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Non-invasive prenatal testing (NIPT) for the detection of foetal aneuploidy through analysis of cell-free DNA (cfDNA) in maternal blood is offered routinely by many healthcare providers across the developed world. This testing has recently been recommended for evaluative implementation in the UK National Health Service (NHS) foetal anomaly screening pathway as a contingent screen following an increased risk of trisomy 21, 18 or 13. In preparation for delivering a national service, we have implemented cfDNA-based NIPT in our Regional Genetics Laboratory. Here, we describe our validation and verification processes and initial experiences of the technology prior to rollout of a national screening service.
Data are presented from more than 1000 patients (215 retrospective and 840 prospective) from ‘high- and low-risk pregnancies’ with outcome data following birth or confirmatory invasive prenatal sampling. NIPT was by the Illumina Verifi® test.
Our data confirm a high-fidelity service with a failure rate of ~0.24% and a high sensitivity and specificity for the detection of foetal trisomy 13, 18 and 21. Secondly, the data show that a significant proportion of patients continue their pregnancies without prenatal invasive testing or intervention after receiving a high-risk cfDNA-based result. A total of 46.5% of patients referred to date were referred for reasons other than high screen risk. Ten percent (76/840 clinical service referrals) of patients were referred with ultrasonographic finding of a foetal structural anomaly, and data analysis indicates high- and low-risk scan indications for NIPT.
NIPT can be successfully implemented into NHS regional genetics laboratories to provide high-quality services. NHS provision of NIPT in patients with high-risk screen results will allow for a reduction of invasive testing and partially improve equality of access to cfDNA-based NIPT in the pregnant population. Patients at low risk for a classic trisomy or with other clinical indications are likely to continue to access cfDNA-based NIPT as a private test.
The use of cover crops in soybean production systems has increased in recent years. There are many questions surrounding cover crops—specifically about benefits to crop production and most effective herbicides for spring termination. No studies evaluating cover crop termination have been conducted across a wide geographic area, to our knowledge. Therefore, field experiments were conducted in 2016 and 2017 in Arkansas, Indiana, Mississippi, Missouri, and Wisconsin for spring termination of regionally specific cover crops. Glyphosate-, glufosinate-, and paraquat-containing treatments were applied between April 15 and April 29 in 2016 and April 10 and April 20 in 2017. Visible control of cover crops was determined 28 days after treatment. Glyphosate-containing herbicide treatments were more effective than paraquat- and glufosinate-containing treatments, providing 71% to 97% control across all site years. Specifically, glyphosate at 1.12 kg ha−1 applied alone or with 2,4-D at 0.56 kg ha−1, saflufenacil at 0.025 kg ha−1, or clethodim at 0.56 kg ha−1 provided the most effective control on all grass cover crop species. Glyphosate-, paraquat-, or glufosinate-containing treatments were generally most effective on broadleaf cover crop species when applied with 2,4-D or dicamba. Results from this research indicate that proper herbicide selection is crucial to successfully terminate cover crops in the spring.
We derive the surface and basal radar reflectance and backscatter coefficients of the southern McMurdo Ice Shelf (SMIS) and part of the nearby Ross Ice Shelf (RIS), Antarctica, from radar statistical reconnaissance using a 60-MHZ airborne survey. The surface coefficients are further inverted in terms of snow density and roughness, providing a spatial distribution of the processes contributing to the surface boundary conditions. We disentangle the basal coefficients from surface transmission losses, and we provide the basal coherent content, an indicator of the boundary geometric disorder that is also self-corrected from englacial attenuation. The basal radar properties exhibit sharp gradients along specific iso-depths, suggesting an abrupt modification of the ice composition and geometric structure. We interpret this behavior as locations where the pressure-melting point is reached, outlining fields of freezing and melting ice. Basal steps are observed at both SMIS and RIS, suggesting a common geometric expression of widespread basal processes. This technique offers a simultaneous view of both the surface and basal boundary conditions to help investigate the ice-shelf stability, while its application to airborne data significantly improves coverage of the difficult-to-observe ice–ocean boundary. It also provides constraints on thermohaline circulation in ice shelves cavities, which are analogs for ice-covered ocean worlds.
