The Importance of Childhood for Adult Health and Development-Study Protocol of the Zurich Longitudinal Studies.

Evidence is accumulating that individual and environmental factors in childhood and adolescence should be considered when investigating adult health and aging-related processes. The data required for this is gathered by comprehensive long-term longitudinal studies. This article describes the protocol of the Zurich Longitudinal Studies (ZLS), a set of three comprehensive cohort studies on child growth, health, and development that are currently expanding into adulthood. Between 1954 and 1961, 445 healthy infants were enrolled in the first ZLS cohort. Their physical, motor, cognitive, and social development and their environment were assessed comprehensively across childhood, adolescence, and into young adulthood. In the 1970s, two further cohorts were added to the ZLS and assessed with largely matched study protocols: Between 1974 and 1979, the second ZLS cohort included 265 infants (103 term-born and 162 preterm infants), and between 1970 and 2002, the third ZLS cohort included 327 children of participants of the first ZLS cohort. Since 2019, the participants of the three ZLS cohorts have been traced and invited to participate in a first wave of assessments in adulthood to investigate their current health and development. This article describes the ZLS study protocol and discusses opportunities, methodological and conceptual challenges, and limitations arising from a long-term longitudinal cohort recruited from a study about development in early life. In the future, the ZLS will provide data to investigate childhood antecedents of adult health outcomes and, ultimately, will help respond to the frequent call of scientists to shift the focus of aging research into the first decades of life and, thus, to take a lifespan perspective on aging.

A quick and qualitative assessment of gross motor development in preschool children.

There is a need for a quick, qualitative, reliable, and easy tool to assess gross motor development for practitioners. The aim of this cross-sectional study is to present the Zurich Neuromotor Assessment-Q (ZNA-Q), which assesses static and dynamic balance in children between 3 and 6 years of age in less than 5 min. A total of 216 children (103 boys; 113 girls; median age 4 years, 4 months; interquartile range 1 year, 3 months) were enrolled from day-care centers, kindergartens, and schools, and were tested with 5 different gross motor tasks: standing on one leg, tandem stance, hopping on one leg, walking on a straight line, and jumping sideways. All ordinal measures (consisting of qualitative measures and scales) featured a marked developmental trend and substantial inter-individual variability. Test-retest reliability was assessed on 37 children. It varied from .17 for tandem stance to .43 for jumping sideways for the individual tasks, and it was .41 and .67 for the static and dynamic balance components, respectively. For the whole ZNA-Q, test-retest reliability was .7.Conclusion: Ordinal scales enable practitioners to gather data on children's gross motor development in a fast and uncomplicated way. It offers the practitioner with an instrument for the exploration of the current developmental motor status of the child. What is Known: • Measurement of gross motor skills in the transitional period between motor mile stones and quantitative assessments is difficult. • Assessment of gross motor skills is relatively easy. What is New: • Supplementary and quick gross motor test battery for children for practitioners. • Normative values of five gross motor skills measured with ordinal scales.

Neuromotor development in children. Part 4: new norms from 3 to 18 years.

AIM: The aim of this cross-sectional study was to provide normative data for motor proficiency (motor performance and contralateral associated movements [CAMs]) in typically developing children between 3 years and 18 years of age using an updated version of the Zurich Neuromotor Assessment (ZNA-2). METHOD: Six-hundred and sixteen typically developing children between 3 years and 18 years of age were enrolled from day-care centres, kindergartens, and schools, and were tested using the ZNA-2 with improved items of the original battery. Motor proficiency was assessed on five components (fine motor tasks, pure motor tasks, static balance, dynamic balance, and CAMs) as a function of age and sex to determine centile curves for each task. Intraobserver, interobserver, and test-retest reliabilities were evaluated. RESULTS: Most ZNA-2 tasks featured a marked developmental trend and substantial interindividual variability. Test-retest reliability was generally high (e.g. static balance 0.67; CAMs 0.81; and total scores 0.84). INTERPRETATION: The ZNA-2 is a reliable and updated test instrument to measure motor proficiency in children from 3 to 18 years with improved properties for assessing motor performance. It allows continuous measurement without changing items for the entire age range; this feature of the ZNA-2 is unique and makes the instrument suitable for clinical purposes. The reduction of CAMs scoring simplifies the clinical procedure and increases its reliability. WHAT THIS PAPER ADDS: The Zurich Neuromotor Assessment, Second Edition (ZNA-2) provides new norms for motor proficiency in children between 3 years and 18 years. High reliabilities suggest that the revised test battery is a useful tool for assessing neuromotor development. Integration of a 'not able to perform' category makes the ZNA-2 suitable for clinical purposes.

