Recurrent mutations in the CDKL5 gene: Genotype-phenotype relationships.

Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) have been described in epileptic encephalopathies in females with infantile spasms with features that overlap with Rett syndrome. With more than 80 reported patients, the phenotype of CDKL5-related encephalopathy is well-defined. The main features consist of seizures starting before 6 months of age, severe intellectual disability with absent speech and hand stereotypies and deceleration of head growth, which resembles Rett syndrome. However, some clinical discrepancies suggested the influence of genetics and/or environmental factors. No genotype-phenotype correlation has been defined and thus there is a need to examine individual mutations. In this study, we analyzed eight recurrent CDKL5 mutations to test whether the clinical phenotype of patients with the same mutation is similar and whether patients with specific CDKL5 mutations have a milder phenotype than those with other CDKL5 mutations. Patients bearing missense mutations in the ATP binding site such as the p.Ala40Val mutation typically walked unaided, had normocephaly, better hand use ability, and less frequent refractory epilepsy when compared to girls with other CDKL5 mutations. In contrast, patients with mutations in the kinase domain (such as p.Arg59X, p.Arg134X, p.Arg178Trp/Pro/Gln, or c.145 + 2T > C) and frameshift mutations in the C-terminal region (such as c.2635_2636delCT) had a more severe phenotype with infantile spasms, refractory epileptic encephalopathy, absolute microcephaly, and inability to walk. It is important for clinicians to have this information when such patients are diagnosed. © 2012 Wiley Periodicals, Inc.

Field testing of arsenic in groundwater samples of Bangladesh using a test kit based on lyophilized bioreporter bacteria.

A test kit based on living, lyophilized bacterial bioreporters emitting bioluminescence as a response to arsenite and arsenate was applied during a field campaign in six villages across Bangladesh. Bioreporter field measurements of arsenic in groundwater from tube wells were in satisfying agreement with the results of spectroscopic analyses of the same samples conducted in the lab. The practicability of the bioreporter test in terms of logistics and material requirements, suitability for high sample throughput, and waste disposal was much better than that of two commercial chemical test kits that were included as references. The campaigns furthermore demonstrated large local heterogeneity of arsenic in groundwater, underscoring the use of well switching as an effective remedy to avoid high arsenic exposure.

Optimisation of a quantitative polymerase chain reaction-based strategy for the detection and quantification of human herpesvirus 6 DNA in patients undergoing allogeneic haematopoietic stem cell transplantation

Human herpesvirus 6 (HHV-6) may cause severe complications after haematopoietic stem cell transplantation (HSCT). Monitoring this virus and providing precise, rapid and early diagnosis of related clinical diseases, constitute essential measures to improve outcomes. A prospective survey on the incidence and clinical features of HHV-6 infections after HSCT has not yet been conducted in Brazilian patients and the impact of this infection on HSCT outcome remains unclear. A rapid test based on real-time quantitative polymerase chain reaction (qPCR) has been optimised to screen and quantify clinical samples for HHV-6. The detection step was based on reaction with TaqMan® hydrolysis probes. A set of previously described primers and probes have been tested to evaluate efficiency, sensitivity and reproducibility. The target efficiency range was 91.4% with linearity ranging from 10-106 copies/reaction and a limit of detection of five copies/reaction or 250 copies/mL of plasma. The qPCR assay developed in the present study was simple, rapid and sensitive, allowing the detection of a wide range of HHV-6 loads. In conclusion, this test may be useful as a practical tool to help elucidate the clinical relevance of HHV-6 infection and reactivation in different scenarios and to determine the need for surveillance.

A combination of ascorbic acid and α-tocopherol to test the effectiveness and safety in the fragile X syndrome: study protocol for a phase II, randomized, placebo-controlled trial.

