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El trabajo corresponde a la investigación pedagógica que se desarrolla en el Ciclo Corto, de la carrera de Geografía en la Universidad de Cienfuegos. En el mismo se fundamenta la relación de la educación ambiental con el proceso de enseñanza-aprendizaje de la Disciplina Geografía Física, además de la fundamentación de la propuesta de actividades a desarrollar. En ellas se tratan conocimientos ambientalistas actualizados sobre el tema, que pueden contribuir eficazmente a la formación de actitudes positivas en los estudiantes de este nivel de enseñanza, con relación al cuidado y protección de las aguas, se aprovechan las potencialidades que para ello brinda la escuela cubana contemporánea. Se analizan los resultados de la aplicación de la propuesta, que permitió elevar el nivel de preparación de los estudiantes y corroborar la factibilidad de la misma.

This work demonstrates the equivalence of two constitutive equations. One is used in Fourier’s law of the heat conduction equation, the other in electric conduction equation; both are based on the numerical Cell Method, using the Finite Formulation (FF-CM). A 3-D pure heat conduction model is proposed. The temperatures are in steady state and there are no internal heat sources. The obtained results are compared with an equivalent model developed using the Finite Elements Method (FEM). The particular case of 2-D was also studied. The errors produced are not significant at less than 0.2%. The number of nodes is the number of the unknowns and equations to resolve. There is no significant gain in precision with increasing density of the mesh.

This article provides the results of classroom research involving university students training to be secondary school teachers of geography and history. The research is based on the analysis of a word association test on Europe and the European Union. The results constitute an approach to the geographical and historical representations these students have of their own European continent. This is a fundamental question considering that this collective group is training to teach the contents and values of European geography in secondary school education. From here on, our intention is no other than to carry out an exercise of synthesis and overall reflection on the test results and introduce issues which could generate some debate in the educational community.

This article presents a didactic model of critical geography, based on instruction recommendations for the teaching and learning of geography and social sciences. This is all with a very clear idea: to depart from a descriptive and reflective geography and move to an active and critical geography. Geography in which students participate in the construction of knowledge and increase their ability to reflect on geographical issues. The proposed didactic model drives active and critical geography in the classrooms. It starts with the analysis of territorial problems in Europe and makes them the object of research and reflection. The idea is not to dictate geography in classrooms but to introduce methodologies, resources and sources to carry out geographic research with students. With this idea in mind, the second part of the article examines the value of our didactic model through the analysis of fifteen research projects on European natural spaces carried out in the academic years of 2014-2015 and 2015-2016 with 74 university students in training to be geography teachers in secondary education. The results show that the students’ didactic expectations grow when given geographic research to do as teaching practice.

Objetivo. Evaluar el proceso de atención y el acceso a servicios de salud en menores de cinco años fallecidos por enfermedad diarreica (ED), en cuatro estados de la República mexicana. Material y métodos. Se realizó un estudio transversal que incluyó defunciones ocurridas durante un año; mediante autopsia verbal se obtuvo información de características clínicas, atención durante la enfermedad y acceso a los servicios de salud; se realizó un análisis descriptivo y comparativo de acuerdo con el tamaño de la localidad. Resultados. De 553 defunciones, la mayoría ocurrió en niños sin derecho a seguridad social o residentes en localidades rurales; la muerte en el hogar, la edad menor a un año y la corta evolución de la enfermedad caracterizaron a más de la mitad de los casos. Se proporcionó terapia de hidratación oral por decisión de la madre a casi 75% de los niños; 20% recibió atención no médica, principalmente de curanderos. La atención médica fue otorgada en 60% de los casos; a una elevada proporción le fue indicado algún medicamento y no se le envió a hospital ni se recomendó regresar ante la presencia de signos de alarma; la indicación de hidratación oral fue mayor por médicos de servicios públicos y en localidades rurales; en éstas, el acceso geográfico y económico fue menor. Conclusiones. Si bien se confirmó el problema de acceso a los servicios de salud, se identificaron fallas importantes en la atención médica primaria. Se propone la creación de unidades docente-asistenciales como una estrategia para la reducción de la mortalidad por ED.

Objetivo. Estimar la frecuencia de subregistro de muerte en niños en localidades rurales e identificar las características asociadas. Material y métodos. El estudio se realizó en tres etapas: en la primera se formaron tres estratos de localidades según el número de habitantes; de cada estrato se eligió, de manera aleatoria, un número representativo de localidades que fueron censadas para identificar las defunciones ocurridas entre junio de 1993 y julio de 1994. En la segunda etapa se realizó autopsia verbal con las madres de los niños fallecidos para identificar la causa de muerte e investigar las variables de estudio. Por último, se identificó el registro de muerte a través de los certificados de defunción. Resultados. Se identificó una frecuencia de subregistro de 68.9%; en las localidades menores de 500 habitantes fue de 73.2%, y en las mayores, de 60.5%. Como características asociadas al subregistro se identificaron: carecer de certificado de defunción y de registro de nacimiento; edad menor de un mes; desconocimiento del concepto y funciones del registro civil; distancia al registro civil y acceso al médico mayor de 30 minutos, y localidad menor de 1 000 habitantes. Conclusiones. Se propone una modificación en la organización actual del procedimiento de registro de muerte, así como el establecimiento del certificado de nacimiento propuesto por el Sistema Nacional de Salud.