Oxygen supply maps for hypoxic microenvironment visualization in prostate cancer.

BACKGROUND: Intratumoral hypoxia plays an important role with regard to tumor biology and susceptibility to radio- and chemotherapy. For further investigation of hypoxia-related changes, areas of certain hypoxia must be reliably detected within cancer tissues. Pimonidazole, a 2-nitroimindazole, accumulates in hypoxic tissue and can be easily visualized using immunohistochemistry. MATERIALS AND METHODS: To improve detection of highly hypoxic versus normoxic areas in prostate cancer, immunoreactivity of pimonidazole and a combination of known hypoxia-related proteins was used to create computational oxygen supply maps of prostate cancer. Pimonidazole was intravenously administered before radical prostatectomy in n = 15 patients, using the da Vinci robot-assisted surgical system. Prostatectomy specimens were immediately transferred into buffered formaldehyde, fixed overnight, and completely embedded in paraffin. Pimonidazole accumulation and hypoxia-related protein expression were visualized by immunohistochemistry. Oxygen supply maps were created using the normalized information from pimonidazole and hypoxia-related proteins. RESULTS: Based on pimonidazole staining and other hypoxia.related proteins (osteopontin, hypoxia-inducible factor 1-alpha, and glucose transporter member 1) oxygen supply maps in prostate cancer were created. Overall, oxygen supply maps consisting of information from all hypoxia-related proteins showed high correlation and mutual information to the golden standard of pimonidazole. Here, we describe an improved computer-based ex vivo model for an accurate detection of oxygen supply in human prostate cancer tissue. CONCLUSIONS: This platform can be used for precise colocalization of novel candidate hypoxia-related proteins in a representative number of prostate cancer cases, and improve issues of single marker correlations. Furthermore, this study provides a source for further in situ tests and biochemical investigations.

Predictive value of low tube voltage and dual-energy CT for successful shock wave lithotripsy: an in vitro study.

This study investigates the capabilities of low tube voltage computed tomography (CT) and dual-energy CT (DECT) for predicting successful shock wave lithotripsy (SWL) of urinary stones in vitro. A total of 33 urinary calculi (six different chemical compositions; mean size 6 ± 3 mm) were scanned using a dual-source CT machine with single- (120 kVp) and dual-energy settings (80/150, 100/150 Sn kVp) resulting in six different datasets. The attenuation (Hounsfield Units) of calculi was measured on single-energy CT images and the dual-energy indices (DEIs) were calculated from DECT acquisitions. Calculi underwent SWL and the number of shock waves for successful disintegration was recorded. The prediction of required shock waves regarding stone attenuation/DEI was calculated using regression analysis (adjusted for stone size and composition) and the correlation between CT attenuation/DEI and the number of shock waves was assessed for all datasets. The median number of shock waves for successful stone disintegration was 72 (interquartile range 30-361). CT attenuation/DEI of stones was a significant, independent predictor (P < 0.01) for the number of required shock waves with the best prediction at 80 kVp (ß estimate 0.576) (P < 0.05). Correlation coefficients between attenuation/DEI and the number of required shock waves ranged between ρ = 0.31 and 0.68 showing the best correlation at 80 kVp (P < 0.001). The attenuation of urinary stones at low tube voltage CT is the best predictor for successful stone disintegration, being independent of stone composition and size. DECT shows no added value for predicting the success of SWL.