Introduction: Telephone Triage Services (TTS) manage phone calls from the public regarding general medical problems and provide telephone advice. This telephone based care can overlap with care provided by Poison Centres. Our objective was to examine the impact of a provincial 811 TTS on the IWK Regional Poison Centre (RPC). Methods: This is a retrospective descriptive study using interrupted time series methodology. We compared monthly IWK RPC call volume in the pre-811 era (January 2007-July 2009) and the post-811 era (September 2009-December 2017). We summarized the characteristics of callers who accessed the IWK RPC in terms of client age, sex, intentionality, time of day, call disposition and outcome. Caller characteristics were compared between the pre- and post-811 eras using chi-square test for categorical variables. We used segmented regression analysis to evaluate changes in slope of call volume in the pre- and post 811 eras. The Durbin-Watson statistic was performed to test for serial correlation and the Dickey-Fuller test to investigate seasonality. Results: The dataset included 82683 calls to the IWK RPC – 27028 pre-811 and 55655 post-811. Overall, 55% of calls were for female clients and the largest age group was children aged 0-5 years (37%). Most calls originated from home (47%), followed by a health care facility (23%). Most calls were managed at home (65%). Less than 3% of calls resulted in major effect or death. The Durbin Watson statistic was not statistically significant (p = 0.94). The Dickey-Fuller test indicated series stationarity (p = 0.001). There was no statistically significant change in call volume to the IWK RPC due to the introduction of 811 (p = 0.39). There was no significant variation by time of day, day of week or month, with most calls occurring in the evening. There were significantly more calls regarding intentional ingestions in the post-811 era (23% vs. 19% pre-811, p < .001). Outcomes in the pre and post 811 eras were as follows: minor/no effect/non-toxic/minimal 80% vs. 78%; moderate 7% vs. 10%; and, major/death 1.7% vs. 2.0%. Conclusion: The introduction of a TTS did not change call volumes at our RPC. The increase in the percentage of calls about intentional ingestions may reflect an increase in call acuity as the 811-TTS likely manages calls about minor/non-toxic ingestions without consulting with the RPC. Our future research will examine the nature of poison related calls to the 811-TTS.
In recent years, the use of cover crops has increased in U.S. crop production systems. An important aspect of successful cover crop establishment is the preceding crop and herbicide program, because some herbicides have the potential to persist in the soil for several months. Few studies have been conducted to evaluate the sensitivity of cover crops to common residual herbicides used in soybean production. The same field experiment was conducted in 2016 in Arkansas, Illinois, Indiana, Missouri, Tennessee, and Wisconsin, and repeated in Arkansas, Illinois, Indiana, Mississippi, and Missouri in 2017 to evaluate the potential of residual soybean herbicides to carryover and reduce cover crop establishment. Herbicides applied during the soybean growing season included acetochlor; acetochlor plus fomesafen; chlorimuron plus thifensulfuron; fomesafen; fomesafen plus S-metolachlor followed by acetochlor; imazethapyr; pyroxasulfone; S-metolachlor; S-metolachlor plus fomesafen; sulfentrazone plus S-metolachlor; sulfentrazone plus S-metolachlor followed by fomesafen plus S-metolachlor; and sulfentrazone plus S-metolachlor followed by fomesafen plus S-metolachlor followed by acetochlor. Across all herbicide treatments, the sensitivity of cover crops to herbicide residues in the fall, from greatest to least, was forage radish = turnip > annual ryegrass = winter oat = triticale > cereal rye = Austrian winter pea = hairy vetch = wheat > crimson clover. Fomesafen (applied 21 and 42 days after planting [(DAP]); chlorimuron plus thifensulfuron and pyroxasulfone applied 42 DAP; sulfentrazone plus S-metolachlor followed by fomesafen plus S-metolachlor; and sulfentrazone plus S-metolachlor followed by fomesafen plus S-metolachlor followed by acetochlor caused the highest visual ground cover reduction to cover crop species at the fall rating. Study results indicate cover crops are most at risk when following herbicide applications in soybean containing certain active ingredients such as fomesafen, but overall there is a fairly low risk of cover crop injury from residual soybean herbicides applied in the previous soybean crop.
