Lower Level Of Sensitivity Research Articles

Analysis of disease free survival in cutaneous melanoma patients subject to sentinel lymph node biopsy.

<b>Introduction:</b> Cutaneous melanoma is estimated for 2% of malignant neoplasms occurring in humans. It is characterized by a high level of malignancy and low sensitivity to cytostatic drugs. The incidence of cutaneous melanoma is increasing in Poland. The lymphatic system is the most common route of dissemination of this neoplasm. The appearance of a sentinel node biopsy technique has made it possible to identify patients with a regionally advanced disease. It is a minimally invasive method with a small percentage of complications. <br><b>Aim: </b>Analysis of disease free survival (DFS) in cutaneous melanoma patients with sentinel lymph node biopsy. <br><b>Material and methods:</b> The analysis included 222 patients with cutaneous melanoma treated in the Department of Oncological Surgery in 2010-2015, who underwent a sentinel node biopsy. The study group consisted of 136 women and 86 men, the average age of patients was 59 years. Patients were qualified for sentinel node biopsy based on clinical evaluation and ultrasound of regional lymph nodes. The average follow-up was 25.1 months. About 2 hours before surgery, patients received a radioisotope, then lymphoscintigraphy SPECT was performed. Additionally, they were administered the Patent Blue dye in the operating room. <br><b>Results:</b> The sentinel node was identified in 217 patients (98%), and the average sentinel nodes were 2.25. Twenty-seven patients (12%) had a metastasis in sentinel nodes. In this group, the duration of symptom free survival was significantly shorter. Sentinel node status and age of the patient were independent factors affecting the prognosis of disease free survival. <br><b>Conclusions:</b> Sentinel node biopsy is a precise method to identify patients with cutaneous melanoma who have metastasis to regional lymph nodes, as well as the most important prognostic factor.

The role of computed tomography in the diagnostic pathway of acute mesenteric ischemia: a nested case-control study

Computed tomography (CT) can be used as the primary screening modality for the evaluation of patients suspected of having acute mesenteric ischemia known to show high sensitivity and specificity rates. To prove the value of CT in patients with pathological abdominal findings following cardiac surgery. In a retrospective case-control study, 12 different CT scan parameters of patients with or without mesenteric ischemia following cardiac surgery were compared using univariate and logistic regression analyses. Of 14,176 patients, 133 (0.9%) received an abdominal CT scan during postoperative care due to pathological abdominal findings. Sixty-eight patients were diagnosed with acute mesenteric ischemia. In-hospital mortality was 73.5% for this group. CT parameters with the highest specificity for indicating colonic ischemia were intestinal (99%) or porto-venous (96%) pneumatosis, abnormal contrast medium enhancement (89%), and occlusion of the proximal inferior mesenteric artery (81%). All of those parameters showed low sensitivity levels in the range of 15%-23%. A statistically significant association between acute mesenteric ischemia and CT appearance was obtained for contrast medium enhancement (odds ratio [OR] 12.2, 95% confidence interval [CI] 1.5-99.2) and intestinal pneumatosis (OR 21.0, 95% CI 2.7-165.2) only. The typical CT criteria indicating mesenteric ischemia lose their accuracy in patients under critical clinical conditions. As CT remains the first-line diagnostic imaging modality for abnormal abdominal findings following cardiac surgery, negative signs should not prevent early laparotomy if clinical suspicion remains high.

A TEN-YEAR ANALYSIS OF CHANGES IN THE SENSITIVITY OF THE LEADING UROPATHOGEN TO ANTIBACTERIAL AGENTS IN CHILDREN WITH URINARY TRACT INFECTION IN THE NEPHROLOGY DEPARTMENT

