Coming into Focus A Needs Assessment and State Plan for Iowans with Brain Injury, November 1998

Coming Into Focus presents a needs assessment related to Iowans with brain injury, and a state action plan to improve Iowa’s ability to meet those needs. Support for this project came from a grant from the Office of Maternal and Child Health to the Iowa Department of Public Health, Iowa’s lead agency for brain injury. The report is a description of the needs of people with brain injuries in Iowa, the status of services to meet those needs and a plan for improving Iowa’s system of supports. Brain injury can result from a skull fracture or penetration of the brain, a disease process such as tumor or infection, or a closed head injury, such as shaken baby syndrome. Traumatic brain injury is a leading cause of death and disability in children and young adults (Fick, 1997). In the United States there are as many as 2 million brain injuries per year, with 300,000 severe enough to require hospitalization. Some 50,000 lives are lost every year to TBI. Eighty to 90 thousand people have moderate to acute brain injuries that result in disabling conditions which can last a lifetime. These conditions can include physical impairments, memory defects, limited concentration, communication deficits, emotional problems and deficits in social abilities. In addition to the personal pain and challenges to survivors and their families, the financial cost of brain injuries is enormous. With traumatic brain injuries, it is estimated that in 1995 Iowa hospitals charged some $38 million for acute care for injured persons. National estimates offer a lifetime cost of $4 million for one person with brain injury (Schootman and Harlan, 1997). With this estimate, new injuries in 1995 could eventually cost over $7 billion dollars. Dramatic improvements in medicine, and the development of emergency response systems, means that more people sustaining brain injuries are being saved. How can we insure that supports are available to this emerging population? We have called the report Coming into Focus, because, despite the prevalence and the personal and financial costs to society, brain injury is poorly understood. The Iowa Department of Public Health, the Iowa Advisory Council on Head Injuries State Plan Task Force, the Brain Injury Association of Iowa and the Iowa University Affiliated Program have worked together to begin answering this question. A great deal of good information already existed. This project brought this information together, gathered new information where it was needed, and carried out a process for identifying what needs to be done in Iowa, and what the priorities will be.

Monitoring of biological markers indicative of doping: the athlete biological passport

The athlete biological passport (ABP) was recently implemented in anti-doping work and is based on the individual and longitudinal monitoring of haematological or urine markers. These may be influenced by illicit procedures performed by some athletes with the intent to improve exercise performance. Hence the ABP is a valuable tool in the fight against doping. Actually, the passport has been defined as an individual and longitudinal observation of markers. These markers need to belong to the biological cascade influenced by the application of forbidden hormones or more generally, affected by biological manipulations which can improve the performance of the athlete. So far, the haematological and steroid profile modules of the ABP have been implemented in major sport organisations, and a further module is under development. The individual and longitudinal monitoring of some blood and urine markers are of interest, because the intraindividual variability is lower than the corresponding interindividual variability. Among the key prerequisites for the implementation of the ABP is its prospect to resist to the legal and scientific challenges. The ABP should be implemented in the most transparent way and with the necessary independence between planning, interpretation and result management of the passport. To ensure this, the Athlete Passport Management Unit (APMU) was developed and the WADA implemented different technical documents associated to the passport. This was carried out to ensure the correct implementation of a profile which can also stand the challenge of any scientific or legal criticism. This goal can be reached only by following strictly important steps in the chain of production of the results and in the management of the interpretation of the passport. Various technical documents have been then associated to the guidelines which correspond to the requirements for passport operation. The ABP has been completed very recently by the steroid profile module. As for the haematological module, individual and longitudinal monitoring have been applied and the interpretation cascade is also managed by a specific APMU in a similar way as applied in the haematological module. Thus, after exclusion of any possible pathology, specific variation from the individual norms will be then considered as a potential misuse of hormones or other modulators to enhance performance.

Continuous sunitinib treatment in patients with unresectable hepatocellular carcinoma (HCC): A multicenter phase II trial (SAKK 77/06 and SASL 23)

