Confirmatory Assessment Research Articles

Abstract PD1-06: Open label phase 1b/2 study of ladiratuzumab vedotin in combination with pembrolizumab for first-line treatment of patients with unresectable locally-advanced or metastatic triple-negative breast cancer

Abstract Background Ladiratuzumab vedotin (LV) is an investigational anti-LIV-1 antibody-drug conjugate with a protease-cleavable linker to monomethyl auristatin E (MMAE). LIV-1 is highly expressed in metastatic triple negative breast cancer (TNBC). LV mediated delivery of MMAE drives antitumor activity through cytotoxic cell killing and has been shown to induce immunogenic cell death (ICD). LV monotherapy has demonstrated encouraging activity in TNBC. Anti-PD-(L)1 agents are emerging as part of the TNBC treatment paradigm and showing promising activity. Combining LV and pembrolizumab (pembro) may result in complementary, as well as synergistic, activity through LV-induced ICD that creates a microenvironment favorable for enhanced anti-PD-(L)1 activity. Methods This ongoing phase 1b/2 study evaluates safety, tolerability, activity, and recommended phase 2 dose of LV + pembro (NCT03310957; 2017-002289-35) in a dose-finding (Part A) followed by expansion phase (Part B) as front-line therapy for TNBC patients (pts). Eligible pts receive LV 2.0 mg/kg or 2.5mg/kg + pembro 200mg every 3 wks. Pts must have TNBC per ASCO/CAP guidelines (absence of HER2, estrogen receptor, and progesterone receptor expression) and are not pre-selected for either LIV-1 or PD-L1 expression. Tumor assessment is performed every 6 weeks per RECIST v1.1. Results As of 23 May 2019, a total of 51 pts have received LV + pembro (7 and 44 pts at LV 2.0 and 2.5 mg/kg, respectively). Nineteen pts enrolled in dose finding (7 and 12 at LV 2.0 and 2.5 mg/kg, respectively) and 32 pts enrolled in dose expansion all at LV 2.5 mg/kg. Median age was 55 yrs (range: 30, 82), ECOG 0/1 was 47%/53%, and invasive ductal carcinoma histology was 69%. All patients were first-line for LA/M TNBC, and 24% of pts had de novo mTNBC at initial diagnosis. Two pts experienced dose-limiting toxicities (DLT) out of 12 pts enrolled at LV 2.5 mg/kg in Part A: Grade 3 colitis and Grade 3 diarrhea. No DLT was observed at LV 2.0mg/kg. Of the 51 pts evaluable for safety (defined as all pts who received any amount of LV or pembro), 44 (86%) reported treatment emergent adverse events (TEAEs). Most common TEAEs across the 2 LV dose levels were nausea (53%); fatigue (45%); diarrhea (43%); alopecia (33%); constipation and hypokalemia (29% each); vomiting (27%); decreased appetite (25%); abdominal pain (24%); decreased weight (22%); and neutropenia and peripheral sensory neuropathy (20% each). Across the 2 dose levels, the most common Grade 3+ AEs were neutropenia (16%); diarrhea, fatigue, hypokalemia, and maculo-papular rash (8% each); and abdominal pain, increased ALT, and urinary tract infection (6% each). The most common SAEs were abdominal pain and constipation (6% each). In this ongoing trial, 26 pts were followed for at least 3 months with an opportunity for 2 post-baseline disease assessments. Among these 26 pts, the confirmed objective response rate was 54% (95% CI, 33.4, 73.4). Two additional pts have a single scan showing PR and are pending confirmatory assessment. Updated data will be provided at the meeting. Conclusion LV + pembro appears tolerable with a manageable safety profile to date. Preliminary efficacy data show encouraging clinical activity as first-line therapy in pts with unresectable LA/M TNBC. Citation Format: Hyo (Heather) Han, Sami Diab, Carlos Alemany, Reva Basho, Ursa Brown-Glaberman, Jane Meisel, Timothy Pluard, Javier Cortes, Patrick Dillon, Johannes Ettl, Sherko Kuemmel, Luis Manso Sanchez, Mafalda Oliveira, Joyce O'Shaughnessy, Steven Papish, Rajni Sinha, Danielle Sterrenberg, Erica Stringer-Reasor, Michaela Tsai, Rafael Villanueva Vazquez, Rachel Wuerstlein, Yinghui Wang, Zejing Wang, Valentina Boni. Open label phase 1b/2 study of ladiratuzumab vedotin in combination with pembrolizumab for first-line treatment of patients with unresectable locally-advanced or metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD1-06.

