Evaluation of a novel assay for detection of the fetal marker RASSF1A: facilitating improved diagnostic reliability of noninvasive prenatal diagnosis

BackgroundAnalysis of cell free fetal (cff) DNA in maternal plasma is used routinely for non invasive prenatal diagnosis (NIPD) of fetal sex determination, fetal rhesus D status and some single gene disorders. True positive results rely on detection of the fetal target being analysed. No amplification of the target may be interpreted either as a true negative result or a false negative result due to the absence or very low levels of cffDNA. The hypermethylated RASSF1A promoter has been reported as a universal fetal marker to confirm the presence of cffDNA. Using methylation-sensitive restriction enzymes hypomethylated maternal sequences are digested leaving hypermethylated fetal sequences detectable. Complete digestion of maternal sequences is required to eliminate false positive results.MethodscfDNA was extracted from maternal plasma (n = 90) and digested with methylation-sensitive and insensitive restriction enzymes. Analysis of RASSF1A, SRY and DYS14 was performed by real-time PCR.ResultsHypermethylated RASSF1A was amplified for 79 samples (88%) indicating the presence of cffDNA. SRY real time PCR results and fetal sex at delivery were 100% accurate. Eleven samples (12%) had no detectable hypermethylated RASSF1A and 10 of these (91%) had gestational ages less than 7 weeks 2 days. Six of these samples were male at delivery, five had inconclusive results for SRY analysis and one sample had no amplifiable SRY.ConclusionUse of this assay for the detection of hypermethylated RASSF1A as a universal fetal marker has the potential to improve the diagnostic reliability of NIPD for fetal sex determination and single gene disorders

Explicit Supersymmetry Breaking on Boundaries of Warped Extra Dimensions

Explicit supersymmetry breaking is studied in higher dimensional theories by having boundaries respect only a subgroup of the bulk symmetry. If the boundary symmetry is the maximal subgroup allowed by the boundary conditions imposed on the fields, then the symmetry can be consistently gauged; otherwise gauging leads to an inconsistent theory. In a warped fifth dimension, an explicit breaking of all bulk supersymmetries by the boundaries is found to be inconsistent with gauging; unlike the case of flat 5D, complete supersymmetry breaking by boundary conditions is not consistent with supergravity. Despite this result, the low energy effective theory resulting from boundary supersymmetry breaking becomes consistent in the limit where gravity decouples, and such models are explored in the hope that some way of successfully incorporating gravity can be found. A warped constrained standard model leads to a theory with one Higgs boson with mass expected close to the experimental limit. A unified theory in a warped fifth dimension is studied with boundary breaking of both SU(5) gauge symmetry and supersymmetry. The usual supersymmetric prediction for gauge coupling unification holds even though the TeV spectrum is quite unlike the MSSM. Such a theory may unify matter and Higgs in the same SU(5) hypermultiplet.Comment: 30 pages, version to appear in Nucl. Phys.

Effect of zinc intake on growth in infants: A meta-analysis

A systematic review and meta-analysis of available randomized controlled trials (RCTs) was conducted to evaluate the effect of zinc (Zn) intake on growth in infants. Out of 5500 studies identified through electronic searches and reference lists, 19 RCTs were selected after applying the exclusion/inclusion criteria. The influence of Zn intake on growth was considered in the overall meta-analysis. Other variables were also taken into account as possible effect modifiers: doses of Zn intake, intervention duration, nutritional status, and risk of bias. From each select growth study, final measures of weight, length, mid upper arm circumference (MUAC), head circumference, weight for age z-score (WAZ), length for age z-score (LAZ), and weight for length z-score (WLZ) were assessed. Pooled β and 95% confidence interval (CI) were calculated. Additionally, we carried out a sensitivity analysis. Zn intake was not associated with weight, length, MUAC, head circumference, and LAZ in the pooled analyses. However, Zn intake had a positive and statistically effect on WAZ (β = 0.06; 95%CI 0.02 to 0.10) and WLZ (β = 0.05; 95%CI 0.01 to 0.08). The dose–response relationship between Zn intake and these parameters indicated that a doubling of Zn intake increased WAZ and WLZ by approximately 4%. Substantial heterogeneity was present only in length analyses (I2 = 45%; p = 0.03). Zn intake was positively associated with length values at short time (four to 20 weeks) (β = 0.01; CI 95% 0 to 0.02) and at medium doses of Zn (4.1 to 8 mg/day) (β = 0.003; CI 95% 0 to 0.01). Nevertheless, the effect magnitude was small. Our results indicate that Zn intake increases growth parameters of infants. Nonetheless, interpretation of these results should be carefully considered

