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Primary care physicians (PCPs) often daily address diagnoses and treatment of mental disorders in their practices. The current study examined the Connected Mind Fast Check (CMFC), a two-tiered electronic screen, assessing six common mental disorders. The eight-item Initial Screen assesses possible symptoms, whereas SAM modules establish provisional diagnoses and areas of clinical concern. With 234 patients from five independent PCP offices, diagnostic accuracy was tested with the SCID-5-RV as the external criterion. Concerningly, many patients were unaware of their current mental disorders and comorbidities. The CMFC Initial Screen evidenced strong sensitivity, identifying with very few missing diagnoses. About two-thirds of provisional SAM diagnoses were confirmed with high specificities. Bipolar Disorder posed the most challenges at both tiers. Importantly, the suicide screen identified all patients with suicide plans and three-fourths with ideation. In general, the CMFC effectively identified provisional diagnoses, impairment, and potential suicidality. Supplementary Information The online version contains supplementary material available at 10.1007/s10880-021-09820-1.

Borderline personality disorder (BPD) is underdiagnosed in clinical practice. One approach towards improving diagnostic detection is the use of screening questionnaires. It is important for a screening test to have high sensitivity because the more time-intensive/expensive follow-up diagnostic inquiry will presumably only occur in patients who are positive on the initial screen. The most commonly studied self-report scale specific for BPD is the McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD). We summarize the performance of the scale across studies, examine the performance of the scale using different cutoff scores, and highlight the approach used by investigators in recommending a cutoff score. Most studies of the scale have taken a case-finding approach in deriving the cutoff score on the scale instead of a screening approach. For the purposes of screening, it may be more appropriate for the cutoff score on the MSI-BPD to be less than the currently recommended cutoff of 7.

Botulinum neurotoxin serotype A (BoNT/A) is an important therapeutic target owing to its extremely potent nature, but also has potential use as a biowarfare agent. Currently, no therapeutic exists to reverse the long-lasting paralysis caused by BoNT/A. Herein, we describe the identification of 3-hydroxy-1,2-dimethylpyridine-4(1H)-thione (3,4-HOPTO) as a metal binding warhead for the inhibition of BoNT/A1. An initial screen of 96 metal binding fragments identified three derivatives containing the 3,4-HOPTO scaffold to inhibit the BoNT/A1 light chain (LC) at >95% at 1 mM. Additional screening of a 3,4-HOPTO sub-library identified structure–activity relationships (SARs) between N-substituted 3,4-HOPTO derivatives and the BoNT/A1 LC. Subsequent synthesis was conducted to improve on inhibitory potency – achieving low μM biochemical IC50 values. Representative compounds were evaluated in a cellular-based assay and showed promising μM activity.

Youth with visual impairments often show difficulties with gross motor skills regardless of age or sex. Gross motor skills support positive developmental trajectories for health warranting the need for assessment. The Total Body Developmental Sequences (TBDS) are fast, easy-to-use, indices of gross motor development with relatively unknown psychometric properties for youth with visual impairments. The primary purpose of this study was to assess the psychometric properties of the TBDS with a secondary purpose to evaluate differential effects of biological sex, age, and degree of vision on gross motor skills. Youth with visual impairments (N = 57, ages 9 – 19 years, Boys = 23, Girls = 34) completed the TBDS and the Test of Gross Motor Development (TGMD-3). Results showed good initial psychometric properties (r = .89, α = .84, p .05). The TBDS may now be used as an initial gross motor screening tool for youth with visual impairments. This initial screen (TBDS) is warranted as youth with visual impairments may show arrested development which may be exacerbated with more severe visual impairments.

To encourage screening for personality disorders (PDs), we developed (in previous work) self-report scales for PDs using the Inventory of Interpersonal Problems (IIP). The combined score from three of the scales—inter-personal sensitivity, interpersonal ambivalence, and aggression—requiring 15 items (IIP-15) did the best job of distinguishing between respondents with any versus no PD. The goals for the present work were (a) to cross-validate the IIP-15 by examining its performance using receiver operating characteristics (ROC) analyses in a new sample (N = 410), and (b) to investigate the utility of a brief three-item variant (IIP-3). The present results again documented the good operating characteristics of the IIP-15. Sensitivity, specificity, and positive and negative predictive values were all above. 70. The operating characteristics of the IIP-3 were nearly as good despite its brevity and support its use as an initial screen for PDs.

Background Trauma is a major cause of death and disability in all ages. Previous reviews have suggested that National Institutes of Health (NIH) funding for trauma is not commensurate with its burden of disease, but a detailed analysis has been lacking. We postulated that NIH spending on trauma research was lower than previously thought and was distributed widely, preventing a comprehensive research strategy that could decrease trauma morbidity and mortality. Methods The NIH Research Portfolio Online Reporting Tool was initially screened using a search of over 20 terms including "trauma," "injury," "shock," "MVC," and excluding clearly unrelated conditions, for example, "cancer." The details of all grants that screened positive underwent manual review to identify true trauma-related grants. An expert panel was used to adjudicate any ambiguity. Results In FY2016, NIH awarded 50,137 grants, of which 6,401 (13%) were captured by our initial screen. Following review, 1,888 (28%) were identified as trauma-related; 3.7% of all NIH grants. These grants (US $720 million) represent only 2.9% of the NIH extramural budget. In addition, the grants were funded and administered by 24 of the institutes and centers across the NIH ranging from 0.01% (National Cancer Institute) to 11% (National Institute of Neurological Disorders and Stroke and National Institute of Arthritis and Musculoskeletal and Skin Diseases) of their extramural portfolios. Conclusion Given the extreme burden of trauma-related disability and years of life lost, this review of extramural NIH funding definitively demonstrates that trauma is severely underfunded. The lack of a dedicated home for trauma research at NIH leads to a diffusion of grants across many institutes and makes it impossible to direct a focused and effective national research endeavor to improve outcomes. These data demonstrate the need for a National Institute of Trauma at the NIH to help set an agenda to reach the national goal of Zero Preventable Deaths.

