Language development at 3 years in pre-term children of birth weight below 1000 g

Language development at 3 years of pre-term children born below 1000 g birth weight was compared with full-term controls matched for social background. The pre-term group used less complex expressive language and showed lower receptive understanding, auditory memory and verbal reasoning. Language outcome was related to intraventricular haemorrhage but not to global indication of postnatal illness such as number of days on the ventilator. Average verbal intelligence in environmentally low risk, extremely low birth weight children is an insufficient indicator of complex language functioning.

Comparison of Wavelet Transform and Time-Domain Analysis of Second Trimester Uterine Artery Doppler Waveforms in Screening for Pre-Eclampsia

The aim of this study was to compare time-domain waveform analysis of second-trimester uterine artery Doppler using the resistance index (RI) with waveform analysis using a mathematical tool known as wavelet transform for the prediction of pre-eclampsia (PE). This was a retrospective, nested case-cohort study of 336 women, 37 of whom subsequently developed PE. Uterine artery Doppler waveforms were analysed using both RI and waveform analysis. The utility of these indices in screening for PE was then evaluated using receiver operating characteristic curves. There were significant differences in uterine artery RI between the PE women and those with normal pregnancy outcome. After wavelet analysis, significant difference in the mean amplitude in wavelet frequency band 4 was noted between the 2 groups. The sensitivity for both Doppler RI and frequency band 4 for the detection of PE at a 10% false-positive rate was 45%. This small study demonstrates the application of wavelet transform analysis of uterine artery Doppler waveforms in screening for PE. Further prospective studies are needed in order to clearly define if this analytical approach to waveform analysis may have the potential to improve the detection of PE by uterine artery Doppler screening.

Fetal and maternal leptin in pre-gestational diabetic pregnancy

Objective: To compare maternal and fetal leptin among women without diabetes, women with type 1 diabetes, and women with type 2 diabetes. 

Methods: In a prospective study at the National Maternity Hospital, Dublin, 40 women with type 1 diabetes, 10 with type 2 diabetes, and 30 without diabetes were enrolled between July 2006 and July 2008. Maternal (36-week) and cord blood leptin was measured by enzyme-linked immunoassay. 

Results: No difference was found in maternal leptin among the groups: without diabetes (mean, range): 325 pg/mL, 36-1492 pg/mL; type 1 diabetes: 343.2 pg/mL, 55.5-1108.2 pg/mL; type 2 diabetes: 2022 pg/mL, 35.1-1553.3 pg/mL (P>0.05). Leptin levels were higher among fetuses of women with type 1 (223 pg/mL, 25.7-810 pg/mL) and type 2 (447.2 pg/mL, 1363-679 pg/mL) diabetes than among women without diabetes (803 pg/mL, 273-623.1 pg/mL; P<0.05). The single significant predictor of fetal leptin for the whole cohort was maternal body mass index (BMI; r=039, P=0.01). Only third-trimester glycosylated hemoglobin (HbA1c) was significantly related to fetal leptin after controlling for maternal BMI among women with diabetes (r=028, P=0.04).

 Conclusion: Fetuses of women with diabetes might have some degree of leptin resistance. This might be important in appetite regulation in extrauterine life. (C) 2012 International Federation of Gynecology and Obstetrics. 

