Halobacteriumsp. NRC-1 is an extremely halophilic archaeon that is easily cultured and genetically tractable. Since its genome sequence was completed in 2000, a combination of genetic, transcriptomic, proteomic, and bioinformatic approaches have provided insights into both its extremophilic lifestyle as well as fundamental cellular processes common to all life forms. Here, we review post-genomic research on this archaeon, including investigations of DNA replication and repair systems, phototrophic, anaerobic, and other physiological capabilities, acidity of the proteome for function at high salinity, and role of lateral gene transfer in its evolution. Halophilic archaea  are extremophiles that grow optimally under conditions of extremely high salinity, 5–10 times that of seawater [Classical studies of haloarchaea contributed significantly to our understanding of adaptive mechanisms, as well as universal features of life . NotableHalobacterium sp. NRC-1 [Haloarcula marismortui, a metabolically versatile microorganism from the Dead Sea [Haloferax volcanii, a prototrophic and moderate halophilic microorganism from Dead Sea mud [Natronomonas pharaonis, an alkaliphile from the soda lakes of the Sinai [Halorubrum lacusprofundi, a cold-adapted extreme halophile from an Antarctic lake [Halobacterium sp. NRC-1, primarily through post-genomic studies [In 2000, the complete genome sequence of p. NRC-1 -11, a typ. NRC-1 , became Dead Sea , Halofer Sea mud , Natronohe Sinai , and Haltic lake . These fHalobacterium sp. NRC-1 is an extreme halophile (with a 4.3 M NaCl optimum) that grows best heterotrophically in a rich organic broth. However, the organism is metabolically versatile , and via arginine fermentation. It also has phototrophic capability through the light-driven proton pumping activity of the retinal protein, bacteriorhodopsin, which is organized into a two-dimensional crystalline array in its purple membrane. Halobacterium sp. NRC-1 cells are highly motile, synthesizing gas vesicles, which are hollow protein structures, intracellularly for buoyancy and flotation, and sensory rhodopsins for phototaxis. Relevant to the study of genetic regulation, Halobacterium sp. NRC-1 responds to many environmental effectors, including high and low temperatures and salinities, and ultraviolet (UV) and ionizing radiation.Halobacterium sp. NRC-1 is its ease of manipulation in the laboratory. Culturing is simple, with a 6 hour generation time at 42°C [ura3 gene, which permit construction of systematic gene knockouts and replacements [Halobacterium sp. NRC-1 cells are easily lysed in hypotonic medium, releasing both soluble and membrane proteins for biochemical and biophysical studies [Halobacterium sp. NRC-1 an excellent model microorganism for research as well as for teaching.A major advantage of studying  at 42°C . Additio at 42°C , and a g at 42°C . Severalacements -22. Wholacements -26. Halo studies . These cHalobacterium NRC-1 possesses the smallest genome to date among halophiles. It is 2,571,010 bp in size, and is composed of a large GC-rich chromosome , and two smaller extrachromosomal replicons, pNRC100  and pNRC200 , with 58–59 % G+C composition [Halobacterium predicted proteins were found to be highly acidic [Halobacterium species, and this point has been the subject of some controversy [Halobacterium sp. NRC-1 genome have been published [position . The twoposition , and theposition . As a reposition . Of the y acidic  and a suy acidic . In additroversy -31. Inteublished .Halobacterium sp. NRC-1 as a model system has been its genetic tractability [2+, thereby weakening the S-layer, and resulting in formation of spheroplasts, followed by treatment with polyethylene glycol, which induces competence [r marker for selection in Halobacterium. The Mevr marker contains an up-promoter allele of the Haloferax volcanii 3-hydroxy-3-methylglutaryl-CoA reductase (mva) gene, required for branched chain lipid biosynthesis [A key factor in the development of tability . Transfompetence . Plasmidmpetence , or natumpetence . For exampetence , containynthesis .Halobacterium sp. NRC-1, the first described for an archaeon [ura3 gene ; the plasmid also contains the ura3 gene under the control of its own promoter. The resulting plasmid is introduced into a Halobacterium Δura3 host via transformation. Integrants are then selected by uracil prototrophy (Ura+) using commercially available uracil-dropout media components. Subsequently, plasmid excisants are selected via ura3 counterselection, 5-fluoroorortic acid-resistance (Foar), giving rise to derivatives containing either the original or mutant allele, which may be distinguishable by PCR or phenotypic analysis.A directed gene replacement and knockout method for archaeon -22, explHalobacterium sp. NRC-1, both PCR microarray and Agilent in situ synthesized oligonucleotide [Halobacterium sp. NRC-1 were problematic in the probe design and exceptionally high data quality was obtained, with low occurrence of data outliers due to non-uniform spot morphology, background noise, or spot-to-spot variation for replicate experiments.For transcriptome analysis in cleotide  microarrcleotide -26. For cleotide . NeitherHalobacterium sp. NRC-1 proteome has also been extensively analyzed by liquid chromatography-tandem mass spectroscopy (LC/MS/MS) [Halobacterium species was analyzed by 2D-GE and MALDI-TOF mass spectrometric analysis of tryptic fragments and a reference map was established [The C/MS/MS) ,40, and ablished ,42.Halobacterium sp. NRC-1: those relevant to success in their extreme environment, such as the purple membrane, gas vesicles, DNA repair and anaerobic physiology, and those that are similar to fundamental eukaryotic processes, such as DNA replication, and transcription systems. Some studies were initiated prior to genome sequencing using genetic approaches have been advanced via genomic, bioinformatic, or functional genomic work, during the post-genomic period.Two types of gene systems have been studied in Halobacterium sp. NRC-1 provided the first opportunity for isolating autonomously replicating sequences from an archaeon and this was accomplished for both the chromosome and the large extrachromosomal replicon, pNRC100 [in vivo origins of replication, were isolated and cloned using their ability to endow autonomous replication ability on E. coli plasmids containing a selectable mevinolin resistance (Mevr) marker. For the chromosome, a directed approach was taken to investigate whether chromosomal loci proximal to orc/cdc6 homologs possessed autonomous replication ability. A region of 2.3 kb containing the orc7 gene (one of ten eukaryotic-type origin recognition complex homologs), plus 750 bp upstream of the orc7 gene translational start, displayed replication ability [ori region corresponded to one of two chromosomal inflection points in cumulative GC-skew analysis (which has been used for bioinformatic prediction of replication origins) [ori region was also conserved in the genome sequences of other halophilic archaea, including Haloarcula marismortui and Haloferax volcanii [orc gene near a second inflection point was not able to confer replication ability, suggesting the existence of only a single chromosomal origin in Halobacterium sp. NRC-1. pNRC100 ,43. The origins) ,44. The repH gene, was isolated using similar methodology [Halobacterium strain [repH, which was necessary for plasmid replication; however, the upstream region could be interrupted and partially deleted without knocking out replication ability. Genome sequencing showed that the repH gene region is present in both pNRC100 and pNRC200, and therefore may be involved in the replication of both replicons. Interestingly, the latter replicon also contains multiple orc gene homologs, the functions of which are unknown [Halobacterium replicating sequences has facilitated the development of vectors, including both shuttle plasmids and expression vectors [Previously, an autonomously replicating region of pNRC100, containing a 550 bp AT-rich region upstream of the hodology . Howeverm strain . For the unknown -11. In a vectors .Halobacterium sp. NRC-1 has been of significant interest. The euryarchaeon, Pyrococcus abyssi, was shown to contain a single chromosomal replication origin composed of similar large inverted repeats 5' to the only orc/cdc6 gene of this archaeon [Sulfolobus solfataricus and S. acidocaldarius, were reported to contain two or three chromosomal replication origins proximal to multiple orc/cdc6 genes in their genomes [Halobacterium sp. NRC-1, a euryarchaeon, the roles and