Early Entry Research Articles

A Single-Center Prospective Cohort Study on Postsplenectomy Sepsis and its Prevention.

BackgroundThis study evaluated the impact of a dedicated outpatient service on vaccination uptake after splenectomy and on the incidence of postsplenectomy sepsis.MethodsFrom 2009 to 2016 at the University Hospital Freiburg (Germany), asplenic patients were referred to a dedicated outpatient service, provided with comprehensive preventive care including vaccinations, and enrolled in a prospective cohort study. The impact of the service on vaccination uptake and the occurrence of severe sepsis/septic shock was compared between patients who had splenectomy (or were asplenic) within 3 months of study entry (“early study entry”) and those who had splenectomy (or were asplenic) >3 months before study entry (“delayed study entry”).ResultsA total of 459 asplenic patients were enrolled, and 426 patients were followed prospectively over a median period of 2.9 years. Pneumococcal vaccine uptake within 3 months of splenectomy or first diagnosis of asplenia was 27% vs 71% among delayed study entry and early study entry patients, respectively (P < .001). Forty-four episodes of severe sepsis or septic shock occurred in study patients: 22 after study entry and 22 before study entry. Streptococcus pneumoniae was more frequent among sepsis episodes that occurred before study entry (8/22) than after study entry (1/22 episodes). For episodes occurring after study entry, only a higher Charlson comorbidity index score was significantly associated with severe sepsis/septic shock postsplenectomy.ConclusionsWith dedicated outpatient care, high uptake of pneumococcal vaccination postsplenectomy was achieved. Sepsis episodes were largely of nonpneumococcal etiology in patients who had received dedicated postsplenectomy care.

Encephalitic Alphaviruses Exploit Caveola-Mediated Transcytosis at the Blood-Brain Barrier for Central Nervous System Entry.

Venezuelan and western equine encephalitis viruses (VEEV and WEEV, respectively) invade the central nervous system (CNS) early during infection, via neuronal and hematogenous routes. While viral replication mediates host shutoff, including expression of type I interferons (IFN), few studies have addressed how alphaviruses gain access to the CNS during established infection or the mechanisms of viral crossing at the blood-brain barrier (BBB). Here, we show that hematogenous dissemination of VEEV and WEEV into the CNS occurs via caveolin-1 (Cav-1)-mediated transcytosis (Cav-MT) across an intact BBB, which is impeded by IFN and inhibitors of RhoA GTPase. Use of reporter and nonreplicative strains also demonstrates that IFN signaling mediates viral restriction within cells comprising the neurovascular unit (NVU), differentially rendering brain endothelial cells, pericytes, and astrocytes permissive to viral replication. Transmission and immunoelectron microscopy revealed early events in virus internalization and Cav-1 association within brain endothelial cells. Cav-1-deficient mice exhibit diminished CNS VEEV and WEEV titers during early infection, whereas viral burdens in peripheral tissues remained unchanged. Our findings show that alphaviruses exploit Cav-MT to enter the CNS and that IFN differentially restricts this process at the BBB.IMPORTANCE VEEV, WEEV, and eastern equine encephalitis virus (EEEV) are emerging infectious diseases in the Americas, and they have caused several major outbreaks in the human and horse population during the past few decades. Shortly after infection, these viruses can infect the CNS, resulting in severe long-term neurological deficits or death. Neuroinvasion has been associated with virus entry into the CNS directly from the bloodstream; however, the underlying molecular mechanisms have remained largely unknown. Here, we demonstrate that following peripheral infection alphavirus augments vesicular formation/trafficking at the BBB and utilizes Cav-MT to cross an intact BBB, a process regulated by activators of Rho GTPases within brain endothelium. In vivo examination of early viral entry in Cav-1-deficient mice revealed significantly lower viral burdens in the brain than in similarly infected wild-type animals. These studies identify a potentially targetable pathway to limit neuroinvasion by alphaviruses.

Pregnancy facilitates maternal liver regeneration after partial hepatectomy.