Integrating a screening possibility for Autism Spectrum Disorder (ASD) within the widely applied Achenbach System of Empirically Based Assessment (ASEBA) scales could be of great value for daily clinical practice. The present study explored the ability of the school-aged Child Behavior Checklist (CBCL) and the Teacher’s Report Form (TRF) to screen for ASD in children and adolescents (aged 6 to 18 years) within a mixed clinically referred sample. Different screening variants were compared for the CBCL, TRF, and the combination of CBCL and TRF: the separate withdrawn/depressed, social problems, and thought problems syndrome scales; combinations of these syndrome scales; and special ASD scales composed of relevant individual items. Analyses were performed for: youth with a DSM-IV-based clinical diagnosis; youth for which the clinical DSM-IV diagnosis was confirmed by a standardized assessment (the Autism Diagnostic Interview-Revised); and youth with a DSM-IV- based clinical diagnosis of ASD that also met the DSM-5 criteria. The results clearly demonstrated that the special ASEBA-based scales – in particular when completed by the parents – were most predictive of ASD. The results also indicate that following the initial screen with these ASEBA scales, further thorough diagnostic assessment is necessary to definitively establish whether young people really suffer from ASD.

The LeadCare Ultra® (LCU) was compared to inductively coupled plasma mass spectrometry ICP-MS for use as a screening test for elevated blood lead levels (BLLs) in capillary samples from children.During the validation, method comparisons between LCU and ICP-MS were analyzed to determine the bias above, near, and below the BLL cut-off of 5 μg/dL. Additionally, capillary samples that screened positive by LCU (above the 5 μg/dL cut-off) were compared to venous samples analyzed by ICP-MS for confirmatory testing.LCU had a positive bias (1.7 μg/dL) below the cut-off of BLL5 μg/dL, no bias near the cut-off from BLL 5-10 μg/dL, and a negative bias (-0.8 μg/dL) for BLL10 μg/dL compared to ICP-MS. Of the 59 capillary samples that screened positive by LCU between May of 2017 to April of 2018, 19 were confirmed positive by ICP-MS, 30 were confirmed negative by ICP-MS, and 10 did not have a confirmed result.The LCU assay is an acceptable screen for capillary samples with the BLL cut-off of 5 μg/dL.

Protein crystallisation has for decades been a critical and restrictive step in macro-molecular structure determination via X-ray diffraction. Crystallisation typically involves a multi-stage exploration of the available chemical space, beginning with an initial sampling (screening) followed by iterative refinement (optimisation). Effective screening is important for reducing the number of optimisation rounds required, reducing the cost and time required to determine a structure. Here, we propose an initial screen (Shotgun II) derived from analysis of the up-to-date Protein Data Bank (PDB) and compare it with the previously derived (2014) Shotgun I screen. In an update to that analysis, we clarify that the Shotgun approach entails finding the crystallisation conditions which cover the most diverse space of proteins by sequence found in the PDB - which can be mapped to the well known Maximum Coverage problem in computer science. With this realisation we are able to apply a more effective algorithm for selecting conditions, such that the Shotgun II screen outperforms the Shotgun I screen both in protein coverage and quantity of data input. Our data demonstrates that the Shotgun I screen, compared with alternatives, has been remarkably successful over the seven years it has been in use, indicating that Shotgun II is likely to be a highly effective screen.

Concerns regarding increased prevalence of daptomycin (DAP)-resistant strains necessitate novel therapies for Enterococcus faecium infections. Obligately lytic bacteriophages are viruses that target, infect, and kill bacterial cells. Limited studies have evaluated phage-antibiotic combinations against E. faecium . After an initial screen of eight E. faecium strains, three strains with varying DAP/phage susceptibilities were selected for further experiments.

Glycolysis with PK-M2 occurs typically in anaerobic conditions and atypically in aerobic conditions, which is known as the Warburg effect. The Warburg effect is found in many oncogenic situations and is believed to provide energy and biomass for oncogenesis to persist. The work presented targets human PK-M2 (hPK-M2) in a virtual high-throughput screen to identify new inhibitors and leads for further study. In the initial screen, one of the 12 candidates selected for experimental validation showed biological activity (hit-rate = 8.13%). In the second screen with retrained models, six of 11 candidates selected for experimental validation showed biological activity (hit-rate: 54.5%). Additionally, four different scaffolds were identified for further analysis when examining the tested candidates and compounds in the training data. Finally, extrapolation was necessary to identify a sufficient number of candidates to test in the second screen. Examination of the results suggested stepwise extrapolation to maximize efficiency.

New on-demand multiplex molecular respiratory viral diagnostics offer superior performance although can be expensive and some platforms cannot process multiple specimens simultaneously. We performed a retrospective study reviewing results of patients tested for respiratory viruses following introduction of a two-stage testing algorithm incorporating an initial screen with Sofia® immunoassay then secondary Biofire Filmarray®, and compared to a period when only Filmarray® was used. Of 2976 testing episodes, 1814 underwent initial Sofia® then follow-up FilmArray®. A diagnosis of influenza was made by Sofia® in 282 patients, and by FilmArray® in an additional 163 (median time to result 1.12 hours versus 3.46 hours, P

Background/Aims: Preterm newborns with a very low birth weight (VLBW) of < 1,500 g have an atypical form of hypothyroidism with a delayed rise in TSH, necessitating a second newborn screening specimen collection. The aims of this study were to survey the compliance with second newborn screening to detect delayed TSH rise in VLBW preterm infants at a tertiary care center, and to determine the rate of atypical hypothyroidism. Methods: Retrospective review of the records of 104 preterm VLBW infants. Late TSH rise was defined as an increase in TSH concentration after 14 days of age in the presence of a normal initial screen. Results: The compliance rate was 92% for the second screening. High rates of hypothyroidism (16.3%) and of late TSH rise (4.8%) were detected. Patients with hypothyroidism had a significantly lower birth weight (p = 0.01) and longer hospital stay (p = 0.004). Patients with late versus those with early TSH rise had a significantly lower mean birth weight (851 ± 302 vs. 1,191 ± 121 g, p = 0.004). Conclusion: The rates of early and late TSH rise in this VLBW population were higher than those in the literature and could be due to the use of povidone-iodine disinfectants. The yield of a second TSH screening in this study was high indicating the need for vigilance in screening VLBW preterm infants.

Evidence suggests that increased use of screens early in life may have negative developmental consequences for children. However, little is known concerning parental factors that predict initial screen exposure in infancy. The primary goal of this study was to examine whether parental educational attainment and maternal stress were associated with infant screen exposure by 6 months of age. A diverse sample of mothers (N = 93) was recruited prenatally. In a follow-up visit when the infants were six months of age (N = 82), we examined factors that may be associated with initial infant exposure to screens. First, mothers reported whether they had already exposed their infants to screens. Thereafter, those mothers who reported already having exposed their infants to screens were further queried to determine the extent of infant screen use. Results demonstrated that among infants exposed to screens, mothers reported an average of nearly 3 h of daily screen use. Average parental educational attainment, but not maternal stress, was significantly associated with initial infant exposure. Of those families who endorsed screen exposure by 6 months, 70 % reported a screen in the room where the child sleeps, nearly half reported using screens to help calm the infant, and about a third reported using a screen at least sometimes during meals, when going to sleep, and while waiting. Parental education around infant screen use behaviors may be important to help promote child development and outcomes.

