Search

This study assessed for the first time the bioremediation potential of an organic horse amendment in soils contaminated with solid wastes of the obsolete pesticide lindane (α-hexachlorocyclohexane (α-HCH) = 80 mg kg -1 , β-HCH = 40 mg kg -1 , γ,δ,ε-HCH≈10 mg kg -1 ) searching for a self-sufficient bio-based economy. Four treatments were implemented: polluted (PS, ΣHCHs = 130 mg kg -1 ) and control (CS, ΣHCHs = 1.24 mg kg -1 ) soils and the respective amended soils (APS and ACS). A commercial amendment, coming from organic wastes, was used for soil biostimulation (5% dry weight), and the temporal evolution of the enzymatic activity (dehydrogenase, β-glucosidase activity, phenoloxidase, arylamidase, phosphatase, and urease) and HCHs concentration of the soils was evaluated over 55 days under controlled humidity and temperature conditions. The horse amendment positively influenced the physicochemical properties of the soil by reducing pH (from 8.3 to 8) and increasing the organic matter (TOC from 0.5 to 3.3%) and nutrient content (P and NH 4 + from 24.1 to 13.7 to 142.1 and 41.2 mg kg -1 , respectively). Consequently, there was a notable enhancement in the soil biological activity, specifically in the enzymatic activity of dehydrogenase, phenol-oxidase, phosphatase, and urease and, therefore, in HCH degradation, which increased from <1 to 75% after the incubation period. According to the chlorine position on the cyclohexane ring, the following ranking has been found for HCHs degradation: β-HCH (46%) < ε-HCH (57%) < α-HCH (91%) ≈ δ-HCH (91%) < γ-HCH (100%). Pentachlorocyclohexene (PCCH) and 1,2,4-trichlorobenzene (1,2,4-TCB) were identified as HCHs degradation metabolites and disappeared at the end of the incubation time. Although further research is required, these preliminary findings suggest that organic amendments represent a sustainable, harmless, and cost-effective biostimulation approach for remediating soils contaminated with recalcitrant HCHs, boosting the circular economy., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Studies have found that sodium-glucose cotransporter 2 inhibitors (SGLT2) and glucagon-like peptide 1 receptor agonists (GLP1) have cardiovascular benefits for patients with type 2 diabetes (DM2) and atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), or heart failure (HF). The literature does not provide evidence specifically for patients with these conditions who are adding one of these medicines to two glucose-lowering medications (ie, as "third-step" therapy). We explored the effects of different third-step medications on cardiovascular outcomes in patients with diabetes and these comorbid conditions. Specifically, we compared third-step SGLT2 or GLP1 to third-step dipeptidyl peptidase-4 inhibitors (DPP4), insulin, or thiazolidinediones (TZD)., Research Design and Methods: We assembled a retrospective cohort of adults at five Kaiser Permanente sites with DM2 and ASCVD, CKD, or HF, initiating third-step treatment between 2016 and 2020. Propensity score weighted Poisson models were used to calculate adjusted rate ratios (ARRs) for all-cause mortality, incident major adverse cardiovascular event (MACE), and incident HF hospitalization in patients initiating SGLT2 or GLP1 compared with DPP4, insulin, or TZD., Results: We identified 27 542 patients initiating third-step treatment with one or more of these conditions (19 958 with ASCVD, 14 577 with CKD, and 3919 with HF). ARRs for GLP1 and SGLT2 versus DPP4, insulin, and TZD in the patient subgroups ranged between 0.22 and 0.55 for all-cause mortality, 0.38 and 0.81 for MACE, and 0.46 and 1.05 for HF hospitalization. Many ARRs were statistically significant, and all significant ARRs showed a benefit (ARR <1) for GLP1 or SGLT2 when compared with DPP4, insulin, or TZD., Conclusions: Third-step SGLT2 and GLP1 are generally associated with a benefit for these outcomes in these patient groups when compared with third-step DPP4, insulin, or TZD. Our results add to evidence of a cardiovascular benefit of SGLT2 and GLP1 and could inform clinical guidelines for choosing third-step diabetes treatment., Competing Interests: Competing interests: JPM provided paid consulting services to an expert panel with the American Academy of HIV Medicine. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Calcium-magnesium-aluminium-silicate (CMAS) attack is a longstanding challenge for yttria stabilized zirconia (YSZ) thermal barrier coatings (TBCs) particularly at higher engine operating temperature. Here, a novel microstructural design is reported for YSZ TBCs to mitigate CMAS attack. The design is based on a drip coating method that creates a thin layer of nanoporous Al 2 O 3 around YSZ columnar grains produced by electron beam physical vapor deposition (EB-PVD). The nanoporous Al 2 O 3 enables fast crystallization of CMAS melt close to the TBC surface, in the inter-columnar gaps, and on the column walls, thereby suppressing CMAS infiltration and preventing further degradation of the TBCs due to CMAS attack. Indentation and three-point beam bending tests indicate that the highly porous Al 2 O 3 only slightly stiffens the TBC but offers superior resistance against sintering in long-term thermal exposure by reducing the intercolumnar contact. This work offers a new pathway for designing novel TBC architecture with excellent CMAS resistance, strain tolerance, and sintering resistance, which also points out new insight for assembly nanoporous ceramic in traditional ceramic structure for integrated functions., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Importance: Prior research found increases in diabetes among youth during the COVID-19 pandemic, but few studies examined variation across sociodemographics., Objective: To examine diabetes incidence rates among a diverse population of youth in the US before and during the COVID-19 pandemic., Design, Setting, and Participants: This cohort study included data from Kaiser Permanente Southern California (KPSC) between January 1, 2016, and December 31, 2021. KPSC members aged from birth to 19 years with no history of diabetes were included. Individuals were followed up using electronic health records for diabetes incidence defined using diagnoses, laboratory values, and medications. Analyses were conducted between November 2022 and January 2023., Main Outcome and Measures: Age- and sex-standardized annual and quarterly incidence rates per 100 000 person-years (PYs) were calculated for type 1 diabetes and type 2 diabetes between 2016 and 2021. Rates were calculated within strata of age (<10 and 10-19 years), sex, and race and ethnicity (Asian/Pacific Islander, Hispanic, non-Hispanic Black, non-Hispanic White, and other/multiple/unknown). Using Poisson regression with robust error variances, incidence rate ratios (IRR) comparing 2020 to 2021 with 2016 to 2019 were calculated by diabetes type and within age, sex, and race and ethnicity strata and adjusting for health care utilization., Results: Between 2016 to 2021, there were 1200, 1100, and 63 patients with type 1 diabetes (mean [SD] age, 11.0 [4.5] years; 687 [57.3%] male), type 2 diabetes (mean [SD] age, 15.7 [2.7] years; 516 [46.9%] male), and other diabetes, respectively. Incidence of type 1 diabetes increased from 18.5 per 100 000 PYs in 2016 to 2019 to 22.4 per 100 000 PYs from 2020 to 2021 with increased IRRs among individuals aged 10 to 19 years, male individuals, and Hispanic individuals. Incidence of type 2 diabetes increased from 14.8 per 100 000 PYs from 2016 to 2019 to 24.7 per 100 000 PYs from 2020 to 2021 with increased IRRs among individuals aged 10 to 19 years, male and female individuals, and those with Black, Hispanic, and other/unknown race and ethnicity., Conclusions and Relevance: In this cohort study of youth in KPSC, incidence of diabetes increased during the COVID-19 pandemic and was more pronounced in specific racial and ethnic groups. Future research to understand differential impacts of physiologic and behavioral risk factors is warranted.