The aim: To study the prevalence of ABR among children with UTI over the past 10 years, with an assessment of the sensitivity of E. Coli to common antibiotics in dynamics. Materials and methods: The study involved 1,044 children with UTI aged from 1 month to 18 years. Examination of patients and interpretation of the results was performed in accordance with the provisions of the Declaration of Helsinki of Human Rights. According to the design, the study included 3 comparison groups: Group 1 - children of the 2009 follow-up year (n = 337), Group 2 - of 2014 (n = 328) and Group 3 - of 2019 (n = 379). Results: Escherichia coli is recognized as the leading uropathogen in all study groups: its percentage in Group 1 was 47 % (158/337), in Group 2 - 64 % (210/328) and in Group 3 - 66.5 % (252/379). The prevalence of antibacterial resistance of E. coli strains and the high dynamics of its growth are shown. So the level of resistance of E. Coli in 2019 was 70 ± 4.06 % (176/252). This was 11 % more compared to 2014 and 18.8 % more compared to 2009. The percentage of multiresistant strains tended to increase and amounted to 28 ± 9.97 % (70/252) among patients with UTI and 40 ± 9.12 % (70/176) in the structure of resistance in 2019. The relative risk of ABR increased by 1.6 times in 2019 compared to 2014 (RR2019 = 2.208 ± 0.207 [1.473;3.310], р < 0.05 vs RR2014 = 1.375 ± 0.209 [0.913;2.063]) and by 3 times compared to 2009 (RR2009 = 0.727 ± 0.209 [0.483;1.095]). Ampicillin and amoxicillin showed an equally low sensitivity level (3.5 ± 32.14 % (9/252)). Only every second child confirmed sensitivity to cefuroxime (53.6 ± 5.76 (135/252)). Ceftazidime and ciprofloxacin showed a relatively high sensitivity level - 77.4 ± 3.34 (195/252) and 83 ± 2.81 (209/252), and at the same time the rapidly growing resistance rates - almost twice as high over the past 5 years. Furazidin K showed a high sensitivity level of 85.7 ± 2.53% (216/252), the lowest level of overall resistance of 14.3 ± 15.15 % (36/252) and a slow rate of its formation. An unfavourable prognosis of an increase in the relative risk of ABR by 2.9-3.7 times in the next 5-10 years was determined among patients with UTI, provided that the existing diagnostic and treatment approaches are maintained. Conclusions: The study results are important for understanding the clinical decision on the benefits of antibacterial therapy and optimizing its empirical choice for a patient with UTI.

Relevance of Low Specific IgE Levels to Egg, Milk and Peanut in Infancy

To evaluate the clinical importance of low specific immunoglobulin E (IgE) to hen’s egg, cow’s milk, and peanut at 6 months in relation to doctor’s diagnosis of allergy-related disease at 5 years of age.Families in Sweden were recruited between 2004 and 2011 (ALADDIN prospective birth cohort). This study included 372 children, all of whom contributed a blood sample at 6 months and at 1, 2, and/or 5 years of age. Fifty percent were girls, 17% were born via cesarean delivery, and 26% were breastfed exclusively for 6 months. At 6 months, 11% had a doctor’s diagnosis of asthma, 12% had a diagnosis of eczema, 3% had a diagnosis of allergic rhinoconjunctivitis, and 8% had a diagnosis of food allergy.Questionnaires regarding lifestyle, background, diet, and health were completed at enrollment, 2 and 6 months, and 1, 2, and 5 years of age. Serum IgE to specific foods and aeroallergens was measured in children at 6 months and 1, 2, and 5 years. For the statistical analysis, 3 categories were designated: nonsensitized (<0.1 kU/L), low sensitized (0.1–0.34 kU/L), and sensitized (≥0.35 kU/L); proportion with allergy-related disease was assessed.For egg and milk, having specific IgE in the interval of 0.1 to 0.34 kU/L at 6 months was significantly associated with being sensitized (≥0.35 kU/L) to that specific allergen at 1 year (P = .01 and <.01, respectively) and to aeroallergens at 5 years (P = <.01 and .01), compared with nonsensitized children. Being sensitized (≥0.35 kU/L) to egg or milk at 6 months was significantly associated with sensitization to the food at 1 and 2 years of age and to any food allergen, but it was not associated with aeroallergen sensitization at 5 years as compared with those with low sensitization (P = .69). Approximately 50% of children with low sensitization to milk or egg at 6 months had IgE that declined to nonsensitized levels at 2 years of age. For peanut, low sensitization at 6 months was only significantly associated with being sensitized to aeroallergens at 5 years of age (P = .04). Low-level sensitization to egg was associated with higher rates of eczema (P < .01).Specific IgE to milk, egg, and peanut in the range of 0.1 to 0.34 kU/L at 6 months appeared to decrease over time. However, low-level sensitization at 6 months appeared to increase the likelihood of sensitization to aeroallergens at 5 years. Compared with those who were nonsensitized at 6 months, children with low sensitization to milk or egg had higher rates of sensitization to that allergen at 1 year of age. Having low sensitization to egg at 6 months was associated with the development of eczema.Researchers in this study evaluated whether specific IgE at 6 months was associated with further IgE sensitization and allergy-related diagnosis. The strengths of the study include that it was population based and managed children over the course of 5 years. The study does not provide any data about the development of clinical food allergy. This study suggests that children with low sensitization at 6 months can be counseled that ∼50% had undetectable IgE to the relevant allergen at 2 years, but the low sensitization could suggest a higher risk of future aeroallergen sensitization as well as potentially eczema for those with egg-specific IgE.

