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In light of the rapid spread of coronavirus disease 2019 (COVID-19) across the United States, the Centers for Disease Control and Prevention (CDC) and hospitals nationwide have developed new protocols to address infection control as well as the care of critical patients. Airway management has been particularly difficult; the challenge of quickly establishing an airway in patients must be balanced by the risk of aerosolizing respiratory secretions and putting the provider at risk of infection. Significant attention has been given to developing protocols for the emergency department and critical care units, but little guidance regarding establishing airway and respiratory support for patients in the prehospital setting has been made available. While some of the recommendations can be extrapolated from hospital guidelines, other factors such as environment and available resources make these protocols unfeasible. Through review of current literature the authors established recommendations regarding airway management and the provision of respiratory support to patients developing respiratory failure related to COVID-19.

Introduction: Little data exists to help urgent care (UC) clinicians predict morbidity and mortality risk. Age, systolic blood pressure (SBP), and heart rate (HR) are easily obtainable and have been used in other settings to predict short-term risk of deterioration. We hypothesized that there is a relationship between advancing age, SBP, HR, and short-term health outcomes in the UC setting. Methods: We collected retrospective data from 28 UC clinics and 22 hospitals in the Intermountain Healthcare system between years 2008-2013. Adult patients (≥18 years) were included if they had a unique UC visit and HR or SBP data. Three endpoints following UC visit were assessed: emergency department (ED) visit within three days, hospitalization within three days, and death within seven days. We analyzed associations between age, SBP, HR and endpoints using local regression with a binomial likelihood. Five age groups were chosen from previously published national surveys. Vital sign (VS) distributions were determined for each age group, and the central tendency was compared against previously published norms (90-120mmHg for SBP and 60-100bpm for HR.) Results: A total of 1,720,207 encounters (714,339 unique patients) met the inclusion criteria; 51,446 encounters (2.99%) had ED visit within three days; 12,397 (0.72%) experienced hospitalization within three days; 302 (0.02%) died within seven days of UC visit. Heart rate and SBP combined with advanced age predicted the probability of ED visit (p

Recent trends suggest that young people in Britain are increasingly rejecting electoral politics. However, evidence suggests that British youth are not apolitical, but are becoming ever more sceptical of the ability of electoral politics to make a meaningful contribution to their lives. Why young people are adopting new political behaviour and values, however, is still a point of contention. Some authors have suggested that neoliberalism has influenced these new patterns of political engagement. This article will advance this critique of neoliberalism, giving attention to three different facets of neoliberalism and demonstrate how they combine to reduce young people’s expectations of political participation and their perceptions of the legitimacy of political actors. We combine ideational and material critiques to demonstrate how young people’s political engagement has been restricted by neoliberalism. Neoliberalism has influenced youth political participation through its critiques of collective democracy, by the subsequent transformations in political practice that it has contributed to, and through the economic marginalisation that has resulted from its shaping of governments’ monetary policy. This approach will be conceptually predicated on a definition of neoliberalism which acknowledges both its focus on reducing interventions in the economy, and also its productive capacity to modify society to construct market relations and galvanise competition amongst agents. From this definition, we develop the argument that neoliberal critiques of democracy, the subsequent changes in political practices which respond to these criticisms and the transformation in socioeconomic conditions caused by neoliberalism have coalesced to negatively influence young people’s electoral participation.

Abstract Objectives In this study, we propose a diagnostic model for automatic detection of otitis media based on combined input of otoscopy images and wideband tympanometry measurements. Methods We present a neural network‐based model for the joint prediction of otitis media and diagnostic difficulty. We use the subclassifications acute otitis media and otitis media with effusion. The proposed approach is based on deep metric learning, and we compare this with the performance of a standard multi‐task network. Results The proposed deep metric approach shows good performance on both tasks, and we show that the multi‐modal input increases the performance for both classification and difficulty estimation compared to the models trained on the modalities separately. An accuracy of 86.5% is achieved for the classification task, and a Kendall rank correlation coefficient of 0.45 is achieved for difficulty estimation, corresponding to a correct ranking of 72.6% of the cases. Conclusion This study demonstrates the strengths of a multi‐modal diagnostic tool using both otoscopy images and wideband tympanometry measurements for the diagnosis of otitis media. Furthermore, we show that deep metric learning improves the performance of the models.

