Traditional Screening Techniques Research Articles

Oxidized mRNA Lipid Nanoparticles for In Situ Chimeric Antigen Receptor Monocyte Engineering

AbstractChimeric antigen receptor (CAR) monocyte and macrophage therapies are promising solid tumor immunotherapies that can overcome the challenges facing conventional CAR T cell therapy. mRNA lipid nanoparticles (mRNA‐LNPs) offer a viable platform for in situ engineering of CAR monocytes with transient and tunable CAR expression to reduce off‐tumor toxicity and streamline cell manufacturing. However, identifying LNPs with monocyte tropism and intracellular delivery potency is difficult using traditional screening techniques. Here, ionizable lipid design and high‐throughput in vivo screening are utilized to identify a new class of oxidized LNPs with innate tropism and mRNA delivery to monocytes. A library of oxidized (oLNPs) and unoxidized LNPs (uLNPs) is synthesized to evaluate mRNA delivery to immune cells. oLNPs demonstrate notable differences in morphology, ionization energy, and pKa, thereby enhancing delivery to human macrophages, but not T cells. Subsequently, in vivo library screening with DNA barcodes identifies an oLNP formulation, C14‐O2, with innate tropism to monocytes. In a proof‐of‐concept study, the C14‐O2 LNP is used to engineer functional CD19‐CAR monocytes in situ for robust B cell aplasia (45%) in healthy mice. This work highlights the utility of oxidized LNPs as a promising platform for engineering CAR macrophages/monocytes for solid tumor CAR monocyte therapy.

A new Approach for Accurate Detection of Chromosome Rearrangements That Affect Fertility in Cattle.

Simple SummaryGlobally, cattle production has more than doubled since the 1960s, with widespread use of artificial insemination (AI) and an emphasis on a small pool of high-genetic-merit animals. Selecting AI bulls with optimal fertility is therefore vital, as impaired fertility reduces genetic gains and reduces production, resulting in heavy financial and environmental losses. Chromosome translocations, where large parts of the genome are inappropriately attached in abnormal patterns, are a common cause of reduced fertility; however, reciprocal translocations are significantly underreported due to the difficulties inherent in analysing cattle chromosomes. Based on our previous work, we have developed an approach for the unambiguous detection of abnormalities that affect fertility. We applied this method on the chromosomes of 39 bulls, detecting multiple abnormalities that affect fertility, including those that would be undetectable using traditional screening techniques. With UK dairy calving rates of only 50–60%, it is vital to reduce further fertility loss in order to maximise productivity. The approach developed here identifies abnormalities that DNA sequencing will not, and has the potential to lead to long-term gains, delivering meat and milk products in a more cost-effective and environmentally-responsible manner to a growing population.Globally, cattle production has more than doubled since the 1960s, with widespread use of artificial insemination (AI) and an emphasis on a small pool of high genetic merit animals. Selecting AI bulls with optimal fertility is, therefore, vital, as impaired fertility reduces genetic gains and production, resulting in heavy financial and environmental losses. Chromosome translocations, particularly the 1;29 Robertsonian translocation, are a common cause of reduced fertility; however, reciprocal translocations are significantly underreported due to the difficulties inherent in analysing cattle chromosomes. Based on our porcine work, we have developed an approach for the unambiguous detection of Robertsonian and reciprocal translocations, using a multiple-hybridization probe detection strategy. We applied this method on the chromosomes of 39 bulls, detecting heterozygous and homozygous 1;29 translocations and a 12;23 reciprocal translocation in a total of seven animals. Previously, karyotype analysis was the only method of diagnosing chromosomal rearrangements in cattle, and was time-consuming and error-prone. With calving rates of only 50–60%, it is vital to reduce further fertility loss in order to maximise productivity. The approach developed here identifies abnormalities that DNA sequencing will not, and has the potential to lead to long-term gains, delivering meat and milk products in a more cost-effective and environmentally-responsible manner to a growing population.