One of the current challenges of working with nanomaterials in bioapplications is having a tool that is biocompatible (non-toxic) and produces stable, intense fluorescence for bioimaging. To address these challenges, we have developed a streamlined and one-pot synthetic route for silicon-based quantum dots (SiQDs) using a hydrothermal method. Part of our unique approach for designing the SiQDs was to incorporate (3-aminopropyl) triethoxysilane (APTES), which is an amphipathic molecule with hydroxyl and amine functional groups available for modification. In order to reduce the toxicity of APTES, we chose glucose as a reducing agent for the reaction. The resulting SiQDs produced potent, stable, potential dual-emissive fluorescence emission peaks in the visible and near-infrared (NIR) ranges. Both peaks could be used as distinguishing fluorescence signals for bioimaging, separately or in combination. The physical and optical properties of the SiQDs were determined under a range of environmental conditions. The morphology, surface composition, and electronic structure of the SiQDs were characterized using high resolution-transmission electronic microscopy (HR-TEM), energy dispersive X-ray spectroscopy (EDS), Fourier-transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The stability of the SiQDs was evaluated under a wide range of pHs. The biocompatibility and imaging potential of the SiQDs were tested in microvascular endothelial cells (MVEC), neural stem cells (NSC), and RAW 264.7 macrophage cells. The images obtained revealed different subcellular localizations, particularly during cell division, with distinct fluorescence intensities. The results demonstrated that SiQDs are a promising, non-toxic labeling tool for a variety of cell types, with the added advantage of having dual emission peaks both in visible and NIR ranges for bioimaging., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

Cell-free systems are useful tools for prototyping metabolic pathways and optimizing the production of various bioproducts. Mechanistically-based kinetic models are uniquely suited to analyze dynamic experimental data collected from cell-free systems and provide vital qualitative insight. However, to date, dynamic kinetic models have not been applied with rigorous biological constraints or trained on adequate experimental data to the degree that they would give high confidence in predictions and broadly demonstrate the potential for widespread use of such kinetic models. In this work, we construct a large-scale dynamic model of cell-free metabolism with the goal of understanding and optimizing butanol production in a cell-free system. Using a combination of parameterization methods, the resultant model captures experimental metabolite measurements across two experimental conditions for nine metabolites at timepoints between 0 and 24 h. We present analysis of the model predictions, provide recommendations for butanol optimization, and identify the aldehyde/alcohol dehydrogenase as the primary bottleneck in butanol production. Sensitivity analysis further reveals the extent to which various parameters are constrained, and our approach for probing valid parameter ranges can be applied to other modeling efforts., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)

Burkitt lymphoma (BL) accounts for most pediatric non-Hodgkin lymphomas, being less common but significantly more lethal when diagnosed in adults. Much of the knowledge of the genetics of BL thus far has originated from the study of pediatric BL (pBL), leaving its relationship to adult BL (aBL) and other adult lymphomas not fully explored. We sought to more thoroughly identify the somatic changes that underlie lymphomagenesis in aBL and any molecular features that associate with clinical disparities within and between pBL and aBL. Through comprehensive whole-genome sequencing of 230 BL and 295 diffuse large B-cell lymphoma (DLBCL) tumors, we identified additional significantly mutated genes, including more genetic features that associate with tumor Epstein-Barr virus status, and unraveled new distinct subgroupings within BL and DLBCL with 3 predominantly comprising BLs: DGG-BL (DDX3X, GNA13, and GNAI2), IC-BL (ID3 and CCND3), and Q53-BL (quiet TP53). Each BL subgroup is characterized by combinations of common driver and noncoding mutations caused by aberrant somatic hypermutation. The largest subgroups of BL cases, IC-BL and DGG-BL, are further characterized by distinct biological and gene expression differences. IC-BL and DGG-BL and their prototypical genetic features (ID3 and TP53) had significant associations with patient outcomes that were different among aBL and pBL cohorts. These findings highlight shared pathogenesis between aBL and pBL, and establish genetic subtypes within BL that serve to delineate tumors with distinct molecular features, providing a new framework for epidemiologic, diagnostic, and therapeutic strategies., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

The versatility of microalgae biomass as candidates for various products and bioremediation needs motivates interests towards design and implementation of novel microalgae bioreactors. Conventional open-reactors are reliant on large quantities of sunlight and space while yields are constrained by outdoor environment conditions. Conversely, closed-reactor systems like bubble columns reduces these constrains on microalgae growth while occupying far less space at the expense of high energy demands, notably from lighting systems. A novel patented closed reactor design has recently been proposed that improves the bubble column concept with an efficient and effective lighting system. The present study uses Life Cycle Assessment approach to compare the environmental performance of conventional reactors and the proposed internally luminated novel closed reactor design, expressing impacts per kg biostimulant for the Scenedesmus almeriensis harvest from such units. All performance data was collected from a pilot facility in Almeria, Spain. Urban-industrial symbiosis scenarios are also portrayed in the study using wastewater and incinerator flue gas. Results show that under synthetic nutrient and carbon inputs in Spanish pilot operations, the cumulative energy demand for the novel photobioreactors is similar to conventional vertically-stacked horizon bioreactors but are substantially more demanding than conventional open reactors. However, when leveraging renewable energy sources and the photosynthesis process to consume wastestreams in urban-industrial symbiosis scenarios, the novel photobioreactor was able to achieve up to 80 % improvements in several impact categories e.g. eutrophication and climate change. Impact mitigation credits per kg dwt biomass across all energy scenarios in symbiosis amount to ≈1.8 kg CO 2 eq and ≈0.09 kg PO4 eq. This highlights that such closed and internally illuminated photobioreactors can be competitive with conventional reactors, and have potential to harness photosynthesis to reduce environmental burdens in an urban-industrial symbiosis setting. Possible economies of scale and the associated potential gains in efficiencies are further discussed., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All Authors reports financial support was provided by SYCTOM, L'AGENCE METROPOLITAINE DES DECHETS MENAGERS. SYCTOM, L'AGENCE METROPOLITAINE DES DECHETS MENAGER has patent #Internally illuminated photo bioreactor with light pipe distributor for photo-reactive microorganism culture (Application number EP21305251.7, PCT submission number 10718919, PCT application number: PCT/EP2022/055315) pending to the European Patent Office for the following Licensee/Assignee: SYCTOM, L'AGENCE METROPOLITAINE DES DECHETS MENAGERS, SETEC ENERGIE ENVIRONNEMENT, LA CORPORATION DE L'ECOLE POLYTECHNIQUE DE MONTREAL, ASSOCIATION POUR LA RECHERCHE ET LE DEVELOPPEMENT DES METHODES ET PROCESSUS INDUSTRIELS, Kungliga Tekniska Högskolan., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: COVID-19 exacerbates the long-standing, low-grade chronic inflammation observed in diabetes leading to heightened insulin resistance and hyperglycemia. Mortality increases with hyperglycemia and poor glycemic variability, hence, this study aims to identify the predictors associated with poor glycemic control and increased glucose variability among patients with COVID-19 and Type 2 Diabetes Mellitus (T2DM)., Methodology: A retrospective chart review of 109 patients with moderate to severe COVID-19 and T2DM admitted from March 2020 to June 2021 was done. Logistic regression was done to determine predictors for hyperglycemia and poor variability., Results: Of the 109 patients, 78% had hyperglycemia and poor variability and 22% had no poor outcomes. Chronic kidney disease (eOR 2.83, CI [1.07-7.46], p = 0.035) was associated with increased glycemic variability. In contrast, increasing eGFR level (eOR 0.97, CI [0.96-0.99], p = 0.004) was associated with less likelihood of increased variability. Hs-CRP (eOR 1.01, CI [1.00-1.01], p = 0.011), HbA1c (eOR 1.86, CI [1.23-2.82], p = 0.003), severe COVID-19 (eOR 8.91, CI [1.77-44.94], p = 0.008) and critical COVID-19 (eOR 4.42, CI [1.65-11.75], p = 0.003) were associated with hyperglycemia. Steroid use (eOR 71.17, CI [8.53-593.54], p <0.001) showed the strongest association with hyperglycemia., Conclusion: Potential clinical, laboratory and inflammatory profiles were identified as predictors for poor glycemic control and variability outcomes. HbA1c, hs-CRP, and COVID-19 severity are predictors of hyperglycemia. Likewise, chronic kidney disease is a predictor of increased glycemic variability., Competing Interests: The authors declared no conflict of interest., (© 2023 Journal of the ASEAN Federation of Endocrine Societies.)