On thin ice: surface order and disorder during pre-melting

The effect of temperature on the structure of the ice Ih (0001) surface is considered through a series of molecular dynamics simulations on an ice slab. At relatively low temperatures (200K) a small fraction of surface self-interstitials (i.e. admolecules) appear that are formed exclusively from molecules leaving the outermost bilayer. At higher temperatures (ca. 250 K), vacancies start to appear in the inner part of the outermost bilayer exposing the underlying bilayer and providing sites with a high concentration of the dangling hydrogen bonds. Around 250-260 K aggregates of molecules formed on top of the outermost bilayer from self-interstitials become more mobile and have diffusivities approaching that of liquid water. At similar to 270-280 K the inner bilayer of one surface noticeably destructures and it appears that at above 285 K both surfaces are melting. The observed disparity in the onset of melting between the two sides of the slab is rationalised by considering the relationship between surface energy and the spatial distribution of protons at the surface; thermodynamic stability is conferred on the surface by maximising separations between dangling protons at the crystal exterior. Local hotspots associated with a high dangling proton density are suggested to be susceptible to pre-melting and may be more efficient at trapping species at the external surface than regions with low concentrations of protons thus potentially helping ice particles to catalyse reactions. A preliminary conclusion of this work is that only about 10-20 K below the melting temperature of the particular water potential employed is major disruption of the crystalline lattice noted which could be interpreted as being "liquid", the thickness of this film being about a nanometre.

Topoisomerase IIα promotes activation of RNA polymerase I transcription by facilitating pre-initiation complex formation

Type II DNA topoisomerases catalyse DNA double-strand cleavage, passage and re-ligation to effect topological changes. There is considerable interest in elucidating topoisomerase II roles, particularly as these proteins are targets for anti-cancer drugs. Here we uncover a role for topoisomerase IIa in RNA polymerase I-directed ribosomal RNA gene transcription, which drives cell growth and proliferation and is upregulated in cancer cells. Our data suggest that topoisomerase IIa is a component of the initiation-competent RNA polymerase Iß complex and interacts directly with RNA polymerase I-associated transcription factor RRN3, which targets the polymerase to promoter-bound SL1 in pre-initiation complex formation. In cells, activation of rDNA transcription is reduced by inhibition or depletion of topoisomerase II, and this is accompanied by reduced transient double-strand DNA cleavage in the rDNA-promoter region and reduced pre-initiation complex formation. We propose that topoisomerase IIa functions in RNA polymerase I transcription to produce topological changes at the rDNA promoter that facilitate efficient de novo pre-initiation complex formation.

Quantitative estimation of retinal nerve fiber layer height in glaucoma and the relationship with optic nerve head topography and visual field

Purpose: The authors estimated the retinal nerve fiber layer height (RNFLH) measurements in patients with glaucoma compared with those in age-matched healthy subjects as obtained by the laser scanning tomography and assessed the relationship between RNFLH measurements and optic and visual field status. Methods: Parameters of optic nerve head topography and RNFLH were evaluated in 125 eyes of 21 healthy subjects and 104 patients with glaucoma using the Heidelberg Retina Tomograph ([HRT] Heidelberg Engineering GmbH, Heidelberg, Germany) for the entire disc area and for the superior 70°(50°temporal and 20°nasal to the vertical midline) and inferior 70°sectors of the optic disc. The mean deviation of the visual field, as determined by the Humphrey program 24-2 (Humphrey Instruments, Inc., San Leonardo, CA, U.S.A) was calculated in the entire field and in the superior and inferior Bjerrum area. Result: Retinal nerve fiber layer height parameters (mean RNFLH and RNFL cross-sectional area) were decreased significantly in patients with glaucoma compared with healthy individuals. Retinal nerve fiber layer height parameters was correlated strongly with rim volume, rim area, and cup/disc area ratio. Of the various topography measures, retinal nerve fiber layer (RNFL) parameters and cup/disc area ratio showed the strongest correlation with visual field mean deviation in patients with glaucoma. Conclusion: Retinal nerve fiber layer height measures were reduced substantially in patients with glaucoma compared with age-matched healthy subjects. Retinal nerve fiber layer height was correlated strongly with topographic optic disc parameters and visual field changes in patients with glaucoma.

Pre-validation methods for developing a patient reported outcome instrument

BACKGROUND: Measures that reflect patients' assessment of their health are of increasing importance as outcome measures in randomised controlled trials. The methodological approach used in the pre-validation development of new instruments (item generation, item reduction and question formatting) should be robust and transparent. The totality of the content of existing PRO instruments for a specific condition provides a valuable resource (pool of items) that can be utilised to develop new instruments. Such 'top down' approaches are common, but the explicit pre-validation methods are often poorly reported. This paper presents a systematic and generalisable 5-step pre-validation PRO instrument methodology.