A systematic review with meta-analysis was performed to estimate the accuracy of IgM ELISA for Leptospirosis diagnosis. A search of Medline, Lilacs, Embase, Cochrane Central Register of Controlled Trials and Grey literature (Google Scholar and British Library) was conducted. The medical subject headings (MeSHs) and the words “leptospirosis”, “human leptospirosis” and “IgM ELISA” were used. Fifty-two studies were analyzed, which included 10,775 samples. The pooled sensitivity of all the studies was 86% (CI 95%, 85%-87%) and specificity was 90% (CI 95%, 89%-91%). In studies of the acute phase, the sensitivity and specificity were 84% (CI 95%, 82%-85%) and 91% (CI 95%, 90%-91%), respectively. In conclusion, IgM ELISA is sensitive for use as an initial screen for leptospiral infections. Resumo O objetivo desta revisão sistemática e meta-análise foi avaliar a acurácia do ELISA IgM para o diagnóstico precoce da leptospirose em humanos. A busca foi realizada nas seguintes bases de dados: Medline, PubMed, LILACS, Embase e Cochrane Central Register of Controlled Trials e Grey literature (Google Scholar and British Library). As palavras-chaves usadas foram: “leptospirosis”, “human leptospirosis” e “IgM ELI-SA”. Foram analisados 52 estudos, que incluíram 10.775 amostras. A sensibilidade e especificidade combinada de todos os estudos foram 86% (CI 95%, 85%-87%) e 90% (CI 95%, 89%-91%), respectivamente. Nos estudos de fase aguda, a sensibilidade e especificidade foram, respectivamente, 84% (CI 95%, 82%-85%) e 91% (CI 95%, 90%-91%). Conclui-se que o ELISA IgM é um teste sensível para rastreamento inicial da leptospirose.

Resumen Las enfermedades cardiovasculares representan una de las principales causas de morbilidad y mortalidad a nivel mundial, lo que se traduce en un fuerte impacto económico en el sector salud. El factor VIII (FVIII) es un cofactor esencial en los procesos hemostáticos que participa en la formación del coágulo ante alguna señal de daño vascular. La proteasa trombina es el principal activador fisiológico del FVIII, pero los mecanismos moleculares de reconocimiento del FVIII por la trombina y la formación de los complejos transitorios Michaelis-Menten correspondientes aún no se han descrito en detalle. La cristalografía de rayos X es una técnica que permite resolver la estructura 3D de complejos proteicos, pero requiere la cristalización previa de la muestra a estudiar. Con el objetivo de favorecer la formación de cristales del FVIIIa3 humano (residuos Glu1649-Arg1689) acomplejado con la trombina, se realizó mutagénesis dirigida para generar los doble-mutantes FVIIIa3 (R1689Q, G1690P) y FVIIIa3 (R1689G, G1690P). Estos fragmentos fueron sobreexpresados de forma heteróloga y purificados, obteniendo rendimientos de ~1.5 mg por cada litro de cultivo bacteriano. Esto permitió generar los complejos proteicos FVIIIa3 (R1689Q, G1690P)•trombina y FVIIIa3 (R1689G, G1690P)•trombina en cantidades suficientes para explorar sus espacios de solubilidad de forma extensiva. En total, en cada caso se evaluaron entre 630 y 820 condiciones de cristalización distintas. A partir de esta búsqueda inicial se obtuvo algún tipo de precipitado cristalino en 22 condiciones, 10 de las cuales lograron ser optimizadas para obtener monocristales de alta calidad para posteriores ensayos de difracción con rayos X. Abstract Cardiovascular diseases are one of the most important causes of morbidity and mortality worldwide, which translates into a strong economic impact in the health sector. Factor VIII (FVIII) is an essential cofactor within the hemostatic processes involved in blood clot formation upon vascular damage. The proteinase thrombin is the most important physiological activator of FVIII, but the molecular mechanisms underlying recognition of FVIII by thrombin and the formation of the corresponding, transient Michaelis-Menten complexes are still only poorly understood. X-ray crystallography allows the resolution of the 3D structure of protein complexes, but a prerequisite is the crystallization of the sample to be analyzed. To grow crystals of the human FVIIIa3 (residues Glu1649-Arg1689) complexed with thrombin, site-directed mutagenesis was performed to generate the double-mutants FVIIIa3 (R1689Q, G1690P) and FVIIIa3 (R1689G, G1690P). Both fragments were overexpressed as heterologous proteins and purified with yields of ~1.5 mg per liter of bacterial culture. Availability of these recombinant proteins allowed in turn generation of FVIIIa3 (R1689Q, G1690P)•thrombin and FVIIIa3 (R1689G, G1690P)•thrombin complexes to perform extensive screenings of their solubility space. Altogether, a total of 630 to 820 different crystallization conditions were evaluated for both complexes. From these initial screen, some sort of crystalline precipitate was obtained in 22 conditions, 10 of which could be optimized to grow high-quality single crystals for subsequent X-ray diffraction analysis.

OBJECTIVE: This study reports a method for measuring the electrically-evoked compound action potential (eCAP) in children with cochlear nerve deficiency (CND). DESIGN: This method was developed based on experience with 50 children with CND who were Cochlear® Nucleus™ cochlear implant (CI) users. RESULTS: This method includes three recommended steps conducted with recommended stimulating and recording parameters: initial screen, pulse phase duration optimization, and eCAP threshold determination (i.e., identifying the lowest stimulation level that can evoke an eCAP). Compared to the manufacturer-default parameters, the recommended parameters used in this method yielded a higher success rate for measuring the eCAP in children with CND. CONCLUSIONS: The eCAP can be measured successfully in children with CND using recommended parameters. This specific method is suitable for measuring the eCAP in children with CND in clinical settings. However, it is not suitable for intra-operative eCAP recordings due to the extensive testing time required.

