Lrba participates in the differentiation of IgA+ B lymphocytes through TGFßR signaling.

Introduction: Lrba is a cytoplasmic protein involved in vesicular trafficking. Lrba-deficient (Lrba-/-) mice exhibit substantially higher levels of IgA in both serum and feces than wild-type (WT) mice. Transforming growth factor ß1 (TGFß1) and its receptors (TGFßR I and II) is essential for differentiating IgA+ B cells. Furthermore, increased IgA production suggests a potential connection between Lrba and the TGFßR signaling pathway in IgA production. However, the specific function of Lrba in B cell biology remains unknown. Aim: Given the increased IgA levels in Lrba-/- mice, the goal in this work was to explore the lymph organs where the switch to IgA occurs, and if TGFßR function is affected. Methods: Non-immunized Lrba-/- mice were compared with Lrba+/+ mice. IgA levels in the serum and feces, as well as during peripheral B cell development, were determined. IgA+ B cells and plasma cells were assessed in the small intestine and secondary lymphoid organs, such as the spleen, mesenteric lymph nodes, and Peyer's patches. The TGFßR signaling pathway was evaluated by determining the expression of TGFßR on B cells. Additionally, SMAD2 phosphorylation was measured under basal conditions and in response to recombinant TGFß. Finally, confocal microscopy was performed to investigate a possible interaction between Lrba and TGFßR in B cells. Results: Lrba-/- mice exhibited significantly higher levels of circulating IgA, IgA+ B, and plasma cells than in peripheral lymphoid organs those in WT mice. TGFßR expression on the membrane of B cells was similar in both Lrba-/- and Lrba+/+ mice. However, intracellular TGFßR expression was reduced in Lrba-/- mice. SMAD2 phosphorylation showed increased levels under basal conditions; stimulation with recombinant TGFß elicited a poorer response than in that in Lrba+/+ B cells. Finally, we found that Lrba colocalizes with TGFßR in B cells. Conclusion: Lrba is essential in controlling TGFßR signaling, subsequently regulating SMAD2 phosphorylation on B cells. This mechanism may explain the increased differentiation of IgA+ B cells and production of IgA-producing plasma cells.

A protease and a lipoprotein jointly modulate the conserved ExoR-ExoS-ChvI signaling pathway critical in Sinorhizobium meliloti for symbiosis with legume hosts.

Sinorhizobium meliloti is a model alpha-proteobacterium for investigating microbe-host interactions, in particular nitrogen-fixing rhizobium-legume symbioses. Successful infection requires complex coordination between compatible host and endosymbiont, including bacterial production of succinoglycan, also known as exopolysaccharide-I (EPS-I). In S. meliloti EPS-I production is controlled by the conserved ExoS-ChvI two-component system. Periplasmic ExoR associates with the ExoS histidine kinase and negatively regulates ChvI-dependent expression of exo genes, necessary for EPS-I synthesis. We show that two extracytoplasmic proteins, LppA (a lipoprotein) and JspA (a lipoprotein and a metalloprotease), jointly influence EPS-I synthesis by modulating the ExoR-ExoS-ChvI pathway and expression of genes in the ChvI regulon. Deletions of jspA and lppA led to lower EPS-I production and competitive disadvantage during host colonization, for both S. meliloti with Medicago sativa and S. medicae with M. truncatula. Overexpression of jspA reduced steady-state levels of ExoR, suggesting that the JspA protease participates in ExoR degradation. This reduction in ExoR levels is dependent on LppA and can be replicated with ExoR, JspA, and LppA expressed exogenously in Caulobacter crescentus and Escherichia coli. Akin to signaling pathways that sense extracytoplasmic stress in other bacteria, JspA and LppA may monitor periplasmic conditions during interaction with the plant host to adjust accordingly expression of genes that contribute to efficient symbiosis. The molecular mechanisms underlying host colonization in our model system may have parallels in related alpha-proteobacteria.

A Case of Prolonged Fever in a Patient Infected With COVID-19 on Ofatumumab.

We discuss a case of a 53-year-old woman with multiple sclerosis on monthly ofatumumab injections, who was infected with SARS-CoV-2 with persistent fevers for seven weeks. She was hospitalized for fever with diagnostic workup being unremarkable with negative SARS-CoV-2 IgM and undetectable nucleocapsid IgG antibodies four weeks out from the initial infection, indicating she may not have mounted an appropriate immune response to the infection. Patients on immunosuppression therapy may have a prolonged course of disease given that medications such as ofatumumab can take up to 24 weeks of B-cell recovery post-treatment discontinuation and a longer road to recovery.

Pfizer-BioNTech vaccine induces the production of cross-reactive antibodies against Trypanosoma cruzi proteins: A preliminary study.

OBJECTIVE: To evaluate the presence of cross-reactivity by anti-severe acute respiratory syndrome coronavirus 2 antibodies induced by the Pfizer-BioNTech vaccine against Trypanosoma cruzi proteins in a screening test. METHODS: Forty-three serum samples were obtained from personnel at the Hospital General Naval de Alta Especialidad in Mexico City who received one or two doses of the vaccine and were tested for T. cruzi infection using four tests: two 'in house' enzyme-linked immunosorbent assays (ELISAs), a commercial ELISA diagnostic kit and an immunoblot test. RESULTS: IgG antibodies against the T. cruzi proteins were present in the serum of unvaccinated subjects and subjects who had received one or two doses of the vaccine. The positivity of the samples against T. cruzi was ruled out by means of a Western Blot assay, where all samples were negative for T. cruzi. CONCLUSION: The data suggest that people convalescing from coronavirus disease 2019 and those who received the Pfizer-BioNTech vaccine exhibit cross-reactive antibodies against T. cruzi antigens in ELISA assays.

Resistance to Diatraea (Lepidoptera: Crambidae) stem borers in sugarcane is independent of species.

Evaluation of host-plant resistance on sugarcane to the sugarcane stem borers of Diatraea spp. is normally conducted in Colombia under field conditions, where environmental variations make the study of the insect-plant relationships difficult. Additionally, several species (i.e., D. saccharalis, D. indigenella, D. tabernella, and D. busckella), which are predominant in Colombia, can overlap in their distribution, raising the question of whether different varieties have the same responses to different pest species. The present study conducted evaluations of host-plant resistance under screen house conditions using two contrasting varieties (CC 93-3895, resistant, and CC 93-3826, susceptible) that were infested with the above-mentioned borer species. Observations of pest injury were conducted on internodes, leaves, and spindles. Survival and size (body mass) of the individuals recovered were analyzed and a Damage Survival Ratio (DSR) was proposed. The resistant CC 93-3895 exhibited less stalk injury, less emergence holes on internodes, and lower DSR; additionally, recovery of pest individuals was lower in comparison with CC 93-3826, independent of the borer species. Insect-plant interactions are discussed, as no previous information was available for three of the species tested (i.e., D. tabernella, D. indigenella, and D. busckella). This screen house protocol is proposed to characterize host-plant resistance among several cultivars from the Colombian sugarcane germplasm bank, using CC 93-3826 and CC 93-3895 as contrasting controls and D. saccharalis as the species model.

Lactantes febriles menores de tres meses sin foco aparente: ¿es necesario cambiar la estrategia de evaluación?: probamos el step by step / Febrile infants of under three months of age without apparent focus: is it necessary to change the assessment strategy?: we tested the step-by-step approach / Lactentes febris com menos de três meses de idade e sem foco aparente: é necessário alterar a estratégia de avaliação?: tentamos o "passo a passo"