Liver resection induces robust liver regrowth or regeneration to compensate for the lost tissue mass. In a clinical setting, pregnant women may need liver resection without terminating pregnancy in some cases. However, how pregnancy affects maternal liver regeneration remains elusive. We performed 70% partial hepatectomy (PH) in nonpregnant mice and gestation day 14 mice, and histologically and molecularly compared their liver regrowth during the next 4 days. We found that compared with the nonpregnant state, pregnancy altered the molecular programs driving hepatocyte replication, indicated by enhanced activities of epidermal growth factor receptor and STAT5A, reduced activities of cMet and p70S6K, decreased production of IL-6, TNFα, and hepatocyte growth factor, suppressed cyclin D1 expression, increased cyclin A1 expression, and early activated cyclin A2 expression. As a result, pregnancy allowed the remnant hepatocytes to enter the cell cycle at least 12 h earlier, increased hepatic fat accumulation, and enhanced hepatocyte mitosis. Consequently, pregnancy ameliorated maternal liver regeneration following PH. In addition, a report showed that maternal liver regrowth after PH is driven mainly by hepatocyte hypertrophy rather than hyperplasia during the second half of gestation in young adult mice. In contrast, we demonstrate that maternal liver relies mainly on hepatocyte hyperplasia instead of hypertrophy to restore the lost mass after PH. Overall, we demonstrate that pregnancy facilitates maternal liver regeneration likely via triggering an early onset of hepatocyte replication, accumulating excessive liver fat, and promoting hepatocyte mitosis. The results from our current studies enable us to gain more insights into how maternal liver regeneration progresses during gestation.NEW & NOTEWORTHY We demonstrate that pregnancy may generate positive effects on maternal liver regeneration following partial hepatectomy, which are manifested by early entry of the cell cycle of remnant hepatocytes, increased hepatic fat accumulation, enhanced hepatocyte mitosis, and overall accelerated liver regrowth.

Parenting with eyes wide open: Young gifted children, early entry and social isolation

This case study outlines the challenges of eight Australian mothers with intellectually gifted preschoolers. The ideal ways of nurturing children’s giftedness, the parents’ role in early identification and the effect of maternal depression and possible association with twice exceptionality (gifted with a disorder) are discussed. The narratives of case study parents then describe how and whether the needs of their preschoolers were understood or met in early childhood services, and the advice they received about early entry. It was found that early entry met the needs of children whose parents chose this acceleration option and that the preschoolers who missed out because of intervention by their educators did not fare so well. Findings also indicated an urgent need for the inclusion of compulsory early childhood giftedness courses for Australian pre-service educators and an equally urgent need for professional development courses about giftedness for educators already working in early childhood services.

High-Resolution Infection Kinetics of Entomopathogenic Nematodes Entering Drosophila melanogaster

Entomopathogenic nematodes (EPNs) have been a useful model for studying wound healing in insects due to their natural mechanism of entering an insect host either through the cuticle or an orifice. While many experiments have shed light on nematode and host behavior, as well as the host immune response, details regarding early nematode entry and proliferative events have been limited. Using high-resolution microscopy, we provide data on the early infection kinetics of Heterorhabditis bacteriophora and its symbiotic bacteria, Photorhabdus luminescens. EPNs appendage themselves to the host and enter through the host cuticle with a drill-like mechanism while leaving their outer sheath behind. EPNs immediately release their symbiotic bacteria in the host which leads to changes in host behavior and septicemia within 6 h while EPNs travel through the host in a predictable manner, congregating in the anterior end of the host. This paper sheds light on the entry and proliferative events of EPN infection, which will further aid in our understanding of wound healing and host immune activation at a high spatiotemporal resolution.

Articles of Significant Interest in This Issue

Influenza virus hemagglutinin (HA) protein binds receptors and is triggered by acidic pH to cause membrane fusion in endosomes. Avian influenza viruses have unstable HA proteins activated at a pH range of 5.6 to 6.2, enabling entry in early endosomes. Human-adapted influenza viruses prefer a stabilized HA activated at pH 5.0 to 5.5. Russier et al. (e01423-19) found that a mutant H1N1 virus (activation pH, 6.0) enhances early replication in mice compared to the wild type (pH 5.5). However, earlier entry and growth via a destabilized HA resulted in enhanced type I interferon responses in dendritic cells. This work connects protein structural changes to the host’s control of infection.