Network screening for large urban road networks: Using GPS data and surrogate measures to model crash frequency and severity

Crash frequency and injury severity are independent dimensions defining crash risk in road safety management and network screening. Traditional screening techniques model crashes using regression and historical crash data, making them intrinsically reactive. In response, surrogate measures of safety have become a popular proactive alternative. The purpose of this paper is to develop models for crash frequency and severity incorporating GPS-derived surrogate safety measures (SSMs) as predictive variables. SSMs based on vehicle manoeuvres and traffic flow were extracted from data collected in Quebec City. The mixed multivariate outcome is estimated using two models; a Full Bayes Spatial Negative Binomial model for crash frequency estimated using the Integrated Nested Laplace Approximation approach and a fractional Multinomial Logit model for crash severity. Model outcomes are combined to generate posterior expected crash frequency at each severity level and rank sites based on crash cost. The crash frequency model was accurate at the network scale, with the majority of proposed SSMs statistically significant at 95% confidence and the direction of their effect generally consistent with previous research. In the crash severity model, fewer variables were significant, yet the direction of the effect of all significant variables was again consistent with previous research. Correlations between rankings predicted by the mixed multivariate model and by the crash data were adequate for intersections (0.46) but were poorer for links (0.25). The ability to prioritize sites based on GPS data and SSMs rather than historical crash data represents a substantial contribution to the field of road safety.

‘Feel the film’: Film projectionists and professional memory

Deploying concepts of professional memory and communities of practice, this article draws on interviews with two generations of film projectionists in Brno in the Czech Republic to investigate the profession of film projectionist as a phenomenon at the boundaries of memory studies, sociology, social anthropology and film history. From this standpoint, a study of cinema employees’ professional memory revises and refines the concept of cinema memory as examined from the cinemagoer’s perspective. The article sets out the key tropes of projectionists’ memories and discusses them in the context of the legal background, professional status, standards of good practice and relationships within the professional community. Analysing the conditions under which the professional identity of film projectionist has been formed, it takes into account the current obsolescence of traditional screening techniques and analyses the significance of film screening quality and the related perception of the projectionist as a creator of a screening as significant motifs in projectionists’ memories.

A Novel, Highly Effective, Chrome-Free, Smart-Release, Economically Viable Corrosion Inhibitor- from Lab Kinetics through to Industrial Coating Incorporation

Novel, smart-release in-coating corrosion-inhibiting pigments for hot dip galvanised (HDG) steel, were investigated as a low cost replacements for hexavalent chromate. Organic anions were exchanged into the smart-release divynl benzene resin based pigment, dispersed in a model coating and analysed using an in-situ scanning kelvin probe (SKP) technique, for their effectiveness at preventing cathodic delamination. SKP allows rapid screening of the inhibitor-containing pigment when dispersed in a model organic polyvinyl butyral (PVB) coating. Each experiment lasts 24 hours, enabling a larger experimental through-put in comparison to traditional screening techniques, such as EIS or salt spray (ASTM-B117). SKP gives spacially resolved corrosion potential (Ecorr) profiles enabling identification of the delamination front and subsequent measurement of its progression and rate kinetics. Figure 1 shows plots of delamination distance vs. time for the anions screened in these experiments. Results indicate that a benzotriazolate-containing pigment system is the most effective, where delamination rates were reduced by 95% and the onset of cathodic delamination was increased by ca. 2160 hours from the point of initiation with an external electrolyte. It has been reported previously that benzotriazole is an effective corrosion inhibitor for a range of metals when in solution (1-5), the divynl benzene matrix allows benzotriazolate to be stored and released only when the coating encounters a corrosive electrolyte, via ion exchange mechanisms. Open circuit potential measurements show an increase in Ecorr measurements where benzotriazole is present in the experimental electrolyte suggesting anodic inhibition. Results from salt-spray testing carried out on a commercial coil coating are also presented where benzotriazole is shown to be effective after a period of 1000 hours. The current study suggests that a benzotriazolate-containing pigment system is a strong, environmentally friendly, contender to replace chromate for the inhibition of corrosion on hot dip galvanised steel. 1. Finšgar M, Milošev I (2010) Corros Sci 52:2737–2749. 2. Kosec T, Merl DK, Milošev I (2008) Corros Sci 50:1987–1997. 3. Aramaki K (2001) Corros Sci 43:1985–2000. 4. Müller B, Imblo G (1996) Corros Sci 38:293–300. 5. LEROY RL (1978) Corrosion 34:98–110. Figure 1

