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'Organs-on-chips' are microengineered biomimetic systems containing microfluidic channels lined by living human cells, which replicate key functional units of living organs to reconstitute integrated human organ-level pathophysiology in vitro . These microdevices can be used to test efficacy and toxicity of drugs and chemicals, and to create in vitro models of human disease. Thus, they potentially represent low-cost alternatives to conventional animal models for pharmaceutical, chemical and environmental applications. Here we describe a protocol for the fabrication, microengineering and operation of these microfluidic organ-on-chip systems. First, microengineering is used to fabricate a multilayered microfluidic device that contains two parallel elastomeric microchannels separated by a thin porous flexible membrane, along with two full-height, hollow vacuum chambers on either side; this requires ∼3.5 d to complete. To create a 'breathing' lung-on-a-chip that mimics the mechanically active alveolar-capillary interface of the living human lung, human alveolar epithelial cells and microvascular endothelial cells are cultured in the microdevice with physiological flow and cyclic suction applied to the side chambers to reproduce rhythmic breathing movements. We describe how this protocol can be easily adapted to develop other human organ chips, such as a gut-on-a-chip lined by human intestinal epithelial cells that experiences peristalsis-like motions and trickling fluid flow. Also, we discuss experimental techniques that can be used to analyze the cells in these organ-on-chip devices.

The majority of microfluidic devices used for cell culture, including Organ-on-a-Chips (Organ Chips), are fabricated using polydimethylsiloxane (PDMS) polymer because it is flexible, optically clear, and easy to mold. However, PDMS possesses significant challenges for high volume manufacturing and its tendency to absorb small hydrophobic compounds limits its usefulness as a material in devices used for drug evaluation studies. Here, we demonstrate that a subset of optically clear, elastomeric, styrenic block copolymers based on styrene-ethylene-butylene-styrene exhibit reduced absorption of small hydrophobic molecules and drug compounds compared to PDMS and that they can be fabricated into microfluidic devices with fine features and the flexibility required for Organ Chips using mass production techniques of injection molding and extrusion.