Objectives Improving medical student placements relies on being able to reliably evaluate how students experience clinical learning environments. The Undergraduate Clinical Education Environment Measure (UCEEM) is an increasingly used validated tool designed to allow such evaluations. This study aims to further characterize how the UCEEM relates to qualitative evaluation. methods Students on placement at one hospital were invited to complete the UCEEM before and after the implementation of an innovative new placement structure. Additionally, focus groups were employed to collect qualitative data on their experiences. a novel protocol to triangulate the output of the UCEEM with the qualitative data was developed. Results The UCEEM showed good internal consistency (Cronbach's Alpha 0.79-0.91) and internal correlation. Implementation of the intervention created significant improvements in the overall UCEEM scores ( P = .008) and in the “Learning in and through work and quality of supervision” ( P = .048), “Preparedness for student entry” ( P = .033) and “Workplace interaction patterns and student inclusion” ( P = .039) domains. The triangulation of qualitative data with UCEEM output showed that the UCEEM allowed evaluation of some perceptions not reached through open questioning. However, mixed interpretations of UCEEM items by students led to the conflation of themes and challenges in deriving the meaning behind the score. This appeared to be the case for 14 of the 24 UCEEM items. Conclusion This investigation adds to the literature supporting the UCEEM as a validated tool. It also elucidates the limitations and relationships to qualitative data that investigators need to be aware of in its use.

The Integrated Data Service (IDS) is a cross-government initiative, designed to transform the way de-identified data is made available for vital research and decision-making about our society and economy. It will improve the capability for researchers, allowing them to link data effectively through state-of-the-art systems and technologies. The IDS will enable more collaborative data research and analysis to take place. The service will enable access to data sets from a range of sources, across government departments and Devolved Administrations, presented alongside analytical and visualisation tools. Linking data to help answer complex policy questions is essential for addressing the cross-cutting and complex issues required to improve today’s society. The Reference Data Management Framework (RDMF) makes it possible to link data on a consistent and convenient basis. The IDS will link data to provide otherwise untapped insight and to allow rapid analysis on a growing range of integrated data assets. This cross-government service will provide policy makers with robust and collaborative evidence, informing the decisions made across UK society. This session will introduce IDS to our academic audience, highlighting the benefits for data suppliers, analysts and the wider public that will be available through standardised data, streamlined data linkage, outputs, and the state-of-the-art dissemination technology. Building on the IDS showcase in April 2023, the presenter will outline the timeline for the continued development of the IDS, and how researchers and existing SRS users can get involved. They will also discuss the ongoing SRS to IDS transition. The service is open to analysts within the UK government, devolved administrations, and external accredited researchers, such as scientists, academics, and researchers, allowing them to carry out analysis that addresses major societal challenges. You will learn the advantages of IDS, and the progression the service has made in the last year. The audience will have an increased awareness of the IDS, how to get involved and what the potential impact will be for analysts, users, contributors, and the public.

Mutations in the nucleocapsid of SARS-CoV-2 may interfere with antigen detection by diagnostic tests. We used several methods to evaluate the effect of various SARS-CoV-2 nucleocapsid mutations on the performance of the Panbio™ and BinaxNOW™ lateral flow rapid antigen tests and a prototype high-throughput immunoassay that utilizes Panbio antibodies. Variant detection was also evaluated by immunoblot and BIAcore™ assay. A panel of 23 recombinant nucleocapsid antigens (rAgs) were produced that included mutations found in circulating SARS-CoV-2 variants, including variants of concern. All mutant rAgs were detected by all assays, at a sensitivity equivalent to wild-type control (Wuhan strain). Thus, using a rAg approach, we found that the SARS-CoV-2 nucleocapsid mutations examined do not directly impact antigen detection or antigen assay performance.