Pediatric Vision Screening

1. Gary L. Rogers, MD 2. Catherine Olson Jordan, MD 1. Department of Ophthalmology, Nationwide Children’s Hospital, Columbus, OH. Although early detection of visual disorders can lead to therapy that will prevent permanent blindness, compliance with screening guidelines of the American Academy of Pediatrics is low. After completing this article, readers should be able to: 1. Be aware of common vision-threatening conditions that can be detected by using basic screening examinations. 2. Become familiar with techniques and findings used in vision screening examinations. 3. Understand the role of commercial screening tools. Early detection of ocular conditions can allow for assessment and treatment of a vision-threatening or life-threatening condition. Amblyopia, or “lazy eye,” can develop if a clear visual image is not projected onto the retina. Amblyopia can be caused by deprivation, strabismus, high refractive error (hyperopia, myopia, or astigmatism), or anisometropia (significant difference in the refractive error between eyes) and can be unilateral or bilateral. The prevalence of amblyopia is estimated to be 1% to 4%. (1) Many factors may prevent the achievement of universal vision screening, including lack of education of families; language, financial, and state legislative barriers; and a lack of available providers. (2) Primary care physicians are crucial providers for detecting and referring vision-threatening ocular conditions. From the newborn examination, through subsequent health supervision visits, and throughout a child’s life, the pediatrician and family physician can perform effective examinations to screen for common and uncommon conditions that may be vision-threatening or even potentially life-threatening. (3) However, vision screening in the primary care office should not take the place of a full eye examination. If a patient cannot be screened effectively after two attempts, a referral should be made to an eye care professional who is comfortable examining children. …

Geometric Filtration Using Proper Orthogonal Decomposition for Aerodynamic Design Optimization

When carrying out design searches, traditional variable screening techniques can find it extremely difficult to distinguish between important and unimportant variables. This is particularly true when only a small number of simulations is combined with a parameterization which results in a large number of variables of seemingly equal importance. Here the authors present a variable reduction technique which employs proper orthogonal decomposition to filter out undesirable or badly performing geometries from an optimization process. Unlike traditional screening techniques, the presented method operates at the geometric level instead of the variable level. The filtering process uses the designs which result from a geometry parameterization instead of the variables which control the parameterization. The method is shown to perform well in the optimization of a two dimensional airfoil for the minimization of drag to lift ratio, producing designs better than those resulting from traditional kriging based surrogate model optimization and with a significant reduction in surrogate tuning cost

Patient choice and the randomized controlled trial

Patient choice and the randomized controlled trial

Predictive Value of Photoscreening and Traditional Screening of Preschool Children

To compare the usefulness of traditional vision screening and photoscreening of 3- and 4-year-old children in the pediatrician's office. Following training of pediatricians and office staff, six pediatric clinics used both the MTI PhotoScreener (Medical Technology Industries, LLC, Riviera Beach, FL) and traditional acuity and stereopsis screening materials (HOTV charts/Random Dot E tests as recommended by established AAP-MCHB-PUPVS guidelines) during well-child exams. Clinics used one testing method for a 6-month period and switched to the other for the following 6 months, in a randomized manner. Referred children received a complete eye examination with cycloplegic refraction by local ophthalmologists or optometrists who forwarded the results to Vanderbilt Ophthalmology Outreach Center. Amblyogenic factors were defined using standardized published criteria. Six hundred five children were screened with the photoscreener and 447 were screened with traditional techniques. Mean time for screening was less with the photoscreener: 2.5 versus 5.9 minutes ( P < 0.01). Untestable rates were similar (18% vs 10%, respectively P = NS), but higher with the photoscreener due to one clinic's 70% unreadable rate. Referral rates were also similar: 3.8% versus 4.5%. The positive predictive value (PPV) rate differed greatly. With follow-up results obtained from 56% of referred children, 73% of photoscreening referred children (8/11 examined) had amblyogenic factors confirmed on formal eye exams, whereas all children referred using traditional screening methods (10/10 examined) were normal. Photoscreening is more time efficient than traditional screening and has a significantly higher PPV in 3- and 4-year-old children. This study was unable to validate traditional screening techniques in this preschool age group. If these results can be replicated, support for traditional vision screening must undergo intense scrutiny, and attention should be turned toward making photoscreening feasible for widespread implementation.