Background: Sunitinib (SU) is a multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenetic activity. Evidence for clinical activity in HCC was reported in 2 phase II trials [Zhu et al and Faivre et al, ASCO 2007] using either a 37.5 or a 50 mg daily dose in a 4 weeks on, 2 weeks off regimen. The objective of this trial was to demonstrate antitumor activity of continuous SU treatment in patients (pts) with HCC. Methods: Key eligibility criteria included unresectable or metastatic HCC, no prior systemic anticancer treatment, measurable disease and Child- Pugh A or B liver dysfunction. Pts received 37.5 mg SU daily until progression or unacceptable toxicity. The primary endpoint was progression free survival at 12 weeks (PFS12) defined as 'success' if the patient was alive and without tumor progression assessed by 12 weeks (±7 days) after registration. A PFS12 of _20% was considered uninteresting and promising if _40%. Using the Simon-two minimax stage design with 90% power and 5% significance the sample size was 45 pts. Secondary endpoints included safety assessments, measurement of serum cobalamin levels and tumor density. Results: From September 2007 to August 2008 45 pts, mostly male (87%), were enrolled in 10 centers. Median age was 63 years, 89% had Child-Pugh A and 47% had distant metastases. Median largest lesion diameter was 84mm (range: 18-280) and 18% had prior TACE. Reasons for stopping therapy were: PD 60%, symptomatic deterioration 16%, toxicity 11%, death 2% (due to tumor), and other reasons 4%; 7% remain on therapy. PFS12 was rated as success in 15 pts (33%) (95% CI: 20%, 49%) and failure in 27 (60%); 3 were not evaluable (due to refusal). Over the whole trial period 1 CR and 40% SD as best response were achieved. Median PFS, duration of disease stabilization, TTP and OS were 2.8, 3.2, 2.8 and 9.3 months, respectively. Grade 3 and 4 adverse events were infrequent and all deaths due to the tumor. Conclusions: Continuous SU treatment with 37.5 mg/d daily is feasible and demonstrates moderate activity in pts with advanced HCC and mild to moderately impaired liver dysfunction. Under this trial design the therapy is considered promising (>13 PFS12 successes).

Recommendations for the use of ultrasound in rheumatoid arthritis: literature review and SONAR score experience.

Ultrasound (US) has become a useful tool in the detection of early disease, differential diagnosis, guidance of treatment decisions and treatment monitoring of rheumatoid arthritis (RA). In 2008, the Swiss Sonography in Arthritis and Rheumatism (SONAR) group was established to promote the use of US in inflammatory arthritis in clinical practice. A scoring system was developed and taught to a large number of Swiss rheumatologists who already contributed to the Swiss Clinical Quality Management (SCQM) database, a national patient register. This paper intends to give a Swiss consensus about best clinical practice recommendations for the use of US in RA on the basis of the current literature knowledge and experience with the Swiss SONAR score. Literature research was performed to collect data on current evidence. The results were discussed among specialists of the Swiss university centres and private practice, following a structured procedure. Musculoskelatal US was found to be very helpful in establishing the diagnosis and monitoring the evolution of RA, and to be a reliable tool if used by experienced examiners. It influences treatment decisions such as continuing, intensifying or stepping down therapy. The definite modalities of integrating US into the diagnosis and monitoring of RA treatments will be defined within a few years. There are, however, strong arguments to use US findings as of today in daily clinical care. Some practical recommendations about the use of US in RA, focusing on the diagnosis and the use of the SONAR score, are proposed.

The Arts (Music, Arts&Crafts and Drama) as a procedure for learning pre-school content: Grupo Edebé Project

There is nothing as amazing and fascinating as children learning process. Between 0 and 6 years old, a child brain develops in a waythat will never be repeated. At this age, children are eager to discover and they have great potential of active and affective life.Because of this, their learning capacity in this period is incalculable. (Jordan-Decarbo y Nelson, 2002; Wild, 1999).Pre-school Education is a unique and special stage, with self identity, which aims are:attending children as a whole,motivate them to learn,give them an affective and stable environment in which they can grow up and get to be balanced and confident people and inwhich they can relate to others, learn, enjoy and be happy.Arts, Music, Visual Arts and Drama (Gardner, 1994) can provide a framework of special, even unique, personal expression.With the aim of introducing qualitative improvements in the education of children and to ensure their emotional wellbeing, and havingnoticed that teachers had important needs and concerns as regards to diversity in their student groups, we developed a programbased on the detection of needs and concerns explained by professionals in education.This program of Grupo edebé, object of our research, is a multicultural, interdisciplinary and globalizing project the aims of which are:developing children's talent and personality,keeping their imagination and creativity and using these as a learning resource,promoting reasoning, favouring expression and communication,providing children with the tools to manage their emotions,and especially, introducing Arts as a procedure to increase learning.We wanted to start the research by studying the impact (Brice, 2003) that this last point had on the learning of five-year-old childrenschooled in multicultural environments.Therefore, the main goal of the research was the assessment of the implementation of a child education programme attending todiversity in a population of five-year-old children, specifically in the practice of procedures based on the use of Arts (music, arts andcrafts and theatre) as a vehicle or procedure for learning contents in Pre-school stage.Because children emotional welfare was a subject of our concern, and bearing in mind that the affective aspects are of vitalimportance for learning and child development (Parke and Gauvain, 2009), Grupo Edebé has also evaluated the starting, evolving andfinal impact in five-year-old children given that they finish Pre-school education at that age.