Introducción: la fiebre es un motivo muy frecuente de consulta y hasta en un 20% de los pacientes no se encuentra la causa. En el ámbito de la emergentología pediátrica clásicamente ha existido interés en homogeneizar la forma de evaluar los lactantes febriles menores de tres meses. Contar con un protocolo que permita detectar precozmente el niño que cursa una infección bacteriana invasiva (IBI) sin realizar conductas desproporcionadas es todo un desafío. Objetivo: evaluar y comparar la capacidad para identificar IBI en la pauta actual de fiebre sin foco (FSF) como en la estrategia step by step, en lactantes con FSF valorados en el DEP-CHPR. Material y métodos: estudio observacional, descriptivo, retrospectivo y de pruebas diagnósticas. Criterios de inclusión: lactantes menores de 90 días de vida que consultaron en 2017 y 2018 en DEP-CHPR con diagnóstico de FSF. Resultados: se incluyeron 261 lactantes evaluados con la pauta de FSF actual, en ellos se aplicó la estrategia step by step. El rango de edad fue de 84 días (4-88 días) con una media de 41 días. Sexo masculino 148 niños (56,7%). Se registraron 37 infecciones bacterianas (14,2%) de las cuales 3 fueron IBI (1,1%) y 34 fueron no-IBI (13,1%). La sensibilidad para step by step fue de 0,94% y de 0,89 para la pauta actual, con un VPN de 0,98 para ambas estrategias. Discusión: los lactantes menores de 3 meses son más susceptibles por características fisiológicas a infecciones bacterianas invasivas y cuanto más pequeño aumenta aún más la frecuencia. El step by step discrimina a menores de 1 mes en menores de 21 días y otro grupo de más de 21 días. Nuestra pauta no hace esta discriminación y realiza por igual laboratorio en sangre, orina y líquido cefalorraquídeo; realizando en ocasiones estudios cruentos no necesarios. Conclusiones: ambas estrategias aplicadas en esta población resultaron altamente sensibles para identificar infección bacteriana con un VPN elevado. La aplicación de step by step presenta como beneficio adicional evitar con seguridad la punción lumbar en recién nacidos entre los 21 y 28 días.

Introduction: fever is a very frequent reason for consultation and in up to 20% of patients the cause has not been found. In the field of pediatric emergentology, there has been a traditional interest in homogenizing the way of assessing febrile infants under three months of age. Having a protocol that enables early detection of children with IBIs without engaging in disproportionate procedures is a challenge. Objective: to evaluate and compare the ability to identify IBIs in the present FSF regimen as in the Step-by-Step strategy, in infants with FSF assessed at the Pereira Rossell Pediatric Hospital Center. Material and methods: observational, descriptive, retrospective study and diagnostic tests. Inclusion criteria: Infants under 90 days of age who consulted in 2017 and 2018 at the DEP-CHPR with a diagnosis of FSF. Results: 261 infants diagnosed with FSF regimen were included and they all received a Step-by-Step approach. The age range was 84 days (4 - 88) days with a mean of 41 days. Males 148 children (56.7%). There were 37 bacterial infections (14.2%), of which 3 were IBI (1.1%) and 34 were Non-IBI (13.1%). The sensitivity for the Step-by-Step approach was 0.94% and 0.89 for the current regimen, with a NPV of 0.98 for both strategies. Discussion: infants younger than 3 months-old are more susceptible due to physiological characteristics to invasive bacterial infections, and the younger they are, the higher the frequency. The Step-by-Step Approach splits children of under 1 month of age into those under or over 21 days of age. Our guideline does not make this discrimination and performs the same blood, urine and cerebrospinal fluid laboratory tests sometimes carrying out blood tests is not necessary. Conclusions: both approaches used in this population were highly sensitive to the identification of bacterial infections with a high NPV. The application of the "Step-by-Step" approach has the additional benefit of avoiding lumbar puncture to newborns of between 21 and 28 days of age.

Introdução: a febre é um motivo muito comum de consulta e em até 20% dos pacientes a causa não é encontrada. No campo da emergência pediátrica, tradicionalmente tem havido interesse em homogeneizar a forma de avaliação de lactentes febris menores de três meses de idade. Ter um protocolo que permita a detecção precoce de uma criança com IBI sem realizar procedimentos desproporcionais é um desafio. Objetivo: avaliar e comparar a capacidade de identificação de IBI na atual Diretriz da FSF e na estratégia Passo a Passo, em lactentes com FSF avaliados no DEP-CHPR. Material e métodos: estudo observacional, descritivo, retrospectivo e de testes diagnósticos. Critérios de inclusão: Lactentes com menos de 90 dias de idade que consultaram em 2017 e 2018 no Hospital Pediátrico Pereira Rossell do Uruguai com diagnóstico de FSF. Resultados: Foram incluídos 261 lactentes avaliados com a atual diretriz da FSF, nos quais foi aplicada a estratégia Passo a Passo. A faixa etária foi de 84 dias (4 - 88) dias com média de 41 dias. Sexo masculino 148 crianças (56,7%). Foram registradas 37 infecções bacterianas (14,2%), sendo 3 IBI (1,1%) e 34 Não IBI (13,1%). A sensibilidade para Passo a Passo foi de 0,94% e 0,89 para o esquema atual, com VPN de 0,98 para ambas estratégias. Discussão: crianças menores de 3 meses de idade são mais suscetíveis a infecções bacterianas invasivas devido às características fisiológicas e quanto menores, mais frequentes. O Passo a Passo separa crianças menores de 1 mês em dois grupos: menores de 21 dias e acima de 21 dias. Nossa diretriz não faz essa discriminação e realiza exames laboratoriais de sangue, urina e líquido cefalorraquidiano da mesma forma; às vezes realizando estudos de sangue que não são necessários. Conclusões: ambas as estratégias aplicadas nesta população foram altamente sensíveis para identificar infecção bacteriana com alto VPN. A aplicação do "Passo a Passo" apresenta como benefício adicional evitar a punção lombar em recém-nascidos entre 21 e 28 dias.

Repercusión de la pandemia por SARS-COV-2 sobre las consultas en los Servicios de Emergencia Pediátrica en Uruguay / Consequences of the SARS-COV-2 pandemic on Pediatric Emergency Services in Uruguay / Repercussão da pandemia de SARS-COV-2 nas consultas nos Serviços de Emergência Pediátrica do Uruguai

En marzo de 2020 se confirma el primer caso de enfermedad por coronavirus en Uruguay, recomendándose un confinamiento social. La atención sanitaria se redujo a servicios de urgencia y emergencia (SE). Objetivo: analizar las características de las consultas pediátricas en los SE del subsector público y privado en Uruguay, durante los primeros 4 meses de la pandemia por SARS-CoV-2. Metodología: estudio descriptivo, retrospectivo, multicéntrico. Resultados: participaron 23 SE de todas las regiones del país. Período 1 prepandemia: 14/03/19-29.07.19, período 2: 14/03/20-29/07/20 Consultas: período 1 n=121.116, período 2 n=33.099 (desciende 73%). Hospitalizaciones desde el SE: período 1 n= .6649 (tasa 5,5%). Período 2: n=2.948 (tasa 9,5%). Diagnósticos período 1: infección respiratoria aguda (IRA) alta 39.892 (33%), IRA baja 86.56 (7%), trauma menor 8.651 (7%), gastroenteritis 8.044 (6,6%), crisis asmática/CBO 7.974 (6,5%), lesiones 4.389 (3,6%), dolor abdominal 3.528 (3%), problemas de salud mental 859 (0,7%), convulsiones 758 (0,7%), patología social 678 (0,5%). Diagnósticos 2020: IRA alta 5.168 (16%), trauma menor 2.759 (8%), lesiones 2.652 (8%), dolor abdominal 1.494 (4,5%), gastroenteritis 1.296 (4%), asma/CBO 1.095 (3,3%), IRA baja 700 (2,1%), patología social 522 (1,6%), problemas de salud mental 471 (1,4%), convulsiones 408 (1,2%). Conclusiones: en los primeros meses de la pandemia hubo una reducción sostenida y significativo de consultas pediátricas en los SE. No hubo aumento en frecuencia absoluta de ninguno de los diagnósticos. Se registró un descenso histórico de las IRA bajas y las hospitalizaciones por esta causa en todo el país. Mantener una vigilancia de las consultas en los SE permitiría identificar e intervenir oportunamente si se produjeran cambios o situaciones de riesgo hasta el momento no detectadas.