Electronically assisted surveillance systems of healthcare-associated infections: a systematic review.

BackgroundSurveillance of healthcare-associated infections (HAI) is the basis of each infection control programme and, in case of acute care hospitals, should ideally include all hospital wards, medical specialties as well as all types of HAI. Traditional surveillance is labour intensive and electronically assisted surveillance systems (EASS) hold the promise to increase efficiency.ObjectivesTo give insight in the performance characteristics of different approaches to EASS and the quality of the studies designed to evaluate them.MethodsIn this systematic review, online databases were searched and studies that compared an EASS with a traditional surveillance method were included. Two different indicators were extracted from each study, one regarding the quality of design (including reporting efficiency) and one based on the performance (e.g. specificity and sensitivity) of the EASS presented.ResultsA total of 78 studies were included. The majority of EASS (n = 72) consisted of an algorithm-based selection step followed by confirmatory assessment. The algorithms used different sets of variables. Only a minority (n = 7) of EASS were hospital-wide and designed to detect all types of HAI. Sensitivity of EASS was generally high (> 0.8), but specificity varied (0.37–1). Less than 20% (n = 14) of the studies presented data on the efficiency gains achieved.ConclusionsElectronically assisted surveillance of HAI has yet to reach a mature stage and to be used routinely in healthcare settings. We recommend that future studies on the development and implementation of EASS of HAI focus on thorough validation, reproducibility, standardised datasets and detailed information on efficiency.

Developing A Learning Continuum on Ecological Aspect from Elementary to Senior High School Based on The Opinions of Biology Education Experts

This research uses survey method aiming to investigate the opinions of biology education experts toward the teaching and the assessment of ecological aspects previewed from the level of competency and characteristic of specific pedagogical materials in order to develop the learning continuum of ecological aspects from elementary to senior high schools was conducted in 2018-2019. The population used in this research was hypothetical population which consisted of the all experts of biology education who taught in public and private universities in Indonesia. The sample used in this research was convenience sample consisted of 85 experts of biology education who taught at 18 public and private universities in Yogyakarta, Central Java, East Java, West Java, and Jakarta determined by using purposive technique. The instrument used was confirmatory assessment questionnaire learning continuum based on mastery of ecological aspects which has been arranged by Subali et al. (2016) and the validty was well examined through the focus group discussion activity by 3 lecturers of UNY and 5 lecturers of UNS. The result of this research showed that learning continuum of ecological aspects according to the biology education experts’ opinion, start be taught and assessed in the fourth and fifth grade of elementary school with the competency level C1 and C2. Then, it will be continued to the higher level in seventh grade of junior high school with the competency level C2 and tenth grade of senior high school with the competency level C3.

Diagnostic Accuracy of Sentence Recall and Past Tense Measures for Identifying Children's Language Impairments.

PurposeMeasures of linguistic processing and grammatical proficiency represent strong candidates for adaptation into language screeners for early elementary students. One key barrier, however, has been the lack of consensus around the preferred reference standard for assigning affected status. Diagnostic accuracies associated with sentence recall and past tense marking index measures were examined relative to 5 different reference standards of language impairment: receipt of language services, clinically significant levels of parental concern, low performance on language measures, a composite requiring at least 2 of these indicators, and a composite requiring convergence across all indicators.MethodOne thousand sixty grade K–3 students participated in school-based language screenings. All students who failed the screenings and a random sampling of those who passed were invited to participate in confirmatory assessments. The community-based sample was supplemented by a clinical sample of 58 students receiving services for language impairment. Two hundred fifty-four students participated in confirmatory testing. Examiners were naive to participants' status.ResultsDiagnostic accuracies for the sentence recall and past tense marking index measures varied across the different reference standards (areas under receiver operating characteristic curves: .67–.95). Higher levels of convergence occurred with reference standards based on behavioral measures. When affected status was defined by receipt of services and/or parental ratings, cases presented with higher levels of performance on the language measures than when affected status was based on behavioral criteria.ConclusionThese results provide additional support for the adaptation of sentence recall and past tense marking to screen for language impairments in early elementary students.Supplemental Material https://doi.org/10.23641/asha.8285786

Clinical Approaches to Assess Post-extubation Dysphagia (PED) in the Critically Ill.

