The evoked compound nerve action potential is shaped by the electrical pulse-width

Introduction: Despite its central role in medicine electrical stimulation (ES) is still limited by its selectivity. Different reports did assess effects of different waveforms, intensities, and frequency on the activation threshold of nerve fibres with different diameters. We aimed to extend this knowledge by investigating the effect of short monophasic rectangular pulses (1, 2, 5, 10, 50, 100 and 200 μs) on the recruitment order. Methods:The sciatic nerve of rats was stimulated, and the evoked compound nerve action potential (CNAP) measured at two sites on the tibialis nerve, using epineural electrodes. Changes in delay, amplitude, and the shape of the CNAP were analyzed. Results:The amplitude and delay of the CNAP were significantly affected by the pulse-width (PW). The delay and duration of the compound nerve action potential increased with longer PW, while the amplitude decreased. Discussion:Found changes are likely caused by changes in the time point of excitation of individual neuron fibres, depending on electrical field strength and exposure time. This might be of particular interest when selecting PWs for design and validation of stimulation patterns and analysis of experimental and clinical observations

Changes in Skin Test Aeroallergen Sensitization in Mexico Over the Past 14 Years and According to Climate

Désirée Larenas-Linnemann,1 Blanca María Morfín-Maciel,2 Victor Gonzalez-Uribe,3 Claudia Ivonne Gallego-Corella,4 Germán Agustín Rico-Solís,5 Luiana Hernández-Velázquez,6 Daniel García-Imperial,7 Chrystopherson Gengyny Caballero-Lopez,8 Ondina Marlene Garibay-Vargas,9 José Luis Gálvez-Romero,10 Daniela García Fajardo,11 Joel Barroso-Santos,12 Herberth de Jesús Pérez-Áviles,13 Jorge Agustín Luna-Pech,14 Cecilia Yvonne García-Cobas,15 Kareli Guadalupe Coronado-Hernández,16 Margarita Ortega-Cisneros,17 Carlos Humberto González-Gutiérrez,18 Daniela Rivero-Yeverino,8 Elsy Maureen Navarrete-Rodríguez,19 Leticia Lezama-Vázquez,20 Karen Lilian Rivera-Alvarado,21 Georgina Guadalupe Ochoa-López,22 Sara Elizabeth Covarrubias-Ramírez,23 Claudia Patricia Reyes-Galindo,24 Beatriz Bayardo-Gutiérrez,25 María del Carmen Calderón-Ezquerro26 1Centro de Excelencia en Asma y Alergia Larenas, Hospital Médica Sur, Mexico City, DF, Mexico; 2Private practice, Mexico City, DF, Mexico; 3AlergiaMx, Mexico City, DF, Mexico; 4Centro de Alergia y Asma de Tijuana, Tijuana, BCN, Mexico; 5Hospital Regional Valentín Gómez Farías, Department of Allergy and Clinical Immunology, Colima, COL, Mexico; 6IMSS Hospital General de Zona Número 8, Ensenada, BCN, Mexico; 7Private Practice, Querétaro, QRO, Mexico; 8Hospital Universitario de Puebla, Benemérita Universidad Autónoma de Puebla, Puebla, PUE, Mexico; 9Private practice, Uruapan, MICH, Mexico; 10Jefatura de investigación, Hospital Regional ISSSTE, Puebla, PUE, Mexico; 11Private Practice, San Luis Potosí, SLP, Mexico; 12Private practice, Pachuca, HGO, Mexico; 13Private Practice, Mérida, YUC, Mexico; 14Departamento de Disciplinas Filosófico, Metodológico e Instrumentales, CUCS, Universidad de Guadalajara, JAL, Mexico; 15Alergia e Inmunología, HGR 46, Instituto Mexicano del Seguro Social, Guadalajara, JAL, Mexico; 16Centro Médico Nacional del Occidente Pediatrics, Guadalajara, JAL, Mexico; 17Centro Médico Nacional de Occidente UMAE Hospital de Especialidades, Department of clinical immunology and allergy, Guadalajara, JAL, Mexico; 18HGZ &num; 1 IMSS, Zacatecas, ZAC, Mexico; 19Hospital Infantil de México ‘Federico Gómez’, Mexico City, DF, Mexico; 20Private practice, Tuxtla-Gutiérrez, CHIS, Mexico; 21IMSS UMAE 14, Veracruz, VER, Mexico; 22Private practice, Ciudad Juárez, CHIH, Mexico; 23Plebitos, Especialidades Pediátricas, Mazatlán, SIN, Mexico; 24ISSSTE, Ciudad Victoria, TAMPS, Mexico; 25Centro Médico Nacional de Occidente UMAE Hospital de Especialidades, Departamento de Inmunología Clínica y Alergia, Hospital Regional ISSSTE, Puebla, PUE, Mexico; 26Instituto de Ciencias de la Atmósfera y Cambio Climático, Universidad Autónoma de México, Mexico City, DF, MexicoCorrespondence: Désirée Larenas-Linnemann, Centro de Excelencia en Asma y Alergia Larenas, Hospital Médica Sur, Torre 2 cons. 602, Puente de Piedra 150, Col. Toriello Guerra, Del. Tlalpan, Ciudad de México, 14050, Mexico, Tel +52-55-5171-2248 ; +5606-6222 Ext.4372 ; +52-55-8509-5950, Email [email protected]: Aeroallergen exposure has an intra- and extra-domiciliary component and varies according to climatological zones. Mexico is a large country with a great variety of climates. A previous study (2009) evaluated skin prick test results (SPT) in different regions. In this study, we compare previous sensitization patterns from 14y ago with current ones and compare them between different climatological zones.Methods: Mexican allergists were asked to share their last 100 SPT results in patients with respiratory allergy. Clinics were grouped in (semi)humid vs (semi)dry zones. Results were analyzed nationwide and compared to the 2009 results, calculating odds ratio (OR) and 95% confidence intervals (95% CIs), with p < 0.05 as cut-off. Similarly, we compared (semi)humid versus dry zones.Results: We collected 2915 SPT results from 28 clinics (19 cities). Dermatophagoides was the most frequently sensitizing allergen. There was a significant increase in SPT positivity from 2009 to 2023 in both in- and outdoor aeroallergens (OR 1.26– 2.65, 95% CI from 1.06– 1.50 to 1.99– 3.52). Comparing dry-humid zones, sensitization to pollen from Oleaceae, Fagaceae (p < 0.0001 all) and most weeds is more frequent in humid zones, as are Dermatophagoides and cockroach (both p < 0.0001). Eucalyptus, mesquite, and all grass pollen sensitizations predominate in dry zones (p < 0.05– 0.0001). There are no differences in sensitization to cat or dog between zones.Conclusion: We found a general increase in SPT sensitization over the past fourteen years, suggesting that this is probably not only due to climate change. The different sensitization profile throughout the country was mainly related to humidity. Repeating epidemiologic SPT studies over the years could help tracking changes in allergen sensitization over time.Keywords: allergy, diagnosis, skin prick testing, aeroallergen, climate change, pollen allergy, allergic rhinitis, allergic asthm