Prostate cancer risk prediction using the novel versions of the European Randomised Study for Screening of Prostate Cancer (ERSPC) and Prostate Cancer Prevention Trial (PCPT) risk calculators: independent validation and comparison in a contemporary European cohort.

OBJECTIVES: To externally validate and compare the two novel versions of the European Randomised Study for Screening of Prostate Cancer (ERSPC)-prostate cancer risk calculator (RC) and Prostate Cancer Prevention Trial (PCPT)-RC. PATIENTS AND METHODS: All men who underwent a transrectal prostate biopsy in a European tertiary care centre between 2004 and 2012 were retrospectively identified. The probability of detecting prostate cancer and significant cancer (Gleason score ≥7) was calculated for each man using the novel versions of the ERSPC-RC (DRE-based version 3/4) and the PCPT-RC (version 2.0) and compared with biopsy results. Calibration and discrimination were assessed using the calibration slope method and the area under the receiver operating characteristic curve (AUC), respectively. Additionally, decision curve analyses were performed. RESULTS: Of 1 996 men, 483 (24%) were diagnosed with prostate cancer and 226 (11%) with significant prostate cancer. Calibration of the two RCs was comparable, although the PCPT-RC was slightly superior in the higher risk prediction range for any and significant prostate cancer. Discrimination of the ERSPC- and PCPT-RC was comparable for any prostate cancer (AUCs 0.65 vs 0.66), while the ERSPC-RC was somewhat better for significant prostate cancer (AUCs 0.73 vs 0.70). Decision curve analyses revealed a comparable net benefit for any prostate cancer and a slightly greater net benefit for significant prostate cancer using the ERSPC-RC. CONCLUSIONS: In our independent external validation, both updated RCs showed less optimistic performance compared with their original reports, particularly for the prediction of any prostate cancer. Risk prediction of significant prostate cancer, which is important to avoid unnecessary biopsies and reduce over-diagnosis and overtreatment, was better for both RCs and slightly superior using the ERSPC-RC.

Similarities and dissimilarities between the movement ABC-2 and the Zurich neuromotor assessment in children with suspected developmental coordination disorder.

An established tool for the assessment of motor performance in children with developmental coordination disorder (DCD) is the Movement-ABC-2 (M-ABC-2). The Zurich Neuromotor Assessment (ZNA) is also widely used for the evaluation of children's motor performance, but has not been compared with the M-ABC-2. Fifty-one children (39 males) between 5 and 7 years of age with suspected DCD were assessed using the M-ABC-2 and the ZNA. Rank correlations between scores of different test components were calculated. The structure of the tests was explored using canonical-correlation analysis. The correlation between total scores of the two motor tests was reasonable (0.66; p<0.001). However, ZNA scores were generally lower than those of M-ABC-2, due to poor performance in the fine motor adaptive component and increased contralateral associated movements (CAM). The canonical-correlation analysis revealed that ZNA measures components like pure motor skills and CAM that are not represented in the M-ABC-2. Furthermore, there was also no equivalent for the aiming and catching items of the M-ABC-2 in ZNA. The two tests measure different motor characteristics in children with suspected DCD and, thus, can be used complementary for the diagnosis of the disorder.

Long-lasting fibrin matrices ensure stable and functional angiogenesis by highly tunable, sustained delivery of recombinant VEGF164.

