early AHA News: Traumatic Childhood Increases Lifelong Risk for Heart Disease, Early Death By www.medicinenet.com Published On :: Wed, 29 Apr 2020 00:00:00 PDT Title: AHA News: Traumatic Childhood Increases Lifelong Risk for Heart Disease, Early DeathCategory: Health NewsCreated: 4/28/2020 12:00:00 AMLast Editorial Review: 4/29/2020 12:00:00 AM Full Article
early Early High School Start Times May Hurt Attendance By www.medicinenet.com Published On :: Mon, 4 May 2020 00:00:00 PDT Title: Early High School Start Times May Hurt AttendanceCategory: Health NewsCreated: 5/1/2020 12:00:00 AMLast Editorial Review: 5/4/2020 12:00:00 AM Full Article
early Antibodies Found in Nearly All People Infected by New Coronavirus: Study By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: Antibodies Found in Nearly All People Infected by New Coronavirus: StudyCategory: Health NewsCreated: 5/8/2020 12:00:00 AMLast Editorial Review: 5/8/2020 12:00:00 AM Full Article
early U.S. Jobless Rate at Nearly 15 Percent as Coronavirus Cases Top 1.2 Million By www.medicinenet.com Published On :: Sat, 9 May 2020 00:00:00 PDT Title: U.S. Jobless Rate at Nearly 15 Percent as Coronavirus Cases Top 1.2 MillionCategory: Health NewsCreated: 5/8/2020 12:00:00 AMLast Editorial Review: 5/8/2020 12:00:00 AM Full Article
early Early Oxygen Therapy Vital for Pregnant Patients With COVID-19 By www.webmd.com Published On :: Wed, 06 May 2020 12:36:12 EST Adjust oxygen and fluid therapy thresholds for pregnant patients with severe disease, experts advise; early use of a high-flow nasal cannula and prone positioning may help avoid mechanical ventilation. Full Article
early New Polio Vaccine Promising in Early Test By www.medicinenet.com Published On :: Mon, 27 Apr 2020 00:00:00 PDT Title: New Polio Vaccine Promising in Early TestCategory: Health NewsCreated: 4/24/2020 12:00:00 AMLast Editorial Review: 4/27/2020 12:00:00 AM Full Article
early Researchers Move Toward Once-Yearly Treatment for HIV By www.medicinenet.com Published On :: Fri, 1 May 2020 00:00:00 PDT Title: Researchers Move Toward Once-Yearly Treatment for HIVCategory: Health NewsCreated: 4/30/2020 12:00:00 AMLast Editorial Review: 5/1/2020 12:00:00 AM Full Article
early AHA News: Nearly Killed in OKC Bombing, She Vowed to Change Her Life By www.medicinenet.com Published On :: Fri, 17 Apr 2020 00:00:00 PDT Title: AHA News: Nearly Killed in OKC Bombing, She Vowed to Change Her LifeCategory: Health NewsCreated: 4/16/2020 12:00:00 AMLast Editorial Review: 4/17/2020 12:00:00 AM Full Article
early How Does Early Menopause Affect a Woman's Heart? By www.medicinenet.com Published On :: Fri, 11 Oct 2019 00:00:00 PDT Title: How Does Early Menopause Affect a Woman's Heart?Category: Health NewsCreated: 10/10/2019 12:00:00 AMLast Editorial Review: 10/11/2019 12:00:00 AM Full Article
early AHA News: Estrogen Therapy in Early Menopause May Help Keep Arteries Clear By www.medicinenet.com Published On :: Wed, 4 Mar 2020 00:00:00 PDT Title: AHA News: Estrogen Therapy in Early Menopause May Help Keep Arteries ClearCategory: Health NewsCreated: 3/3/2020 12:00:00 AMLast Editorial Review: 3/4/2020 12:00:00 AM Full Article
early Pot Use Among U.S. Seniors Nearly Doubled in 3 Years By www.medicinenet.com Published On :: Tue, 25 Feb 2020 00:00:00 PDT Title: Pot Use Among U.S. Seniors Nearly Doubled in 3 YearsCategory: Health NewsCreated: 2/24/2020 12:00:00 AMLast Editorial Review: 2/25/2020 12:00:00 AM Full Article
early Global Transcriptome Analysis Identifies a Diagnostic Signature for Early Disseminated Lyme Disease and Its Resolution By mbio.asm.org Published On :: 2020-03-17T01:30:14-07:00 ABSTRACT A bioinformatics approach was employed to identify transcriptome alterations in the peripheral blood mononuclear cells of well-characterized human subjects who were diagnosed with early disseminated Lyme disease (LD) based on stringent microbiological and clinical criteria. Transcriptomes were assessed at the time of presentation and also at approximately 1 month (early convalescence) and 6 months (late convalescence) after initiation of an appropriate antibiotic regimen. Comparative transcriptomics identified 335 transcripts, representing 233 unique genes, with significant alterations of at least 2-fold expression in acute- or convalescent-phase blood samples from LD subjects relative to healthy donors. Acute-phase blood samples from LD subjects had the largest number of differentially expressed transcripts (187 induced, 54 repressed). This transcriptional profile, which was dominated by interferon-regulated genes, was sustained during early convalescence. 6 months after antibiotic treatment the transcriptome of LD subjects was indistinguishable from that of healthy controls based on two separate methods of analysis. Return of the LD expression profile to levels found in control subjects was concordant with disease outcome; 82% of subjects with LD experienced at least one symptom at the baseline visit compared to 43% at the early convalescence time point and only a single patient (9%) at the 6-month convalescence time point. Using the random forest machine learning algorithm, we developed an efficient computational framework to identify sets of 20 classifier genes that discriminated LD from other bacterial and viral infections. These novel LD biomarkers not only differentiated subjects with acute disseminated LD from healthy controls with 96% accuracy but also distinguished between subjects with acute and resolved (late convalescent) disease with 97% accuracy. IMPORTANCE Lyme disease (LD), caused by Borrelia burgdorferi, is the most common tick-borne infectious disease in the United States. We examined gene expression patterns in the blood of individuals with early disseminated LD at the time of diagnosis (acute) and also at approximately 1 month and 6 months following antibiotic treatment. A distinct acute LD profile was observed that was sustained during early convalescence (1 month) but returned to control levels 6 months after treatment. Using a computer learning algorithm, we identified sets of 20 classifier genes that discriminate LD from other bacterial and viral infections. In addition, these novel LD biomarkers are highly accurate in distinguishing patients with acute LD from healthy subjects and in discriminating between individuals with active and resolved infection. This computational approach offers the potential for more accurate diagnosis of early disseminated Lyme disease. It may also allow improved monitoring of treatment efficacy and disease resolution. Full Article