The role of epilepsy in early language development in a child with a congenital lesion in the right hemisphere

Early epilepsy is known to worsen the developmental prognosis of young children with a congenital focal brain lesion, but its direct role is often very difficult to delineate from the other variables. This requires prolonged periods of follow-up with simultaneous serial electrophysiological and developmental assessments which are rarely obtained. We studied a male infant with a right prenatal infarct in the territory of the right middle cerebral artery resulting in a left spastic hemiparesis, and an epileptic disorder (infantile spasms with transient right hemihypsarrhythmia and focal seizures) from the age of 7 months until the age of 4 years. Pregnancy and delivery were normal. A dissociated delay of early language acquisition affecting mainly comprehension without any autistic features was documented. This delay was much more severe than usually expected in children with early focal lesions, and its evolution, with catch-up to normal, was correlated with the active phase of the epilepsy. We postulate that the epilepsy specifically amplified a pattern of delayed language emergence, mainly affecting lexical comprehension, reported in children with early right hemisphere damage.

Antiretroviral therapy during pregnancy and premature birth: analysis of Swiss data.

BACKGROUND: There is an ongoing debate as to whether combined antiretroviral treatment (cART) during pregnancy is an independent risk factor for prematurity in HIV-1-infected women. OBJECTIVE: The aim of the study was to examine (1) crude effects of different ART regimens on prematurity, (2) the association between duration of cART and duration of pregnancy, and (3) the role of possibly confounding risk factors for prematurity. METHOD: We analysed data from 1180 pregnancies prospectively collected by the Swiss Mother and Child HIV Cohort Study (MoCHiV) and the Swiss HIV Cohort Study (SHCS). RESULTS: Odds ratios for prematurity in women receiving mono/dual therapy and cART were 1.8 [95% confidence interval (CI) 0.85-3.6] and 2.5 (95% CI 1.4-4.3) compared with women not receiving ART during pregnancy (P=0.004). In a subgroup of 365 pregnancies with comprehensive information on maternal clinical, demographic and lifestyle characteristics, there was no indication that maternal viral load, age, ethnicity or history of injecting drug use affected prematurity rates associated with the use of cART. Duration of cART before delivery was also not associated with duration of pregnancy. CONCLUSION: Our study indicates that confounding by maternal risk factors or duration of cART exposure is not a likely explanation for the effects of ART on prematurity in HIV-1-infected women.

Improvement of therapeutic drug monitoring of imatinib by Bayesian prediction of trough levels. Personalized drug dosage

Aims: Plasma concentrations of imatinib differ largely between patients despite same dosage, owing to large inter-individual variability in pharmacokinetic (PK) parameters. As the drug concentration at the end of the dosage interval (Cmin) correlates with treatment response and tolerability, monitoring of Cmin is suggested for therapeutic drug monitoring (TDM) of imatinib. Due to logistic difficulties, random sampling during the dosage interval is however often performed in clinical practice, thus rendering the respective results not informative regarding Cmin values.Objectives: (I) To extrapolate randomly measured imatinib concentrations to more informative Cmin using classical Bayesian forecasting. (II) To extend the classical Bayesian method to account for correlation between PK parameters. (III) To evaluate the predictive performance of both methods.Methods: 31 paired blood samples (random and trough levels) were obtained from 19 cancer patients under imatinib. Two Bayesian maximum a posteriori (MAP) methods were implemented: (A) a classical method ignoring correlation between PK parameters, and (B) an extended one accounting for correlation. Both methods were applied to estimate individual PK parameters, conditional on random observations and covariate-adjusted priors from a population PK model. The PK parameter estimates were used to calculate trough levels. Relative prediction errors (PE) were analyzed to evaluate accuracy (one-sample t-test) and to compare precision between the methods (F-test to compare variances).Results: Both Bayesian MAP methods allowed non-biased predictions of individual Cmin compared to observations: (A) - 7% mean PE (CI95% - 18 to 4 %, p = 0.15) and (B) - 4% mean PE (CI95% - 18 to 10 %, p = 0.69). Relative standard deviations of actual observations from predictions were 22% (A) and 30% (B), i.e. comparable to the intraindividual variability reported. Precision was not improved by taking into account correlation between PK parameters (p = 0.22).Conclusion: Clinical interpretation of randomly measured imatinib concentrations can be assisted by Bayesian extrapolation to maximum likelihood Cmin. Classical Bayesian estimation can be applied for TDM without the need to include correlation between PK parameters. Both methods could be adapted in the future to evaluate other individual pharmacokinetic measures correlated to clinical outcomes, such as area under the curve(AUC).