relationships of multiple (10) orc/cdc6 and repH genes in replication require further experimentation for complete understanding.The number of replication origins and their coordination in archaeon ,47. Howe genomes ,49. In HHalobacterium sp. NRC-1 because of the observed high levels of radiation resistance and the presence of homologs of both bacterial and eukaryotic-type repair genes [phr gene homologs in the genome [2, specific induction of radA1 and replication factor A genes  was observed [Sulfolobus solfataricus, replication factor A was found to bind to UV damaged DNA [Repair of DNA damage has been investigated in ir genes . For UV e genome . Photolye genome ,26; howeobserved . In a biaged DNA . In a staged DNA .Halobacterium sp. NRC-1 contains the light-driven proton pump, bacteriorhodopsin, a complex of a protein, bacterio-opsin (bop gene product), and a retinal chromophore  domain, PAS/PAC (redox-sensing) domain, and C-terminal DNA-binding helix-turn-helix (HTH) motif [brp in the oxidative cleavage of β-carotene to form retinal was shown using the ura3-based gene knockout system, which also led to the identification of an unlinked gene, blh, capable of performing the same function [crtY), was also identified by a genetic knockout [The purple membrane of  cluster ,54. The H) motif . Additiofunction . Anotherknockout .bop gene promoter region was studied by a combination of saturation mutagenesis and bioinformatic analysis [Halobacterium sp. NRC-1 genome suggested the use of alternative Tbp-Tfb pairs in promoter selection and transcriptional regulation, similar to that proposed for higher organisms [bop [brp and crtB1, which are coordinately regulated with bop [The analysis -60. The analysis . In thisrganisms . Mutagensms [bop . Additiowith bop . Similarwith bop ,54.Halobacterium sp. NRC-1 includes anaerobic respiration using DMSO and TMAO as electron acceptors and fermentation with arginine via the arginine deiminase pathway  under anaerobic conditions, allowing the cells to float to more aerobic zones in the water column. In a different study where Halobacterium strains overproducing or lacking purple membrane  were compared, it was deduced that during phototrophy, genes required for arginine fermentation are repressed [The metabolic capability of p. NRC-1 , bioinfonditions . Gene kntor, Bat ,25. DNA epressed .Halobacterium sp. NRC-1 to float, increasing their access to light and oxygen. A large gene cluster on pNRC100 (gvpMLKJIHGFEDACNO) is necessary and sufficient to produce gas vesicles [gvpD-A intergenic region [gvp genes are inducible under microaerobic, anaerobic, and other stressful conditions [gvpA and gvpC, encoding the two most abundant gas vesicle proteins, was induced in early exponential growth phase [gvpA transcription. A combination of genetic and bioinformatic analysis suggested that GvpE functions as an activator, with a leucine-zipper motif mediating dimer formation, and that GvpD, which contains an NTP-binding site, likely functions as a repressor by blocking GvpE-mediated activation [Gas vesicles are hollow, buoyant protein structures that allow vesicles -69. Tranc region ,67 and Dnditions . Rightwativation .Halobacterium sp. NRC-1 gas vesicles was studied using immunoblotting [Halobacterium NRC-1 gas vesicles, and coiled-coil domains were identified in GvpF and GvpL, suggestive of self-association [gvp genes are present in all gas vesicle containing organisms examined [The protein composition of blotting . In addiblotting . The Gvpblotting ,73. Threociation . This waexamined ,74-77.Halobacterium sp. NRC-1 is resistant to arsenic, a heavy metal which is frequently found in hypersaline environments [arsMR2ADR1C, organized into three operons, was shown to be involved through construction and analysis of gene knockouts. Deletion of the arsADRC gene region increased sensitivity to arsenite. However, knockout of a putative arsB gene homolog on the chromosome showed no phenotypic effect, suggesting the existence of a novel arsenite pump in Halobacterium sp. NRC-1. Interestingly, knockout of the arsM gene also produced increased sensitivity to arsenite, indicating a second novel mechanism of arsenic resistance involving an arsenite methyltransferase. The arsenite resistance elements were shown to be regulated, with resistance to arsenic being inducible by exposure to a sublethal concentration of the metal [Halobacterium sp. NRC-1 containing two arsenite detoxification systems.ronments . A gene he metal . These r12 metabolism has been explored in Halobacterium sp. NRC-1 using a combination of physiological and genetic approaches [12 precursors from the environment was shown to require a previously unidentified amidohydrolase, the cbiZ gene product, which converts adenosylcobinamide to adenosylcobyric acid, an intermediate of the de novo coenzyme B12 biosynthetic route [12 precursors by the CbiZ enzyme appears to be a uniquely archaeal strategy, because all of the genomes of B12-producing archaea have a cbiZ ortholog. Genetic studies showed that uptake of cobalamins for Halobacterium occurs via an ABC transporter similar to the bacterial Btu system [Coenzyme Bproaches -81. Salvic route . The salHalobacterium sp. NRC-1 genes, e.g. using Escherichia coli as host for complementation analysis and heterologous expression. An RNase H similar to the Type 1 bacterial enzyme, required for primer removal in DNA replication, was found to suppress the temperature-sensitive growth defect in E. coli, although the basic region present in the E. coli protein is absent in the haloarchaeal protein [Cys by the bacterial-type cysteinyl-tRNA synthetase of Halobacterium sp. NRC-1 was studied after expression in E. coli and showed similarities to its bacterial counterpart [Several additional experimental studies have been carried out on  protein . The halnterpart .Halobacterium sp. NRC-1 since genome sequencing. They include studies of protein acidity, proteome structure prediction, and phylogenetic analysis of genes that may have been acquired through lateral gene transfer (LGT), as well as a number of broad or narrowly focused comparative studies.A large number of bioinformatics investigations have been carried out on Halobacterium sp. NRC-1 provided deep insight into the ability of this organism to survive under hypersaline conditions [Halobacterium proteins and the generality of this observation was confirmed through analysis of subsequent haloarchaeal genome sequences. In contrast, the median pI of nearly all non-halophilic proteomes has been found to be close to neutral, usually with a bimodal distribution of basic (pI ~10) and acidic (pI ~5) proteins. Notable exceptions were for some methanogenic archaea and an extremely halophilic bacterium, Salinibacter ruber, which sometimes coexist with Halobacterium in hypersaline environments and also contain relatively high internal salt concentrations [Isoelectric point analysis of the predicted proteome of nditions -11,28. Atrations -86. The trations .Halobacterium proteins was correlated to a high concentration of surface negative charge in modeled structures [The acidic pI of ructures . A transructures , the surde novo structure prediction was conducted on 1,185 proteins and protein domains of Halobacterium sp. NRC-1 [In another study, p. NRC-1 . PutativHalobacterium sp. NRC-1 confirmed the archaeal status of Halobacterium sp. NRC-1 [Bacillus subtilis, and the radiation-resistant bacterium, Deinococcus radiodurans. Subsequent whole-genome analysis using a larger number of completed genomes produced phylogenetic trees with Halobacterium branching near the base of the archaeal branch, or even within the bacteria [Halobacterium within the archaeal clade [Initial whole-genome phylogenetic analysis of p. NRC-1 , but alsbacteria ,91. Thisal clade . One intal clade .E. coli operons  [Halobacterium genes and a phylogenetic study indicated their grouping with bacterial genes. A further detailed study of the nuoI gene showed clear phylogenetic affinity with proteobacteria [In spite of the initial uncertainties, several cases for LGT now appear to be convincing. Some components of the electron transport chain and biosynthetic proteins were found to have gene organization identical to homologous nthesis) . GC compbacteria . These sbacteria .argS) gene of Halobacterium sp. NRC-1, which is found on pNRC200 [Halobacterium does not group with other archaeal  ArgS proteins, but is most closely related to a class of ArgS proteins from bacteria  declare that they have no competing interests.All authors participated in drafting of this manuscript.