OBJECTIVES/SPECIFIC AIMS: The central goal of this proposal is to characterize the mechanisms that mediate success or failure of immature intestinal barrier in necrotizing enterocilitis. METHODS/STUDY POPULATION: To do this, I will utilize stem cell derived human intestinal organoids (HIOs), an innovative model of the immature intestine, and a cohort of bacterial isolates collected from premature infants who developed NEC to interrogate the cause-effect relationship of these strains on maintenance of the intestinal barrier. I hypothesize that the epithelial response to bacterial colonization is strain-dependent and results in differences in inflammatory signaling that shape epithelial barrier function in the immature intestine. RESULTS/ANTICIPATED RESULTS: Preliminary data shows that colonization of HIOs with different bacteria leads to species-specific changes in barrier function, and some species selectively damage the epithelial barrier while others enhance epithelial barrier function. I have identified key inflammatory signals that serve as central drivers of intestinal barrier function. DISCUSSION/SIGNIFICANCE OF IMPACT: Characterization of this process is expected to substantially advance scientific understanding of early events in NEC pathogenesis and lead to new opportunities for targeted therapeutic intervention to accelerate barrier maturation or prevent hyperinflammatory reactivity in the neonatal intestine. The research proposed in this application represents an entirely novel approach to studying host-microbial interactions in the immature. Conceptually, this novel translational approach will help to define the pivotal role of colonizing bacteria in initiating epithelial inflammation in NEC patients.
The aim of the study was to examine racism and the Pinkerton syndrome in Singapore. Specifically, the study examined the effects of race on hiring decisions in a simulated hiring decision task. Participants were 171 (61% males) Singaporean Chinese undergraduates from a private university in Singapore. They were randomly assigned into one of nine groups and asked to review a resume of a job applicant. The study used a 3 (Academic qualifications: strong, moderate, or weak) × 3 (Race: White, Chinese, or Malay) between-subjects design with perceived warmth, competence, applicant suitability and recommended salary as the dependent variables. The results showed that while Chinese participants discriminated against Malay applicants (racism), they discriminated in favor of White applicants (the Pinkerton syndrome). The results provided a potential explanation to the economic disparities between Malays and the other races, and first experimental evidence for racism and the Pinkerton syndrome in Singapore.
Background Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness.
Methods The European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated.
Results Besides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated?
Conclusions ADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD.
The kinetoplastid parasite Trypanosoma brucei causes African trypanosomiasis in both humans and animals. Infections place a significant health and economic burden on developing nations in sub-Saharan Africa, but few effective anti-parasitic treatments are currently available. Hence, there is an urgent need to identify new leads for drug development. The T. brucei neutral sphingomyelinase (TbnSMase) was previously established as essential to parasite survival, consequently being identified as a potential drug target. This enzyme may catalyse the single route to sphingolipid catabolism outside the T. brucei lysosome. To obtain new insight into parasite sphingolipid catabolism, the substrate specificity of TbnSMase was investigated using electrospray ionization tandem mass spectrometry (ESI-MS/MS). Recombinant TbnSMase was shown to degrade sphingomyelin, inositol-phosphoceramide and ethanolamine-phosphoceramide sphingolipid substrates, consistent with the sphingolipid complement of the parasites. TbnSMase also catabolized ceramide-1-phosphate, but was inactive towards sphingosine-1-phosphate. The broad-range specificity of this enzyme towards sphingolipid species is a unique feature of TbnSMase. Additionally, ESI-MS/MS analysis revealed previously uncharacterized activity towards lyso-phosphatidylcholine despite the enzyme's inability to degrade phosphatidylcholine. Collectively, these data underline the enzyme's importance in choline homoeostasis and the turnover of sphingolipids in T. brucei.
Silicon carbide together with amorphous carbon are the main components of dust grains in the atmospheres of C-rich AGB stars. Small gaseous Si-C bearing molecules (such as SiC, SiCSi, and SiC2) are efficiently formed close to the stellar photosphere. They likely condense onto dust seeds owing to their highly refractory nature at the lower temperatures (i.e., below about 2500 K) in the dust growth zone which extends a few stellar radii from the photosphere. Beyond this region, the abundances of Si-C bearing molecules are expected to decrease until they are eventually reformed in the outer shells of the circumstellar envelope, owing to the interaction between the gas and the interstellar UV radiation field. Our goal is to understand the time-dependent chemical evolution of Si-C bond carriers probed by molecular spectral line emission in the circumstellar envelope of IRC+10216 at millimeter wavelengths.