Clustering the Brain With "CluB": A New Toolbox for Quantitative Meta-Analysis of Neuroimaging Data.

In this paper we describe and validate a new coordinate-based method for meta-analysis of neuroimaging data based on an optimized hierarchical clustering algorithm: CluB (Clustering the Brain). The CluB toolbox permits both to extract a set of spatially coherent clusters of activations from a database of stereotactic coordinates, and to explore each single cluster of activation for its composition according to the cognitive dimensions of interest. This last step, called “cluster composition analysis,” permits to explore neurocognitive effects by adopting a factorial-design logic and by testing the working hypotheses using either asymptotic tests, or exact tests either in a classic inference, or in a Bayesian-like context. To perform our validation study, we selected the fMRI data from 24 normal controls involved in a reading task. We run a standard random-effects second level group analysis to obtain a “Gold Standard” of reference. In a second step, the subject-specific reading effects (i.e., the linear t-contrast “reading > baseline”) were extracted to obtain a coordinates-based database that was used to run a meta-analysis using both CluB and the popular Activation Likelihood Estimation method implemented in the software GingerALE. The results of the two meta-analyses were compared against the “Gold Standard” to compute performance measures, i.e., sensitivity, specificity, and accuracy. The GingerALE method obtained a high level of accuracy (0.967) associated with a high sensitivity (0.728) and specificity (0.971). The CluB method obtained a similar level of accuracy (0.956) and specificity (0.969), notwithstanding a lower level of sensitivity (0.14) due to the lack of prior Gaussian transformation of the data. Finally, the two methods obtained a good-level of concordance (AC1 = 0.93). These results suggested that methods based on hierarchical clustering (and post-hoc statistics) and methods requiring prior Gaussian transformation of the data can be used as complementary tools, with the GingerALE method being optimal for neurofunctional mapping of pooled data according to simpler designs, and the CluB method being preferable to test more specific, and localized, neurocognitive hypotheses according to factorial designs.

Efficiency of Rapid Antigen Test in Diagnosis of Acute Streptococcal Tonsillopharyngitis

Objective: Group A beta hemolytic streptococcus (GABHS) is the most common bacterial cause of acute tonsillopharyngitis. Cases with bacterial infection suspicion should undergo rapid antigen test (RAT) and/or throat culture test in addition to clinical criteria, since it may lead to serious complications.Method: A total of 220 adult and pediatric patients admitted to the emergency department between April-May 2016 with complaints of fever and sore throat, and diagnosed as acute tonsillopharyngitis were prospectively enrolled to the study. All participants had Centor score ≥2 and they underwent RAT. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of RAT results of both groups were compared. Throat culture was considered as gold standard method.Results: Mean age of the study population was 22,5±16,9 (1-72) years. 57% (n=61) of the pediatric group, and 42.5% (n=48) of adult group were male. Sensitivity of RAT in adults and pediatric group was 62% vs. 57%, and specificity of the test was 96% vs. 97%, PPV was 55% vs. 80%, and NPV was 97% vs. 93%, respectively.Conclusion: We found low sensitivity and PPV values of RAT. Also, low levels of sensitivity decrease the possibility of RAT to be a diagnostic tool for the diagnosis of GABHS.

Rectal Exploration: its Importance in Diagnosing Prostate Cancer

This paper deals with the importance of rectal exploration in order to diagnose a possible prostate cancer. This article describes in details the correct procedure of rectal exploration, its preeminent importance in discovering diseases and every possible how is possible to hypothesize some disease through this exploration. For this reason, a correct rectal exploration is considered as the fastest way to identify prostate cancer (or any kind of disease), before making any other examination; actually it should be regularly done even in absence of symptoms. The rectal exploration (RE) must constitute the first diagnostic approach to the patient that presents symptoms referable to a possible prostatic pathology. Given that prostate cancer occurs in more than 70% of cases at the peripheral portion of the gland, the neoplastic nodule can often be detected already with the simple palpation. In particular, this is easier when the lesion has a volume of 0.2 mL or greater. About 18% of prostatic neoplasms are detected by rectal exploration alone, regardless of PSA values. A suspected palpatory to the RE, associated with a PSA>2ng/ml, presents a positive predictive value between 5 and 30%. An at least dubious RE is also associated with an increased risk of disease with a high Gleason score and therefore leads to taking into account the execution of post-operative biopsy. However, the RE, although indispensable in the evaluation of the patient, cannot be used singularly as the only diagnostic method, as it presents low levels of sensitivity (positive predictive value), and specificity. In large series of patients it has been shown that the ER fails the diagnosis of cancer in about half of the cases, as there is no demonstrated correspondence between a palpatory alteration and the presence of tumor.

