Long-term outcomes of esophageal atresia

Esophageal atresia (EA), a common congenital anomaly comprising interrupted esophagus with or without a tracheoesophageal fistula (TEF), affects one in 2840 newborns. Over half have associated anomalies. After EA repair in infancy, gastroesophageal reflux (GER) and esophageal dysmotility and respiratory problems are common. As there exist no previous population-based long-term follow-up-studies on EA, its long-term sequelae are unclear. The aims of this study were to assess the cancer incidence (I), esophageal morbidity and function (II), respiratory morbidity (III), and the spinal defects (IV) in adults with repaired EA. All patients treated for EA at the Hospital for Children and Adolescents, University of Helsinki, from 1947 to 1985 were identified, and those alive with their native esophagus were contacted, and the first hundred who replied made up the study group. The patients were interviewed, they filled in symptom questionnaires, and they underwent esophageal endoscopy and manometry, pulmonary function tests, and a full orthopedic evaluation was performed with radiographs of the spine. The questionnaire was also sent by mail to adults with repaired EA not attending the clinical study, and to 287 general population-derived controls matched for age, gender, and municipality of residence. Incidence of cancer among the study population was evaluated from the population-based countrywide cancer registry. 169 (72%) adults with repaired EA replied; 101 (42%) (58 male) participated in the clinical studies at a median age of 36 years (range, 22-56). Symptomatic GER occurred in 34% and dysphagia in 85% of the patients and in 8% and 2% of the controls (P<0.001 for both). The main endoscopic findings included hiatal hernia (28%), Barrett´s esophagus (11%), esophagitis (8%), and stenotic anastomosis (8%). Histology revealed esophagitis in 25 individuals, and epithelial metaplasia in another 21. At immunohistochemistry, CDX2-positive columnar epithelial metaplasia was present in all 21 individuals, and 6 of these also demonstrated goblet cells and MUC2 positivity. In all histological groups, GER and dysphagia were equally common (P=ns). Esophageal manometry demonstrated non-propagating peristalsis in most of the patients, and low ineffective pressure of the distal esophageal body in all. The changes were significantly worse in those with epithelial metaplasia (P≤0.022). Anastomotic complications (OR 8.6-24, 95%CI 1.7-260, P=0.011-0.008), age (OR 20, 95%CI 1.3-310, P=0.034), low distal esophageal body pressure (OR 2.6, 95%CI 0.7-10, P=0.002), and defective esophageal peristalsis (OR 2.2, 95%CI 0.4-11, P=0.014) all predicted development of epithelial metaplasia. Despite the high incidence of esophageal metaplasia, none of the EA patients had suffered esophageal cancer, according to the Finnish Cancer Registry. Although three had had cancer (SIR, 1.0; 95% CI, 0.20-2.8). The overall cancer incidence among adults with repaired EA did not differ from that of the general Finnish population. Current respiratory symptoms occurred in 11% of the patients and 2% of the controls (P<0.001). Of the patients, 16%, and 6% of the controls had doctor-diagnosed asthma (P<0.001). A total of 56% and 70% of the patients and 20% and 50% of the controls had a history of pneumonia and of bronchitis (P<0.001 for both). Respiratory-related impaired quality of life was observable in 11% of the patients in contrast to 6% of the controls (P<0.001). PFT revealed obstruction in 21 of the patients, restriction in 21, and both in 36. A total of 41 had bronchial hyper-responsiveness (BHR) in HCT, and 15 others had an asthma-like response. Thoracotomy-induced rib fusion (OR 3.4, 95%CI 1.3-8.7, P=0.01) and GER-associated epithelial metaplasia in adulthood (OR 3.0, 95%CI 1.0-8.9, P=0.05) were the most significant risk factors for restrictive ventilatory defect. Vertebral anomalies were evident in 45 patients, predominating in the cervical spine in 38. The most significant risk factor for the occurrence of vertebral anomalies was any additional anomaly (OR 27, 95%C I8-100). Scoliosis (over 10 degrees) was observable in 56 patients, over 20 degrees in 11, and over 45 degrees in one. In the EA patients, risk for scoliosis over 10 degrees was 13-fold (OR 13, 95%CI 8.3-21) and over 20 degrees, 38-fold (OR 38, 95%CI 14-106) when compared to that of the general population. Thoracotomy-induced rib fusion (OR 3.6, 95%CI 0.7-19) and other associated anomalies (OR 2.1, 95%CI 0.9-2.9) were the strongest predictive factors for scoliosis. Significant esophageal morbidity associated with EA extends into adulthood. No association existed between the esophageal symptoms and histological findings. Surgical complications, increasing age, and impaired esophageal motility predicted development of epithelial metaplasia after repair of EA. According to our data, the risk for esophageal cancer is less than 500-fold that of the general population. However, the overall cancer incidence among adults with repaired EA did not differ from that of the general population. Adults with repaired EA have had significantly more respiratory symptoms and infections, as well as more asthma, and allergies than does the general population. Thoracotomy-induced rib fusion and GER-associated columnar epithelial metaplasia were the most significant risk factors for the restrictive ventilatory defect that occurred in over half the patients. Over half the patients with repaired EA are likely to develop scoliosis. Risk for scoliosis is 13-fold after repair of EA in relation to that of the general population. Nearly half the patients had vertebral anomalies. Most of these deformities were diagnosed neither in infancy nor during growth. The natural history of spinal deformities seems, however, rather benign, with spinal surgery rarely indicated.