Abstract Background Elucidating the genomic basis of adaptation and speciation is a major challenge in natural systems with large quantities of environmental and phenotypic data, mostly because of the scarcity of genomic resources for non-model organisms. The Atlantic molly (Poecilia mexicana, Poeciliidae) is a small livebearing fish that has been extensively studied for evolutionary ecology research, particularly because this species has repeatedly colonized extreme environments in the form of caves and toxic hydrogen sulfide containing springs. In such extreme environments, populations show strong patterns of adaptive trait divergence and the emergence of reproductive isolation. Here, we used RNA-sequencing to assemble and annotate the first transcriptome of P. mexicana to facilitate ecological genomics studies in the future and aid the identification of genes underlying adaptation and speciation in the system. Description We provide the first annotated reference transcriptome of P. mexicana. Our transcriptome shows high congruence with other published fish transcriptomes, including that of the guppy, medaka, zebrafish, and stickleback. Transcriptome annotation uncovered the presence of candidate genes relevant in the study of adaptation to extreme environments. We describe general and oxidative stress response genes as well as genes involved in pathways induced by hypoxia or involved in sulfide metabolism. To facilitate future comparative analyses, we also conducted quantitative comparisons between P. mexicana from different river drainages. 106,524 single nucleotide polymorphisms were detected in our dataset, including potential markers that are putatively fixed across drainages. Furthermore, specimens from different drainages exhibited some consistent differences in gene regulation. Conclusions Our study provides a valuable genomic resource to study the molecular underpinnings of adaptation to extreme environments in replicated sulfide spring and cave environments. In addition, this study adds to the increasing number of genomic resources in the family Poeciliidae, which are widely used in comparative analyses of behavior, ecology, evolution, and medical genetics.

IntroductionPruritus is a major and burdensome symptom in atopic dermatitis (AD). The number of systemic treatments available for AD has increased recently, enabling improved patient relief.ObjectiveTo evaluate the effect of AD treatments on pruritus.MethodsA systematic literature review and a meta-analysis were conducted to evaluate and compare the effects of treatment used in AD on pruritus. PubMed and Embase databases were searched to find articles published between January 1990 and December 2021. Topical and systemic treatments were studied in patients aged ≥10 years.ResultsAmong the 448 articles identified, 56 studies were retained in the systematic review. A total of 15 studies evaluated topical treatments: topical corticosteroids (TCS; 2), calcineurin inhibitors (6), PDE4 inhibitors (3), and Jak inhibitors (4). A total of five studies were included in the meta- analysis. All treatments had a positive effect on pruritus, with a mean overall reduction of 3.32/10, 95% IC [2.32–4.33]. The greatest reduction was observed with halometasone (mean: 4.75), followed by tofacitinib 2% (mean: 4.38). A total of 41 studies evaluated systemic therapies: cyclosporine (6), phototherapy (5), azathioprine (2), dupilumab (9), anti-IL 13 (5), nemolizumab (3), Jak inhibitors (9), mepolizumab (1), and apremilast (1). A total of 17 studies were included in 2 meta-analyses according to the concomitant use or not of TCS. In the meta-analysis without TCS, the overall decrease was 3.07/10, 95% IC [2.58–3.56]. The molecules with the highest efficacy on pruritus were upadacitinib 30 mg (mean: 4.90) and nemolizumab (mean: 4.81).DiscussionThe therapeutic arsenal for AD has increased rapidly, and many molecules are under development. The primary endpoint of clinical trials is most often a score that assesses the severity of AD; however, the assessment of pruritus is also essential. The majority of molecules have a positive effect on pruritus, but the improvement varies between them. Efficacy on pruritus is not always correlated with efficacy on AD lesions; therefore, these two criteria are crucial to evaluate. The limitations of this study were the heterogeneity in the assessment of pruritus, the moment of the assessment, and the concomitant application of TCS or not for studies evaluating systemics. In the future, it would be useful to use standardized criteria for assessing pruritus.

Objective: Oral (PO) nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat phlebitis and thrombus extension postendovenous ablation. Few studies have evaluated diclofenac topical gel for treating postablation phlebitis. This study assesses diclofenac 1% topical gel as a first-line treatment for patients with moderate to severe phlebitis after ablation., Methods: From December 2021 to March 2024, a retrospective cohort study was performed to identify patients who developed postablation phlebitis and were treated with either diclofenac topical gel (with or without PO NSAIDs) vs PO NSAIDs alone. All patients were evaluated with a numeric pain rating scale (NPRS, 0-10) at four time intervals (1, 7, 14, and 30 days) after initiating treatment., Results: Overall, 45 patients were included in the study, with 38 in the diclofenac ± PO NSAIDs group (9 males and 29 females) and 7 in the PO NSAIDs alone group (all females). NPRS scores showed similar pain reduction trends at all time intervals. Topical diclofenac gel was noninferior to PO treatments and resulted in partial to complete relief in most patients at 30 days. At the 30-day follow-up interview, 57% of patients preferred the diclofenac topical gel owing to its ease of use and immediate local pain reduction., Conclusions: Patients with moderate to severe postablation phlebitis respond well to diclofenac topical gel with or without PO NSAIDs. Moreover, patients often had significant pain relief without additional need for PO NSAIDs. Longitudinal studies are needed to support the use of diclofenac topical gel for postablation phlebitis., Competing Interests: Disclosures None., (Copyright © 2024. Published by Elsevier Inc.)

