Over-expressing the C(3) photosynthesis cycle enzyme Sedoheptulose-1-7 Bisphosphatase improves photosynthetic carbon gain and yield under fully open air CO(2) fumigation (FACE).
Biochemical models predict that photosynthesis in C(3) plants is most frequently limited by the slower of two processes, the maximum capacity of the enzyme Rubisco to carboxylate RuBP (V(c,max)), or the regeneration of RuBP via electron transport (J). At current atmospheric [CO(2)] levels Rubisco is not saturated; consequently, elevating [CO(2)] increases the velocity of carboxylation and inhibits the competing oxygenation reaction which is also catalyzed by Rubisco. In the future, leaf photosynthesis (A) should be increasingly limited by RuBP regeneration, as [CO(2)] is predicted to exceed 550 ppm by 2050. The C(3) cycle enzyme sedoheptulose-1,7 bisphosphatase (SBPase, EC 188.8.131.52) has been shown to exert strong metabolic control over RuBP regeneration at light saturation. We tested the hypothesis that tobacco transformed to overexpressing SBPase will exhibit greater stimulation of A than wild type (WT) tobacco when grown under field conditions at elevated [CO(2)] (585 ppm) under fully open air fumigation. Growth under elevated [CO(2)] stimulated instantaneous A and the diurnal photosynthetic integral (A') more in transformants than WT. There was evidence of photosynthetic acclimation to elevated [CO(2)] via downregulation of V(c,max) in both WT and transformants. Nevertheless, greater carbon assimilation and electron transport rates (J and J(max)) for transformants led to greater yield increases than WT at elevated [CO(2)] compared to ambient grown plants. These results provide proof of concept that increasing content and activity of a single photosynthesis enzyme can enhance carbon assimilation and yield of C(3) crops grown at [CO(2)] expected by the middle of the 21st century.


Psychomotor coordination and intelligence in childhood and health in adulthood--testing the system integrity hypothesis.
To examine associations between intelligence and psychomotor coordination in childhood and risk of psychological distress, poorer self-rated health, and obesity in adulthood. To investigate whether psychomotor coordination as a potential marker of the construct "system integrity" explains associations between intelligence and these outcomes. Participants were members of two British national birth cohorts: the 1958 National Child Development Survey (n = 6147) and the 1970 British Cohort Study (n = 6475). They took tests of psychomotor coordination and intelligence at age 10 to 11 years and reported on their health when in their early 30s. For a standard deviation increase in psychomotor coordination score, sex-adjusted odds ratios (95% CI) for the 1958 and 1970 cohorts, respectively, were 0.79 (0.72-0.87) and 0.83 (0.77-0.89) for psychological distress, 0.79 (0.73-0.85) and 0.85 (0.78-0.91) for fair/poor self-rated health, and 0.81 (0.75-0.88) and 0.85 (0.78-0.92) for obesity. These associations were independent of childhood intelligence and most remained significant after adjustment for other covariates. Higher intelligence quotient was associated with a reduced risk of psychological distress, fair/poor self-rated health, and obesity in adulthood. These associations were not explained by potential confounding factors or by psychomotor coordination in childhood. Having better psychomotor coordination in childhood seems protective for some aspects of health in adulthood. Examination of the role played by other markers of the efficiency of the central nervous system may help reveal the extent to which system integrity underlies the link between intelligence and health.


European Society for Pediatric Gastroenterology, Hepatology, and Nutrition syllabus for subspecialty training: moving towards a European standard.
The requirements for and conditions of subspecialty training in paediatric gastroenterology, hepatology, and nutrition (PGHN) are rather variable across European countries. The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) agreed on a training syllabus aimed to foster a harmonised European PGHN curriculum and to support national PGHN societies and governmental bodies to promote and establish high-quality training programmes and levels of certification in the field. The document provides PGHN training prerequisites and objectives and the basic knowledge elements to acquire the clinical, technical, and management skills needed. Guidelines and instruments for self-monitoring and appraisal are proposed, and a logbook is available online. These training standards are a first step towards a European certification and recognition as a specialist in PGHN.


Least-squares fitting of carrier phase distribution by using a rational function in fringe projection profilometry [corrected].
A least-squares fitting technique for the carrier phase component in fringe projection profilometry is presented. The carrier phase distribution for an arbitrary measurement system can be perfectly described with a rational function, whose coefficients can be estimated by least-squares fitting to the measured reference phases, so that the restrictions and limitations in the existing techniques are eliminated.