early Estimating the Timing of Early Simian-Human Immunodeficiency Virus Infections: a Comparison between Poisson Fitter and BEAST By mbio.asm.org Published On :: 2020-03-24T01:31:01-07:00 ABSTRACT Many HIV prevention strategies are currently under consideration where it is highly informative to know the study participants’ times of infection. These can be estimated using viral sequence data sampled early in infection. However, there are several scenarios that, if not addressed, can skew timing estimates. These include multiple transmitted/founder (TF) viruses, APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like)-mediated mutational enrichment, and recombination. Here, we suggest a pipeline to identify these problems and resolve the biases that they introduce. We then compare two modeling strategies to obtain timing estimates from sequence data. The first, Poisson Fitter (PF), is based on a Poisson model of random accumulation of mutations relative to the TF virus (or viruses) that established the infection. The second uses a coalescence-based phylogenetic strategy as implemented in BEAST. The comparison is based on timing predictions using plasma viral RNA (cDNA) sequence data from 28 simian-human immunodeficiency virus (SHIV)-infected animals for which the exact day of infection is known. In this particular setting, based on nucleotide sequences from samples obtained in early infection, the Poisson method yielded more accurate, more precise, and unbiased estimates for the time of infection than did the explored implementations of BEAST. IMPORTANCE The inference of the time of infection is a critical parameter in testing the efficacy of clinical interventions in protecting against HIV-1 infection. For example, in clinical trials evaluating the efficacy of passively delivered antibodies (Abs) for preventing infections, accurate time of infection data are essential for discerning levels of the Abs required to confer protection, given the natural Ab decay rate in the human body. In such trials, genetic sequences from early in the infection are regularly sampled from study participants, generally prior to immune selection, when the viral population is still expanding and genetic diversity is low. In this particular setting of early viral growth, the Poisson method is superior to the alternative approach based on coalescent methods. This approach can also be applied in human vaccine trials, where accurate estimates of infection times help ascertain if vaccine-elicited immune protection wanes over time. Full Article
early CDC: Vaccine for recent flu season cut visits to doctors by nearly half By thenationshealth.aphapublications.org Published On :: 2020-05-01T05:00:17-07:00 This season’s flu vaccine was 45% effective overall and 55% effective among children and teens, the Centers for Disease Control and Prevention reported in February. Full Article
early Special Issue for Early Career Researchers: editorial By sjg.lyellcollection.org Published On :: 2019-11-29T02:21:48-08:00 Thematic collection: This article is part of the ‘Early Career Researchers’ available at: https://www.lyellcollection.org/cc/SJG-early-career-research Full Article
early Early and Often: The Need for Comprehensive Discussion of Treatment-Induced Cancer Late Effects By pediatrics.aappublications.org Published On :: 2020-05-01T01:00:46-07:00 Full Article
early Exploring Early Childhood Factors as an Avenue to Address Chronic Peer Victimization By pediatrics.aappublications.org Published On :: 2020-05-01T01:00:46-07:00 Full Article
early Early Childhood Factors Associated With Peer Victimization Trajectories From 6 to 17 Years of Age By pediatrics.aappublications.org Published On :: 2020-05-01T01:00:46-07:00 OBJECTIVES: To describe (1) the developmental trajectories of peer victimization from 6 to 17 years of age and (2) the early childhood behaviors and family characteristics associated with the trajectories. METHODS: We used data from 1760 children enrolled in the Quebec Longitudinal Study of Child Development, a population-based birth cohort. Participants self-reported peer victimization at ages 6, 7, 8, 10, 12, 13, 15, and 17 years. Participants’ behavior and family characteristics were measured repeatedly between ages 5 months and 5 years. RESULTS: We identified 4 trajectories of peer victimization from 6 to 17 years of age: low (32.9%), moderate-emerging (29.8%), childhood-limited (26.2%), and high-chronic (11.1%). Compared with children in the low peer victimization trajectory, children in the other 3 trajectories were more likely to exhibit externalizing behaviors in early childhood, and those in the high-chronic and moderate-emerging trajectories were more likely to be male. Paternal history of antisocial behavior was associated with moderate-emerging (odds ratio [OR] = 1.54; 95% confidence interval [CI] = 1.09–2.19) and high-chronic (OR = 1.93; 95% CI = 1.25–2.99) relative to low peer victimization. Living in a nonintact family in early childhood was associated with childhood-limited (OR = 1.48; 95% CI = 1.11–1.97) and high-chronic (OR = 1.59; 95% CI = 1.09–2.31) relative to low peer victimization. CONCLUSIONS: Early childhood externalizing behaviors and family vulnerabilities were associated with the development of peer victimization. Some children entered the cascade of persistent peer victimization at the beginning of primary school. Support to these children and their families early in life should be an important component of peer victimization preventive interventions. Full Article