Motion - computerized tomographic colography is a better method for screening for polyps: arguments for the motion.

Colorectal cancer is an important public health problem that is amenable to prevention and early treatment. Traditional screening techniques - fecal occult blood testing, flexible sigmoidoscopy, barium enema and colonoscopy - each have limitations in terms of diagnostic accuracy, cost and/or patient acceptability. Compliance with recommendations for screening has been poor, in part, because of negative perceptions about the available modalities. Virtual colonoscopy, or computerized tomographic colography, is a minimally invasive technique that safely evaluates the entire colon and does not require sedation. Thorough cleansing as well as immobilization and air insufflation of the colon is crucial to a successful examination. Sensitivity and specificity rates are reasonable, compared with conventional colonoscopy, and it has been shown that the latter technique can be averted in over two-thirds of cases, with few false-negative examinations. Most patients find virtual colonoscopy more acceptable than the conventional technique, and would prefer it if a repeat procedure were warranted. An economic analysis that found that computerized tomographic colography was less cost effective than conventional colonoscopy did not consider the indirect costs of the latter, which is an important limitation. Virtual colonoscopy is a novel radiological technique that may revolutionize screening for colorectal cancer.

Computer-aided screening for hallucinogenic and stimulant amphetamines with gas chromatography-Fourier transform infrared spectroscopy (GC-FTIR).

An expert system applied as a screening test for amphetamine analogues found in recreational-drug exhibits (tablets or powders) is described. The knowledge base defining the reference Fourier transform infrared spectroscopic (FTIR) spectral patterns has been built according to criteria encompassing toxicological, pharmacological, and neurochemical aspects. The class identity of a compound is determined within seconds using soft independent modeling of class analogy (SIMCA). The predictive value of the system, as assessed at a testing accuracy of 95%, is expressed by a total correct classification rate of 93.93% and by a 96.30% rate of true-positive amphetamines. The specificity and the selectivity of the screening test, evaluated by testing 159 toxicologically relevant compounds, are discussed, emphasizing the chemical and physical factors affecting these parameters. Medicinal amphetamines giving cross-reactions with traditional screening techniques produce a negative result. The specificity of the system characterizes the expert system as a highly sensitive, selective, fast, and user-friendly screening test that screens for amphetamines with prediction accuracy adequate for investigations in analytical toxicology.

Molecular imprinting of Ricin and its A and B chains to organic silanes: fluorescence detection