Hand-held Raman spectroscopy is a potential tool for a confirmatory, non-invasive, and non-destructive detection and identification of rose rosette disease. Using this spectroscopic approach, structural changes in roses that are associated with this viral infection can be revealed. The commercial rose shrub industry in the United States is one of the largest of its kind. All commercial rose varieties are susceptible to rose rosette disease (RRD), a deadly viral disease vectored by eriophyid mites. This disease is typically diagnosed visually and/or by PCR-based detection assays. The present work demonstrates that Raman spectroscopy can detect RRD in intact leaf tissue. It is shown that chemometric analysis can distinguish between spectra collected from symptomatic and asymptomatic tissue, as well as between healthy and asymptomatic tissue. This method will be useful as an initial screen for RRD prior to PCR analysis to help conserve reagents and save time.

Drought can be a critical limitation on peanut yield. A physiological trait that may help to ameliorate drought is limited transpiration (TRlim), defined as a limitation on further increases in transpiration rate (TR) under high vapour pressure deficit (VPD) conditions. The advantage of the TRlim trait is that it allows plant water conservation to increase soil water availability for use during late-season drought. While this trait has been identified in peanut, there is no information of how readily the trait may be transfer to progeny lines. The objective of this study was to obtain preliminary information on the expression of the TRlim trait in two peanut progeny populations. One population was runner type of 88 RILs derived from the mating of Tifrunner × NC 3033. The second set was selected for the virginia-type phenotype of large pods obtained from mating of PI 585005 (ICGV 86015) and N0808olJCT, both of which expressed the TRlim trait. A two-tier screen was applied to both populations. The initial screen was based on exposure of de-rooted shoots to silver ions. Fifteen runner type and 12 virginia type were selected for direct measures of transpiration response to varying VPD. The results from each of the two populations showed that an effective expression of the TRlim trait occurred in about 30% of the progeny in each population. While these results do not offer a definitive index of inheritance, they do indicate that there appears to be a strong possibility of transferring the TRlim trait to progeny genotypes.

Purpose: To measure changes in breast density in a screening population. Method: Unprocessed mammograms were collected for 8,268 women (6034 and 2234 women with two and three sequential screening rounds respectively) with normal breasts (routine recall), from the OPTIMAM image database. The volumetric breast density (VBD), fibroglandular volume (FGV) and breast volume (BV) were determined and the changes between screening rounds calculated. Linear regression determined if the rate of change in these breast density measures varied significantly with age at initial screen. The women were split into four quartiles according to VBD in both screening rounds, and any changes in the quartile allocation of each woman determined. The VBD for these women was compared to our previously published data for women with screen detected and interval cancers. Results: Averaged over all women, the percentage change in VBD, FGV and BV, over 6 years was -11.2% (95%CI: - 12.2% to -10.2%), -5.3% (95%CI: -6.1% to -4.5%) and 11.5% (95%CI: 10.4% to 12.6%) respectively. The percentage change per month, of VBD, FGV and BD decreased significantly with age (p

Crystallization is in many cases a critical step for solving the three-dimensional structure of a protein molecule. Determining which set of chemicals to use in the initial screen is typically agnostic of the protein under investigation; however, crystallization efficiency could potentially be improved if this were not the case. Previous work has assumed that sequence similarity may provide useful information about appropriate crystallization cocktails; however, the authors are not aware of any quantitative verification of this assumption. This research investigates whether, given current information, one can detect any correlation between sequence similarity and crystallization cocktails. BLAST was used to quantitate the similarity between protein sequences in the Protein Data Bank, and this was compared with three estimations of the chemical similarities of the respective crystallization cocktails. No correlation was detected between proteins of similar (but not identical) sequence and their crystallization cocktails, suggesting that methods of determining screens based on this assumption are unlikely to result in screens that are better than those currently in use.

To determine whether Pteropine orthoreovirus (PRV) exposure has occurred in Singapore, we tested 856 individuals from an existing serum panel collected from 2005-2013. After an initial screen with luciferase immunoprecipitation system and secondary confirmation with virus neutralization test, we identified at least seven individuals with specific antibodies against PRV in both assays. Our findings confirm that PRV spillover into human populations is relatively common in this region of the world.

OBJECTIVEThe use of vancomycin powder in spine surgery for prophylaxis against surgical site infections (SSIs) is well debated in the literature, with the majority of studies demonstrating improvement and some studies demonstrating no significant reduction in infection rate. It is well known in certain populations that vancomycin powder reduces the general rate of infection, but its effects on reducing the rate of infection due to gram-negative pathogens are not well reviewed. The goal of this paper was to review studies that investigated the efficacy of vancomycin powder as a prophylactic agent against SSI and demonstrate whether the rate of infections by gram-negative pathogens is impacted.METHODSAn electronic search of the published literature was performed using PubMed and Google Scholar in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A variety of combinations of the search terms “vancomycin powder,” “infection,” “spine,” “gram-negative,” “prophylaxis,” and “surgical site” was used. Inclusion criteria were studies that 1) described an experimental group that received intraoperative intrawound vancomycin powder; 2) included adequately controlled groups that did not receive intraoperative intrawound vancomycin powder; 3) included the number of patients in both the experimental and control groups who developed infection after their spine surgery; and 4) identified the pathogen-causing infection. Studies not directly related to this review’s investigation were excluded from the initial screen. Among the studies that met the criteria of the initial screen, additional reasons for exclusion from the systematic review included lack of a control group, unspecified size of control groups, and inconsistent use of vancomycin powder in the experimental group.RESULTSThis systematic review includes 21 studies with control groups. Vancomycin powder significantly reduced the relative risk of developing an SSI (RR 0.55, 95% CI 0.45–0.67, p < 0.0001). In addition, the use of vancomycin powder did not significantly increase the risk of infection by gram-negative pathogens (RR 1.11, 95% CI 0.66–1.86, p = 0.701).CONCLUSIONSThe results of this systematic review suggest that intrawound vancomycin powder is protective against SSI. It is less clear if this treatment increases the risk of gram-negative infection. Further studies are required to investigate whether rates of infection due to gram-negative pathogens are affected by the use of vancomycin powder.

The identification of compounds for dissecting biological functions and the development of novel drug molecules are central tasks that often require screening campaigns. However, the required architecture is cost- and time-intensive. Herein we describe the devices and technologies that comprise a Robotics-Assisted Screening Platform for Efficient Ligand Discovery (RASPELD), which we set up in an academic laboratory. RASPELD provides semi-automated high-end screening, and it can be maintained by graduate students. We demonstrate its successful application in biochemical and cellular screens for the identification and validation of bioactive chemical entities as candidate cancer-relevant inhibitors. Specifically, we examined the interaction between a transcription factor, Nrf2, and its key regulator, Keap1. We also examined drug-resistant mutants of the epidermal growth factor receptor (EGFR). Screening campaigns with more than 30 000 compounds were performed in a reasonable period of time. We identified the molecule RSL6586 as a starting point for hit optimization, which is currently ongoing.