early Network Implementation of Guideline for Early Detection Decreases Age at Cerebral Palsy Diagnosis By pediatrics.aappublications.org Published On :: 2020-05-01T01:00:46-07:00 BACKGROUND AND OBJECTIVES: Early diagnosis of cerebral palsy (CP) is critical in obtaining evidence-based interventions when plasticity is greatest. In 2017, international guidelines for early detection of CP were published on the basis of a systematic review of evidence. Our study aim was to reduce the age at CP diagnosis throughout a network of 5 diverse US high-risk infant follow-up programs through consistent implementation of these guidelines. METHODS: The study leveraged plan-do-study-act and Lean methodologies. The primary outcome was age at CP diagnosis. Data were acquired during the corresponding 9-month baseline and quarterly throughout study. Balancing measures were clinic no-show rates and parent perception of the diagnosis visit. Clinic teams conducted strengths, weaknesses, opportunities, and threats analyses, process flow evaluations, standardized assessments training, and parent questionnaires. Performance of a 3- to 4-month clinic visit was a critical process step because it included a Hammersmith Infant Neurologic Examination, a General Movements Assessment, and standardized assessments of motor function. RESULTS: The age at CP diagnosis decreased from a weighted average of 19.5 (95% confidence interval 16.2 to 22.8) to 9.5 months (95% confidence interval 4.5 to 14.6), with P = .008; 3- to 4-month visits per site increased from the median (interquartile range) 14 (5.2–73.7) to 54 (34.5–152.0), with P < .001; and no-show rates were not different. Parent questionnaires revealed positive provider perception with improvement opportunities for information content and understandability. CONCLUSIONS: Large-scale implementation of international guidelines for early detection of CP is feasible in diverse high-risk infant follow-up clinics. The initiative was received positively by families and without adversely affecting clinic operational flow. Additional parent support and education are necessary. Full Article
early Early Endothelial Activation Precedes Glycocalyx Degradation and Microvascular Dysfunction in Experimentally Induced Plasmodium falciparum and Plasmodium vivax Infection [Host Response and Inflammation] By iai.asm.org Published On :: 2020-04-20T08:00:39-07:00 Endothelial activation and microvascular dysfunction are key pathogenic processes in severe malaria. We evaluated the early role of these processes in experimentally induced Plasmodium falciparum and P. vivax infection. Participants were enrolled in induced blood-stage malaria clinical trials. Plasma osteoprotegerin, angiopoietin-2, and von Willebrand Factor (vWF) levels were measured as biomarkers of endothelial activation. Microvascular function was assessed using peripheral arterial tonometry and near-infrared spectroscopy, and the endothelial glycocalyx was assessed by sublingual videomicroscopy and measurement of biomarkers of degradation. Forty-five healthy, malaria-naive participants were recruited from 5 studies. Osteoprotegerin and vWF levels increased in participants following inoculation with P. vivax (n = 16) or P. falciparum (n = 15), with the angiopoietin-2 level also increasing in participants following inoculation with P. falciparum. For both species, the most pronounced increase was seen in osteoprotegerin. This was particularly marked in participants inoculated with P. vivax, where the osteoprotegerin level correlated with the levels of parasitemia and the malaria clinical score. There were no changes in measures of endothelial glycocalyx or microvascular function. Plasma biomarkers of endothelial activation increased in early P. falciparum and P. vivax infection and preceded changes in the endothelial glycocalyx or microvascular function. The more pronounced increase in osteoprotegerin suggests that this biomarker may play a role in disease pathogenesis. Full Article
early The Transcriptional Cofactor VGLL1 Drives Transcription of Human Papillomavirus Early Genes via TEAD1 [Genome Replication and Regulation of Viral Gene Expression] By jvi.asm.org Published On :: 2020-05-04T08:00:47-07:00 The TEAD family of transcription factors requires associating cofactors to induce gene expression. TEAD1 is known to activate the early promoter of human papillomavirus (HPV), but the precise mechanisms of TEAD1-mediated transactivation of the HPV promoter, including its relevant cofactors, remain unexplored. Here, we reveal that VGLL1, a TEAD-interacting cofactor, contributes to HPV early gene expression. Knockdown of VGLL1 and/or TEAD1 led to a decrease in viral early gene expression in human cervical keratinocytes and cervical cancer cell lines. We identified 11 TEAD1 target sites in the HPV16 long control region (LCR) by in vitro DNA pulldown assays; 8 of these sites contributed to the transcriptional activation of the early promoter in luciferase reporter assays. VGLL1 bound to the HPV16 LCR via its interaction with TEAD1 both in vitro and in vivo. Furthermore, introducing HPV16 and HPV18 whole genomes into primary human keratinocytes led to increased levels of VGLL1, due in part to the upregulation of TEADs. These results suggest that multiple VGLL1/TEAD1 complexes are recruited to the LCR to support the efficient transcription of HPV early genes. IMPORTANCE Although a number of transcription factors have been reported to be involved in HPV gene expression, little is known about the cofactors that support HPV transcription. In this study, we demonstrate that the transcriptional cofactor VGLL1 plays a prominent role in HPV early gene expression, dependent on its association with the transcription factor TEAD1. Whereas TEAD1 is ubiquitously expressed in a variety of tissues, VGLL1 displays tissue-specific expression and is implicated in the development and differentiation of epithelial lineage tissues, where HPV gene expression occurs. Our results suggest that VGLL1 may contribute to the epithelial specificity of HPV gene expression, providing new insights into the mechanisms that regulate HPV infection. Further, VGLL1 is also critical for the growth of cervical cancer cells and may represent a novel therapeutic target for HPV-associated cancers. Full Article
