disease, or any other tauopathy. Computational 3-D and finite element models predict the perivascular and sulcal location of p-tau pathology as these brain regions undergo the greatest mechanical deformation during head impact injury. Presently, CTE can be definitively diagnosed only by postmortem neuropathological examination; the corresponding clinical condition is known as traumatic encephalopathy syndrome (TES). Over 97% of CTE cases published have been reported in individuals with known exposure to repetitive head impacts (RHI), including concussions and nonconcussive impacts, most often experienced through participation in contact sports. While some suggest there is uncertainty whether a causal relationship exists between RHI and CTE, the preponderance of the evidence suggests a high likelihood of a causal relationship, a conclusion that is strengthened by the absence of any evidence for plausible alternative hypotheses. There is a robust dose–response relationship between CTE and years of American football play, a relationship that remains consistent even when rigorously accounting for selection bias. Furthermore, a recent study suggests that selection bias underestimates the observed risk. Here, we present the advances in the neuropathological diagnosis of CTE culminating with the development of the NINDS–NIBIB criteria, the multiple international studies that have used these criteria to report CTE in hundreds of contact sports players and others, and the evidence for a robust dose–response relationship between RHI and CTE.

Effects of climate change can already be observed in many regions of the world. The basin of the Paraná River, in South America, has been suffering an important drought since 2019 in the whole region. The extension of the crisis has increased the risks in the flora and fauna, losses in logistics of navigation, besides the problems of urban water cleansing. In this regard, the novel proposal presents a new mathematical model to study the impact of this crisis. Besides the traditional constraints of the literature for hydraulic systems, this paper enhances inventory constraints, connections with electric systems, and other considerations as the head effects in electricity generation. Because several equations related to electricity generation are nonlinear (which the subsequent computational effort impacts), this proposal applies linearization techniques to reduce CPU times. The core is related to hydropower production, and the consequences of the water crisis in the regional markets. The mathematical model analyzes the interrelationships between reservoirs and water flows of the basin. To study the effectiveness of the novel proposal, the reported situation of the basin of the Paraná River is studied by considering two scenarios (normal conditions of the river flow and the conditions related to the drought). Results show that the crisis implies daily net economic losses of about 7 million USD for the operators of the power plants. Other problems (different from the ones related to the energy field) are also mentioned and analyzed.

Chronic traumatic encephalopathy (CTE) is a tauopathy associated with repetitive mild head impacts characterized by perivascular hyperphosphorylated tau (p-tau) in neurofibrillary tangles (NFTs) and neurites in the depths of the neocortical sulci. In moderate to advanced CTE, NFTs accumulate in the hippocampus, potentially overlapping neuroanatomically with primary age-related tauopathy (PART), an age-related tauopathy characterized by Alzheimer disease-like tau pathology in the hippocampus devoid of amyloid plaques. We measured p-tau burden using positive-pixel counts on immunohistochemically stained and neuroanatomically segmented hippocampal tissue. Subjects with CTE had a higher total p-tau burden than PART subjects in all sectors (p = 0.005). Within groups, PART had significantly higher total p-tau burden in CA1/subiculum compared to CA3 (p = 0.02) and CA4 (p = 0.01) and total p-tau burden in CA2 trended higher than CA4 (p = 0.06). In CTE, total p-tau burden in CA1/subiculum was significantly higher than in the dentate gyrus; and CA2 also trended higher than dentate gyrus (p = 0.01, p = 0.06). When controlling for p-tau burden across the entire hippocampus, CA3 and CA4 had significantly higher p-tau burden in CTE than PART (p lt; 0.0001). These data demonstrate differences in hippocampal p-tau burden and regional distribution in CTE compared to PART that might be helpful in differential diagnosis and reveal insights into disease pathogenesis.