Complex tasks like hunting moving prey in an unpredictable environment require high levels of motor and sensory integration. An animal needs to detect and track suitable prey objects, measure their distance and orientation relative to its own position, and finally produce the correct motor output to approach and capture the prey. In the insect brain, the central complex (CX) is one target area where integration is likely to take place. In this study, we performed extracellular multi-unit recordings on the CX of freely hunting praying mantises ( Tenodera sinensis ). Initially, we recorded the neural activity of freely moving mantises as they hunted live prey. The recordings showed activity in cells that either reflected the mantis's own movements or the actions of a prey individual, which the mantises focused on. In the latter case, the activity increased as the prey moved and decreased when it stopped. Interestingly, cells ignored the movement of the other prey than the one to which the mantis attended. To obtain quantitative data, we generated simulated prey targets presented on an LCD screen positioned below the clear floor of the arena. The simulated target oscillated back and forth at various angles and distances. We identified populations of cells whose activity patterns were strongly linked to the appearance, movement, and relative position of the virtual prey. We refer to these as sensory responses. We also found cells whose activity preceded orientation movement toward the prey. We call these motor responses. Some cells showed both sensory and motor properties. Stimulation through tetrodes in some of the preparations could also generate similar movements. These results suggest the crucial importance of the CX to prey-capture behavior in predatory insects like the praying mantis and, hence, further emphasize its role in behaviorally and ecologically relevant contexts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wosnitza, Martin, Pollack, Svenson and Ritzmann.)

Objective: The role of uncontrolled blood pressure (BP) in COVID-19 severity among patients with hypertension is unclear. We evaluated the association between uncontrolled BP and the risk of hospitalization and/or mortality in patients with hypertension from a large US integrated healthcare system., Methods: We identified patients with hypertension and a positive RT-PCR test result or a diagnosis of COVID-19 between March 1 - September 1, 2020 from Kaiser Permanente Southern California. BP categories was defined using the most recent outpatient BP measurement during 12 months prior to COVID-19 infection. The primary outcome of interest was all-cause hospitalization or mortality within 30 days from COVID-19 infection., Results: Among 12,548 patients with hypertension and COVID-19 (mean age = 60 years, 47% male), 63% had uncontrolled BP (≥130/80 mm Hg) prior to COVID-19. Twenty-one percent were hospitalized or died within 30 days of COVID-19 infection. Uncontrolled BP was not associated with higher hospitalization or mortality (adjusted rate ratios for BP ≥ 160/100 mm Hg vs < 130/80 mm Hg = 1.00 [95% CI: 0.87, 1.14]; BP 140-159/90-99 mm Hg vs < 130/80 mm Hg = 1.02 [95% CI: 0.93, 1.11]). These findings were consistent across different age groups, treatment for antihypertensive medications, as well as atherosclerotic cardiovascular disease risk., Conclusion: Among patients with hypertension, uncontrolled BP prior to COVID-19 infection did not appear to be an important risk factor for 30-day mortality or hospitalization., (© 2021 The Authors.)

Background: Approximately 1 in 20 cases of colorectal cancer are caused by monogenic syndromes. Published guidelines recommend that patients with 10 or more adenomas be referred for genetic testing, based on evidence that colorectal cancer risk is associated with adenoma multiplicity., Objective: The aim of this study was to determine adherence to guidelines on referral for genetic screening in patients with 10 or more adenomas., Design: A cross-sectional study was performed of prospectively collected data from the UK Bowel Cancer Screening Programme between May 2007 and June 2018. Only histologically confirmed adenomas were included. Clinicopathological data were recorded from patient records, and referrals to clinical genetics services were ascertained., Setting: Data were obtained from 3 centers in London, United Kingdom., Patients: A total of 17,450 subjects underwent colonoscopy following an abnormal fecal occult blood test., Main Outcome Measures: We quantified patients with 10 or more adenomas and the proportion referred for genetic screening., Results: The adenoma detection rate was 50.6% among 17,450 patients who underwent colonoscopy (8831 had 1 or more adenomas). Three hundred forty-seven patients (2.0%) had 10 or more adenomas. Patients with 10 or more adenomas were more likely to be male than those with fewer than 10 adenomas (76.9% vs 53.4%; p < 0.0001). A family history was collected in 37.8% of the multiple adenoma population. Of 347 patients with 10 or more adenomas, 28 (8.1%) were referred for genetic assessment., Limitations: All 3 screening centers were in a single city. No genetic outcome data were available to permit analysis of actual rates of inherited cancer syndromes in this population., Conclusions: In this study, almost 1 in 50 patients had 10 or more adenomas. Despite guidelines advising genetic testing in this group, referral rates are low. A referral pathway and management strategies should be established to address this patient population. See Video Abstract at http://links.lww.com/DCR/B630., Tasas Bajas De Derivacin Para La Evaluacin Gentica De Pacientes Con Adenomas Mltiples En Los Programas De Deteccin Del Cncer De Intestino Del Reino Unido: ANTECEDENTES:Aproximadamente uno de cada veinte casos de cáncer colorrectal son causados por síndromes monogénicos. Las pautas publicadas recomiendan que los pacientes con diez o más adenomas sean derivados para pruebas genéticas, basándose en la evidencia de que el riesgo de cáncer colorrectal está asociado con la multiplicidad de adenomas.OBJETIVO:El objetivo de este estudio fue determinar la adherencia a las guías de derivación para cribado genético en pacientes con diez o más adenomas.DISEÑO:Se realizó un estudio transversal de datos recolectados prospectivamente del Programa de Detección de Cáncer de Intestino del Reino Unido entre mayo de 2007 y junio de 2018. Solo se incluyeron los adenomas confirmados histológicamente. Los datos clínico-patológicos se registraron a partir de los registros de los pacientes y se determinaron las derivaciones a los servicios de genética clínica.AJUSTE ENTORNO CLINICO:Los datos se obtuvieron de tres centros en Londres, Reino Unido.PACIENTES:Un total de 17.450 17450 sujetos pacientes se sometieron a una colonoscopia después de una prueba de sangre oculta en heces anormal positiva.PRINCIPALES MEDIDAS DE RESULTADO VOLARACION:cuantificamos los pacientes con diez o más adenomas y la proporción remitida para cribado genético.RESULTADOS:La tasa de detección de adenomas fue del 50,6% entre 17.450 17450 pacientes que se sometieron a colonoscopia (8.831 8831 tenían uno o más adenomas). 347 pacientes (2,0%) tenían 10 o más adenomas. Los pacientes con 10 o más adenomas tenían más probabilidades de ser hombres que aquellos con menos de 10 adenomas (76,9% frente versus a 53,4%; p <0,0001). Se recogieron antecedentes familiares en el 37,8% de la población de adenomas múltiples. De 347 pacientes con 10 o más adenomas, 28 (8,1%) fueron remitidos para evaluación genética.LIMITACIONES:Los tres centros de detección se encontraban en una sola ciudad. No se disponía de datos de resultados genéticos que permitieran el análisis de las tasas reales de síndromes de cáncer hereditario en esta población.CONCLUSIONES:En este estudio, casi uno de cada cincuenta pacientes tenía diez o más adenomas. A pesar de las pautas que recomiendan las pruebas genéticas en este grupo, las tasas de derivación son bajas. Se debe establecer una vía de derivación y estrategias de manejo para abordar esta población de pacientes. Consulte Video Resumen en http://links.lww.com/DCR/B630., (Copyright © The ASCRS 2021.)