early In utero MRI identifies consequences of early-gestation alcohol drinking on fetal brain development in rhesus macaques [Neuroscience] By www.pnas.org Published On :: 2020-05-05T10:31:24-07:00 One factor that contributes to the high prevalence of fetal alcohol spectrum disorder (FASD) is binge-like consumption of alcohol before pregnancy awareness. It is known that treatments are more effective with early recognition of FASD. Recent advances in retrospective motion correction for the reconstruction of three-dimensional (3D) fetal brain MRI... Full Article
early Loss of the neural-specific BAF subunit ACTL6B relieves repression of early response genes and causes recessive autism [Neuroscience] By www.pnas.org Published On :: 2020-05-05T10:31:24-07:00 Synaptic activity in neurons leads to the rapid activation of genes involved in mammalian behavior. ATP-dependent chromatin remodelers such as the BAF complex contribute to these responses and are generally thought to activate transcription. However, the mechanisms keeping such “early activation” genes silent have been a mystery. In the course... Full Article
early The hydrodynamic regime drives flow reversals in suction-feeding larval fishes during early ontogeny [RESEARCH ARTICLE] By jeb.biologists.org Published On :: 2020-04-06T07:24:08-07:00 Krishnamoorthy Krishnan, Asif Shahriar Nafi, Roi Gurka, and Roi HolzmanFish larvae are the smallest self-sustaining vertebrates. As such, they face multiple challenges that stem from their minute size, and from the hydrodynamic regime in which they dwell. This regime, of intermediate Reynolds numbers, was shown to affect the swimming of larval fish and impede their ability to capture prey. Prey capture is impeded because smaller larvae produce weaker suction flows, exerting weaker forces on the prey. Previous observations on feeding larvae also showed prey exiting the mouth after initially entering it (hereafter "in-and-out"), although the mechanism causing such failures had been unclear. In this study, we used numerical simulations to investigate the hydrodynamic mechanisms responsible for the failure to feed caused by this in-and-out prey movement. Detailed kinematics of the expanding mouth during prey capture by larval Sparus aurata were used to parameterize age-specific numerical models of the flows inside the mouth. These models revealed that for small larvae which expand their mouth slowly, fluid entering the mouth cavity is expelled through the mouth before it is closed, resulting in flow reversal at the orifice. This relative efflux of water through the mouth was >8% of the influx through the mouth for younger ages. However similar effluxes were found when we simulated slow strikes by larger fish. The simulations can explain the observations of larval fish failing to fish due to the in-and-out movement of the prey. These results further highlight the importance of transporting the prey from the gape deeper into the mouth cavity in determining suction-feeding success. Full Article
early Non-photopic and photopic visual cycles differentially regulate immediate, early, and late phases of cone photoreceptor-mediated vision [Molecular Bases of Disease] By www.jbc.org Published On :: 2020-05-08T03:41:14-07:00 Cone photoreceptors in the retina enable vision over a wide range of light intensities. However, the processes enabling cone vision in bright light (i.e. photopic vision) are not adequately understood. Chromophore regeneration of cone photopigments may require the retinal pigment epithelium (RPE) and/or retinal Müller glia. In the RPE, isomerization of all-trans-retinyl esters to 11-cis-retinol is mediated by the retinoid isomerohydrolase Rpe65. A putative alternative retinoid isomerase, dihydroceramide desaturase-1 (DES1), is expressed in RPE and Müller cells. The retinol-isomerase activities of Rpe65 and Des1 are inhibited by emixustat and fenretinide, respectively. Here, we tested the effects of these visual cycle inhibitors on immediate, early, and late phases of cone photopic vision. In zebrafish larvae raised under cyclic light conditions, fenretinide impaired late cone photopic vision, while the emixustat-treated zebrafish unexpectedly had normal vision. In contrast, emixustat-treated larvae raised under extensive dark-adaptation displayed significantly attenuated immediate photopic vision concomitant with significantly reduced 11-cis-retinaldehyde (11cRAL). Following 30 min of light, early photopic vision was recovered, despite 11cRAL levels remaining significantly reduced. Defects in immediate cone photopic vision were rescued in emixustat- or fenretinide-treated larvae following exogenous 9-cis-retinaldehyde supplementation. Genetic knockout of Des1 (degs1) or retinaldehyde-binding protein 1b (rlbp1b) did not eliminate photopic vision in zebrafish. Our findings define molecular and temporal requirements of the nonphotopic or photopic visual cycles for mediating vision in bright light. Full Article
early Basement-cover relationships and deformation in the Northern Paraguai Belt, central Brazil: implications for the Neoproterozoic-early Paleozoic history of western Gondwana By jgs.lyellcollection.org Published On :: 2020-05-04T02:10:48-07:00 The Northern Paraguai Belt, at the SE border of the Amazonian Craton, central Brazil, has been interpreted as a Brasiliano–Pan-African (c. 650–600 Ma) belt with a foreland basin, recording collisional polyphase tectonism and greenschist-facies metamorphism extending from the late Precambrian to the Cambrian–Ordovician. New structural investigations indicate that the older metasedimentary rocks of the Cuiabá Group represent a Tonian–Cryogenian basement assemblage deformed in two contemporaneous fault-bounded structural sub-domains of wrench-dominated (rake <10°) and contraction-dominated (rake ~30–40°) sinistral transpression, with tectonic vergence towards the SE. The younger late Cryogenian to early Cambrian sedimentary rocks lying to the NW of the Cuiabá Group are non-metamorphic and display only pervasive brittle transtension characterized by normal-oblique faults, fractures and forced drag folds with no consistent vergence pattern. Our analyses suggest that an unconformity separates the metasedimentary Cuiabá Group basement of the Northern Paraguai Belt from the unmetamorphosed sedimentary cover. It is proposed that the latter units were deposited during a post-glacial marine transgression (after c. 635 Ma) in a post-collisional basin. The Paraguai Belt basement and its post-collisional sedimentary cover share a number of significant geological similarities with sequences in the Bassarides Belt and Taoudéni Basin in the SW portion of the West African Craton. Full Article