This study sought to examine the implementation of MTB-MLE in schools where the majority of the students are indigenous learners. It specifically aimed to describe the (1) teachers' experiences with MTB-MLE implementation and the (2) the teachers' concerns in implementation. Purposive sampling was used; 6 Primary Teachers were interviewed using a semi-structured interview technique. Results show that the teachers believe in the program's purpose of the program, but in practice, it has some issues that call for reflection among policymakers and program implementers. The teachers see MTB-MLE as something irrelevant because it is a duplication of the Filipino subject which is not the Mother Tongue of the learners in the first place. Another issue that was revealed is the implication of having a multilingual classroom. The diversity of the linguistic backgrounds of the learners poses a problem. Teacher says that they receive training on MTB-MLE, but such training has no practical relevance to their day-to-day instruction. The teachers also mention the dearth of teaching and learning materials. It could be safely said that the implementation of MTB-MLE failed to achieve its purpose, and it needs more re-thinking. The researchers believe in the goal of Deped in implementing the program but that more research is needed. Collaborating with teachers, anthropologists, linguists, and artists is necessary.

Many tropical and subtropical plant lineages have independently evolved C4 photosynthesis. The convergent evolution of this complex functional trait from different ancestors is reflected in variations in the structural and biochemical characteristics of C4 components such as enzymes and cellular specializations. The mechanism of C4 carbon concentration mostly involves coordinated function of mesophyll and bundle sheath cells. Important adaptations of the C4 syndrome include increased vein density and the development of photosynthetic bundle sheath cells with low gas conductance. In addition, the enzymes and transporters of the C4 pathway evolved via the co-option of multiple genes, each derived from a specific lineage of isoforms present in nonC4-ancestors. In particular, the adaptation of C4 enzymes resulted in a variety of structural and biochemical modifications, generally leading to increased catalytic efficiency and regulation by metabolites and post-translational modifications. Differences in these adaptations are particularly evident in the C4-acid decarboxylation step, which can be catalyzed by three decarboxylases that define the C4 subtypes. Associated with the biochemical subtypes, there are also differences in the extend of grana staking and localization of bundle sheath cells chloroplasts. The presence of a suberin layer and symplastic connections also likely vary among the different C4-subtypes. This review examines the current understanding of the diversity of structural and functional changes in key components of the C4 carbon concentration mechanism. This knowledge is necessary not only to identify divergent solutions for convergent optimization of C4 components in different C4 lineages, but also to guide their creation for rational synthetic biology approaches.

In plants, the establishment of broad and long-lasting immunity is based on programs that control systemic resistance and immunological memory or “priming”. Despite not showing activated defenses, a primed plant induces a more efficient response to recurrent infections. Priming might involve chromatin modifications that allow a faster/stronger activation of defense genes. The Arabidopsis chromatin regulator “Morpheus Molecule 1” (MOM1) has been recently suggested as a priming factor affecting the expression of immune receptor genes. Here, we show that mom1 mutants exacerbate the root growth inhibition response triggered by the key defense priming inducers azelaic acid (AZA), β-aminobutyric acid (BABA) and pipecolic acid (PIP). Conversely, mom1 mutants complemented with a minimal version of MOM1 (miniMOM1 plants) are insensitive. Moreover, miniMOM1 is unable to induce systemic resistance against Pseudomonas sp. in response to these inducers. Importantly, AZA, BABA and PIP treatments reduce the MOM1 expression, but not miniMOM1 transcript levels, in systemic tissues. Consistently, several MOM1-regulated immune receptor genes are upregulated during the activation of systemic resistance in WT plants, while this effect is not observed in miniMOM1. Taken together, our results position MOM1 as a chromatin factor that negatively regulates the defense priming induced by AZA, BABA and PIP.

The genomes of most protozoa encode families of variant surface antigens. In some parasitic microorganisms, it has been demonstrated that mutually exclusive changes in the expression of these antigens allow parasites to evade the host’s immune response. It is widely assumed that antigenic variation in protozoan parasites is accomplished by the spontaneous appearance within the population of cells expressing antigenic variants that escape antibody-mediated cytotoxicity. Here we show, both in vitro and in animal infections, that antibodies to Variant-specific Surface Proteins (VSPs) of the intestinal parasite Giardia lamblia are not cytotoxic, inducing instead VSP clustering into liquid-ordered phase membrane microdomains that trigger a massive release of microvesicles carrying the original VSP and switch in expression to different VSPs by a calcium-dependent mechanism. This novel mechanism of surface antigen clearance throughout its release into microvesicles coupled to the stochastic induction of new phenotypic variants not only changes current paradigms of antigenic switching but also provides a new framework for understanding the course of protozoan infections as a host/parasite adaptive process.

Millions of individuals are exposed to repetitive head impacts (RHI) each year through contact sports, military blast, and interpersonal violence. RHI is the major risk factor for developing chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy. Recent consensus criteria defined the pathognomonic lesion in CTE as perivascular, hyperphosphorylated tau (p-tau) in neuronal aggregates. Astroglial p-tau is an inconsistent supporting feature and not in itself diagnostic of CTE. This study quantitated the spatial and cellular distribution of p-tau pathology in postmortem dorsolateral frontal cortex of 150 individuals with CTE, from ages 21 to 80 years old, without comorbid pathology. p-Tau-immunoreactive cells were quantitated in the gray matter sulcus, crest, subpial region, and within pathognomonic CTE lesions. Significantly more neuronal p-tau than astrocytic p-tau was found across all cortical regions (p

Several global parameters of compact stars are related via empirical relations, which are (nearly) independent of the underlying equation of state (EoS) of dense matter and, therefore, are said to be universal. We investigate the universality of relations that express the maximum mass and the radius of non-rotating and maximally rapidly rotating configurations, as well as their moment of inertia, in terms of the compactness of the star. For this, we first utilize a collection of cold (zero-temperature) and hot (isentropic) nucleonic EoS and confirm that the universal relations are holding for our collection of EoS. We then go on, to add to our collection and test for the same universality models of EoS that admit a strong first-order phase transition from nucleonic to deconfined quark matter. Also in this case we find that the universal relations hold, in particular for hot, isentropic hybrid stars. By fitting the universal relations to our computed data, we determine the coefficients entering these relations and the accuracy to which they hold., Comment: 16 pages, 8 figures, published in MNRAS, Vol. 515, p. 3539 (2022)

BACKGROUND: In June 2019, the Bolivian Ministry of Health reported a cluster of cases of hemorrhagic fever that started in the municipality of Caranavi and expanded to La Paz. The cause of these cases was unknown. METHODS: We obtained samples for next-generation sequencing and virus isolation. Human and rodent specimens were tested by means of virus-specific real-time quantitative reverse-transcriptase–polymerase-chain-reaction assays, next-generation sequencing, and virus isolation. RESULTS: Nine cases of hemorrhagic fever were identified; four of the patients with this illness died. The etiologic agent was identified as Mammarenavirus Chapare mammarenavirus, or Chapare virus (CHAPV), which causes Chapare hemorrhagic fever (CHHF). Probable nosocomial transmission among health care workers was identified. Some patients with CHHF had neurologic manifestations, and those who survived had a prolonged recovery period. CHAPV RNA was detected in a variety of human body fluids (including blood; urine; nasopharyngeal, oropharyngeal, and bronchoalveolar-lavage fluid; conjunctiva; and semen) and in specimens obtained from captured small-eared pygmy rice rats (Oligoryzomys microtis). In survivors of CHHF, viral RNA was detected up to 170 days after symptom onset; CHAPV was isolated from a semen sample obtained 86 days after symptom onset. CONCLUSIONS: M. Chapare mammarenavirus was identified as the etiologic agent of CHHF. Both spillover from a zoonotic reservoir and possible person-to-person transmission were identified. This virus was detected in a rodent species, O. microtis. (Funded by the Bolivian Ministry of Health and others.)

This study addresses a gap in the literature by examining K–12 administrators’ perceptions of school social workers’ usage of student data. Before the start of the 2020–2021 school year, school social workers from a national organization invited their administrators via email to complete a survey, producing 48 responses. Administrators perceived that the top tasks of school social workers were in the areas of crisis intervention, community resource referrals, and student consultations for teachers and staff. Administrators also indicated that the data most frequently reported to them by school social workers were attendance-related information, and they were not aware of other educational-related data reported by school social workers. Administrators shared that, while they would prefer formal reporting, school social workers were more likely to report data through informal conversations. Overall, this article underscores the need for school social workers to examine their data use practices with K–12 administrators to better advocate for student needs and place greater emphasis on their data use practices in promoting systematic changes. Data use is a powerful tool in demonstrating the relationship between school social work and student outcomes.

Background Very little is known about the etiology of personality and psychiatric disorders. Because the core neurobiology of many such traits is evolutionarily conserved, dogs present a powerful model. We previously reported genome scans of breed averages of ten traits related to fear, anxiety, aggression and social behavior in multiple cohorts of pedigree dogs. As a second phase of that discovery, here we tested the ability of markers at 13 of those loci to predict canine behavior in a community sample of 397 pedigree and mixed-breed dogs with individual-level genotype and phenotype data. Results We found support for all markers and loci. By including 122 dogs with veterinary behavioral diagnoses in our cohort, we were able to identify eight loci associated with those diagnoses. Logistic regression models showed subsets of those loci could predict behavioral diagnoses. We corroborated our previous findings that small body size is associated with many problem behaviors and large body size is associated with increased trainability. Children in the home were associated with anxiety traits; illness and other animals in the home with coprophagia; working-dog status with increased energy and separation-related problems; and competitive dogs with increased aggression directed at familiar dogs, but reduced fear directed at humans and unfamiliar dogs. Compared to other dogs, Pit Bull-type dogs were not defined by a set of our markers and were not more aggressive; but they were strongly associated with pulling on the leash. Using severity-threshold models, Pit Bull-type dogs showed reduced risk of owner-directed aggression (75th quantile) and increased risk of dog-directed fear (95th quantile). Conclusions Our association analysis in a community sample of pedigree and mixed-breed dogs supports the interbreed mapping. The modeling shows some markers are predictive of behavioral diagnoses. Our findings have broad utility, including for clinical and breeding purposes, but we caution that thorough understanding is necessary for their interpretation and use.

The development of sensitive and affordable testing devices for infectious diseases is essential to preserve public health, especially in pandemic scenarios. In this work, we have developed an attractive analytical method to monitor products of genetic amplification, particularly the loop-mediated isothermal amplification reaction (RT-LAMP). The method is based on electrochemical impedance measurements and the distribution of relaxation times model, to provide the so-called time-constant-domain spectroscopy (TCDS). The proposed method is tested for the SARS-CoV-2 genome, since it has been of worldwide interest due to the COVID-19 pandemic. Particularly, once the method is calibrated, its performance is demonstrated using real wastewater samples. Moreover, we propose a simple classification algorithm based on TCDS data to discriminate among positive and negative samples. Results show how a TCDS-based method provides an alternative mechanism for label-free and automated assays, exhibiting robustness and specificity for genetic detection.

In this paper we investigate the following fractional order in time integrodifferential problem $$ \mathbb{D}_{t}^{\alpha}u(t)+Au(t)=f \bigl(t,u(t) \bigr)+ \int _{-\infty}^{t} k(t-s)g \bigl(s,u(s) \bigr)\,ds, \quad t \in \mathbb{R}. $$ D t α u ( t ) + A u ( t ) = f ( t , u ( t ) ) + ∫ − ∞ t k ( t − s ) g ( s , u ( s ) ) d s , t ∈ R . Here, $\mathbb{D}_{t}^{\alpha}$ D t α is the Caputo derivative. We obtain results on the existence and uniqueness of $(\omega ,c)$ ( ω , c ) -periodic mild solutions assuming that −A generates an analytic semigroup on a Banach space X and f, g, and k satisfy suitable conditions. Finally, an interesting example that fits our framework is given.

American football players and other individuals exposed to repetitive head impacts can exhibit a constellation of later-life cognitive and neuropsychiatric symptoms. While tau-based diseases such as chronic traumatic encephalopathy can underpin certain symptoms, contributions from non-tau pathologies from repetitive head impacts are increasingly recognized. We examined cross-sectional associations between myelin integrity using immunoassays for myelin-associated glycoprotein and proteolipid protein 1 with risk factors and clinical outcomes in brain donors exposed to repetitive head impacts from American football. Immunoassays for myelin-associated glycoprotein and proteolipid protein 1 were conducted on dorsolateral frontal white matter tissue samples of 205 male brain donors. Proxies of exposure to repetitive head impacts included years of exposure and age of first exposure to American football play. Informants completed the Functional Activities Questionnaire, Behavior Rating Inventory of Executive Function-Adult Version (Behavioral Regulation Index), and Barratt Impulsiveness Scale-11. Associations between myelin-associated glycoprotein and proteolipid protein 1 with exposure proxies and clinical scales were tested. Of the 205 male brain donors who played amateur and professional football, the mean age was 67.17 (SD = 16.78), and 75.9% (n = 126) were reported by informants to be functionally impaired prior to death. Myelin-associated glycoprotein and proteolipid protein 1 correlated with the ischaemic injury scale score, a global indicator of cerebrovascular disease (r = −0.23 and −0.20, respectively, Ps < 0.01). Chronic traumatic encephalopathy was the most common neurodegenerative disease (n = 151, 73.7%). Myelin-associated glycoprotein and proteolipid protein 1 were not associated with chronic traumatic encephalopathy status, but lower proteolipid protein 1 was associated with more severe chronic traumatic encephalopathy (P = 0.03). Myelin-associated glycoprotein and proteolipid protein 1 were not associated with other neurodegenerative disease pathologies. More years of football play was associated with lower proteolipid protein 1 [beta = −2.45, 95% confidence interval (CI) [−4.52, −0.38]] and compared with those who played

In this paper, we investigate the existence and uniqueness of $$(\omega ,Q)$$ ( ω , Q ) -periodic mild solutions for the following problem $$\begin{aligned} x'(t)=Ax(t)+f(t,x(t)),\quad t\in \mathbb {R}, \end{aligned}$$ x ′ ( t ) = A x ( t ) + f ( t , x ( t ) ) , t ∈ R , on a Banach space X. Here, A is a closed linear operator which generates an exponentially stable $$C_0$$ C 0 -semigroup and the nonlinearity f satisfies suitable properties. The approaches are based on the well-known Banach contraction principle. In addition, a sufficient criterion is established for the existence and uniqueness of $$(\omega ,Q)$$ ( ω , Q ) -periodic mild solutions to the Hopfield-type neural network model.

The World Health Organization's (WHO) Constitution affirms, in its preamble, a fundamental and non-discriminatory right to health and health care. In doing so, it echoes a number of widely ratified treaties and other international legal instruments with a strong claim to having the status of customary international law, including the International Convention on the Elimination of All Forms of Racial Discrimination, the International Covenant on Economic, Social and Cultural Rights (ICESCR), the Convention on the Elimination of All Forms of Discrimination Against Women, the Universal Declaration of Human Rights, the Convention on the Rights of the Child, the ILO Convention on Indigenous and Tribal peoples in Independent Countries, and the Standard Minimum Rules for the Treatment of Prisoners. Most recently, the Institut de Droit affirmed that same fundamental right in Article 4 of its September 2021 Resolution on Epidemics, Pandemics, and International Law.

Este artículo tiene por objetivo determinar la influencia del uso de Quizizz en las actitudes y motivación de las estudiantes de Educación Primaria, durante el confinamiento por la pandemia COVID-19. El diseño es cuantitativo descriptivo. Se seleccionó una muestra de 200 estudiantes desde el tercer hasta el sexto grado de primaria, a quienes se les aplicó dos cuestionarios. Los resultados demuestran que el uso de Quizizz influye positivamente en las actitudes y motivación de las estudiantes.

While the literature regarding return to play and recovery protocols from mild traumatic brain injury (mTBI) and sports-related concussions (SRC) is growing, there continues to be a paucity of data regarding when air travel is safe for athletes after sustaining certain brain injuries, such as mTBI and SRC. Although it is known hypoxia can negatively affect severe TBI patients, it is unclear whether mild hypoxia, which may be experienced during commercial air travel, is clinically significant for athletes who have recently sustained mTBI injuries. Further research is required to provide more standardized recommendations on when air travel is safe. With the current available literature, clinicians still need to weigh the evidence, consider how it applies to each individual patient, and engage in shared decision making to ultimately decide what is best for the patient.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repetitive head impacts (RHI) and characterized by perivascular hyperphosphorylated tau (p-tau) deposits. The role of vascular injury, blood-brain barrier leakage, and neuroinflammation in CTE pathogenesis is not well understood. We performed quantitative immunoassays for intercellular adhesion molecule 1 (ICAM1), vascular cellular adhesion molecule 1 (VCAM1), and C-reactive protein (CRP) within the postmortem dorsolateral frontal cortex of participants with and without a history of RHI and CTE (n = 156), and tested for associations with RHI, microgliosis, and tau pathology measures. Levels of vascular injury-associated markers ICAM1, VCAM1, and CRP were increased in CTE compared to RHI-exposed and -naïve controls. ICAM1 and CRP increased with RHI exposure duration (p

OBJECTIVE To evaluate the voluntary acceptance of 10 commercially available compounding flavors in cats. ANIMALS 46 healthy cats between 1 and 12 years of age. PROCEDURES Each cat underwent a 14-day study period consisting of a 4-day acclimation period followed by a 10-day trial period in which each cat was randomly offered 10 different compounding flavors. Owners completed a presurvey along with a daily observation logbook. Kits, including residual amounts of flavors, were returned and weighed to determine residual weight and calculate the amount ingested. RESULTS Overall, cats did not voluntarily accept most of the compounding flavors; 58.8% (124/211) and 84.5% (267/311) of offered samples of oil-based and water-based compounding flavors, respectively, were rejected or minimally accepted. Cats were significantly (P < .001) more likely to accept oil-based flavors, compared to water-based flavors. The sweet water-based flavors were least accepted, compared to water-based control and water-based savory flavors (P = .040 and P < .001, respectively). Owner-perceived acceptance was moderately correlated with residual flavor weights (Kendall tau [τ] = –0.466; P < .001). Owners were not able to accurately predict which flavors their cats would accept. CLINICAL RELEVANCE Cats should be offered oil-based compounding flavorings when available, whereas water-based sweet flavorings should be avoided. Owner perception of acceptance is a valid metric to assess flavor acceptance, which can be used in future studies evaluating flavor acceptance. Owners may not accurately predict their cats’ flavor preferences, limiting their ability to guide optimal flavor selection.

Artificial intelligence approaches in medicine are more and more used and are extremely promising due to the growing number of data produced and the variety of data they allow to exploit. Thus, the computational analysis of medical images in particular, radiological (radiomics), or anatomopathological (pathomics), has shown many very interesting results for the prediction of the prognosis and the response of cancer patients. Radiotherapy is a discipline that particularly benefits from these new approaches based on computer science and imaging. This review will present the main principles of an artificial intelligence approach and in particular machine learning, the principles of a radiomic and pathomic approach and the potential of their use for the prediction of the prognosis of patients treated with radiotherapy.

Behavioral traits like aggression, anxiety, and trainability differ significantly across dog breeds and are highly heritable. However, the neural bases of these differences are unknown. Here we analyzed structural MRI scans of 62 dogs in relation to breed-average scores for the 14 major dimensions in the Canine Behavioral Assessment and Research Questionnaire, a well-validated measure of canine temperament. Several behavior categories showed significant relationships with morphologically covarying gray matter networks and regional volume changes. Networks involved in social processing and the flight-or-fight response were associated with stranger-directed fear and aggression, putatively the main behaviors under selection pressure during wolf-to-dog domestication. Trainability was significantly associated with expansion in broad regions of cortex, while fear, aggression, and other “problem” behaviors were associated with expansion in distributed subcortical regions. These results closely overlapped with regional volume changes with total brain size, in striking correspondence with models of developmental constraint on brain evolution. This suggests that the established link between dog body size and behavior is due at least in part to disproportionate enlargement of later-developing regions in larger brained dogs. We discuss how this may explain the known correlation of increasing reactivity with decreasing body size in dogs.

RESUMEN La evaluación en laboratorio de la respuesta de materiales granulares no ligados (e.g., subbases y bases granulares para pavimentación) bajo carga dinámica es limitada en Colombia. Este estado de la práctica se relaciona, entre otros aspectos, con que el equipo triaxial dinámico requerido para su determinación es costoso y los protocolos de ensayo complejos. Como alternativa, en la última década se han realizado desarrollos sobre el ensayo CBR dinámico (dCBR), que emplea el equipo, pero modifica el protocolo del ensayo de CBR convencional. Esta investigación propone las bases de un nuevo protocolo para el ensayo de dCBR, para determinar la rigidez de materiales granulares (i.e., módulo resiliente equivalente) mediante la aplicación de siete etapas de carga repetida, donde cada etapa está definida por una deformación objetivo. El estudio incluyó dos materiales granulares marginales (MGMs), con índices de plasticidad altos (IP>6). Los resultados sugieren que el protocolo propuesto para el ensayo de dCBR permite la estimación del módulo resiliente equivalente. Adicionalmente, este protocolo discrimina el efecto de la plasticidad de la fracción fina del mgm sobre su rigidez (i.e., reducción de módulo resiliente equivalente al incrementar el índice de plasticidad). Con base en los resultados obtenidos, se propone avanzar en la caracterización de un mayor número de materiales para validar los resultados preliminares presentados e indagar sobre una posible correlación entre valores de módulo resiliente y módulo resiliente equivalente. ABSTRACT Laboratory evaluation of unbound granular materials response (e.g., paving granular subbases and bases), subjected to dynamic load is limited in Colombia. This state of the practice is related, among other aspects, to the fact that the dynamic triaxial equipment required for its determination is expensive, and the test protocols are complex. In the last decade, work has been carried out to develop the dynamic CBR test (dCBR) that employs the CBR equipment but modifies the testing protocol applied in the CBR test. This research proposes the basis of a new protocol for the dCBR test to determine the stiffness of granular materials (i.e., equivalent resilient modulus) by applying seven steps repeated load, where each step is defined by a target strain. The study included two marginal granular materials (MGMs) with high plasticity indexes. The results suggest that the proposed dCBR test protocol allows for estimating the equivalent resilient modulus. In addition, the proposed protocol differentiates the effect of the plasticity index on the stiffness of the MGM (i.e., reduction of equivalent resilient modulus as the plasticity index increases). Therefore, we propose to extend the range of materials characterized to validate the preliminary results presented and inquire about a possible correlation between the values of resilient modulus and equivalent resilient modulus.

Research on working dogs is growing rapidly due to increasing global demand. Here we report genome scanning of the risk of puppies being eliminated for behavioral reasons prior to entering the training phase of the US Transportation Security Administration’s (TSA) canine olfactory detection breeding and training program through 2013. Elimination of dogs for behavioral rather than medical reasons was based on evaluations at three, six, nine and twelve months after birth. Throughout that period, the fostered dogs underwent standardized behavioral tests at TSA facilities, and, for a subset of tests, dogs were tested in four different environments. Using methods developed for family studies, we performed a case-control genome wide association study (GWAS) of elimination due to behavioral observation and testing results in a cohort of 528 Labrador Retrievers (2002–2013). We accounted for relatedness by including the pedigree as a covariate and maximized power by including individuals with phenotype, but not genotype, data (approximately half of this cohort). We determined genome wide significance based on Bonferroni adjustment of two quasi-likelihood score tests optimized for either small or nearly-fully penetrant effect sizes. Six loci were significant and five suggestive, with approximately equal numbers of loci for the two tests and frequencies of loci with single versus multiple mapped markers. Several loci implicate a single gene, including CHD2, NRG3 and PDE1A which have strong relevance to behavior in humans and other species. We briefly discuss how expanded studies of canine breeding programs could advance understanding of learning and performance in the mammalian life course. Although human interactions and other environmental conditions will remain critical, our findings suggest genomic breeding selection could help improve working dog populations.