BACKGROUND Fragile X syndrome (FXS) is an inherited neurodevelopmental condition characterised by behavioural, learning disabilities, physical and neurological symptoms. In addition, an important degree of comorbidity with autism is also present. Considered a rare disorder affecting both genders, it first becomes apparent during childhood with displays of language delay and behavioural symptoms.Main aim: To show whether the combination of 10 mg/kg/day of ascorbic acid (vitamin C) and 10 mg/kg/day of α-tocopherol (vitamin E) reduces FXS symptoms among male patients ages 6 to 18 years compared to placebo treatment, as measured on the standardized rating scales at baseline, and after 12 and 24 weeks of treatment.Secondary aims: To assess the safety of the treatment. To describe behavioural and cognitive changes revealed by the Developmental Behaviour Checklist Short Form (DBC-P24) and the Wechsler Intelligence Scale for Children-Revised. To describe metabolic changes revealed by blood analysis. To measure treatment impact at home and in an academic environment. METHODS/DESIGN A phase II randomized, double-blind pilot clinical trial. SCOPE male children and adolescents diagnosed with FXS, in accordance with a standardized molecular biology test, who met all the inclusion criteria and none of the exclusion criteria. INSTRUMENTATION clinical data, blood analysis, Wechsler Intelligence Scale for Children-Revised, Conners parent and teacher rating scale scores and the DBC-P24 results will be obtained at the baseline (t0). Follow up examinations will take place at 12 weeks (t1) and 24 weeks (t2) of treatment. DISCUSSION A limited number of clinical trials have been carried out on children with FXS, but more are necessary as current treatment possibilities are insufficient and often provoke side effects. In the present study, we sought to overcome possible methodological problems by conducting a phase II pilot study in order to calculate the relevant statistical parameters and determine the safety of the proposed treatment. The results will provide evidence to improve hyperactivity control and reduce behavioural and learning problems using ascorbic acid (vitamin C) and α-tocopherol (vitamin E). The study protocol was approved by the Regional Government Committee for Clinical Trials in Andalusia and the Spanish agency for drugs and health products. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01329770 (29 March 2011).

The Effect Of Induced Intraocular Straylight (cataract Simulation) On Sensitivity Measures Of Standard Automated Perimetry, Pulsar Perimetry And Moorfields Motion Displacement Test

Purpose: To investigate the effect of incremental increases in intraocular straylight on threshold measurements made by three modern forms of perimetry: Standard Automated Perimetry (SAP) using Octopus (Dynamic, G-Pattern), Pulsar Perimetry (PP) (TOP, 66 points) and the Moorfields Motion Displacement Test (MDT) (WEBS, 32 points).Methods: Four healthy young observers were recruited (mean age 26yrs [25yrs, 28yrs]), refractive correction [+2 D, -4.25D]). Five white opacity filters (WOF), each scattering light by different amounts were used to create incremental increases in intraocular straylight (IS). Resultant IS values were measured with each WOF and at baseline (no WOF) for each subject using a C-Quant Straylight Meter (Oculus, Wetzlar, Germany). A 25 yr old has an IS value of ~0.85 log(s). An increase of 40% in IS to 1.2log(s) corresponds to the physiological value of a 70yr old. Each WOFs created an increase in IS between 10-150% from baseline, ranging from effects similar to normal aging to those found with considerable cataract. Each subject underwent 6 test sessions over a 2-week period; each session consisted of the 3 perimetric tests using one of the five WOFs and baseline (both instrument and filter were randomised).Results: The reduction in sensitivity from baseline was calculated. A two-way ANOVA on mean change in threshold (where subjects were treated as rows in the block and each increment in fog filters was treated as column) was used to examine the effect of incremental increases in straylight. Both SAP (p<0.001) and Pulsar (p<0.001) were significantly affected by increases in straylight. The MDT (p=0.35) remained comparatively robust to increases in straylight.Conclusions: The Moorfields MDT measurement of threshold is robust to effects of additional straylight as compared to SAP and PP.

A novel pediatric biventricular assist device: in vitro test results.

Most ventricular assist devices (VADs) currently used in infants are extracorporeal. These VADs require long-term anticoagulation therapy and extensive surgery, and two devices are needed for biventricular support. We designed a biventricular assist device based on shape memory alloy that reproduces the hemodynamic effects of cardiomyoplasty, supporting the heart with a compressing movement, and evaluated its performance in a dedicated mockup system. Nitinol fibers are the device's key component. Ejection fraction (EF), cardiac output (CO), and generated systolic pressure were measured on a test bench. Our test bench settings were a preload range of 0-15 mm Hg, an afterload range of 0-160 mm Hg, and a heart rate (HR) of 20, 30, 40, and 60 beats/min. A power supply of 15 volts and 3.5 amperes was necessary. The EF range went from 34.4% to 1.2% as the afterload and HR increased, along with a CO from 180 to 6 ml/min. The device generated a maximal systolic pressure of 25 mm Hg. Cardiac compression for biventricular assistance in child-sized heart using shape memory alloy is technically feasible. Further testing remains necessary to assess this VAD's in vivo performance range and its reliability.