Pigments serve a multitude of functions in biology including light harvesting for photosynthesis, radiation protection, membrane support, and defense. The ubiquity of pigments-especially within extremophiles found in high-radiation, high-salinity, and dry environments-and their detectability via mission-ready techniques have elevated these molecules as promising targets in the search for evidence of life elsewhere. Moreover, the detection of pigments has been proposed as a "smoking gun" for extraterrestrial life as it has been suggested that these molecules cannot be generated abiotically. However, while pigments may hold promise as a biosignature, current understanding of their possible prebiotic origins remains understudied and uncertain. Better understanding of the abiotic synthesis of pigments is critical for evaluating the biogenicity of any pigment detected during missions, including by the Mars Perseverance rover or from returned samples. Compounding this uncertainty is the broad definition of pigment as it includes any compound capable of absorbing visible light and by itself does not specify a particular chemical motif. While not experimentally verified, there are promising prebiotic routes for generating pigments including hemes, chlorophylls, and carotenoids. Herein, we review the biochemistry of pigments, the inherent assumptions made when searching for these molecules in the field, their abiotic synthesis in industry and prebiotic reactions, prebiotically relevant molecules that can mimic their spectral signatures, and implications/recommendations for future work.

Background: Insurance companies have adopted variable and inconsistent approval criteria for chronic venous disease (CVD) treatment. Although vein ablation (VA) is accepted as the standard of care for venous ulcers, the treatment criteria for patients with milder forms of CVD remain controversial. This study aims to identify factors associated with a lack of clinical improvement (LCI) in patients with less severe CVD without ulceration undergoing VA to improve patient selection for treatment., Methods: We performed a retrospective analysis of patients undergoing VA for CEAP C2 to C4 disease in the Vascular Quality Initiative varicose veins database from 2014 to 2023. Patients who required intervention in multiple veins, had undergone prior interventions, or presented with CEAP C5 to C6 disease were excluded. The difference (Δ) in venous clinical severity score (VCSS; VCSS before minus after the procedure) was used to categorize the patients. Patients with a ΔVCSS of ≤0 were defined as having LCI after VA, and patients with ≥1 point decrease in the VCSS after VA (ΔVCSS ≥1) as having some benefit from the procedure and, therefore, "clinical improvement." The characteristics of both groups were compared, and multivariable regression analysis was performed to identify factors independently associated with LCI. A second analysis was performed based on the VVSymQ instrument, which measures patient-reported outcomes using five specific symptoms (ie, heaviness, achiness, swelling, throbbing pain, and itching). Patients with LCI showed no improvement in any of the five symptoms, and those with clinical improvement had a decrease in severity of at least one symptom., Results: A total of 3544 patients underwent initial treatment of CVD with a single VA. Of the 3544 patients, 2607 had VCSSs available before and after VA, and 420 (16.1%) had LCI based on the ΔVCSS. Patients with LCI were more likely to be significantly older and African American and have CEAP C2 disease compared with patients with clinical improvement. Patients with clinical improvement were more likely to have reported using compression stockings before treatment. The vein diameters were not different between the two groups. The incidence of complications was overall low, with minor differences between the two groups. However, the patients with LCI were significantly more likely to have symptoms after intervention than those with improvement. Patients with LCI were more likely to have technical failure, defined as vein recanalization. On multivariable regression, age (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00-1.02) and obesity (OR, 1.47; 95% CI, 1.09-2.00) were independently associated with LCI, as was treatment of less severe disease (CEAP C2; OR, 1.82; 95% CI, 1.30-2.56) compared with more advanced disease (C4). The lack of compression therapy before intervention was also associated with LCI (OR, 6.05; 95% CI, 4.30-8.56). The analysis based on the VVSymQ showed similar results., Conclusions: LCI after VA is associated with treating patients with a lower CEAP class (C2 vs C4) and a lack of compression therapy before intervention. Importantly, no significant association between vein size and clinical improvement was observed., Competing Interests: Disclosures None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Within the first billion years of Earth's history, the planet transformed from a hot, barren, and inhospitable landscape to an environment conducive to the emergence and persistence of life. This chapter will review the state of knowledge concerning early Earth's (Hadean/Eoarchean) geochemical environment, including the origin and composition of the planet's moon, crust, oceans, atmosphere, and organic content. It will also discuss abiotic geochemical cycling of the CHONPS elements and how these species could have been converted to biologically relevant building blocks, polymers, and chemical networks. Proposed environments for abiogenesis events are also described and evaluated. An understanding of the geochemical processes under which life may have emerged can better inform our assessment of the habitability of other worlds, the potential complexity that abiotic chemistry can achieve (which has implications for putative biosignatures), and the possibility for biochemistries that are vastly different from those on Earth.

The question "What is life?" has existed since the beginning of recorded history. However, the scientific and philosophical contexts of this question have changed and been refined as advancements in technology have revealed both fine details and broad connections in the network of life on Earth. Understanding the framework of the question "What is life?" is central to formulating other questions such as "Where else could life be?" and "How do we search for life elsewhere?" While many of these questions are addressed throughout the Astrobiology Primer 3.0, this chapter gives historical context for defining life, highlights conceptual characteristics shared by all life on Earth as well as key features used to describe it, discusses why it matters for astrobiology, and explores both challenges and opportunities for finding an informative operational definition.

The Astrobiology Primer 3.0 (ABP3.0) is a concise introduction to the field of astrobiology for students and others who are new to the field of astrobiology. It provides an entry into the broader materials in this supplementary issue of Astrobiology and an overview of the investigations and driving hypotheses that make up this interdisciplinary field. The content of this chapter was adapted from the other 10 articles in this supplementary issue and thus represents the contribution of all the authors who worked on these introductory articles. The content of this chapter is not exhaustive and represents the topics that the authors found to be the most important and compelling in a dynamic and changing field.