Public-health and individual approaches to antiretroviral therapy: township South Africa and Switzerland compared.

BACKGROUND: The provision of highly active antiretroviral therapy (HAART) in resource-limited settings follows a public health approach, which is characterised by a limited number of regimens and the standardisation of clinical and laboratory monitoring. In industrialized countries doctors prescribe from the full range of available antiretroviral drugs, supported by resistance testing and frequent laboratory monitoring. We compared virologic response, changes to first-line regimens, and mortality in HIV-infected patients starting HAART in South Africa and Switzerland. METHODS AND FINDINGS: We analysed data from the Swiss HIV Cohort Study and two HAART programmes in townships of Cape Town, South Africa. We included treatment-naïve patients aged 16 y or older who had started treatment with at least three drugs since 2001, and excluded intravenous drug users. Data from a total of 2,348 patients from South Africa and 1,016 patients from the Swiss HIV Cohort Study were analysed. Median baseline CD4+ T cell counts were 80 cells/mul in South Africa and 204 cells/mul in Switzerland. In South Africa, patients started with one of four first-line regimens, which was subsequently changed in 514 patients (22%). In Switzerland, 36 first-line regimens were used initially, and these were changed in 539 patients (53%). In most patients HIV-1 RNA was suppressed to 500 copies/ml or less within one year: 96% (95% confidence interval [CI] 95%-97%) in South Africa and 96% (94%-97%) in Switzerland, and 26% (22%-29%) and 27% (24%-31%), respectively, developed viral rebound within two years. Mortality was higher in South Africa than in Switzerland during the first months of HAART: adjusted hazard ratios were 5.90 (95% CI 1.81-19.2) during months 1-3 and 1.77 (0.90-3.50) during months 4-24. CONCLUSIONS: Compared to the highly individualised approach in Switzerland, programmatic HAART in South Africa resulted in similar virologic outcomes, with relatively few changes to initial regimens. Further innovation and resources are required in South Africa to both achieve more timely access to HAART and improve the prognosis of patients who start HAART with advanced disease.

Parents - child role reversal in trilogue play: case studies of trajectories from pregnancy to toddlerhood

Role reversal, whereby a child attempts to meet her parent's adult needs for parenting, intimacy, or companionship, has been identified as a risk factor for developmental disturbances. It has been defined from diverse perspectives as a child attachment strategy, a parent - toddler relational disturbance, and a boundary disturbance between parents and child. The recently discovered infant's triangular capacity, namely the sharing of her attention and affects with both parents, allows one to analyse the infant's contribution to early family dynamics. Role reversal was detected in 4 out of 45 father - mother - infant interactions observed in trilogue play from pregnancy to toddlerhood. The developmental trajectories towards role reversal are explored by means of case analyses. Results are compared with cases of problematic triangulation encountered in the same sample. In role reversal, family interactions are rigidly organized around a "two against one" coalition, whereby the normative hierarchy between parents and child is reversed. The child's triangular capacity is overactivated, controlling the tension between her parents by provocation - animation strategies

Respiratory distress in a one-month-old child suffering brachial plexus palsy.

This paper describes a one-month-old girl presenting with respiratory and growth failure due to diaphragmatic paralysis associated with left brachial plexus palsy after forceps delivery. Despite continuous positive pressure ventilation and nasogastric feeding, the situation did not improve and a laparoscopic diaphragmatic plication had to be performed. When dealing with a child born with brachial plexus palsy, one must think of this possible association and if necessary proceed to the complementary radiological examinations. The treatment must avoid complications like feeding difficulties and failure to thrive, respiratory infections or atelectasis. It includes intensive support and a good evaluation of the prognosis of the lesion to decide the best moment for a surgical therapy.

Association of moderate alcohol use and binge drinking during pregnancy with neonatal health.