METHODS: The method is illustrated using the example of the Aberdeen Glaucoma Questionnaire (AGQ). The five steps are: 1) Generation of a pool of items; 2) Item de-duplication (three phases); 3) Item reduction (two phases); 4) Assessment of the remaining items' content coverage against a pre-existing theoretical framework appropriate to the objectives of the instrument and the target population (e.g. ICF); and 5) qualitative exploration of the target populations' views of the new instrument and the items it contains.

RESULTS: The AGQ 'item pool' contained 725 items. Three de-duplication phases resulted in reduction of 91, 225 and 48 items respectively. The item reduction phases discarded 70 items and 208 items respectively. The draft AGQ contained 83 items with good content coverage. The qualitative exploration ('think aloud' study) resulted in removal of a further 15 items and refinement to the wording of others. The resultant draft AGQ contained 68 items.

CONCLUSIONS: This study presents a novel methodology for developing a PRO instrument, based on three sources: literature reporting what is important to patient; theoretically coherent framework; and patients' experience of completing the instrument. By systematically accounting for all items dropped after the item generation phase, our method ensures that the AGQ is developed in a transparent, replicable manner and is fit for validation. We recommend this method to enhance the likelihood that new PRO instruments will be appropriate to the research context in which they are used, acceptable to research participants and likely to generate valid data.

Tip leakage flow and heat transfer on turbine blade tip and casing, Part 1: Effect of tip clearance height and rotation speed

Steady simulations were performed to investigate tip leakage flow and heat transfer characteristics on the rotor blade tip and casing in a single-stage gas turbine engine. A typical high-pressure gas turbine stage was modeled with a pressure ratio of 3.2. The predicted isentropic Mach number and adiabatic wall temperature on the casing showed good agreement with available experimental data under similar operating condition. The present numerical study focuses extensively on the effects of tip clearance heights and rotor rotational speeds on the blade tip and casing heat transfer characteristics. It was observed that the tip leakage flow structure is highly dependent on the height of the tip gap and the speed of the rotor. In all cases, the tip leakage flow was seen to separate and recirculate just around the corner of the pressure side of the blade tip. This region of re-circulating flow enlarges with increasing clearance heights. The separated leakage flow reattaches afterwards on the tip surface. Leakage flow reattachment was shown to enhance surface heat transfer at the tip. The interaction between tip leakage flow and secondary flows that is induced by the relative casing motion is found to significantly influence the blade tip and casing heat transfer distribution. A region of critical heat transfer exists on the casing near the blade tip leading edge and along the pressure-side edge for all the clearance heights that were investigated. At high rotation speed, the region of critical heat transfer tends to move towards the trailing edge due to the change in inflow angle.

Reduced soluble receptor for advanced glycation end-products (sRAGE) scavenger capacity precedes pre-eclampsia in Type 1 diabetes