Simultaneous detection of aneuploidies for chromosomes 4, 6, 10 and 17 by automated four colour I-FISH in high hyperdiploid acute lymphoblastic leukemia : diagnostic assessment, clonal heterogeneity and chromosomal instability in adults

SummarySimultaneous detection of aneuploidies for chromosomes 4, 6,10 and 17 by automated four color l-FISH in high hyperdiploid acute lymphoblastic leukemia: diagnostic assessment, clonal heterogeneity and chromosomal instability in adultsAnna Talamo BlandinService de Génétique Médicale, Unité de Cytogénétique du Cancer, CHUVAcute lymphoblastic leukemia (ALL) is a malignant hemopathy characterized by the accumulation of the immature lymphoid cells in the bone marrow and, most often, in the peripheral blood. ALL is a heterogeneous disease with distinct biological and prognostic entities. At diagnosis, cytogenetic and molecular findings constitute important and independent prognostic factors. High hyperdiploidy with 51-67 chromosomes (HeH), one of the largest cytogenetic subsets of ALL, in childhood particularly, is generally associated with a relatively favorable outcome. Chromosome gain is nonrandom, extracopies of some chromosome occurring more frequently than those of others. Concurrent presence of trisomy for chromosomes 4, 10 and 17 confers an especially good prognosis. The first aim of our work was to develop an automated four color interphase fluorescence in situ hybridization (l-FISH) methodology and to assess its ability to detect concurrent aneuploidies 4, 6, 10 and 17 in 10 ALL patients. Various combinations of aneuploidies were identified. All clones detected by conventional cytogenetics were also observed by l-FISH. However, in all patients, l-FISH revealed numerous additional abnormal clones, leading to a high level of clonal heterogeneity. Our second aim has been to investigate the nature and origin of this clonal heterogeneity and to test for the presence of chromosome instability (CIN) in HeH ALL at initial presentation. Ten HeH ALL and 10 non-HeH ALL patients were analysed by four colour l-FISH and numerical CIN values were determined for all four chromosomes together and for each chromosome and patient group, an original approach in ALL. CIN values in HeH ALL proved to be much higher than#iose in non-HeH ALL, suggesting that numerical CIN may be at the origin of the high level of clonal heterogeneity revealed by l-FISH. Our third aim has been to study the evolution of these cytogenetic features during the course of the disease in 10 HeH ALL patients. Clonal heterogeneity was also observed again during disease progression, particularly at relapse. Clones detected at initial presentation generally reappeared in relapse, in most cases with newly generated ones. A significant correlation between the number of abnormal clones and CIN suggested that the higher the instability, the larger the number of abnormal clones. Whereas clonal heterogeneity and its evolution most probably result from underlying chromosome instability, operating processes remain conjectural.RésuméLa leucémie lymphoblastique aiguë (LLA) est une hémopathie maligne qui résulte de l'accumulationde cellules lymphoïdes immatures dans la moelle osseuse, et, le plus souvent, dans le sangpériphérique également. La LLA est une affection hétérogène au sein de laquelle se distinguentplusieurs entités biologiques et pronostiques. Les données cytogénétiques et moléculaires font partieintégrante du diagnostic et jouent un rôle essentiel dans l'évaluation du pronostic. L'hyperdiploïdieélevée à 51-­67 chromosomes (HeH), relativement fréquente, en particulier chez l'enfant, s'associe àun pronostic favorable. Le gain de chromosomes ne relève pas du hasard, certains chromosomesétant plus fréquemment impliqués que d'autres. La présence simultanée des trisomies 4, 6, et 17s'associe à un pronostic particulièrement bon. Le premier but du travail a été de développer uneméthode d'analyse automatique par hybridation in situ fluorescente interphasique (I-­FISH) à 4couleurs et de tester sa capacité à identifier la présence simultanée d'aneuploïdies 4, 6, 10 et 17 dans10 cas de LLA. Différentes combinaisons d'aneuploïdies ont été identifiées. Tous les clones détectéspar cytogénétique conventionnelle l'ont été par I-­FISH. Or, chez tous les patients, l'I-­FISH a révélé denombreux clones anormaux additionnels générant un degré élevé d'hétérogénéité clonale. Notredeuxième but a été d'investiguer la nature et l'origine de cette hétérogénéité et de tester la présenced'instabilité chromosomique (CIN) chez les patients avec une LLA HeH en presentation initiale. DixLLA HeH et 10 LLA non-­HeH ont été analysées par I-­FISH et les valeurs de CIN numérique ont étédéterminées pour les 4 chromosomes ensemble et pour chaque chromosome et groupe de patients,approche originale dans la LLA. Ces valeurs étant beaucoup plus élevées dans la LLA HeH que dansla LLA non-­HeH, elles favorisent l'hypothèse selon laquelle la CIN serait à l'origine de l'hétérogénéitéclonale révélée par I-­FISH. Le troisième but de notre travail a été d'étudier l'évolution de cescaractéristiques cytogénétiques au cours de la maladie dans 10 cas de LLA HeH. L'hétérogénéitéclonale a été retrouvée lors de la progression de la maladie, en particulier en rechute, où les clonesanormaux détectés en présentation initiale réapparaissent, généralement accompagnés de clonesnouveaux. La corrélation existant entre nombre de clones anormaux et valeurs de CIN suggère queplus l'instabilité est élevée, plus le nombre de clones anormaux est grand. Bien que l'hétérogénéitéclonale et son évolution résultent très probablement de l'instabilité chromosomique, les processus àl'oeuvre ne sont pas entièrement élucidés.

Teaching motivational interviewing to medical students : a pre-post test pilot study

Objective: To test the efficacy of teaching motivational interviewing (MI) to medical students. Methods: Thirteen 4th year medical students volunteered to participate. Seven days before and 7 days after an 8-hour interactive training MI workshop, each student performed a videorecorded interview with two standardized patients: a 60 year old alcohol dependent woman and a 50 year old cigarette smoking man. Students' counseling skills were coded by two blinded clinicians using the Motivational Interviewing Treatment Integrity 3.0 (MITI). Inter-rater reliability was calculated for all interviews and a test-retest was completed in a sub-sample of 10 consecutive interviews three days apart. Difference between MITI scores before and after training were calculated and tested using non-parametric tests. Effect size was approximated by calculating the probability that posttest scores are greater than pretest scores (P*=P(Pre<Post)+1/2P(Pre=Post)), P*>1/2 indicating greater scores in posttest, P*=1/2 no effect, and P*<1/2 smaller scores in posttest. Results: Median differences between MITI scores before and after MI training indicated a general progression in MI skills: MI spirit global score (median difference=1.5, Inter quartile range=1.5, p<0.001, P*=0.90); Empathy global score (med diff=1, IQR=0.5, p<0.001, P*=0.85); Percentage of MI adherent skills (med diff=36.6, IQR=50.5, p<0.001, P*=0.85); Percentage of open questions (med diff=18.6, IQR=21.6, p<0.001, P*=0.96); reflections/ questions ratio (med diff=0.2, IQR=0.4, p<0.001, P*=0.81). Only Direction global score and the percentage of complex reflections were not significantly improved (med diff=0, IQR=1, p=0.53, P*=0.44, and med diff=4.3, IQR=24.8, p=0.48, P*=0.62, respectively). Inter-rater reliability indicated weighted kappa ranged between 0.14 for Direction to 0.51 for Collaboration and ICC ranged between 0.28 for Simple reflection to 0.95 for Closed question. Test-retests indicated weighted kappa ranged between 0.27 for Direction to 0.80 for Empathy and ICC ranged between 0.87 for Complex reflection to 0.98 for Closed question. Conclusion: This pilot study indicated that an 8-hour training in MI for voluntary 4th year medical students resulted in significant improvement of MI skills. Larger sample of unselected medical students should be studied to generalize the benefit of MI training to medical students. Interrater reliability and test-retests suggested that coders' training should be intensified.

Effect of Lactobacillus paracasei ST11 on a nasal provocation test with grass pollen in allergic rhinitis.

Cite this as: J. Wassenberg, S. Nutten, R. Audran, N. Barbier, V. Aubert, J. Moulin, A. Mercenier and F. Spertini, Clinical & Experimental Allergy, 2011 (41) 565-573. SUMMARY: Background Probiotics have been associated with prevention and improvement of symptoms in atopic diseases such as atopic dermatitis. However, few studies exist that document their efficacy for upper airways allergies such as allergic rhinitis. Objective To investigate the effect of short-term oral administration of Lactobacillus paracasei ST11 on a nasal provocation test (NPT) with grass pollen. Methods Thirty-one adult volunteers with allergic rhinitis were enrolled in a randomized, double-blind, placebo-controlled study, based on two 4-week cross-over periods of product consumption (ST11-fermented milk vs. placebo), separated by a wash-out period of 6-8 weeks. Objective and subjective clinical parameters of NPT as well as systemic and nasal immunological parameters were compared between the two treatment periods (registration number: NCT 011 50 253). Results Subjects that received ST11-fermented milk had lower nasal congestion than subjects under placebo (visual analogical scale; P<0.05). Nasal pruritus followed the same trend. However, no significant change in combined nasal reaction threshold was observed between the two periods. IL-5 secretion by peripheral blood mononuclear cells and serum allergen-specific IgG4 were significantly lower in ST11-fermented milk group compared to placebo group. IL-8 and IL-10 secretion followed the same trend. Conclusion and Clinical Relevance Short-term treatment with ST11-fermented milk before NPT significantly improved a clinical marker of NPT (subjective nasal congestion) and down-regulated systemic immune markers (IL-5 from peripheral blood mononuclear cells and serum IgG4). These data strongly suggest that probiotics may down modulate key parameters of allergic rhinitis and warrant future evaluation in seasonal trials.

Evaluation of neuromotor development by means of the Harris Infant Neuromotor Test

Objective: To investigate the neuromotor development of at-risk children between three and 12 months of life, administering the Brazilian version of the Harris Infant Neuromotor Test (HINT).Method: A longitudinal study, with 78 children and 76 parents/guardians discharged from a neonatal intensive care unit in Fortaleza-CE/Brazil. Two instruments were administered: HINT and a socioeconomic questionnaire, between July/2009 to August/2010. Data from 55 preterm and 23 term children were analyzed. Results: The final mean scores ranged from 14.6 to 25.2 and from 11.2 to 24.7, for preterm and term, respectively, showing that 91% of children demonstrated good neuromotor performance; seven premature infants showed alterations which led to the referral of three children to a specialized clinic for examination and diagnostics.Conclusion: The test allowed nurses to assess infant development, identify deviations early, and plan interventions.

Examining the Agreement of Structural Loss Measured With Heidelberg Retinal Tomograhy and Functional Loss With Standard Automated Perimetry (SAP; Octopus), Pulsar Perimetry (PP), and Moorfields Motion Displacement Test (MDT) Perimetry

Purpose: To examine the relationship of functional measurements with structural measures. Methods: 146 eyes of 83 test subjects underwent Heidelberg Retinal Tomography (HRTIII) (disc area<2.43, mphsd<40), and perimetry testing with Octopus (SAP; Dynamic), Pulsar (PP; TOP) and Moorfields MDT (ESTA). Glaucoma was defined as progressive structural or functional loss (20 eyes). Perimetry test points were grouped into 6 sectors based on the estimated optic nerve head angle into which the associated nerve fiber bundle enters (Garway-Heath map). Perimetry summary measures (PSM) (MD SAP/ MD PP/ PTD MDT) were calculated from the average total deviation of each measured threshold from the normal for each sector. We calculated the 95% significance level of the sectorial PSM from the respective normative data. We calculated the percentage agreement with group1 (G1), healthy on HRT and within normal perimetric limits, and group 2 (G2), abnormal on HRT and outside normal perimetric limits. We also examined the relationship of PSM and rim area (RA) in those sectors classified as abnormal by MRA (Moorfields Regression Analysis) of HRT. Results: The mean age was 65 (range= [37, 89]). The global sensitivity versus specificity of each instrument in detecting glaucomatous eyes was: MDT 80% vs. 88%, SAP 80% vs. 80%, PP 70% vs. 89% and HRT 80% vs. 79%. Highest percentage agreement of HRT (respectively G1, G2, sector) with PSM were MDT (89%, 57%, nasal superior), SAP (83%, 74%, temporal superior), PP (74%, 63%, nasal superior). Globally percentage agreement (respectively G1, G2) was MDT (92%, 28%), SAP (87%, 40%) and PP (77%, 49%). Linear regression showed there was no significant trend globally associating RA and PSM. However, sectorally the supero-nasal sector had a statistically significant (p<0.001) trend with each instrument, the associated r2 coefficients are (MDT 0.38 SAP 0.56 and PP 0.39). Conclusions: There were no significant differences in global sensitivity or specificity between instruments. Structure-function relationships varied significantly between instruments and were consistently strongest supero-nasally. Further studies are required to investigate these relationships in detail.

