Pain and distress reactivity and recovery as early predictors of temperament in toddlers born preterm

Pain reactivity may reflect underlying mechanisms of constitutional aspects of temperament.

Multicenter Blinded Analysis of RT-PCR Detection Methods for Paramyxoviruses in Relation to Paget's Disease of Bone

Conflicting results have been reported on the detection of paramyxovirus transcripts in Paget's disease, and a possible explanation is differences in the sensitivity of RT-PCR methods for detecting virus. In a blinded study, we found no evidence to suggest that laboratories that failed to detect viral transcripts had less sensitive RT-PCR assays, and we did not detect measles or distemper transcripts in Paget's samples using the most sensitive assays evaluated.

Introduction: There is conflicting evidence on the possible role of persistent paramyxovirus infection in Paget's disease of bone (PDB). Some workers have detected measles virus (MV) or canine distemper virus (CDV) transcripts in cells and tissues from patients with PDB, but others have failed to confirm this finding. A possible explanation might be differences in the sensitivity of RT-PCR methods for detecting virus. Here we performed a blinded comparison of the sensitivity of different RT-PCR-based techniques for MV and CDV detection in different laboratories and used the most sensitive assays to screen for evidence of viral transcripts in bone and blood samples derived from patients with PDB.

Materials and Methods: Participating laboratories analyzed samples spiked with known amounts of MV and CDV transcripts and control samples that did not contain viral nucleic acids. All analyses were performed on a blinded basis.

Results: The limit of detection for CDV was 1000 viral transcripts in three laboratories (Aberdeen, Belfast, and Liverpool) and 10,000 transcripts in another laboratory (Manchester). The limit of detection for MV was 16 transcripts in one laboratory (NIBSC), 1000 transcripts in two laboratories (Aberdeen and Belfast), and 10,000 transcripts in two laboratories (Liverpool and Manchester). An assay previously used by a U.S.-based group to detect MV transcripts in PDB had a sensitivity of 1000 transcripts. One laboratory (Manchester) detected CDV transcripts in a negative control and in two samples that had been spiked with MV. None of the other laboratories had false-positive results for MV or CDV, and no evidence of viral transcripts was found on analysis of 12 PDB samples using the most sensitive RT-PCR assays for MV and CDV.

Conclusions: We found that RT-PCR assays used by different laboratories differed in their sensitivity to detect CDV and MV transcripts but found no evidence to suggest that laboratories that previously failed to detect viral transcripts had less sensitive RT-PCR assays than those that detected viral transcripts. False-positive results were observed with one laboratory, and we failed to detect paramyxovirus transcripts in PDB samples using the most sensitive assays evaluated. Our results show that failure of some laboratories to detect viral transcripts is unlikely to be caused by problems with assay sensitivity and highlight the fact that contamination can be an issue when searching for pathogens by sensitive RT-PCR-based techniques.

Mitomycin-C supplemented trabeculectomy, phacoemulsification, and foldable lens implantation

Purpose: To evaluate the outcome of combined mitomycin-C filtering surgery, phacoemulsification, and foldable intraocular lens (IOL) implantation. Setting: Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. Methods: This retrospective study evaluated 182 eyes of 174 patients who had combined mitomycin-C trabeculectomy, phacoemulsification, and insertion of a foldable IOL through a 3.5 mm incision. Success of the combined procedure was defined as intraocular pressure (IOP) below 21 mm Hg, with or without medications, and no serious complication. Success rates were calculated using the Kaplan-Meier actuarial method. Results: Mean follow-up was 16.7 months ± 5.4 (SD). The probability of success at 6, 12, 18, and 24 months was 98.3, 95.6, 90.6, and 88.0%, respectively. When compared with preoperativety, visual acuity improved one or more lines in 148 eyes (81.3%) and worsened one or more lines in 15 (8.2%); 111 eyes (61.0%) achieved visual acuity of 20/40 or better. The most frequent complication was posterior capsule opacification requiring capsulotomy, which occurred in 22 cases (12.0%). Conclusion: The 1 year and 2 year IOP control rate of combined mitomycin-C filtering procedures and phacoemulsification in glaucoma patients was high.