Long-term outcome and extraintestinal manifestations in congenital chloride diarrhea

The rare autosomal recessive disease congenital chloride diarrhea (CLD) is caused by mutations in the solute carrier family 26 member 3 (SLC26A3) gene on chromosome 7q22.3-31.1. SLC26A3 encodes for an apical epithelial chloride-bicarbonate exchanger, the intestinal loss of which leads to profuse chloride-rich diarrhea, and a tendency to hypochloremic and hypokalemic metabolic alkalosis. Although untreated CLD is usually lethal in early infancy, the development of salt substitution therapy with NaCl and KCl in the late 1960s made the disease treatable. While the salt substitution allows normal childhood growth and development in CLD, data on long-term outcome have remained unclarified. One of the world s highest incidences of CLD 1:30 000 to 1:40 000 occurs in Finland, and CLD is part of the Finnish disease heritage. We utilized a unique sample of Finnish patients to characterize the long-term outcome of CLD. Another purpose of this study was to search for novel manifestations of CLD based on the extraintestinal expression of the SLC26A3 gene. This study on a sample of 36 patients (ages 10-38) shows that the long-term outcome of treated CLD is favorable. In untreated or poorly treated cases, however, chronic contraction and metabolic imbalance may lead to renal injury and even to renal transplantation. Our results demonstrate a low-level expression of SLC26A3 in the human kidney. Although SLC26A3 may play a minor role in homeostasis, post-transplant recurrence of renal changes shows the unlikelihood of direct transporter modulation in the pathogenesis of CLD-related renal injury. Options to resolve the diarrheal symptoms of CLD have been limited. Unfortunately, our pilot trial indicated the inefficacy of oral butyrate as well. This study reveals novel manifestations of CLD. These include an increased risk for hyperuricemia, inguinal hernias, and probably for intestinal inflammation. The most notable finding of this study is CLD-associated male subfertility. This involves a low concentration of poorly motile spermatozoa with abnormal morphology, high seminal plasma chloride with a low pH, and a tendency to form spermatoceles. That SLC26A3 immunoexpression appeared at multiple sites of the male reproductive tract in part together with the main interacting proteins cystic fibrosis transmembrane conductance regulator (CFTR) and sodium-hydrogen exchanger 3 (NHE3) suggests novel sites for the cooperation of these proteins. As evidence of the cooperation, defects occurring in any of these transporters are associated with reduced male fertility. Together with a finding of high sweat chloride in CLD, this study provides novel data on extraintestinal actions of the SLC26A3 gene both in the male reproductive tract and in the sweat gland. These results provide the basis for future studies regarding the role of SLC26A3 in different tissues, especially in the male reproductive tract. Fortunately, normal spermatogenesis in CLD is likely to make artificial reproductive technologies to treat infertility and even make unassisted reproduction possible.

Long-term Accelerated Multistress Aging of Composite Outdoor Polymeric Insulators

Polymeric outdoor insulators are being increasingly used for electrical power transmission and distribution in the recent years. One of the current topics of interest for the power transmission community is the aging of such outdoor polymeric insulators. A few research groups are carrying out aging studies at room temperature with wet period as an integral part of multistress aging cycle as specified by IEC standards. However, aging effect due to dry conditions alone at elevated temperatures and electric stress in the presence of radiation environment has probably not been explored. It is interesting to study and understand the insulator performance under dry conditions where wet periods are either rare or absent and to estimate the extent of aging caused by multiple stresses. This paper deals with the long-term accelerated multistress aging on full-scale 11 kV distribution class composite silicone rubber insulators. In order to assess the long-term synergistic effect of electric stress, temperature and UV radiation on insulators, they are subjected to accelerated aging in a specially designed multistress-aging chamber for 3800 hours. All the stresses are applied at an accelerated level. Using a data acquisition system developed for the work, leakage current has been monitored in LabVIEW environment. Chemical changes due to degradations have been studied using Energy Dispersive X-Ray analysis, Scanning Electron Microscope and Fourier transform Infrared Spectroscopy. Periodically different parameters like low molecular weight (LMW) molecular content, hydrophobicity, leakage current and surface morphology were monitored. The aging study is under progress and only intermediate results are presented in this paper.

Long-term Accelerated Weathering of Outdoor Silicone Rubber Insulators

Multistress aging/weathering of outdoor composite polymeric insulators has been a topic of interest for power transmission research community in the last few decades. This paper deals with the long-term accelerated weathering of full-scale distribution class silicone rubber composite insulators. To evaluate the long-term synergistic effect of electric stress, temperature and UV radiation on insulators, they were subjected to accelerated weathering in a specially designed multistress-aging chamber for 30,000 h. All the insulators were subjected to the same level of electrical and thermal stresses but different UV radiation levels. Chemical, physical and electrical changes due to degradation have been assessed using various techniques. It was found that there was a monotonous reduction of the content of low molecular weight (LMW) molecules with the duration of the weathering. Further, due to oxidation and weathering there is an appreciable increase in surface roughness and atomic percentage of oxygen. There is no change in the leakage current of new and aged insulators under both wet and dry conditions at the end of the aging. The results also indicate that there is no influence of UV radiation on the silicone rubber for the durations and conditions under which the studies were made.

Cannabis use and involuntary admission may mediate long-term adherence in first-episode psychosis patients: a prospective longitudinal study

Background: This study aimed to examine factors associated with treatment adherence in first-episode psychosis (FEP) patients followed up over 8 years, especially involuntary first admission and stopping cannabis use. Methods: This prospective, longitudinal study of FEP patients collected data on symptoms, adherence, functioning,and substance use. Adherence to treatment was the main outcome variable and was categorized as ‘good’ or ‘bad’. Cannabis use during follow-up was stratified as continued use, stopped use, and never used. Bivariate and logistic regression models identified factors significantly associated with adherence and changes in adherence over the 8-year follow-up period. Results: Of the 98 FEP patients analyzed at baseline, 57.1% had involuntary first admission, 74.4% bad adherence,and 52% cannabis use. Good adherence at baseline was associated with Global Assessment of Functioning score (p = 0.019), Hamilton Depression Rating Scale score (p = 0.017) and voluntary admission (p < 0.001). Adherence patterns over 8 years included: 43.4% patients always bad, 26.1% always good, 25% improved from bad to good. Among the improved adherence group, 95.7% had involuntary first admission and 38.9% stopped cannabis use. In the subgroup of patients with bad adherence at baseline, involuntary first admission and quitting cannabis use during follow up were associated with improved adherence. Conclusions: The long-term association between treatment adherence and type of first admission and cannabis use in FEP patients suggest targets for intervention to improve clinical outcomes.

The effect of long term exploitation by the gill net fishery on the multispecies fish stocks in Kainji Lake, Nigeria, 1969-1997

The findings are presented of an assessment made of the gillnet fishery in Kainji Lake, Nigeria from 1969 to the present, on the basis of data sets from commercial and experimental gillnet fishing, with the purpose to detect trends in some key fishery monitoring indicators. During this period, there has been an increase in the number of small meshed nets in the fishery resulting in a shift in the mode to lower mesh sizes; consequently, the average mesh size declined gradually in the fishery. This trend is found to be directly correlated with the decline in the CPUE and mean weight of the fish species. It is argued that the observed trend in CPUE and mean weight is forcing the fishermen to switch effort to gears such as traps which have very small meshes and can indescriminately take all sizes of the fish. It is shown that the catch composition by weight of Citharinus citharus, Lates niloticus and tilapias declined in the gillnet fishery in the late 70's and early 80's. Recent data, from 1994 to 1996, however indicates that C. citharus is recovering, but with declining mean weight. This suggests that the exploitation pattern is shifting to the smaller fish through the use of small meshed nets. In general, however, there has not been drastic changes in species bio-diversity in the Lake as a result of predatory effect and ecosystem overfishing as has happened in other great African Lakes. The species composition since lake formation continued to be dominated by fewer that 20 species. The potential yield for the lake has been estimated to be 32,166 tonnes (excluding clupeids) and the required optimum fishing effort to be 1,814 fishing canoes. In view of the relative stability of the species diversity in the lake and the current fish production level, it is proposed here that this MSY be adopted for all species. This would be achieved with the current effort level in the lake assuming that the efficiency of the fishermen and their gears do not improve. It should be reviewed after 10 or more years of catch and effort data collection. (PDF contains 65 pages)

Long-term Trends in Catch Composition from Elasmobranch Derbies in Elkhorn Slough, California

Long-term trends in the elasmobranch assemblage of Elkhorn Slough, Monterey Bay, California, were analyzed by documenting species composition and catch per unit effort (CPUE) from 55 sport fishing derbies that occurred during May, June, and July, from 1951 until 1995. The most abundant species (bat ray, Myliobatis californica; shovelnose guitarfish, Rhinobatos productus; and leopard shark, Triakis semifasciata) were also analyzed for size-weight relationships, trends in size class distribution, stage of maturity, and sex ratios. Changes in species composition over the course of the derbies included the near complete disappearance of shovelnose guitarfish by the 1970’s and a slight increase in the abundance of minor species (mainly smoothhounds, Mustelus spp., and thornback, Platyrhinoidis triseriata) starting in the mid 1960’s. The relative abundance of bat rays in the catch steadily increased over the years while the relative abundance of leopard sharks declined during the last two decades. However the average number of bat rays and leopard sharks caught per derby declined during the last two decades. Fishing effort appeared to increase over the course of the derbies. There were no dramatic shifts in the size class distribution data for bat rays, leopard sharks, or shovelnose guitarfish. The catch of bat rays and leopard sharks was consistently dominated by immature individuals, while the catch of shovelnose guitarfish was heavily dominated by adults. There was evidence of sexual segregation in either immature or mature fish in all the species. Female bat rays and shovelnose guitarfish were larger than their male counterparts and outnumbered males nearly 2:1. Female and male leopard sharks were more nearly equal in size and sex ratio. Changes in species composition are likely due to fishing pressure, shifts in the prevailing oceanographic conditions, and habitat alteration in Elkhorn Slough. The sex ratios, stage of maturity, and size class distributions provide further evidence for the theory that Elkhorn Slough functions as a nursery habitat for bat rays and leopard sha

Meteorological and hydrologic studies in the Alaskan Arctic in support of long-term ecological research

Long-term hydrologic studies in the Arctic simply do not exist. Although the Arctic has been identified as an area that is extremely sensitive to climate change, continuous scientific research has been limited to the past seven years. Earlier research was spotty, of short duration, and directed at only one or two hydrologic elements. Immediate future research needs to encompass all the major hydrologic elements, including winter processes, and needs to address the problem of scaling from small to larger areas in hydrologic models. Also, an international program of cooperation between northern countries is needed to build a greater scientific base for monitoring and identifying potential changes wrought by the climate.

Trends and long-term variability of ocean properties at Ocean Station P in the northeast Pacific Ocean [abstract]

Twenty-seven years (1956-1983) of oceanographic data collected at Ocean Station P (50°N/145°W), as well as supplementary data obtained in its neighborhood, have been examined for trends and interannual variability in the northeast Pacific Ocean. There is evidence that the water is warming and freshening and that the isopycnal surfaces are deepening. Trends in oxyty are mostly not significant. The most common periods for the interannual variability appear to be 2 1/2 and 6-7 years. The vertical movement of water accounts for one half of the changes in temperature and salinity and 30% of those in oxyty. Other factors, such as a shift of water masses, may also be important.

Long-term monitoring of habitats and reef fish found inside and outside the U.S. Virgin Islands Coral Reef National Monument: a comparative assessment

The primary objective of this study was to assess the efficacy of the Virgin Islands Coral Reef National Monument (VICR), a marine protected area in St John, US Virgin Islands. Surveys of habitat and fishes inside and outside of VICR were conducted in 2003-2008. Areas outside the VICR had significantly more scleractinian corals, greater habitat complexity, and greater species richness and density of reef fishes than areas inside., Areas inside and outside the VICR exhibited significant decreases in percent scleractinian coral coverage over the study period. A contrasting trend of increasing macroalgal cover was also observed. No clear effect of the severe 2005 coral bleaching event was observed suggesting other causal factors. No obvious trends in the fish community were observed across the study period. The significant decline in habitat condition, coupled with the initial incorporation of some of the more degraded reefs into the marine protected area may result in a longer time period necessary to detect positive changes in the St. John coral reef ecosystem and associated reef fish abundance and community structure.

Population status, seasonal variation in abundance, and long-term population trends of Steller sea lions (Eumetopias jubatus) at the South Farallon Islands, California

We examined seasonal and annual variation in numbers of Steller (northern) sea lions (Eumetopias jubatus) at the South Farallon Islands from counts conducted weekly from 1974 to 1996. Numbers of adult and subadult males peaked during the breeding season (May–July), whereas numbers of adult females and immature individuals peaked during the breeding season and from late fall through early winter (September–December). The seasonal pattern varied significantly among years for all sexes and age classes. From 1977 to 1996, numbers present during the breeding season decreased by 5.9% per year for adult females and increased by 1.9% per year for subadult males. No trend in numbers of adult males was detected. Numbers of immature individuals also declined by 4.5% per year during the breeding season but increased by 5.0% per year from late fall through early winter. Maximum number of pups counted declined significantly through time, although few pups were produced at the South Farallon Islands. The ratio of adult females to adult males averaged 5.2:1 and declined significantly with each year, whereas no trend in the ratio of pups to adult females was discernible. Further studies are needed to determine if reduced numbers of adult females in recent years have resulted from reduced survival of juvenile or adult females or from changes in the geographic distribution of females.

Modelling of long-term ground response to tunnelling under St James's Park, London

Following a tunnel excavation in low-permeability soil, it is commonly observed that the ground surface continues to settle and ground loading on the tunnel lining changes, as the pore pressures in the ground approach a new equilibrium condition. The monitored ground response following the tunnelling under St James's Park, London, shows that the mechanism of subsurface deformation is composed of three different zones: swelling, consolidation and rigid body movement. The swelling took place in a confined zone above the tunnel crown, extending vertically to approximately 5 m above it. On the sides of the tunnel, the consolidation of the soil occurred in the zone primarily within the tunnel horizon, from the shoulder to just beneath the invert, and extending laterally to a large offset from the tunnel centreline. Above these swelling and consolidation zones the soil moved downward as a rigid body. In this study, soil-fluid coupled three-dimensional finite element analyses were performed to simulate the mechanism of long-term ground response monitored at St James's Park. An advanced critical state soil model, which can simulate the behaviour of London Clay in both drained and undrained conditions, was adopted for the analyses. The analysis results are discussed and compared with the field monitoring data. It is found that the observed mechanism of long-term subsurface ground and tunnel lining response at St James's Park can be simulated accurately only when stiffness anisotropy, the variation of permeability between different units within the London Clay and non-uniform drainage conditions for the tunnel lining are considered. This has important implications for future prediction of the long-term behaviour of tunnels in clays.

Spatial exploration induces a persistent reversal of long-term potentiation in rat hippocampus

Experience-dependent long-lasting increases in excitatory synaptic transmission in the hippocampus are believed to underlie certain types of memory(1-3). Whereas stimulation of hippocampal pathways in freely moving rats can readily elicit a long-term potentiation (LTP) of transmission that may last for weeks, previous studies have failed to detect persistent increases in synaptic efficacy after hippocampus-mediated learning(4-6). As changes in synaptic efficacy are contingent on the history of plasticity at the synapses(7), we have examined the effect of experience-dependent hippocampal activation on transmission after the induction of LTP, We show that exploration of a new, non-stressful environment rapidly induces a complete and persistent reversal of the expression of high-frequency stimulation-induced early-phase LTP in the CA1 area of the hippocampus, without affecting baseline transmission in a control pathway. LTP expression is not affected by exploration of familiar environments. We found that spatial exploration affected LTP within a defined time window because neither the induction of LTP nor the maintenance of long-established LTP was blocked. The discovery of a novelty-induced reversal of LTP expression provides strong evidence that extensive long-lasting decreases in synaptic efficacy may act in tandem with enhancements at selected synapses to allow the detection and storage of new information by the hippocampus.

Long-term depression in rat CA1-subicular synapses depends on the G-protein coupled mACh receptors

The subiculum, which is the primary target of CA1 pyramidal neurons and sending efferent fibres to many brain regions, serves as a hippocampal interface in the neural information processes between hippocampal formation and neocortex. Long-term depression (LTD) is extensively studied in the hippocampus, but not at the CA1-subicular synaptic transmission. Using whole-cell EPSC recordings in the brain slices of young rats, we demonstrated that the pairing protocols of low frequency stimulation (LFS) at 3 Hz and postsynaptic depolarization of -50 mVelicited a reliable LTD in the subiculum. The LTD did not cause the changes of the paired-pulse ratio of EPSC. Furthermore, it did not depend on either NMDA receptors or voltage-gated calcium channels (VGCCs). Bath application of the G-protein coupled muscarinic acetylcholine receptors (mAChRs) antagonists, atropine or scopolamine, blocked the LTD, suggesting that mAChRs are involved in the LTD. It was also completely blocked by either the Ca2+ chelator BAPTA or the G-protein inhibitor GDP-beta-S in the intracellular solution. This type of LTD in the subiculum may play a particular role in the neural information processing between the hippocampus and neocortex. (c) 2005 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

GABA Transporter-1 Activity Modulates Hippocampal Theta Oscillation and Theta Burst Stimulation-Induced Long-Term Potentiation

The network oscillation and synaptic plasticity are known to be regulated by GABAergic inhibition, but how they are affected by changes in the GABA transporter activity remains unclear. Here we show that in the CA1 region of mouse hippocampus, pharmacolog