Control of anthocyanin and non-flavonoid compounds by anthocyanin-regulating MYB and bHLH transcription factors in Nicotiana benthamiana leaves

Coloration of plant organs such as fruit, leaves and flowers through anthocyanin production is governed by a combination of MYB and bHLH type transcription factors. In this study we introduced Rosea1 (ROS1, a MYB type) and Delila (DEL, a bHLH type), into Nicotiana benthamiana leaves by agroinfiltration. ROS1 and DEL form a pair of well-characterized transcription factors from Snapdragon (Antirrhinum majus), which specifically induce anthocyanin accumulation when expressed in tomato fruit. In N. benthamiana, robust induction of a single anthocyanin, delphinidin-3-rutinoside (D3R) was observed after expression of both ROS1 and DEL. Surprisingly in addition to D3R, a range of additional metabolites were also strongly and specifically up-regulated upon expression of ROS1 and DEL. Except for the D3R, these induced compounds were not derived from the flavonoid pathway. Most notable among these are nornicotine conjugates with butanoyl, hexanoyl and octanoyl hydrophobic moieties, and phenylpropanoid-polyamine conjugates such as caffeoyl-putrescine. The defensive properties of the induced molecules were addressed in bioassays using the tobacco specialist lepidopteran insect Manduca sexta. Our study showed that the effect of ROS1 and DEL expression in N. benthamiana leaves extends beyond the flavonoid pathway. Apparently the same transcription factor may regulate different secondary metabolite pathways in different plant species

Behavior change interventions to increase physical activity in hospitalized patients: A systematic review, meta-analysis and meta-regression

© The Author(s) 2021. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/)Background Low physical activity levels are a major problem for people in hospital and are associated with adverse outcomes. Objective This systematic review, meta-analysis and meta-regression aimed to determine the effect of behaviour change interventions on physical activity levels in hospitalised patients. Methods Randomised controlled trials of behaviour change interventions to increase physical activity in hospitalised patients were selected from a database search, supplemented by reference list checking and citation tracking. Data were synthesised with random-effects meta-analyses and meta-regression analyses, applying Grades of Recommendation, Assessment, Development and Evaluation criteria. The primary outcome was objectively measured physical activity. Secondary measures were patient-related outcomes (e.g. mobility), service level outcomes (e.g. length of stay), adverse events and patient satisfaction. Results Twenty randomised controlled trials of behaviour change interventions involving 2,568 participants (weighted mean age 67 years) included six trials with a high risk of bias. There was moderate-certainty evidence that behaviour change interventions increased physical activity levels (SMD 0.34, 95% CI 0.14–0.55). Findings in relation to mobility and length of stay were inconclusive. Adverse events were poorly reported. Meta-regression found behaviour change techniques of goal setting (SMD 0.29, 95% CI 0.05–0.53) and feedback (excluding high risk of bias trials) (SMD 0.35, 95% CI 0.11–0.60) were independently associated with increased physical activity. Conclusions Targeted behaviour change interventions were associated with increases in physical activity in hospitalised patients. The trials in this review were inconclusive in relation to the patient-related or health service benefits of increasing physical activity in hospital.Peer reviewe

Identifying the genetic basis of antigenic change in influenza A(H1N1)

Determining phenotype from genetic data is a fundamental challenge. Influenza A viruses undergo rapid antigenic drift and identification of emerging antigenic variants is critical to the vaccine selection process. Using former seasonal influenza A(H1N1) viruses, hemagglutinin sequence and corresponding antigenic data were analyzed in combination with 3-D structural information. We attributed variation in hemagglutination inhibition to individual amino acid substitutions and quantified their antigenic impact, validating a subset experimentally using reverse genetics. Substitutions identified as low-impact were shown to be a critical component of influenza antigenic evolution and by including these, as well as the high-impact substitutions often focused on, the accuracy of predicting antigenic phenotypes of emerging viruses from genotype was doubled. The ability to quantify the phenotypic impact of specific amino acid substitutions should help refine techniques that predict the fitness and evolutionary success of variant viruses, leading to stronger theoretical foundations for selection of candidate vaccine viruses