Anxiety disorders are common problems that result in enormous suffering and economic costs. The efficacy of Web-based self-help approaches for anxiety disorders has been demonstrated in a number of controlled trials. However, there is little data regarding the patterns of use and effectiveness of freely available Web-based interventions outside the context of controlled trials. To examine the use and longitudinal effectiveness of a freely available, 12-session, Web-based, cognitive behavioral therapy (CBT) program for panic disorder and agoraphobia. Cumulative anonymous data were analyzed from 99695 users of the Panic Center. Usage statistics for the website were examined and a longitudinal survey of self-reported symptoms for people who registered for the CBT program was conducted. The primary outcome measures were self-reported panic-attack frequency and severity at the beginning of each session (sessions 2-12).P<.002) in self-reported panic attack frequency and severity, comparing 2 weeks of data against data after 3, 6, or 8 weeks. For example, the 152 users completing only 3 sessions of the program reduced their average number of attacks per day from 1.03 (week 2) to 0.63 (week 3) (P<.001). Between September 1, 2002 and February 1, 2004, there were 484695 visits and 1148097 page views from 99695 users to the Panic Center. In that same time period, 1161 users registered for the CBT program. There was an extremely high attrition rate with only 12 (1.03%) out of 1161 of registered users completing the 12-week program. However, even for those who remained in the program less than 12 weeks we found statistically significant reductions ( Freely available Web-based self-help will likely be associated with high attrition. However, for the highly self-selected group who stayed in the program, significant improvements were observed. Anxiety disorders are common problems that result in enormous suffering and economic costs . UnfortuSelf-help therapy for anxiety disorders has been found to be effective, especially when the interventions are tailored to the individual's specific symptoms and situation and administered with a minimal amount of professional guidance and support -10. Web-There has been some research on Web-based programs designed to provide relatively generic CBT interventions for depression and anxiety , programAlthough the evidence for the efficacy of Web-based self-help for mood and anxiety disorders from controlled trials is encouraging, it is important to determine how such programs are utilized and to estimate their effectiveness when accessed by diverse, less well-selected groups of users under less controlled conditions. To this end, Christensen et al  recentlyIn contrast to previous reports of the efficacy of computer-assisted and Web-based interventions for anxiety in well-controlled research settings, in the present study we examined the use and effectiveness in an uncontrolled visitor population of a freely available Web-based CBT program for panic disorder.The Panic Center  is an in                                        As illustrated in As an alternative to using the Web-based treatment program, users can download an Adobe version of the 12-session program and use the hard copy as a traditional self-help book. Although this option reduces the number of people using the Web-based program and options for collecting data about the use and effectiveness of the program, it is offered in the interest in maximizing the dissemination and use of the program.The following describes some of the components in more detail.The support group format consists of asynchronous communication (bulletin board format) between members of the support community and the moderators. Users of the support group also have access to individualized email support and advice from the moderators, who are Registered Nurses (Multimedia Appendix Slide 8).International Classification of Diseases and Related Health Problems, tenth revision (ICD-10)  = 3.633, P=.004). At session 1, 8 out of these 12 users met screening criteria for panic disorder with agoraphobia; at session 12, only 2 continued to meet screening criteria for the disorder. In addition, 3 out of these 12 users met screening criteria for social anxiety at session 1, whereas only one met screening criteria at session 12.Only 12 users completed all outcome measures, including the WB-DAT. At session 1, those 12 individuals met criteria for an average of 1.42 (SD 0.90) DSM-IV Axis 1 Disorders according to the screener. At session 12, they met criteria for an average of 0.42 (SD 0.79) disorders , as compared to 0.42 (SD 0.77) at the end of treatment . At the end of session 12 users were also asked to rate the degree to which their fear/and or avoidance interfered with their normal daily life, with 0 being none/no interference and 4 meaning extreme/severe interference. On average, the 12 users who completed the survey rated this question as 0.42 (SD = 0.90).At registration and at the end of session 12, users were asked a number of questions, including a question about the degree to which their panic attacks interfered with their normal daily lives on a 0 to 4 scale with 0 being In response to the survey at the end of session 12, 12 out of 12 (100.00%) users reported that since challenging the Panic Program they were challenging their anxious thoughts, 11 out of 12 (91.67%) reported that they were getting better at setting goals and designing exposure plans, 12 out of 12 (100.00%) reported that since starting the Panic Program they had gained confidence in their ability to challenge their fears and win, and 12 out of 12 (100.00%) reported that they believed that their hard work was paying off. Out of 12 users, 10 (83.33%) reported that they used the Support Group and 10 out of 10 (100%) rated the Support Group as “extremely helpful.”This study evaluated the patterns of use and effectiveness of a Web-based self-help program for panic disorder and agoraphobia. We found that the website is popular and well utilized. Users tend to visit the website several times and spend considerable time on the website. With respect to the goal of increasing collaborative disease management and promoting communication between consumers and health care professionals, it would appear that the website is being used for that purpose. For example, approximately 50% of users who complete the WB-DAT report that they either intend to share the results with a health care professional or are considering doing so, and approximately 10% of users reported that they were using the CBT program in collaboration with a health care professional. A small but noteworthy percentage of people who registered to use the WB-DAT and CBT program, and those who downloaded the print version of the CBT program identified themselves as health care professionals.Among the interesting findings from this study is the fact that a fairly high proportion of users who completed the WB-DAT met criteria for one or more anxiety disorders. It appears that users of the website are likely people who are self-selected because they are suffering from some type of anxiety disorder and perhaps especially panic disorder or agoraphobia. It is also interesting that most support group users were passive visitors and viewers as opposed to users who post information.The data regarding the usage and effectiveness of the CBT program are also interesting. Although many people used the program for a few weeks, only a few used it for the entire 12 sessions. However, consistent with the literature -11,27,28It is important to note that these data were collected in an uncontrolled fashion. In contrast to previous reports of controlled trials of computer and Web-based interventions, we analyzed cumulative anonymous data from a freely available program. In addition, the sample was not demographically well characterized. In order to ensure anonymity, only minimal demographic data were collected. Because this was a longitudinal design with no control group we do not know whether the highly self-selected group of users who stayed in the program would have become better also without the intervention.The most notable problem is the high attrition rate, which is consistent with other research on self-help interventions ,10. For The high attrition rate may also be caused by the option of downloading a PDF file of the entire Panic Program. Given that 1161 users registered for the program and 1159 users downloaded the PDF version, it seems likely that many users preferred to read from the hard copy. They may have stopped using the Web-based program and their data regarding their usage of the program was therefore lost. However, they may have continued to use the hard copy to some effect. It also may be that many people choose to use self-help resources in a nonlinear manner.The results of this study are consistent with the results of recent research demonstrating the efficacy of Web-based self-help for panic disorder , the effIn summary, despite the high attrition rate, these data suggest that freely available Web-based self-help for panic disorder can be effective for self-selected individuals. Such a result is interesting given the cost-effectiveness of Web-based treatments compared to conventional psychotherapeutic treatment and the potential for Web-based interventions to reach people in need , 38,39.


An earthquake measuring 6.8 on the Richter scale struck the Niigata-Chuetsu region of Japan at 5.56 P.M. on the 23rd of October, 2004. The earthquake was followed by sustained occurrence of numerous aftershocks, which delayed reconstruction of community lifelines. Even one year after the earthquake, 9,160 people were living in temporary housing. Such a devastating earthquake and life after the earthquake in an unfamiliar environment should cause psychological distress, especially among the elderly.Psychological distress was measured using the 12-item General Health Questionnaire (GHQ-12) in 2,083 subjects (69% response rate) who were living in transient housing five months after the earthquake. GHQ-12 was scored using the original method, Likert scoring and corrected method. The subjects were asked to assess their psychological status before the earthquake, their psychological status at the most stressful time after the earthquake and their psychological status at five months after the earthquake. Exploratory and confirmatory factor analysis was used to reveal the factor structure of GHQ12. Multiple regression analysis was performed to analyze the relationship between various background factors and GHQ-12 score and its subscale.GHQ-12 scores were significantly elevated at the most stressful time and they were significantly high even at five months after the earthquake. Factor analysis revealed that a model consisting of two factors  using corrected GHQ scoring showed a high level of goodness-of-fit. Multiple regression analysis revealed that age of subjects affected GHQ-12 scores. GHQ-12 score as well as its factor 'social dysfunction' scale were increased with increasing age of subjects at five months after the earthquake.Impaired psychological recovery was observed even at five months after the Niigata-Chuetsu Earthquake in the elderly. The elderly were more affected by matters relating to coping with daily problems. An earthquake measuring 6.8 on the Richter scale struck the Niigata-Chuetsu region of Japan at 5.56 P.M. on the 23rd of October, 2004. The earthquake was followed by sustained occurrence of numerous aftershocks, one of which measuring 5.0 occurred even on 28th of December, 2004. The earthquake and the following aftershocks left more than 4,500 injured and 120,000 houses completely or partially destroyed. About 100,000 people were displaced from their homes, and some of them moved into temporary housing. Because of the sustained occurrence of aftershocks and delayed reconstruction of community lifelines, 9,160 people who lost their houses were still living in temporary housing even in November 2005, one year after the earthquake. The impact of the devastating earthquake and the following life in an unfamiliar environment should cause psychological distress for people affected by the earthquake , among pPrevious studies have shown that the elderly are at high risk for psychological distress as a result of a large disaster ,8. HowevFive months after the earthquake, 3,026 subjects who lost houses at the earthquake and had continued to live in temporary housing were asked to reply to questionnaire surveys prepared to measure their psychological distress. A total of 2,083 subjects replied to the questionnaire, a response rate of 69%. Characteristics of the study subjects are outlined in Table tetrachoric correlations, we used binary data as continuous data in spite of problems over handling binary data in factor analysis . Goodness-of-fit of the models was tested by using F0 (estimated population discrepancy), root mean square error of approximation (RMSEA) and ECVI  [33].To study factor structure of GHQ-12, exploratory factor analysis was performed -15,17-27Scheffe post hoc tests was used to evaluate differences over time in the GHQ-12 scores as well as lower scale points of the identified factors. In all tests, a p value less than 0.05 was considered as statistically significant. Analysis other than confirmatory factor analysis was performed using SPSS 14.0J.Multiple regression analysis was conducted to evaluate the impact of subjects' background on the GHQ-12 scores. Independent variables used in the analysis are shown in Table This study was approved by the Ethics Committee of Niigata Graduate School of Medical and Dental Sciences. Informed written consent was obtained from all subjects.GHQ-12 scored by the three scoring methods was significantly elevated when the subjects felt the most stressful compared to the scores before the earthquake. Although the scores had decreased five months after the earthquake, they were still higher than the scores before the earthquake  declare that they have no competing interests.ST contributed to concept and design of the article and analysis of data. TS1, HK and TE contributed to acquisition of data. NT contributed to statistical analysis of data. TS2 and AK supervised all aspects of the study and revised the article. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Recently the financial status of primary care trusts has come under considerable scrutiny by the government, and financial deficits have been blamed on poor local management of resources. This paper examines the factors that differ between those Primary Care Trusts (PCT) in financial deficit and those in surplus, using readily available data at PCT level. PCTs are the National Health Service organisations in England responsible for improving the health of their population, developing primary and community health services, and commissioning secondary care services.A descriptive comparative study using data from 58 PCTs; 29 in greatest financial surplus and 29 in greatest deficit in the English National Health Service.Nearly half the study deficit PCTs (14 out of 29) are in the East of England and of the 29 surplus PCTs, five each are in Birmingham and Black Country Strategic Health Authority (SHA), and Greater Manchester SHA. The median population density of the deficit PCTs is almost seven times lower than that of surplus PCTs (p = 0.004). Surplus PCTs predominantly serve deprived communities. Nearly half the surplus PCTs are 'spearhead' PCTs compared to only one of the deficit PCTs. Percentage population increase by local authority of the PCT showed that on average deficit PCTs had 2.7 times higher change during 1982–2002 (13.37% for deficit and 4.94% for surplus PCTs). Work pressure felt by staff is significantly higher in deficit PCTs, and they also reported working higher amount of extra hours due to work pressures. The proportion of dispensing general practitioners is significantly higher in deficit PCTs 40.5% vs. 12.9% (p = 0.002). Deficit PCTs on average received £123 less per head of registered population compared to surplus PCTs.The two groups of PCTs serve two distinct populations with marked differences between the two. Deficit PCTs tend to be in relatively affluent and rural areas. Poor management alone is unlikely to be the cause of deficits, and potential reasons for deficits including rurality and increased demand for health services in more affluent communities need further in-depth studies. The financial status of many NHS organisations including Primary Care Trusts (PCTs) has come under considerable scrutiny in recent months and this has attracted much political and media interest. Department of Health figures show that in the year 2004–05, 90 of the 303 PCTs in England were overspent, 92 broke even and 121 were in surplus [However, the King's Fund found in their study  of hospiIt is particularly important for PCTs trying to cope with a deficit to understand possible contributory factors. As a first step, this paper examines the factors that differ between those PCTs in financial deficit and those in surplus, using PCT level data from various sources.Our aim was to determine the factors that might influence the financial status of PCTs in England. A wide range of factors might impact on their financial status and a number of key areas were identified in advance of data analysis. Only variables considered relevant to the research question, with few missing values, and showing discrimination between PCTs were included. These were measures of: PCT demographic and socioeconomic profile, health and health needs, performance and staffing profile, primary and secondary care activity, and resource allocation.Data on the financial status of the PCTs was gathered from the DH web site . The finThe variables included in the analysis are demographic, morbidity & mortality, geographic, socio-economic, performance and staffing. This information was downloaded from the NHS National workforce projects web page ,7. We alQOF achievement information at PCT level for the year 2004–05 was downloaded from the Health and Social Care Information Centre . GMS praFinished consultant episodes at PCT level was retrieved from the Health Care Workforce PCT profile .PCTs receive their financial allocation from the DH on the basis of a weighted capitation formula, which takes into account factors including age and gender structure of the population, geographic and social factors, and morbidity and mortality rates. Closing composite distance from target for the year 2004–05 and 2006–07 for all the PCTs was abstracted from the Unified Exposition Books ,12. Expo2 or Fisher's exact test for categorical variables, and 't' test or rank test for continuous variables as appropriate. Due to the multiple testing of many variables, a p value of <0.01 was considered statistically significant.Data for the 58 PCTs were collated and analysed using the Statistical Package for Social Sciences version 14 . The twoNearly half of the deficit PCTs (14 out of 29) are in the East of England and one third (9 out of 29) are concentrated in the Norfolk Suffolk and Cambridgeshire Strategic Health Authority (SHA). Of the 29 surplus PCTs 5 each are in Birmingham and Black Country SHA, and Greater Manchester SHA.There was no difference between the two groups of PCTs in mean age or proportion of those aged under 6, or 65 years and over. Fifteen of the 29 surplus PCTs belong to the Office for National Statistics (ONS) bands 1 to 4 as opposed to 3 deficit PCTs (Fisher's exact test p = 0.000); . Deficit PCTs predominantly belong to band 5 and 6 . There is marked difference in the population density of the two groups of PCTs, with the median density being nearly 7 times lower in the deficit PCTs (p = 0.004). Nearly half (14) surplus PCTs were spearhead PCTs compared to only one of the deficit PCTs.Table There were no major differences in the performance of the two groups of PCTs using the Health Care Commission's Star rating data  apart frThere were no significant differences in staffing variables, except that surplus PCTs employed 1 Health Visitor (HV) per 5137 registered population as opposed to 1 HV per 6570 by deficit PCTs (p = 0.002). The work pressure felt by staff is significantly higher (p = 0.006) in deficit PCTs (3.3) compared to surplus PCTs (3.2) and a higher % of staff in deficit PCTs (66.3% vs. 62.0%) also reported working more extra hours owing to work pressures; (p = 0.005).The average practice size (PCT population divided by number of practices) was significantly higher in deficit PCTs (7132) compared to surplus PCTs (5555) (p = 0.000). The proportion of dispensing GPs was significantly higher in deficit PCTs 40.5% vs. 12.9% (p = 0.002). Practices in deficit PCTs had a marginally higher average total QOF points but this was not statistically significant .On average deficit PCTs had a higher number of finished consultant episodes (FCE) per 1000 population .Deficit PCTs received on average £205 per head of resident population and £123 per head of registered population less than the surplus PCTs (p = 0.000). Comparison of 2004–05 closing composite DFT showed a marked difference, with deficit PCTs being over target by an average of 1.5% and surplus PCTs under target by 2.73% (p = 0.001). However in their 2006–07 allocation deficit PCTs were under target on average by 1% in 2006–07.Not required.The factors influencing financial status of PCTs are probably very complex and have not been studied in detail. It is unlikely that deficits are due to poor management alone, and if this were the case, one would not expect to see a clustering of the PCTs most in deficit in one region of the country as observed in this study. The aim of this study was to identify factors that differ between PCTs in financial deficit and those in surplus, and a number of striking differences were observed.The analysis compared the 29 English PCTs most in deficit with the 29 PCTs in the best financial position. The profiles of these PCTs showed that the two groups serve quite different populations. The PCTs in financial surplus have been shown to be in the less prosperous areas of the country, with significantly higher levels of deprivation on measures such as unemployment, educational achievement, proportion of benefit claimants, proportion of poorer housing, standardised mortality ratios, and life expectancy for men. These are the factors that are taken into account in the distribution of resources within the NHS, with positive discrimination in favour of deprived areas, intended to take account of their extra health care needs and to reduce health inequalities.As other authors have noted: "The current resource allocation formula responds well to the higher relative needs of the urban populations. Yet, it is generally agreed that the NHS  has relatively little to contribute towards the reduction of health inequalities compared to other sources of variation such as income distribution, education and so on. Thus, the targeting of additional services at urban deprived populations is likely to be an ineffective response to health inequalities. It is one, moreover, that introduces a new form of inequity by underestimating the needs of rural populations" .Other government initiatives such as the introduction of health trainers, which are being targeted in the first instance at deprived communities  and whicThe results of the study further demonstrate the effects of Resource Allocation when the differences in funding per head of population in the two groups of PCTs are considered. It is noteworthy that deficit PCTs receive on average £205 less per resident population and £123 less per registered population than the surplus PCTs . Different data sources covering different time periods were used, and although this could be a weakness, as the data were gathered for purposes other than the one under study , and came from multiple sources, this further strengthens the study observations. Qualitative information from clinicians, managers and patients from the two groups of PCTs might have thrown further light on the difference. We did not attempt to gather this data due to resource constraints. Another important point to note is that associations observed do not imply causation. Finally, as the analysis was undertaken at group level the issue of ecological fallacy needs to be borne in mind. In other words, apparent associations measured at a group level (i.e. PCTs in surplus or deficit), may not necessarily be applicable to individual PCTs.This preliminary study has demonstrated that the PCTs in England that are most in financial deficit represent a markedly different population from the PCTs most in surplus. The PCTs in financial surplus appear to be those that have benefited from the positive discrimination of the Department of Health's Resource Allocation Formula. With the Government committed to reducing health inequalities in the UK, targeting funding to those areas of the country with the poorest health must be a sound policy objective. Indeed a recent study  on inequThe author(s) of this paper are all employed by a PCT, which is in financial deficit.PB developed the original idea, identified the data bases and abstracted the data, performed the analysis and wrote the manuscript. RAC abstracted the data, performed the analysis, interpreted the results and wrote the manuscript. PMB was involved in the further development of the original idea, interpreted the results and wrote the manuscript. All authors approved the final version of the manuscript. PB and RAC are the guarantors of the paper.The pre-publication history for this paper can be accessed here:


Dietary fat and low fruit and vegetable intake are linked to many chronic diseases, and U.S. population intake does not meet recommendations. Interventions are needed that incorporate effective behavior-change principles and that can be delivered inexpensively to large segments of the population.Employees at a corporate worksite were invited to participate in a program, delivered entirely by e-mail, to reduce dietary fat and increase fruit and vegetable intake. Behavior-change principles underlying the intervention included tailoring to the participant's dietary lifestyle, baseline assessment and feedback about dietary intake, family participation, and goal setting. Assessment, tailoring, and delivery was fully automated. The program was delivered weekly to participants' e-mail inboxes for 12 weeks. Each e-mail included information on nutrition or on the relationship between diet and health, dietary tips tailored to the individual, and small goals to try for the next week. In this nonrandomized pilot study, we assessed technical feasibility, acceptability to employees, improvement in Stage of Change, increase in fruit and vegetable consumption, and decrease in fat intake.P <.001). In addition, results suggest significant increase in fruit and vegetable consumption  and significant decrease in intake of fat sources .Approximately one third (n = 84) of employees who were offered the 12-week program signed up for it, and satisfaction was high. There was significant improvement in Stage of Change: 74% of those not already at the top had forward movement (This inexpensive program is feasible and appears to be effective. A randomized controlled trial is needed. Diets high in fat and low in fruits and vegetables have been associated with numerous health outcomes, including cardiovascular disease, cancer, diabetes, and obesity . UnfortuLarge-scale programs such as the 5 A Day for Better Health program and campaigns aimed at reducing fat intake have increased awareness in many Americans, but changes in actual dietary habits are small . In partIn-person counseling can and does use those principles, and there is ample evidence that it is possible to improve dietary behaviors through intensive counseling and intervention ,6. SucceThe purpose of the e-mailed Worksite Internet Nutrition (WIN) program is to fill this gap by applying effective behavior-change principles on a large scale through technology. Computer technology permits the application of behavioral principles such as tailoring of messages to participant characteristics. E-mail technology permits the delivery of such effective programs directly to the participant. The WIN program was developed to deliver effective, science-based interventions and deliver them broadly and inexpensively.The California Cancer Research Program of the California Department of Health Services (DHS) provided funding for the WIN program development and for the pilot study described here to test the technical feasibility and acceptability of the program to recipients in a corporate worksite. Although we tested the program in a worksite setting, it could be used in any setting with e-mail access. In addition to feasibility and acceptability results, we also provide data on evidence of effectiveness in promoting dietary behavior change and in Stage of Readiness for Change.The WIN program is a 12-week nutrition intervention delivered entirely by e-mail. The goal of WIN is to move people toward a more healthful diet with respect to dietary fat, fruits, and vegetables. The program was reviewed by the California DHS Institutional Review Board.first needs to engage with information that may be useful to him or her. An initial introduction to all members of the worksite was used to generate "community" interest in exploring this health intervention. The promise of a personalized assessment of dietary habits provided a significant initial incentive. Two, once engaged, the individual needs to be moved to undertake some initial action, even if it is a modest "small step," to begin to change from a passive recipient of information to a practitioner of new behaviors. The simple choice of pursuing either a fat-reducing program or a fruit- and vegetable-enhancing program provided an easy first step. Subsequently, very simple, lifestyle-relevant food practices made for an easy next step to initial behavioral changes. Three, once those first new behaviors are experienced as achievable, enhanced self-efficacy can facilitate the acquisition of a whole cluster of relevant new behaviors. Each week, reinforcement was provided in addition to a choice of new "small steps." Four, this process needs to continue long enough to establish this new complex of behaviors as a habitual part of a person's daily routine. The regularity and ease of responding to an e-mail–delivered message made it very easy to continue in the program over many weeks. The novelty of new information and new behavioral guidance each week also helped sustain participation. Finally, a steadily increasing understanding of the health impacts of diet raised the salience of this aspect of the individual's lifestyle. The intent was to increase the sustainability of more healthy behaviors, both those suggested by WIN and others.The WIN program is based on principles of effective health education and behavior change. The principles incorporated into WIN are described below, and the program components through which they were implemented are shown in The principles implemented in the WIN program are discussed below.Research has shown that many people overestimate their fruit and vegetable intake  and thinTo be acted upon, behavioral recommendations must be not only perceived to be needed but also must be feasible in the context of the individual's lifestyle ,12. ThroThe ability to make individual choices enhances participation and attention . Particitips on easy ways to increase fruit and vegetable intake or decrease fat intake; nutrition information ; links to sites providing recipes or health information; and the sharing of strategies and ideas with coworkers via an online bulletin board.Skills in making healthier food choices and behaviors were enhanced through Extensive research indicates that goal setting is an important component of successful behavior change . Each weReminders keep the topic salient, and reinforcement helps to increase self efficacy. Reminders and reinforcement were provided to participants by the weekly messages, goal-setting opportunities, and opportunity to comment on their success. In addition, family members were encouraged to participate in the program, providing additional reminders and support.To achieve behavior change, learners typically must hear messages from different people, in different contexts and repeatedly . We accoFamily participation and social support. Family members could also sign up for WIN, and were encouraged to do so, creating a supportive environment for the participant.Bulletin board to facilitate development of social networks and social support for behavior change.Did you know? and Health Notes information (described below) to stimulate discussion and raise interest and awareness.Electronic links to other sites, such as the National Cancer Institute, National Heart, Lung and Blood Institute, and the American Dietetic Association.WIN was piloted at a corporate worksite employing 230 individuals . EmployeDietary fat, fiber, and fruit and vegetable intake were assessed in the initial e-mail using the Block screening questionnaires ,17. A seStage of Readiness for Change was assessed at baseline and at the end of the 12-week program. It was categorized in three stages, corresponding to Precontemplation, Contemplation/Preparation, and Action/Maintenance . Self-efEach message contained the following components:"Did you know…?" These were brief, interesting facts, designed to catch the attention of and promote discussion among recipients. Most included a table or figure and a link to Internet sources of further information.Health Notes. These were more extensive sections containing scientific information on nutrition or on the link between diet and health. For example, one Health Notes summarized evidence for the role of fruits and vegetables in reducing cancer risk. Others focused on the role of folic acid, the Food Guide Pyramid, "What is a serving?," heart disease, and other topics.Tips and Ideas. Each week, four new tips and suggestions focused on easily achievable actions. They were tailored to the participant in two ways: in their chosen dietary emphasis  and in their lifestyle path. While some tips applied to all persons with the particular dietary emphasis , others applied to both dietary emphasis and lifestyle path . Goals for next week. Each week, four new goals were suggested, usually related to the "Tips and Ideas" provided that week. Participants were asked to choose one or two to try during the following week. Goals were tailored to dietary emphasis and lifestyle path. . For this 12-week program, 168 sets of messages were developed (12 weeks x 2 dietary emphases x 7 lifestyle paths). The program was completely automated; computer programming determined the lifestyle characteristics for each individual and delivered weekly tailored messages.Linear regression and correlation techniques were used for continuous data, and classification and chi-square evaluation for categorical data. Differences between respondents and nonrespondents to the evaluation questionnaire were examined, and variables that differed were evaluated for confounding. To evaluate the effectiveness of the program, analysis of covariance was used, with change score as the dependent variable and baseline level as a covariate.Raw scores ranged from 0–5 for each of the seven fruit and vegetable items and from 0–4 for each of the 17 dietary fat items. Scores represented categories of frequency of consumption, from "rarely/never" to "every day" for fat items or to "2+/day" for fruit and vegetable items. We then converted the responses to times per day. The follow-up questionnaire on diet presented participants with the same food items and their initial responses on fat, fiber, and fruits and vegetables, and assessed differences in frequency consumed . Changes in responses were summed over the 17 fat items and the seven fruit and vegetable items.Additionally, we created a separate Change in Stage-of-Change score for fat and fruits and vegetables, in which 0 indicated no change, 1 indicated progression by one step , and 2 indicated progression by two steps .To avoid the potential self-selection bias inherent in the 56% response rate to the evaluation questionnaire, persons who did not respond to the follow-up questionnaire were assigned a follow-up score identical to their baseline score. This conservative approach assumes that those who did not respond had no improvement. To avoid an artificially low variance for such nonrespondents, change in dietary intake was calculated after adding a random number to their imputed follow-up score. The random number, with mean equal to zero and standard deviation equal to the standard deviation of the participants who did return a follow-up score, could be either negative or positive. The resulting imputed follow-up score thus had a mean equal to the baseline score for these nonrespondents, but had a variance similar to the variance among respondents.In addition to the self-reports obtained in the final evaluation questionnaire, the program automatically captured the number of times the participant interacted with the program by choosing a goal or using the online bulletin board. This variable was not biased by self-report and was used in analyses of internal consistency and dose-response.Of the 84 persons participating in the 12-week program, age ranged from 21–63, and 73% were female. Forty-one percent said they had children at home, 72% said they do most of the food preparation, and 54% said they were budget-conscious when purchasing food. At baseline, approximately 50% were in the Precontemplation or Contemplation/Preparation stage of change in fat intake, and 46% were in those stages of change in fruit and vegetable intake.P = .03), and mean age among evaluation respondents was slightly older compared to nonrespondents (P = .06).Forty-seven participants (56%) completed the evaluation questionnaire at the end of the 12-week program. Nonrespondents to the evaluation questionnaire were more likely to have been in the Action/Maintenance Stage at baseline, but this difference was not statistically significant. Respondents and nonrespondents did not differ significantly in baseline fat score , fruit and vegetable score , lifestyle path, dietary emphasis, or confidence in ability to make changes. Men were more likely to complete the evaluation questionnaire than women were  among the non-budget–conscious. Similarly, among the 50% of the participants who at baseline did not claim to already have a healthful diet, 100% would recommend the program, while 76% of the already "health-conscious/healthful diet" would do so. Perhaps consistent with the health-consciousness observation, 100% of the male respondents would recommend the program, and 83% of the women would do so.Forward movement in Stage of Change was notable and statistically significant . This waP = .03) and change in Stage of Change for fat (P = .04) (data not shown). This was true even though change had been set to zero for persons not responding to the evaluation questionnaire.We examined the data for internal consistency. The number of weeks that each person interacted with the program was captured by the program rather than self-report. Thus, all initial participants could be included , and the variable "number of weeks interacted" was not subject to reporting bias among those who responded to the evaluation questionnaire. In multiple linear regression, the number of weeks the participants interacted with the program was significantly related to change in Stage of Change for fruits and vegetables (P < .001) and an increase of 0.73 servings of fruits/vegetables/day (P < .001) (P = .013) and an increase of 0.37 servings of fruits/vegetables/day (P = .002).Among respondents to the evaluation questionnaire, there was a mean change in reported frequency of consumption of dietary fat sources of –0.39 times/day ( < .001) . When alP = .01) (data not shown). This was true despite the fact that nonrespondents to the evaluation were assigned a change score of zero plus a random variate. There was no significant association between change in consumption of fat sources and number of weeks the participant had interacted with the program.Again, we examined the internal consistency of relationships between reported dietary change and the extent of participation in the program. Extent of participation was captured by the program and was not biased by self-report. Change in fruit and vegetable consumption was significantly associated with number of weeks the participant had interacted with the program   . The proWIN is particularly appropriate for population-wide health promotion. As of 2001, 56.5% of U.S. households had a personal computer, and two thirds of Americans used a computer at some location, including at work, a public library, a community center, or someone else's home . InterneE-mail, in particular, is becoming a part of the fabric of American life. As of December 2002, 102 million Americans were e-mail users  . The parMore directly, this pilot study of the WIN program is relevant to worksite health promotion. Worksite interventions can be effective in changing behaviors and may reduce health care costs ,29. HoweThe present study demonstrates the feasibility of delivering an e-mail–based tailored dietary intervention in a worksite and provides evidence that such an intervention may produce improvements in both Stage of Change and in dietary intake of fruits and vegetables and of fat. This intervention, with its emphasis on dietary assessment and tailoring to the participant's lifestyle, could bring widespread dietary screening, counseling, and effective behavior change to large numbers of Americans at relatively low cost.The WIN program may be obtained by contacting Block Dietary Systems, www.nutritionquest.com.


We compared simultaneous measurements of blood lactate concentration ([Lac]) in the right atrium (RA) and in the pulmonary artery (PA). Our aim was to determine if the mixing of right atrial with coronary venous blood, having substantially lower [Lac], results in detectable decreases in [Lac] from the RA to the PA.2 saturation (SO2) and [Lac]. We defined Δ[Lac] as ([Lac]ra - [Lac]pa), ΔSO2 as (SraO2 - SpaO2) and the change in O2 consumption (ΔVO2) as the difference in systemic VO2 calculated using Fick's equation with either SraO2 or SpaO2 in place of mixed venous SO2. Data were compared by paired Student's t-test, Spearman's correlation analysis and by the method of Bland and Altman.A prospective, sequential, observational study was conducted in a medical-surgical intensive care unit. We enrolled 45 critically ill adult individuals of either sex requiring pulmonary artery catheters (PACs) to guide fluid therapy. Immediately following the insertion of the PAC, one paired set of blood samples per patient was drawn in random order from the PAC's proximal and distal ports for measurement of hemoglobin concentration, OraO2 > SpaO2  and [Lac]ra > [Lac]pa . Δ[Lac] correlated with ΔVO2 .We found S2 and [Lac] from the RA to PA support the hypothesis that these gradients are produced by mixing RA with coronary venous blood of lower SO2 and [Lac]. The present study is a preliminary observation of this phenomenon and further work is needed to define the physiological and clinical significance of Δ[Lac].We found decreases in [Lac] from the RA to PA in this sample of critically ill individuals. We conclude that parallel decreases in SO The insertion technique is described elsewhere . Care wa2 saturation was determined from a previously in vivo calibrated pulse oximeter.Immediately after the insertion of the PA catheter, each patient had one set of paired blood samples drawn in rapid succession, and in random order, from the proximal and distal port. We took proximal port blood to be representative of RA blood, whereas distal port blood was considered to be PA blood. The first 2 ml of blood drawn for each sample were discarded to prevent contamination with flushing fluid. Blood samples were drawn with the catheter balloon deflated to avoid contamination of the distal port sample with pulmonary capillary blood. Arterial O2 saturation . We measured cardiac output (CO) by the thermodilution method as the average of three sequential determinations.Blood samples were placed on ice and taken to a central laboratory for measurement of [Lac] , hemoglobin concentration ([Hb]) and O2 delivery (DO2), O2 consumption (VO2), O2 extraction ratio (ERO2), double product  × mean arterial pressure (MAP)) and left ventricular stroke work index (LVSWI) were computed using standard formulae. We defined ΔVO2 as the difference in systemic VO2 calculated with Fick's equation with either SpaO2 or SraO2 in place of the mixed venous SO2 (SvO2); ΔVO2 = Qpa × 13.4 × [Hb] × (SraO2 - SpaO2) ml.min-1.Systemic Ora and [Lac]pa were compared by Spearman's correlation analysis analysis . The metanalysis  was usedWe enrolled 45 patients in the study, including 18 women. The study group was composed of 31 post-operative patients (26 post-cardiac surgery), 11 patients in septic shock from various medical conditions, 2 patients with severe gastrointestinal bleeding and 1 patient in congestive heart failure. Demographic and hemodynamic parameters for the group are listed in Table 2 and lactate concentrations for RA and PA blood samples are shown in Table raO2 was greater than SpaO2 (p < 0.001), with ΔSO2 = 5.2 ± 4.8%. [Lac]ra was greater than [Lac]pa (p < 0.001), with Δ[Lac] = 0.2 ± 0.2 mmol.l-1.The mean SOra and [Lac]pa. There was a bias towards greater [Lac]ra of 0.2 mmol.l-1 (p < 0.001) with a 95% confidence interval for the population of -0.15 to 0.56 mmol.l-1. There was no discernable relationship between [Lac]ra and Δ[Lac] , indicating that Δ[Lac] was not a concentration dependent phenomenon. Moreover, we found no significant relationships between [Lac]ra and SraO2 or between [Lac]pa and SpaO2.Shown in Fig. 2  with a standard error of the estimate of 0.15 mmol.l-1  drawn from 12 critically ill patients [Only one other study in the literature has compared central venous [Lac] to [Lac]-1. Even assuming a worst case scenario of a systematic instrument bias of -0.1 mmol.l-1, the difference in [Lac] between RA and PA would have remained statistically significant.We used a standard clinical laboratory instrument to measure [Lac] having a 95% precision of ± 0.1 mmol.lThe declining [Lac] gradient from RA to PA is likely the result of mixing RA blood with blood of lower [Lac] emanating from the coronary venous system. Lactate oxidation accounts for 10% to 20% of total myocardial aerobic energy production , a propopa. A factual resolution of this question can only be achieved by direct measurement of [Lac] from IVC to PA.Since RA blood is the mixture of superior vena cava and inferior vena cava (IVC) blood, the possibility exists that these blood streams had not thoroughly mixed at the proximal PAC sampling port. In this case, one could expect further mixing to occur between IVC and RA blood while flowing into the pulmonary artery. Our results do not support this hypothesis. Direct measurements in humans show that IVC blood has the highest [Lac] of any major vein  and furtra < [Lac]pa. These patients had no distinguishing features to help us differentiate them from others in the group. It is possible that accidental mislabeling of the samples may have accounted for a negative Δ[Lac] but we think it unlikely, given the care taken with the labeling and measuring of the samples. Another possibility is that these individuals experienced myocardial ischemia, a condition associated with an upsurge in glucose metabolism and net lactate release by the heart [ra < [Lac]pa.Only three individuals in our group had [Lac]he heart -19. Myoc2 consumption (MVO2) and myocardial lactate uptake, reflecting the O2 cost of lactate utilization by the heart  (Fig. 2 and myocardial lactate uptake. This finding suggests that Δ[Lac] also may be related, in a yet to be established fashion, to MVO2.Others have noted a linear relationship between myocardial Ohe heart . We did 2 and [Lac] from RA to PA support the hypothesis that these gradients are produced by mixing RA with coronary venous blood of lower SO2 and [Lac]. The present study is a preliminary observation of this phenomenon and further work is needed to define the physiological and clinical significance of Δ[Lac].We found decreases in [Lac] from RA to PA in this sample of critically ill individuals. We conclude that parallel decreases in SO• 	Oxygen and lactate concentrations are lower in PA blood than in RA blood.• 	The oxygen and lactate concentration gradients from RA to PA are likely the result of mixing atrial with coronary venous blood.• 	The possibility exists that these concentration gradients may reflect changes in myocardial energy requirements.2 = systemic O2 delivery; DP = double product; ERO2 = oxygen extraction ratio; [Hb] = hemoglobin concentration; HR = heart rate; IVC = inferior vena cava; Δ[Lac] = lactate concentration gradient from right atrium to pulmonary artery; [Lac] = blood lactate concentration; LVSWI = left ventricular stroke work index; MAP = mean arterial pressure; MPP = mean pulmonary pressure; MVO2 = myocardial O2 consumption; PA = pulmonary artery; PAC = pulmonary artery catheter; PAOP = pulmonary artery occlusion pressure; RA = right atrium; SO2 = O2 saturation; ΔSO2 = O2 saturation gradient from right atrium to pulmonary artery; SVRI = systemic vascular resistance index; VO2 = O2 consumption.CV = coronary venous; CVP = central venous pressure; DOThe authors declare that they have no competing interests.GG conceived the study, participated in its design, performed statistical analysis and drafted the manuscript. LSC and HZ participated in the design of the study, collected data and helped to draft the manuscript. MGS and NMK conducted the study, collected data and helped to draft the manuscript. All authors read and approved the final manuscript.