Background:  Heavy drinking and smoking during pregnancy are known to have a negative impact on the unborn child. However, the impact of low-to-moderate alcohol consumption and binge drinking has been debated recently. The aim of this study was to examine the relationship of moderate prenatal drinking and binge drinking with birthweight, being small for gestational age (SGA) at birth, preterm birth, and neonatal asphyxia. Methods:  Moderate alcohol drinking, binge drinking, and several possible confounders were assessed in 1,258 pregnant women; information on neonatal health was obtained at birth. Results:  Results indicate that 30.8% of the women drank at low levels (<2 glasses/wk), 7.9% drank moderately (2 to 4 glasses/wk), and 0.9% showed higher levels of drinking (≥5 glasses/wk); 4.7% reported binge drinking (defined as ≥3 glasses/occasion). 6.4% of the children were SGA (<10th percentile of birthweight adjusted for gestational age), 4.6% were preterm (<37th week of gestation), and 13.0% showed asphyxia (arterial cord pH <7.10 and/or arterial cord lactate >6.35 mmol and/or Apgar score <7 at 5 minutes). When controlling for maternal age, citizenship, occupational status, parity, smoking, use of prescription/over-the-counter drugs, illicit drug use, and child gender moderate drinking was related to lower birthweight (p < 0.01), and moderate drinking and binge drinking were associated with neonatal asphyxia at trend level (p = 0.06 and p = 0.09). Moderate drinking and binge drinking were not related to length of gestation. Conclusions:  In contrast to recent reviews in the field, our results assume that moderate drinking and binge drinking are risk factors for neonatal health.

Implementation of a Pilot Continuous Monitoring System: Iowa Falls Arch Bridge, HR-1088, 2015

The goal of this work was to move structural health monitoring (SHM) one step closer to being ready for mainstream use by the Iowa Department of Transportation (DOT) Office of Bridges and Structures. To meet this goal, the objective of this project was to implement a pilot multi-sensor continuous monitoring system on the Iowa Falls Arch Bridge such that autonomous data analysis, storage, and retrieval can be demonstrated. The challenge with this work was to develop the open channels for communication, coordination, and cooperation of various Iowa DOT offices that could make use of the data. In a way, the end product was to be something akin to a control system that would allow for real-time evaluation of the operational condition of a monitored bridge. Development and finalization of general hardware and software components for a bridge SHM system were investigated and completed. This development and finalization was framed around the demonstration installation on the Iowa Falls Arch Bridge. The hardware system focused on using off-the-shelf sensors that could be read in either “fast” or “slow” modes depending on the desired monitoring metric. As hoped, the installed system operated with very few problems. In terms of communications—in part due to the anticipated installation on the I-74 bridge over the Mississippi River—a hardline digital subscriber line (DSL) internet connection and grid power were used. During operation, this system would transmit data to a central server location where the data would be processed and then archived for future retrieval and use. The pilot monitoring system was developed for general performance evaluation purposes (construction, structural, environmental, etc.) such that it could be easily adapted to the Iowa DOT’s bridges and other monitoring needs. The system was developed allowing easy access to near real-time data in a format usable to Iowa DOT engineers.

Molecular characterization and pathogenicity of isolates of Beauveria spp. to fall armyworm

The objective of this work was to evaluate the pathogenicity of 24 Beauveria isolates to Spodoptera frugiperda larvae, and characterize them molecularly through rDNA-ITS sequencing and RAPD markers. Sequencing of rDNA-ITS fragments of 570 bp allowed the identification of isolates as B. bassiana or B. brongniarti by sequence comparison to GenBank. Sixty seven polymorphic RAPD fragments were capable to differentiate 20 among 24 Beauveria isolates, grouping them according to the derived host insect and to pathogenicity against maize fall armyworm larvae. Three RAPD markers were highly associated to the pathogenicity against S. frugiperda, explaining up to 67% of the phenotypic variation. Besides identification and molecular characterization of Beauveria isolates, ITS sequence and RAPD markers proved to be very useful in selecting the isolates potentially effective against S. frugiperda larvae and in monitoring field release of these microorganisms in biocontrol programs.

Evaluación de la psicopatología del preescolar mediante el Early Childhood Inventory-4 (ECI-4): concordancia entre padres y maestros.= Assessment of psychopathology in preschool age children through the Early Childhood Inventory-4 (ECI-4): Agreement among parents and teachers

El objetivo principal de este estudio es conocer la concordancia entre informantes, padres y maestros,en cada una de las dimensiones o categorías diagnósticas del Early Childhood Inventory-4 (ECI-4).Además, se pretende analizar la influencia de la presencia de problemas de salud en los padres en ladescripción y valoración de la conducta de una muestra de 204 alumnos de preescolar (3 a 6 años) deperfiles socioeconómicos diferentes. Los resultados indican que los padres tienden a valorar con mayorseveridad los síntomas, observándose una mayor concordancia entre informantes en los relativos alos trastornos del desarrollo