The stable physical properties of molecular imprints make them ideal artificial receptors, i.e., biosensor sensing elements, for detection systems against chemical and biological toxins, drugs, and environmental contaminants [B. Dave, B. Dunn, J. Selverstone Valentine, J. Zink, Anal. Chem. 66 (1994) 1120–1127; O. Lev, M. Tsionsky, L. Rabinovich, V. Glezer, S. Sampath, I. Pankratov, J. Gun, Anal. Chem. 67 (1995) 22–30; R. Wang, U. Narang, P. Prasad, F. Bright, Anal. Chem. 65 (1993) 2671–2675; S.A. Piletsky, Y.P. Parhometz, N.V. Lavryk, T.L. Panasyuk, A.V. El'skaya, Sens. Actuators, B 18–19 (1994) 629–631; M.P. Byfield, R.A. Abuknesha, Biosens. Bioelectron. 9 (1994) 373–400] and afford them advantages over traditional screening techniques such as purified receptors and antibodies which require elaborate preparative techniques and complex environments. Molecular imprints to the deadly castor bean lectin Ricin ( Ricinus communis, Toxin RCA 60) and its ‘A’ and ‘B’ chains were prepared, and their respective binding constants determined using steady-state fluorescence. Stern–Volmer fluorescence quenching plots using iodide and acrylamide suggest imprint associated Ricin B chain tryptophans are more accessible to the solvent environment than those of the Ricin A chain. Scatchard analysis revealed two affinities for Ricin binding to Ricin imprints, i.e., K d=34 nM and 319 nM. Similarly, high affinity interaction of Ricin A and B chains with their respective imprints were observed ( K d≅100 nM). Interestingly, Scatchard analysis of Ricin B chain binding to Ricin imprints revealed two apparent affinities ( K d=0.23 and 25 nM) whereas, Ricin B chain binding to A chain imprints exhibited one high affinity constant ( K d=8.9 nM). These data support the usefulness of intrinsic fluorescence and molecular imprints for detection of large proteins and biological toxins.

Molecular cloning by hybrid arrest of translation in Xenopus laevis oocytes. Identification of a cDNA encoding the type I iodothyronine 5'-deiodinase from rat liver

The enzyme(s) catalyzing the 5'-monodeiodination of thyroxine and 3,3',5'-triiodothyronine has not yet been purified, and antibodies of demonstrated specificity are not available. Thus, molecular cloning strategies which rely on the traditional screening techniques of using cDNA probes or monospecific antibodies are problematic. We previously reported that expression of type I 5'-deiodinase can be induced in Xenopus laevis oocytes by the injection of poly (A)+ RNA prepared from rat liver (St. Germain, D.L., and Morganelli, C.M. (1989) J. Biol. Chem. 264, 3054-3056). Using this expression system, we developed a hybrid arrest assay, and with it identified a 241-base pair cDNA which encodes part of this enzyme. The cDNA inhibits translation of 5'-deiodinase activity in oocytes by greater than 99% and 5'-deiodinase mRNA from rat liver poly(A)+ RNA in hybrid selection experiments. The cDNA hybridizes to a 1.9-kilobase RNA species on Northern analysis and demonstrates no significant homology to any previously cloned protein. The application of this hybrid arrest strategy for molecular cloning may prove useful for the isolation of cDNAs for proteins that are low in abundance, difficult to purify, or are subunits of a polymeric functional unit.

Kindergarten and first grade: A time for developing and nurturing gifted behaviors in young children

This article concludes that there is a tremendous need for gifted programs at the kindergarten and first grade levels. A review of the literature suggests that it is difficult to identify young gifted children through traditional screening techniques. The author concludes that Renzulli's Enrichment Triad Model may prove useful for identifying young gifted children.

Intelligent Strategy with Distributed Database for High-Volume LSI Testing

As semiconductor technology has matured, the advent of LSI chips such as microprocessors with substantially increased device functionality and complexity has created unparalleled challenges to test philosophy. Most traditional screening techniques become inadequate in defining the worst cases of test patterns and test sequences out of an enormous number of sequential-combinational candidates and in tracking reliability data following the various stages of product life to provide corrective action. A computerized automatic-optimization strategy is conceived using a systematic approach based on statistical, cumulative and time dependent processes. It integrates device characterization, on-line screening, product and subsequent reliability monitoring via distributed data base management in a closed-loop self-corrective manner. Preliminary evaluation of the intelligent test pattern/sequence generation has been conducted for on-line device screening; the conceived algorithms detects 99 percent of the total defects and consumes only 10 percent test-time of the conventional approach, a significant savings in cost, labor, and equipment expenditure requirement. This test strategy shows the approach to combat ever increasing device complexity while still providing a substantially improved performance-to-cost ratio.