early Is APOE {varepsilon}4 associated with cognitive performance in early MS? By nn.neurology.org Published On :: 2020-05-01T12:45:10-07:00 Objective To assess the impact of APOE polymorphisms on cognitive performance in patients newly diagnosed with clinically isolated syndrome (CIS) or relapsing-remitting MS (RRMS). Methods This multicenter cohort study included 552 untreated patients recently diagnosed with CIS or RRMS according to the 2005 revised McDonald criteria. The single nucleotide polymorphisms rs429358 (4) and rs7412 (2) of the APOE haplotype were assessed by allelic discrimination assays. Cognitive performance was evaluated using the 3-second paced auditory serial addition test and the Multiple Sclerosis Inventory Cognition (MUSIC). Sum scores were calculated to approximate the overall cognitive performance and memory-centered cognitive functions. The impact of the APOE carrier status on cognitive performance was assessed using multiple linear regression models, also including demographic, clinical, MRI, and lifestyle factors. Results APOE 4 homozygosity was associated with lower overall cognitive performance, whereas no relevant association was observed for APOE 4 heterozygosity or APOE 2 carrier status. Furthermore, higher disability levels, MRI lesion load, and depressive symptoms were associated with lower cognitive performance. Patients consuming alcohol had higher test scores than patients not consuming alcohol. Female sex, lower disability, and alcohol consumption were associated with better performance in the memory-centered subtests of MUSIC, whereas no relevant association was observed for APOE carrier status. Conclusion Along with parameters of a higher disease burden, APOE 4 homozygosity was identified as a potential predictor of cognitive performance in this large cohort of patients with CIS and early RRMS. Full Article
early A Fully Automated Multiplex Assay for Diagnosis of Lyme Disease with High Specificity and Improved Early Sensitivity [Immunoassays] By jcm.asm.org Published On :: 2020-04-23T08:00:29-07:00 Lyme borreliosis is a tick-borne disease caused by the Borrelia burgdorferi sensu lato complex. Bio-Rad Laboratories has developed a fully automated multiplex bead-based assay for the detection of IgM and IgG antibodies to B. burgdorferi. The BioPlex 2200 Lyme Total assay exhibits an improved rate of seropositivity in patients with early Lyme infection. Asymptomatic subjects from endemic and nonendemic origins demonstrated a seroreactivity rate of approximately 4% that was similar to other commercial assays evaluated in this study. Coupled to this result was the observation that the Lyme Total assay retained a high first-tier specificity of 96% while demonstrating a relatively high sensitivity of 91% among a well-characterized CDC Premarketing Lyme serum panel. The Lyme Total assay also performs well under a modified two-tier algorithm (sensitivity, 84.4 to 88.9%; specificity, 98.4 to 99.5%). Furthermore, the new assay is able to readily detect early Lyme infection in patient samples from outside North America. Full Article
early Early 18F-FDG PET/CT Response Predicts Survival in Relapsed or Refractory Hodgkin Lymphoma Treated with Nivolumab By jnm.snmjournals.org Published On :: 2020-05-01T06:31:37-07:00 Monoclonal antibodies (mAbs) against programmed cell death 1 (PD-1), such as nivolumab and pembrolizumab, are associated with high response rates in patients with relapsed or refractory classic Hodgkin lymphoma (HL). To date, no prognostic factor for overall survival (OS) has been established with these agents in HL. We examined whether the first early response assessment evaluated using 18F-FDG PET/CT may be associated with OS in this setting. Methods: This retrospective study included 45 patients from 34 institutions. In a masked, centralized review, 3 independent radiologists classified PET/CT scans obtained at a median of 2.0 mo (interquartile range, 1.7–3.7 mo) after nivolumab initiation using existing criteria (i.e., 2014 Lugano classification and 2016 LYRIC). Patients were classified according to 4 possible response categories: complete metabolic response (CMR), partial metabolic response (PMR), no metabolic response (NMR), or progressive metabolic disease (PMD). Because the OS of patients with NMR and PMR was similar, they were grouped together. OS was estimated using the Kaplan–Meier method and compared between groups using log-rank testing. Results: Eleven patients (24%) died after a median follow-up of 21.2 mo. The classification was identical between Lugano and LYRIC because all 16 progression events classified as indeterminate response per LYRIC were confirmed on subsequent evaluations. Both Lugano and LYRIC classified patients as CMR in 13 cases (29%), PMD in 16 (36%), NMR in 4 (9%), and PMR in 12 (27%). The 2-y OS probability was significantly different in patients with PMD (0.53; 95% confidence interval [95%CI], 0.32–0.87), NMR or PMR (0.80; 95%CI, 0.63–1.00), and CMR (1.00; 95%CI, 1.00–1.00) in the overall population (P = 0.02, 45 patients), as well as according to a landmark analysis at 3 mo (P = 0.05, 32 patients). Conclusion: In relapsed or refractory HL patients treated with anti-PD-1 mAbs, the first early PET/CT assessment using either Lugano or LYRIC predicted OS and allowed early risk stratification, suggesting that PET/CT might be used to develop risk-adapted strategies. Full Article