Cities will transform and morph into something completely different for the next generation. Just as the car replaced the horse, the car will shortly be replaced, because of fossil fuel, and with, it the road system that exists in towns and cities everywhere. The high street is also under stress as more and more of us use on-line shopping, meaning that they are littered with second-hand shops and coffee take-away. However, cities are popular and will continue to grow, especially as more and more people are displaced due to climate change and weather disasters. The following is a rambling through these thoughts about what might just happen.

The responses of stomatal aperture to light intensity and CO2 concentration were studied in both Vicia faba (C3) and Kalanchoë fedtschenkoi (Crassulacean acid metabolism; CAM), in material sampled from both light and dark periods. Direct comparison was made between intact leaf segments, epidermises grafted onto exposed mesophyll, and isolated epidermal peels, including transplantations between species and between diel periods. We reported the stomatal opening in response to darkness in isolated CAM peels from the light period, but not from the dark. Furthermore, we showed that C3 mesophyll has stimulated CAM stomata in transplanted peels to behave as C3 in response to light and CO2. By using peels and mesophyll from plants sampled in the dark and the light period, we provided clear evidence that CAM stomata behaved differently from C3. This might be linked to stored metabolites/ions and signalling pathway components within the guard cells, and/or a mesophyll-derived signal. Overall, our results provided evidence for both the involvement of guard cell metabolism and mesophyll signals in stomatal responses in both C3 and CAM species.

Group B streptococcus (GBS) is a leading bacterial cause of neonatal sepsis and meningitis in many countries as well as an important cause of disease in pregnant women. Currently, serotype-specific conjugate vaccines are being developed. We conducted an epidemiological analysis of health administrative data to estimate the burden of infant GBS disease in Ontario, Canada and combined these estimates with literature on serotype distribution to estimate the burden of disease likely to be vaccine-preventable. Between 1st January 2005 and 31st December 2015, 907 of 64320 health care encounters in Ontario in patients under 1 year old had codes specifically identifying GBS as the cause of the disease, of which 717 were under one month of age. In addition, application of epidemiological data to the remaining patients allowed us to estimate a further 2322 cases and among them 1822 were under one month of age. In the same period, 579 confirmed neonatal invasive GBS cases in patients up to one month of age were reported to public health. Depending on serotype distribution, vaccination coverage and early versus late onset disease (0–6 days and 7–90 days of age respectively), the preventable fraction ranged widely. With a vaccine that is 90% effective and 60% immunization coverage, up to 52% of early and late onset disease could be prevented by forthcoming vaccines. GBS is under-reported in Ontario. Uncertainty about the potential impact of vaccine indicates that further analysis and research may be needed to prepare for policy-decision making, including clinical validation studies and an economic evaluation of GBS vaccination in Ontario.

ObjectivesAuditory perceptual learning studies tend to focus on the nature of the target stimuli. However, features of the background noise can also have a significant impact on the amount of benefit that participants obtain from training. This study explores whether perceptual learning of speech in background babble noise generalizes to other, real-life environmental background noises (car and rain), and if the benefits are sustained over time.DesignNormal-hearing native English speakers were randomly assigned to a training (n = 12) or control group (n = 12). Both groups completed a pre- and post-test session in which they identified Bamford-Kowal-Bench (BKB) target words in babble, car, or rain noise. The training group completed speech-in-babble noise training on three consecutive days between the pre- and post-tests. A follow up session was conducted between 8 and 18 weeks after the post-test session (training group: n = 9; control group: n = 7).ResultsParticipants who received training had significantly higher post-test word identification accuracy than control participants for all three types of noise, although benefits were greatest for the babble noise condition and weaker for the car- and rain-noise conditions. Both training and control groups maintained their pre- to post-test improvement over a period of several weeks for speech in babble noise, but returned to pre-test accuracy for speech in car and rain noise.ConclusionThe findings show that training benefits can show some generalization from speech-in-babble noise to speech in other types of environmental noise. Both groups sustained their learning over a period of several weeks for speech-in-babble noise. As the control group received equal exposure to all three noise types, the sustained learning with babble noise, but not other noises, implies that a structural feature of babble noise was conducive to the sustained improvement. These findings emphasize the importance of considering the background noise as well as the target stimuli in auditory perceptual learning studies.

The Wnt/β-catenin signaling pathway has been implicated in human proliferative diseases such as cancer and fibrosis. The functions of β-catenin and several other components of this pathway have been investigated in fibrosis. However, the potential role of R-spondin proteins (RSPOs), enhancers of the Wnt/β-catenin signaling, has not been described. A specific interventional strategy targeting this pathway for fibrosis remains to be defined. We developed monoclonal antibodies against members of the RSPO family (RSPO1, 2, and 3) and probed their potential function in fibrosis in vivo. We demonstrated that RSPO3 plays a critical role in the development of fibrosis in multiple organs. Specifically, an anti-RSPO3 antibody, OMP-131R10, when dosed therapeutically, attenuated fibrosis in carbon tetrachloride (CCl4)-induced liver fibrosis, bleomycin-induced pulmonary and skin fibrosis models. Mechanistically, we showed that RSPO3 induces multiple pro-fibrotic chemokines and cytokines in Kupffer cells and hepatocytes. We found that the anti-fibrotic activity of OMP-131R10 is associated with its inhibition of β-catenin activation in vivo. Finally, RSPO3 was found to be highly elevated in the active lesions of fibrotic tissues in mouse models of fibrosis and in patients with idiopathic pulmonary fibrosis (IPF) and nonalcoholic steatohepatitis (NASH). Together these data provide an anti-fibrotic strategy for targeting the Wnt/β-catenin pathway through RSPO3 blockade and support that OMP-131R10 could be an important therapeutic agent for fibrosis.

Abstract Background The ATTUNE Knee by DePuy Synthes was introduced in 2013. It is designed to provide better range of motion and address patient-reported instability. The PFC Sigma Knee, an earlier prosthesis by DePuy Synthes, is a common knee replacement with a strong clinical track record. Our aim is to compare the outcomes after primary total knee replacement for end-stage knee osteoarthritis of the PFC and ATTUNE knee systems in 21 patients who each have prosthesis in opposite knees using WOMAC, Oxford Knee and SF-12 scores and evaluation of range of motion. Methods A review was carried out on 21 patients who underwent primary total knee replacement with both the ATTUNE and PFC knee systems. These were staged operations performed in the same institution and by the same surgeon. All cases were followed up for a minimum of 6 months. WOMAC, Oxford Knee and SF-12 scores, as well as knee range of motion were recorded preoperatively and at 6 months postoperatively. Results There was a significant difference in pre- to 6-month post-operative outcomes in PFC and ATTUNE groups with regard to improvement in range of motion (10° ± 8 and 13° ± 11, respectively). There was also a significant improvement in WOMAC scores (PFC group) and Oxford Knee Scores (ATTUNE group) (8.9 ± 7.7 and 12.1 ± 8.4, respectively). There was a significant improvement in SF-12 Score in both groups (10.1 ± 9.3 for PFC and 15.8 ± 13.3 for ATTUNE). The minimum clinically important difference (MCID) in scoring systems at 6 months was reached by 6 patients in the PFC group and 12 in the ATTUNE group. Conclusion A significant difference was demonstrated in clinical outcome at 6 months postoperatively between PFC and ATTUNE knee systems in patients who underwent total knee arthroplasty with both prostheses. Superior results were recorded for the ATTUNE knee system.