More than 125 years have elapsed since the "Maison Lüer" in Paris produced their quintessential all-glass hypodermic syringe. The product would subsequently conquer the medical world, with billions of plastic syringes produced on a yearly basis nowadays. One wonders how a world would look without this priceless diagnostic and therapeutic tool, facilitating the administration of drugs, fluids, and blood products to billions of patients worldwide. The Lüer syringe dates to 1894, when Parisian medical instrument maker Hermann Wülfing-Lüer manufactured a unique graduated all-glass hypodermic syringe. Its conical tip allowed accurate injections with rapid leak-free connections, and was heat-resistant without breaking while autoclaving at 120 °C. The authors of this article rectified several inaccuracies of historical facts, and obtained copies of original patents, documents and syringes to reveal accurate details regarding the originators of the all-glass syringes. The Lüer fittings are simple devices that connect virtually all syringes, needles and tubing. They are used in medicine and beyond, whether it is a Lüer-Slip or a Lüer-Lok™ (Lüer-Lock) version. In 1995, The International Organization of Standardization recommended the standard use of the Lüer-tipped syringe worldwide. Despite this, their popularity has sustained significant setbacks at times, including when reports were published on misconnections and wrong-route administration of drugs, resulting in harm to patients with sometimes fatal outcomes. Healthcare workers mistakenly connected devices with a specific use to other devices used for a different application. Current syringes are now mostly mass-produced, disposable plastic syringes, which still come with Lüer fittings for intravascular and hypodermic needles, whereas specific non-Lüer connectors are designed for other systems., (Copyright © 2021 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Objective: Although recent evidence suggests no increased risk of severe COVID-19 outcomes associated with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) use, the relationship is less clear among patients with hypertension and diverse racial/ethnic groups. This study evaluates the risk of hospitalization and mortality among patients with hypertension and COVID-19 in a large US integrated healthcare system., Methods: Patients with hypertension and COVID-19 (between March 1- September 1, 2020) on ACEIs or ARBs were compared with patients on other frequently used antihypertensive medications., Results: Among 14,129 patients with hypertension and COVID-19 infection (mean age 60 years, 48% men, 58% Hispanic), 21% were admitted to the hospital within 30 days of COVID-19 infection. Of the hospitalized patients, 24% were admitted to intensive care units, 17% required mechanical ventilation, and 10% died within 30 days of COVID-19 infection. Exposure to ACEIs or ARBs prior to COVID-19 infection was not associated with an increased risk of hospitalization or all-cause mortality (rate ratios for ACEIs vs other antihypertensive medications ​= ​0.98, 95% CI: 0.88, 1.08; ARBs vs others ​= ​1.00, 95% CI: 0.90, 1.11) after applying inverse probability of treatment weights. These associations were consistent across racial/ethnic groups. Use of ACEIs or ARBs during hospitalization was associated with a lower risk of all-cause mortality (odds ratios for ACEIs or ARBs vs others ​= ​0.50, 95% CI: 0.34, 0.72)., Conclusion: Our study findings support continuation of ACEI or ARB use for patients with hypertension during the COVID-19 pandemic and after COVID-19 infection., Competing Interests: An reports grants from Novartis Pharma AG, Vital Strategies/Resolve to Save Lives, Merck & Co., and AstraZeneca Pharmaceuticals LP outside the submitted work. Wei and Luong report grants from Novartis Pharma AG and Vital Strategies/Resolve to Save Lives outside the submitted work. Zhou reports grants from AstraZeneca Pharmaceuticals LP. Gould, Mefford, Harrison, Creekmur, Lee, Sim, Brettler, Martin, and Ong‐Su have no financial disclosures. Reynolds reports grants from Novartis Pharma AG, Merck & Co., Amgen, and Vital Strategies/Resolve to Save Lives outside the submitted work., (© 2021 The Authors.)

Professional engineering organizations (PEOs) have the potential to provide women and underrepresented and minoritized (URM) students with social capital (i.e., resources gained from relationships) that aids their persistence in their engineering undergraduate programs and into the workforce. We hypothesize that women and URM students engineering students who participate in PEOs are more likely to persist in their engineering major and that PEOs contribute to their persistence by providing them access to insider information that supports their persistence. Each year for five years we administered surveys with closed- and open-ended items to examine the association between participating in PEOs and the persistence of a cohort of engineering majors from 11 diverse universities. We used logistic regression and thematic analysis to analyze the data. URM students who participated in PEOs and other engineering related activities were more likely to persist to the second year than URM students who did not (adjusted odds ratio = 2.18, CI: 1.09, 4.37). Students reported that PEOs contributed to their persistence by enabling them to network, reduce gender and race/ethnic isolation, and access professional resources. URM students should be encouraged to participate in PEOs beginning in their first year to increase their integration in their major, which we have found to increase their persistence., Competing Interests: Author EP was employed by the company Beta Research Associates, Author GD was employed by the company The MacDonald Research Institute. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Smith, Wao, Kersaint, Campbell-Montalvo, Gray-Ray, Puccia, Martin, Lee, Skvoretz and MacDonald.)

Meditation is an umbrella term for a number of mental training practices designed to improve the monitoring and regulation of attention and emotion. Some forms of meditation are now being used for clinical intervention. To accompany the increased clinical interest in meditation, research investigating the neural basis of these practices is needed. A central hypothesis of contemplative neuroscience is that meditative states, which are unique on a phenomenological level, differ on a neurophysiological level. To identify the electrophysiological correlates of meditation practice, the electrical brain activity of highly skilled meditators engaging in one of six meditation styles (shamatha, vipassana, zazen, dzogchen, tonglen, and visualization) was recorded. A mind-wandering task served as a control. Lempel-Ziv complexity showed differences in nonlinear brain dynamics (entropy) during meditation compared with mind wandering, suggesting that meditation, regardless of practice, affects neural complexity. In contrast, there were no differences in power spectra at six different frequency bands, likely due to the fact that participants engaged in different meditation practices. Finally, exploratory analyses suggest neurological differences among meditation practices. These findings highlight the importance of studying the electroencephalography (EEG) correlates of different meditative practices., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Young, Arterberry and Martin.)

Background Previous reports suggest that the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may upregulate angiotensin-converting enzyme 2 receptors and increase severe acute respiratory syndrome coronavirus 2 infectivity. We evaluated the association between ACEI or ARB use and coronavirus disease 2019 (COVID-19) infection among patients with hypertension. Methods and Results We identified patients with hypertension as of March 1, 2020 (index date) from Kaiser Permanente Southern California. Patients who received ACEIs, ARBs, calcium channel blockers, beta blockers, thiazide diuretics (TD), or no therapy were identified using outpatient pharmacy data covering the index date. Outcome of interest was a positive reverse transcription polymerase chain reaction test for COVID-19 between March 1 and May 6, 2020. Patient sociodemographic and clinical characteristics were identified within 1 year preindex date. Among 824 650 patients with hypertension, 16 898 (2.0%) were tested for COVID-19. Of those tested, 1794 (10.6%) had a positive result. Overall, exposure to ACEIs or ARBs was not statistically significantly associated with COVID-19 infection after propensity score adjustment (odds ratio [OR], 1.06; 95% CI, 0.90-1.25) for ACEIs versus calcium channel blockers/beta blockers/TD; OR, 1.10; 95% CI, 0.91-1.31 for ARBs versus calcium channel blockers/beta blockers/TD). The associations between ACEI use and COVID-19 infection varied in different age groups ( P -interaction=0.03). ACEI use was associated with lower odds of COVID-19 among those aged ≥85 years (OR, 0.30; 95% CI, 0.12-0.77). Use of no antihypertensive medication was significantly associated with increased odds of COVID-19 infection compared with calcium channel blockers/beta blockers/TD (OR, 1.32; 95% CI, 1.11-1.56). Conclusions Neither ACEI nor ARB use was associated with increased likelihood of COVID-19 infection. Decreased odds of COVID-19 infection among adults ≥85 years using ACEIs warrants further investigation.

Genotypic diversity among multi-drug-resistant (MDR) aquatic E. coli isolated from different sites of Yamuna River was analyzed using repetitive element PCR (rep-PCR) methods viz. ERIC-PCR and (GTG) 5 -PCR and compared with the MDR animal fecal isolates. The 97 E. coli isolates belonging to different serotypes, phylogroups, and multi-drug resistance patterns were analyzed. High genetic diversity was observed by both the methods; however, (GTG) 5 typing showed higher discriminating potential. Combination of ERIC types (E1-E32) and (GTG) 5 types (G1-G46) generated 77 genotypes. The frequency of genotypes ranged from 0.013 to 0.065. The genotype composition of E. coli isolates was highly diverse at all the sampling sites across Yamuna River except at its entry site in Delhi. The sampling sites under the influence of high anthropogenic activities showed an increase in number of unique genotype isolates. These sites also exhibited high multiple antibiotic resistance (MAR) indexes (above 0.25) suggesting high risk of contamination. Principal coordinate analysis (PCoA) showed limited clustering of genotypes based on the sampling sites. The most frequent genotypes were grouped in the positive zone of both the principal coordinates (PC1 and PC2). The genotypes of most of the animal fecal isolates were unique and occupied a common space in the negative PC1 area forming a separate cluster. High genotypic diversity among the aquatic E. coli and the drain isolates, discharging the untreated municipal waste in the river, was observed, suggesting that the sewage effluents contribute substantially to contamination of this river system than animal feces. The presence of such a high diversity among the MDR E. coli isolates in the natural river systems is of great public health significance and highlights the need of an efficient surveillance system for better management of Indian natural water bodies.