The same pneumococcal conjugate vaccines (PCVs) have been used in adults and children in many settings. Differences in the epidemiology of pneumococcal disease between populations necessitates an adult-specific PCV. We aimed to assess the safety, tolerability, and immunogenicity of V116, an investigational 21-valent PCV designed for adults. This randomised, double-blind, active comparator controlled, international phase 3 trial enrolled adults with or without stable chronic medical conditions at 112 clinical sites in 11 countries or territories. Random assignment was performed using a central electronic interactive response technology system. Cohort 1 (≥50 years) was stratified by age (50–64, 65–74, 75–84, and ≥85 years) and randomised 1:1 to receive one intramuscular dose of V116, or the active comparator, PCV20. Cohort 2 (18–49 years) was randomised 2:1 to receive one intramuscular dose of V116 or PCV20. Pneumococcal serotype-specific opsonophagocytic activity (OPA) and IgG responses were measured before (day 1) and after vaccination (day 30). Four primary immunogenicity outcomes were assessed per-protocol. First, in cohort 1, non-inferiority of V116 to PCV20 was tested using serotype-specific OPA geometric mean titres (GMT) ratios for serotypes common to both vaccines; the lower bound of the 95% CI had to be greater than 0·5 for non-inferiority. Second, superiority of V116 to PCV20 was tested for OPA GMT ratios for the serotypes unique to V116; the lower bound of the 95% CI had to be greater than 2·0 for superiority. Third, superiority of V116 to PCV20 was evaluated by the proportions of participants with a four-fold or greater rise from day 1 to day 30 for serotypes unique to V116; the lower bound of the 95% CI of the differences in proportions (V116 – PCV20) had to be greater than 10% for superiority. Finally, in cohort 2, immunobridging was assessed for all 21 serotypes in V116 for adults aged 18–49 years to 50–64 years; the lower bound of the 95% CI for the OPA GMTs had to be greater than 0·5 for non-inferiority. The safety analysis included all randomly assigned participants who received study vaccine. The primary safety outcome was the proportion of participants with solicited injection site and solicited systemic adverse events until day 5 and vaccine-related serious adverse events up to 6 months after vaccination. This trial is registered at ClinicalTrials.gov (NCT05425732). Between July 13, and Nov 22, 2022, 2754 individuals were screened and 2663 participants were randomly assigned. 2656 individuals were vaccinated (1179 in V116 cohort 1; 1177 in PCV20 cohort 1; 200 in V116 cohort 2; and 100 in PCV20 cohort 2). V116 met non-inferiority criteria compared with PCV20 for the ten serotypes common to both vaccines at day 30 in cohort 1 (p<0·0001 for each common serotype). V116 met superiority criteria compared with PCV20 in cohort 1 for ten of the 11 serotypes unique to V116 at day 30 (OPA GMT ratio: p<0·0001 for all unique serotypes except 15C, which was p=0·41; four-fold or greater rise in OPA from day 1–30: p<0·0001 for all serotypes except 15C, which was p=0·67). Immune responses in V116 participants aged 18–49 years were non-inferior compared with V116 participants aged 50–64 years for all V116 serotypes (p<0·0001 for all V116 serotypes). In cohort 1, 685 (58·2%) of participants in V116, and 778 (66·2%) of participants in PCV20 reported one or more adverse event. In cohort 2, 164 (82·0%) participants in V116 and 79 participants (79·0%) in PCV20 reported one or more adverse event. Six deaths were reported, all in cohort 1, none of which were considered vaccine-related (in V116: one due to sepsis, one due to cerebrovascular accident, one due to myocardial infarction, and one due to hepatic cirrhosis and hepatic encephalopathy; in PCV20: one due to cardiac arrest and one due to abdominal abscess). There were no vaccine-related serious adverse events. V116 was non-inferior to PCV20 for the ten serotypes common to both vaccines and superior to PCV20 for all serotypes unique to V116, except for 15C. Immune responses successfully immunobridged between younger and older adults for all serotypes in V116. V116 was generally well tolerated with safety profile similar to PCV20. Merck Sharp & Dohme, subsidiary of Merck & Co, Rahway, NJ, USA (MSD).

Allopathic, osteopathic, and naturopathic medical education all prepare students to practice medicine yet diverge in certain respects. Despite the significant changes that have occurred in the education of each discipline, a more recent comparison and analysis of these three pathways hasn't been published. The review intended to examine the five segments of the educational process common to all three pathways: admissions, preclinical education, clinical education, graduate medical education, and continuing medical education. The research team's evaluations and assessments of each pathway are based on publicly available data collected from each pathway's accrediting organizations and from accredited institutions, because these organizations and institutions accurately reflect the generally-accepted standards and practices within each pathway. The research team performed data collection for this study in 2019 to 2020, and the article reflects the changes in the literature up to that point. The study took place at Rocky Vista University - Southern Utah in Ivins, Utah; the University of Texas at Austin Dell Medical School in Austin, Texas; the Albany Medical Center in Albany, New York; and the National University of Health Sciences in Lombard, Illinois. Naturopathic, allopathic, and osteopathic all undergo rigurous pre clinical training which highlights the basic sciences. Naturopathic schools generally have more in classroom hours and less in person clinical experience than osteopathic and allopathic training programs. All three professions have standardized board exams that cover the required curriculum. Many osteopathic students both take and pass the USMLE which highlights the similarities of their curriculum with the allopathic model. A similar comparison can not be made with naturopathic students as they do not take the USMLE. While all three education models have residency programs, naturopathic are more flexible and less standardized than ostopathic and allopathic residency programs. Some data points had to be drawn from conversations as they were not publicly avalable. Credit hours are not sufficient to compare the scope of the curriculum of each education pathway. The NPLEX needs to be compared to both COMLEX and USMLE. Since 1997, the three major branches of educating physicians have continued to converge pedagogically. The currently most-notable similarity among the three pathways is the preclinical years and their basic-science curriculum. The combined match of allopathic and osteopathic residents, as well as increasing similarities and crossovers in curriculum and methods of practice, highlight this fact. Philosophy and methodologies of practice continue to distinguish these educational pathways, but their increasing similarities may lead to further convergence of practice and pedagogical models.