Zusammenfassung. Das differenzialdiagnostische Spektrum der chronischen Durchfallerkrankungen ist vielfältig und deren Abklärung anforderungsreich. Dieser Beitrag vermittelt einen Ansatz für eine rationelle und rationale diagnostische Strategie, um einerseits eine Überdiagnostik zu vermeiden und andererseits keine bedeutenden Erkrankungen zu verpassen. Die exakte Anamnese, die körperliche Untersuchung und ein Basislabor bilden die Grundlage in der Abklärung der chronischen Diarrhö. Ist diese Primärdiagnostik unauffällig, hat die Mehrzahl der jüngeren Patienten (50 Jahren gehört ergänzend die Koloskopie zur Primärdiagnostik. Wenn die Ursache nach dieser Diagnostik unklar bleibt, lohnt sich der Ansatz «categorize, test & treat», d.h. die Klassifizierung in entzündliche bzw. nicht-entzündliche chronische Diarrhö.

Objectives The study aimed to determine the validity of a smartphone hearing screening technology (hearScreen™) compared with conventional screening audiometry in terms of (1) sensitivity and specificity, (2) referral rate, and (3) test time. Design One thousand and seventy school-age children in grades 1 to 3 (8 ± 1.1 average years) were recruited from five public schools. Children were screened twice, once using conventional audiometry and once with the smartphone hearing screening. Screening was conducted in a counterbalanced sequence, alternating initial screen between conventional or smartphone hearing screening. Results No statistically significant difference in performance between techniques was noted, with smartphone screening demonstrating equivalent sensitivity (75.0%) and specificity (98.5%) to conventional screening audiometry. While referral rates were lower with the smartphone screening (3.2 vs. 4.6%), it was not significantly different (p > 0.05). Smartphone screening (hearScreen™) was 12.3% faster than conventional screening. Conclusion Smartphone hearing screening using the hearScreen™ application is accurate and time efficient.

6,6-Fused ring systems including tetrahydroisoquinolines and tetrahydropyrido[3,4-d]pyrimidines have been explored as possible replacements for the piperazine benzamide portion of the HIV-1 attachment inhibitor BMS-663068. In initial studies, the tetrahydroisoquinoline compounds demonstrate sub-nanomolar activity in a HIV-1 pseudotype viral infection assay used as the initial screen for inhibitory activity. Analysis of SARs and approaches to optimization for an improved drug-like profile are examined herein.

Synopsis Objectives Most of the cosmetic compounds with preservative properties available in the market pose some risks concerning safety, such as the possibility of causing sensitization. Due to the fact that there are few options, the proper development of new molecules with this purpose is needed. Xylitol is a natural sugar, and the antimicrobial properties of xylitol-derived compounds have already been described in the literature. C-8 xylitol monoester and xylitol phosphate esters may be useful for the development of skincare products. As an initial screen for safety of chemicals, the combination of in silico methods and in vitro testing can aid in prioritizing resources in toxicological investigations while reducing the ethical and monetary costs that are related to animal and human testing. This study was designed to evaluate the safety of C-8 xylitol monoester and xylitol phosphate esters regarding carcinogenicity, mutagenicity, skin and eye irritation/corrosion and sensitization through alternative methods. Methods For the initial safety assessment, quantitative structure-activity relationship methodology was used. The prediction of the parameters carcinogenicity/mutagenicity, skin and eye irritation/corrosion and sensitization was generated from the chemical structure. The analysis also comprised physical–chemical properties, Cramer rules, threshold of toxicological concern and Michael reaction. In silico results of candidate molecules were compared to 19 compounds with preservative properties that are available in the market. Additionally, in vitro tests (Ames test for mutagenicity, cytotoxicity and phototoxicity tests and hen's egg test – chorioallantoic membrane for irritation) were performed to complement the evaluation. Results In silico evaluation of both molecules presented no structural alerts related to eye and skin irritation, corrosion and sensitization, but some alerts for micronucleus and carcinogenicity were detected. However, by comparison, C-8 xylitol monoester, xylitol phosphate esters showed similar or better results than the compounds available in the market. Concerning experimental data, phototoxicity and mutagenicity results were negative. As expected for compounds with preservative activity, xylitol-derived substances presented positive result in cytotoxicity test. In hen's egg test, both molecules were irritants. Conclusion Our results suggested that xylitol-derived compounds appear to be suitable candidates for preservative systems in cosmetics. Resume Objectifs La plupart des composes cosmetiques possedant des proprietes antimicrobiennes disponibles sur le marche posent certains risques en matiere de securite, telles que la possibilite de provoquer une sensibilisation. Le developpement de nouvelles molecules a cet effet est donc necessaire. Le xylitol est un sucre naturel et les proprietes antimicrobiennes des composes de xylitol derives ont deja ete decrites dans la litterature. Les esters C-8 et monophosphate du Xylitol peuvent etre utiles pour le developpement de produits de soins de la peau. La combinaison de methodes in silico et de tests in vitro peut aider a prioriser les ressources dans les etudes toxicologiques pour effectuer un criblage quant a la securite des produits chimiques, tout en reduisant les couts ethiques et monetaires qui sont lies a des essais sur animaux et humains. Cette etude a ete concue pour evaluer l'innocuite des esters C-8 et monophosphate du Xylitol concernant le potential cancerogene, mutagene, d'irritation cutanee et oculaire/corrosion et de la sensibilisation a travers des methodes alternatives. Methodes Pour l'evaluation initiale de la securite, la methodologie relation structure-activite quantitative (QSAR) a ete utilisee. La prediction des parametres suivants: irritation/cancerogenicite/mutagenese, corrosionde la peau et des yeux/et sensibilisation a ete generee a partir de la structure chimique. L'analyse comprend egalement des proprietes physico-chimiques, les regles de Cramer, le Seuil de preoccupation toxicologique (TTC) et la reaction de Michael. Les resultats in silico des molecules candidates ont ete compares aux 19 composes ayant des proprietes conservatrices qui sont disponibles sur le marche. En outre, des tests in vitro (test d'Ames pour la mutagenicite, cytotoxicite et de phototoxicite et de HETCAM) ont ete realisees pour completer l'evaluation. Resultats L'evaluation in silico des deux molecules ne presente aucune alerte structurelle concernant l'irritation cutanee ou oculaire, la corrosion et la sensibilisation, mais certaines alertes pour le critere micronoyau et la cancerogenicite ont ete detectees. Cependant, dans la comparaison, les esters C-8 et monophosphate du Xylitol ont montre des resultats similaires ou meilleurs que les composes disponibles sur le marche. Concernant les donnees experimentales, les resultats de phototoxicite et de mutagenicite etaient negatifs. Comme on pouvait s'y attendre pour les composes ayant une activite conservatrice, les substances derives de xylitol presentent un resultat positif dans le test de cytotoxicite. Dans le test HETCAM les deux molecules sont irritants. Conclusion Nos resultats suggerent que les composes derives de xylitol semblent convenir comme candidats pour les systemes de conservation dans les cosmetiques.