Rapid Detection of Botulinum Neurotoxins-A Review.

A toxin is a poisonous substance produced within living cells or organisms. One of the most potent groups of toxins currently known are the Botulinum Neurotoxins (BoNTs). These are so deadly that as little as 62 ng could kill an average human; to put this into context that is approximately 200,000 × less than the weight of a grain of sand. The extreme toxicity of BoNTs leads to the need for methods of determining their concentration at very low levels of sensitivity. Currently the mouse bioassay is the most widely used detection method monitoring the activity of the toxin; however, this assay is not only lengthy, it also has both cost and ethical issues due to the use of live animals. This review focuses on detection methods both existing and emerging that remove the need for the use of animals and will look at three areas; speed of detection, sensitivity of detection and finally cost. The assays will have wide reaching interest, ranging from the pharmaceutical/clinical industry for production quality management or as a point of care sensor in suspected cases of botulism, the food industry as a quality control measure, to the military, detecting BoNT that has been potentially used as a bio warfare agent.

Abstract 1662: Detection of chromosomal allelic imbalances from RNAseq data using hapLOHseq

Abstract RNA-seq is commonly used to profile tumors through transcript quantification and detection of alternative transcripts and gene fusions. Recent advancements enabled assessment of allele-specific gene expression. In this study, we characterize chromosomal allelic-imbalances (AI) through the identification of haplotype-specific patterns in RNA-seq data. We processed SNP-array, whole-exome sequencing (WES), and RNA-seq data for two cancer sites from The Cancer Genome Atlas (TCGA): colon adenocarcinoma (COAD) and lung adenocarcinoma (LUAD). For the WES and RNA-seq data, we phased variants in the 1000 Genomes Project database and then used the hapLOHseq algorithm to detect AI. AI events detected in the Affymetrix SNP array 6.0 data were used as a gold standard, as it queries a much larger proportion of heterozygous sites relative to WES and RNA-seq. A comparison of AI calls derived from the TCGA COAD RNA-seq and WES data to the gold standard events inferred from SNP-array yielded similar specificity estimates of 92% and 96% in WES and RNA-seq, respectively. However, with a sensitivity of 43%, RNA-seq derived AI calls had decreased overlap with gold standard events, compared to WES derived AI calls with 86% sensitivity. The TCGA LUAD analysis resulted in specificity estimates of 88% and 95% in WES and RNA-seq, respectively, and sensitivity estimates of 84% and 35%, respectively, for identifying gold standard events. Events detected exclusively in RNA-seq are classified as false positives in our sensitivity/specificity calculations. Possible validity of those events was assessed by investigating clinical correlations between RNA-seq only events and clinical phenotypes such as cancer stage, overall survival, and mutations in 21 bona fide tumor suppressor genes (TSG) involved in chromatin modification. We found a marginally significant correlation between the number of RNA-seq only events and the number of mutations in this set of TSG genes (p value = 0.07, corr. = 0.19) for the COAD study; however, we did not observe such a correlation in the LUAD study. This may be explained by a potential larger influence of extrinsic environmental factors, smoking, leading to epigenetic changes in the LUAD. In the LUAD, we observed a potential clinical association between the existence of RNA-specific events and worse overall survival (p-value = 0.15). Although at lower sensitivity levels, our results suggest that RNA-seq may be used to detect AI in the absence of available DNA profiles. Clinically, our results may indicate that higher RNA-specific AI load may have a worse overall prognosis and we are exploring this further in additional TCGA datasets. The AI we detect in the RNA-seq samples may reflect long-range epigenetic dysregulation. RNA-exclusive AI may be caused by mutations in cancer driver and lineage genes may lead to selective cis-epigenetic chromatin alterations affecting large genomic regions. Citation Format: Zuhal Ozcan, F. Anthony San Lucas, Yasminka Yakubek, Yihua Liu, Richard G. Fowler, Paul A. Scheet. The University of Texas M.D. Detection of chromosomal allelic imbalances from RNAseq data using hapLOHseq [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1662.

Antenatal interpersonal sensitivity as an early predictor of vulnerable mother-infant relationship quality.