Swallowing disorders and respective consequences (including aspiration-induced pneumonia) are often observed in extubated ICU patients with data indicating that a large number of patients are affected. We recently demonstrated in a large-scale analysis that the incidence of post-extubation dysphagia (PED) is 12.4% in a general ICU population and about 18% in emergency admissions to the ICU. Importantly, PED was mostly sustained until hospital discharge and independently predicted 28- and 90-day mortality. Although oropharyngeal/laryngeal trauma, neuromuscular ICU-acquired weakness, reduced sensation/sensorium, dyssynchronous breathing, and gastrointestinal reflux, are all considered to contribute to PED, little is known about the underlying pathomechanisms and risk factors leading to PED in critically ill patients. Systematic screening of all potential ICU patients for oropharyngeal dysphagia (OD) seems key for early recognition and follow-up, as well as the design and testing of novel therapeutic interventions. Today, screening methods and clinical investigations for dysphagia differ considerably. In the context of a recently proposed pragmatic screening algorithm introduced by us, we provide a concise review on currently available non-instrumental techniques that could potentially serve for non-instrumental OD assessment in critically ill patients. Following systematic literature review, we find that non-instrumental OD assessments were mostly tested in different patient populations with only a minority of studies performed in critically ill patients. Due to little available data on non-instrumental dysphagia assessment in the ICU, future investigations should aim to validate respective approaches in the critically ill against an instrumental (gold) standard, for example, flexible endoscopic evaluation of swallowing. An international expert panel is encouraged to addresses critical illness-related definitions, screening and confirmatory assessment approaches, treatment recommendations, and identifies optimal patient-centered outcome measures for future clinical investigations.

What Is the Role of A1C in Comorbidities?

The ADAG Study Group defined the relationship between average blood glucose (AG) and A1C. They derived an equation valid across diabetes types but excluded comorbidities known to impact A1C. The goal of this study is to examine the relationship between AG and A1C in patients omitted from prior analyses. A retrospective chart review was performed of downloaded glucose data from patients prescribed insulin at the UW Diabetes Center between 1/2011-10/2017. Patients were identified who had either 1) documentation and/or laboratory confirmation of anemia; 2) CKD; or 3) NAFLD. Eligible charts required: 1) 2 weeks of fingerstick glucose (SMBG) data with ≥14 checks or 1 month of CGM with ≥14 complete days and, 2) an A1C measured within 1 month of the encounter. The SMBG and CGM means were obtained from downloads. An AG was extrapolated from the A1c using the ADAG equation. The downloaded data and A1C-derived AGs were compared. There was a linear correlation between AG and A1C (R2=0.48) in anemic patients regardless of etiology. Non-anemic patients (N=220) had better ADAG agreement (70% of AGs inside 15% of predicted) than anemic patients (55% of AGs, N=123, p=0.006). Normal GFR yielded 71% of AGs inside 15% of ADAG estimation (N=440). This decreased to 59% if limited to anemic patients (N=83, p<0.001). ADAG agreement decreased as a function of renal impairment. The impact of anemia was only significant in CKD stage 3A (N=49, p=0.02). In CKD stage 4/ESRD there was no correlation between AG and A1C (N=14, R2=0.0004). Abnormal LFTs did not affect ADAG agreement. In NAFLD there was no correlation between AG and A1C (N=14, R2=0.03) but 64% of AGs were inside 15% of ADAG projection. For many, SMBG and CGM data provide an important confirmatory assessment of A1C. However, in certain conditions there is significant discordance between AG and A1C. There is a complete lack of correlation between AG and A1C in advanced renal dysfunction and NAFLD as measured by our lab. These findings suggest glucose downloads are a better assessment of diabetes control in several common comorbidities. Disclosure J.E. Perlman: None. J.L. Rosenbaum: None. B.K. McNulty: None. I.B. Hirsch: Research Support; Self; Medtronic MiniMed, Inc.. Consultant; Self; Abbott, Bigfoot Biomedical, Roche Diabetes Care Health and Digital Solutions, ADOCIA.

A1C vs. Glucose Downloads—Which Is the Better Gold Standard?