Human bipedal gait is exceptionally stable, but the underlying strategies to maintain stability are unclear, especially in the frontal plane. Our study investigated balance strategies of healthy adults subjected to continuous mediolateral oscillations at the trunk during walking. We used a backpack with a passive inverted pendulum to create perturbations that were fixed, in-phase or out-of-phase with subjects' trunk. We evaluated subjects' corrective strategies and whether they yielded equivalent stability, measured by the margin of stability and the local divergence exponent. The margin of stability measure quantified adjustments in step behaviour relative to the centre of mass, and the local divergence exponent measure characterized the chaotic behaviour of the system throughout the entire trial. Among the conditions, there was no significant difference in the step width. We found a higher margin of stability for the out-of-phase condition and the lowest local divergence exponent for the in-phase condition and the highest for the fixed condition. These results indicate that the in-phase condition was more stable with respect to fluctuations throughout gait cycles, and the out-of-phase condition was more stable in terms of foot placement relative to centre of mass. To maintain equivalent or greater gait stability, subjects elected to reduce the motion of their centre of mass rather than alter step width. The reduction in centre of mass motion without a reduction in step width suggests direct control of the centre of mass to maintain stability was preferred over adjusting stepping behaviour., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

Objective: To assess whether implementation of age-dependent therapeutic targets for high hemoglobin A1c (HbA1c) changed clinicians' ordering of diabetes medications for older adults., Background: In 2016, Kaiser Permanente Southern California (KPSC) changed the therapeutic targets for alerting clinicians about high HbA1c results in the electronic health record, KP HealthConnect (KPHC). Previously, all HbA1c results ≥7.0 percent were flagged as high in adult patients with diabetes. Starting in 2016, HbA1c therapeutic targets were relaxed to <7.5 percent for patients age 65 to 75, and to <8.0 percent for patients over age 75 to reduce treatment intensity and adverse events., Methods: This retrospective analysis used logistic regression models to calculate the change in odds of a medication change following an HbA1c result after age-dependent HbA1c flags were introduced., Results: The odds of medication change decreased among patients whose HbA1c targets were relaxed: Odds Ratio (OR) 0.72 (95 percent CI 0.67-0.76) for patients age 65-75 and HbA1c 7.0 percent-7.5 percent; OR 0.72 (95 percent CI 0.65-0.80) for patients over age 75 and HbA1c 7.0 percent-7.5 percent; and OR 0.67 (95 percent CI 0.61-0.75) for patients over age 75 and HbA1c 7.5 percent-8.0 percent. In the age and HbA1c ranges for which the alerts did not change, the odds of medication change generally increased or stayed the same. There was little evidence of medication de-intensification in any group., Conclusions: These findings suggest that the change in therapeutic targets was associated with a reduction in medication intensification among older adults with diabetes., Competing Interests: The authors have no competing interests to declare.

Biomechanical energy harvesters generate electricity, from human movement, to power portable electronics. We developed an energy harvesting module to be used in conjunction with a load carriage device that allows carried mass in a backpack to oscillate in the medial-lateral (M-L) direction. The energy harvesting module was designed to tune M-L oscillations of the carried mass to create favourable device-user interaction. We tested seven energy harvesting conditions and compared them to walking with the device when the weight was rigidly fixed to the backpack frame. For each energy harvesting condition, we changed the external load resistance: altering how much electricity was being generated and how much the carried mass would oscillate. We then correlated device behaviour to the biomechanical response of the user. The energy harvesting load carriage system generated electricity with no significant increase in the metabolic power required to walk, when compared to walking with the carried weight rigidly fixed. The device was able to generate up to 0.22 ± 0.03 W of electricity, while walking with 9 kg of carried weight. The device also reduced the interaction forces experienced by the user, in the M-L direction, compared to walking with the device when the mass was rigidly fixed., Competing Interests: The authors declare no competing interests.

At any given moment, behavior is controlled by a combination of external stimuli and an animal's internal state. As physiological conditions change, vastly different behaviors might result from the same stimuli. For example, the motivation to hunt and hunting strategy are influenced by satiety. Here, we describe how sensory responsiveness and motor activity of a praying mantis ( Tenodera sinensis ) change as the insect feeds, leading to an altered hunting strategy. We further show that these changes can be induced by injection of insulin, which likely functions as a metabotropic indicator. Praying mantises directed their attention toward real and simulated prey less often as they fed and became sated. The range of distance and azimuth at which prey was detected decreased as did pursuit of prey, while opportunistic close-range attacks persisted. Together, these sensorimotor changes are indicative of a behavioral paradigm shift from 'pursuit' to 'ambush'. A similar effect was induced in starved praying mantises injected with 0.05 ml of 200 μg ml -1 bovine insulin. These experiments showed that insulin injection into the circulating hemolymph is sufficient to decrease prey orientation as well as in prey-directed locomotor behaviors (tracking and pursuit). The effects of prey consumption and insulin injection were similarly dose dependent. These results suggest that insulin is a signal of internal, physiological conditions that can modify responses to external stimuli. A change in hunting strategy thus results from coordinated effects of a neurohormone on a set of independent sensorimotor processes and the overall activity level of the animal., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

When walking, the trunk not only oscillates in the vertical direction, but also in the medial-lateral direction. We developed a novel backpack that uses the medial-lateral oscillations of the trunk as input motion to drive medial-lateral oscillations of weight carried in a modified backpack. We use a combination of spring and damping elements to control mass motion, resulting in the ability to prescribe a variety of mass oscillation amplitudes and phase angles. We propose the device as a platform that can be used to study medial-lateral stability during walking. In particular, if the body's ability to predict medial-lateral centre-of-mass state is affected by an oscillating external mass. In this paper, we present the design, model, and model evaluation of our novel load carriage device. During testing, our model was able to predict the oscillation dynamics of the carried mass while walking: demonstrating its capability to create a variety of load carriage scenarios for the user.

Although generally curable with intensive chemotherapy in resource-rich settings, Burkitt lymphoma (BL) remains a deadly disease in older patients and in sub-Saharan Africa. Epstein-Barr virus (EBV) positivity is a feature in more than 90% of cases in malaria-endemic regions, and up to 30% elsewhere. However, the molecular features of BL have not been comprehensively evaluated when taking into account tumor EBV status or geographic origin. Through an integrative analysis of whole-genome and transcriptome data, we show a striking genome-wide increase in aberrant somatic hypermutation in EBV-positive tumors, supporting a link between EBV and activation-induced cytidine deaminase (AICDA) activity. In addition to identifying novel candidate BL genes such as SIN3A , USP7 , and CHD8 , we demonstrate that EBV-positive tumors had significantly fewer driver mutations, especially among genes with roles in apoptosis. We also found immunoglobulin variable region genes that were disproportionally used to encode clonal B-cell receptors (BCRs) in the tumors. These include IGHV4-34, known to produce autoreactive antibodies, and IGKV3-20, a feature described in other B-cell malignancies but not yet in BL. Our results suggest that tumor EBV status defines a specific BL phenotype irrespective of geographic origin, with particular molecular properties and distinct pathogenic mechanisms. The novel mutation patterns identified here imply rational use of DNA-damaging chemotherapy in some patients with BL and targeted agents such as the CDK4/6 inhibitor palbociclib in others, whereas the importance of BCR signaling in BL strengthens the potential benefit of inhibitors for PI3K, Syk, and Src family kinases among these patients., (© 2019 by The American Society of Hematology.)