Clinical trials of therapeutic angiogenesis by vascular endothelial growth factor (VEGF) gene delivery failed to show efficacy. Major challenges include the need to precisely control in vivo distribution of growth factor dose and duration of expression. Recombinant VEGF protein delivery could overcome these issues, but rapid in vivo clearance prevents the stabilization of induced angiogenesis. Here, we developed an optimized fibrin platform for controlled delivery of recombinant VEGF, to robustly induce normal, stable, and functional angiogenesis. Murine VEGF164 was fused to a sequence derived from α2-plasmin inhibitor (α2-PI1-8) that is a substrate for the coagulation factor fXIIIa, to allow its covalent cross-linking into fibrin hydrogels and release only by enzymatic cleavage. An α2-PI1-8-fused variant of the fibrinolysis inhibitor aprotinin was used to control the hydrogel degradation rate, which determines both the duration and effective dose of factor release. An optimized aprotinin-α2-PI1-8 concentration ensured ideal degradation over 4 wk. Under these conditions, fibrin-α2-PI1-8-VEGF164 allowed exquisitely dose-dependent angiogenesis: concentrations ≥25 µg/mL caused widespread aberrant vascular structures, but a 500-fold concentration range (0.01-5.0 µg/mL) induced exclusively normal, mature, nonleaky, and perfused capillaries, which were stable after 3 mo. Optimized delivery of fibrin-α2-PI1-8-VEGF164 was therapeutically effective both in ischemic hind limb and wound-healing models, significantly improving angiogenesis, tissue perfusion, and healing rate. In conclusion, this optimized platform ensured (i) controlled and highly tunable delivery of VEGF protein in ischemic tissue and (ii) stable and functional angiogenesis without introducing genetic material and with a limited and controllable duration of treatment. These findings suggest a strategy to improve safety and efficacy of therapeutic angiogenesis.

Bilaterally positive biopsy cores are associated with non-organ-confined disease in prostate cancer patients eligible for active surveillance.

PURPOSE: To investigate the association between the laterality of diagnostic prostate cancer-positive biopsy cores and definitive tumor stage on final pathology (organ-confined versus non-organ-confined). PATIENTS AND METHODS: This is a retrospective analysis of 165 men after radical prostatectomy fulfilling our active surveillance criteria at the time of surgery. Nominal variables were compared using Fisher's exact test, continuous variables using Mann-Whitney test. Odds ratios including 95% Wald and probabilities including 95% Wilson confidence intervals are provided. RESULTS: 5 (3%) patients had non-organ-confined disease: 2 out of 144 (1%) patients with unilateral and 3 out of 17 (18%) patients with bilateral cancer-positive biopsy cores (p = 0.009). The estimated odds ratio for non-organ-confined disease was 14.67 (95% confidence interval 1.55-189.23) for patients with bilateral compared to patients with unilateral cancer-positive biopsy cores. The sensitivity, specificity and accuracy of bilaterally positive biopsies as an additional criterion to identify non-organ-confined disease are 60, 91 and 90%, respectively. CONCLUSION: In our cohort, patients with bilaterally positive biopsy cores were significantly more likely to harbor a non-organ-confined tumor than patients with unilaterally positive cores. Due to their high specificity, bilaterally positive biopsies may represent a reasonable exclusion criterion for active surveillance if our results are corroborated in further studies.

Adipose-derived stem cells (ADSCs) and muscle precursor cells (MPCs) for the treatment of bladder voiding dysfunction.

PURPOSE: Bladder outflow obstruction (BOO) is common in the elderly and can result in bladder voiding dysfunction (BVD) due to severe bladder muscle damage. The goal of this research was to evaluate the use of adult stem cells for the treatment of BVD due to decreased muscle contractility in a rat model. MATERIALS AND METHODS: Adipose-derived stem cells (ADSCs) and muscle precursor cells (MPCs) were harvested from male Lewis rats and expanded in culture. BOO was induced by tying a suture around the urethra. Six weeks after obstruction, the development of BVD was confirmed by cystometric analysis in conscious rats, histology and molecular investigations. Injection of ADSCs or MPCs into the bladder wall and synchronous deligation was performed 6 weeks after the obstruction. After stem-cell treatment, morphological and functional changes were assessed. Age-matched rats and animals without cellular therapy but deligation-only served as controls. RESULTS: Voiding pressures decreased progressively 6 weeks after obstruction with increased bladder capacities. Structural changes of the detrusor muscle occurred during the time of obstruction with an increased connective tissue-to-smooth muscle ratio and decreased SMA/smoothelin expression. After stem-cell injection, improved voiding pressures and voiding volumes were observed together with recovered tissue architecture. RT-PCR and Western blotting showed an up-regulation of important contractile proteins. CONCLUSIONS: We established a reliable model for BVD and demonstrated that ADSCs and MPCs can prevent pathophysiological remodelling and provide regenerated bladder tissue and function.

Lateral temperature spread of monopolar, bipolar and ultrasonic instruments for robot-assisted laparoscopic surgery.

OBJECTIVE: To assess critical heat spread of cautery instruments used in robot-assisted laparoscopic (RAL) surgery. MATERIALS AND METHODS: Thermal spread along bovine musculofascial tissues was examined by infrared camera, histology and enzyme assay. Currently used monopolar, bipolar and ultrasonic laparoscopic instruments were investigated at various power settings and application times. The efficacy of using an additional Maryland clamp as a heat sink was evaluated. A temperature of 45 °C was considered the threshold temperature for possible nerve damage. RESULTS: Monopolar instruments exhibited a mean (sem) critical thermal spread of 3.5 (2.3) mm when applied at 60 W for 1 s. After 2 s, the spread was >20 mm. For adjustable bipolar instruments the mean (sem) critical thermal spread was 2.2 (0.6) mm at 60 W and 1 s, and 3.6 (1.3) mm at 2 s. The PK and LigaSure forceps had mean (sem) critical thermal spreads of 3.9 (0.8) and 2.8 (0.6) mm respectively, whereas the ultrasonic instrument reached 2.9 (0.8) mm. Application of an additional Maryland clamp as a heat sink, significantly reduced the thermal spread. Histomorphometric analyses and enzyme assay supported these findings. CONCLUSIONS: All coagulation devices used in RAL surgery have distinct thermal spreads depending on power setting and application time. Cautery may be of concern due to lateral temperature spread, causing potential damage to sensitive structures including nerves. Our results provide surgeons with a resource for educated decision-making when using coagulation devices during robotic procedures.

Long-term biostability and bioactivity of "fibrin linked" VEGF121in vitro and in vivo.

Despite major advances in understanding angiogenesis over the last few years, the ability to induce angiogenesis in ischemic wounds or larger tissue-engineering constructs remains elusive. Serious risks and limited control over dose, duration, and localization of growth factor delivery make materials-based approaches viable alternatives. In an effort to minimize passive diffusion and control the release profile of delivered growth factors, matrix properties have been engineered with regard to pore size, growth factor affinity or stable growth factor binding. Recently, fibrin or biomimetic hydrogels have been engineered towards the covalent immobilization of vascular endothelial growth factor (VEGF). Most of the studies pertaining to VEGF delivery by fibrin gel constructs have focused on characterizing release profiles, receptor activation, and the angiogenic response in vitro and in vivo. Herein we demonstrate that gels containing covalently-linked VEGF (α2PI1-8-VEGF121), compared to diffusible VEGF, elicit stronger and longer-lasting angiogenic responses in subcutaneous implants of mice. This superior angiogenic response was due to both the sustained release and significant retention of bioactivity (80%) of the delivered engineered VEGF over a 12-day period. To the best of our knowledge, this is the first report to characterize long-term matrix liberated α2PI1-8-VEGF121 bioactivity, important for future efforts in angiogenesis research.

Pure bipolar plasma vaporization of the prostate: the Zürich experience.

INTRODUCTION AND OBJECTIVES: Bipolar plasma vaporization (BPV) has been introduced as an alternative to transurethral resection of the prostate (TURP). Promising short-term results, but inferior mid-term results compared to TURP have been reported following first-generation bipolar electrovaporization. Outcome data following second-generation BPV are still scarce. The aim of this investigation was to evaluate the intra- and postoperative outcomes of contemporary BPV in a center with long-standing expertise on laser vaporization of the prostate. METHODS: A consecutive series of 83 patients undergoing BPV in a tertiary referral center was prospectively evaluated. The investigated outcome parameters included the maximum flow rate (Qmax), postvoid residual volume, International Prostate Symptom Score (IPSS)/quality of life (Qol), and prostate-specific antigen (PSA) tests. Follow-up investigations took place after 6 weeks, 6 months, and 12 months. The Wilcoxon signed-rank test was used to compare pre- and post-treatment parameters. RESULTS: The median (range) preoperative prostate volume was 41 mL (17-111 mL). The preoperative IPSS, Qol, Qmax, and residual volume were 16 (2-35), 4 (0-6), 10.1 mL/s (3-29.3 mL/s), and 87 mL (0-1000 mL), respectively. One third of the patients were undergoing platelet aggregation inhibition (PAI). No intraoperative complications occurred. Postoperatively, 13 patients (15.7%) had to be recatheterized. Three patients (3.6%) had clot retention and 28 patients (34%) reported any grade of dysuria. After 6 weeks, all outcome parameters improved significantly and remained improved over the 12-month observation period [IPSS: 3 (0-2); Qol: 1 (0-4); Qmax: 17.2 mL/s (3.2-56 mL/s); residual volume 11 mL (0-190 mL)]. The PSA reduction was 60% at study conclusion. Three patients (3.6%) developed a urethral stricture and four patients (4.8%) bladder neck sclerosis. Re-resections were not necessary. CONCLUSIONS: Contemporary BPV is a safe and efficacious treatment option even for patients undergoing PAI. Early urinary retention and temporary dysuria seem to be specific side effects of the treatment. Bleeding complications are rare. Long-term follow-up is needed to confirm these promising short-term results.

A comparison of pubertal maturity and growth.

BACKGROUND: Growth and pubertal development have each been studied in detail, but rarely in conjunction. AIM: The study aim was to determine what somatic and pubertal development have in common and how they differ and to quantify the association between milestones for growth and for pubertal development (in terms of pubic hair and genitalia/breast, Age of Peak Testes Velocity, APTV and menarche) in relation both to chronological (CA) and bone age (RUS). SUBJECTS AND METHODS: The data analysed are from the 1st Zurich Longitudinal Growth Study, with 120 boys and 112 girls with almost complete data from birth to adulthood. RESULTS: Variability of pubertal milestones was somewhat reduced in terms of RUS, in particular in later phases. Pubic hair phase PH2 appeared ∼1 year after the onset of the pubertal spurt. Around the age of maximal deceleration (T9) an adult-like appearance of pubic hair, genitalia and breasts was reached in most cases. APTV occurred close to T8. Correlations were large between milestones for growth and PH stages and also with menarche or APTV. CONCLUSIONS: A successful modelling of testis growth led to a new pubertal milestone, APTV. The high correlations between the phenomenologically different domains "linear growth" and "pubertal development", and the high correlations between RUS and linear growth previously established allow the conclusion that these different domains develop along similar biological mechanisms, which are steered mainly by genetic factors.

Neuromotor development in children. Part 3: motor performance in 3- to 5-year-olds.

AIM: The aim of this cross-sectional study was to provide normative data (ordinal scores and timed performances) for gross and fine motor tasks in typically developing children between 3 and 5 years of age using the Zurich Neuromotor Assessment (ZNA). METHOD: Typically developing children (n=101; 48 males, 53 females) between 3 and 5 years of age were enrolled from day-care centres in the greater Zurich area and tested using a modified version of the ZNA; the tests were recorded digitally on video. Intraobserver reliability was assessed on the videos of 20 children by one examiner. Interobserver reliability was assessed by two examiners. Test-retest reliability was performed on an additional 20 children. The modelling approach summarized the data with a linear age effect and an additive term for sex, while incorporating informative missing data in the normative values. Normative data for adaptive motor tasks, pure motor tasks, and static and dynamic balance were calculated with centile curves (for timed performance) and expected ordinal scores (for ordinal scales). RESULTS: Interobserver, intraobserver, and test-retest reliability of tasks were moderate to good. Nearly all tasks showed significant age effects, whereas sex was significant only for stringing beads and hopping on one leg. INTERPRETATION: These results indicate that timed performance and ordinal scales of neuromotor tasks can be reliably measured in preschool children and are characterized by developmental change and high interindividual variability.