Cerebral angiography is an invasive procedure utilized without supporting guidelines in preoperative evaluations of infective endocarditis (IE). It is used to identify mycotic intracranial aneurysm, which is suspected to increase the risk of intracranial bleeding during cardiac surgery. Our objectives were to: (1) assess the utility of cerebral angiography by determining which subset of IE patients benefit from its performance; and (2) identify clinical and noninvasive screening tests that can preclude the need for invasive cerebral angiography. Retrospective analysis was performed of all patients treated surgically for IE from 7/2007 to 1/2012 and discharged with medical treatment for IE from 7/2007 to 7/2009 presenting to a large academic center. Of the 151 patients who underwent cerebral angiography, mycotic aneurysm was identified in seven (prevalence=4.6%; 95% CI 2.3–9.3%). Five had viridans group streptococci as the causative IE microorganism (p=0.0017). Noninvasive imaging and particularly absence of intracranial bleed on magnetic resonance imaging conveys a negative predictive value (NPV) of 0.977 (95% CI 0.879–0.996). Absence of a focal neurologic deficit or altered mental status convey a NPV of 0.990 (95% CI 0.945–0.998) and 0.944 (95% CI 0.883–0.974), respectively. Clinical suspicion for mycotic aneurysm and thus utilization of cerebral angiography is likely necessary only in the setting of acute neurologic deficits and when noninvasive imaging demonstrates acute intracranial bleed. A novel association between viridans group streptococci and intracranial mycotic aneurysm is demonstrated.

Recent observations on the western Antarctic Peninsula have suggested that changing climatic conditions may be increasing pressure on breeding seabirds due to higher exploitation rates by the tick Ixodes uriae. Using data from 8 microsatellite markers and ticks from 6 Pygoscelis spp. colonies, we employed a population genetics approach to specifically test the hypothesis that I. uriae is expanding south-westward along the peninsula from the Subantarctic region. Contrary to expectations, tick genetic diversity was high within all colonies, and no remaining signal of colonisation events was evident. Although significant geographic genetic structure occurred among ticks from different colonies, these ectoparasites tended to belong to 2 major genetic groups, one found principally in south-western locations (Palmer Station area) and the other in more north-eastern areas (South Shetland Islands). More central colonies showed a mixture of ticks from each genetic group, suggesting that this area represents a hybridisation zone of ticks from 2 distinct origins. A subsequent clustering analysis, including ticks from 2 Subantarctic locations, did not reveal the source population for the northern peninsula group. Overall, our data refute the hypothesis of a recent south-westward expansion of I. uriae along the peninsula and suggest that this tick has been present at more southern latitudes for an extended period of time. Further studies on the distribution and genetic characteristics of this ectoparasite around Antarctica are now required to better understand the colonisation process and predict how changing environmental conditions may affect its presence and diversity in seabird colonies.

A double-blind, randomized study involving 264 toddlers attending day care centers was conducted to document the effect of a 9-valent pneumococcal conjugate vaccine on the carriage rate of pneumococci. Of 3750 cultures done on nasopharyngeal samples obtained from subjects during a 2-year follow-up period after vaccination, 65% were positive for Streptococcus pneumoniae. In all age windows, the rate of carriage of vaccine-type pneumococci was lower among subjects who received the pneumococcal vaccine than among control subjects, because the acquisition rate was lower in the former group. The effect was most pronounced among subjects aged ⩽36 months. The sample size enabled us to study protection against carriage of S. pneumoniae serotypes 6B, 9V, 14, 19F, and 23F; significant protection against all serotypes except 19F was seen in the pneumococcal-vaccine group. The rate of carriage of serotype 6A (not included in the vaccine) was also reduced significantly, but the rate of carriage of serotype 19A (not included in the vaccine) was not. The rate of carriage of non-vaccine-type pneumococci (excluding serotype 6A) was higher in the pneumococcal-vaccine group than in the control group.