In grapevine, trans-Resveratrol (tR) is produced as a defence mechanism against stress or infection. tR is also considered to be important for human health, which increases its interest to the scientific community. Transcriptomic analysis in grapevine cell cultures treated with the defence response elicitor methyl-β-cyclodextrin (CD) revealed that both copies of PHOSPHOENOLPYRUVATE CARBOXYLASE KINASE (PPCK) were down-regulated significantly. A role for PPCK in the defence response pathway has not been proposed previously. We therefore analysed the control of PPCK transcript levels in grapevine cell cultures and leaves elicited with CD. Moreover, phosphoenolpyruvate carboxylase (PPC), stilbene synthase (STS), and the transcription factors MYB14 and WRKY24, which are involved in the activation of STS transcription, were also analysed by RT-qPCR. The results revealed that under CD elicitation conditions PPCK down-regulation, increased stilbene production and loss of PPC activity occurs in both tissues. Moreover, STS transcripts were co-induced with MYB14 and WRKY24 in cell cultures and leaves. These genes have not previously been reported to respond to CD in grape leaves. Our findings thus support the hypothesis that PPCK is involved in diverting metabolism towards stilbene biosynthesis, both for in vitro cell culture and whole leaves. We thus provide new evidence for PEP being redirected between primary and secondary metabolism to support tR production and the stress response.

Abstract  Although the connections of Hedwig Conrad-Martius’ ontological phenomenology, what she called, “realontology,” to Husserl’s transcendental phenomenology were constant concerns that usually remained in the background of her work, on occasion they became foreground. Similarly the problems surrounding the individuation of the person and spirit were persistent but rather marginal in her writings. In this paper I want first to review some of the issues as they are connected to ontological and transcendental phenomenology. Then I want to relate them to the cosmological and theological issues that were no less important for Conrad-Martius. [ABSTRACT FROM AUTHOR]

Objective: To compare the effectiveness of plasma-derived human thrombin and bovine thrombin for achieving hemostasis during surgery.Methods: Adults (N = 305) with ≥ 1 mild or moderate bleeding site not manageable by conventional modalities during elective cardiovascular, neurologic, or general surgical procedures at multiple study centers were randomized to human (n = 153) or bovine (n = 152) thrombin, applied topically with an absorbable gelatin sponge. Bleeding was assessed 3, 6, and 10 min post-application. Other evaluations included laboratory assessments, vital signs, blood loss, blood transfusions, time in specialty-care units, procedure duration, and length of hospital stay. Blood samples for antibody assessment were collected at baseline and postoperative week 5.Results: The proportion of patients achieving hemostasis within 10 min (primary outcome) was equivalent for human and bovine thrombin (97.4 vs. 97.4%, respectively; ratio, 1.00; 95% CI, 0.96–1.05). The proportions of patients achieving hemostasis at 6 min (94.8 vs. 92.8%) and 3 min (73.2 vs. 72.4%) were also equivalent. No clinically meaningful differences were noted for other variables. The products had similar adverse event profiles. More patients (12.7%) who received bovine thrombin demonstrated seroconversion for ≥ 1 of the 4 antibodies assayed than patients who received human thrombin (3.3%). No patients in the human thrombin group developed seroconversion for anti-human thrombin or anti-human factor V/Va antibodies. Limitations of this study include the lack of a placebo-control group, the potential for inter-surgeon variability, and the fact that antibody assessment was not evaluable in all patients.Conclusions: Plasma-derived human thrombin and bovine thrombin were equivalent in achieving hemostasis within 10, 6, and 3 min and had comparable safety profiles. None of the patients receiving human thrombin developed seroconversion for antibodies to any of the human antigens. [ABSTRACT FROM AUTHOR]

Crassulacean acid metabolism (CAM) is a metabolic adaptation of photosynthesis that enhances water use efficiency. Here, via genomic analysis of Kalanchoë, the authors provide evidence for convergent evolution of protein sequence and temporal gene expression underpinning the multiple independent emergences of CAM.

Muchos de los artículos publicados en International Journal of Clinical and Health Psychology describen los resultados obtenidos en estudios que han utilizado escalas tipo Likert. Estas escalas tienen una serie de ventajas y de desventajas. En este artículo se comentan algunas de ellas. En particular, se discute sobre los efectos del uso de escalas que comienzan en un extremo positivo y terminan en el negativo, así como las que presentan altos índices a la izquierda a diferencia de la derecha. También se señala que las puntuaciones en los ítems redactados de forma negativa difieren de las obtenidas en ítems positivos y que, por tanto, no es apropiada una simple inversión de las puntuaciones obtenidas en dichos ítems. Por último, cabe señalar que algunos ítems de estas escalas plantean más de una cuestión, siendo difícil saber si a la hora de contestarlos, los encuestados responden a todo el ítem o sólo a una parte.

