The fetal profile line:a proposal for a sonographic reference line to classify forehead and mandible anomalies in the second and third trimester

Objectives To test the fetal profile (FP) line, defined as the line that passes through the anterior border of the mandible and the nasion, as a reference line for forehead and mandible anomalies. Methods Volumes of 248 normal and 24 pathological fetuses (1636 and 1937?weeks gestation, respectively) were analysed retrospectively. When the FP line passes anteriorly, across or posteriorly to the frontal bone, this was defined as negative, zero or positive, respectively. When the FP line was positive the distance (F distance) between the FP line and the frontal bone was measured. Results No cases with a negative FP line were found in the normal fetuses. Before 27?weeks gestation the FP line was always zero except in one case. After 27?weeks gestation the FP line was positive in up to 25% (F distance (mean, range): 2.8, 2.13.6?mm). The FP line correctly identified 13 cases with retrognathia, 5 cases with frontal bossing and 3 cases with a sloping forehead. Conclusion Although large prospective studies are needed, the FP line may be a useful tool to detect second trimester profile anomalies such as retrognathia, sloping forehead and frontal bossing with the possibility of quantifying the latter. (c) 2012 John Wiley & Sons, Ltd

Improvement in the ability to have sex in patients with Peyronie's disease treated with Collagenase Clostridium histolyticum

Objective: To describe the results of intralesional Collagenase Clostridium histolyticum (CCH) treatment in patients with Peyronie's disease (PD) in real-world setting. PD is characterized by curvature of the erect penis caused by fibrotic tissue in the tunica albuginea.Patients and methods: Patients with stable PD and curvature of 30° to 90° were prospectively enrolled. CCH injections were initially given using a scheme of four cycles of two injections within 48–72 h every 6 weeks. Later using a modified scheme of three injections every 4 weeks, combined with a vacuum erection device (VED) twice daily. All patients were requested to take pictures of the erect penis prior to and following treatment, from above and laterally. Curvature was measured by three independent researchers based on the provided pictures using a goniometer. Furthermore, patients filled in the Peyronie Disease Questionnaire-NL (PDQ-NL) and Patient Reported Outcome Measurement (PROM).The primary outcome was reduction in curvature and the ability to have penetrating sex again. Secondary outcomes include pain scores during injections, changes in PDQ-NL, PROM and complications of CCH treatment.Results: Sixty-three patients were included, mean age was 56.0 years (range 39–70) and mean reduction in curvature 20.6° (SD 10.2, range 5–49); 74.5% of the patients were able to have penetrating sex again following treatment, compared with 41.2% prior to treatment. According to the PROM questions, sexual improvement was seen in 66.7% of patients. The satisfaction rate was 6.8 (SD 1.8). All patients save two recommend treatment.Conclusions: Intralesional treatment with CCH in men with PD leads to a mean curvature improvement of 20.6°. Following treatment, 74.5% of men were able to have sexual intercourse and 54.9% of the couples were satisfied with their sex life. No major complications occurred in the patients treated with CCH. CCH is not available in Europe anymore despite good results.</p

Organising knowledge generation and dissemination in the Dutch high-water protection programme–a sender-receiver approach

In 2012 the Dutch High-Water Protection Programme (HWPP) was initiated. This programme prioritised dike strengthening projects for the near future with a yearly budget of around 350 million Euros. A safety assessment 2011–2013 indicated the need to strengthen 748 km of dikes. To achieve this, it was recognised that generation and dissemination of state-of-the-art-knowledge was necessary. For this purpose, four Spatial and Technical Research Projects (STRPs) were initiated. The challenge for these STRPs is to generate and disseminate the developed knowledge that is relevant for other dike strengthening projects within the HWPP. This paper examines whether the STRPs have successfully undertaken activities to generate and disseminate new knowledge to relevant stakeholders. We examine how the generation and dissemination of knowledge from the STRPs to the HWP

HWBP: Kennisdoorwerking : Stand van zaken rondom het laten stromen van kennis vanuit POV's naar projecten toe