Background: Vein ablation is a common and effective treatment for patients with chronic venous insufficiency. The overuse of vein ablation despite the existence of evidence-based guidelines has resulted in insurance companies developing restrictive policies for coverage that create barriers to appropriate care. This study compares the insurance coverage by single-state carriers (SSCs) and multistate carriers (MSCs), highlighting the variations and inconsistencies in the various policies., Methods: The American Venous Forum Venous Policy Navigator was reviewed for the various policies available in the United States. The policies were divided into SSCs and MSCs. The characteristics of the policies, including the anatomic and hemodynamic criteria for specific veins, duration of conservative treatment, disease severity, symptoms, and types of procedures covered, were compared between the two groups. SAS, version 9.4 (SAS Institute Inc) was used for statistical analysis., Results: A total of 122 policies were analyzed and divided between SSCs (n = 85; 69.7%) and MSCs (n = 37; 30.3%). A significant variation was found in the size requirement for great saphenous vein ablation. Although 48% of the policies did not specify a size criterion, the remaining policies indicated a minimal size, ranging from 3 to 5.5 mm. However, no significant differences were found between SSCs and MSCs. Similar findings were encountered for the small and anterior accessory saphenous veins. MSCs were more likely to define a saphenous reflux time >500 ms compared with SSCs (81.1% vs 58.8%; P = .04). A significant difference was found between the SSCs and MSCs in the criteria for perforator ablation in terms of size and reflux time. MSCs were significantly more likely to provide coverage for mechanochemical ablation than were SSCs (24.3% vs 8.2%; P = .03). SSCs were more likely to require ≥12 weeks of compression stocking therapy than were MSCs (76.5% vs 48.7%; P = .01). No significant differences were found in the clinical indications between the two groups; however, MSCs were more likely to mention major hemorrhage than were SSCs., Conclusions: The results of this study highlight the variations in policies for venous ablation, in particular, the striking inconsistencies in size criteria. MSCs were more likely to cover mechanochemical ablation and require a shorter duration of conservative therapy before intervention compared with SSCs. Evidence-based guidance is needed to develop more coherent policies for venous ablation coverage., Competing Interests: Disclosures None., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Beginning in 2022, Nuevo Leon, Mexico, experienced an outbreak of rickettsioses that is still ongoing despite multidisciplinary control efforts. A total of 57 cases have been confirmed, particularly affecting children. We report a high mortality rate among hospitalized persons in Nuevo Leon. Continuing efforts are required to control the outbreak.

CD3 bispecific T-cell engagers (TCE), comprised of a tumor-targeting domain linked to a CD3 binding domain, function by bridging target-positive tumors and CD3-expressing effector T cells enabling redirected T cell-mediated killing of tumor cells. Although the majority of CD3 bispecific molecules in clinical development incorporate tumor-targeting antibody-based binding domains, many tumor-associated antigens derive from intracellular proteins and are not accessible to targeting via antibody. Intracellular proteins processed into short peptide fragments and presented on the cell surface by MHC proteins are recognized by T-cell receptors (TCR) on the surface of T cells. Here we describe the generation and preclinical evaluation of ABBV-184, a novel TCR/anti-CD3 bispecific composed of a highly selective soluble TCR that binds a peptide derived from the oncogene survivin (BIRC5) bound to the class I MHC allele human leukocyte antigen (HLA)-A*02:01 expressed on tumor cells, linked to a specific binder to the CD3 receptor on T cells. ABBV-184 drives an optimal distance between T cell and target cell thereby enabling sensitive recognition of low-density peptide/MHC targets. Consistent with the expression profile of survivin across a broad range of both hematologic and solid tumors, treatment of acute myeloid leukemia (AML) and non-small cell lung cancer (NSCLC) cell lines with ABBV-184 results in T-cell activation, proliferation, and potent redirected cytotoxicity of HLA-A2-positive target cell lines, both in vitro and in vivo, including patient-derived AML samples. These results indicate that ABBV-184 is an attractive clinical candidate for the treatment of patients with AML and NSCLC., (©2023 American Association for Cancer Research.)

Zircon s reveal the geochemistry of Earth's earliest hydrothermal systems.