Bats in the anthropogenic matrix: Challenges and opportunities for the conservation of chiroptera and their ecosystem services in agricultural landscapes

Intensification in land-use and farming practices has had largely negative effects on bats, leading to population declines and concomitant losses of ecosystem services. Current trends in land-use change suggest that agricultural areas will further expand, while production systems may either experience further intensification (particularly in developing nations) or become more environmentally friendly (especially in Europe). In this chapter, we review the existing literature on how agricultural management affects the bat assemblages and the behavior of individual bat species, as well as the literature on provision of ecosystem services by bats (pest insect suppression and pollination) in agricultural systems. Bats show highly variable responses to habitat conversion, with no significant change in species richness or measures of activity or abundance. In contrast, intensification within agricultural systems (i.e., increased agrochemical inputs, reduction of natural structuring elements such as hedges, woods, and marshes) had more consistently negative effects on abundance and species richness. Agroforestry systems appear to mitigate negative consequences of habitat conversion and intensification, often having higher abundances and activity levels than natural areas. Across biomes, bats play key roles in limiting populations of arthropods by consuming various agricultural pests. In tropical areas, bats are key pollinators of several commercial fruit species. However, these substantial benefits may go unrecognized by farmers, who sometimes associate bats with ecosystem disservices such as crop raiding. Given the importance of bats for global food production, future agricultural management should focus on “wildlife-friendly” farming practices that allow more bats to exploit and persist in the anthropogenic matrix so as to enhance provision of ecosystem services. Pressing research topics include (1) a better understanding of how local-level versus landscape-level management practices interact to structure bat assemblages, (2) the effects of new pesticide classes and GM crops on bat populations, and (3) how increased documentation and valuation of the ecosystem services provided by bats could improve attitudes of producers toward their conservation