early Mobilising community networks for early identification of tuberculosis and treatment initiation in Cambodia: an evaluation of a seed-and-recruit model By openres.ersjournals.com Published On :: 2020-05-04T00:29:32-07:00 Background and objectives The effects of active case finding (ACF) models that mobilise community networks for early identification and treatment of tuberculosis (TB) remain unknown. We investigated and compared the effect of community-based ACF using a seed-and-recruit model with one-off roving ACF and passive case finding (PCF) on the time to treatment initiation and identification of bacteriologically confirmed TB. Methods In this retrospective cohort study conducted in 12 operational districts in Cambodia, we assessed relationships between ACF models and: 1) the time to treatment initiation using Cox proportional hazards regression; and 2) the identification of bacteriologically confirmed TB using modified Poisson regression with robust sandwich variance. Results We included 728 adults with TB, of whom 36% were identified via the community-based ACF using a seed-and-recruit model. We found community-based ACF using a seed-and-recruit model was associated with shorter delay to treatment initiation compared to one-off roving ACF (hazard ratio 0.81, 95% CI 0.68–0.96). Compared to one-off roving ACF and PCF, community-based ACF using a seed-and-recruit model was 45% (prevalence ratio (PR) 1.45, 95% CI 1.19–1.78) and 39% (PR 1.39, 95% CI 0.99–1.94) more likely to find and detect bacteriologically confirmed TB, respectively. Conclusion Mobilising community networks to find TB cases was associated with early initiation of TB treatment in Cambodia. This approach was more likely to find bacteriologically confirmed TB cases, contributing to the reduction of risk of transmission within the community. Full Article
early Evidence from a mouse model on the dangers of thirdhand electronic cigarette exposure during early life By openres.ersjournals.com Published On :: 2020-04-19T07:30:11-07:00 Electronic cigarettes (e-cigarettes) have been used in many countries for >10 years and in this time, there has been a division of opinions amongst both the general public and health professionals regarding the benefit or harms of e-cigarettes. Prior to the reporting of a new phenomenon known as vaping-associated pulmonary injury (VAPI), public opinion about the relative harm of e-cigarettes were increasing but they were perceived as less harmful than cigarettes by one third of people [1]. The recent cases of severe illness and death attributable to VAPI were first described in September 2019 [2]. VAPI appears to be related to either the addition of cannabis/cannabis derivates or vitamin E acetate [3], and as such has not caused radical swing away from the use of e-cigarettes without cannabis or cannabis derivates. Full Article
early Early Childhood Antibiotic Treatment for Otitis Media and Other Respiratory Tract Infections Is Associated With Risk of Type 1 Diabetes: A Nationwide Register-Based Study With Sibling Analysis By care.diabetesjournals.org Published On :: 2020-04-20T12:00:32-07:00 OBJECTIVE The effect of early-life antibiotic treatment on the risk of type 1 diabetes is debated. This study assessed this question, applying a register-based design in children up to age 10 years including a large sibling-control analysis. RESEARCH DESIGN AND METHODS All singleton children (n = 797,318) born in Sweden between 1 July 2005 and 30 September 2013 were included and monitored to 31 December 2014. Cox proportional hazards models, adjusted for parental and perinatal characteristics, were applied, and stratified models were used to account for unmeasured confounders shared by siblings. RESULTS Type 1 diabetes developed in 1,297 children during the follow-up (median 4.0 years [range 0–8.3]). Prescribed antibiotics in the 1st year of life (23.8%) were associated with an increased risk of type 1 diabetes (adjusted hazard ratio [HR] 1.19 [95% CI 1.05–1.36]), with larger effect estimates among children delivered by cesarean section (P for interaction = 0.016). The association was driven by exposure to antibiotics primarily used for acute otitis media and respiratory tract infections. Further, we found an association of antibiotic prescriptions in pregnancy (22.5%) with type 1 diabetes (adjusted HR 1.15 [95% CI 1.00–1.32]). In general, sibling analysis supported these results, albeit often with statistically nonsignificant associations. CONCLUSIONS Dispensed prescription of antibiotics, mainly for acute otitis media and respiratory tract infections, in the 1st year of life is associated with an increased risk of type 1 diabetes before age 10 years, most prominently in children delivered by cesarean section. Full Article
early Markers of Early Life Infection in Relation to Adult Diabetes: Prospective Evidence From a National Birth Cohort Study Over Four Decades By care.diabetesjournals.org Published On :: 2020-04-20T12:00:33-07:00 Full Article
early Association of early disease progression and very poor survival in the GALLIUM study in follicular lymphoma: benefit of obinutuzumab in reducing the rate of early progression By www.haematologica.org Published On :: 2020-05-01T00:05:42-07:00 Full Article
early Early growth response 1 regulates hematopoietic support and proliferation in human primary bone marrow stromal cells By www.haematologica.org Published On :: 2020-05-01T00:05:41-07:00 Human bone marrow stromal cells (BMSC) are key elements of the hematopoietic environment and they play a central role in bone and bone marrow physiology. However, how key stromal cell functions are regulated is largely unknown. We analyzed the role of the immediate early response transcription factor EGR1 as key stromal cell regulator and found that EGR1 was highly expressed in prospectively-isolated primary BMSC, down-regulated upon culture, and low in non-colony-forming CD45neg stromal cells. Furthermore, EGR1 expression was lower in proliferative regenerating adult and fetal primary cells compared to adult steady-state BMSC. Overexpression of EGR1 in stromal cells induced potent hematopoietic stroma support as indicated by an increased production of transplantable CD34+CD90+ hematopoietic stem cells in expansion co-cultures. The improvement in bone marrow stroma support function was mediated by increased expression of hematopoietic supporting genes, such as VCAM1 and CCL28. Furthermore, EGR1 overexpression markedly decreased stromal cell proliferation whereas EGR1 knockdown caused the opposite effects. These findings thus show that EGR1 is a key stromal transcription factor with a dual role in regulating proliferation and hematopoietic stroma support function that is controlling a genetic program to co-ordinate the specific functions of BMSC in their different biological contexts. Full Article