Op dit moment lopen er vier project overstijgende verkenningen (POVs) bij het Hoogwaterbeschermingsprogramma (HWBP). Deze POVs zijn kennisintensief en er wordt dan ook veel kennis ontwikkeld. Deze kennis is soms te vatten in documenten, maar soms betreft het ervaringskennis, welke moeilijker overdraagbaar is. Het leren tussen de betrokken partijen (overheden, kennisinstellingen en bedrijfsleven) wordt als een belangrijk aspect gezien om de overall ambitie van het HWBP te halen. De programmadirectie faciliteert en stimuleert het overstijgend leren tussen de verschillende projecten en POVs. Een belangrijk aspect hierbij is om aandacht te besteden aan het ontsluiten, borgen en toepassen van de in de POVs opgedane kennis/ervaring in de HWBP-projecten. Bij het voorliggende onderzoeksrapport staat dit centraal. De programmadirectie wil graag in kaart brengen op welke wijze de POVs en relevante projecten de ontwikkelde kennis gaan borgen - of dat al reeds hebben gedaan - opdat toekomstige HWBP projecten bij alle waterschappen hier gebruik van kunnen maken. Onderzoeksvraag hierbij is op welke wijze wordt de kennis en kunde uit de vier lopende POVs geborgd en hoe werkt het door in uitvoeringsprojecten van het HWBP, de daarbij betrokken organisaties en nationaal beleid (ontwerp- en toetsinstrumentarium)? In deze rapportage wordt per POV aangegeven welke activiteiten zijn ondernomen om de kennis door te laten stromen. Per POV worden enkele adviezen gegeven. Tevens zijn er generieke aanbevelingen voor de huidige POVs, nog op te starten POVs en op systeemniveau

Acute cholecystitis in high risk surgical patients: percutaneous cholecystostomy versus laparoscopic cholecystectomy (CHOCOLATE trial): Study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Laparoscopic cholecystectomy in acute calculous cholecystitis in high risk patients can lead to significant morbidity and mortality. Percutaneous cholecystostomy may be an alternative treatment option but the current literature does not provide the surgical community with evidence based advice.</p> <p>Methods/Design</p> <p>The CHOCOLATE trial is a randomised controlled, parallel-group, superiority multicenter trial. High risk patients, defined as APACHE-II score 7-14, with acute calculous cholecystitis will be randomised to laparoscopic cholecystectomy or percutaneous cholecystostomy. During a two year period 284 patients will be enrolled from 30 high volume teaching hospitals. The primary endpoint is a composite endpoint of major complications within three months following randomization and need for re-intervention and mortality during the follow-up period of one year. Secondary endpoints include all other complications, duration of hospital admission, difficulty of procedures and total costs.</p> <p>Discussion</p> <p>The CHOCOLATE trial is designed to provide the surgical community with an evidence based guideline in the treatment of acute calculous cholecystitis in high risk patients.</p> <p>Trial Registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2666">NTR2666</a></p

LC-MS/MS-based reference intervals for hair cortisol in healthy children

Background: Human scalp hair is a valuable matrix for determining long-term cortisol concentrations, with wide-spread applicability in clinical care as well as research. However, pediatric reference intervals are lacking. The aim of this cross-sectional study is to establish age-adjusted reference intervals for hair cortisol in children and to gain insight into hair growth velocity in children up to 2 years old. Methods: A total of 625 healthy children were enrolled through recruitment in pregnancy, infant-welfare clinics, and school visits. Scalp hair cortisol levels were measured using liquid chromatography-tandem mass spectrometry. Age-adjusted reference intervals were established in children from birth to 18 years old. Hair growth velocity was determined in children 0−2 years of age by measuring hair length at 4- to 10-week intervals. Results: Hair cortisol levels were high (162.4 pg/mg, 2.5th-97.5th percentile: 28.8–961) after birth with a sharp fall in the first 3 months of life. This is followed by lower values until age 6 and then by graduated and subtle higher values to adult concentrations are reached at the age of 18 years (3.0 pg/mg, 2.5th-97.5th percentile: 0.53–17.8). Average hair growth velocity measured in mm/month was significantly lower in infants 0–6 months of age compared to children 12–24 months (3.5 versus 9.4, P < 0.001). Conclusions: This is the first study to provide age-adjusted reference intervals for hair cortisol in children from 0−18 years. Higher hair cortisol concentrations in infants might be explained by the significantly lower hair growth rate in the first year of life. The establishment of pediatric hair cortisol reference ranges broadens the potential applications of this biomarker in pediatric clinical care

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways