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Purpose of review To explore the immunological underpinnings of psychosis in the COVID-19 patients. Recent findings COVID-19 pandemic led to a surge in psychiatric morbidities, including psychosis. Various putative biological and psychosocial changes have been implicated in COVID-19-related psychosis. COVID-19 is a proinflammatory state. Alterations in immunological processes both as a direct consequence of infection or secondary to the hyperimmune response heuristically explain the etiopathogenesis of psychosis in the affected individual. The uses of immunosuppressant and immunomodulatory drugs may be the other moderators of a psychotic presentation in COVID-19 patients. Evidence to substantiate this hypothesis is still lacking however, which further studies should address. Because of its management implications, a better understanding of the involved immunological mechanisms becomes extremely important. Summary Evidence suggests a putative role of immunological alterations in the pathogenesis of COVID-19-related psychosis. The immunological abnormalities are primarily attributed to the pathophysiology of COVID-19 infection, medications used, and stress.

We study support recovery for a $k \times k$ principal submatrix with elevated mean $\lambda/N$, hidden in an $N\times N$ symmetric mean zero Gaussian matrix. Here $\lambda>0$ is a universal constant, and we assume $k = N \rho$ for some constant $\rho \in (0,1)$. We establish that {there exists a constant $C>0$ such that} the MLE recovers a constant proportion of the hidden submatrix if $\lambda {\geq C} \sqrt{\frac{1}{\rho} \log \frac{1}{\rho}}$, {while such recovery is information theoretically impossible if $\lambda = o( \sqrt{\frac{1}{\rho} \log \frac{1}{\rho}} )$}. The MLE is computationally intractable in general, and in fact, for $\rho>0$ sufficiently small, this problem is conjectured to exhibit a \emph{statistical-computational gap}. To provide rigorous evidence for this, we study the likelihood landscape for this problem, and establish that for some $\varepsilon>0$ and $\sqrt{\frac{1}{\rho} \log \frac{1}{\rho} } \ll \lambda \ll \frac{1}{\rho^{1/2 + \varepsilon}}$, the problem exhibits a variant of the \emph{Overlap-Gap-Property (OGP)}. As a direct consequence, we establish that a family of local MCMC based algorithms do not achieve optimal recovery. Finally, we establish that for $\lambda > 1/\rho$, a simple spectral method recovers a constant proportion of the hidden submatrix., Comment: 42 pages, 1 figure

La década del 70 al 80 fue un momento de efervescencias fruto del Vaticano II al interior de la Iglesia. La Orden de San Agustín no podía estar ajena a estos cambios, sobre todo, después del Capítulo General Intermedio del año 1968, celebrado en Villanova. La primera reunión de lo que habría de ser en el futuro la Organización de Agustinos en América Latina (OALA) se celebraría en Quito (Ecuador) al año siguiente, en abril de 1969. Sería el comienzo de un largo proceso que culminaría con la reunión de Chile de este acontecimiento agustiniano. Fuerzas diferentes, progresistas y conservadores, han animado este proyecto durante estas cuatro décadas, que al autor describe minuciosamente. Concluye con una serie de observaciones y recomendaciones.

Longitudinal polarisation of the weak bosons is a direct consequence of Electroweak symmetry breaking mechanism providing an insight into its nature, and is instrumental in searches for physics beyond the Standard Model. We perform a polarisation study of the diboson production in the $p p \to e^+\nu_e\mu^-\bar\nu_\mu$ process at NNLO QCD in the fiducial setup inspired by experimental measurements at ATLAS. This is the first polarisation study at NNLO. We employ the double-pole approximation framework for the polarised calculation, and investigate NNLO effects arising in differential distributions., Comment: corrected typos, added a reference, amended and clarified discussion with comments on top-quark loop effects, etc; matches JHEP published version

Aim of this work is to substantiate the hypothesis that the absence of lice in bats is associated with the electrification of the surface of their body during the flight.Discussion. The paper analyzes the physical phenomenon of friction electrification, the triboelectric series of substances with special attention to the objects of atmospheric electricity, and the Cohen rule that relates the dielectric properties of a substance to its permittivity. The electrical properties of the atmosphere are described including the occurrence of a potential difference between the Earth's surface and the ionosphere and the mechanism of maintaining this potential as a result of charging the ground with negative electricity by thunderstorms. The results of experimental data on the formation of a positive electrostatic charge on the surface covers of insects and birds are presented. It is hypothesized that the hair and skin membranes of bats should also be positively electrified during flight. The reasons that prevent lice from living in electrified bat hair are described. It is proposed to explain the presence of developed sebaceous glands in bats as a way of discharging electrostatic charge before returning to the shelter and the bell structure of the hair cuticle as a device for retaining the secretion of sweat glands.Conclusion. The absence of lice in bats is a direct consequence of their adaptation to active flight.

It is a fact that the use of antibiotics is inducing a growing resistance on bacteria. This situation is not only the consequence of a drugs’ misuse, but a direct consequence of a widespread and continuous use. Current studies suggest that this effect could be reversed by using abandoned antibiotics to which bacteria have lost their resistance, but this is only a temporary solution that in near future would lead to new resistance problems. Fortunately, current nanotechnology offers a new life for old and new antibiotics, which could have significantly different pharmacokinetics when properly delivered; enabling new routes able to bypass acquired resistances. In this contribution, we will focus on the use of porous silica nanoparticles as functional carriers for the delivery of antibiotics and biocides in combination with additional features like membrane sensitizing and heavy metal-driven metabolic-disrupting therapies as two of the most interesting combination therapies.

A standard incomplete-information war of attrition is extended to incorporate experimentation and private learning. We obtain a characterization of all equilibria in this extended setup and use this setup to illuminate a tradeoff between short-run and long-run gains of experimentation. The extension yields qualitative impacts on the strategic nature of the problem. The option value of experimentation serves as a credible commitment device to stay in the game, which is instrumental in inducing the other player to concede earlier. As a direct consequence, there may be an equilibrium in which the strictly less efficient player can get the better end of the deal, implying that slow learning can be a blessing in this type of competition. Our analysis gives insight into why an apparently inferior technology often survives in many standards competitions and more broadly offers implications for technology adoption and industry dynamics. We also show that there is a non-degenerate set of parameters that can support the Pareto-efficient allocation as an equilibrium outcome whereas it is never possible in the standard setup.

The International Association for the Study of Pain defines neuropathic pain as "pain arising as a direct consequence of a lesion or disease affecting the somatosensory system" (Treede et al., 2008). The associated changes can be observed in the peripheral as well as the central nervous system. The available literature discusses a wide variety of causes as predisposing for the development and amplification of neuropathic pain. Further, key interactions within sensory pathways have been discovered, but no common molecular mechanism leading to neuropathic pain has been identified until now. In the first part of this review, the pain mediating lateral spinothalamic tract is described. Different in vivo models are presented that allow studying trauma-, chemotherapy-, virus-, and diabetes-induced neuropathic pain in rodents. We furthermore discuss approaches to assess neuropathic pain in these models. Second, the current knowledge about cellular and molecular mechanisms suggested to underlie the development of neuropathic pain is presented and discussed. A summary of established therapies that are already applied in the clinic and novel, promising approaches closes the paper. In conclusion, the established animal models are able to emulate the diversity of neuropathic pain observed in the clinics. However, the assessment of neuropathic pain in the presented in vivo models should be improved. The determination of common molecular markers with suitable in vitro models would simplify the assessment of neuropathic pain in vivo. This would furthermore provide insights into common molecular mechanisms of the disease and establish a basis to search for satisfying therapeutic approaches.

Background: The direct effect of the COVID‐19 pandemic on patients with intestinal failure (IF) has not been described. Methods: We conducted a nationwide study of U.K. IF centres to evaluate the infection rates, presentations and outcomes in patients with types 2 and 3 IF. Results: A total of 45 patients with IF contracted COVID‐19 between March and August 2020; this included 26 of 2191 (1.2%) Home Parenteral Nutrition (HPN)‐dependent adults and 19 of 298 (6.4%) adults hospitalized with type 2 IF. The proportion of patients receiving nursing care for HPN administration was higher in those with community‐acquired COVID‐19 (66.7%) than the proportion in the entire HPN cohort (26.1%; p

La crisis económica ocurrida en Ecuador durante los años 2020 – 2021 como consecuencia directa de la pandemia del Covid19 agravó un problema que ya se experimentaba con la falta de empleo con la caída drástica del mercado laboral. El presente trabajo analiza los indicadores a través de varias fuentes sobre el desempleo en diferentes sectores económicos del Ecuador tomando como referencia los datos de años previos hasta la presente, se evidencia que en la actualidad solo dos de cada diez ecuatorianos tienen pleno empleo, esto quiere decir que cuentan con un trabajo que garantiza el cumplimiento de sus derechos laborales. Desde el Estado, se han tomado decisiones que, en lugar de beneficiar a las personas en condición de desempleo, han precarizado más su situación y han generado más perdidas de fuentes de empleo.

In the search for new molecules capable of treating intestinal parasitosis with less risk in the short, medium and long term, the potential of medicinal plants is explored. Psidium guajava is plant used traditional medicine to treat gastrointestinal disorders and intestinal parasitosis. According to the synthesis of reviews presented here, very few studies have been devoted to the evaluation of anthelmintic activities of Psidium guajava. Psidium guajava has secondary metabolisms responsible for its demonstrated biological activities and reported medicinal uses. The leaves and fruits of Psidium guajava contain essential oils that know a great variation in the content of compounds. Geographic and edaphic conditions, and genetic factors are factors that influence the composition of essential oils. The direct consequence is the observation of several chemotypes of essential oils of Psidium guajava. Further studies are important to demonstrate the efficacy of Psidium guajava in the treatment of intestinal parasitosis.

Scientific interest in cheese crystals extends back more than a century. However, starting around the 1970s, industry interest, and interest on the part of cheese scientists, grew dramatically as changes in cheesemaking technology and market changes caused the presence of crystals in the marketplace to increase; advanced analytical capabilities enabled new crystalline species to be identified, their origins and causative factors to be elucidated, and their contributions to cheese texture to be better understood. It is now evident that a host of organic- and inorganic-based crystals occur in natural cheeses. Some crystals form preferentially at the surface of rindless or rinded cheeses, others in the irregular openings or spherical eyes that occur within the body of some cheeses, and still others embedded within the cheese matrix. It is also evident that crystals may profoundly influence cheese texture, both as a direct consequence of their abundance, size, shape, and hardness, and as an indirect result of cascading physiochemical events initiated by crystal formation. Consumer response to increased incidence of crystals in the marketplace has been mixed. On the one hand, surface crystals of calcium lactate pentahydrate on Cheddar cheese came to be viewed quite negatively in some markets, often being mistaken for mold growth and spoilage. This triggered industry concern and led to considerable research to determine the underlying causes and to develop strategies to limit or prevent calcium lactate pentahydrate formation. At the same time, other forms of crystallization increasingly came to be viewed as positive features in the growing market dedicated to artisanal and traditional cheeses, giving rise to a bifurcated consumer response to cheese crystals that is evident today. Traditional artisanal cheesemakers perhaps have the most to gain from advances in cheese-crystal research. Traditional artisanal cheeses rely heavily on stories that are weaved around their identity to create uniqueness and add value. A challenge and opportunity for these cheesemakers in the United States and globally will be to translate the fascinating science of their cheese crystals into engaging narratives that capture the imagination, add value to their cheese, and enhance the enjoyment of their cheese by consumers.

Whereas the COVID-19 pandemic induces in people both uncertainty and angst, the latter may not be a direct consequence of uncertainty as such, but rather of the possible negative outcomes whose subjective certainty increased under the pandemic. From this perspective, we discuss the psychological determinants of people’s reactions to the pandemic and their modes of self-affirmation in response to pandemic-implied threats. Those reactions are guided by value-oriented narratives that may variously drive people’s pro- and anti-social behaviors during the pandemic.

espanolEn este trabajo planteamos un breve ensayo de las epidemias o pandemias que ocurrieron en el mundo occidental y de las cuales tenemos documentacion fehaciente desde el siglo XIV hasta el momento presente. En la misma linea exponemos que estamos inmersos en la epidemia del siglo XXI como consecuencia directa de la bonanza economica que estamos atravesando. En nuestro caso el escenario lo aplicamos a Espana y a Asturias; reflejando el numero de fallecidos. La lucha por la vida con las carencias alimenticias que arrostro la humanidad de manera constante hasta el siglo XVIII que anulan toda posibilidad de defensa innata frente al mal, la muerte subita de la peste bubonica, las deformaciones de la viruela, etc. ocupan la parte dura, pero es la realidad de la senda humana. En un segundo plano exponemos una serie de peliculas o de novelas que guardan cierta relacion con los brotes epidemicos. Esto es pura fantasia. Creemos que ambas visiones se pueden complementar porque el temor, el odio al extranjero, la inseguridad ante lo incierto, el aislamiento, el reflejo de huida, el miedo a la muerte o la busqueda de un remedio curativo son situaciones reales en ambos mundos. EnglishIn this work we presented a brief essay of the epidemics or pandemics that took place in the Western world and from which we have reliable documentation from the fourteenth century to the present moment. In the same vein we say that we are immersed in the epidemic of the 21st century as a direct consequence of the economic bonanza we are going through. In our case the scenario is applied to Spain and Asturias; reflecting the number of deaths. The struggle for life with the food deficiencies that constantly engrified humanity until the eighteenth century that nullify any possibility of innate defense against evil, the sudden death of bubonic plague, the deformations of smalllpox, etc. occupy the hard part, but it is the reality of the human path. In the background we expose a series of films or novels correlated with outbreaks. This is pure fantasy. We believe that both visions can be complemented because fear, hatred of the foreigner, insecurity about future, isolation, the reflection of flight, the fear of death or the search for a healing remedy are real situations in both worlds.

Organic materials possessing solid-state emission responsive to external stimuli have significance in a variety of material, biomedical, and optoelectronic applications. Organic molecules having different donor-acceptor architectures integrated with aggregation-induced emission (AIE) fluorophores have been utilized in development of mechanofluorochromic (MFC) materials. In this work, we have designed and synthesized phenanthroimidazole (PI) based derivatives TPE-PI-1, TPE-PI-2, TPE-PI-3, PTZ-PI-1, PTZ-PI-2, and PTZ-PI-3 where in donors tetraphenylethylene-TPE (D) and phenothiazine-PTZ (D') of contrasting donor abilities are attached to the N and C atom positions of PI. The position and mode of attachment of the donors have been changed, and an additional PTZ spacer has been introduced which has a direct consequence on their photophysical and electronic properties. The PI derivatives manifest AIE, solvatochromic, and mechanochromic behavior. The single crystal X-ray analysis of TPE-PI-1 and PTZ-PI-2 reveals bent structures for the PTZ unit and a twisted conformation for TPE moieties. The density functional theory calculations were used to obtain optimized ground-state structures of the PI derivatives. The work shows a comprehensive comparison of the photophysical, electronic, AIE, and MFC properties of the PI derivatives as an effect of variations in the position of donor, donor-acceptor strength, and change in molecular conformation on use of spacer.

espanolLa dermatitis de contacto es un motivo de consulta dermatologica frecuente en Atencion Primaria (AP), con importante repercusion en la calidad de vida de los pacientes y en el consumo de recursos sanitarios. Entre un 2 y un 4 % de estas dermatitis estan relacionadas con el uso de cosmeticos y tienen una causa alergica. El Kathon Cosmetic Grade (Kathon CG) es una combinacion de metilcloroisotiazolinona/isotiazolinona, utilizada en cosmetica por su poder conservante (biocida); sin embargo, tambien es conocido su poder sensibilizante y se le relaciona como causa de dermatitis alergica por contacto, cuya frecuencia aumenta progresivamente en nuestra sociedad actual, posiblemente por el mayor interes y uso de productos de cuidado personal. Es posible que el aumento de casos tambien sea secundario a un aumento del consumo, dado que la preocupacion por el cuidado corporal se ha convertido en una conducta en auge en nuestra sociedad, por lo que va a ser dificilmente modificable. Se debera valorar como posible solucion un cambio legislativo, con limites mas estrictos. El poder sensibilizante y alergeno del Kathon CG es observable a pesar de las limitaciones europeas impuestas, con restricciones en las concentraciones a 7,5 ppm y 15 ppm en cosmeticos leave-on y rinse-off. Esta revision tiene como objetivo visibilizar los problemas derivados del uso de productos con Kathon CG y plantear la necesidad de reevaluar las concentraciones de Kathon CG en los productos cosmeticos y de limpieza. EnglishContact dermatitis is a very frequent reason for consulting Primary Health Services, it has a significant impact on patient quality of life and requires a high input of healthcare resources. 2-4% of these dermatitis cases are related to the use of cosmetics and are mainly allergic reactions. Kathon CG is a combination of methylchloroisothiazolinone and isothiazolinone, used in cosmetics because of its preservative qualities (biocide). It is also known to be a strong skin sensitizer and is often the cause of allergic contact dermatitis, which is increasingly frequent, probably because of the increase of both use of and interest in personal care products. It is possible that the increase in the number of cases is related to the increase in the use of personal care products, which is a direct consequence of the importance given in society to bodycare. This new behaviour is going to be difficult to change, therefore we should consider having stricter legislative controls. Kathon CG sensitizer and allergen power is often seen despite European Union laws; with restriction on the concentration of 7.5 parts per million in leave-on cosmetics and 15 parts per million in rinse-off cosmetics. The purpose of this paper is to highlight the problems caused by the use of products that contain Kathon CG and reassess the concentration of Kathon CG permitted in both cosmetics and cleaning products.

The article deals with the transformation of the marriage and family structures of the population of Udmurtia in the period between 1939 to 1959. Attention is paid to the study of the infl uence of the Great Patriotic War on the family and marriage in the republic. Sources used include census materials from 1939 and 1959 and statistical records from the period in question. With the beginning of the war, the number of marriages in Udmurtia sharply decreased. The smallest number of marriages was observed in 1942. In the countryside, this was a reduction of more than three times, indicating a unusually great shortage of men. A direct consequence of the war was a reduction in the average family size as well as an increase in families headed by women. By 1959, 38.5 % of families in the countryside were led by women. With the beginning of the Great Patriotic War, remarriages became more frequent in Udmurtia. Between 1944 and 1951 they were mostly concluded by women who presumably had lost their husbands in the fi ghting. The extramarital birth rate also sharply increased. In the post-war period, particularly in the rural areas many children were born out of wedlock. The extramarital birth rate reached its peak in 1950, when every third child in Udmurtia was born out of wedlock.

Toxicology division of Forensic Science Labs (FSLs) frequently receives samples containing insecticides. Due to pendency of medico legal cases, biological samples are often stored for some time i.e from the time of collection until analysis. The role of temperature and putrefaction that may inevitably interfere with analysis results which is often ignored in such cases. In the present study, an attempt has been made to produce evidences by differentiating Thin Layer Chromatographic (TLC) results of the insecticides- Carbofuran and Carbaryl (1-naphthyl methylcarbamate) as a direct consequence of changes in the preservation methods of samples. Research must be extensively done taking into consideration of the factors like temperature, humidity, duration of time etc. so as to support studies on better preservation methodologies of Forensic samples. Keywords: Insecticides, Carbofuran, Carbaryl, Toxicology, Temperature, Putrefaction, Chromatography

This paper comments on a judgment of the Supreme Court and deals with the content of the expropriation compensation, regarding pecuniary damage. The foregoing, in order to indicate that said content is not limited to compensating the loss of property, but that, by virtue of the constitutional rule, it also includes any other effective damaging patrimonial consequence caused to the owner, as a direct and immediate consequence of the expropriation. Thus, in a partial expropriation, in addition to the replacement cost of the expropriated property, the compensation may include the cost of the material damage caused to the existing buildings in the non-expropriated fraction of the property, as long as it is verified as an immediate and direct consequence of the expropriation, and the subsequent concretion of the works that motivate the ablatory act.

The electromagnetic enhancement mechanism is a major contributor to surface-enhanced Raman scattering enhancements, which are a direct consequence of the roughness present on noble metal surfaces. The electromagnetic enhancement mechanism is a twofold phenomenon that involves the enhancement of both the incident excitation and scattered Raman fields. In this paper, we report a direct observation of the double-enhancement mechanism using a Ag nanorod array/SiO₂ dielectric layer/Ag mirror multilayer thin-film “local plasmon resonator”. The effect of light interference was controlled by adjusting the film thickness of the SiO₂ phase control layer (PCL), and the absorption rate in the Raman scattering wavelength range was tuned from 90 to 0%. In addition to the characteristic Raman peak of an aqueous solution of 4, 4-bipyridine, the background of the Raman scattering spectrum was also enhanced. By examining the relationship between the background Raman emission and the absorption spectrum, we demonstrated that the intensity of the background emission is closely related to the surface-enhanced Raman scattering (SERS) enhancement. We further illustrated that the Raman scattered field and background were enhanced when the absorption was high in the wavelength range of the scattering field. The present results not only suggest that the PCL layer may increase the intensity of plasmon-mediated broadband emission but also provide us with sufficient evidence for a twofold SERS enhancement mechanism.

The Estonian Citizens’ Assembly (ECA) was initiated in late 2012 as a direct consequence of a legitimacy crisis of Estonian political parties and representative institutions. The spark igniting this crisis was the unraveling of a scheme of illegal party financing. The response from governmental institutions took the form of a democratic innovation involving public crowd‐sourcing and deliberative mini‐publics. This study reports on a survey among the participants in the online crowd‐sourcing process of the ECA (n = 847). The study examines how this democratic innovation influenced participants’ social and political trust as well as the impact of participants' predispositions and level of satisfaction with the ECA on changes in trust. We find that participants that had positive predispositions and who were satisfied with the ECA were more likely to gain trust. Furthermore, we also find that the participants, in general, became more distrustful of political institutions, while their participation fostered increased social trust. This outcome differs from the intentions of the Estonian institutions which organized the ECA and sheds new light on the role of democratic innovations in the context of legitimacy crises. This is an important step forward in the scholarly understanding of the relationship between democratic innovation and trust. (Less)

This paper deals with school evaluation and aims to analyze perceptions and transformations in the implementation of the progressive evaluation model in a regular high school state school in the municipality of Redencao/CE. To understand this process, we sought to understand the perception of school agents - teachers, managers and students -, as well as to observe the approval, disapproval, transfer and avoidance rates comparatively before and after the implementation of this evaluation model. The main theoretical references in the area of education and curriculum were Jose Carlos Libâneo, Tomaz Tadeu da Silva, Heloisa Luck, Cipriano Luckesi and Antoni Zabala. The results indicated that the implementation of the progressive evaluation in the school did not have as a direct consequence a higher approval rate, but teachers and students feel that the model facilitates learning. These results lead to consider other aspects that interfere in teaching-learning as the increase in the number of students per room. It is concluded that, in view of the observed, school management must continue to rethink the processes of evaluation in the face of educational dynamics. Key-words: progressive evaluation; high school; school.

Intraovarianism refers to mechanisms within an ovary that affect the local follicle and luteal dynamics and is well-represented in heifers by greater frequency of ovulation from the right ovary (RO) than the left ovary (LO). On average, the RO has more 6-mm follicles than the LO before one follicle is selected to deviate in diameter and become the future ovulatory follicle. Therefore, the ovulatory follicle is more frequently selected from the RO. More follicles in the RO likely develop before birth as indicated by greater weight of the RO with more 0.3- to 4.8-mm follicles in recently born calves. It has been proposed that differences in intraovarianism between sides are a consequence of differences between sides in the inherent intraovarian angioarchitecture. The frequency of the pair of ovulations at the beginning and end of 900 interovulatory intervals (IOI) was lowest for the left/left (LL) pair (16%) and higher and similar among the RR, LR, and RL pairs (28% each). The lower frequency of LO ovulation was entirely a function of the LL pair as indicated by the lower frequency of the LL than RR pairs without a difference among the RR, LR, and RL pairs. Ovulations from the opposite sides at the beginning and end of an IOI (LR and RL pairs) would not have contributed to a difference in ovulation frequency between LO and RO. In conclusion, the greater frequency of RO (56%) than LO (44%) ovulation was mathematically and functionally a direct consequence of the low frequency of the LL pair of ovulations.Summary sentenceThe greater frequency of ovulation from the right ovary is mathematically and functionally attributable to the left ovary.Graphical Abstract

The early interest that EU law has demonstrated for public procurement contracts has gradually been molded into a sector-specific paradigm of European administrative law. Despite the constant movement of the sector counting already four generations of substantive and two generations of procedural EU law, its qualification as administrative law provides some pillars of stability; as an expression of a sui generis principle of legality, the award of public contracts is organized via formalistic, yet sometimes rigid and time-consuming procedures, due process emerging as a common principle among national and supranational administrative systems. Even though due process constitutes the gateway to accountability, the aim of the paper is limited to underlining the indicators of administrative procedure in the award of public contracts.

Absenting and/or substituting words or morphemes that are considered purely grammatical in the discourse is the defining symptom of the so-called “telegraphic speech”. Depending on the theory, the instability with the grammatical resources may be considered a direct consequence of deficits in very specific language levels. In this text, we have addressed a discussion concerning the grammatical functioning aiming, overall, to uphold the notion that all linguistic levels are genetically imbricated in language functioning. It was also aimed to outstand the importance to consider this imbricated nature in order to blueprint a comprehension about linguistic-cognitive phenomena, mainly concerning the phenomena related to the linguistic production in nonfluent cases of aphasia. The reflection was grounded on socio-historic-cultural approach to Neuropsychology; on theoretic-methodological assumptions of Enunciative-Discursive Neurolinguistics and on the principles held by Functional Discourse Grammar.

Advances in our understanding of molecular mechanisms of tumorigenesis have translated into knowledge-based therapies directed against specific oncogenic signaling targets. These therapies often induce dramatic responses in susceptible tumors. Unfortunately, most advanced cancers, including those with robust initial responses, eventually acquire resistance to targeted therapies and relapse. Even though immune-based therapies are more likely to achieve complete cures, acquired resistance remains an obstacle to their success as well. Acquired resistance is the direct consequence of pre-existing intratumor heterogeneity and ongoing diversification during therapy, which enables some tumor cells to survive treatment and facilitates the development of new therapy resistant phenotypes. In this review, we discuss the sources of intratumor heterogeneity and approaches to capture and account for it during clinical decision making. Finally, we outline potential strategies to improve therapeutic outcomes by directly targeting intratumor heterogeneity.

Introduction Tinnitus is the perception of sound in the absence of external sound stimulation. There is a general agreement that it is a direct consequence of irreversible and permanent cochlear damage. Objectives The present work is designed to study the distortion product otoacoustic emissions (DPOAEs) in tinnitus patients with normal hearing in comparison with normal hearing control and to study any possible correlation between DPOAEs recording and patients' complaints. Methods The present study included 80 subjects divided into 2 groups: Control group: consisted of 30 normal-hearing adults not complaining of tinnitus and Study group: consisted of 50 normal-hearing adults complaining of tinnitus. The methodology includes full audiological history, otoscopic examination, basic audiological evaluation, DPOAEs including both DP-gram and DPOAEs input/output functions. Results Basic audiological evaluation showed within normal hearing sensitivity in both groups, however, with significant higher hearing thresholds in tinnitus patients at all frequency ranges. The Tinnitus Handicap Inventory Questionnaire showed mean scores of 35.2 ± 16.9 in the study group. The DP-gram showed higher amplitudes in the control group when compared with tinnitus patients. The DPOAEs input-output functions at different frequencies (1, 2, 4 and 6kHz) also showed higher amplitudes at all frequencies and different input levels. The slope of the I/O function tends to be steeper in tinnitus cases. Conclusion Patients with tinnitus might have neural dysfunction at either the level of the cochlea, as shown in reduced DPOAE levels, and changes in the normal DP-I/O function recorded in the present work.

To analyze effects of the COVID-19 pandemic on the consumption of personal protective equipment and products (PPEP), as well as the frequency of surgical site infection (SSI) among non-COVID-19 patients submitted to cesarean sections. A retrospective study was conducted in a maternity unity of a public teaching hospital which was not part of the reference service for COVID-19 treatment. It compared PPEP consumption and the occurrence of SSI after cesarean sections in monthly periods before and after the occurrence of the first case of COVID-19 in Porto Alegre, state of Rio Grande do Sul, Brazil. Personal protective equipment and products consumption was measured as units of masks, gloves, gowns, and caps, and use of alcohol-based products or soap for hand sanitation as ml/patient/day. The SSI index was calculated as the proportion of cases of SSI over the number of cesarean sections performed monthly during the study period. There was an increase in all measured items of PPEP, with consumption of disposable masks with a median of 1,450 units in the pre-COVID period, and of 2550 in the post-COVID period (a 75.9% increase). A decrease of 49% in SSI was detected, with a median of 1.74 in the pre-COVID period and of 0.89 in the post-COVID period. The increase in consumption of PPEP could be a result of safer practices adopted by healthcare workers with the advent of COVID-19, of which the following reduction in the occurrence of SSI could be a direct consequence. Despite the severity of the crisis, one could state that extreme situations can lead to valuable reflections and opportunities for improvement. Analisar os efeitos da pandemia de COVID-19 sobre o consumo de equipamentos e produtos de proteção individual (EPPI), assim como a frequência de infecção de sítio cirúrgico (ISC) em pacientes não infectadas por COVID-19 submetidas a cesarianas. MéTODOS: Foi realizado um estudo retrospectivo em uma maternidade de um hospital público de ensino que não fazia parte do serviço de referência para o tratamento do COVID-19. Foram comparados o consumo de EPPI e a ocorrência de ISC após cesárea nos períodos mensais antes e após a ocorrência do primeiro caso de COVID-19 em Porto Alegre, RS, Brasil. O consumo de EPPI foi medido em unidades de máscaras, luvas, aventais e gorros, e o uso de produtos à base de álcool ou de sabonete para higienização das mãos em ml/paciente/dia. O índice SSI foi calculado como a proporção de casos de ISC sobre o número de cesarianas realizadas mensalmente durante o período do estudo. Houve aumento em todos os itens medidos do EPPI, com o consumo de máscaras descartáveis apresentando uma mediana de 1.450 no período pré-COVID e de 2550 no período pós-COVID (aumento de 75,9%). Detectou-se também diminuição de ISC, com medianas de 1,74 no período pré-COVID e de 0,89 no período pós-COVID, com redução de 49% no valor da mediana. CONCLUSãO: O aumento do consumo de EPPI pode ser resultado de práticas mais seguras adotadas pelos profissionais de saúde com o advento do COVID-19, do qual a redução na ocorrência de ISC pode ser uma consequência direta. Apesar da gravidade da crise, pode-se afirmar que situações extremas podem gerar reflexões valiosas e oportunidades de melhorias.

Significance Primary cilia are important organelles that exist in almost all eukaryotic cells. Intraflagellar transport (IFT) is a motor-protein–driven bidirectional intracellular transport mechanism in cilia. Previous studies have shown that motors in Caenorhabditis elegans chemosensory cilia undergo rapid turnarounds to effectively work together in driving orderly IFT. The mechanism of motor turnarounds has, however, remained unclear. Here, using a combination of advanced fluorescence imaging and single-molecule analysis, we directly show that the individual turnarounds are due to motors switching between opposite-direction IFT trains. Furthermore, we show that switching events consist of motors detaching from a train, diffusing to another one followed by attachment. This directly demonstrates that motors switch trains by diffusion, which clarifies the mechanism of motor turnarounds., Intraflagellar transport (IFT), a bidirectional intracellular transport mechanism in cilia, relies on the cooperation of kinesin-2 and IFT-dynein motors. In Caenorhabditis elegans chemosensory cilia, motors undergo rapid turnarounds to effectively work together in driving IFT. Here, we push the envelope of fluorescence imaging to obtain insight into the underlying mechanism of motor turnarounds. We developed an alternating dual-color imaging system that allows simultaneous single-molecule imaging of kinesin-II turnarounds and ensemble imaging of IFT trains. This approach allowed direct visualization of motor detachment and reattachment during turnarounds and accordingly demonstrated that the turnarounds are actually single-motor switching between opposite-direction IFT trains rather than the behaviors of motors moving independently of IFT trains. We further improved the time resolution of single-motor imaging up to 30 ms to zoom into motor turnarounds, revealing diffusion during motor turnarounds, which unveils the mechanism of motor switching trains: detach–diffuse–attach. The subsequent single-molecule analysis of turnarounds unveiled location-dependent diffusion coefficients and diffusion times for both kinesin-2 and IFT-dynein motors. From correlating the diffusion times with IFT train frequencies, we estimated that kinesins tend to attach to the next train passing in the opposite direction. IFT-dynein, however, diffuses longer and lets one or two trains pass before attaching. This might be a direct consequence of the lower diffusion coefficient of the larger IFT-dynein. Our results provide important insights into how motors can cooperate to drive intracellular transport.

The COVID‐19 pandemic has been associated with worsening mental health but it is unclear whether this is a direct consequence of containment measures, like “Stay at Home” orders, or due to other considerations, such as fear and uncertainty about becoming infected. It is also unclear how responsive mental health is to a changing situation. Exploiting the different policy responses to COVID‐19 in England and Scotland and using a difference‐in‐difference analysis, we show that easing lockdown measures rapidly improves mental health. The results were driven by individuals with lower socioeconomic position, in terms of education or financial situation, who benefited more from the end of the strict lockdown, whereas they suffered a larger decline in mental health where the lockdown was extended. Overall, mental health appears to be more sensitive to the imposition of containment policies than to the evolution of the pandemic itself. As lockdown measures may continue to be necessary in the future, further efforts (both financial and mental health support) are required to minimize the consequences of COVID‐19 containment policies for mental health.

Purpose: The outcome of radiotherapy is a direct consequence of the dose delivered to the patient. Yet image-guidance and motion management to date focus on geometrical considerations as a practical surrogate for dose. Here, we propose real-time dose-guidance realized through continuous motion-including dose reconstructions and demonstrate this new concept in simulated liver stereotactic body radiotherapy (SBRT) delivery. Materials and methods: During simulated liver SBRT delivery, in-house developed software performed real-time motion-including reconstruction of the tumor dose delivered so far and continuously predicted the remaining fraction tumor dose. The total fraction dose was estimated as the sum of the delivered and predicted doses, both with and without the emulated couch correction that maximized the predicted final CTV D95% (minimum dose to 95% of the clinical target volume). Dose-guided treatments were simulated for 15 liver SBRT patients previously treated with tumor motion monitoring, using both sinusoidal tumor motion and the actual patient-measured motion. A dose-guided couch correction was triggered if it improved the predicted final CTV D95% with 3, 4 or 5 %-points. The final CTV D95% of the dose-guidance strategy was compared with simulated treatments using geometry guided couch corrections (Wilcoxon signed-rank test). Results: Compared to geometry guidance, dose-guided couch corrections improved the median CTV D95% with 0.5–1.5 %-points (p < 0.01) for sinusoidal motions and with 0.9 %-points (p < 0.01, 3 %-points trigger threshold), 0.5 %-points (p = 0.03, 4 %-points threshold) and 1.2 %-points (p = 0.09, 5 %-points threshold) for patient-measured tumor motion. Conclusion: Real-time dose-guidance was proposed and demonstrated to be superior to geometrical adaptation in liver SBRT simulations.

Dose is one of the parameters that any pharmacologist seriously considers when studying the effects of a drug. If the necessary dose to achieve a desired pharmacological effect is in a toxic or very toxic range for human use, the drug will probably fall out from further research. The concentration that a drug can reach at its target organ or cell is a direct consequence of the administered dose and its pharmacodynamic properties. Basic researchers investigate at the cellular level or eventually with xenografts. They use different concentrations of the drug in order to determine its cellular effects. However, in many cases, these concentrations require doses that are in the toxic range or well beyond any clinically achievable level. Therefore, in these cases, research is in the realm of Toxicology rather than therapeutics. This paper will show some examples about this exercise in futility which is time and resource consuming but that pullulates the pages of many prestigious journals. Many seasoned researchers seem to have forgotten the Paracelsus Paradox.

Earth's bow shock, resulting from the interaction of the super-magnetosonic solar wind and Earth's magnetic field, has been studied for over 50 years and serves as an ideal astrophysical laboratory to study collisionless shocks. The Earth's bow shock offers a unique opportunity to study it through in-situ measurements. Shocks are one of nature's most powerful particle accelerators and have been connected to relativistic electron acceleration and cosmic rays. Upstream shock observations include wave generation, wave-particle interactions and SLAMS, while at the shock and downstream, particle acceleration, magnetic reconnection and plasma jets can be observed. Here, using Magnetospheric Multiscale (MMS) we show the first in-situ evidence of super-magnetosonic downstream flows (jets) generated at the Earth’s bow shock as a direct consequence of shock reformation. Jets are observed downstream due to a combined effect of upstream plasma wave evolution and an ongoing reformation cycle of the bow shock. This generation process can also be applicable to planetary and astrophysical plasmas where collisionless shocks are commonly found.

We describe a correspondence between the infinitesimal deformations of a periodic bar-and-joint framework and periodic arrangements of quadrics. This intrinsic correlation provides useful geometric characteristics. A direct consequence is a method for detecting auxetic deformations, identified by a pattern consisting of homothetic ellipsoids. Examples include frameworks with higher crystallographic symmetry.

The study conducts research on lean product development (PD) methodology and presents a case study of its practical application into a specific one-of-a-kind development of large power transformers. The demonstrated framework is the result of a 5-year intensive research that led to an extensive transformation of a traditional PD environment into a highly efficient process according to lean principles. Paper explains how lean PD integrates with robust, concurrent and smart design strategies in highly individualized PD business. A generalized framework of PD and design process renovation is presented, comprising three main fields of interest: Process & Tools, People, and Knowledge. A direct consequence of implied renovation are significant savings. Case-study company cut down engineering changes by 32 % in three year test period and experienced performance improvement between 25 % and 83 % across designated process indicators. (Less)

Introduction: Child feeding practices have a direct consequence on the nutritional status of children under two year which ultimately have impact on child survival. Socio-cultural barriers is one of the main factors in infant and young child feeding in various community. This study aims to explore socio-cultural barriers of infant and young child feeding practices among mothers of Kumal community in Nuwakot district. Methods: Cross-sectional descriptive study was carried out among mother of 6-23 months children’s in Kumal community. Data was collected from 67 respondents through face-to-face interview. The collected data was entered in Epi-data version 3.1 and analyzed using SPSS, version 20. Results: Our study reveals that 83.6% of the respondents had initiated early breastfeeding. More than half (56.7%) of the respondents had exclusive breastfeeding and 97% had extended breastfeeding. Half (50.7%) of the respondents introduce complementary feeding in time, sex of child was associated with exclusive breastfeeding and complementary feeding. Similarly, size of household, mother and father education was associated with continuation of breastfeeding practice. Conclusions: The prevalence of exclusive breastfeeding and appropriate complementary feeding is still low due to many factors and one being socio cultural practices and beliefs. Interventions that can hit the socio-cultural beliefs should be given priority to exterminate the socio-cultural taboos from root level.

In this paper, we first give a multiset version of the graph-theoretical interpretation of the classic determinant of a matrix A based on a multiset generalization of the cycle cover of its associated digraph D ( A ) . Then, as a direct consequence of this interpretation, we present another algebraic proof of a weighted version of the original coin arrangements lemma.

This paper provides an overview of credit risk assessment and operational risk prevention and coverage methods. Bank management is based on profit maximization and risk minimization objectives. The level of profit obtained by a bank is also a direct consequence of the type of strategy adopted in the bank's management in the sense of accepting or not the risks in the performed activity. The risk of unexpected losses are treated as recorded in the banking business developments due to the registration of the results to the effects anticipated. Operational risk is the danger of unexpected losses, a result of the action of the bank's internal and external factors affecting conducting operational activity. So, we are presented methods of prevention and operational risk coverage.

The book Trends of Private Law, edited jointly by the publishers Dike and Santiago de Cali University, has the objective of making the reader reflect on some problems that private law currently knows, analyzed from a labor, societal and civil perspective . As pointed out by the coordinator of the book Erica Florina Carmona Bayona, the law is transformed, as well as private law, which entails as a direct consequence that "the classic dividing line between the public and the private, is becoming weaker in a globalized world "(p.17).

We show that any virtual or welded period of a classical knot $K$ can be realized as a classical period. A direct consequence is that a classical knot admits only finitely many virtual or welded periods.

Resumen: El artículo aborda los Cahiers de Simone Weil entendidos como espacio de un pensar que se hace en escritura. Desde la confrontación de La gravedad y la gracia con los Cuadernos, se plantean las problemáticas en la recepción de los Cuadernos como consecuencia directa del modo de escritura que los configura. Desde ahí, se reflexiona acerca de los cuadernos como lugar de una escritura íntima, exiliada, retirada del discurso y que se da necesariamente en forma fragmentaria. Se muestra también cómo, en la experiencia de Simone Weil, la tensión entre fragmentariedad y unidad se corresponde con la imposibilidad de comunicar la verdad.

We compute the leading order (LO) $qg\to q \gamma$ and next-to-leading order (NLO) $gg\to q{\bar q} \gamma$ contributions to inclusive photon production in proton-proton (p+p) collisions at the LHC. These channels provide the dominant contribution at LO and NLO for photon transverse momenta $k_{\gamma\perp}$ corresponding to momentum fractions of $x\leq 0.01$ in the colliding protons. Our computations, performed in the dilute-dense framework of the Color Glass Condensate effective field theory (CGC EFT), show that the NLO contribution dominates at small-$x$ because it is sensitive to $k_\perp$-dependent unintegrated gluon distributions in both of the protons. We predict a maximal $10\%$ modification of the cross section at low $k_{\gamma\perp}$ as a direct consequence of the violation of $k_\perp$-factorization. The coherence effects responsible for this modification are enhanced in nuclei and can be identified from inclusive photon measurements in proton-nucleus collisions. We provide numerical results for the isolated inclusive photon cross section for $k_{\gamma\perp}\leq 20$ GeV in p+p collisions that can be tested in the future at the LHC., Comment: 9 pages, 5 figures

Summary Cells can communicate mechanically by responding to mechanical deformations generated by their neighbors. Here, we describe a new role for mechanical communication by demonstrating that mechanical coupling between cells acts as a signaling cue that reduces intrinsic noise in the interacting cells. We measure mechanical interaction between beating cardiac cells cultured on a patterned flexible substrate and find that beat-to-beat variability decays exponentially with coupling strength. To demonstrate that such noise reduction is indeed a direct consequence of mechanical coupling, we reproduce the exponential decay in an assay where a beating cell interacts mechanically with an artificial stochastic ‘mechanical cell’. The mechanical cell consists of a probe that mimics the deformations generated by a stochastically beating neighboring cardiac cell. We show that noise reduction through mechanical coupling persists long after stimulation stops and identify microtubule integrity, NOX2, and CaMKII as mediators of noise reduction., Graphical Abstract, Highlights • Mechanical communication reduces intrinsic noise in interacting cells • Cardiac cell beating noise decays exponentially with the strength of mechanical coupling • Identical exponential decay length is obtained using a stochastic mechanical cell • NOX2, ROS, and CaMKII are involved in mechanical communication-induced noise reduction, Biological Sciences; Cell Biology; Physical Sciences

For the last two decades we have been observing a huge increase in discoveries of long-period comets (LPCs), especially those with large-perihelion distances. We collected data for a full sample of LPCs discovered over the 1801-2017 period including their osculating orbits, discovery moments (to study the discovery distances), and original semimajor axes (to study the number ratio of large-perihelion to small-perihelion LPCs in function of 1/a-original, and to construct the precise distribution of an 1/a-original). To minimize the influence of parabolic comets on these distributions we determined definitive orbits (which include eccentricities) for more than 20 LPCs previously classified as parabolic comets. We show that the percentage of large-perihelion comets is significantly higher within Oort spike comets than in a group of LPCs with a

MLKL phosphorylation by RIP3 is the commitment step of necroptosis execution, which could induce MLKL activation featured as MLKL monomer-oligomer transition. Here, we reported that the dimerization of the MLKL kinase-like domain was the direct consequence of RIP3 triggered MLKL-phosphorylation. Two inter-dimer interfaces were found in the crystal structure of human MLKL. Mutations destroying both interfaces could prevent RIP3-induced MLKL oligomerization and necroptosis efficiently. Moreover, we confirmed MLKL self-assembly by the internal coiled-coil region is necessary for MLKL oligomerization and function. The mutations disrupting coiled-coil self-assembly repressed necroptosis, but it did not prevent RIP3-induced dimerization of the MLKL kinase-like domain. So that, MLKL activation is a sequential process, which begins with kinase-like domain dimerization, and followed by internal coiled-coil region self-assembly to form a proper MLKL oligomer. Besides human MLKL, structural and functional analysis showed the kinase-like domain dimerization was conserved among mammalian species, suggesting it is a general step of the RIP3-induced MLKL activation process.

Targeting protein-protein interactions (PPIs) has been recently recognized as an emerging therapeutic approach for several diseases. Up today, more than half a million PPI dysregulations have been found to be involved in pathological events. The dynamic nature of these processes and the involvement of large protein surfaces discouraged anyway the scientific community in considering them promising therapeutic targets. More recently peptide drugs received renewed attention since drug discovery has offered a broad range of structural diverse sequences, moving from traditionally endogenous peptides to sequences possessing improved pharmaceutical profiles. About 70 peptides are currently on the marked but several others are in clinical development. In this review we want to report the update on these novel APIs, focusing our attention on the molecules in clinical development, representing the direct consequence of the drug discovery process of the last 10 years. The comprehensive collection will be classified in function of the structural characteristics (native, analogous, heterologous) and on the basis of the therapeutic targets. The mechanism of interference on PPI will also be reported to offer useful information for novel peptide design.

The analysis of circulating tumor DNA (ctDNA) released by tumor cells holds great promise for patients with lymphoma, to refine the diagnostic procedure, clarify the prognosis, monitor the response to treatment, and detect relapses earlier. One of the main challenges of the coming years is to adapt techniques from highly specialized translational teams to routine laboratories as this requires a careful technical and clinical validation, and we have to achieve this as fast as possible to transform a promising biomarker into a routine analysis to have a direct consequence on patient care. Whatever the analytical technology used, the prerequisite is to obtain high yields of ctDNA of optimal quality. In this review, we propose a step-by-step description of the preanalytical process to obtain high-quality ctDNA, emphasizing the technical choices that need to be made and the experimental data that can support these choices.

The $\{0,\frac{1}{2}\}$-closure of a rational polyhedron $\{ x \colon Ax \le b \}$ is obtained by adding all Gomory-Chv\'atal cuts that can be derived from the linear system $Ax \le b$ using multipliers in $\{0,\frac{1}{2}\}$. We show that deciding whether the $\{0,\frac{1}{2}\}$-closure coincides with the integer hull is strongly NP-hard. A direct consequence of our proof is that, testing whether the linear description of the $\{0,\frac{1}{2}\}$-closure derived from $Ax \le b$ is totally dual integral, is strongly NP-hard., Comment: 7 pages

Very severe Myalgic Encephalomyelitis (ME), (also known as Chronic Fatigue Syndrome) can lead to problems with nutrition and hydration. The reasons can be an inability to swallow, severe gastrointestinal problems tolerating food or the patient being too debilitated to eat and drink. Some patients with very severe ME will require tube feeding, either enterally or parenterally. There can often be a significant delay in implementing this, due to professional opinion, allowing the patient to become severely malnourished. Healthcare professionals may fail to recognize that the problems are a direct consequence of very severe ME, preferring to postulate psychological theories rather than addressing the primary clinical need. We present five case reports in which delay in instigating tube feeding led to severe malnutrition of a life-threatening degree. This case study aims to alert healthcare professionals to these realities.

The history of modern humans in the Iberian Peninsula includes a variety of population arrivals sometimes presenting admixture with resident populations. Genetic data from current Iberian populations revealed an overall east - west genetic gradient that some authors interpreted as a consequence of the Reconquista, where Catholic Kingdoms expanded their territories towards the south while displacing Muslims. However, this interpretation has not been formally evaluated. Here, we present a qualitative analysis of the causes of the current genetic gradient observed in the Iberian Peninsula using extensive spatially-explicit computer simulations based on a variety of evolutionary scenarios. Our results indicate that the Neolithic range expansion clearly produces the orientation of the observed genetic gradient. Concerning the Reconquista (including political borders among Catholic Kingdoms and regions with different languages), if modelled upon a previous Neolithic expansion it effectively favoured the orientation of the observed genetic gradient and shows local isolation of certain regions (i.e., Basques and Galicia). Despite further evolutionary scenarios could be evaluated to obtain an accurate understanding of the causes of the Iberian genetic gradient, here we suggest that this gradient has a more complex explanation than that previously hypothesized., The simulated data and corresponding PC maps associated to this study are here deposited. See README.txt for details about the provided data.