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Numerosos textos y artículos proporcionan guías sobre cómo escribir artículos académicos. El objetivo de este documento, en particular, consiste en centrarse en las técnicas más recientes al respecto que pueden ser consideradas por los autores a la hora de escribir o revisar textos. Utilizando ejemplos mayoritariamente sacados de los números recientes de International Journal of Clinical and Health Psychology (IJCHP), se comentan nuevas aproximaciones a la presentación de títulos, resúmenes, orientaciones de lectura, introducciones, métodos, resultados, tablas, figuras y conclusiones. Es más, dónde resulta apropiado, se hace referencia a las posibles diferencias en los estilos de autores españoles y anglosajones, dado que IJCHP publica artículos en ambos idiomas. Parece que hay varias maneras de mejorar este aspecto particular de escritura académica, aunque algunas de las maneras de hacerlo pueden parecer más aceptables para la escritura de los autores bien establecidos en comparación con los más novatos, sobre todo si escriben en un segundo idioma.

We describe a novel, simple and low-cost protein microarray strategy wherein the microarrays are generated by printing expression ready plasmid DNAs onto slides that can be converted into protein arrays on-demand. The printed expression plasmids serve dual purposes as they not only direct the synthesis of the protein of interest; they also serve to capture the newly synthesized proteins through a high affinity DNA-protein interaction. To accomplish this we have exploited the high-affinity binding (approximately 3-7 x 10 (-13) M) of E. coli Tus protein to Ter, a 20 bp DNA sequence involved in the regulation of E. coli DNA replication. In our system, each protein of interest is synthesized as a Tus fusion protein and each expression construct directing the protein synthesis contains embedded Ter DNA sequence. The embedded Ter sequence functions as a capture reagent for the newly synthesized Tus fusion protein. This "all DNA" microarray can be converted to a protein microarray on-demand without need for any additional capture reagent.

Abstract Physical activity and a healthy lifestyle are crucial factors for delaying and reducing the effects of sarcopenia. Cycling has gained popularity in the last decades among midlife men. While the cardiovascular benefits of cycling and other endurance exercises have been extensively proved, the potential benefits of lifelong aerobic exercise on muscle health have not been adequately studied. Our aim was to quantify the benefits of cycling in terms of muscle health in middle-aged men, using magnetic resonance imaging. We ran a cross-sectional study involving two groups of middle-aged male adults (mean age 49 years, range 30–65) that underwent Dixon MRI of the pelvis. The groups consisted of 28 physically inactive (PI) and 28 trained recreational cyclists. The latter had cycled more than 7000 km in the last year and have been training for 15 years on average, while the PI volunteers have not practiced sports for an average of 27 years. We processed the Dixon MRI scans by labelling and computing the fat fraction (FF), volume and lean volume of gluteus maximus (GMAX) and gluteus medius (GMED); and measuring the volume of subcutaneous adipose tissue (SAT). We found that the cyclists group had lower FF levels, a measure of intramuscular fat infiltration, compared to the PI group for GMAX (PI median FF 21.6%, cyclists median FF 14.8%, p

Objectives This study aims to quantitatively evaluate whether there are muscle mass differences between male and female recreational cyclists and compare muscle quality and body composition in the pelvis region between two well-matched groups of fit and healthy male and female adults.Methods This cross-sectional study involved 45 female and 42 male recreational cyclists. The inclusion criteria for both groups were to have cycled more than 7000 km in the last year, have an absence of injuries and other health problems, have no contraindication to MRI, and be 30–65 years old. Our main outcome measures were fat fraction, as a measure of intramuscular fat (IMF) content, and volume of the gluteal muscles measured using Dixon MRI. The gluteal subcutaneous adipose tissue (SAT) volume was evaluated as a secondary measure.Results We found that there were no sex differences in the IMF content of gluteus maximus (GMAX, p=0.42), gluteus medius (GMED, p=0.69) and gluteus minimus (GMIN, p=0.06) muscles, despite females having more gluteal SAT (p