Introduction: The ADAG Study Group defined the relationship between average blood glucose (AG) and A1C. They derived a linear equation valid across diabetes types and the complete spectrum of glucose control. This study aims to determine appropriate clinical use of the ADAG equation to substitute home glucose monitoring for A1C. Methods: A retrospective chart review was performed of downloaded glucose data from patients prescribed insulin at the UW Diabetes Center between 1/2011-10/2017. Eligible charts required: 1) 2 weeks of fingerstick glucose (SMBG) data with >14 checks or 1 month of CGM with >14 complete days and, 2) an A1C measured within 1 month of the encounter. The SMBG and CGM means were obtained from downloads. The associated A1C was used to extrapolate AG via the ADAG equation. The downloaded data and A1C-derived averages were compared. The analysis was repeated excluding comorbidities known to impact A1C. Results: The downloaded AG was within 15% of that predicted by ADAG in 68% of patients (N=537). This criterion was met by 65% of patients using SMBG (N=401) and 67% of those checking >1x/day (N=359). The percentage was not different in patients checking >3x/day (71%; N=189). For CGM data, 79% of AGs were within 15% of A1C projection (N=136). CGM had superior ADAG agreement compared to SMBG (p<0.01). After excluding comorbidities (N=209), 72% of AGs were within 15% of ADAG estimation. This was higher than when looking at comorbidities alone (57%, N=228, p<0.001). In CGM users (no comorbidities, N=72), 82% of AGs were within 15% of expected. CGM again had better ADAG agreement than SMBG (p<0.01). Diabetes type did not predict ADAG agreement in any population. Our data replicated the ADAG equation following exclusion of comorbidities. Conclusion: For most patients, SMBG and CGM data provide an important confirmatory assessment of A1C. However, in over 40% with (and about 30% without) a comorbidity, home glucose data are discordant with A1C. For many, downloaded glucose data gives a better assessment of overall diabetes control. Disclosure J.E. Perlman: None. J.L. Rosenbaum: None. B.K. McNulty: None. I.B. Hirsch: Research Support; Self; Medtronic MiniMed, Inc.. Consultant; Self; Abbott, Bigfoot Biomedical, Roche Diabetes Care Health and Digital Solutions, ADOCIA.

Numerical prediction of a flashing flow of saturated water at high pressure

Abstract Transient fluid velocity and pressure fields in a pressurized water reactor (PWR) steam generator (SG) secondary side during the blowdown period of a feedwater line break (FWLB) accident were numerically simulated employing the saturated water flashing model. This model is based on the assumption that compressed water in the SG is saturated at the beginning and decompresses into the two-phase region where saturated vapor forms, creating a mixture of steam bubbles in water by bulk boiling. The numerical calculations were performed for two cases of which the outflow boundary conditions are different from each other; one is specified as the direct blowdown discharge to the atmosphere and the other is specified as the blowdown discharge to an extended calculation domain with atmospheric pressure on its boundary. The present simulation results obtained using the two different outflow boundary conditions were discussed through a comparison with the predictions using a simple non-flashing model neglecting the effects of phase change. In addition, the applicability of each of the non-flashing water discharge and saturated water flashing models for the confirmatory assessments of new SG designs was examined.

Is magnetic resonance imaging-targeted biopsy a useful addition to systematic confirmatory biopsy in men on active surveillance for low-risk prostate cancer? A systematic review and meta-analysis.

To systematically review and meta-analyse evidence regarding the additional value of magnetic resonance imaging (MRI) and MRI-targeted biopsies to confirmatory systematic biopsies in identifying high-grade prostate cancer in men with low-risk disease on transrectal ultrasonography (TRUS) biopsy, as active surveillance (AS) of prostate cancer is recommended for men with Gleason 3 + 3 on standard TRUS-guided biopsy. Confirmatory assessment can include repeat standard TRUS-guided biopsy, and/or MRI with targeted biopsy when indicated. A systematic review of the Embase, Medline, Web-of-science, Google scholar, and Cochrane library was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Identified reports were critically appraised according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 criteria. Studies reporting men with Gleason 3 + 3 prostate cancer who had chosen AS based on transrectal systematic biopsy findings and had undergone MRI with systematic ± targeted biopsy at confirmatory assessment were included. The primary outcome was detection of any Gleason pattern ≥4. Included reports (six) of men on AS (n = 1 159) showed cancer upgrading (Gleason ≥3 + 4) in 27% (95% confidence interval [CI] 22-34%) using a combined approach of MRI-targeted biopsies and confirmatory systematic biopsies. MRI-targeted biopsies alone would have missed cancer upgrading in 10% (95% CI 8-14%) and standard biopsies alone would have missed cancer upgrading in 7% (95% CI 5-10%). No pathway was more favourable than the other (relative risk [RR] 0.92, 95% CI 0.79-1.06). In all, 35% (95% CI 27-43%) of men with a positive MRI were upgraded, compared to 12% (95% CI 8-18%) of men with a negative MRI being upgraded (RR 2.77, 95% CI 1.76-4.38). A pre-biopsy MRI should be performed before confirmatory systematic TRUS-guided biopsies in men on AS, together with MRI-targeted biopsies when indicated. A combined approach maximises cancer detection, although other factors within multivariate risk prediction can be used to aid the decision to biopsy in these men.