Maternal mental health problems in the perinatal period incur significant human and economic costs attributable to adverse child outcomes. In response, governments invest in screening for perinatal depressive symptoms. Mother-infant relationship quality (MIRQ) is a key mechanism linking maternal perinatal mental health to child outcomes. Perinatal depressive symptoms are typically transient while personality style, including interpersonal sensitivity, is a more stable construct. We have demonstrated that antenatal interpersonal sensitivity independently predicted MIRQ at 12 months postpartum. Building on our previous work, the objective of this study was to examine the associations of antenatal interpersonal sensitivity and depressive symptoms with MIRQ 1 year postnatal. A sample of 73 women attending routine antenatal care, 61 (84%) from ethnically diverse populations, were studied across the perinatal period. At ⩽26 weeks, gestation interpersonal sensitivity and depressive symptoms were measured. At 12 months, postnatal mental health and MIRQ was assessed in 35 of the mother-infant dyads. We found no significant statistical association between antenatal interpersonal sensitivity and depressive symptoms with postnatal MIRQ. Interpersonal sensitivity (r = -.24) showed weak association with MIRQ. Depressive symptom scores were not associated (r =-.01). Maternal sensitivity assessment (MIRQ) using the CARE-Index identified low mean scores signifying low levels of maternal sensitivity (potential range 0-14; mean score = 6.3). We cautiously suggest that the findings raise questions about the presentation and assessment of perinatal mental health status among ethnically diverse populations and scoping of parenting support needs within this population.

Detection of Human Microchimerism following Allogeneic Cell Transplantation Using Droplet Digital PCR.

Background Cell transplantation is in clinical development for the treatment of various ailments including acquired and inborn hepatic diseases. Detection and quantification of the donor cells after infusion remain difficult. Traditional methods (sex-based FISH, HLA mismatch, and Short Tandem Repeat PCR) can only achieve low levels of sensitivity (1%) and therefore are seldom used. The use of a droplet digital PCR (ddPCR) assay based on mismatch of null alleles is a promising alternative. Methods We selected genes with a high frequency of null genotype in the general population (SRY, RHD, TRY6, LEC3C, GSTM1, and GSTT1) and investigated their expression by liver progenitor cell donors and liver cell therapy recipients, in order to identify genes of interest for each donor/recipient couple. We first validated the detection of microchimerism by ddPCR and then used these assays to detect and quantify microchimerism in pre- and postinfusion liver biopsies. Results We validated the ddPCR detection of the selected genes based on linearity, precision, lack of inhibition, and accuracy, and we established limits of blank, limits of detection, and limits of quantification to ensure the reliability of the results. After genotyping donors and recipients, we were able to identify at least one gene of interest for each donor/recipient couple. We detected donor cells in the three patients posttransplantation. However, analysis of several biopsies taken at the same timepoint revealed a heterogeneous cell distribution. In addition, the values obtained remained below the limit of quantification. Therefore, the actual quantification of microchimerism may not be entirely accurate. Conclusions Overall, our study demonstrates that the detection of microchimerism post-liver cell transplantation can be performed using ddPCR amplification of null allele genes expressed by the donor but absent from the recipient. However, this technique can be extended to other cell types and target organs in cell transplantation.

Normative Data for the Montreal Cognitive Assessment in Greek Older Adults With Subjective Cognitive Decline, Mild Cognitive Impairment and Dementia.

The aim of the study was to provide normative data for the MoCA in a Greek cohort of people older than 60 years who meet criteria for subjective cognitive decline (SCD), mild cognitive impairment (MCI), or dementia in order to optimize cutoff scores for each diagnostic group. Seven hundred forty-six community-dwelling older adults, visitors of the Day Center of Alzheimer Hellas were randomly chosen. Three hundred seventy-nine of them met the criteria for dementia, 245 for MCI and 122 for SCD. Initial statistical analyses showed that the total MoCA score is not affected by gender (P = .164), or age (P = .144) but is affected by educational level (P < .001). A cutoff score of 23 for low educational level (≤6 years) can distinguish people with SCD from MCI (sensitivity 71.4%, specificity 84.2%), while 26 is the cutoff score for middle educational level (7-12 years; sensitivity 73.2%, specificity 67.0%) and high educational level (≥13 years; sensitivity 77.6%, specificity 74.7%). Montreal Cognitive Assessment can discriminate older adults with SCD from dementia, with a cutoff score of 20 for low educational level (sensitivity 100%, specificity 92.3%) and a cutoff score 23 for middle educational level (sensitivity 97.6%, specificity 92.7%) and high educational level (sensitivity 98.5%, specificity 100%). Montreal Cognitive Assessment is not affected by age or gender but is affected by the educational level. The discriminant potential of MoCA between SCD and MCI is good, while the discrimination of SCD from dementia is excellent.