Physical activity is a leading health indicator  and has The Diabetes Prevention Program, a study funded by the National Institute of Diabetes & Digestive & Kidney Diseases, found that participants with impaired glucose tolerance who were assigned to an intensive lifestyle intervention reduced their risk of getting type 2 diabetes by 58%. On average, this group maintained their physical activity at 30 minutes per day, usually with walking or other moderate-intensity exercise, and lost 5% to 7% of their body weight .It is likely that health educators at local health departments addressing diabetes and other chronic diseases will be asked to evaluate a physical activity program, because evaluation has a central role not only in improving programs but also in satisfying accountability requirements. A carefully planned evaluation can engage community members and build community capacity, and the results can be used to influence policy makers, share what works and what doesn't work with other communities, and help ensure funding and sustainability.Framework for Program Evaluation in Public Health (The Centers for Disease Control and Prevention (CDC) has published the c Health , which rThe Guide to Community Preventive Services (Community Guide)  , availab-aim.org/), which Community Guide. (A description of this strategy is available from www.thecommunityguide.org/pa/pa-int-create-access.pdf.) This strategy involves the efforts of worksites, coalitions, agencies, and communities to change the local environment to create or improve access to opportunities for physical activity.For this article, we selected the strategy of creating or enhancing access to places for physical activity, combined with informational outreach activities, from the Framework for Program Evaluation in Public Health will be used to guide this step-by-step example , accuracy , and propriety .The CDC's six-step  example . These sHandbook , availabpartners; these partners will carry out the intervention strategy. For an intervention to create or enhance places for physical activity, potential partners might include a city park, a shopping mall, the YMCA, the tourism bureau, and the community college. Also of great importance in terms of meeting the utility standard are decision makers — individuals who can use evaluation results to allocate future funds or cut programs. Examples might include the city mayor, the president of the community college, and the county-level director of parks and recreation.Important stakeholders for you as a health educator at a local health department are You should invite all of the partner and decision-maker stakeholders to a meeting to describe the recommended strategy. The group should then discuss its role in making this strategy into a reality in its community and what evaluation resources it can offer.participants, individuals at high risk of developing diabetes. One way to engage participants is to invite them to a focus group or town meeting. At such a gathering, their ideas about the program can be assessed and used to refine the program to meet their needs. For the "creating access" strategy, for example, the participants can reveal what physical activity offerings would interest them and what venues might best reach them with information about these offerings.Another group of stakeholders is the The partners should be invited back for a second meeting to work on a logic model to depict graphically the proposed relationship between activities and expected outcomes. In this step, the work pertains to planning both the intervention and its evaluation. On the basis of step 1, the health educator is able to share the list of activities discussed at the first meeting and indicate which ones seem more popular or less popular among participants in the focus groups or town meetings.specific, measurable, achievable, relevant, and time-bound.  and, eventually, decreased incidence of diabetes morbidity and mortality. It is the role of the health educator to insist that the group set short-term objectives that include measurable outcomes. Objectives should be SMART — that is, Handbook .) After As a health educator, you want to be sure that the evaluation is useful not only to your health department but also to the partner organizations that help to implement the program. To ensure buy-in and later use of the evaluation, ask stakeholders to develop questions that they would like to have answered. For example, the YMCA staff may want to know whether their membership increases. Increased membership becomes an outcome in the logic model. Note that the logic model can be made from right to left, that is, by asking, "How will we increase membership?" and then proposing some activities that might lead toward that outcome. Or it can be made from left to right, by asking, "Why are we doing that?" and then stating the expected outcomes of such activities. Either way, a focused evaluation will be one that poses questions based on the program and one that results in answers that serve the purpose of the evaluation. The purpose often will be to improve the program; other purposes may include gaining insight and assessing program effects. Defining your purpose is an important component of this step.In our example, the stakeholders have already agreed on a logic model in step 2 , and so ProcessAre the proposed activities being carried out by the partners? If not, why not?What seem to be the most popular activities, and why?Are we reaching individuals at risk for diabetes?OutcomeDid awareness of opportunities increase?Did participation increase? Why or why not?Did HbA1c levels decrease among the population with diabetes?To answer the questions posed in step 3, evidence needs to be collected. How much evidence (quantity) and what kind of evidence  are central to feasibility and accuracy. There must be a balance between collecting enough data and assuring it is of high quality. Sometimes a mix of quantitative and qualitative data will help achieve that balance: quantitative data can provide the numbers you need to answer some questions , and qualitative data can help you understand why you got those numbers . Data are available from people, documents, observations, and existing information.triangulation and is recommended to increase accuracy. There are many tools available for collecting physical activity data. There are three parts to this step: 1) analyze the data, 2) interpret the results, and 3) make judgments about the program. Having the performance measures helps to justify your conclusions. Perhaps a community college student needs an internship. You can hire him or her  to help with the evaluation. With guidance from you and the supervising professor, the student can analyze the data. Analysis for some questions will be easier than for others. For example, the difference between participation rates preintervention and postintervention is simple math, whereas analyzing focus group and interview data takes more time because all of the text must be read and common themes identified to answer the appropriate evaluation question.Physical Activity Evaluation Handbook, p. 26 [After the analyses, you should convene a meeting of stakeholders to go over the results. Talk about possible alternative explanations to the findings of the evaluation. Discuss the limitations. One common limitation is having no control community; if possible, use a selected community as a basis of comparison in a quasi-experimental design.  Comparhttp://apps.nccd.cdc.gov/DNPAProg/.The findings can be printed in the local newspaper, which, in our case, has the beneficial effect of increasing awareness of physical activity opportunities even further. The best features of the program should be highlighted. You can send the findings electronically to the CDC, where they can be widely distributed through the Physical Activity Listserv; in addition, examples of state physical activity programs can be posted on the State-based Physical Activity Directory at To ensure use of your evaluation findings, formulate action-oriented recommendations. To help share lessons learned, consider your audience: use appropriate communications strategies and consider the most effective format for information  and venue .Although the principles of evaluation transcend topical areas, we hope that this step-by-step guide provides insight and examples for evaluating physical activity programs. There are evidence-based strategies for promoting physical activity in a community setting, and there are diabetes programs across the nation that could implement these strategies by engaging partners and initiating systems change. In our examples for creating access to places for physical activity, systems were engaged, and the strategies depended on these system changes. Partner organizations benefit by learning principles of evaluation that they can use for continuous quality improvement. Program evaluation plays a key role in ensuring success and sustainability of these programs.