Late ultrastructural changes in the retina of the rat following low-dose X-irradiation

This study describes ultrastructural changes in the pigmented hooded Lister rat retina, 3-12 months following X-irradiation with single doses of between 200 and 2000 cGy. The extreme radiosensitivity of the photoreceptor cells was underlined by the continued manifestation of fine structural changes and cell death up to 6 months post-radiation in animals receiving doses above 500 cGy. The retinal pigment epithelial (RPE) cells were more radioresistant than photoreceptors and RPE cell loss was only observed at doses of more than 1500 cGy. One year after irradiation with 1500 cGy the retinal vasculature showed capillary occlusion with some evidence of recanalisation. Telangiectasia was observed in the large retinal veins. Although the inner retinal neurones and glial cells showed no evidence of direct radiation damage, the nerve fibre layer adjacent to occluded retinal vessels demonstrated ultrastructural evidence of ischaemic neuropathy and retinal oedema. At doses above 1500 cGy the choriocapillaris showed platelet aggregation and capillary loss.

Impact of the number of users on error probabilities in multiuser diversity systems

Multiuser diversity gain has been investigated well in terms of a system capacity formulation in the literature. In practice, however, designs on multiuser systems with nonzero error rates require a relationship between the error rates and the number of users within a cell. Considering a best-user scheduling, where the user with the best channel condition is scheduled to transmit per scheduling interval, our focus is on the uplink. We assume that each user communicates with the base station through a single-input multiple-output channel. We derive a closed-form expression for the average BER, and analyze how the average BER goes to zero asymptotically as the number of users increases for a given SNR. Note that the analysis of average BER even in SI SO multiuser diversity systems has not been done with respect to the number of users for a given SNR. Our analysis can be applied to multiuser diversity systems with any number of antennas.

How to classify the Oldest Old according to Health Status: A study of 1160 subjects belonging to 552 90+ Italian sibships characterised by familial longevity recruited within the GeHA EU project

The health status of the oldest old, the fastest increasing population segment worldwide, progressively becomes more heterogeneous, and this peculiarity represents a major obstacle to their classification. We compared the effectiveness of four previously proposed criteria (Franceschi et al., 2000; Evert et al., 2003; Gondo et al., 2006; Andersen-Ranberg et al., 2001) in 1160 phenotypically fully characterized Italian siblings of 90 years of age and older (90+, mean age: 93 years; age range: 90–106 years) belonging to 552 sib-ships, recruited in Northern, Central and Southern Italy within the EU-funded project GEHA, followed for a six-year-survival. Main findings were: (i) ‘‘healthy’’ subjects varied within a large range, i.e. 5.2% (Gondo), 8.7% (Evert), 17.7% (Franceschi), and 28.5% (Andersen-Ranberg); (ii) Central Italy subjects showed better health than those from Northern and Southern Italy; (iii) mortality risk was correlated with health status independently of geographical areas; and (iv) 90+ males, although fewer in number, were healthier than females, but with no survival advantage. In conclusion, we identified a modified version of Andersen-Ranberg criteria, based on the concomitant assessment of two basic domains (cognitive, SMMSE; physical, ADL), called ‘‘Simple Model of Functional Status’’ (SMFS), as the most effective proxy to distinguish healthy from not-healthy subjects. This model showed that health status was correlated within sib-ships, suggesting a familial/genetic component.

Blocking in children's causal learning depends on working memory and reasoning abilities.