Satisfying Newcomers’ Needs: The Role of Socialization Tactics and Supervisor Autonomy Support

We investigate a novel approach to newcomer socialization based on self-determination theory (SDT). A core assumption of SDT is that when social contexts support basic psychological needs for autonomy, competence, and relatedness, people are more likely to integrate new experience effectively and thrive in their environment. We sought to examine the role of psychological need support within the context of newcomer socialization and the period of early entry where newcomers learn their new role and become integrated within the organization. We propose that organizational socialization tactics and perceived autonomy-supportive supervision jointly influence newcomers’ basic psychological needs and, in turn, their organizational commitment and withdrawal cognitions. Results from structural equation modeling analyses from a time-lagged study of 489 MBA interns supported our hypothesized model. There were significant indirect effects of institutionalized socialization tactics and supervisor autonomy support on both affective organizational commitment and withdrawal cognitions, via psychological need satisfaction. Use of institutionalized tactics also was negatively associated with interns’ specific need for autonomy, suggesting that individualized tactics may play a role in supporting newcomers’ sense of self-determination. A post hoc moderation analysis further suggested a substitutive pattern in the interaction between supervisor autonomy support and institutionalized tactics, emphasizing the central role that supervisors play in newcomer socialization, particularly when it pertains to newcomers’ psychological need satisfaction. Our results indicate that SDT is a promising theoretical framework for studying newcomer adjustment.

Redefining the Care Continuum to Create a Pipeline to Dementia Care for Minority Populations

Multiple studies show that racial and ethnic minorities with low socioeconomic status are diagnosed with Alzheimer’s disease and Alzheimer’s disease–related dementias (AD/ADRD) in more advanced disease stages, receive fewer formal services, and have worse health outcomes. For primary care providers confronting this challenge, community-based organizations can be key partners in supporting earlier identification of AD/ADRD and earlier entry into treatment, especially for minority groups. The New York University Center for the Study of Asian American Health, set out to culturally adapt and translate The Kickstart-Assess-Evaluate-Refer (KAER) framework created by the Gerontological Society of America to support earlier detection of dementia in Asian American communities and assist in this community-clinical coordinated care. We found that CBOs play a vital role in dementia care, and are often the first point of contact for concerns around cognitive impairment in ethnically diverse communities. A major strength of these centers is that they provide culturally appropriate group education that focuses on whole group quality of life, rather than singling out any individual. They also offer holistic family-centered care and staff have a deep understanding of cultural and social issues that affect care, including family dynamics. For primary care providers confronting the challenge of delivering evidence-based dementia care in the context of the busy primary care settings, community-based organizations can be key partners in supporting earlier identification of AD/ADRD and earlier entry into treatment, especially for minority groups.

Interleaf, Inc.—1981 to 2000

INTERLEAF, INC., was an early entry into the computer-based publishing business, initially based on computer workstations and focusing on technical publishing. The company was formed in 1981, shipped its fi rst product in 1984, which included a variety of hardware and software innovations, and was in a strong position to go public in 1986. In the later 1980s, other companies entered the business in competition with Interleaf, and personal computers then had the power that once required an expensive workstation; there was also standardization around window systems such as the X Window System, Motif on top of X, and Microsoft Windows. Also some of Interleaf's innovations were no longer competitive advantages as the industry coalesced around alternative technologies such as PostScript and Acrobat Reader. Redirecting its business strategy once and then again, Interleaf continued on with up and down success until 2000 when it was acquired by Broad Vision.

Family structure patterns from childhood through adolescence and the timing of cohabitation among diverse groups of young adult women and men.