Clients of sex workers in Switzerland: it makes sense to counsel and propose rapid test for HIV on the street, a preliminary report.

BACKGROUND: Clients of street sex workers may be at higher risk for HIV infection than the general population. Furthermore, there is a lack of knowledge regarding HIV testing of clients of sex workers in developed countries. METHOD: This pilot study assessed the feasibility and acceptance of rapid HIV testing by the clients of street-based sex workers in Lausanne, Switzerland. For 5 evenings, clients in cars were stopped by trained field staff for face-to-face interviews focusing on sex-related HIV risk behaviors and HIV testing history. The clients were then offered a free anonymous rapid HIV test in a bus parked nearby. Rapid HIV testing and counselling were performed by experienced nurse practitioners. Clients with reactive tests were offered confirmatory testing, medical evaluation, and care in our HIV clinic. RESULT: We intercepted 144 men, 112 (77.8%) agreed to be interviewed. Among them, 50 (46.6%) had never been tested for HIV. A total of 31 (27.7%) rapid HIV tests were performed, 16 (51.6%) in clients who had not previously been tested. None were reactive. Initially, 19 (16.9%) additional clients agreed to HIV testing but later declined due to the 40-minute queue for testing. CONCLUSION: This pilot study showed that rapid HIV testing in the red light district of Lausanne was feasible, and that the clients of sex workers accepted testing at an unexpectedly high rate. This setting seems particularly appropriate for targeted HIV screening, since more than 40% of the clients had not previously been tested for HIV even though they engaged in sex-related HIV risk behaviour.

Developing a Simple and Rapid Test for Monitoring the Heat Evolution of Concrete Mixtures for Both Laboratory and Field Applications, January 2006

Various test methods exist for measuring heat of cement hydration; however, most current methods require expensive equipment, complex testing procedures, and/or extensive time, thus not being suitable for field application. The objectives of this research are to identify, develop, and evaluate a standard test procedure for characterization and quality control of pavement concrete mixtures using a calorimetry technique. This research project has three phases. Phase I was designed to identify the user needs, including performance requirements and precision and bias limits, and to synthesize existing test methods for monitoring the heat of hydration, including device types, configurations, test procedures, measurements, advantages, disadvantages, applications, and accuracy. Phase II was designed to conduct experimental work to evaluate the calorimetry equipment recommended from the Phase I study and to develop a standard test procedure for using the equipment and interpreting the test results. Phase II also includes the development of models and computer programs for prediction of concrete pavement performance based on the characteristics of heat evolution curves. Phase III was designed to study for further development of a much simpler, inexpensive calorimeter for field concrete. In this report, the results from the Phase I study are presented, the plan for the Phase II study is described, and the recommendations for Phase III study are outlined. Phase I has been completed through three major activities: (1) collecting input and advice from the members of the project Technical Working Group (TWG), (2) conducting a literature survey, and (3) performing trials at the CP Tech Center’s research lab. The research results indicate that in addition to predicting maturity/strength, concrete heat evolution test results can also be used for (1) forecasting concrete setting time, (2) specifying curing period, (3) estimating risk of thermal cracking, (4) assessing pavement sawing/finishing time, (5) characterizing cement features, (6) identifying incompatibility of cementitious materials, (7) verifying concrete mix proportions, and (8) selecting materials and/or mix designs for given environmental conditions. Besides concrete materials and mix proportions, the configuration of the calorimeter device, sample size, mixing procedure, and testing environment (temperature) also have significant influences on features of concrete heat evolution process. The research team has found that although various calorimeter tests have been conducted for assorted purposes and the potential uses of calorimeter tests are clear, there is no consensus on how to utilize the heat evolution curves to characterize concrete materials and how to effectively relate the characteristics of heat evolution curves to concrete pavement performance. The goal of the Phase II study is to close these gaps.