Systematics of Coupling Flows in AdS Backgrounds

We give an effective field theory derivation, based on the running of Planck brane gauge correlators, of the large logarithms that arise in the predictions for low energy gauge couplings in compactified AdS}_5 backgrounds, including the one-loop effects of bulk scalars, fermions, and gauge bosons. In contrast to the case of charged scalars coupled to Abelian gauge fields that has been considered previously in the literature, the one-loop corrections are not dominated by a single 4D Kaluza-Klein mode. Nevertheless, in the case of gauge field loops, the amplitudes can be reorganized into a leading logarithmic contribution that is identical to the running in 4D non-Abelian gauge theory, and a term which is not logarithmically enhanced and is analogous to a two-loop effect in 4D. In a warped GUT model broken by the Higgs mechanism in the bulk,we show that the matching scale that appears in the large logarithms induced by the non-Abelian gauge fields is m_{XY}^2/k where m_{XY} is the bulk mass of the XY bosons and k is the AdS curvature. This is in contrast to the UV scale in the logarithmic contributions of scalars, which is simply the bulk mass m. Our results are summarized in a set of simple rules that can be applied to compute the leading logarithmic predictions for coupling constant relations within a given warped GUT model. We present results for both bulk Higgs and boundary breaking of the GUT gauge group.Comment: 22 pages, LaTeX, 3 figures. Comments and references adde

Warped Supersymmetric Grand Unification

We construct a realistic theory of grand unification in AdS_5 truncated by branes, in which the unified gauge symmetry is broken by boundary conditions and the electroweak scale is generated by the AdS warp factor. We show that the theory preserves the successful gauge coupling unification of the 4D MSSM at leading-logarithmic level. Kaluza-Klein (KK) towers, including those of XY gauge and colored Higgs multiplets, appear at the TeV scale, while the extra dimension provides natural mechanisms for doublet-triplet splitting and proton decay suppression. In one possible scenario supersymmetry is strongly broken on the TeV brane, in which case the lightest SU(3)_C x SU(2)_L x U(1)_Y gauginos are approximately Dirac and the mass of the lightest XY gaugino is pushed well below that of the lowest gauge boson KK mode, improving the prospects for its production at the LHC. The bulk Lagrangian possesses a symmetry that we call GUT parity. If GUT parity is exact, the lightest GUT particle, most likely an XY gaugino, is stable. Once produced in a collider, the XY gaugino hadronizes to form mesons, some of which will be charged and visible as highly ionizing tracks. The lightest supersymmetric particle is the gravitino of mass \sim 10^{-3} eV, which is also stable if R parity is conserved.Comment: 41 pages, LaTeX, version to appear in Phys. Rev.

Hadoop neural network for parallel and distributed feature selection

In this paper, we introduce a theoretical basis for a Hadoop-based neural network for parallel and distributed feature selection in Big Data sets. It is underpinned by an associative memory (binary) neural network which is highly amenable to parallel and distributed processing and fits with the Hadoop paradigm. There are many feature selectors described in the literature which all have various strengths and weaknesses. We present the implementation details of five feature selection algorithms constructed using our artificial neural network framework embedded in Hadoop YARN. Hadoop allows parallel and distributed processing. Each feature selector can be divided into subtasks and the subtasks can then be processed in parallel. Multiple feature selectors can also be processed simultaneously (in parallel) allowing multiple feature selectors to be compared. We identify commonalities among the five features selectors. All can be processed in the framework using a single representation and the overall processing can also be greatly reduced by only processing the common aspects of the feature selectors once and propagating these aspects across all five feature selectors as necessary. This allows the best feature selector and the actual features to select to be identified for large and high dimensional data sets through exploiting the efficiency and flexibility of embedding the binary associative-memory neural network in Hadoop

Low-Dose Nitric Oxide as Targeted Anti-biofilm Adjunctive Therapy to Treat Chronic Pseudomonas aeruginosa Infection in Cystic Fibrosis

Despite aggressive antibiotic therapy, bronchopulmonary colonization by Pseudomonas aeruginosa causes persistent morbidity and mortality in cystic fibrosis (CF). Chronic P. aeruginosa infection in the CF lung is associated with structured, antibiotic-tolerant bacterial aggregates known as biofilms. We have demonstrated the effects of non-bactericidal, low-dose nitric oxide (NO), a signaling molecule that induces biofilm dispersal, as a novel adjunctive therapy for P. aeruginosa biofilm infection in CF in an ex vivo model and a proof-of-concept double-blind clinical trial. Submicromolar NO concentrations alone caused disruption of biofilms within ex vivo CF sputum and a statistically significant decrease in ex vivo biofilm tolerance to tobramycin and tobramycin combined with ceftazidime. In the 12-patient randomized clinical trial, 10 ppm NO inhalation caused significant reduction in P. aeruginosa biofilm aggregates compared with placebo across 7 days of treatment. Our results suggest a benefit of using low-dose NO as adjunctive therapy to enhance the efficacy of antibiotics used to treat acute P. aeruginosa exacerbations in CF. Strategies to induce the disruption of biofilms have the potential to overcome biofilm-associated antibiotic tolerance in CF and other biofilm-related diseases