In March 2020 the first case of coronavirus disease was confirmed in Uruguay, and lockdown was recommended. Health care services were reduced to Urgency and Emergency Services (ES). Objectives: to analyze the epidemiological characteristics of pediatric visits to the ES of the public and private subsector in Uruguay, during the first 4 months of the SARS-CoV-2 pandemic. Methods: descriptive, retrospective. Results: 23 institutions participated. 2 periods were considered: 1) pre-pandemic, 03/14/19 to 07/29/19, 2) 03/14/20 to 07/29/20. Visits: period 1: n=121,116 (< 15 years), period 2: n=33.099 (73% decrease). Hospital admissions: period 1: n=6,649 (rate 5.5). Period 2: n=2.948 (rate 9,5). Diagnoses period 1: High acute respiratory infection 39,892 (33%), low acute respiratory infection 8,656 (7%), minor trauma 8,651 (7%), gastroenteritis 8,044 (6,6%), asthmatic crisis/CBO 7.974 (6,5%), injuries 4,389 (3,6%), abdominal pain (3,528) 3%, mental health problems 859 (0.7%), seizures 758 (0.7%), social pathology 678 (0.5% ). 2020 diagnoses: high acute respiratory infection 5.168 (16%), minor trauma 2,759 (8%), injuries 2,652 (8%), abdominal pain 1,494 (4.5%), gastroenteritis 1,296 (4%), asthma/CBO 1,095 (3,3%), low acute respiratory infection 700 (2,1%), social pathology 522 (1,6%), mental health problems 471 (1,4%), seizures 408 (1,2%). Conclusions: in the first months of the pandemic there was a sustained and significant reduction in pediatric consultations in ES. There was no increase in absolute frequency of any of the diagnoses. There was a historical decrease in low respiratory infections and hospitalizations due to this cause in the whole country. Maintaining a surveillance of the visits in the ES would enable practitioners to identify and take action in case of changes or previously undetected risk situations.

Em março de 2020, foi confirmado o primeiro caso de doença por coronavírus no Uruguai, recomendando o confinamento. A assistência à saúde foi reduzida a serviços de urgência e emergência (SE). Objetivo: analisar as características das consultas pediátricas no SE do subsetor público e privado no Uruguai, durante os primeiros 4 meses da pandemia de SARS-CoV-2. Metodologia: estudo descritivo, retrospectivo, multicêntrico. Resultados: participaram 23 SEs de todas as regiões do país. Período pré-pandemia 1: 14/03/19-29/07/19, período 2: 14/03/20-29/07/20 Consultas: período 1 n=121.116, período 2 n=33.099 (redução de 73%) . Internações da SE: período 1 n= 0,6649 (taxa 5,5%). Período 2: n=2.948 (taxa de 9,5%). Diagnósticos do período 1: infecção respiratória aguda alta (IRA) 39.892 (33%), LRA baixa 86,56 (7%), trauma menor 8.651 (7%), gastroenterite 8.044 (6,6%), crise asmática/CBO 7.974 (6, 5% ), lesões 4.389 (3,6%), dor abdominal 3.528 (3%), problemas de saúde mental 859 (0,7%), convulsões 758 (0,7%), patologia social 678 (0,5%). Diagnósticos 2020: IRA alta 5.168 (16%), trauma leve 2.759 (8%), lesões 2.652 (8%), dor abdominal 1.494 (4,5%), gastroenterite 1.296 (4%), asma/CBO 1.095 (3, 3%), IRA baixa 700 (2,1%), patologia social 522 (1,6%), problemas de saúde mental 471 (1,4%), convulsões 408 (1,2%). Conclusões: nos primeiros meses da pandemia houve uma redução sustentada e significativa das consultas pediátricas no SE. Não houve aumento na frequência absoluta de nenhum dos diagnósticos. Foi registrado um decréscimo histórico de IRAs baixas e internações por essa causa em todo o país. A manutenção de uma vigilância das consultas no SE permitiria identificar e intervir atempadamente nos casos de alterações ou situações de risco que até agora não tinham sido detectadas.