early Early high plasma ST2, the decoy IL-33 receptor, in children undergoing hematopoietic cell transplantation is associated with the development of post-transplant diabetes mellitus By www.haematologica.org Published On :: 2020-05-01T00:05:42-07:00 Full Article
early Insight into the structure and tasks of the Early Career Members Committee of the European Respiratory Society By breathe.ersjournals.com Published On :: 2020-03-18T06:44:39-07:00 The Early Career Members Committee (ECMC) of the European Respiratory Society (ERS) consists of 14 members, one Early Career Member (ECM) representative per assembly. In September 2019, seven recently elected representatives joined the ECMC. An overview is given of the tasks performed by each representative within the ECMC (table 1). In addition, a short summary about the content of these tasks is provided. Full Article
early Promoting Early Inpatient Transition From IV to Oral Antibiotics By aapgrandrounds.aappublications.org Published On :: 2020-05-01T00:59:36-07:00 Full Article
early Early Bactericidal Activity Trial of Nitazoxanide for Pulmonary Tuberculosis [Clinical Therapeutics] By aac.asm.org Published On :: 2020-04-21T08:01:09-07:00 This study was conducted in treatment-naive adults with drug-susceptible pulmonary tuberculosis in Port-au-Prince, Haiti, to assess the safety, bactericidal activity, and pharmacokinetics of nitazoxanide (NTZ). This was a prospective phase II clinical trial in 30 adults with pulmonary tuberculosis. Twenty participants received 1 g of NTZ orally twice daily for 14 days. A control group of 10 participants received standard therapy over 14 days. The primary outcome was the change in time to culture positivity (TTP) in an automated liquid culture system. The most common adverse events seen in the NTZ group were gastrointestinal complaints and headache. The mean change in TTP in sputum over 14 days in the NTZ group was 3.2 h ± 22.6 h and was not statistically significant (P = 0.56). The mean change in TTP in the standard therapy group was significantly increased, at 134 h ± 45.2 h (P < 0.0001). The mean NTZ MIC for Mycobacterium tuberculosis isolates was 12.3 μg/ml; the mean NTZ maximum concentration (Cmax) in plasma was 10.2 μg/ml. Negligible NTZ levels were measured in sputum. At the doses used, NTZ did not show bactericidal activity against M. tuberculosis. Plasma concentrations of NTZ were below the MIC, and its negligible accumulation in pulmonary sites may explain the lack of bactericidal activity. (This study has been registered at ClinicalTrials.gov under identifier NCT02684240.) Full Article
early Serum PIWI-Interacting RNAs piR-020619 and piR-020450 Are Promising Novel Biomarkers for Early Detection of Colorectal Cancer By cebp.aacrjournals.org Published On :: 2020-05-01T00:05:36-07:00 Background: Early diagnosis can significantly reduce colorectal cancer deaths. We sought to identify serum PIWI-interacting RNAs (piRNAs) that could serve as sensitive and specific noninvasive biomarkers for early colorectal cancer detection. Methods: We screened the piRNA expression profile in sera from 7 patients with colorectal cancer and 7 normal controls using small RNA sequencing. Differentially expressed piRNAs were measured in a training cohort of 140 patients with colorectal cancer and 140 normal controls using reverse transcription quantitative PCR. The identified piRNAs were evaluated in two independent validation cohorts of 180 patients with colorectal cancer and 180 normal controls. Finally, the diagnostic value of the identified piRNAs for colorectal adenoma (CRA) was assessed, and their expression was measured in 50 patients with lung cancer, 50 with breast cancer, and 50 with gastric cancer. Results: The piRNAs piR-020619 and piR-020450 were consistently elevated in sera of patients with colorectal cancer as compared with controls. A predicative panel based on the two piRNAs was established that displayed high diagnostic accuracy for colorectal cancer detection. The two-piRNA panel could detect small-size and early-stage colorectal cancer with an area under the ROC curve of 0.863 and 0.839, respectively. Combined use of the two piRNAs could effectively distinguish CRA from controls. Aberrant elevation of the two piRNAs was not observed in sera of patients with lung, breast, and gastric cancer. Conclusions: Serum piR-020619 and piR-020450 show a strong potential as colorectal cancer-specific early detection biomarkers. Impact: The field of circulating piRNAs could allow for novel tumor biomarker development. Full Article