Although antibiotic-resistant pneumococci have been frequently detected among day care center (DCC) attendees, the transmission of these organisms to other members of the community has not been adequately studied. Nasopharyngeal cultures were obtained from 152 children and 244 adult members of a closed community (a kibbutz) in Israel. Serotyping, antibiogram, and pulsed-field gel electrophoresis were performed to determine the relatedness of isolated pneumococci. Twenty (30%) of the 66 isolates from children showed decreased susceptibility to penicillin and 9 isolates (14%) were resistant to ⩾3 drugs. Of the 16 isolates from adults, 5 (31%) were intermediately resistant to trimethoprim-sulfamethoxazole. Resistant strains carried by DCC attendees were not isolated either from their parents or from other adult members of the community. Despite the high degree of interpersonal contact occurring in a closed community, resistant pneumococcal strains carried by DCC attendees do not appear to be easily transmitted to the adult population, which suggests the existence of an immunological barrier.

We use deep, \\(\\mu_{r} \\lesssim 28\\,\\text{mag}\\,\\text{arcsec}^{-2}\\), \\(r\\)-band imaging from the Dark Energy Camera Legacy Survey (DECaLS) to search for past, or ongoing, merger activity in a sample of \\(282\\) Low Excitation Radio Galaxies (LERGs) at \\(z<0.07\\). Our principle aim is to assess the the role of mergers in the evolution of LERGs. Exploiting the imaging depth, we classify tidal remnants around galaxies as both minor and major morphological disturbances for our LERG sample and \\(1,622\\) control galaxies matched in redshift, stellar mass, and environment. In groups and in the field, the LERG minor merger fraction is consistent with the control population. In galaxy clusters, \\(8.8 \\pm 2.9\\,\\) % of LERGs show evidence of recent minor mergers in contrast to \\(23.0\\pm 2.0\\,\\) % of controls. This \\(\\sim 4 \\sigma \\) deficit of minor mergers in cluster LERGs suggests these events may inhibit this type of nuclear activity for galaxies within the cluster environment. We observe a \\(> 4\\sigma\\) excess of major mergers in the LERGs with \\(M_{*} \\lesssim 10^{11}\\,\\text{M}_{\\odot}\\), with \\(10 \\pm 1.5\\,\\) % of these AGN involved in such large-scale interactions compared to \\(3.2 \\pm 0.4\\,\\)% of control galaxies. This excess of major mergers in LERGs decreases with increasing stellar mass, vanishing by \\(M_{*} > 10^{11.3}\\,\\text{M}_{\\odot}\\). These observations show that minor mergers do not fuel LERGs, and are consistent with typical LERGs being powered by accretion of matter from their halo. Where LERGs are associated with major mergers, these objects may evolve into more efficiently accreting active galactic nuclei as the merger progresses and more gas falls on to the central engine.

We have identified a population of passive spiral galaxies from photometry and integral field spectroscopy. We selected z<0.035 spiral galaxies that have WISE colours consistent with little mid-infrared emission from warm dust. Matched aperture photometry of 51 spiral galaxies in ultraviolet, optical and mid-infrared show these galaxies have colours consistent with passive galaxies. Six galaxies form a spectroscopic pilot study and were observed using the Wide-Field Spectrograph (WiFeS) to check for signs of nebular emission from star formation. We see no evidence of substantial nebular emission found in previous red spiral samples. These six galaxies possess absorption-line spectra with 4000\\AA\\ breaks consistent with an average luminosity-weighted age of 2.3 Gyr. Our photometric and IFU spectroscopic observations confirm the existence of a population of local passive spiral galaxies, implying that transformation into early-type morphologies is not required for the quenching of star formation.