Purinergic dysregulation in pulmonary hypertension.
Despite the fact that nucleotides and adenosine help regulate vascular tone through purinergic signaling pathways, little is known regarding their contributions to the pathobiology of pulmonary arterial hypertension, a condition characterized by elevated pulmonary vascular resistance and remodeling. Even less is known about the potential role that alterations in CD39 (ENTPD1), the ectonucleotidase responsible for the conversion of the nucleotides ATP and ADP to AMP, may play in pulmonary arterial hypertension. In this study we identified decreased CD39 expression on the pulmonary endothelium of patients with idiopathic pulmonary arterial hypertension. We next determined the effects of CD39 gene deletion in mice exposed to normoxia or normobaric hypoxia (10% oxygen). Compared with controls, hypoxic CD39(-/-) mice were found to have a markedly elevated ATP-to-adenosine ratio, higher pulmonary arterial pressures, more right ventricular hypertrophy, more arterial medial hypertrophy, and a pro-thrombotic phenotype. In addition, hypoxic CD39(-/-) mice exhibited a marked increase in lung P2X1 receptors. Systemic reconstitution of ATPase and ADPase enzymatic activities through continuous administration of apyrase decreased pulmonary arterial pressures in hypoxic CD39(-/-) mice to levels found in hypoxic CD39(+/+) controls. Treatment with NF279, a potent and selective P2X1 receptor antagonist, lowered pulmonary arterial pressures even further. Our study is the first to implicate decreased CD39 and resultant alterations in circulating purinergic signaling ligands and cognate receptors in the pathobiology of pulmonary arterial hypertension. Reconstitution and receptor blocking experiments suggest that phosphohydrolysis of purinergic nucleotide tri- and diphosphates, or blocking of the P2X1 receptor could serve as treatment for pulmonary arterial hypertension.


A novel and fast method for proton range verification using a step wedge and 2D scintillator.
To implement and evaluate a novel and fast method for proton range verification by using a planar scintillator and step wedge. A homogenous proton pencil beam plan with 35 energies was designed and delivered to a 2D flat scintillator with a step wedge. The measurement was repeated 15 times (3 different days, 5 times per day). The scintillator image was smoothed, the Bragg peak and distal fall off regions were fitted by an analytical equation, and the proton range was calculated using simple trigonometry. The accuracy of this method was verified by comparing the measured ranges to those obtained using an ionization chamber and a scanning water tank, the gold standard. The reproducibility was evaluated by comparing the ranges over 15 repeated measurements. The sensitivity was evaluated by delivering to same beam to the system with a film inserted under the wedge. The range accuracy of all 35 proton energies measured over 3 days was within 0.2 mm. The reproducibility in 15 repeated measurements for all 35 proton ranges was ±0.045 mm. The sensitivity to range variation is 0.1 mm for the worst case. This efficient procedure permits measurement of 35 proton ranges in less than 3 min. The automated data processing produces results immediately. The setup of this system took less than 5 min. The time saving by this new method is about two orders of magnitude when compared with the time for water tank range measurements. A novel method using a scintillator with a step wedge to measure the proton range was implemented and evaluated. This novel method is fast and sensitive, and the proton range measured by this method was accurate and highly reproducible.


Disinfection of gloved hands for multiple activities with indicated glove use on the same patient.
Most hand hygiene guidelines recommend that gloves should be changed during patient care when an indication for hand disinfection occurs. Observational studies indicate that the majority of healthcare workers (HCWs) do not disinfect their hands at all during continued glove wear. The aim of this narrative review is to assess the potential benefits and risks for disinfecting gloved hands during patient care for multiple activities with indicated glove use on the same patient. Continued glove wear for multiple activities on the same patient often results in performing procedures, including aseptic procedures with contaminated gloves, especially in a setting where there are many indications in a short time, e.g. anaesthetics or accident and emergency departments. Of further note is that hand hygiene compliance is often lower when gloves are worn. To date, three independent studies have shown that decontamination is at least as effective on gloved hands as on bare hands and that puncture rates are usually not higher after up to 10 disinfections. One study on a neonatal intensive care unit showed that promotion of disinfecting gloved hands during care on the same patient resulted in a significant reduction in the incidence of late-onset infections and of necrotizing enterocolitis. We conclude that disinfection of gloved hands by HCWs may substantially reduce the risk of transmission when gloves are indicated for the entire episode of patient care and when performed during multiple activities on the same patient.