early A Systematic Review on Cost-effectiveness Studies Evaluating Ovarian Cancer Early Detection and Prevention Strategies By cancerpreventionresearch.aacrjournals.org Published On :: 2020-05-04T05:35:14-07:00 Ovarian cancer imposes a substantial health and economic burden. We systematically reviewed current health-economic evidence for ovarian cancer early detection or prevention strategies. Accordingly, we searched relevant databases for cost-effectiveness studies evaluating ovarian cancer early detection or prevention strategies. Study characteristics and results including quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICER) were summarized in standardized evidence tables. Economic results were transformed into 2017 Euros. The included studies (N = 33) evaluated ovarian cancer screening, risk-reducing interventions in women with heterogeneous cancer risks and genetic testing followed by risk-reducing interventions for mutation carriers. Multimodal screening with a risk-adjusted algorithm in postmenopausal women achieved ICERs of 9,800–81,400 Euros/QALY, depending on assumptions on mortality data extrapolation, costs, test performance, and screening frequency. Cost-effectiveness of risk-reducing surgery in mutation carriers ranged from cost-saving to 59,000 Euros/QALY. Genetic testing plus risk-reducing interventions for mutation carriers ranged from cost-saving to 54,000 Euros/QALY in women at increased mutation risk. Our findings suggest that preventive surgery and genetic testing plus preventive surgery in women at high risk for ovarian cancer can be considered effective and cost-effective. In postmenopausal women from the general population, multimodal screening using a risk-adjusted algorithm may be cost-effective. Full Article
early Sci-Fi Action Platformer Dark Light Launches May 8 for Steam Early Access, Later for Switch By feedproxy.google.com Published On :: Thu, 07 May 2020 15:15:32 GMT Developer Mirari & Co. announced the science-fiction action platformer Dark Light for Windows PC via Steam Early Access on May 8 and later for the Nintendo Switch when the game leaves Steam Early Access. Mirari & Co. is looking to release the game within one year of the Steam Early Access release, however, it depends "on how we are taking players suggestions and advice to shaping the game." View the latest trailer of the game below: Here is an overview of the game: Dark Light is a science-fiction action-platformer with unique gameplay. Explore an apocalyptic cyberpunk world full of supernatural beings. Encounter and defeat creatures of darkness invisible to the naked eye, detected only with the light source from your drone. Experience the horror and feel their presence as they surround you. As a Dark Hunter you were dropped into a wreaked world. To survive, you need to equip yourself, fight your way through, and collect ‘shards’ from killing supernatural creatures to reinforce your energy. Through survival, you will explore the mysterious dark zones of the apocalypse world. Key Features: Cinematic quality graphic, detailed characters and environment design, and vivid animation with lush visual effect. A variety of range, melee, and throwable weapons; unique items; and multiple ways to upgrade weapons, special equipment, and the player to shape your own character skills. Non-linear map structure for you to choose your own path to explore the dark zones. Encounter horrifying supernatural enemies, fearsome bosses, and friendly NPCs, and fight with invisible creatures that can only be seen in a special light source. Detect invisible enemies and reveal hidden paths with the special light source from your drone. A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.Full Article - https://www.vgchartz.com/article/443411/sci-fi-action-platformer-dark-light-launches-may-8-for-steam-early-access-later-for-switch/ Full Article Analysis Charts Industry
early Neutrinos determined where galaxies formed in the early universe By www.newscientist.com Published On :: Fri, 06 Mar 2020 11:00:29 +0000 In the early universe, particles called neutrinos had a starring role in determining where galaxy clusters formed and which elements were created when stars exploded Full Article
early Black hole from the early universe is blasting us with a powerful jet By www.newscientist.com Published On :: Fri, 06 Mar 2020 17:53:22 +0000 A huge black hole from when the universe was less than a billion years old is shooting a powerful jet at Earth, and studying it could help us understand the young cosmos Full Article
early Nearly 90 coronavirus cases reported at Polyus unit in Siberia By news.yahoo.com Published On :: Sat, 09 May 2020 05:32:17 -0400 Full Article
early Early Devonian Fossil Provides Earliest Evidence for Advanced Reproductive Biology in Land Plants By feedproxy.google.com Published On :: Wed, 06 May 2020 18:26:20 +0000 A species of plant that grew about 400 million years ago (Early Devonian period) produced a spectrum of spore sizes, which is an essential innovation necessary for all advanced plant reproductive strategies, including seeds and flowers. The Devonian period is one of the most important time periods for the evolution of land plants. It witnessed [...] Full Article Paleontology Barinophyte Campbellton Formation Canada Chaleuria Devonian Heterospory Plant Reproductive behavior Sporangia Spore
early Deep, Perennial or Semi-Perennial Rivers Flowed on Early Mars By feedproxy.google.com Published On :: Thu, 07 May 2020 15:24:54 +0000 While the present-day Martian surface is generally dry and cold, its sedimentary rocks contain compelling evidence for the former presence of liquid water. According to a new analysis of orbital images of 3.7-billion-year-old sedimentary layers at Izola mensa, an outcrop in the northwestern rim of the Hellas impact crater on Mars, deep rivers were active [...] Full Article Planetary Science Space Exploration Face on Mars Hellas basin Hellas Planitia HiRISE Izola mensa Mars Mars Reconnaissance Orbiter NASA Noachian River Solar System Water
early Higher step count linked to lower yearly risk of death, up to a point By www.newscientist.com Published On :: Tue, 24 Mar 2020 14:56:12 +0000 An analysis of the daily steps taken by about 5000 people in the US has found that a higher step count is linked to a lower yearly risk of death, although the effect tails off above 12,000 steps Full Article
early Blood test shows promise for detecting the deadliest cancers early By www.newscientist.com Published On :: Tue, 31 Mar 2020 00:01:43 +0000 A blood test developed and checked using blood samples from 4000 people can accurately detect more than 50 cancer types Full Article
early 'Great entertainer' Stokes clearly deserving of world's best honour, says Ford By in.news.yahoo.com Published On :: Sat, 09 May 2020 08:08:34 -0500 Graham Ford hailed Ben Stokes as a "great entertainer" after the England all-rounder's recent recognition by Wisden. Full Article