For the data on the observation times and directions of the motion of extensive air showers, which are observed at two stations of the GELATICA network, for the first time we apply the method we have developed previously for identifying pairs of mutually remote extensive air showers, the ancestor particles of which arose, possibly, in a single process. A brief description of the GELATICA network, a review of the properties of used samples of data on shower observations at two stations of the network during the 2019–2021 session, and the result of applying the above method to them are given. Some properties of a single peculiar pair of remote showers are discussed. A side question arose about the cause of the observed temporal asymmetry in the locations of the regions of mutual approach of independent primary cosmic ray particles.

In January 2022, there was a global and rapid surge of the Omicron variant of SARS-CoV-2 related to more transmission. This coincided with an increase in the incidence in Asturias, a region where rapid diagnosis and containment measures had limited the circulation of variants. Methods: From January to June 2022, 34,591 variants were determined by the SNP method. From them, 445 were characterized by the WGS method and classified following pangolin program and phylogenic analysis. Results: The Omicron variant went from being detected in 2438 (78%) samples in the first week of January 2021 to 4074 (98%) in the third week, according to the SNP method. Using the WGS method, 159 BA.1 (35.7%), 256 BA.2 (57.6%), 1 BA.4 (0.2%) and 10 BA.5 (2.2%) Omicron variants were found. Phylogenetic analysis detected that three new sub-clades, BA.2,3.5, BA.2.56 and BF1, were circulating. Conclusions: The increase in the incidence of SARS-CoV2 caused the circulation of new emerging variants. Viral evolution calls for continuous genomic surveillance.

Structure–function studies contribute to deciphering how small modifcations in the primary structure could introduce desirable characteristics into enzymes without afecting its overall functioning. Malic enzymes (ME) are ubiquitous and responsible for a wide variety of functions. The availability of a high number of ME crystal structures from diferent species facilitates comparisons between sequence and structure. Specifcally, the structural determinants necessary for fumarate allosteric regulation of ME has been of particular interest. NADP-ME2 from Arabidopsis thaliana exhibits a distinctive and complex regulation by fumarate, acting as an activator or an inhibitor according to substrate and efector concentrations. However, the 3D structure for this enzyme is not yet reported. In this work, we characterized the NADP-ME2 allosteric site by structural modeling, molecular docking, normal mode analysis and mutagenesis. The regulatory site model and its docking analysis suggested that other C4 acids including malate, NADP-ME2 substrate, could also ft into fumarate’s pocket. Besides, a non-conserved cluster of hydrophobic residues in the second sphere of the allosteric site was identifed. The substitution of one of those residues, L62, by a less fexible residue as tryptophan, resulted in a complete loss of fumarate activation and a reduction of substrate afnities for the active site. In addition, normal mode analysis indicated that conformational changes leading to the activation could originate in the region surrounding L62, extending through the allosteric site till the active site. Finally, the results in this work contribute to the understanding of structural determinants necessary for allosteric regulation providing new insights for enzyme optimization. Fil: Gerrard Wheeler, Mariel Claudia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Centro de Estudios Fotosintéticos y Bioquímicos (CEFOBI-CONICET); Argentina. Fil: Arias, Cintia Lucía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Centro de Estudios Fotosintéticos y Bioquímicos (CEFOBI-CONICET); Argentina. Fil: Da Fonseca Rezende e Mello, Juliana. Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Laboratório de Modelagem Molecular & QSAR (ModMolQSAR); Brazil. Fil: Cirauqui Diaz, Nuria. Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Laboratório de Modelagem Molecular & QSAR (ModMolQSAR); Brazil. Fil: Rodrigues, Carlos Rangel. Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Laboratório de Modelagem Molecular & QSAR (ModMolQSAR); Brazil. Fil: Drincovich, María Fabiana. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Centro de Estudios Fotosintéticos y Bioquímicos (CEFOBI-CONICET); Argentina. Fil: Mendonça Teles de Souza, Alessandra. Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Laboratório de Modelagem Molecular & QSAR (ModMolQSAR); Brazil. Fil: Alvarez, Clarisa Ester. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Centro de Estudios Fotosintéticos y Bioquímicos (CEFOBI-CONICET); Argentina.