Drawing Firmer Conclusions: Autistic Children Show No Evidence of a Local Processing Bias in a Controlled Copying Task.
Drawing tasks are frequently used to test competing theories of visuospatial skills in autism. Yet, methodological differences between studies have led to inconsistent findings. To distinguish between accounts based on local bias or global deficit, we present a simple task that has previously revealed dissociable local/global impairments in neuropsychological patients. Autistic and typical children copied corner elements, arranged in a square configuration. Grouping cues were manipulated to test whether global properties affected the accuracy of reproduction. All children were similarly affected by these manipulations. There was no group difference in the reproduction of local elements, although global accuracy was negatively related to better local processing for autistic children. These data speak against influential theories of visuospatial differences in autism.


Transoral robotic surgery: a multicenter study to assess feasibility, safety, and surgical margins.
Our objective was to determine the safety, feasibility, and the adequacy of surgical margins for transoral robotic surgery (TORS), by reviewing the early results from independent institutional review board-approved clinical trials in three separate institutions. Pooled Data from Independent Prospective Clinical Trials. One hundred ninety-two patients were initially screened, but inadequate exposure did not permit TORS in 13 (6.7%). For two additional patients, TORS was begun but intraoperatively converted to an open procedure. Thus, the intent-to-treat population was 177 patients (average age, 59 years; 81% male), predominantly comprised of tumors arising in the oropharynx (139, 78%) and larynx (26, 15%). TORS was performed for 161 (91%) patients with malignant disease: 153 (95%) with squamous cell carcinoma (T1 [50, 32.7%], T2 [74, 48.4%], T3 [21, 13.7%], T4 [8, 5.2%]), six patients (3.72%) with salivary gland tumors, and two patients with carcinoma in situ. The average follow-up was 345 days. There was no intraoperative mortality or death in the immediate postoperative period. Average estimated blood loss was 83 mL; no patient required transfusion. The rate of positive margins was 4.3%. Twenty-nine patients (16%) experienced 34 serious adverse events that required hospitalization or intervention (grade 3) or were considered life threatening (grade 4, 2.3%). Tracheostomy was performed in 12.4% of all patients (22/177), but only 2.3% had a tracheostomy at last follow-up. For all patients undergoing TORS without previous therapy, the percutaneous endoscopic gastrostomy dependency rate was 5.0%. The average hospital stay was 4.2 days. Based on this multicenter study, TORS appears to be safe, feasible, and as such play an important role in the multidisciplinary management of head and neck cancer.


ACOG Practice Bulletin No. 208: Benefits and Risks of Sterilization.
Female and male sterilization are both safe and effective methods of permanent contraception used by more than 220 million couples worldwide (). Approximately 600,000 tubal occlusions and 200,000 vasectomies are performed in the United States annually (2-4). For women seeking permanent contraception, sterilization obviates the need for user-dependent contraception throughout their reproductive years and provides an excellent alternative for those with medical contraindications to reversible methods. The purpose of this document is to review the evidence for the safety and effectiveness of female sterilization in comparison with male sterilization and other forms of contraception.


A stress process model of family caregiver service utilization: factors associated with respite and counseling service use.
This study examines whether caregivers' differential utilization of respite and counseling support services is associated with different situational stress processes. A multinomial regression analysis was conducted to compare respite users, counseling users, and those who used neither service, using data collected on a statewide random sample of 1,643 California caregivers providing assistance to individuals aged 50 or older. Compared with caregivers who used neither service, respite service users were more likely to have demanding care situations giving rise to physical symptoms of stress, and were more likely to use community services for the care recipient to augment their care. In contrast, counseling service users were more likely to be managing the meaning of their care situation by seeking out information about services and talking with a confidant about their situation, while coping with both emotional and physical symptoms of stress. Tailoring caregiver interventions to meet the support needs and coping strategies stemming from diverse caregiving situations and caregiver characteristics may increase the likelihood that those interventions will be effective in alleviating or preventing deleterious secondary stress frequently experienced by family caregivers.


A multiple sclerosis cluster associated with a small, north-central Illinois community.
The authors investigated a reported incidence cluster of multiple sclerosis (MS) cases in a small, north-central Illinois community to determine validity and statistical significance. DePue, Illinois--a small, north-central Illinois community--has previously been the site of significant environmental heavy-metal exposure from a zinc smelter. Significant contamination of soil and water with zinc and other metals has been documented in this community during the time period of interest. In the mid-1990s, several cases of MS were reported to the Illinois Department of Public Health within the geographic limits of this community. Available medical records from purported MS cases reported to the Illinois Department of Public Health were reviewed, and living individuals were seen and examined. Statistical analyses were conducted with clinically definite MS cases; onset dates were determined by first symptom, and expected incidence rates were determined from published epidemiologic studies. Nine new cases of clinically definite MS occurred among residents of DePue, Illinois, during the period between 1971 and 1990. Seven of the 8 living subjects included in the final analyses were examined by one author (RS). The computed incidence rate deriving from these cases within DePue Township, Illinois, represented a statistically significant excess of new MS cases over expected. During the period from 1971 through 1990, a significant excess of MS cases occurred within the population of DePue, Illinois. Significant exposure of this population to mitogenic trace metals, including zinc, was also documented during this time period.


Genetic analysis of the phenobarbital regulation of the cytochrome P-450 2b-9 and aldehyde dehydrogenase type 2 mRNAs in mouse liver.
The aim of this study was to investigate the effect of the genetic background on the phenobarbital inducibility of cytochrome P-450 2b-9, cytochrome P-450 2b-10 and aldehyde dehydrogenase type 2 mRNAs in mice. We analysed the basal expression and the phenobarbital inducibility of both cytochrome P-450 mRNAs by semi-quantitative specific reverse transcription-PCR analyses in five inbred mouse strains (A/J,BALB/cByJ,C57BL/6J, DBA/2J and SWR/J). Male mice constitutively expressed cytochrome P-450 2b-9 and cytochrome P-450 2b-10 mRNAs, but a number of differences in their response to phenobarbital were observed. In all these mouse strains, phenobarbital induced cytochrome P-450 2b-10 mRNA whereas it could have either a positive or a negative effect on cytochrome P-450 2b-9 expression, depending on the strain and the sex of the mice. Specifically, phenobarbital increased cytochrome P-450 2b-9 expression in C57BL/6J males while it decreased it in DBA/2J mice. Interestingly, dexamethasone was able to mimic the phenobarbital effect on both cytochromes P-450 in these two strains. Aldehyde dehydrogenase type 2 mRNA was always induced by phenobarbital, except in the C57BL/6J strain. Genetic analysis revealed that the phenobarbital-inducible phenotype was either a semi-dominant or a recessive trait in F1 animals from a C57BL/6J x DBA/2J cross for the cytochrome P-450 2b-9 and the aldehyde dehydrogenase type 2 genes, respectively. This study suggests that the genetic basis for phenobarbital induction in mice depends on the target gene, and that more than one regulatory step would by involved in this response pathway.


Planar self-calibration for stereo cameras with radial distortion.
In this paper, we present a robust technique of stereo calibration using homography constraints. Our method is novel as stereo calibration is performed by solving a polynomial equation system including two radial distortion parameters, using a minimal number of five image point correspondences. This enables us to calibrate from only a pair of stereo images of a planar scene, and to provide the exact algebraic solution to the stereo calibration problem. The minimal case solution is useful to reduce the computation time and increase the calibration robustness when using random sample consensus (RANSAC) from the correspondences of the stereo image pair. Further, a non-linear parameter optimization for the intrinsic and extrinsic parameters of stereo cameras is performed using the inliers, which are determined after RANSAC. In addition, our method can achieve more robust calibration results with multiple stereo image pairs by performing joint optimization. In contrast to the previous stereo calibration methods, our method works without requiring any special hardware and has no problems with one stereo image pair, even corrupted by severe radial distortions. Finally, by evaluating our method on both synthetic and real scene data, we demonstrate that our method is both efficient and accurate for stereo calibration.


Risk factors for symptomatic mitochondrial toxicity in HIV/hepatitis C virus-coinfected patients during interferon plus ribavirin-based therapy.
To evaluate the incidence, clinical features, and risk factors for symptomatic mitochondrial toxicity in HIV/hepatitis C virus (HCV)-coinfected patients receiving anti-HCV therapy. All cases of symptomatic mitochondrial toxicity reported in 416 patients participating in an open, randomized trial of peg-interferon alpha-2b plus ribavirin vs. interferon alpha-2b plus ribavirin for 48 weeks were reviewed. Associations with antiretroviral treatments and with clinical and laboratory findings were sought by univariate and multivariate analysis. Eleven of the 383 patients who received at least 1 dose of anti-HCV treatment developed symptomatic mitochondrial toxicity (symptomatic hyperlactatemia and pancreatitis in 6 and 5 patients, respectively). All cases occurred in patients being treated for HIV infection, and the incidence of symptomatic mitochondrial toxicity was 47.5 per 1000 patient-years. In multivariate analysis, symptomatic mitochondrial toxicity was significantly associated with didanosine-containing antiretroviral regimens (odds ratio 46; 95% CI, 7.4 to infinity; P < 0.001), but not with stavudine or with nucleoside reverse transcriptase inhibitor regimens not containing didanosine. The incidence of symptomatic mitochondrial toxicity was 200.2 per 1000 patient-years in patients receiving didanosine. Demographic characteristics were not associated with symptomatic mitochondrial toxicity. Coadministration of ribavirin with didanosine should be avoided. If unavoidable, patients should be monitored closely for mitochondrial toxicity. Didanosine should be suspended if clinical signs or symptoms of mitochondrial toxicity occur.


Upregulated thymic stromal lymphopoietin receptor expression in children with asthma.
Thymic stromal lymphopoietin (TSLP) plays an important role in pathogenesis in patients with asthma. However, the role of thymic stromal lymphopoietin receptor (TSLPR) and correlation with IL-7Rα and clinical severity in asthmatic or nonasthmatic children remain unclear. We investigated TSLPR and IL-7Rα mRΝΑ levels in asthma and nonasthma and assessed TSLPR expression in children who were sensitive to mites. We enrolled asthmatic and nonasthmatic children. To minimize the influence of allergy, we also divided participants into following 4 groups: nonallergic and nonasthmatic group (NN) (healthy children), allergic but nonasthmatic group (AN), nonallergic but asthmatic group (NA) and allergic asthmatic group (AA). We drew blood samples to check total IgE, allergen-specific IgE and TSLP and measured the expression of the TSLPR and IL-7Rα genes using reverse-transcription polymerase chain reaction (RT-PCR) and real-time PCR. Asthma symptom score was also recorded. Thymic stromal lymphopoietin and TSLPR levels were found to be significantly higher in asthmatic than in nonasthmatic children. The levels of TSLP were found to be significantly different between AA and NN groups (P < 0·05). TSLPR expression in NA and AA groups was found to be significantly higher than in NN group (P < 0·05). TSLPR did not differ significantly between NA and AA groups. The TSLPR expression correlated strongly with IL-7Rα and weakly with mite-specific IgE. Clinical asthmatic severity of children was found to exert no influence on TSLPR level. Thymic stromal lymphopoietin receptor might be a significant disease biomarker for asthma. The levels of TSLPR were found to be higher in asthmatic patients than in healthy children, but were found to be not different between allergic and nonallergic asthmatic patients.


Scaling Properties of Dimensionality Reduction for Neural Populations and Network Models.
Recent studies have applied dimensionality reduction methods to understand how the multi-dimensional structure of neural population activity gives rise to brain function. It is unclear, however, how the results obtained from dimensionality reduction generalize to recordings with larger numbers of neurons and trials or how these results relate to the underlying network structure. We address these questions by applying factor analysis to recordings in the visual cortex of non-human primates and to spiking network models that self-generate irregular activity through a balance of excitation and inhibition. We compared the scaling trends of two key outputs of dimensionality reduction-shared dimensionality and percent shared variance-with neuron and trial count. We found that the scaling properties of networks with non-clustered and clustered connectivity differed, and that the in vivo recordings were more consistent with the clustered network. Furthermore, recordings from tens of neurons were sufficient to identify the dominant modes of shared variability that generalize to larger portions of the network. These findings can help guide the interpretation of dimensionality reduction outputs in regimes of limited neuron and trial sampling and help relate these outputs to the underlying network structure.


Interarm difference in blood pressure: reproducibility and association with peripheral vascular disease.
The present study aimed at examining the interarm difference in blood pressure and its use as an indicator of peripheral arterial disease (PAD). Data were included from consecutive patients referred from their general practitioner to our vascular laboratory for possible PAD aged 50 years or older without known cardiac disease, renal disease, or diabetes mellitus. 824 patients (453 women) with mean age of 72 years (range: 50-101) were included. 491 patients had a diagnosis of hypertension and peripheral arterial disease (PAD) was present in 386 patients. Systolic blood pressure was 143 ± 24 mmHg and 142 ± 24 mmHg on the right and left arm, respectively (P = 0.015). The interarm difference was greater in patients with hypertension (P = 0.002) and PAD (P < 0.0005). 443 patients were measured on two separate occasions and the interarm difference for systolic blood pressure was reproducible for differences >20 mmHg. This study confirmed the presence of a systematic but clinically insignificant difference in systolic blood pressure between arms. The interarm difference was larger in hypertension and PAD. Consistent lateralisation is present for differences ≥20 mmHg and an interarm difference >25 mmHg is a reliable indicator of PAD in the legs.