Background: Tumor mutational burden (TMB) is an increasingly important biomarker for immune checkpoint inhibitors. Recent publications have described strong association between high TMB and objective response to mono- and combination immunotherapies in several cancer types. Existing methods to estimate TMB require large amount of input DNA, which may not always be available., Methods: In this study, we develop a method to estimate TMB using the Oncomine Tumor Mutation Load (TML) Assay with 20 ng of DNA, and we characterize the performance of this method on various formalin-fixed, paraffin-embedded (FFPE) research samples of several cancer types. We measure the analytical performance of TML workflow through comparison with control samples with known truth, and we compare performance with an orthogonal method which uses matched normal sample to remove germline variants. We perform whole exome sequencing (WES) on a batch of FFPE samples and compare the WES TMB values with TMB estimates by the TML assay., Results: In-silico analyses demonstrated the Oncomine TML panel has sufficient genomic coverage to estimate somatic mutations with a strong correlation (r 2 =0.986) to WES. Further, in silico prediction using WES data from three separate cohorts and comparing with a subset of the WES overlapping with the TML panel, confirmed the ability to stratify responders and non-responders to immune checkpoint inhibitors with high statistical significance. We found the rate of somatic mutations with the TML assay on cell lines and control samples were similar to the known truth. We verified the performance of germline filtering using only a tumor sample in comparison to a matched tumor-normal experimental design to remove germline variants. We compared TMB estimates by the TML assay with that from WES on a batch of FFPE research samples and found high correlation (r 2 =0.83). We found biologically interesting tumorigenesis signatures on FFPE research samples of colorectal cancer (CRC), lung, and melanoma origin. Further, we assessed TMB on a cohort of FFPE research samples including lung, colon, and melanoma tumors to discover the biologically relevant range of TMB values., Conclusions: These results show that the TML assay targeting a 1.7-Mb genomic footprint can accurately predict TMB values that are comparable to the WES. The TML assay workflow incorporates a simple workflow using the Ion GeneStudio S5 System. Further, the AmpliSeq chemistry allows the use of low input DNA to estimate mutational burden from FFPE samples. This TMB assay enables scalable, robust research into immuno-oncology biomarkers with scarce samples., Competing Interests: Conflicts of Interest: Employees of Thermo Fisher Scientific: R Chaudhary, D Cyanam, V Mittal, W Tom, J Au-Young, S Sadis, F Hyland. The other authors have no conflicts of interest to declare.

Altering mechanical compliance in load carriage structures has shown to reduce metabolic cost and accelerative forces of carrying weight. Currently, modifications to load carriage structures have been primarily targeted at vertical motion of the carried mass. No study to date has investigated altering load carriage compliance in the medial-lateral direction. We developed a backpack specifically for allowing a carried mass to oscillate in the horizontal direction, giving us the unique opportunity to understand the effects of lateral mass motion on human gait. Previous modelling work has shown that walking economy can be improved through the interaction of a bipedal model with a laterally oscillating walking surface. To test whether a laterally oscillating mass can experimentally improve walking economy, we systematically varied step width above and below the preferred level and compared the effects of carrying an oscillating and fixed mass. Walking with an oscillating mass was found to reduce the accelerative forces of load carriage in both horizontal and vertical directions. However, load eccentricity caused the vertical force component to create a significant bending moment in the frontal plane. Walking with an oscillating mass led to an increase in the metabolic energy expenditure during walking and an increase in positive hip work during stance. The device's ability to reduce forces experienced by the user, due to load carriage, holds promise. However, the requirement of additional metabolic energy to walk with the device requires future study to improve.

Background: Vertical jump performance has been evaluated with several devices: force platforms, contact mats, Vertec, accelerometers, infrared cameras and high-velocity cameras; however, the force platform is considered the gold standard for measuring vertical jump height. The purpose of this study was to validate an iPhone app called My Jump, that measures vertical jump height by comparing it with other methods that use the force platform to estimate vertical jump height, namely, vertical velocity at take-off and time in the air., Methods: A total of 40 sport sciences students (age 21.4±1.9 years) completed five countermovement jumps (CMJs) over a force platform. Thus, 200 CMJ heights were evaluated from the vertical velocity at take-off and the time in the air using the force platform, and from the time in the air with the My Jump mobile application. The height obtained was compared using the intraclass correlation coefficient (ICC)., Results: Correlation between APP and force platform using the time in the air was perfect (ICC=1.000, P<0.001). Correlation between APP and force platform using the vertical velocity at take-off was also very high (ICC=0.996, P<0.001), with an error margin of 0.78%., Conclusions: Therefore, these results showed that application, My Jump, is an appropriate method to evaluate the vertical jump performance; however, vertical jump height is slightly overestimated compared with that of the force platform.

Background: Robust quantitative analysis in positron emission tomography (PET) and in single-photon emission computed tomography (SPECT) typically requires the time-activity curve as an input function for the pharmacokinetic modeling of tracer uptake. For this purpose, a new automated tool for the determination of blood activity as a function of time is presented. The device, compact enough to be used on the patient bed, relies on a peristaltic pump for continuous blood withdrawal at user-defined rates. Gamma detection is based on a 20 × 20 × 15 mm 3 cadmium zinc telluride (CZT) detector, read by custom-made electronics and a field-programmable gate array-based signal processing unit. A graphical user interface (GUI) allows users to select parameters and easily perform acquisitions., Results: This paper presents the overall design of the device as well as the results related to the detector performance in terms of stability, sensitivity and energy resolution. Results from a patient study are also reported. The device achieved a sensitivity of 7.1 cps/(kBq/mL) and a minimum detectable activity of 2.5 kBq/ml for 18 F. The gamma counter also demonstrated an excellent stability with a deviation in count rates inferior to 0.05% over 6 h. An energy resolution of 8% was achieved at 662 keV., Conclusions: The patient study was conclusive and demonstrated that the compact gamma blood counter developed has the sensitivity and the stability required to conduct quantitative molecular imaging studies in PET and SPECT.

Insects use highly distributed nervous systems to process exteroception from head sensors, compare that information with state-based goals, and direct posture or locomotion toward those goals. To study how descending commands from brain centers produce coordinated, goal-directed motion in distributed nervous systems, we have constructed a conductance-based neural system for our robot MantisBot, a 29 degree-of-freedom, 13.3:1 scale praying mantis robot. Using the literature on mantis prey tracking and insect locomotion, we designed a hierarchical, distributed neural controller that establishes the goal, coordinates different joints, and executes prey-tracking motion. In our controller, brain networks perceive the location of prey and predict its future location, store this location in memory, and formulate descending commands for ballistic saccades like those seen in the animal. The descending commands are simple, indicating only 1) whether the robot should walk or stand still, and 2) the intended direction of motion. Each joint's controller uses the descending commands differently to alter sensory-motor interactions, changing the sensory pathways that coordinate the joints' central pattern generators into one cohesive motion. Experiments with one leg of MantisBot show that visual input produces simple descending commands that alter walking kinematics, change the walking direction in a predictable manner, enact reflex reversals when necessary, and can control both static posture and locomotion with the same network., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The luminol test has been used for over 60 years by forensic investigators for presumptive identification of blood and visualization of blood splatter patterns. Multiple studies have estimated the limit of detection (LD) for bloodstains when luminol is employed, with results ranging from 100× to 5,000,000× dilute. However, these studies typically have not identified and controlled important experimental variables which may affect the luminol LD for bloodstains. Without control of experimental parameters in the laboratory, variables which affect the potential of presumptive bloodstain test methods remain largely unknown, and comparisons required to establish new, more powerful detection methods are simply impossible. We have developed a quantitative method to determine the relationship between the amount of blood present and its reaction with luminol by measuring, under controlled conditions, the resulting chemiluminescent intensity with a video camera, combined with processing of the digital intensity data. The method resulted in an estimated LD for bloodstains on cotton fabric at ∼200,000× diluted blood with a specific luminol formulation. Although luminol is the focus of this study, the experimental protocol used could be modified to study effects of variables using other blood detection reagents., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose of Review: The purpose of this review was to provide an overview of the Kaiser Permanente Southern California (KPSC) Complete Care management strategy., Recent Findings: The KPSC Complete Care program allows members of care management teams to coordinate the administration of care for patients with diabetes. This program encompasses teams of physicians, physician assistants, pharmacists, nurse practitioners, registered nurse (RN) care managers, office-based RNs, health educators, and many others to contribute to the glycemic and overall health outcomes for our patients with diabetes. The 2016 Kaiser Permanente National Clinical Practice Guideline for Adult Diabetes Clinician Guide and the supplemental KPSC Treat-to-Target (TTT) Type 2 Diabetes A1c Control algorithm are used to assist KPSC clinicians by providing guidance for shared decision-making, as well as the selection and sequence of appropriate pharmacological treatment. Collaboration with pharmacy through the Formulary and the Drug Utilization Action Team (DUAT) allows the organization to manage member resources while consistently offering patients the highest quality and value health care possible. Recent technology integrations have also contributed to the success of the program.