Objective Increased advanced glycation end-products (AGEs) and their soluble receptors (sRAGE) have been implicated in the pathogenesis of pre-eclampsia (PE). However, this association has not been elucidated in pregnancies complicated by diabetes. We aimed to investigate the serum levels of these factors in pregnant women with Type 1 diabetes mellitus (T1DM), a condition associated with a four-fold increase in PE. Design Prospective study in women with T1DM at 12.2 ± 1.9, 21.6 ± 1.5 and 31.5 ± 1.7 weeks of gestation [mean ± standard deviation (SD); no overlap] before PE onset. Setting Antenatal clinics. Population Pregnant women with T1DM (n = 118; 26 developed PE) and healthy nondiabetic pregnant controls (n = 21). Methods Maternal serum levels of sRAGE (total circulating pool), N -(carboxymethyl)lysine (CML), hydroimidazolone (methylglyoxal-modified proteins) and total AGEs were measured by immunoassays. Main outcome measures Serum sRAGE and AGEs in pregnant women with T1DM who subsequently developed PE (DM PE+) versus those who remained normotensive (DM PE-). Results In DM PE+ versus DM PE-, sRAGE was significantly lower in the first and second trimesters, prior to the clinical manifestation of PE (P <0.05). Further, reflecting the net sRAGE scavenger capacity, sRAGE:hydroimidazolone was significantly lower in the second trimester (P <0.05) and sRAGE:AGE and sRAGE:CML tended to be lower in the first trimester (P <0.1) in women with T1DM who subsequently developed PE versus those who did not. These conclusions persisted after adjusting for prandial status, glycated haemoglobin (HbA1c), duration of diabetes, parity and mean arterial pressure as covariates. Conclusions In the early stages of pregnancy, lower circulating sRAGE levels, and the ratio of sRAGE to AGEs, may be associated with the subsequent development of PE in women with T1DM. © 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.

Anti-angiogenic factors and pre-eclampsia in type 1 diabetic women

Aims/hypothesis: Elevated anti-angiogenic factors such as soluble fms-like tyrosine kinase 1 (sFlt1), a soluble form of vascular endothelial growth factor receptor, and endoglin, a co-receptor for TGFß1, confer high risk of pre-eclampsia in healthy pregnant women. In this multicentre prospective study, we determined levels of these and related factors in pregnant women with type 1 diabetes, a condition associated with a fourfold increase in pre-eclampsia.
Methods: Maternal serum sFlt1, endoglin, placental growth factor (PlGF) and pigment epithelial derived factor were measured in 151 type 1 diabetic and 24 healthy non-diabetic women at each trimester and at term.
Results: Approximately 22% of the diabetic women developed pre-eclampsia, primarily after their third trimester visit. In women with pre-eclampsia (diabetic pre-eclampsia, n?=?26) vs those without hypertensive complications (diabetic normotensive, n?=?95), significant changes in angiogenic factors were observed, predominantly in the early third trimester and prior to clinical manifestation of pre-eclampsia. Serum sFlt1 levels were increased approximately twofold in type 1 diabetic pre-eclampsia vs type 1 diabetic normotensive women at the third trimester visit (p?<?0.05) and the normal rise of PlGF during pregnancy was blunted (p?<?0.05). Among type 1 diabetic women, third trimester sFlt1 and PlGF were inversely related (r2?=?42%, p?<?0.0001). Endoglin levels were increased significantly in the diabetic group as a whole vs the non-diabetic group (p?<?0.0001).
Conclusions/interpretation: Higher sFlt1 levels, a blunted PlGF rise and an elevated sFlt1/PlGF ratio are predictive of pre-eclampsia in pregnant women with type 1 diabetes. Elevated endoglin levels in women with type 1 diabetes may confer a predisposition to pre-eclampsia and may contribute to the high incidence of pre-eclampsia in this patient group.

Pre-storage of gelified reagents in a lab-on-a-foil system for rapid nucleic acid analysis

Reagent pre-storage in a microfluidic chip can enhance operator convenience, simplify the system design, reduce the cost of storage and shipment, and avoid the risk of cross-contamination. Although dry reagents have long been used in lateral flow immunoassays, they have rarely been used for nucleic acid-based point-of-care (POC) assays due to the lack of reliable techniques to dehydrate and store fragile molecules involved in the reaction. In this study, we describe a simple and efficient method for prolonged on-chip storage of PCR reagents. The method is based on gelification of all reagents required for PCR as a ready-to-use product. The approach was successfully implemented in a lab-on-a-foil system, and the gelification process was automated for mass production. Integration of reagents on-chip by gelification greatly facilitated the development of easy-to-use lab-on-a-chip (LOC) devices for fast and cost-effective POC analysis.