A sample of 99 children completed a causal learning task that was an analogue of the food allergy paradigm used with adults. The cue competition effects of blocking and unovershadowing were assessed under forward and backward presentation conditions. Children also answered questions probing their ability to make the inference posited to be necessary for blocking by a reasoning account of cue competition. For the first time, children's working memory and general verbal ability were also measured alongside their causal learning. The magnitude of blocking and unovershadowing effects increased with age. However, analyses showed that the best predictor of both blocking and unovershadowing effects was children's performance on the reasoning questions. The magnitude of the blocking effect was also predicted by children's working memory abilities. These findings provide new evidence that cue competition effects such as blocking are underpinned by effortful reasoning processes. 

A Prospective Study of Growth and Biomarkers of Exposure to Aflatoxin and Fumonisin during Early Childhood in Tanzania

BACKGROUND: Aflatoxin and fumonisin are toxic food contaminants. Knowledge about effects of their exposure and co-exposure on child growth is inadequate.

OBJECTIVE: To investigate the association between child growth and aflatoxin and fumonisin exposure in Tanzania.

METHODS: A total of 166 children were recruited at 6 to 14 months of age and studied at recruitment, and at the sixth and twelfth month following recruitment. Blood and urine samples were collected and analysed for plasma aflatoxin albumin adducts (AF-alb) using ELISA, and urinary fumonisin B1 (UFB1) using LC-MS, respectively. Anthropometric measurements were taken and growth index Z-scores were computed.

RESULTS: AF-alb geometric mean concentrations (95% confidence intervals) were 4.7 (3.9, 5.6), 12.9 (9.9, 16.7) and 23.5 (19.9, 27.7) pg/mg albumin at recruitment, six months, and 12 months from recruitment, respectively. At these respective sampling times, geometric mean UFB1 concentrations (95% CI) were 313.9 (257.4, 382.9), 167.3 (135.4, 206.7) and 569.5 (464.5, 698.2) pg/mL urine, and the prevalence of stunted children were 44%, 55% and 56%, respectively. UFB1 concentrations at recruitment were negatively associated with length for age Z-scores (LAZ) at six months (p = 0.016) and at 12 months from recruitment (p = 0.014). The mean UFB1 of the three sampling times (at recruitment, at six and 12 months from recruitment) in each child was negatively associated with LAZ (p < 0.001) and length velocity (p = 0.004) at 12 months from recruitment. The negative association between AF-alb and child growth did not reach statistical significance.

CONCLUSIONS: Exposure to fumonisin alone, or co-exposure with aflatoxins may contribute to child growth impairment.

Urethral atrophy after artificial urinary sphincter placement:Is cuff downsizing effective?

Purpose: We reviewed the outcome of cuff downsizing with an artificial urinary sphincter for treating recurrent incontinence due to urethral atrophy.

Materials and Methods: We analyzed the records of 17 patients in a 7-year period in whom clinical, radiological and urodynamic evidence of urethral atrophy was treated with cuff downsizing. Cuff downsizing was accomplished by removing the existing cuff and replacing it with a 4 cm. cuff within the established false capsule. Incontinence and satisfaction parameters before and after the procedure were assessed by a validated questionnaire.

Results: Mean patient age was 70 years (range 62 to 79). Average time to urethral atrophy was 31 months (range 5 to 96) after primary sphincter implantation. Mean followup after downsizing was 22 months (range 1 to 64). Cuff downsizing caused a mean decrease of 3.9 to 0.5 pads daily. The number of severe leakage episodes decreased from a mean of 5.4 to 2.1 The mean SEAPI (stress leakage, emptying, anatomy, protection, inhibition) score decreased from 8.2 to 2.4. Patient satisfaction increased from 15% to 80% after cuff downsizing. In 1 patient an infected cuff required complete removal of the device.

Conclusions: Patient satisfaction and continence parameters improved after cuff downsizing. We believe that this technique is a simple and effective method of restoring continence after urethral atrophy.

All-Cause Mortality up to and After Coronary Heart Disease and Stroke Events in European Middle-Aged Men The PRIME Study

Background and Purpose-The aim was to investigate prospectively the all-cause mortality risk up to and after coronary heart disease (CHD) and stroke events in European middle-aged men.