Femoral neck osteotomy creates a critical anatomical landmark for surgeons performing primary Total Hip Arthroplasty (THA); it affects the final height and position of the femoral component. Patient Specific Instrumentation (PSI) has been developed to guide the osteotomy. We aimed to assess the accuracy of a patient-specific (PS) femoral osteotomy guide in primary THA using three-dimensional (3D) computed tomography (CT) analysis. We included pre- and post-operative CT data of 103 THAs. All patients underwent 3D planning to define the optimal femoral neck osteotomy level. Our primary objective was to quantify the discrepancy between the achieved and planned osteotomy level; our secondary objective was to evaluate the clinical outcome. The median (Interquartile Range—IQR) discrepancy between the achieved and planned osteotomy level was 0.3 mm (−1 mm to 2 mm). We found a strong positive correlation between the planned and achieved osteotomy level (R2 = 0.9, p < 0.001). A satisfactory clinical outcome was recorded. Our findings suggest that surgeons can use 3D-printed PS guides to achieve a femoral neck osteotomy with a high level of accuracy to the plan.

L-selectin (CD62L) is a type-I transmembrane glycoprotein and cell adhesion molecule that is expressed on most circulating leukocytes. Since its identification in 1983, L-selectin has been extensively characterized as a tethering/rolling receptor. There is now mounting evidence in the literature to suggest that L-selectin plays a role in regulating monocyte protrusion during transendothelial migration (TEM). The N-terminal calcium-dependent (C-type) lectin domain of L-selectin interacts with numerous glycans, including sialyl Lewis X (sLex) for tethering/rolling and proteoglycans for TEM. Although the signals downstream of L-selectin-dependent adhesion are poorly understood, they will invariably involve the short 17 amino acid cytoplasmic tail. In this review we will detail the expression of L-selectin in different immune cell subsets, and its influence on cell behavior. We will list some of the diverse glycans known to support L-selectin-dependent adhesion, within luminal and abluminal regions of the vessel wall. We will describe how each domain within L-selectin contributes to adhesion, migration and signal transduction. A significant focus on the L-selectin cytoplasmic tail and its proposed contribution to signaling via the ezrin-radixin-moesin (ERM) family of proteins will be outlined. Finally, we will discuss how ectodomain shedding of L-selectin during monocyte TEM is essential for the establishment of front-back cell polarity, bestowing emigrated cells the capacity to chemotax toward sites of damage.

After several decades of research we now have evidence that at least six interventions are suitable for immediate use in contemporary clinical practice within high-resource settings and can be expected to safely reduce the rate of preterm birth. These interventions involve strategies to prevent non-medically indicated late preterm birth; use of maternal progesterone supplementation; surgical closure of the cervix with cerclage; prevention of exposure of pregnant women to cigarette smoke; judicious use of fertility treatments; and dedicated preterm birth prevention clinics. Quantification of the extent of success is difficult to predict and will be dependent on other clinical, cultural, societal and economic factors operating in each environment. Further success can be anticipated in the coming years as other research discoveries are translated into clinical practice, including new approaches to treating intra-uterine infection, improvements in maternal nutrition and lifestyle modifications to ameliorate maternal stress. The widespread use of human papillomavirus (HPV) vaccination in girls and young women will decrease the need for surgical interventions on the cervix and can be expected to further reduce the risk of early birth.Together, this array of clinical interventions, each based on a substantial body of evidence, is likely to reduce rates of preterm birth and prevent death and disability in large numbers of children. The process begins with an acceptance that early birth is not an inevitable and natural feature of human reproduction. Preventative strategies are now available and need to be applied. The best outcomes may come from developing integrated strategies designed specifically for each health care environment.