Heavy drinking is responsible for major health and social problems. Brief interventions have been shown to be effective, but there have been difficulties in reaching those who might benefit from them. Pilot studies have indicated that a Web-based intervention is likely to be acceptable to heavy drinkers and may produce some health benefits. However, there are few data on how many people might use such a program, the patterns of use, and potential benefits. The aim was to examine the demographic characteristics of users of a free, Web-based, 6-week intervention for heavy drinkers and to describe the methods by which users identified the site, the pattern of site use and attrition, the characteristics associated with completing the program, and the self-reported impact on alcohol-related outcomes. Cohort study. Visitors to the Web site were offered screening with the Fast Alcohol Screening Test, and those scoring above the cutoff for risky drinking were invited to register with the program. Demographic information was collected routinely at registration, and questionnaires were completed at the end of weeks 1 and 6. The outcome measures assessed dependency (Short Alcohol Dependency Data Questionnaire), harms (modified Alcohol Problems Questionnaire), and mental health . The records of 10000 users were analyzed. The mean age was 37.4 years, 51.1% were female, 37.5% were single, and 42.4% lived with children. The majority were White British, lived in the United Kingdom, and reported occupations from the higher socioeconomic strata. Over 70% connected to the Down Your Drink (Down Your Drink) site from another Internet-based resource, whereas only 5.8% heard about the site from a health or other professional. Much of the Web site use (40%) was outside normal working hours. Attrition from the program was high, with only 16.5% of registrants completing the whole 6 weeks. For those who completed the program, and the final outcome measures, measures of dependency, alcohol-related problems, and mental health symptoms were all reduced at week 6. The Web-based intervention was highly used, and those who stayed with the program showed significant reductions in self-reported indicators of dependency, alcohol-related problems, and mental health symptoms; however, this association cannot be assumed to be causal. Programs of this type may have the potential to reach large numbers of heavy drinkers who might not otherwise seek help. There are significant methodological challenges and further research is needed to fully evaluate such interventions. Excess alcohol consumption, and the harm caused by it, is a major public health concern throughout the developed world -3. RegulBrief interventions seek to change views of the personal acceptability of excessive drinking and to encourage self-directed behavior change. They can be delivered by practitioners or as self-help materials. There is a substantial body of evidence demonstrating that brief interventions for individuals at risk can have significant impact on reducing alcohol consumption and, in some cases, alcohol-related harm when delivered both in primary and secondary health care settings -8. HowevUntil recently, self-help materials were almost exclusively paper-based. However, the Internet has triggered a growth in more interactive self-help materials. It is thought that this interactivity is likely to enhance the potential for behavior change . In publOne exception is the Alcohol Help Centre, which provided online personal feedback to users of an online eHealth service . A modifDown Your Drink is a well-established, comprehensive, freely available, interactive Web-based treatment program for people with alcohol problems. An initial pilot study demonstrated the feasibility of the approach , and thiThe aims of the present study were to describe the patterns of use and self-reported effectiveness among users of Down Your Drink. The study set out to describe the demographic characteristics of users, the methods employed to identify and access Down Your Drink, the patterns of use, the demographic and clinical characteristics associated with completing the 6-week program, and self-reported changes in alcohol-related outcomes associated with use of Down Your Drink.This was a pragmatic cohort study of the first 10000 people who registered to use the site, after the end of the pilot phase .The study was approved by the Camden and Islington Local Research Ethics Committee.Down Your Drink was developed with support from the Alcohol Education and Research Council as a Web-based interactive program of brief interventions to reduce alcohol consumption in heavy drinkers and is hosted on a single dedicated Web site .The animated home page invited visitors to assess their level of drinking by taking the Fast Alcohol Screening Test (FAST) . Feedbac                The Web site content was structured as a set of six consecutive intervention modules designed to be accessed by the registrants at weekly intervals. Once a given module had been completed, access to the subsequent module was barred for 7 days. The 6-week program was based on the stages of change model  and cont                An off-line advertising campaign was run in September 2001 to coincide with the launch of the Web site and the early part of the pilot study. All off-line advertising ceased at the end of 2001 (Multimedia Appendix 2). The site was also registered with the Yahoo search engine and was listed in the information pages of a number of UK-based health-related periodicals. By the time this study started (September 2003), there had been no off-line advertising for this Web site for over 18 months. All visitors to the Down Your Drink site were invited to complete an initial assessment using the FAST . The maxIn order to participate, users were invited to read the policy on confidentiality, complete the consent procedure, and then choose a username and password. Those who agreed to register were required to submit information about their age, gender, marital status, family composition, ethnicity, occupation, country of residence, and how they had learned about the site.The primary outcome measure was the 14-item Short Alcohol Dependency Questionnaire (SADD), which measures dependency on alcohol . This waAll the data for the study were collected automatically on a live database located on a secure dedicated Web site. Access to this database was by password only and was restricted to members of the research team. This database was initially launched simultaneously with the Down Your Drink Web site in October 2001, but was withdrawn at the end of the pilot phase for re-development. The upgraded database was subsequently re-launched in September 2003, and the data presented here are from the first 10000 users after the launch of the revised database.Usage data were collected automatically on the Down Your Drink Web server and analyzed by a Web server log file analysis program . These data were stored separately from the Down Your Drink registrant database. The usage data reported here are from a subset of the total participants in the study collected between January and December 2004.Data for the first 10000 users were extracted from the live database on March 1, 2006, and transferred into SPSS, version 12.0.1 for Windows via Microsoft Access, where all data related to individual Web site users were linked using the unique identifier created by the Down Your Drink site.t tests were performed to compare the mean scores of Web site users at the beginning and end of the 6-week program. In addition, the demographic variables of age, gender, marital status (with or without partner), and family status (with or without children) were tested using a chi-square test to determine if a statistically significant relationship existed between particular demographic characteristics and the likelihood of completing the online program.These data were then subjected to frequency analysis and paired It took just over 27 months, from the launch date on September 24, 2003, to January 3, 2006, to complete recruitment of 10000 users.The self-reported demographic characteristics of the sample are shown in The great majority (83.9%) lived in the United Kingdom, and 9.3% reported living in other English-speaking countries . Over 100 countries of residence were given by the remaining 6.7% of users.Nearly three quarters of registrants  visited the Down Your Drink site from another Internet-based resource. Most of these connected via a link from another Web site  or from a search engine , whereas a smaller group responded to a banner advert on another site . Relatively few registrants had been directed to Down Your Drink from the health service .The daily pattern of Down Your Drink use between January and December 2004 (represented by number of “hits” per hour) is shown in                     There was a high attrition rate from the program with only 1654 (16.5%) of the original 10000 registrants completing the 6-week program . The greIn order to determine whether there were demographic or clinical characteristics that were associated with completion of the 6-week program, we compared the characteristics of those who completed the sixth week with those who had only completed the first week. We chose first week completers as the reference, as we did not have data on the outcome measures from those who had dropped out before completing the first week. We defined anyone who had done some part of week 6 as a completer, whether or not they filled in the questionnaires at the end of week 6. It can be seen that female users, users who were married or living with a partner, and users without children were more likely to complete the program than men, single users, or users with children . The basOf the program completers, 57% also fully completed the outcome questionnaires at the end of the 6-week program. The mean scores for the SADD and modified APQ were significantly lower for these people at week 6 than week 1, indicating that alcohol dependency and alcohol-related harm were significantly reduced at the end of the program . Mental This large pragmatic cohort study of users of a freely available online program for nondependent drinkers at risk of harm from alcohol use suggests that a small but significant (16.5% or 1 in 6) proportion of users will complete the 6-week program. Those that completed the program and provided outcome measures reported clinically significant benefit, with reduction in mean dependency and harm from alcohol, and improved mental health. Women, users with a partner, and users without children were more likely to complete the program.Our findings add to the growing body of literature suggesting that behavior change can be achieved through online interventions -36. ThisThis online service, in common with other studies ,40, was This was a pragmatic cohort study aimed at exploring the usage patterns of a freely available online intervention. All data were self-reported, and we have no objective confirmation of any of the data reported here. Some users may have provided false or inaccurate data. However, there is no particular reason why registrants should have systematically lied at registration, and, given the large sample size (10000 registrants), the demographic data probably provide a reasonable description of the characteristics of users. Users who completed the 6-week course showed considerable motivation and commitment. The outcome measures were an integral part of the intervention, and users completed them entirely for their own benefit. It is difficult to know how truthful they were in completing these questionnaires, but there is some evidence to support the suggestion that responses to online questionnaires are comparable to traditional paper-based versions ,43.As this was an uncontrolled study, the data can only suggest an association between use of the program and an improvement in health outcomes. This study cannot determine whether this association was causal.If confirmed, these data suggest that an online intervention aimed at nondependent heavy drinkers can make a useful addition to the public health armamentarium. Although only 16% of those who registered completed the course, in public health terms this still represents a significant number of people who could benefit. The advantages of such an intervention are that the costs are unaffected by the number of users and that the intervention can be used at home, at any time of day or night, unlike more traditional services. Future work should explore whether adapting the program, including increasing the options for flexible use, removing the requirement to work through the elements sequentially, and introducing more personalized feedback, can improve “stickiness” or adherence to the program, and whether the association between use of the program and improved outcomes is causal. We are currently undertaking a randomized controlled trial to explore both these questions.


It is a time of new beginnings for the Superfund Basic Research Program, a university-based grants program established in 1987. While maintaining the program’s premise of supporting basic research for practical application to address the problems associated with the nation’s hazardous waste sites, the program continues to evolve and develop new approaches to address these concerns. An important component of achieving the program’s goals is the routine recompetition of the program. We are pleased to announce that as a result of the most recent recompetition, NIEHS has made awards to nine programs. Included in these nine awards are one new grantee, Brown University, and eight grantees that are continuing participants in the program. These grantees include Boston University, Dartmouth College, Duke University, Texas A & M University, the University of Arizona, the University of California at Davis, the University of California at San Diego, and the University of Kentucky. These nine awards in addition to the eleven existing grantees comprise the current Superfund Basic Research Program.The new program has a strong emphasis on interdisciplinary and system approaches to addressing the complex issues associated with hazardous waste sites. Grantees are using integrated research models to understand how contaminants are transformed as they move through soils, sediments, and groundwater and how they interact with ecosystems and ultimately affect human health. These robust research efforts are augmented with graduate and postdoctoral training in interdisciplinary environmental research and with community outreach activities. Each grantee is also required to engage proactively in research translation to other federal agencies, industry, and the community at large.For interested investigators who are not already part of this vital and exciting program but would like to be, please contact program staff about future opportunities. We anticipate that there will be annual solicitations beginning in the summer of 2006. It is not too early to start the planning process! We are available to assist you as you begin to conceptualize a future program at your university.William Suk, PhD, Director | (919) 541-0797Claudia Thompson, PhD | (919) 541-4638Beth Anderson | (919) 541-4481