A screening questionnaire for generalized tonic-clonic seizures: Hospital-based validation vs field-validation method.

SummaryThe majority of the screening questionnaires for epilepsy have been validated in hospital settings. We previously developed and used for field validation a screening tool to detect generalized tonic‐clonic seizures (GTCS) in the rural communities of the Chaco region of Bolivia. The objective of the present study was to perform a hospital‐based validation of the same questionnaire and to compare the levels of accuracy obtained when validated in the field or in a hospital‐based context. We carried out a hospital‐based validation in the Hospital Hernandez Vera of Santa Cruz, Bolivia, where we enrolled patients affected by epilepsy with GTCS and controls. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were calculated. One hundred twenty questionnaires were administered to 59 patients (27 men [45.8%]; mean age ± SD = 32.4 ± 14.2 years) and 61 controls (27 men [44.3%]; mean age ± SD = 32.6 ± 14.3 years). We obtained levels of accuracy of 100%. Sensitivity and PPV were significantly higher than the estimates obtained in the field‐validation study (sensitivity 100% vs 76.3%; PPV 100% vs 69.0%). Our screening questionnaire showed a significantly lower level of sensitivity when validated in the field, confirming that hospital‐based validation can lead to an overestimation of sensitivity.

Electrophysiological indices of amplitude modulated sounds and sensitivity to noise

Annoyance to unwanted sound differs across individuals, though why noise sensitive individuals are more reactive to noise while others are more resilient remains unanswered. The Information Processing Hypothesis posits that noise sensitive individuals are vulnerable to higher-order auditory processing deficits. The aim of this study was to test the veracity of this hypothesis by documenting differences in pre-attentive auditory evoked potentials (ERP) between high noise sensitive and low noise sensitive individuals. Participants provided annoyance measures for three amplitude-modulated sounds, and were exposed to the sounds while undergoing electroencephalogram recording. Results indicated that annoyance increased with modulation, and that modulation affected both N1 and P2 components. At the group level, highly noise sensitive individuals exhibited significantly greater annoyance to a low-frequency tone, alongside significantly higher P2 amplitude, than individuals reporting low levels of noise sensitivity. Overall, the results partially supported the Information Processing Hypothesis of noise sensitivity, but also suggest that acoustic features may be more important than hitherto argued.

Effort valuation and psychopathology in children and adults.

The Research Domain Criteria initiative was launched by the US National Institute of Mental Health to establish a multi-level framework for understanding psychological constructs relevant to human psychiatric disorders, and identified 'effort valuation/willingness to work' as a clinically useful construct worthy of further study. This construct encompasses the processes by which the cost(s) of obtaining an outcome are calculated, and the tendency to overcome response costs to obtain a reinforcer. The current study aims to examine effort valuation as a correlate of psychopathology in children and adults, and the moderating effects of sex on this relationship. Participants were 1215 children aged 6-12 and their parents (n = 1044). All participants completed the Effort Expenditure for Rewards Task as a measure of effort expenditure. Child psychopathology was measured via the Child Behavior Checklist, while adult psychopathology was measured via the Adult Self Report. Additionally, the Social Adjustment Inventory for Children and Adolescents and Injury Behavior Checklist were used to examine child social impairments/problem behaviors. In children, significant interactions between reward sensitivity and sex were observed in association with anxiety and thought problems, specifically at low reward sensitivity levels. In adults, main effects of effort expenditure were seen in drug and alcohol abuse, where higher effort was associated with higher degrees of abuse. These results establish effort valuation as a relevant psychological construct for understanding psychopathology, but with different profiles of associated psychopathology across sex in children and adults.

Residual Clonal Plasma Cells Detected By Flow Cytometry at 10-4level within Autologous Stem Cell Grafts Is Associated with Significantly Less Overall Survival