We examined whether hypotension in very low birth weight infants aged⩽1 week was associated with hospital morbidities and overall mortality. Further, we studied whether hypotension was associated with poor neurodevelopmental outcomes in these patients at the corrected age of 18 months. A total of 166 very low birth weight infants were studied during this period. Hospital outcomes and neurodevelopmental outcomes at the corrected age of 18 months were evaluated. Among the 166 very low birth weight infants, 95 patients (57.2%) experienced hypotension at⩽1 week and were associated with an increased incidence of morbidities and mortality. At the corrected age of 18 months, hypotension of the⩽1 week group had significantly lower scores in all three – cognitive, language, and motor – composites of the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) screening tests. In addition, a multivariable logistic regression analysis showed that longer mechanical ventilation and periventricular leukomalacia were additionally associated with worse cognitive and language neurodevelopmental outcomes. Hypotension in very low birth weight infants within 1 week of life was associated with increased morbidities and overall mortality. It was also associated with an increased risk of cognitive and language outcomes.
Knowledge of the effects of burial depth and burial duration on seed viability and, consequently, seedbank persistence of Palmer amaranth (Amaranthus palmeri S. Watson) and waterhemp [Amaranthus tuberculatus (Moq.) J. D. Sauer] ecotypes can be used for the development of efficient weed management programs. This is of particular interest, given the great fecundity of both species and, consequently, their high seedbank replenishment potential. Seeds of both species collected from five different locations across the United States were investigated in seven states (sites) with different soil and climatic conditions. Seeds were placed at two depths (0 and 15 cm) for 3 yr. Each year, seeds were retrieved, and seed damage (shrunken, malformed, or broken) plus losses (deteriorated and futile germination) and viability were evaluated. Greater seed damage plus loss averaged across seed origin, burial depth, and year was recorded for lots tested at Illinois (51.3% and 51.8%) followed by Tennessee (40.5% and 45.1%) and Missouri (39.2% and 42%) for A. palmeri and A. tuberculatus, respectively. The site differences for seed persistence were probably due to higher volumetric water content at these sites. Rates of seed demise were directly proportional to burial depth (α=0.001), whereas the percentage of viable seeds recovered after 36 mo on the soil surface ranged from 4.1% to 4.3% compared with 5% to 5.3% at the 15-cm depth for A. palmeri and A. tuberculatus, respectively. Seed viability loss was greater in the seeds placed on the soil surface compared with the buried seeds. The greatest influences on seed viability were burial conditions and time and site-specific soil conditions, more so than geographical location. Thus, management of these weed species should focus on reducing seed shattering, enhancing seed removal from the soil surface, or adjusting tillage systems.
OBJECTIVES/SPECIFIC AIMS: We sought to investigate the role of the host microbiome during severe, acute respiratory infection (ARI) to understand the drivers of both acute clinical pathogenesis. METHODS/STUDY POPULATION: Nasopharyngeal swabs comprised of mixed cell populations at the active site of infection were collected from 192 hospitalized pediatric patients with ARI. We combined comprehensive respiratory virus detection and virus genome sequencing with 16S rRNA gene sequencing to evaluate the microbial content of the airway during ARI. This data was coupled with 11 clinical parameters, which were compiled to create a clinical severity score. The microbiome profiles were assessed to determine if clinical severity of infection, and/or specific virus was associated with increased clinical severity. RESULTS/ANTICIPATED RESULTS: We identified 8 major microbiome profiles classified by dominant bacterial genus, Moraxella, Corynebacterium, Staphylococcus, Haemophilus, Streptococcus, Alloiococcus, Schlegelella, and Diverse. Increased clinical severity was significantly associated with microbiome profiles dominated by Haemophilus, Streptococcus, and Schlegelella, whereas Corynebacterium and Alloiococcus were more prevalent in children with less severe disease. Independent of the microbial community, more than 60% of patients with the highest clinical severity were infected with either respiratory syncytial virus or rhinovirus. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results indicate that individually and in combination, both virus and microbial composition may drive clinical severity during acute respiratory viral infections. It is still unclear how the complex interplay between virus, bacterial community, and the host response influence long-term respiratory impacts, such as the development of asthma. Nonetheless, during ARIs therapeutic interventions such as antibiotics and probiotics may be warranted in a subset of patients that are identified to have both a virus and microbiome profile that is associated with increased pathogenesis to limit both acute and long-term phenotypes.