Early discharge of newborns (24h after birth) from birthing centres is an important barrier to successful newborn hearing screening (NHS) in developing countries. This study evaluated the outcome of NHS within the first 48 h using an automated auditory brainstem response (AABR) device without the need for costly disposables typically required, and transient evoked otoacoustic emissions (TEOAE).NHS was performed on 150 healthy newborns (300 ears) with TEOAE and AABR techniques before discharge at a hospital. A three-stage screening protocol was implemented consisting of an initial screen with TEOAE (GSI AUDIOscreener+) and AABR (BERAphone(®) MB 11). Infants were screened at several time points as early as possible after birth. Infants were only re-screened if either screening technique (TEOAE or AABR) initially yielded a refer outcome. The same audiologist performed all TEOAE and AABR screenings.Over the three-stage screen AABR had a significantly lower refer rate of 16.7% (24/144 subjects) compared to TEOAE (37.9%; 55/145 subjects). Screening refer rate showed a progressive decrease with increasing age. For both TEOAE and AABR, refer rate per ear screened 24h post birth was significantly lower than for those screened before 24h. For infants screened before 12h post birth, the AABR refer rate per ear (51.1%) was significantly lower than the TEOAE refer rate (68.9%). Overall AABR refer rate per ear was similar for infants screened between 24 to 36 h (20.2%) and 36 to 48 h (18.9%) but significantly lower than for TEOAE (40.7% and 41.9%, respectively). Lowest initial refer rates per ear (TEOAE 25.8%, AABR 3.2%) were obtained after 48 h post birth.In light of the early post birth discharge typical in developing countries like South Africa, in-hospital screening with AABR technology is significantly more effective than TEOAEs. AABR screening with a device like the MB 11 is particularly appropriate because disposable costs are negligible.

Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating antibodies against complexes of platelet factor 4 (PF4) and heparin. The diagnosis of HIT is contingent on accurate and timely laboratory testing. Recently, alternative anticoagulants for the treatment of HIT have been introduced along with algorithms for better HIT diagnosis. However, the increased reliance on immunoassays for the diagnosis of HIT may have harmful consequences due to the high rate of false positive results. To compare trends and implications of current HIT testing approaches, we analyzed results over a six-year period from the McMaster University Platelet Immunology Reference Laboratory. From 2008 to 2013, 8,546 samples were investigated for HIT using both an in-house IgG-specific anti-PF4/heparin enzyme immunoassay (EIA) and the serotonin-release assay (SRA). Of 8,546 samples tested, 13.4% were true-positives (positive in both assays); 65.6% were true-negatives (negative in both assays); 20.9% were presumed false positive for HIT (EIA-positive/SRA-negative); and 0.2% were EIA-negative/SRA-positive. The frequency of EIA-positive/SRA-negative results increased over time (from 12.9% in 2008 to 22.9% in 2013). We found that the number of SRA-negative samples was reduced from referring centers that used an immunoassay as an initial screen; however, 41% of those samples tested negative in the immunoassay and in the SRA at the reference laboratory. The suspicion of HIT continues at a high rate and the agreement between the EIA and SRA test results remains problematic. Am. J. Hematol. 90:629–633, 2015. © 2015 Wiley Periodicals, Inc.

Healthcare providers use antinuclear antibodies (ANAs) to screen and diagnose patients with autoimmune diseases. In the recent years, commercial multiplex ANA kits have emerged as a convenient and fast diagnostic method. Diagnostic testing should follow sequenced algorithms: initial screen followed by specific antibody analysis. Second-level testing as an initial screen for autoimmune disease is inappropriate. We reviewed 68 patients with ANA comprehensive panels over a 6-month period from May 2015 to October 2015. We assessed appropriateness and estimated incurred losses from inappropriate testing. We found 92.6% (63 out of 68) of the ANA comprehensive panel results to be negative. Incurred losses from inappropriate ANA comprehensive panel testing were $66,000. Physicians should become familiar with ANA-sequenced diagnostic algorithms to avoid unnecessary higher level testing.

When high quality crystals are obtained that diffract X-rays, the crystal structure may be solved at near atomic resolution. The conditions to crystallize proteins, DNAs, RNAs, and their complexes can however not be predicted. Employing a broad variety of conditions is a way to increase the yield of quality diffraction crystals. Two fully automated systems have been developed at the MRC Laboratory of Molecular Biology (Cambridge, England, MRC-LMB) that facilitate crystallization screening against 1,920 initial conditions by vapor diffusion in nanoliter droplets. Semi-automated protocols have also been developed to optimize conditions by changing the concentrations of reagents, the pH, or by introducing additives that potentially enhance properties of the resulting crystals. All the corresponding protocols will be described in detail and briefly discussed. Taken together, they enable convenient and highly efficient macromolecular crystallization in a multi-user facility, while giving the users control over key parameters of their experiments.

Competition authorities regularly use simple price indicators within merger control procedures those affect differentiated product markets, from initial screen to underpinning of final decisions. The fundamental flaw of these indicators is that their prediction properties and, as a consequence, their usefulness is almost completely unknown. This paper reveals these properties: the merger-subpopulations they flag as problematic and, assuming linear or isoelastic demand, the type I and II errors. This knowledge creates the opportunity for a more conscious use of these tools.