Background: The aim of this study is to compare how instructions for use (IFU) affected perioperative and intermediate term outcomes for common iliac artery aneurysms (CIAA) treated with the Gore Excluder iliac branch endoprosthesis (IBE)., Methods: A retrospective analysis was performed of all patients treated at two affiliated academic centers from September 2016 to May 2020. Outcomes were compared between IFU and nonIFU IBE cases. Criteria for nonIFU included: (1) use with a nonGore aortic endoprosthesis (n = 10), (2) isolated IBE (n = 3), and (3) requiring nondedicated covered stents for additional extension into a more suitable landing zone in the ipsilateral internal iliac artery or one of its branches (n = 11). Perioperative and intermediate term data were collected for both groups. The primary end points were free from the major adverse event (MAE) at 30 days and primary effectiveness at 1 year., Results: A total of 51 CIAA (39 patients) were treated with an IBE. Overall, 15 patients were treated under IFU and 24 under nonIFU. The IFU group mean age was older (72 vs. 67 years, P = 0.03), and males (97%) were primarily treated. Comorbidities were similar except nonIFU had more patients with previous endovascular abdominal aortic aneurysm repair on presentation (0 vs. 4 cases, P = 0.04). Procedure (178 vs. 264 min, P = 0.02) and fluoroscopy (52 vs. 74 min, P = 0.04) times were longer in the nonIFU group. Technical success was 100% for both groups, and there was no difference in device related reintervention at 30 days (0 vs. 1, P = 0.44). There was no MAE in either group at 30 days. Intervention for any endoleak was similar between the groups (2 vs. 3, P = 0.94). Percent CIAA sac regression was similar between the groups (19% vs. 18%, P = 0.21). There was no difference for primary effectiveness at 1 year (93% vs. 92%, P = 0.85). There was one death per group at one year not related to an aortic or iliac cause., Conclusions: In properly selected patients with complex anatomy, IBE can be used with nondedicated aortic and internal iliac components with good early term outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The field of prebiotic chemistry has demonstrated that complex organic chemical systems that exhibit various life-like properties can be produced abiotically in the laboratory. Understanding these chemical systems is important for astrobiology and life detection since we do not know the extent to which prebiotic chemistry might exist or have existed on other worlds. Nor do we know what signatures are diagnostic of an extant or "failed" prebiotic system. On Earth, biology has suppressed most abiotic organic chemistry and overprints geologic records of prebiotic chemistry; therefore, it is difficult to validate whether chemical signatures from future planetary missions are remnant or extant prebiotic systems. The "biosignature threshold" between whether a chemical signature is more likely to be produced by abiotic versus biotic chemistry on a given world could vary significantly, depending on the particular environment, and could change over time, especially if life were to emerge and diversify on that world. To interpret organic signatures detected during a planetary mission, we advocate for (1) gaining a more complete understanding of prebiotic/abiotic chemical possibilities in diverse planetary environments and (2) involving experimental prebiotic samples as analogues when generating comparison libraries for "life-detection" mission instruments.

Background: Central venous occlusive disease is a common cause of upper extremity arteriovenous access dysfunction in hemodialysis patients. When refractory to balloon angioplasty, the treatment options include central venous stenting and hemodialysis reliable outflow (HeRO; Merit Medical, South Jordan, Utah) graft. The purpose of the present study was to evaluate the outcomes of these options., Methods: A retrospective review was performed of patients who had undergone central venous stenting or HeRO placement for central venous obstruction from December 2008 to March 2018. The primary outcomes were the reintervention rates, patency, and mortality., Results: A total of 75 hemodialysis patients were identified after failed balloon angioplasty for central venous obstruction. Of the 75 patients, 44 underwent central venous stenting comprising coverage of the subclavian vein (n = 27), innominate vein (n = 18), and/or superior vena cava (n = 5). Six stent patients later underwent HeRO placement. The stents used were stent grafts in 65% (Viabahn, n = 9; Fluency/Flair, n = 19; iCast, n = 2; and other, n = 1) and bare metal stents in 35% (Wall-stent, n = 6; Protégé, n = 1; Cobalt, n = 1; and other, n = 9). The remaining 31 patients underwent HeRO graft placement. The venous outflow component insertion sites were the internal jugular (n = 20), external jugular (n = 1), subclavian (n = 6), axillary (n = 2), and other (n = 2). The stent and HeRO groups were similar in the previous central venous intervention rates (median, 0.6 [interquartile range (IQR), 0-3.0]; vs median, 3.5 [IQR, 0-10.1] annually; P = .679). After the index procedure, no difference was found between the two groups in the frequency of dialysis circuit interventions annually (median, 2.0 [IQR, 0-6.0]; vs median, 2.0 [IQR, 0-7.0]; P = .291) nor central venous interventions (ie, angioplasty of the central veins or within the portion of the HeRO inside the central veins) annually (median, 2.0 [IQR, 0-4.1]; vs median, 0 [IQR, 0-2.4]; P = .419). The 1-year access circuit primary patency was 8.1% for stenting and 22.2% for HeRO (P = .109). The 2-year access circuit secondary patency was 40.0% for stenting and 52.4% for HeRO (P = .401). The all-cause mortality was similar at 1 year (3.7% vs 4.8%; P = .856) and 2 years (11.8% vs 23.5%; P = .368)., Conclusions: Central venous stenting and HeRO were shown to have similar rates of reintervention and patency. The results from the present study suggest that the multiple treatment options available for this problematic disease process can yield similar results when careful patient selection is applied., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

As the exploration of Mars and other worlds for signs of life has increased, the need for a common nomenclature and consensus has become significantly important for proper identification of nonterrestrial/non-Earth biology, biogenic structures, and chemical processes generated from biological processes. The fact that Earth is our single data point for all life, diversity, and evolution means that there is an inherent bias toward life as we know it through our own planet's history. The search for life "as we don't know it" then brings this bias forward to decision-making regarding mission instruments and payloads. Understandably, this leads to several top-level scientific, theoretical, and philosophical questions regarding the definition of life and what it means for future life detection missions. How can we decide on how and where to detect known and unknown signs of life with a single biased data point? What features could act as universal biosignatures that support Darwinian evolution in the geological context of nonterrestrial time lines? The purpose of this article is to generate an improved nomenclature for terrestrial features that have mineral/microbial interactions within structures and to confirm which features can only exist from life ( biotic ), features that are modified by biological processes ( biogenic ), features that life does not affect ( abiotic ), and properties that can exist or not regardless of the presence of biology ( abiogenic ). These four categories are critical in understanding and deciphering future returned samples from Mars, signs of potential extinct/ancient and extant life on Mars, and in situ analyses from ocean worlds to distinguish and separate what physical structures and chemical patterns are due to life and which are not. Moreover, we discuss hypothetical detection and preservation environments for extant and extinct life, respectively. These proposed environments will take into account independent active and ancient in situ detection prospects by using previous planetary exploration studies and discuss the geobiological implications within an astrobiological context.

Background: Prolactin receptor (PRLR) is an attractive antibody therapeutic target with expression across a broad population of breast cancers. Antibody efficacy, however, may be limited to subtypes with either PRLR overexpression and/or those where estradiol no longer functions as a mitogen and are, therefore, reliant on PRLR signaling for growth. In contrast a potent PRLR antibody-drug conjugate (ADC) may provide improved therapeutic outcomes extending beyond either PRLR overexpressing or estradiol-insensitive breast cancer populations., Methods: We derived a novel ADC targeting PRLR, ABBV-176, that delivers a pyrrolobenzodiazepine (PBD) dimer cytotoxin, an emerging class of warheads with enhanced potency and broader anticancer activity than the clinically validated auristatin or maytansine derivatives. This agent was tested in vitro and in vivo cell lines and patient derived xenograft models., Results: In both in vitro and in vivo assays, ABBV-176 exhibits potent cytotoxicity against multiple cell line and patient-derived xenograft breast tumor models, including triple negative and low PRLR expressing models insensitive to monomethyl auristatin (MMAE) based PRLR ADCs. ABBV-176, which cross links DNA and causes DNA breaks by virtue of its PBD warhead, also demonstrates enhanced anti-tumor activity in several breast cancer models when combined with a poly-ADP ribose polymerase (PARP) inhibitor, a potentiator of DNA damage., Conclusions: Collectively the efficacy and safety profile of ABBV-176 suggest it may be an effective therapy across a broad range of breast cancers and other cancer types where PRLR is expressed with the potential to combine with other therapeutics including PARP inhibitors.

Purpose: To evaluate the response of various stent-grafts after laser fenestration and dilation with noncompliant balloons to determine the optimal therapeutic combination for this treatment technique., Materials and Methods: Five aortic stent-grafts were evaluated ex vivo: the Bolton RelayPlus, Jotec E-vita Thoracic 3G, Medtronic Valiant, Cook Zenith Alpha, and Vascutek Anaconda. Small holes were created using an excimer laser with the grafts submerged in saline. Five rows of 5 fenestrations were created, 4 holes in each row were dilated once with a 6-, 8-, 10-, or 12-mm-diameter noncompliant balloon to the specified nominal pressure (one hole served as the control). The saline solution from each stent-graft was collected and qualitatively analyzed for debris. The fenestrations were evaluated under light and scanning electron microscopes. The maximum diameter and area for each fenestration were measured. The direction and length of tears were assessed., Results: The fenestration was feasible and reproducible in all the stent-grafts. The mean area of fenestration ranged from 7.63±1.63 to 14.75±0.73 mm 2 when using balloons of 6- and 8-mm diameter, respectively. The 10- and 12-mm-diameter balloons caused a significant increase in area, variability, and tearing. The Anaconda graft tended to tear in the weft direction, while the other devices tore in the warp direction when using the 10- and 12-mm-diameter balloons. Dilation of the RelayPlus and Anaconda grafts with 6- and 8-mm-diameter balloons provided minimal tearing and precise fenestrations. Melted fiber remnants were observed after filtration of the saline solution for all devices., Conclusion: Laser fenestration and dilation with noncompliant balloons is a relatively simple and reproducible option for revascularization in urgent, complex aortic endovascular repairs. In our model, large balloons (ie, >10 mm) increased the destruction and tearing of the fabric. The maximum dilation recommended is 6 to 8 mm to avoid significant tears. Development of stent-grafts or novel fabrics designed explicitly for fenestration is needed to reduce potential complications.

This article presents a five-part dataset for human gait analysis in a healthy older adult population (37 women and seven men; age 69.98 ± 8.57 years, body mass index 27.71 ± 4.57). Part 1 compromises demographic data for the 44 participants, along with the results of the Short Physical Performance Battery (SPPB) motor function test and the Mini-Mental State Examination (MMSE). We used the MMSE to ensure the participants could understand the experimental protocol instructions. Part 2 presents the anthropometric measurements of the participants. Part 3 shows the results for each item of the Gait component of the Performance Oriented Mobility Assessment (POMA-G). Part 4 contains five files per participant, storing motion-capture data for the lower limb in the Coordinate 3D (C3D) format. These files were generated using a Vicon motion analysis system, consisting of 24 reflective markers and seven cameras (Vantage V5) sampled at 100 Hz. Part 5 contains 26 gait parameters for each C3D file obtained using Nexus 2.9.3. The dataset is available in a Mendeley repository (Reserved DOI: 10.17632/xgw6bg3g8h.1)., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have, or could be perceived to have, influenced the work reported in this article., (© 2020 The Author(s).)

This paper proposes a low-cost portable electronic system for estimating step width during the human gait cycle. This device, intended to support the Walking Stance item of the fall risk assessment test Performance Oriented Mobility Assessment (POMA), contains three electronic boards, comprising two sensing nodes and a concentrator. Each sensing node contains a force sensitive resistor (FSR) and time-of-flight camera (TOF). Each FSR is placed inside the subject's shoe, while each TOF camera is located at the back of their foot. The FSR detects contact between heel and ground, and the TOF measures the distance to a barrier located on the right side of the walking path. Step width is calculated as the difference between the TOF measurements. After the walk is complete, the information obtained by the FSRs and TOFs is sent via a 433 MHz wireless communication to the concentrator board, which is connected to the USB port of a personal computer (PC). The proposed step width measurement system was validated with an infrared based motion capture (Vicon Corp.), giving an error equal to 11.4%  ±  5.5%., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors.)

A 24-hour-old male presented with bruising and swelling of the right hemiscrotum and groin. Testicular torsion was ruled out in a Doppler sonography, signs of an evolving right adrenal hemorrhage was demonstrated in the abdominal ultrasound. The imaging follow-up proved the disappearance of both scrotal and adrenal hematomas. Including the adrenal hemorrhage of the newborn in the differential diagnosis of an acute scrotum can prevent unnecessary surgical explorations., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The ability to store information is believed to have been crucial for the origin and evolution of life; however, little is known about the genetic polymers relevant to abiogenesis. Nitrogen heterocycles (N-heterocycles) are plausible components of such polymers as they may have been readily available on early Earth and are the means by which the extant genetic macromolecules RNA and DNA store information. Here, we report the reactivity of numerous N-heterocycles in highly complex mixtures, which were generated using a Miller-Urey spark discharge apparatus with either a reducing or neutral atmosphere, to investigate how N-heterocycles are modified under plausible prebiotic conditions. High throughput mass spectrometry was used to identify N-heterocycle adducts. Additionally, tandem mass spectrometry and nuclear magnetic resonance spectroscopy were used to elucidate reaction pathways for select reactions. Remarkably, we found that the majority of N-heterocycles, including the canonical nucleobases, gain short carbonyl side chains in our complex mixtures via a Strecker-like synthesis or Michael addition. These types of N-heterocycle adducts are subunits of the proposed RNA precursor, peptide nucleic acids (PNAs). The ease with which these carbonylated heterocycles form under both reducing and neutral atmospheres is suggestive that PNAs could be prebiotically feasible on early Earth.

Using a sub-millimeter exciton-polariton waveguide suitable for integrated photonics, we experimentally demonstrate nonlinear modulation of pico-Joule pulses at the same time as amplification sufficient to compensate the system losses. By comparison with a numerical model we explain the observed interplay of gain and nonlinearity as amplification of the interacting polariton field by stimulated scattering from an incoherent continuous-wave reservoir that is depleted by the pulses. This combination of gain and giant ultrafast nonlinearity operating on picosecond pulses has the potential to open up new directions in low-power all-optical information processing and nonlinear photonic simulation of conservative and driven-dissipative systems.

Persistent sciatic vein is a rare anomaly of mesodermal development. When found, it is often associated with varicosities in abnormal distributions, pain, limb congestion, and hypertrophy. In this report, we describe a case of an isolated, complete persistent sciatic vein with an atypical anatomy and onset., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: In this study we assess the impact of a "rapid imaging protocol" (RIP) on outcomes in patients with suspected acute cholecystitis (AC)., Methods: From January 2017 to January 2018, a prospective cohort study was implemented using a RIP with hepatoscintigraphy (HIDA) or CT scan (first available, goal within 4 h) in patients (n = 52) presenting with highly suspected AC and a clinical feature score of ≥1. For the latter, the following presenting features were scored as follows: 1 point for WBC count ≥10,000 (10 9 /L), 1.5 points for glucose ≥140 (mg/dl), and/or 1 point for age ≥50 yrs. The historical control was all patients admitted with suspected AC in a 1.5-year period (n = 117) under our previous "delayed imaging protocol" (DIP), which used US ± HIDA (post-admission) in select patients. Primary end points included: compare outcome and quality measures between the groups, evaluate diagnostic imaging performance for AC, and evaluate our proposed clinical feature score in the setting of AC., Results: Histopathologic features consistent with AC was more frequent in patients in the RIP (64% vs 39%, p = 0.008). The pooled positive predictive value of HIDA and CT scan for AC were 85% vs 94%, respectively. The RIP was associated with a significant reduction in time to surgery, length of stay, and conversions to open (p < 0.001, respectively). A clinical feature score of 3.5 predicted the likelihood of AC in 95% of the cases (x 2 for linear trend = 42, p < 0.001)., Conclusion: A protocol centered around rapid identification, defined clinical criteria (i.e. clinical feature score), and confirmation with non-user dependent imaging modalities has resulted in favorable outcomes. CT may be the study of choice when the likelihood of AC is high because it is superior at identifying severity., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Novel biologics that redirect cytotoxic T lymphocytes (CTLs) to kill tumor cells bearing a tumor associated antigen hold great promise in the clinic. However, the ability to safely and potently target CD3 on CTL toward tumor associated antigens (TAA) expressed on tumor cells remains a challenge of both technology and biology. Herein we describe the use of a Half DVD-Ig format that can redirect CTL to kill tumor cells. Notably, Half DVD-Ig molecules that are monovalent for each specificity demonstrated reduced non-specific CTL activation and conditional CTL activation upon binding to TAA compared to intact tetravalent DVD-Ig molecules that are bivalent for each specificity, while maintaining good drug like properties and appropriate PK properties.

Exciton-polaritons in semiconductor microcavities form a highly nonlinear platform to study a variety of effects interfacing optical, condensed matter, quantum and statistical physics. We show that the complex polariton patterns generated by picosecond pulses in microcavity wire waveguides can be understood as the Cherenkov radiation emitted by bright polariton solitons, which is enabled by the unique microcavity polariton dispersion, which has momentum intervals with positive and negative group velocities. Unlike in optical fibres and semiconductor waveguides, we observe that the microcavity wire Cherenkov radiation is predominantly emitted with negative group velocity and therefore propagates backwards relative to the propagation direction of the emitting soliton. We have developed a theory of the microcavity wire polariton solitons and of their Cherenkov radiation and conducted a series of experiments, where we have measured polariton-soliton pulse compression, pulse breaking and emission of the backward Cherenkov radiation.

Neurological disorders frequently affect walking function which is one of the most fundamental skills to improve quality of life and autonomy, and Lokomat has been a key piece for gait's rehabilitation. In this study, a diagnosis about the development of the Robot-assisted therapy rehabilitation with Lokomat in Colombia is made. The study was performed by collecting some anthropometric and demographic data of the patients that use Lokomat, followed by a survey of cognitive aspects. With the purpose to compare the current state of the robotic therapies it was found that in Colombia the benefits of this treatment have not being fully exploited. Regarding the cognitive aspects, most of the patients that use Lokomat as a rehabilitation therapy feel comfortable (47%), very safe (68%) and have a perpective of significant results with the therapy (68%). However, when compared the number of patients in therapy with Lokomat with the number of the population that has gait disabilities, it is found that few Colombians have access to this type of therapy.

Background: We assess the performance of ultrasound (US) and hepatobiliary scintigraphy (HIDA) as confirmatory studies in acute cholecystitis (AC) and demonstrate our current imaging protocol's impact on outcomes., Study Design: Between January 2013 to July 2014, 117 patients were admitted through the emergency room with a preliminary diagnosis of AC. Overall, 106/117 (91%) of the patients received US preadmission and 34/117 (29%) received a HIDA post admission. Primary end points included: 1) diagnostic test reliability for AC, and 2) outcome and quality measures (time to surgery, LOS, costs, etc.)., Results: Laparoscopic cholecystectomy was performed in 96/117 (82%) and open cholecystectomy in 21/117 (18%) of the patients. Overall, histopathologic features consistent with AC was present in 46/117 (39%). AC alone was present in 23/117 (20%), and AC superimposed on chronic cholecystitis was present in 23/117 (20%). For AC, US had a sensitivity and specificity of 26% and 80%, respectively. HIDA scan had a sensitivity and specificity of 87% and 79%, respectively. Time to surgery (TTS) was 4 vs 2.3 days in patients who received HIDA vs US alone (p = 0.001), and length of stay (LOS) was 6.7 vs 4.3 days, respectively (p = 0.001). Age >50 years, glucose >140 (mg/dl), and WBC count >10 (×10 9 /L) were statistically significant independent variables associated with AC., Conclusion: HIDA scan is superior to US as a diagnostic study in the setting of AC. Our current protocol of delayed HIDA (post-admission) was associated with increased TTS, LOS, and overall costs. Early confirmation with HIDA in high risk patients may hasten treatment allocation and improve outcomes in the setting of AC., (Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Unlabelled: Poly(ADP-ribose) polymerases (PARP1, -2, and -3) play important roles in DNA damage repair. As such, a number of PARP inhibitors are undergoing clinical development as anticancer therapies, particularly in tumors with DNA repair deficits and in combination with DNA-damaging agents. Preclinical evidence indicates that PARP inhibitors potentiate the cytotoxicity of DNA alkylating agents. It has been proposed that a major mechanism underlying this activity is the allosteric trapping of PARP1 at DNA single-strand breaks during base excision repair; however, direct evidence of allostery has not been reported. Here the data reveal that veliparib, olaparib, niraparib, and talazoparib (BMN-673) potentiate the cytotoxicity of alkylating agents. Consistent with this, all four drugs possess PARP1 trapping activity. Using biochemical and cellular approaches, we directly probe the trapping mechanism for an allosteric component. These studies indicate that trapping is due to catalytic inhibition and not allostery. The potency of PARP inhibitors with respect to trapping and catalytic inhibition is linearly correlated in biochemical systems but is nonlinear in cells. High-content imaging of γH2Ax levels suggests that this is attributable to differential potentiation of DNA damage in cells. Trapping potency is inversely correlated with tolerability when PARP inhibitors are combined with temozolomide in mouse xenograft studies. As a result, PARP inhibitors with dramatically different trapping potencies elicit comparable in vivo efficacy at maximum tolerated doses. Finally, the impact of trapping on tolerability and efficacy is likely to be context specific., Implications: Understanding the context-specific relationships of trapping and catalytic inhibition with both tolerability and efficacy will aid in determining the suitability of a PARP inhibitor for inclusion in a particular clinical regimen., (©2015 American Association for Cancer Research.)

Background: Anaesthetists need to know the different causes of persistent headache or a change in level of consciousness following epidural analgesia for labour. Failure to recognise these neurological complications can lead to delayed diagnoses, with subsequent serious implications., Methods: We present a patient who was re-admitted for postural headache resulting from an unrecognised dural puncture during an epidural for pain relief while in labour. During the interview, the patient confirmed drug use (cocaine), so she was evaluated by a psychiatrist with possible post-partum psychosis or drug withdrawal syndrome. Afterwards, the patient deteriorated neurologically, showing impaired consciousness and seizures., Results: The cranial computed tomography showed bilateral frontoparietal subdural collections with intraparenchymal and subarachnoid haemorrhaging. She improved by burr hole drainage of subdural hygroma and a blood patch., Conclusions: Neurological signs should alert the clinician to the possibility of subdural collection and other possible complications such as sinking of the brain in order not to delay the request for imaging tests for diagnoses and effective treatments., (© 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)