Methods-The study population comprised 10 424 men 50 to 59 years of age recruited between 1991 and 1994 in France (N=7855) and Northern Ireland (N=2747) within the Prospective Epidemiological Study of Myocardial Infarction. Incident CHD and stroke events and deaths from all causes were prospectively registered during the 10-year follow-up. In Cox's proportional hazards regression analysis, CHD and stroke events during follow-up were used as time-dependent covariates.

Results-A total of 769 CHD and 132 stroke events were adjudicated, and 569 deaths up to and 66 after CHD or stroke occurred during follow-up. After adjustment for study country and cardiovascular risk factors, the hazard ratios of all-cause mortality were 1.58 (95% confidence interval 1.18-2.12) after CHD and 3.13 (95% confidence interval 1.98-4.92) after stroke.

Conclusions-These findings support continuous efforts to promote both primary and secondary prevention of cardiovascular disease.

Comprehensive profiling and localisation of the matrix metalloproteinases in urothelial carcinoma

The matrix metalloproteinases (MMPs) are endopeptidases which break down the extracellular matrix and regulate cytokine and growth factor activity. Several MMPs have been implicated in the promotion of invasion and metastasis in a broad range of tumours including urothelial carcinoma. In this study, RNA from 132 normal bladder and urothelial carcinoma specimens was profiled for each of the 24 human MMPs, the four endogenous tissue inhibitors of MMPs (TIMPs) and several key growth factors and their receptors using quantitative real time RT-PCR. Laser capture microdissection (LCM) of RNA from 22 tumour and 11 normal frozen sections was performed allowing accurate RNA extraction from either stromal or epithelial compartments. This study confirms the over expression in bladder tumour tissue of well-documented MMPs and highlights a range of MMPs which have not previously been implicated in the development of urothelial cancer. In summary, MMP-2, MT1-MMP and the previously unreported MMP-28 were very highly expressed in tumour samples while MMPs 1, 7, 9, 11, 15, 19 and 23 were highly expressed. There was a significant positive correlation between transcript expression and tumour grade for MMPs 1, 2, 8, 10, 11, 12, 13, 14, 15 and 28 (P < 0.001). At the same confidence interval, TIMP-1 and TIMP-3 also correlated with increasing tumour grade. LCM revealed that most highly expressed MMPs are located primarily within the stromal compartment except MMP-13 which localised to the epithelial compartment. This work forms the basis for further functional studies, which will help to confirm the MMPs as potential diagnostic and therapeutic targets in early bladder cancer.

A Parametric Study of a Drive by Bridge Inspection System Based on the Morlet Wavelet

Many of the bridges currently in use worldwide are approaching the end of their design lives. However, rehabilitating and extending the lives of these structures raises important safety issues. There is also a need for increased monitoring which has considerable cost implications for bridge management systems. Existing structural health monitoring (SHM) techniques include vibration-based approaches which typically involve direct instrumentation of the bridge and are important as they can indicate the deterioration of the bridge condition. However, they can be labour intensive and expensive. In the past decade, alternative indirect vibration-based approaches which utilise the response of a vehicle passing over a bridge have been developed. This paper investigates such an approach; a low-cost approach for the monitoring of bridge structures which consists of the use of a vehicle fitted with accelerometers on its axles. The approach aims to detect damage in the bridge while obviating the need for direct instrumentation of the bridge. Here, the effectiveness of the approach in detecting damage in a bridge is investigated using a simplified vehicle-bridge interaction (VBI) model in theoretical simulations and a scaled VBI model in a laboratory experiment. In order to identify the existence and location of damage, the vehicle accelerations are recorded and processed using a continuous Morlet wavelet transform and a damage index is established. A parametric study is carried out to investigate the effect of parameters such as the bridge span length, vehicle speed, vehicle mass, damage level and road surface roughness on the accuracy of results.