A comparison of skeletal maturity and growth.

BACKGROUND: Somatic and bone development have each been studied in detail, but rarely in conjunction. AIM: The aim of this study was to determine what somatic and bone development have in common and how they differ. A second aim was to check for a pubertal spurt in bone age (BA) and to quantify it in a similar way as has been done for height. The Preece-Baines model is used to fit longitudinal data for BA. SUBJECTS AND METHODS: The data analysed are from the 1st Zurich Longitudinal Growth Study comprising 120 boys and 112 girls with almost complete data from birth to adulthood. RESULTS: Variability of somatic milestones was reduced in terms of BA and there was an aftergrowth after reaching adult RUS score 1000. A strong increase in the RUS score was seen at a late stage of the pubertal spurt (PS). Somatic milestones correlated with the RUS score attained at these ages and more so at an early stage of the PS. A PS for BA was clearly identified with a location at 14.2 years for boys and 12.2 years for girls. Age of peak bone development correlated highly with age of peak velocity of somatic variables. CONCLUSIONS: BA can be successfully modelled as a semi-quantitative entity. Bone development shows marked associations with somatic development, despite the fact that the latter reflects changes in size, while the former is essentially a maturity index and reflects changes in biochemical composition of tissues.

Electrosurgery in urology: recent advances.

Inadequate hemostasis is one of the most important causes of morbidity and mortality following urological surgery. Despite the long-term usage of coagulation, there is an ongoing development of new devices, including bipolar transurethral resection of the prostate or new vessel-sealing devices. A thorough understanding of the advantages and disadvantages of these new instruments can improve the operative experience for both the urologist and patient. The optimal coagulation system should be small, efficient, easy to handle and with low heat spread. In this article, we analyze different electrothermal coagulation systems and modern tissue-sealing devices in urological applications with the aim to substantiate the advantages and disadvantages of each technique in terms of efficacy and safety.

Children with congenital hypothyroidism: long-term intellectual outcome after early high-dose treatment.

We aim to determine long-term intellectual outcome of adolescents with early high-dose treated congenital hypothyroidism (CH). Sixty-three prospectively followed children with CH were assessed at age of 14 y with the Wechsler Intelligence Scale for Children-Revised and compared with 175 healthy controls. Median age at onset of treatment was 9 d (range 5-18 d) and median starting dose of levothyroxine (L-T4) was 14.7 microg/kg/d (range 9.9-23.6 microg/kg/d). Full-scale intelligence quotient (IQ) was significantly lower than in controls after adjustment for socioeconomic status (SES) and gender (101.7 versus 111.4; p < 0.0001). Children with athyreosis had a lower performance IQ than those with dysgenesis (adjusted difference 7.6 IQ scores, p < 0.05). Lower initial thyroxine (T4) levels correlated with poorer IQ (r = 0.27, p = 0.04). Lower SES was associated with poorer IQ, in particular in children with CH (interaction, p = 0.03). Treatment during childhood was not related to IQ at age 14 y. Adolescents with CH manifest IQ deficits when compared with their peers despite early high-dose treatment and optimal substitution therapy throughout childhood. Those adolescents with athyreosis and lower SES are at particular risk for adverse outcome. Therefore, early detection of intellectual deficits is mandatory in children with CH.

Reliability of the Zurich Neuromotor Assessment.

Reliability of measurements of timed performance and ratings of associated movements (AMs) for tasks of the Zurich Neuromotor Assessment is investigated and methods to improve it are proposed. Better results were found for timed performance than for AMs. On average, intra-rater, inter-rater, and test-retest reliability (measured via intraclass correlation) were around 0.95, 0.9, and 0.65 for timed performance, and around 0.8, 0.7, and 0.45 for AMs. Reliability can be dramatically improved by considering neuromotor components (i.e., summary measures of individual measurements obtained at different tasks) instead of single tasks, which is significant for clinical work and research.