A dynamic systems model of organic waste management for the province of Quebec, Canada, was built. Six distinct modules taking into account social, economical and environmental issues and perspectives were included. Five scenarios were designed and tested to identify the potential consequences of different governmental and demographic combinations of decisions over time. Among these scenarios, one examines Quebec's organic waste management policy (2011-2015), while the other scenarios represent business as usual or emphasize ecology, economy or social benefits in the decision-making process. Model outputs suggest that the current governmental policy should yield favorable environmental benefits, energy production and waste valorization. The projections stemming from the current policy action plan approach the benefits gained by another scenario emphasizing the environmental aspects in the decision-making process. As expected, without the current policy and action plan in place, or business as usual, little improvements are expected in waste management compared to current trends, and strictly emphasizing economic imperatives does not favor sustainable organic waste management., (Copyright © 2017. Published by Elsevier Ltd.)

Skin disease occur worldwide, affecting people of all nationalities and all skin types. These diseases may have a genetic component and may manifest differently in specific population groups; however, there has been little study on this aspect. If population-based differences exist, it is reasonable to assume that understanding these differences may optimize treatment. While there is a relative paucity of information about similarities and differences in skin diseases around the world, the knowledge-base is expanding. One challenge in understanding population-based variations is posed by terminology used in the literature: including ethnic skin, Hispanic skin, Asian skin, and skin of color. As will be discussed in this article, we recommend that the first three descriptors are no longer used in dermatology because they refer to nonspecific groups of people. In contrast, "skin of color" may be used - perhaps with further refinements in the future - as a term that relates to skin biology and provides relevant information to dermatologists.

A biomechanical energy harvester is a wearable device that generates electricity from human motion. Walking on a treadmill has been used almost exclusively by researchers for studying the energetic effects of biomechanical energy harvesters and wearable robotics. A treadmill provides the advantage of having long duration trials within a stationary motion capture volume. However, no consensus exists on whether the results from treadmill walking accurately represent overground walking. We aim to investigate how a biomechanical energy harvester performs overground compared to on a treadmill by measuring energy expenditure and muscle activity. Participants (n=15) walked both overground and on a treadmill with and without a lower limb-driven biomechanical energy harvester. Energy expenditure was measured using indirect calorimetry and muscle activity was collected with surface electromyograms on seven superficial lower limb muscles. We observed a similar increase in metabolic cost of transport (Δ overground : 0.28±0.24J/kgm, Δ treadmill : 0.30±0.24J/kgm) from normal walking (overground: 2.56±0.33J/kgm, treadmill: 3.39±0.31J/kgm) to harvester walking (overground: 2.83±0.35J/kgm, treadmill: 3.69±0.32J/kgm) in both walking modes (p>0.05). This was accompanied a significant increase in muscle activity of select muscle groups (p<0.05). There was also a significant increase observed during walking on a treadmill compared to overground walking (p<0.05). In conclusion, our results suggest that although the metabolic cost of transport and muscle activation for treadmill walking is higher than that of overground, when studying the effects of a biomechanical energy harvester, treadmill will give similar net increases when compared to a controlled walking condition, such as normal walking, on the same walking surface., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Cockroaches are scavengers that forage through dark, maze-like environments. Like other foraging animals, for instance rats, they must continually asses their situation to keep track of targets and negotiate barriers. While navigating a complex environment, all animals need to integrate sensory information in order to produce appropriate motor commands. The integrated sensory cues can be used to provide the animal with an environmental and contextual reference frame for the behavior. To successfully reach a goal location, navigational cues continuously derived from sensory inputs have to be utilized in the spatial guidance of motor commands. The sensory processes, contextual and spatial mechanisms, and motor outputs contributing to navigation have been heavily studied in rats. In contrast, many insect studies focused on the sensory and/or motor components of navigation, and our knowledge of the abstract representation of environmental context and spatial information in the insect brain is relatively limited. Recent reports from several laboratories have explored the role of the central complex (CX), a sensorimotor region of the insect brain, in navigational processes by recording the activity of CX neurons in freely-moving insects and in more constrained, experimenter-controlled situations. The results of these studies indicate that the CX participates in processing the temporal and spatial components of sensory cues, and utilizes these cues in creating an internal representation of orientation and context, while also directing motor control. Although these studies led to a better understanding of the CX's role in insect navigation, there are still major voids in the literature regarding the underlying mechanisms and brain regions involved in spatial navigation. The main goal of this review is to place the above listed findings in the wider context of animal navigation by providing an overview of the neural mechanisms of navigation in rats and summarizing and comparing our current knowledge on the CX's role in insect navigation to these processes. By doing so, we aimed to highlight some of the missing puzzle pieces in insect navigation and provide a different perspective for future directions.

Phytoseiid mites are commonly used as biological control agents of mite and small insect pests. To facilitate the production of phytoseiids, alternative food sources have been evaluated. The aim of this study was to evaluate the suitability of different food sources for the rearing of the phytoseiids Amblyseius tamatavensis Blommers, Euseius concordis (Chant) and Neoseiulus anonymus (Chant and Baker). This study evaluated the levels of oviposition of these predators when fed with 15 Astigmatina (Sarcoptiformes) mite species, one species of a bacteriophagous nematode, and pollen from five plant species. The highest oviposition rates of A. tamatavensis were obtained when fed on the mites Thyreophagus cracentiseta Barbosa, OConnor & Moraes and Aleuroglyphus ovatus (Troupeau) (2.6 and 2.1 eggs/female/day, respectively). The five highest oviposition levels of E. concordis occurred when the food source was pollen, especially of Ricinus communis L. (1.7 eggs/female/day). The evaluated oviposition levels of N. anonymus were at most 0.5 eggs/female/day on all food sources. The construction of life tables of A. tamatavensis and E. concordis with the two most favorable food sources showed that in both cases the values of r m were higher when the predator was fed with T. cracentiseta and R. communis, respectively. The possible use of pollen of Elaeis guineensis L. should be further evaluated, given the acceptance of this type of pollen by E. concordis and the ease of obtaining large amounts of this pollen in areas where this crop is grown.

Aims: To investigate the discontinuation of oral antihyperglycemic agents (OHA), and examine factors associated with OHA discontinuation, and the effect of OHA discontinuation on glycemic control and healthcare utilization among diabetes patients prescribed dual OHA therapy., Methods: We identified 23,612 adult patients aged >18years with a diagnosis of type 2 diabetes who initiated dual OHA therapy between 1/1/2005 and 6/30/2010. The date of initiation of the second OHA was defined as the index date. Discontinuation was defined as a gap >1.5 times the last days' supply without subsequent reinitiation., Results: Over 24months, 16.9% discontinued 1 OHA and 9.2% discontinued both. Patients who discontinued were more likely to be female, younger, Black or of Hispanic ethnicity, have more comorbidities, higher medication co-pays, start both OHAs together, have higher healthcare utilization before the index date and less likely to use prescription mail order compared with patients who did not discontinue. In multivariable regression models, patients who discontinued were more likely to be hospitalized or have emergency department visits during follow-up., Conclusions: Discontinuation of OHAs is common among patients with diabetes and is associated with several patient factors and increased healthcare utilization. Future research should further examine reasons for OHA discontinuation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Electrocardiographic changes can be present in marathon runners. These findings may be misinterpreted as malignant by healthcare providers. For example, incomplete right bundle branch block, early ventricular repolarization, and left ventricular hypertrophy by voltage criteria alone are quite common in athletes, yet considered benign.