RAPID-B® is a high performance, integrated microbiology/infectious disease diagnostic system. The system uses hardware and software that are specifically designed for optimal detection using custom, immuno-based reagents designed to react to cell surface antigens of the target bacteria. The Vivione Bioscience RAPID-B Escherichia coli O157 and non-O157 Shiga toxin-producing E. coli (STEC) kits were validated alongside the U.S. Department of Agriculture, Food Safety and Inspection Service (FSIS), Microbiology Laboratory Guidebook (MLG) 5.07 (for E. coli O157) and FSIS MLG 5B.04 (fornon-O157 STEC) reference methods for the detection of E. coli O157 and STEC. The matrixes, ground beef and beef trim, were inoculated with appropriate CFU/test portion of E. coli O157 and STEC so as to generate fractional positives results, 5 to 15 positives out of 20 inoculated samples. Samples were enriched in prewarmed Brain Heart Infusion broth at 42 ± 1°C for 6.5–7.5 h or 8.5–9.5 h depending on thesample size. All samples were confirmed using the MLG reference method, regardless of initial screen result. The RAPID-B test methods were statistically equivalent to the reference method for the detection ofE. coli O157 and STEC in all testedsamples. Inclusivity and exclusivity testing of the RAPID-B methods showed 100% specificity for both kits. Finally, the RAPID-B test methods were shown to be robust when variations were applied to enrichment time, broth temperature, and vortexing time.

Foul-release marine coatings are viable alternatives to broad-spectrum biocidal coatings. Efficient and economical methods for field testing and screening of novel foul-release coatings are needed to address performance and stability. Short-term tests that challenge coatings with heavy fouling conditions, by employing small coupons, are desirable to coating developers as this method allows many formulations to be screened at lower material cost and time. By coupling the field test to a miniature waterjet cleaning test, foul-release coatings may also be assessed for ease of fouling removal. Here, the feasibility of using small coupons over large panels for screening of foul-release coatings in static immersion field tests is investigated. Experimental and commercial foul-release coatings were field tested using a large panel, long term (1 year) test and a small coupon, short term (1 month) test. Results were very similar between the two assays, with each clearly distinguishing coating that performed well from those that performed poorly. The method may serve as a useful initial screen for early stage coatings.

The traditional ways of conceiving learning — a process of transferring knowledge — leads to a privileging of knowledge management systems which reduce, codify and transfer information as if it were usable knowledge. This chapter explores the problematic assumptions which lie behind such approaches to knowledge management and present an alternative, Computerized Evaluative Learning Tool (CELT), which is being used to facilitate the learning of GPs. It has been designed in a way which seeks to escape some of the problems of traditional knowledge management. The chapter explores an alternative metaphor for learning 镃 that of travel – and apply post-dichotomous thinking to the learning framework. It shows the main CELT splash screen. The initial screen identifies different routes into using the system. Once the learner has completed the initial screens, they can conduct further analysis. It is important to acknowledge the social environment of learning, particularly when the learning carries emotional connotations.

Summary Infection control effectiveness at 6 English hospitals was compared using whole-genome sequencing of C. difficile isolates. Proportions of isolates sufficiently genetically related to suggest transmission from a previous isolate ranged from 7% at the best institution to 22–26% in most others., Background. Variation in Clostridium difficile infection (CDI) rates between healthcare institutions suggests overall incidence could be reduced if the lowest rates could be achieved more widely. Methods. We used whole-genome sequencing (WGS) of consecutive C. difficile isolates from 6 English hospitals over 1 year (2013–14) to compare infection control performance. Fecal samples with a positive initial screen for C. difficile were sequenced. Within each hospital, we estimated the proportion of cases plausibly acquired from previous cases. Results. Overall, 851/971 (87.6%) sequenced samples contained toxin genes, and 451 (46.4%) were fecal-toxin-positive. Of 652 potentially toxigenic isolates >90-days after the study started, 128 (20%, 95% confidence interval [CI] 17–23%) were genetically linked (within ≤2 single nucleotide polymorphisms) to a prior patient’s isolate from the previous 90 days. Hospital 2 had the fewest linked isolates, 7/105 (7%, 3–13%), hospital 1, 9/70 (13%, 6–23%), and hospitals 3–6 had similar proportions of linked isolates (22–26%) (P ≤ .002 comparing hospital-2 vs 3–6). Results were similar adjusting for locally circulating ribotypes. Adjusting for hospital, ribotype-027 had the highest proportion of linked isolates (57%, 95% CI 29–81%). Fecal-toxin-positive and toxin-negative patients were similarly likely to be a potential transmission donor, OR = 1.01 (0.68–1.49). There was no association between the estimated proportion of linked cases and testing rates. Conclusions. WGS can be used as a novel surveillance tool to identify varying rates of C. difficile transmission between institutions and therefore to allow targeted efforts to reduce CDI incidence.

This study aimed to explore the association between screen exposure in early life and preschool myopia. During the baseline survey of the Longhua Child Cohort Study (LCCS), data of 29,595 preschoolers were collected via a caregiver-reported questionnaire regarding children&rsquo, s socio-demographic characteristics, visual status, screen exposure and relevant parental information. Data of 26,433 preschoolers with normal eyesight or myopia were included in the analysis and cox regression modelling was employed to assess the associations. Results suggested the hypothesis that screen exposure in early life could be significantly and positively associated with preschool myopia, and in agreement with this hypothesis was the association being strengthened with the increasing daily exposure duration and total years of exposure, in the stratification analysis based on the presence of parental myopia, these associations still existed, and the strength of associations was stronger in preschoolers with myopic parents than those without. Moreover, a statistically significant association was only observed between initial screen exposure that occurred during 0&ndash, 1-years old and myopia for preschoolers without myopic parents, while the significant associations were observed between initial screen exposure that occurred during 0&ndash, 1, 1&ndash, 2, 2&ndash, 3, and after 3 years old and myopia for preschoolers who had myopic parents, with the strongest association found in the group of children initially exposed to electronic screens during 0&ndash, 1 year old. Thus our findings indicated the hypothesis that screen exposure in early life might be associated with the occurrence of preschool myopia, and that the postnatal first year might be the sensitive period for the association. However, it is premature to conclude that early screen time leads to myopia with current data. Further longitudinal studies performed with cycloplegia are necessary to verify the hypothesis and shed light on the more urgent question whether early screen exposure contributes to the later myopia epidemic of school-aged children.