Equivalent Formulations of Optimal Control Problems with Maximum Cost and Applications.

We revisit the optimal control problem with maximum cost with the objective to provide different equivalent reformulations suitable to numerical methods. We propose two reformulations in terms of extended Mayer problems with state constraints, and another one in terms of a differential inclusion with upper-semi-continuous right member without state constraint. For the latter we also propose a scheme that approximates from below the optimal value. These approaches are illustrated and discussed in several examples.

High baseline expression of IL-6 and IL-10 decreased CCR7 B cells in individuals with previous SARS-CoV-2 infection during BNT162b2 vaccination.

The current pandemic generated by SARS-CoV-2 has led to mass vaccination with different biologics that have shown wide variations among human populations according to the origin and formulation of the vaccine. Studies evaluating the response in individuals with a natural infection before vaccination have been limited to antibody titer analysis and evaluating a few humoral and cellular response markers, showing a more rapid and intense humoral response than individuals without prior infection. However, the basis of these differences has not been explored in depth. In the present work, we analyzed a group of pro and anti-inflammatory cytokines, antibody titers, and cell populations in peripheral blood of individuals with previous SARS-CoV-2 infection using BNT162b2 biologic. Our results suggest that higher antibody concentration in individuals with an earlier disease could be generated by higher production of plasma cells to the detriment of the presence of memory B cells in the bloodstream, which could be related to the high baseline expression of cytokines (IL-6 and IL-10) before vaccination.

Biology of the Most Widely Distributed Sugarcane Stem Borers, Diatraea spp. (Lepidoptera: Crambidae), in Colombia.

Most studies on insect biology and ecology of sugarcane borers have focused on Diatraea saccharalis (Fabricius), the most widely distributed species in the Americas. Little information is available on the biology of other borer species present in Colombia, such as D. indigenella Dyar & Heinrich, D. busckella Dyar & heinrich, and D. tabernella Dyar, that present greater expansion and damage in sugarcane-growing regions. The biology of all four species was accordingly studied under laboratory conditions. Diatraea saccharalis presented the shortest development time (39.4 days) and D. busckella the longest (58.2 days). Immature survival was higher for D. saccharalis (83%) and D. tabernella (77%), with the latter also presenting the highest pupal weight (256.6 mg). Observations on reproduction indicate that D. tabernella develops a larger number of egg masses per female (67.3) as compared with D. saccharalis (28.7). All three species spent more time in the pupal stage and resulted in greater pupal size than D. saccharalis; in particular, D. indigenella showed longer female longevity than D. saccharalis. High immature survival rate and greater reproductive success in D. tabernella could potentially generate a larger population in the field, whereas D. busckella takes longer to complete its development, thus increasing the chances of causing greater injury to sugarcane plants. Discussion on biology, ecology, and pest management of these little-known species is done using as model the better-known D. saccharalis.

Extended Remdesivir Infusion for Persistent Coronavirus Disease 2019 Infection.

Persistent severe acute respiratory syndrome coronavirus 2 infection is difficult to treat. Here, we report a case of 5-month persistent coronavirus disease 2019 in an immunocompromised patient who was successfully treated with 30 consecutive days of remdesivir. Prolonged remdesivir infusion with concurrent cycle threshold monitoring might provide a potential solution to cure these patients with difficult-to-treat infections.

Experimental Study of the Validity of Entangled Two-Photon Absorption Measurements in Organic Compounds.

Entangled two-photon absorption (ETPA) has recently become a topic of lively debate, mainly due to the apparent inconsistencies in the experimentally reported ETPA cross sections of organic molecules obtained by a number of groups. In this work, we provide a thorough experimental study of ETPA in the organic molecules Rhodamine B (RhB) and zinc tetraphenylporphirin (ZnTPP). Our contribution is 3-fold: first, we reproduce previous results from other groups; second, we on the one hand determine the effects of different temporal correlations─introduced as a controllable temporal delay between the signal and idler photons to be absorbed─on the strength of the ETPA signal, and on the other hand, we introduce two concurrent and equivalent detection systems with and without the sample in place as a useful experimental check; third, we introduce, and apply to our data, a novel method to quantify the ETPA rate based on taking into account the full photon-pair behavior rather than focusing on singles or coincidence counts independently. Through this experimental setup we find that, surprisingly, the purported ETPA signal is not suppressed for a temporal delay much greater than the characteristic photon-pair temporal correlation time. While our results reproduce the previous findings from other authors, our full analysis indicates that the signal observed is not actually due to ETPA but simply to linear losses. Interestingly, for higher RhB concentrations, we find a two-photon signal that, contrary to expectations, likewise does not correspond to ETPA.

Reliability and validity of a clinical competence test for dietitians caring patients with early chronic kidney disease.

The aim of the present study was to develop and validate a test to evaluate dietitian's clinical competence (CC) about nutritional care in patients with early chronic kidney disease (CKD). The study was conducted through five steps: (1) CC and its dimensions were defined; (2) test items were elaborated, and choice of response format and scoring system was selected; (3) content and face validity were established; (4) test was subjected to a pilot test and those items with inadequate performance were removed; (5) criterion validity and internal consistency for final validation were established. A 120-items test was developed and applied to 207 dietitians for validation. Dietitians with previous CKD training obtained higher scores than those with no training, confirming the test validity criterion. According to item analysis, Cronbach's α was 0⋅85, difficulty index 0⋅61 ± 0⋅22, discrimination index 0⋅26 ± 0⋅15 and inter-item correlation 0⋅19 ± 0⋅11, displaying adequate internal consistency.

Effective Michelson interference observed in fiber-optical analogue of Hawking radiation.

We experimentally observe the stimulated analogue of Hawking radiation produced in a photonic-crystal fiber, with a pulsed pump and a continuous-wave probe. In particular, we propose and demonstrate an innovative method to boost the efficiency and probe the coherence characteristics of the analogue Hawking effect relying on a double pump pulse with a controlled temporal delay. We show that the emitted analogue Hawking radiation corresponds to the coherently-added, interfering Hawking signals resulting from the probe interacting with each pump pulse. We introduce a simple effective Michelson interference model, and demonstrate excellent agreement between our experimental data and the predictions derived from this model. Importantly, while naively increasing the pump power in an attempt to boost the Hawking-radiation generation efficiency results in the distortion of the output signal, we show that at the maxima of the observed Hawking-signal interference pattern, the signal can be increased by a factor of >3 (up to 4 under ideal experimental conditions). This approach could be extended to the use of sequences of m pulses, resulting in a Hawking-signal enhancement of m2.

CD38 a biomarker and therapeutic target in non-hematopoietic tumors.

The type II transmembrane glycoprotein CD38 has recently been implicated in regulating metabolism and the pathogenesis of multiple conditions, including aging, inflammation and cancer. CD38 is overexpressed in several tumor cells and microenvironment tumoral cells, associated to migration, angiogenesis, cell invasion and progression of the disease. Thus, CD38 has been used as a progression marker for different cancer types as well as in immunotherapy. This review focuses on describing the involvement of CD38 in various non-hematopoietic cancers.

An Overview on Irreversible Port-Hamiltonian Systems.

A comprehensive overview of the irreversible port-Hamiltonian system's formulation for finite and infinite dimensional systems defined on 1D spatial domains is provided in a unified manner. The irreversible port-Hamiltonian system formulation shows the extension of classical port-Hamiltonian system formulations to cope with irreversible thermodynamic systems for finite and infinite dimensional systems. This is achieved by including, in an explicit manner, the coupling between irreversible mechanical and thermal phenomena with the thermal domain as an energy-preserving and entropy-increasing operator. Similarly to Hamiltonian systems, this operator is skew-symmetric, guaranteeing energy conservation. To distinguish from Hamiltonian systems, the operator depends on co-state variables and is, hence, a nonlinear-function in the gradient of the total energy. This is what allows encoding the second law as a structural property of irreversible port-Hamiltonian systems. The formalism encompasses coupled thermo-mechanical systems and purely reversible or conservative systems as a particular case. This appears clearly when splitting the state space such that the entropy coordinate is separated from other state variables. Several examples have been used to illustrate the formalism, both for finite and infinite dimensional systems, and a discussion on ongoing and future studies is provided.

Can the implementation of clinical practice guidelines improve clinical competence of physicians and kidney function of patients with type 2 diabetes mellitus?

Background: There are many clinical practice guidelines (CPGs) in Nephrology; however, there is no evidence that their availability has improved the clinical competence of physicians or the outcome of patients with chronic kidney disease (CKD). This study was aimed to evaluate the effect of implementation of CPGs for early CKD on family physicians (FP) clinical competence and subsequently on kidney function preservation of type 2 diabetes mellitus (DM2) patients at a primary healthcare setting. Methods: A prospective educative intervention (40-h) based on CPGs for Prevention, Diagnosis and Treatment of Early CKD was applied to FP; a questionnaire to evaluate clinical competence was applied at the beginning and end of the educative intervention (0 and 2 months), and 12 months afterwards. DM2 patients with CKD were evaluated during 1-year of follow-up with estimated glomerular filtration rate (eGFR) and albuminuria. Results: After educative intervention, there was a significant increase in FP clinical competence compared to baseline; although it was reduced after 1 year, it remained higher compared to baseline. One-hundred thirteen patients with early nephropathy (58 stage 1, 55 stage 2) and 28 with overt nephropathy (23 stage 3, 5 stage 4) were studied. At final evaluation, both groups maintained eGFR [(mean change) early 0.20 ± 19 pNS; overt 0.51 ± 13 mL/min pNS], whereas albuminuria/creatinuria (early -67 ± 155 p < 0.0001; overt -301 ± 596 mg/g p < 0.0001), systolic blood pressure (early -10 ± 18 p < 0.05; overt -8 ± 20 mmHg p < 0.05), and total cholesterol (early -11 ± 31 p < 0.05; overt -17 ± 38 mg/dL p < 0.05) decreased. Diastolic blood pressure, waist circumference and LDL-cholesterol were also controlled in early nephropathy patients. Conclusions: CPGs for Prevention, Diagnosis and Treatment of CKD, by means of an educative intervention increases FP clinical competence and improves renal function in DM2 patients with CKD.

Frontline Nurse Feedback During the Development of a System to Track Cleaning of Portable Medical Equipment.

As part of the development and testing of an innovative technology for tracking disinfection of portable medical equipment, end-user feedback was obtained during an initial trial on two acute care hospital units. The disinfection tracking device was installed on the computers-on-wheels and vital signs machines. Each device had the capability of detecting a cleaning event, reporting the event to an online database, and displaying the time since last cleaning event on a visual display. End-user feedback regarding functionality, usefulness of information provided, and impact on workflow was obtained by survey and facilitated group discussions. Seventeen frontline nurses completed the anonymous survey, and 22 participated in the facilitated group discussions. End users found the system functionally easy to use and the information about time since last cleaning useful and reported minimum disruption of workflow. Functionality of the system was confirmed by consistency between recorded and self-reported cleaning patterns. Managers found the data on cleaning of portable medical equipment helpful in validating compliance with hospital equipment cleaning policy. Frontline staff expressed appreciation for technology that helps them and improves outcomes but also discussed concerns about the potential for technology that creates extra work and disruption in the busy frontline nursing care delivery environment. Nurses were appreciative of opportunities to provide feedback and input into efforts to develop and introduce technology. Recorded cleaning events coincided with self-reported equipment cleaning patterns and illustrated that the device efficiently collects information deemed useful by the end user.