A Diabetic Retinopathy Screening Tool for Low-Income Adults in Mexico.

IntroductionA national diabetic retinopathy screening program does not exist in Mexico as of 2017. Our objective was to develop a screening tool based on a predictive model for early detection of diabetic retinopathy in a low-income population.MethodsWe analyzed biochemical, clinical, anthropometric, and sociodemographic information from 1,000 adults with diabetes in low-income communities in Mexico (from 11,468 adults recruited in 2014–2016). A comprehensive ophthalmologic evaluation was performed. We developed the screening tool through the following stages: 1) development of a theoretical predictive model, 2) performance assessment and validation of the model using cross-validation and the area under the receiver operating characteristic curve (AUC ROC), and 3) optimization of cut points for the classification of diabetic retinopathy. We identified points along the AUC ROC that minimized the misclassification cost function and considered various scenarios of misclassification costs and diabetic retinopathy prevalence.ResultsTime since diabetes diagnosis, high blood glucose levels, systolic hypertension, and physical inactivity were considered risk factors in our screening tool. The mean AUC ROC of our model was 0.780 (validation data set). The optimized cut point that best represented our study population (z = −0.640) had a sensitivity of 82.9% and a specificity of 61.9%.ConclusionWe developed a low-cost and easy-to-apply screening tool to detect people at high risk of diabetic retinopathy in Mexico. Although classification performance of our tool was acceptable (AUC ROC > 0.75), error rates (precision) depend on false-negative and false-positive rates. Therefore, confirmatory assessment of all cases is mandatory.

HIV status and hearing loss among children between 6 and 12 years of age at a large urban health facility in south western Uganda

IntroductionPediatric HIV infection and treatment may increase the risk for hearing loss (HL), both sensorineural (SNHL) and conductive hearing loss (CHL). There is limited data on this subject, especially from sub Saharan Africa. The aim of this study was therefore to compare the prevalence of hearing loss among HIV positive and negative children, to determine the types of hearing loss and whether Nevirapine (NVP) based antiretroviral therapy (ART) is associated with HL. MethodsWe conducted a cross sectional study at two tertiary health facilities in south western Uganda. We consecutively enrolled 79 HIV negative and 148 HIV positive children aged between 6 and 12 years. Inclusion criteria were completion of written consent, ability to follow instructions to perform an audiogram and absence of congenital HL. We conducted hearing screening using the iPad Shoebox® audiometer, and confirmatory assessments were conducted using pure tone audiometry. Hearing was classified as either normal hearing, CHL, SNHL or mixed. ResultsOf the 227 children enrolled, 115 (50.7%) were female. The mean age was 9.2 years (median = 9). Based on self-report, frequency of HL among HIV positive children was 6.8% and 20.3% among HIV negative children (p=<0.01). Using objective measures, prevalence of HL among the HIV positive children was 8.8% compared to 10.1% among the HIV negative children (p = 0.74). CHL was generally more frequent than SNHL but SNHL occurred more frequently among HIV positive (7.4%) compared to HIV negative children (3.8%). No association was found between NVP based ART and HL (p = 0.41). Logistic regression showed that older age of the child (p = 0.01), previous ear infection (p=<0.01), tuberculosis (TB) treatment (p=<0.01) and long term duration on ART (p=<0.01) were significantly associated with HL. Age (p = 0.02), previous ear infection (p = 0.01) and TB treatment (p = 0.005) remained significant in the multiple regression model. ConclusionPrevalence of HL is similar among HIV positive and negative children. Older age of the child, previous ear infection, use of TB drugs and long duration on ART among the HIV positive children increase the odds of having hearing loss among children. However, use of NVP was not associated with HL.

Ublituximab and ibrutinib for previously treated genetically high-risk chronic lymphocytic leukemia: Results of the GENUINE phase 3 study.