Worldwide comparison of survival from childhood leukaemia for 1995–2009, by subtype, age, and sex (CONCORD-2): a population-based study of individual data for 89 828 children from 198 registries in 53 countries

Background Global inequalities in access to health care are reflected in differences in cancer survival. The CONCORD programme was designed to assess worldwide differences and trends in population-based cancer survival. In this population-based study, we aimed to estimate survival inequalities globally for several subtypes of childhood leukaemia. Methods Cancer registries participating in CONCORD were asked to submit tumour registrations for all children aged 0-14 years who were diagnosed with leukaemia between Jan 1, 1995, and Dec 31, 2009, and followed up until Dec 31, 2009. Haematological malignancies were defined by morphology codes in the International Classification of Diseases for Oncology, third revision. We excluded data from registries from which the data were judged to be less reliable, or included only lymphomas, and data from countries in which data for fewer than ten children were available for analysis. We also excluded records because of a missing date of birth, diagnosis, or last known vital status. We estimated 5-year net survival (ie, the probability of surviving at least 5 years after diagnosis, after controlling for deaths from other causes [background mortality]) for children by calendar period of diagnosis (1995-99, 2000-04, and 2005-09), sex, and age at diagnosis (< 1, 1-4, 5-9, and 10-14 years, inclusive) using appropriate life tables. We estimated age-standardised net survival for international comparison of survival trends for precursor-cell acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Findings We analysed data from 89 828 children from 198 registries in 53 countries. During 1995-99, 5-year agestandardised net survival for all lymphoid leukaemias combined ranged from 10.6% (95% CI 3.1-18.2) in the Chinese registries to 86.8% (81.6-92.0) in Austria. International differences in 5-year survival for childhood leukaemia were still large as recently as 2005-09, when age-standardised survival for lymphoid leukaemias ranged from 52.4% (95% CI 42.8-61.9) in Cali, Colombia, to 91.6% (89.5-93.6) in the German registries, and for AML ranged from 33.3% (18.9-47.7) in Bulgaria to 78.2% (72.0-84.3) in German registries. Survival from precursor-cell ALL was very close to that of all lymphoid leukaemias combined, with similar variation. In most countries, survival from AML improved more than survival from ALL between 2000-04 and 2005-09. Survival for each type of leukaemia varied markedly with age: survival was highest for children aged 1-4 and 5-9 years, and lowest for infants (younger than 1 year). There was no systematic difference in survival between boys and girls. Interpretation Global inequalities in survival from childhood leukaemia have narrowed with time but remain very wide for both ALL and AML. These results provide useful information for health policy makers on the effectiveness of health-care systems and for cancer policy makers to reduce inequalities in childhood survival

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Search for strongly interacting massive particles generating trackless jets in proton-proton collisions at s = 13 TeV

A search for dark matter in the form of strongly interacting massive particles (SIMPs) using the CMS detector at the LHC is presented. The SIMPs would be produced in pairs that manifest themselves as pairs of jets without tracks. The energy fraction of jets carried by charged particles is used as a key discriminator to suppress efficiently the large multijet background, and the remaining background is estimated directly from data. The search is performed using proton-proton collision data corresponding to an integrated luminosity of 16.1 fb - 1 , collected with the CMS detector in 2016. No significant excess of events is observed above the expected background. For the simplified dark matter model under consideration, SIMPs with masses up to 100 GeV are excluded and further sensitivity is explored towards higher masses

Search for Higgs boson pair production in the gamma gamma b(b)over-bar final state in pp collisions at root s=13 TeV

A search is presented for the production of a pair of Higgs bosons, where one decays into two photons and the other one into a bottom quark-antiquark pair. The analysis is performed using proton-proton collision data at root s = 13 TeV recorded in 2016 by the CMS detector at the LHC, corresponding to an integrated luminosity of 35.9 fb(-1) . The results are in agreement with standard model (SM) predictions. In a search for resonant production, upper limits are set on the cross section for new spin-0 or spin-2 particles. For the SM-like nonresonant production hypothesis, the data exclude a product of cross section and branching fraction larger than 2.0 fb at 95% confidence level (CL), corresponding to about 24 times the SM prediction. Values of the effective Higgs boson self-coupling K X are constrained to be within the range -11 < K-lambda < 17 at 95% CL, assuming all other Higgs boson couplings are at their SM value. The constraints on K-lambda, are the most restrictive to date. (C) 2018 The Author(s). Published by Elsevier B.V.Peer reviewe

Evidence for Top Quark Production in Nucleus-Nucleus Collisions

Peer reviewe