Family structure changes experienced by children are likely to shape their transitions into young adulthood, including the formation of their own romantic relationships. This study examined links between children's family structure trajectories from childhood through adolescence and their timing of entry into cohabitation as young adults, a transition with implications for future relationship instability through adulthood. Repeated measures latent class analysis identified configurations of family structures and family structure changes from birth through age 15 among 10,706 young people in the National Longitudinal Survey of Youth, 1979 Children and Young Adults. A Cox proportional hazard model then used the resulting classes to predict timing into cohabitation over the period from age 15 to age 38. Both timing of family structure transitions and the type of transitions (e.g., early transitioning into a stepfamily home) were associated with earlier entry into cohabitation. Notably, links between family structure trajectories and the timing of cohabitation differed by gender and race/ethnicity (Latinx, African American, White), such as a faster entry into cohabitation by women who experienced early entry into stepfamily structures. Regardless of gender, Latinx and White young adults were faster to enter into cohabitation if they lived in a stepfamily structure during early childhood. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

558: Increasing prompt prenatal care after a prior preterm birth: potential interventions from the patient perspective

In our clinic, up to 20% of women with a prior preterm birth (PTB) present for care beyond the 20-week gestational age ideal to initiate PTB preventions. We aimed to identify patient suggestions for interventions that could potentially increase early entry into care in this high risk group. We conducted qualitative in-depth interviews of pregnant women with a prior PTB. Interviewees included early and late presenters (before and at/after 20 weeks gestations) to care in their current pregnancy. Interviews were conducted by trained qualitative interviewers and followed a semi-structured interview guide. Interviews were transcribed verbatim and analyzed using applied thematic analysis. Here we present themes that emerged for potential interventions as well as response frequencies to describe participants’ pregnancy context. We interviewed 28 early presenters and 11 late presenters (table 1). Half of early presenters reported planning their current pregnancy and 73% of late presenters did not plan their current pregnancy. While 93% of early presenters learned of their pregnancy via a home pregnancy test, 64% of late presenters learned via an emergency room visit. Over 70% of early and late presenters reported they have no barriers to initiating prenatal care. Among both early and late presenters, the most commonly cited interventions to increase early presentation to care were patient education, peer sharing, television advertisements, internet and community based interventions (table 2). Our qualitative findings from a diverse group of early and late presenting women with a history of PTB suggests multiple interventions that could potentially improve early entry into care within this high-risk group. Suggested interventions were similar from early and late presenting patients. Therefore interventions in our clinic focused on patient education and dissemination of information could have a significant impact on presentation to care and thus PTB prevention.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

POSITIONING MODES SIMULATION OF OPTIMIZED IN TIME DOMAIN SLIDING MODE CONTROL SYSTEM WHEN CHANGING THE CALCULATED VOLTAGE AMPLITUDE

Electric drives are characterized by the restriction of intermediate coordinates in transient modes. Such restrictions are implemented by a system with cascade controllers. The N-i switching method, which has a relatively simple mathematical apparatus, provides optimization for the speed of cascade sliding mode control systems. In this work, a comparative study of the typical operating modes of the control system for the position of the output shaft of the electric drive is carried out. At the same time, the parameters of the optimal regulators were varied based on a change in the calculated voltage value of the power converter. Performance optimization is based on the calculated trajectories of the idealized control object. The study of the positional electric drive control system revealed deviations of the transition trajectory from the calculated one. The reason for this effect is the influence of the internal feedback of the electromechanical system, leading to the early entry of the regulators into the sliding mode. The obtained families of transient characteristics make it possible to construct empirical dependences of the duration of regulation on the relative value of the calculated jerk of the output shaft for all typical positioning modes. Such dependencies have pronounced extremes, which makes it possible to tune the drive to near optimal speed by preventing premature entry of the regulators into the sliding mode. The results of the research open the prospect on practical realization of adaptive algorithms for the synthesis of cascade sliding mode control systems based on the N-i switching method.

Gynecologic Management of Pediatric and Adolescent Patients with Ehlers-Danlos Syndrome.

Ehlers-Danlos syndrome (EDS) is a connective tissue disorder resulting in abnormal collagen synthesis leading to skin, joint, ligament, blood vessel, and organ abnormalities. Studies in adult women show an association with heavy menstrual bleeding, dysmenorrhea, and pelvic organ prolapse. We aimed to evaluate gynecologic complaints in pediatric and adolescent patients with EDS and their management by pediatric and adolescent gynecology (PAG) Providers. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Charts of female individuals less than 21years of age with an International Classification of Diseases (ICD) Ninth or Tenth revision diagnosis of EDS who were evaluated between July 1, 2007, and July 31, 2017, were reviewed for menstrual history, gynecologic complaints, and interventions prescribed. A total of 156 patients met inclusion criteria, and 26 (16.7%) were seen by PAG providers. The mean age was 14.5±1.9years. Fifteen (57.7%) reported dysmenorrhea, 13 (50%) complained of heavy menstrual bleeding (HMB), 10 (38.5%) reported irregular menses, and 7 (26.9%) sought contraception. Concurrent medical problems were reviewed, as this affected hormone choice. The cohort was stratified into 2 groups: patients whose menstrual cycles were well controlled on a single method (group A), and patients who tried multiple medications (group B). Progesterone-only pills were most commonly used in froup A. Eleven (73%) patients in group B tried depot medroxyprogesterone acetate (DMPA), but ultimately a levonorgestrel intrauterine device (IUD) was the most popular final choice of treatment and was used by 4 (27%) patients. Few adolescents with EDS are referred to PAG providers despite the prevalence of gynecologic complaints and potential for obstetric and gynecologic complications. In this population, early entry to gynecologic care would be beneficial.

Educação escolar, tradição e oralidade Negro-Brasileira

O presente texto foi elaborado a partir de um estudo de caso sobre educação e oralidade negro-brasileira e consiste em uma abordagem acadêmico-reflexiva sobre alguns aspectos da educação escolar de negros; da tradição e culturas africanas; e, da oralidade negro-brasileira. Esta abordagem se embasa teoricamente, em especial, nas seguintes obras, com seus respectivos autores: Cultura Tradicional Banto, de Raul Ruiz de Asúa Altuna; O Local da Cultura, de Homi Kuane Bhabha; Tradição Viva, de Hampâté Bâ; e, Políticas Públicas de Ações Afirmativas: Educação e Abá (pensamento) Negro-Brasileiro Diásporico, de Jorge Manoel Adão. Ao mesmo tempo em que constatamos que a tradição oral é parte constituinte da matriz formadora da cultura brasileira, em suas expressões artísticas, festivas, religiosas e populares; percebemos que, desde os indicadores, temos um sistema educacional ainda pouco atraente aos pardos e pretos por não agregar a sua identidade cultural e por não reconhecer às singularidades deste grupo específico. Singularidades como: a entrada precoce no mercado de trabalho; a falta de uma qualidade social no ensino público, em que majoritariamente estes têm acesso; e, a um conteúdo programático que não reconhece o universo cultural, a partir de suas raízes, dos negros e que não incentiva a construção de um saber identitário. Assim como o racismo e o preconceito no ambiente escolar e em sala de aula que, consequentemente, se traduz em evasão e descontinuidade dos estudos e falta de referenciais, de perspectivas para a realização de uma trajetória de sucesso pessoal, acadêmico e profissional.

Uber’s early entry decisions in the US

ABSTRACTEarly entry decisions of the firm are crucial to its success. Ride-sharing businesses developed due to technology and government regulation. With the advent of the ride-sharing technology, firms like Uber, Lyft, etc. were faced with the decision of which markets to enter first. For this paper, a model is developed of a profit-maximizing firm constrained from entering all markets simultaneously. The entry decision of Uber into the 50 most populous US metropolitan statistical areas (MSA) is examined. The results suggest Uber’s entry decision was constrained and affected by both revenue potential and regulation in the local taxi industry.

Ratcheting Up: Adjusting the Incentives in the NBA Draft

Abstract: In this paper, we develop a modified salary scale for NBA rookies that adjusts player financial incentives to enter the draft early. Our proposed “ratcheting” salary schedule pays different salary amounts depending on draft pick and the number of years the player delayed entry to the draft to alter the financial incentives of declaring early. We analyze this proposed new salary scale using a put option analogy to determine early exercise boundary positions in which there is no value in the option to delay entry into the draft. The results show that under a ratchet salary system the incentives for early entry to the draft can be greatly altered, especially for freshmen and sophomores unless they are expected to be lottery picks. This information may help players make better decisions of when to enter the draft and can address unraveling in the NBA labor market.