7504 Background: Patients (pts) with high-risk chronic lymphocytic leukemia (CLL) defined by interruptions in TP53 (either by mutation or deletion) or loss of chromosome 11q experience inferior outcomes with ibrutinib (IB) monotherapy (O’Brien ASH 2016). Ublituximab (UTX) is a novel glycoengineered mAb with enhanced ADCC targeting a unique epitope on the CD20 antigen. GENUINE is the first randomized Ph 3 trial conducted assessing the addition of a novel agent to ibrutinib in high-risk rel/ref CLL, and evaluates IB monotherapy vs. UTX + IB. Methods: Eligible pts with rel/ref CLL and centrally confirmed del17p, del11q, and/or a TP53 mutation were randomized 1:1 to receive IB (420 mg QD) alone or with UTX (900 mg on D1, 8, 15 of Cycle 1, D1 of Cycle 2-6, and Q3 Cycles thereafter). There was no limit on number of prior therapies. Prior IB exposure was excluded. The primary endpoint was overall response rate (ORR) per iwCLL 2008 criteria, with secondary endpoints including CR rate, MRD negativity, PFS, time to response (TTR) and safety. Results: 126 pts were randomized at sites in the US and Israel, with 117 pts treated (59 on UTX + IB, 58 on IB alone). Median age 67, median 3 prior therapies (range 1-8), &gt; 70% of were male. High-risk cytogenetics were relatively balanced with ~ 50% of pts having del17p. UTX+IB was well tolerated, with infusion reactions the most prevalent AE (44%, GR3/4 5%). Neutropenia was comparable with the combination (17%, Gr3/4 7% vs. 10%, Gr3/4 9%), and other AE’s were similar or lower with UTX+IB vs. IB alone (all grades), including fatigue (17% vs. 31%), dizziness (12% vs. 21%), contusion (12% vs. 26%), anemia (10% vs. 16%), and myalgia (9% vs. 14%). At median follow-up of 12 mo, best ORR per independent central review was 80% for UTX + IB vs. 47% for IB alone (p &lt; 0.001). While not powered for secondary endpoints, observed advantages were seen in PFS and radiographic CR rate in the UTX + IB arm. CR and MRD confirmation is ongoing. Median TTR for the combo was 1.97 mo vs. 3.8 mo for IB alone. Both arms have responses pending confirmatory assessments. Conclusions: The addition of UTX to IB demonstrated a superior response rate compared to IB alone without additional clinically significant toxicity. Clinical trial information: NCT02301156.

A new measure of psychological inflexibility related to eating behavior in adolescence: Confirmatory factor analysis and validity assessment

IntroductionOn the onset of adolescence there is an increased vulnerability for mental health problems, namely disordered eating symptomatology. Disordered eating symptomatology has been described as a problem of psychological inflexibility. Psychological inflexibility related to eating behaviors, i.e., the adoption of inflexible idiosyncratic dietary rules without considering external and internal contingencies, is associated with disordered eating symptoms in adult populations. Nonetheless, the study of psychological inflexibility related to eating behaviors in adolescence is scarce.AimsThe current study aimed at examining the factor structure and psychometric properties of the Inflexible Eating Questionnaire for Adolescents (IEQ-A).MethodsParticipated in this study, 728 adolescents (513 girls and 215 boys), aged 14 to 18 years, who completed self-report measures of psychological inflexibility related to eating behaviors, body image, disordered eating symptoms and general psychopathology symptoms.ResultsResults of the confirmatory factor analysis indicated that the IEQ-A replicated the 11-item one-dimensional structure previously identified in adult samples. A multigroup analysis also demonstrated the scale's structure invariance between genders. The scale presented high internal reliability for both boys and girls (95). Correlation analyses confirmed the scale's convergence with psychological inflexibility with body image. IEQ-A was also positively associated with disordered eating symptoms and depression, anxiety and stress symptoms.ConclusionsFindings corroborated the adequacy of the IEQ-A factor structure and supported that this is a valid measure to assess psychological inflexibility related to eating behavior in adolescence. This measure is therefore of potential utility for clinicians and researchers focusing on eating-related difficulties in this vulnerable developmental stage.Disclosure of interestThe authors have not supplied their declaration of competing interest.