The power of microseed matrix screening is demonstrated in the crystallization of a panel of antibody Fab fragments., The crystallization of 16 human antibody Fab fragments constructed from all pairs of four different heavy chains and four different light chains was enabled by employing microseed matrix screening (MMS). In initial screening, diffraction-quality crystals were obtained for only three Fabs, while many Fabs produced hits that required optimization. Application of MMS, using the initial screens and/or refinement screens, resulted in diffraction-quality crystals of these Fabs. Five Fabs that failed to give hits in the initial screen were crystallized by cross-seeding MMS followed by MMS optimization. The crystallization protocols and strategies that resulted in structure determination of all 16 Fabs are presented. These results illustrate the power of MMS and provide a basis for developing future strategies for macromolecular crystallization.

Screening for mental health problems on reception into custody has been criticised. However, there have been few studies on care pathways through custody as a result of screening identification. We aimed to identify what actions were taken as a result of screening positive for suicidal ideation and mental health problems. Case records for 2166 prisoners newly received into five prisons in England and documented contact with health care professionals in the following month were examined by hand over a four-month period. Altogether, 3% of prisoners were screened as having current suicidal ideas, of whom 30% had no contact with mental health services or risk assessment documentation. Another 21% of new receptions received psychotropic medication, for whom over 60% received no primary mental health assessment, and only 36% received psychotropic medication in prison. Care pathways need to be defined, and screening needs to be delivered as originally intended by initial screen for life-threatening matters, foll...

Adalimumab is a TNF specific monoclonal widely used therapeutically. Monitoring adalimumab levels is important for guiding treatment strategies and is predominantly performed using an ELISA. The homogeneous mobility shift assay (HMSA) has many advantages over an ELISA for adalimumab monitoring but current HMSA methodologies do not discriminate between adalimumab and other TNF specific monoclonals such as infliximab. The development and validation of a competitive binding HMSA (cHMSA) specific for adalimumab is reported here. The cHMSA had a lower limit of quantitation of 1.25 μg/ml and the intra-assay and inter-assay coefficents of variation (CV) were20%. No signal was detected in adalimumab naïve control serum including those containing rheumatoid factor or infliximab. The majority (14/20) of adalimumab patient samples containing anti-adalimumab antibodies gave a cHMSA signal3 standard deviations lower than the controls. The performance of the cHMSA and an ELISA was compared using adalimumab patient samples (n = 82). There was a strong correlation between the assays (r = 0.91) and the intra-class correlation coefficient (0.88) was indicative of good-excellent inter-assay reliability. Bland-Altman plots showed little overall bias and comparison of the sub-groups defined using cut-points (1.25 or 7.3 μg/ml) gave percent agreement (90%) and Cohens kappa (95% CI: 0.61-0.93) values indicative of substantial-almost perfect agreement. These results demonstrate that cHMSA provides an accurate and specific method for monitoring adalimumab levels and can additionally provide an initial screen for the presence of anti-adalimumab antibodies.

In reviewing manuscripts or in reading published research studies, the reader should always ask about the appropriateness of statistical methods. For the clinician, a clear algorithm will usually remove a lot of the guesswork when deciphering statistical language. Most studies submitted to medical journals, unless they are large population outcomes studies targeting novel metrics, can be analyzed using time-tested, universally understood methods. The intent of this article is to help the clinician perform an initial screen for appropriateness of the statistic methods chosen by the investigators.

Schizophrenia is a prevalent neurodevelopmental psychiatric disorder with poor prognosis and limited understanding of its etiology. This limited etiological understanding renders developing animal models of schizophrenia difficult. Although attempts are made to recreate putative etiologies in models, these models may only enable the generation of treatments targeted at the mechanisms manipulated. Although the chakragati mouse was not created as a result of a specific gene target, reports to date suggest these mice exhibit behavioral abnormalities that are consistent with some observed in patients with schizophrenia. As an initial screen on the relevance of these mice to schizophrenia, we tested the exploration and sensorimotor gating of male and female chakragati mice in the cross-species tests behavioral pattern monitor (BPM) and prepulse inhibition (PPI), respectively. The chakragati mice exhibited hyperactive yet more meandering/circling movements of exploration compared with wildtype (WT) littermates. Moreover, chakragati mice exhibited impaired PPI compared with WT mice, primarily at high prepulse intensity levels. Thus, chakragati mice share some of the abnormal exploratory and PPI behaviors that are observed in patients with schizophrenia. These behaviors can be used to screen for novel antipsychotics which may be based on novel mechanisms of action. The multivariate abnormal exploration of these mice may also yield further information for treatment effects. Further characterization of these mice in tasks with putative links to negative or cognitive symptoms may further advance the utility of these mice as a screen for novel treatments for schizophrenia.

A rapid screening method to identify the best conditions for chiral separations is described. We analyzed a representative set of 80 racemic compounds against 25 different chiral stationary phases with three different mobile phases to identify the combination of columns and mobile phases that will separate the most compounds on the initial screen. While the OD separated the largest number of compounds, we found the best combination of six columns to be the AD, AS, AY, CC4, ID and Whelk-O1. The second team included the CCC, Cellulose-1, Cellulose-3 or OJ, IA, IE and IF. All 80 compounds were separated with a resolution range of 0.65-15.36. Screening the covalently bonded phases provided separation for 79 of the 80 compounds. We also found ethanol (0.1% NH4OH) separated more compounds than methanol (0.1% NH4OH) or isopropanol (0.1% NH4OH). As part of this study, we also compared the effectiveness of stationary phases that have the same chiral selector. Finally, we demonstrated the effectiveness of using a fast, 1.5-min screening method that utilizes a 1.7μm coated polysaccharide chiral stationary phase.

Summary Aims Overseas studies have shown equivalent sensitivity and specificity between computer-assisted screening and manual screening, with increased screener productivity. This study was undertaken to test these in a New Zealand laboratory setting. Methods A total of 9232 slides were read manually alone, and following ThinPrep Imager-assisted screening, and the results compared. Two senior screeners and a cytopathologist reviewed the slides with discordant results. Results: The detection rate for abnormalities was 7.30% for Imager-assisted screening and 7.83% for manual screening. The concordance in diagnosis of abnormalities ranged from 72.7% to 100% with the lowest concordance for high-grade abnormalities diagnosed by Imager-assisted screening. The rate of unsatisfactory smears with Imager-assisted screening is half that of manual screening. There was a screener productivity increase of 140%. In all but one case, abnormal cells were identified by the Imager but screeners varied in their interpretations. Conclusions Overall, Imager-assisted screening was as sensitive as manual screening, and more sensitive for high- grade lesions, with a halving of the rate of unsatisfactory smears. In the setting of the New Zealand cervical screening program, the initial screen by the Imager removes the need for a second, rapid rescreen required by the program for manual screening.