Within this work, the family of cyanophenylalanine spectroscopic reporters is extended by showing the ortho and meta derivatives have intrinsic photophysical properties that are useful for studies of protein structure and dynamics. The molar absorptivities of 2-cyanophenylalanine and 3-cyanophenylalanine are shown to be comparable to that of 4-cyanophenylalanine with similar spectral features in their absorbance and emission profiles, demonstrating that these probes can be utilized interchangeably. The fluorescence quantum yields are also on the same scale as commonly used fluorophores in peptides and proteins, tyrosine and tryptophan. These new cyano-fluorophores can be paired with either 4-cyanophenylalanine or tryptophan to capture distances in peptide structure through Förster resonance energy transfer. Additionally, the spectroscopic properties of these chromophores can report the local solvent environment via changes in fluorescence emission intensity as a result of hydrogen bonding and/or hydration. A decrease in the quantum yield is also observed in basic environments due to photoinduced electron transfer from a deprotonated amine in the free PheCN species and at the N-terminus of a short peptide, providing an avenue to detect pH in biological systems. Our results show the potential of these probes, 2-cyanophenylalanine and 3-cyanophenylalanine, to be incorporated into a single peptide chain, either individually or in tandem with 4-cyanophenylalanine, tryptophan, or tyrosine, in order to obtain information about peptide structure and dynamics.

Biomedical applications of terahertz (THz) radiation are appealing because THz radiation is nonionizing and has the demonstrated ability to detect intrinsic contrasts between cancerous and normal tissue. A linear polarization-sensitive detection technique for tumor margin delineation has already been demonstrated; however, utilization of a circular polarization-sensitive detection technique has yet to be explored at THz frequencies. A reflective, continuous-wave THz imaging system capable of illuminating a target sample at 584 GHz with either linearly or circularly polarized radiation, and capable of collecting both cross- and copolarized signals remitted from the target, is implemented. To demonstrate the system’s utility, a fresh ex vivo human skin tissue specimen containing nonmelanoma skin cancer was imaged. Both polarization-sensitive detection techniques showed contrast between tumor and normal skin tissue, although some differences in images were observed between the two techniques. Our results indicate that further investigation is required to explain the contrast mechanism, as well as to quantify the specificity and sensitivity of the circular polarization-sensitive detection technique.

Background: Prior radiation therapy, pelvic dead space, and a dependent location contribute to perineal dehiscence rates as high as 66 percent after primary closure of pelvic wounds. Various regional flaps have been described to reconstruct pelvic defects, but an algorithmic pairing of individual flaps to specific anatomical regions has not been described., Methods: A retrospective review of a prospectively maintained database was performed to identify consecutive pelvic reconstructions from 2010 to 2013 with at least 6 months' follow-up. Pelvic defects and resulting flaps were described by anatomical subunits involved: anterolateral thigh flap for mons, gracilis flap for labia majora and introitus, vertical rectus abdominis myocutaneous flap for vagina and/or perineal raphe, and gluteus musculocutaneous flap for isolated perianal defects., Results: Twenty-seven women and three men underwent consecutive pelvic reconstruction with a mean age of 60 years (range, 26 to 83 years) and a mean body mass index of 28 kg/m(2) (range, 17 to 40 kg/m(2)). Twenty-one patients (70 percent) had prior radiation therapy. In total, 45 flaps were performed according to the subunit principle. Three patients had a minor dehiscence (<5 cm), one patient had a major dehiscence, and one required reoperation for abscess. There were two partial flap losses necessitating débridement and readvancement of the flap. Twenty-five percent of female patients were sexually active after vaginal reconstruction., Conclusions: The pelvic subunit principle provides an effective algorithm for choosing the ideal pedicled flap for each region involved in acquired pelvic defects. This algorithm is based on individual attributes that make each flap most appropriate for each subunit. Complications were minimal and patient satisfaction with appearance and function was excellent.

Background: Intraoperative tranexamic acid (TXA) administration has been used to abate blood loss in a variety of surgical procedures. Several recent studies have supported its efficacy in reducing transfusion requirements in pediatric cranial vault reconstruction (CVR)., Objective: To conduct a retrospective chart review to determine whether a significant reduction in packed red blood cell (PRBC) and fresh frozen plasma (FFP) transfusions exists when TXA is used., Methods: A retrospective cohort study of 28 patients who underwent CVR for sagittal craniosynostosis was performed. Transfusion requirements for 14 patients who did not receive TXA were compared with 14 patients who did. Predictors of increased blood product transfusion were also studied., Results: Total volume of PRBC transfusion was reduced by 50% with the use of TXA (P=0.004) with a 34% reduction in intraoperative PRBC transfusion (P=0.017) and a 67% reduction in postoperative PRBC transfusion (P<0.001). Total volume of FFP transfusion was reduced by 46% (P=0.002) and postoperative FFP transfusion was reduced by 100% (P=0.001). The use of TXA was associated with a lower total volume of PRBC (P=0.003) and FFP (P=0.003) transfusions. Older patient age was associated with lower total volume of PRBC transfused (P=0.046 and P=0.002), but not with FFP (P=0.183 and P=0.099) transfusion volumes. Increasing patient weight was associated with lower PRBC (P=0.010 and P=0.020) and FFP (P=0.045 and P=0.016) transfusion volumes., Conclusion: TXA decreased blood product transfusion requirements in patients undergoing CVR for sagittal craniosynostosis, and should be a routine part of the strategy to reduce blood loss in these procedures.

Praying mantises hunt by standing on their meso- and metathoracic legs and using them to rotate and translate (together, 'pivot') their bodies toward prey. We have developed a neuromechanical software model of the praying mantis Tenodera sinensis to use as a platform for testing postural controllers that the animal may use while hunting. Previous results showed that a feedforward model was insufficient for capturing the diversity of posture observed in the animal (Szczecinski et al 2014 Biomimetic and Biohybrid Syst. 3 296-307). Therefore we have expanded upon this model to make a flexible controller with feedback that more closely mimics the animal. The controller actuates 24 joints in the legs of a dynamical model to orient the head and translate the thorax toward prey. It is controlled by a simulation of nonspiking neurons assembled as a highly simplified version of networks that may exist in the mantid central complex and thoracic ganglia. Because of the distributed nature of these networks, we hypothesize that descending commands that orient the mantis toward prey may be simple direction-of-intent signals, which are turned into motor commands by the structure of low-level networks in the thoracic ganglia. We verify this through a series of experiments with the model. It captures the speed and range of mantid pivots as reported in other work (Yamawaki et al 2011 J. Insect Physiol. 57 1010-6). It is capable of pivoting toward prey from a variety of initial postures, as seen in the animal. Finally, we compare the model's joint kinematics during pivots to preliminary 3D kinematics collected from Tenodera.

To navigate in the world, an animal's brain must produce commands to move, change direction, and negotiate obstacles. In the insect brain, the central complex integrates multiple forms of sensory information and guides locomotion during behaviors such as foraging, climbing over barriers, and navigating to memorized locations. These roles suggest that the central complex influences motor commands, directing the appropriate movement within the current context. Such commands are ultimately carried out by the limbs and must therefore interact with pattern generators and reflex circuits that coordinate them. Recent studies have described how neurons of the central complex encode sensory information: neurons subdivide the space around the animal, encoding the direction or orientation of stimuli used in navigation. Does a similar central-complex code directing movement exist, and if so, how does it effect changes in the control of limbs? Recording from central-complex neurons in freely walking cockroaches (Blaberus discoidalis), we identified classes of movement-predictive cells selective for slow or fast forward walking, left or right turns, or combinations of forward and turning speeds. Stimulation through recording wires produced consistent trajectories of forward walking or turning in these animals, and those that elicited turns also altered an inter-joint reflex to a pattern resembling spontaneous turning. When an animal transitioned to climbing over an obstacle, the encoding of movement in this new context changed for a subset of cells. These results indicate that encoding of movement in the central complex participates in motor control by a distributed, flexible code targeting limb reflex circuits., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Smart applications of the Internet of Things are improving the performance of buildings, reducing energy demand. Local and smart networks, soft computing methodologies, machine intelligence algorithms and pervasive sensors are some of the basics of energy optimization strategies developed for the benefit of environmental sustainability and user comfort. This work presents a distributed sensor-processor-communication decision-making architecture to improve the acquisition, storage and transfer of thermal energy in buildings. The developed system is implemented in a near Zero-Energy Building (nZEB) prototype equipped with a built-in thermal solar collector, where optical properties are analysed; a low enthalpy geothermal accumulation system, segmented in different temperature zones; and an envelope that includes a dynamic thermal barrier. An intelligent control of this dynamic thermal barrier is applied to reduce the thermal energy demand (heating and cooling) caused by daily and seasonal weather variations. Simulations and experimental results are presented to highlight the nZEB thermal energy reduction.