The dimensions and effects of excessive change

Purpose – Change excessiveness is argued as a critical contextual aspect of change management. The purpose of this paper is to identify three major dimensions to change excessiveness: change frequency, extent, and impact. A three-factor structure is proposed to broaden the emerging study on the contextual aspects of change. Its pertinence is proposed in addressing healthcare employees’ exhaustion, change-related uncertainty, and support for change. Design/methodology/approach – Using questionnaires, a first pilot sample (n=131) was recruited to test the psychometric properties and validity of the three-factor structure, while controlling for affectivity. Structural equation modeling techniques following a two-step approach were used on a second sample (n=363). First a confirmatory assessment of the three-factor structure of excessive change is tested. Second, a full mediation effect of excessive change, as a second-order latent factor, regrouping change frequency, impact and extent as first-order factors, was modeled to predict a tripartite conception of change-related reactions: exhaustion, uncertainty, and support for change. Findings – The excessive change three-factor structure is validated, while showing its superiority over alternative models. The fully mediated model is confirmed. Therefore, the significant added effects of change frequency, impact, and extent are positively related to emotional exhaustion and cognitive uncertainty, while negatively related with behavioral support for change. Originality/value – This study contributes by proposing a three-factor structure to excessive change assessment based on previous and independent findings in the literature. It also contributes in modeling the added effect of change frequency, extent, and impact in the full mediation relationship of change excessiveness on a tripartite reactions to change in healthcare management settings.

High-resolution ultrasound of the posterior femoral cutaneous nerve: visualization and initial experience with patients.

The posterior femoral cutaneous nerve (PFCN) is a sensory nerve originating from the sacral plexus. PFCN neuropathy leads to pain within the inferior gluteal region and the posterior aspect of the thigh. As electrophysiological assessment is challenging, diagnosis of PFCN neuropathy has been, thus far, primarily based on clinical findings, which can result in misdiagnosis. Therefore, alternative confirmatory assessments such as an imaging modality that could aid in the diagnosis of PFCN neuropathy would be desirable. The purpose of this study was to determine the feasibility of visualization of the PFCN with high-resolution ultrasound (HRUS) and to test this technique in our clinical routine. The study consisted of two parts. In the first part, HRUS-guided perineural ink injections along the course of the PFCN were performed at the posterior aspect of the thigh in 26 lower limbs of 14 fresh non-embalmed cadavers. Subsequent dissection confirmed correct identification of the nerve. In the second part, patients with a suspected PFCN neuropathy were examined and a selective HRUS-guided nerve block was performed to verify the suspected diagnosis. The PFCN was correctly identified with HRUS in 96.2% (25/26) of cadavers. Further, six patients with a suspected lesion of the PFCN were examined, and the diagnosis was proven by successful HRUS-guided block in all cases. We confirmed the reliable visualization of the PFCN using HRUS. This offers a new technique for the assessment of the PFCN, which could also be demonstrated with the case series presented.

How reliable are non-instrumental assessment tools for dysphagia?

The requirement for otorhinolaryngologists and phoniatricians to diagnose dysphagia and evaluate its extent is on the rise, particularly in light of demographic changes. The gold standards in confirmatory diagnostics are fiberoptic endoscopic evaluation of swallowing (FEES) and the videofluoroscopic swallowing examination (VFS). Standardized assessments, such as questionnaires or assessments involving probatory swallows are often applied as screening or supportive measures. This article aims to give a critical overview of the assessment tools frequently used in clinical routine. Test quality is assessed, particularly compared to FEES and VFS. A selective literature search using PubMed has been conducted. On the basis of this lierature search, 48assessment tools were identified. These can be classified into screening tools, instrument-based tools (implementation standards and evaluation protocols) and questionnaire-based assessment inventories. In order to diagnose and evaluate dysphagia on the basis of assessment critieria, clinicians should be aware of indications for, as well as the advantages, disadvantages and test quality of the assessment tools. Considering the different assessment tools for anamnesis and probatory swallowing, rather low sensitivities and specificities for possible penetration and aspiration are evident. In cases where these symptoms of dysphagia are not evident and reliably assessable, confirmatory assessment via FEES or VFS is essential.

Utility of population pharmacokinetic modeling in the assessment of therapeutic protein-drug interactions

Assessment of pharmacokinetic (PK) based drug-drug interactions (DDI) is essential for ensuring patient safety and drug efficacy. With the substantial increase in therapeutic proteins (TP) entering the market and drug development, evaluation of TP-drug interaction (TPDI) has become increasingly important. Unlike for small molecule (e.g., chemical-based) drugs, conducting TPDI studies often presents logistical challenges, while the population PK (PPK) modeling may be a viable approach dealing with the issues. A working group was formed with members from the pharmaceutical industry and the FDA to assess the utility of PPK-based TPDI assessment including study designs, data analysis methods, and implementation strategy. This paper summarizes key issues for consideration as well as a proposed strategy with focuses on (1) PPK approach for exploratory assessment; (2) PPK approach for confirmatory assessment; (3) importance of data quality; (4) implementation strategy; and (5) potential regulatory implications. Advantages and limitations of the approach are also discussed.