Benzobicyclon will be the first 4-hydroxyphenylpyruvate dioxygenase (HPPD)–inhibiting herbicide available in US rice production pending registration completion. An observation of benzobicyclon controlling weedy rice in two field trials prompted a greenhouse and field evaluation to determine if benzobicyclon would control weedy rice accessions from Arkansas, Mississippi, and southeastern Missouri. A total of 100 accessions were screened in the greenhouse and field. Percentage mortality was determined in the greenhouse, and percentage control was recorded in the field. Benzobicyclon at 371 g ai ha–1 caused at least 80% mortality of 22 accessions in the greenhouse and at least 80% control of 30 accessions in the field. For most accessions, individual plants within the accession varied in response to benzobicyclon. Based on these results, the sensitivity of weedy rice to benzobicyclon varies across accessions collected in the midsouthern United States, and it may provide an additional control option for weedy rice in some fields.
Jatropha curcas L. is a potential bioenergy crop but has a lack of improved cultivars with high yields and oil content. Therefore, increasing our understanding of J. curcas germplasm is important for designing breeding strategies. This study was performed to investigate the genetic diversity and population structure of Indonesian J. curcas populations from six different islands. To construct a reference, we de novo assembled the scaffolds (N50 = 355.5 kb) using 182 Gb Illumina HiSeq sequencing data from Thai J. curcas variety Chai Nat. Genetic diversity analysis among 52 Indonesian J. curcas accessions was conducted based on yield traits and single nucleotide polymorphism (SNP) markers detected by mapping genotyping-by-sequencing reads from Indonesian population to Chai Nat scaffolds. Strong variation in yield traits was detected among accessions. Using J. integerrima as an outgroup, 13,916 SNPs were detected. Among J. curcas accessions, including accessions from other countries (Thailand, the Philippines and China), 856 SNPs were detected, but only 297 SNPs were detected among Indonesian J. curcas populations, representing low genetic diversity. Through phylogenetic and structural analysis, the populations were clustered into two major groups. Group one consists of populations from Bangka and Sulawesi in the northern part of Indonesia, which are located at a distance of 1572.59 km. Group two contains populations from islands in the southern part: Java, Lombok-Sumbawa, Flores and Timor. These results indicate that introduction of diverse J. curcas germplasms is necessary for the improvement of the genetic variation in the Indonesian collections.
This report describes the effective public health response to a measles outbreak involving a university campus in Brisbane, Australia. Eleven cases in total were notified, mostly university students. The public health response included targeted measles vaccination clinics which were established on campus and focused on student groups most likely to have been exposed. The size of the university population, social interaction between students on and off campus, as well as limited vaccination records for the university community presented challenges for the control of this extremely infectious illness. We recommend domestic students ensure vaccinations are current prior to matriculation. Immunisation information should be included in university student enrolment packs. Incoming international students should ensure routine vaccinations are up-to-date prior to arrival in Australia, thereby reducing the risk of importation of measles and other infectious diseases.
Anti-retroviral therapy (ART) regimes for HIV are associated with raised levels of circulating triglycerides (TGs) in western populations. However, there are limited data on the impact of ART on cardiometabolic risk in sub-Saharan African (SSA) populations.
Pooled analyses of 14 studies comprising 21 023 individuals, on whom relevant cardiometabolic risk factors (including TG), HIV and ART status were assessed between 2003 and 2014, in SSA. The association between ART and raised TG (>2.3 mmol/L) was analysed using regression models.
Among 10 615 individuals, ART was associated with a two-fold higher probability of raised TG (RR 2.05, 95% CI 1.51–2.77, I2 = 45.2%). The associations between ART and raised blood pressure, glucose, HbA1c, and other lipids were inconsistent across studies.
Evidence from this study confirms the association of ART with raised TG in SSA populations. Given the possible causal effect of raised TG on cardiovascular disease (CVD), the evidence highlights the need for prospective studies to clarify the impact of long term ART on CVD outcomes in SSA.