СРАВНИТЕЛЬНАЯ ОЦЕНКА СЕЗОННОГО РАЗВИТИЯ ЯБЛОНИ НА КОЛЛЕКЦИОННОМ УЧАСТКЕ БОТАНИЧЕСКОГО САДА ИМ. ВС. М. КРУТОВСКОГО

The paper presents data on the occurrence of phenological phases in Apple trees of different maturation periods in the collection area of the Vs. M. Krutovsky Botanical garden. The differences in the dates of entry into a particular phenophase, depending on the variety affiliation. Phenological phases, characterized by the highest intervariety variation established. Trees and varieties with early and late entry into the main phenological phases are identified.

FTSE/JSE Index migration: Testing for a tradeable index effect

ABSTRACTThis paper studies whether periodic changes to the constituents in the Swix Top 40 Index leads to price distortions at quarterly rebalancing. Following large and predictable spikes in trade of affected stocks around rebalancing, the natural question is whether this produces a profitable arbitrage trade. Considering excess returns over key rebalancing dates we find that a profitable (yet risky) long-short trade exists, but that the timing of this strategy is key (notably early entry and exit). We also find no evidence of medium-term benefits to being included in the Swix Top 40, apart from higher liquidity for entrants.

DETERMINING THE OPTIMAL TIME TO LAUNCH AN EMERGING INNOVATION IN A MARKET

Investments in emerging technologies and the development of related emerging innovations are necessary to compete in the long term. The market entry timing plays an important role in generating decisive competitive advantages over competitors through investments in emerging innovations. Different market entry strategies offer varied opportunities and risks, which firms must take into account when choosing the optimal time to enter the market. This study develops an optimisation model to make an economically appropriate ex-ante decision in this choice by accounting for several relevant factors and weighing up possible opportunities and risks of the chosen market entry strategy. The evaluation of the simulation results shows that the considered factors influence the optimal market entry to varying extents and that both early and late market entry can be advantageous for companies.

Using detergent-enhanced LAMP for African trypanosome detection in human cerebrospinal fluid and implications for disease staging.

ObjectiveWhere human African trypanosomiasis (HAT) patients are seen, failure to microscopically diagnose infections by Trypanosoma brucei gambiense in blood smears and/or cerebrospinal fluid (CSF) in the critical early stages of the disease is the single most important factor in treatment failure, a result of delayed treatment onset or its absence. We hypothesized that the enhanced sensitivity of detergent-enhanced loop-mediated isothermal amplification (LAMP) will allow for point of care (POC) detection of African trypanosomes in the CSF of HAT patients where the probability for detecting a single parasite or parasite DNA molecule in 1 μL of CSF sample is negligible by current methods.MethodologyWe used LAMP targeting the multicopy pan-T. brucei repetitive insertion mobile element (RIME LAMP) and the Trypanosoma brucei gambiense 5.8S rRNA-internal transcribed spacer 2 gene (TBG1 LAMP). We tested 1 μL out of 20 μL sham or Triton X-100 treated CSFs from 73 stage-1 and 77 stage-2 HAT patients from the Central African Republic and 100 CSF negative controls.ResultsUnder sham conditions, parasite DNA was detected by RIME and TBG1 LAMP in 1.4% of the stage-1 and stage-2 gambiense HAT CSF samples tested. After sample incubation with detergent, the number of LAMP parasite positive stage-2 CSF’s increased to 26%, a value which included the 2 of the 4 CSF samples where trypanosomes were identified microscopically. Unexpected was the 41% increase in parasite positive stage-1 CSF’s detected by LAMP. Cohen’s kappa coefficients for RIME versus TBG1 LAMP of 0.92 (95%CI: 0.82–1.00) for stage-1 and 0.90 (95%CI: 0.80–1.00) for stage-2 reflected a high level of agreement between the data sets indicating that the results were not due to amplicon contamination, data confirmed in χ2 tests (p<0.001) and Fisher’s exact probability test (p = 4.7e-13).ConclusionThis study detected genomic trypanosome DNA in the CSF independent of the HAT stage and may be consistent with early CNS entry and other scenarios that identify critical knowledge gaps for future studies. Detergent-enhanced LAMP could be applicable for non-invasive African trypanosome detection in human skin and saliva or as an epidemiologic tool for the determination of human (or animal) African trypanosome prevalence in areas where chronically low parasitemias are present.