A Survey on the relationship between Aspects of Knowledge Management and the extent of readiness of the Personnel Transition in North Khorasan Education Organization

The purpose of this survey is to introduce the relationship between aspects of knowledge management and the extent of readiness of the personnel for transition in North Khorasan Education Organization and it is assumed that there is a relationship between aspects of knowledge management (strategy, structure, procedure, technology, personnel and their roles) and the extent of readiness for transition. Therefore, to prove the hypotheses, measurement field survey has been used and the statistical population in question includes the whole 426 personnel of North Khorasan Education Organization from whom 202 statistical samples were chosen by means of Morgan Table and relative random classificatory sampling and for assessing hypotheses, 47 questionnaires were used. To evaluate the authenticity of the questionnaire, confirmatory factorial assessment and to evaluate its constancy, Cronbach's alpha was used indicating that the results demonstrate a direct, positive and meaningful relationship between the aspects of knowledge management and the extent of readiness for transition and in the survey all hypotheses and variables have had a positive and direct effect. International Journal of Academic Research in Business and Social Sciences November 2013, Vol. 3, No. 11 ISSN: 2222-6990 347 www.hrmars.com/journals

Suitable test substances for proof of concept regarding infochemical effects in surface waters

Abstract Background Infochemical effects have been defined as the manipulation of the odour perception of organisms by anthropogenic substances which may result in ecologically relevant behavioural disorder. However, the environmental relevance of infochemical effects has not yet been confirmed by experimental observations. This project aims to test for infochemical effects on chemical communication in water bodies with systematic experimental investigations. The first crucial step is to select suitable test substances. Repellents (PT 19 biocides) and odourants may be assumed to affect the response of aquatic populations and communities. These mostly polar and stable compounds may disturb chemical communication between organisms and may cause organismic effects like drift (downstream dislocation of e.g. crustacean and insect larvae in streams). Repellents enter surface waters mainly indirectly via wastewater discharges from sewage treatment plants or directly by being washed off from the skin and clothes of bathers. Results In this literature study, suitable chemicals were selected for confirmatory assessments of suspected infochemical effects by laboratory tests in a subsequent second part of the project. The use pattern and physico-chemical properties of the substances selected, in combination with their limited biological degradability, indicate potential aquatic relevance with possible chronic impact caused by disturbed communication. After due consideration of advantages and limitations, three PT 19 repellents appear suitable test compounds for proof of concept in the subsequent experimental part of the project: • DEET (CAS 134-62-3) • Icaridine (CAS 119515-38-7) • EBAAP (CAS 52304-36-6) Another promising candidate for infochemical effects is isophorone (CAS 78-59-1), a natural attractant and an anthropogenic high production volume solvent. Conclusions Four chemicals were selected with the expectation that they may be suitable test substances for experimental proof of concept of infochemical effects in the subsequent part of the project. The experimental results may then help to answer the question of whether PT 19 biocides and other odourants entering aquatic ecosystems give rise for concern about potential infochemical effects.

Vegetable producers’ perceptions of food safety hazards in the Midwestern USA

The perspectives, practices and potential gaps in knowledge regarding fresh produce safety hazards among Midwestern US vegetable producers were measured using a survey-based confirmatory assessment. Although the majority of vegetable producers considered themselves familiar with national Good Agricultural Practices (GAPs) and agreed that implementing GAPs could reduce the risk of produce contamination, they were not consistently practicing GAPs. Irrigation and run-off water, worker hygiene, raw and composted animal manure, wildlife droppings, field proximity to livestock or wildlife habitats, plant diseases and insects were acknowledged as important potential sources of pre-harvest microbial contamination of produce, but paradoxically, producers disagreed that contamination most frequently originated on-farm. There was significant variation in producers’ level of agreement with regard to the importance and economic feasibility of various management practices for the prevention of on-farm food contamination. In general, vegetable producers did not declare an immediate need for more information on food safety, but did nevertheless, indicate that they would like more information on the sources of produce contamination, how contamination occurs, and GAPs guidelines. Vegetable producers preferred in-person modes of communication over mass media, fact sheets or electronic modes, with only 17% having a preference for Internet or email based information. These findings aid in the development and delivery of targeted, science-based, farm management guidelines and knowledge translation programs aimed at enhancing the safety of produce on the farm.