Introduction:High-dose Melphalan followed by autologous hematopoietic cell transplantation (ASCT) compared to conventional chemotherapies has been shown to improve survival and progression free survival (PFS) in eligible patients with multiple myeloma (MM). However cells that are resistant to the high-dose therapy and remaining in the patient and/or PBSC grafts may eventually lead to relapse. Over the past decade, data have been published on the role of circulating plasma cells (CPCs) as a poor prognostic feature at the time of diagnosis and prior to auto HSCT. But these studies have not sought this issue exclusively in PBSC grafts. The aim of this study was to analyze the impact of flow cytometric measurement of residual clonal cells within the apheresis products on outcome following ASCT.Materials and Methods:Patients with a diagnosis of MM who underwent auto HSCT at our center between January 2008- Mart 2018 were prospectively analyzed. PBSC grafts were tested for the presence of abnormal PCs (APC) and the number of normal PCs (NPC) by multi-parameter flow cytometry (FCM). Standard panel was set up with CD138FITC/CD38PE/CD45ECD/CD56PC5, CD45-CD56+PCs were identified as APC if any aberrant expression (including; CD20(loss)CD27(loss)CD28(gain)CD33(loss)CD34(gain)CD81(loss) CD117(gain)) is detected at diagnosis, the corresponding antibody was also added to the panel. Since maintenance was not an approved treatment in myeloma most patients did not receive any. Outcome was determined as response to transplant, PFS and overall survival (OS) in months by Kaplan-Meier analysis using SPSS (IBM SPSS Statistics 21; IBM Corp., Chicago, IL) statistical tool kit.Results: A total of 209 patients with MM with routine assessment for APC in the apheresis product were included in the analysis. Of these patients, 195 who underwent ASCT, met the predetermined criteria for inclusion. There were 81 (41.5%) female and 114 (58.5%) male patients. The median age at diagnosis of MM was 56 years (range, 31-71 years). The interval from the time of diagnosis to ASCT was median 7 months and median follow-up from ASCT was 49 months (range, 3-198 months). Among 195 patients, 36 (18.5%) had evidence of APC contamination in the PBSC grafts ranging between 1x10-4-12.8 x10-4of total cells. Subtypes of MM were similar among those w/wo APC. Seventy-four patients had pre and post ASCT PET-CT imaging done with 28.2% still active lesions post-ASCT. There was no correlation between PET-CR and absence of APC in grafts. Neither was there a statistically significant association between disease response <VGPR at mobilization and the number of APC in the apheresis product. Post-transplant responses were closely associated with pre-transplant responses. A total of 25 and 57 patients relapsed/progressed in respectively 6 and 12 months after ASCT. Post-transplant response was significantly associated with relapse at 6 months (≥VGPR vs. <VGPR; 37.5% vs. 62.5%, p=0.000). Estimated median OS was significantly different between patients w/o APC contamination; 20.4±8.1 and 63.3±3.8, respectively (p=0.000) (Figure 1). There were no differences in OS among the patients achieving VGPR/CR at the time of mobilization and also two months after the ASCT. We performed a subgroup analysis of patients in grouping together VGPR/CR or only CR and among those patients presence of APC was correlated with worse OS (Figure 1). PFS at 2 years were 60.3±4.3% and 75.6±9.7% in patients receiving APC free PBSC grafts compared with grafts with evidence of APC contamination, respectively (p=0.595).Discussion:PostASCT immune response was predictive for OS only when combined with APC results. Our study provides new insight suggesting a survival advantage value of residual APC detected by FCM, even at a low sensitivity level, on OS but not PFS following ASCT. The impact of such analysis may be more relevant on PFS with better assessment of residual APC with next generation flow cytometric/sequencing approaches while taking into account maintenance. [Display omitted] DisclosuresIlhan:Roche: Speakers Bureau; BMS: Speakers Bureau; Alexion: Speakers Bureau; Celgene: Speakers Bureau.

Determination of Cotinine in Urine and Wastewaters by High Performance Liquid Chromatography Coupled with Tandem Mass-Spectrometric Detection

A technique of extracting cotinine in urine and wastewaters, followed by its quantitative determination, using high performance liquid chromatography combined with tandem mass-spectrometric detection is presented. The method is characterized by low detection limits and high levels of efficiency and sensitivity. The optimal conditions for the solid-phase extraction of cotinine from urine and wastewaters are found. This technique makes it possible to reliably estimate the content of cotinine in the urine of active and passive smokers and in wastewaters.

Factors Associated With Efficacy of Cognitive Behavior Therapy vs Education for Patients With Irritable Bowel Syndrome

Among patients with irritable bowel syndrome (IBS), it would be helpful to identify those most likely to respond to specific treatments, yet few factors have been identified that reliably predict positive outcome. We sought to identify pretreatment baseline characteristics that associate with gastrointestinal symptom improvement in patients who received empirically validated regimens of cognitive behavior therapy (CBT) or IBS education. We analyzed data from the IBS Outcome Study, in which 436 patients with IBS (average age, 41years; 80%, female) were randomly assigned to groups that received 4 or 10 sessions of cognitive behavior therapy or education over 10 weeks. Baseline data were collected from all participants on sociodemographic and clinical features and comorbidities. Interaction analyses used a modified linear probability model with Huber-White robust estimators to identify baseline factors that moderated as a function of treatment condition GI symptom improvement based on the IBS-version of the Clinical Global Impressions-Improvement Scale. Whether the primary outcome of IBS symptom improvement was rated by patients or physician assessors blind to treatment 2 weeks after it ended, higher percentages of patients had symptom improvement after CBT compared with EDU among those with low levels of trait anxiety (71.3% vs 34.9%; P < .05) or anxiety sensitivity (71.7% vs 38.6%; P < .05) and for those with baseline typical levels of trait anxiety (66.0% vs 47.1%; P < .05) or anxiety sensitivity (66.3% vs 47.1%; P<.05). For patients with high trait anxiety or anxiety sensitivity, the difference in percentage ofresponders to CBT vs EDU was non-significant for trait anxiety (60.6% vs 59.2%) and anxiety sensitivity (60.9% vs 55.9%). If patients scored at or below 22 on the Trait Anxiety Inventory, CBThad a statistically significant advantage over EDU. If patients scored at or below 29 on the AnxietySensitivity Inventory, there was a statistically significant advantage for CBT vs EDU. In analyses of outcomes of patients with treatment-refractory IBS, baseline levels of trait anxiety and anxiety sensitivity (fear of arousal symptoms) were associated with improved gastrointestinal symptoms following CBT compared to IBS education. These findings and approaches might be used to optimize selection of treatment for patients with IBS.

The use of Design of Experiments for steady-state and transient inverse melanoma detection problems

Melanoma is one of the most fatal skin cancers; for this reason, there is a need for the development of new safe, non-invasive and efficient diagnostic techniques. Dynamic thermography is showing to be a promising technique for the early detection of skin cancers. Therefore, this paper investigates two different inverse bioheat problems using steady-state and transient skin temperature measurements. Both problems are investigated numerically to estimate how accurate blood perfusion rate, metabolic heat generation, diameter and thickness of the tumour can be estimated simultaneously under exact and noisy measurement data, based on a complex numerical model describing multilayer tissue. The inverse problems have been tested using different melanoma size, Clark II and Clark IV. The Design of Experiments (DOE) technique has been used to solve and analyse the inverse problems. A substantial number of numerical model evaluations, totalling 2,306,486 simulations, had to be undertaken as part of the full factorial DOE. The results show that it is always possible to obtain tumour parameters using exact static or dynamic measurement data. However, for noisy temperature data, the use of a dynamic approach showed an advantage over the steady-state one, which failed because of the very small temperature differences between the healthy skin and the tumour. The dynamic thermography can retrieve blood perfusion rate, thickness and diameter of the tumour as well as the metabolic heat generation despite the low sensitivity for low and high levels of measurement error; however, to detect melanoma lesions at an early stage, the measurement and model errors should be kept as low as possible.

Longevity, effectiveness, safety, and impact on quality of life of low-concentration hydrogen peroxides in-office bleaching: a randomized clinical trial.

The study evaluated the longevity, effectiveness, safety, and impact on the oral health-related quality of life of in-office dental bleaching using low-concentration hydrogen peroxides. Randomized, parallel, and double-blinded clinical trial was performed with 54 participants using 6% or 15% hydrogen peroxide (HP) in-office bleaching activated via hybrid LED/laser light. Tooth color was evaluated at baseline (T1), 1week of bleaching (T2), 2weeks of bleaching (T3) and 1week (T4) and 6months (T5) after finishing the bleaching using the Classical Vita™ scale and spectrophotometer. Tooth sensitivity and gingival irritation were measured with Visual Numeric Scale and Modified Gingival Index. The impact on quality of life was evaluated using the Oral Impact on Daily Performance. The data were analyzed using the Friedman, Mann-Whitney, and McNemar tests (p < 0.05). The group HP15% presented significant color change (ΔE) from T1 to T4 (p = 0.002) and T1 to T5 (p < 0.001). Parameters L, a*, and b* differed significantly at T3, T4, and T5 compared T1 for both groups. At 6-month follow-up, 57.1% of HP6 and 43.7% of HP15% participants migrated from B1 to a darker color. No significant differences were observed between the groups in tooth sensitivity, gingival irritation, or impact on quality of life. Both agents showed bleaching effectiveness, but HP15% presented greater color stability than HP6%, at 6-month follow-up. The agents showed low levels of tooth sensitivity, gingival irritation, and did not affect the oral health-related quality of life of the participants. Despite the greater presence of sensitivity during treatment compared with 6% hydrogen peroxide, 15% hydrogen peroxide demonstrated better bleaching effectiveness, and greater color stability at the end of bleaching and at 6-month follow-up. The use of 15% hydrogen peroxide presents more suitable results.