Chromosomal aberrations and sister-chromatid exchanges in Lithuanian populations: effects of occupational and environmental exposures.
Cytogenetic analysis of chromosomal aberrations (CA) in 175,229 cells from 1113 individuals, both unexposed and occupationally or environmentally exposed to heavy metals (mercury and lead), organic (styrene, formaldehyde, phenol and benzo(a)pyrene) and inorganic (sulfur and nitrogen oxides, hydrogen and ammonium fluorides) volatile substances and/or ionizing radiation was performed. In addition, 11,250 cells from 225 individuals were scored for the frequency of sister-chromatid exchanges (SCE). Increased frequencies of CA were found in all occupationally exposed groups. A principal difference between the exposure to heavy metals and organic substances was found: increase in the CA frequency was dependent on duration of exposure to mercury but not dependent on duration of exposure to styrene, formaldehyde and phenol. A higher CA incidence was found in lymphocytes of children living in the vicinity of a plant manufacturing phosphate fertilizers. This indicates that children are a sensitive study group for the assessment of environmental exposure. However, the results of SCE analysis in these children were inconclusive. Exposure to ionizing radiation was found to cause chromosome breaks and chromatid exchanges in Chernobyl clean-up workers and chromatid breaks, chromatid exchanges, dicentric chromosomes and chromosome translocations in workers from the Ignalina Nuclear Power Plant. The increased frequency of chromatid exchanges in individuals exposed to ionizing radiation was quite unexpected. This may be attributed to the action of some unrecognized life-style or occupational factors, or to be a result of radiation-induced genomic instability. Also an increased SCE frequency was found in lymphocytes of Chernobyl clean-up workers.


Genetic Characterization of Dog Personality Traits.
The genetic architecture of behavioral traits in dogs is of great interest to owners, breeders, and professionals involved in animal welfare, as well as to scientists studying the genetics of animal (including human) behavior. The genetic component of dog behavior is supported by between-breed differences and some evidence of within-breed variation. However, it is a challenge to gather sufficiently large datasets to dissect the genetic basis of complex traits such as behavior, which are both time-consuming and logistically difficult to measure, and known to be influenced by nongenetic factors. In this study, we exploited the knowledge that owners have of their dogs to generate a large dataset of personality traits in Labrador Retrievers. While accounting for key environmental factors, we demonstrate that genetic variance can be detected for dog personality traits assessed using questionnaire data. We identified substantial genetic variance for several traits, including fetching tendency and fear of loud noises, while other traits revealed negligibly small heritabilities. Genetic correlations were also estimated between traits; however, due to fairly large SEs, only a handful of trait pairs yielded statistically significant estimates. Genomic analyses indicated that these traits are mainly polygenic, such that individual genomic regions have small effects, and suggested chromosomal associations for six of the traits. The polygenic nature of these traits is consistent with previous behavioral genetics studies in other species, for example in mouse, and confirms that large datasets are required to quantify the genetic variance and to identify the individual genes that influence behavioral traits.


Advancing a health equity agenda across multiple policy domains: a qualitative policy analysis of social, trade and welfare policy.
While there is urgent need for policymaking that prioritises health equity, successful strategies for advancing such an agenda across multiple policy sectors are not well known. This study aims to address this gap by identifying successful strategies to advance a health equity agenda across multiple policy domains. We conducted in-depth qualitative case studies in three important social determinants of health equity in Australia: employment and social policy (Paid Parental Leave); macroeconomics and trade policy (the Trans Pacific Partnership agreement); and welfare reform (the Northern Territory Emergency Response). The analysis triangulated multiple data sources included 71 semistructured interviews, document analysis and drew on political science theories related to interests, ideas and institutions. Within and across case studies we observed three key strategies used by policy actors to advance a health equity agenda, with differing levels of success. The first was the use of multiple policy frames to appeal to a wide range of actors beyond health. The second was the formation of broad coalitions beyond the health sector, in particular networking with non-traditional policy allies. The third was the use of strategic forum shopping by policy actors to move the debate into more popular policy forums that were not health focused. This analysis provides nuanced strategies for agenda-setting for health equity and points to the need for multiple persuasive issue frames, coalitions with unusual bedfellows, and shopping around for supportive institutions outside the traditional health domain. Use of these nuanced strategies could generate greater ideational, actor and institutional support for prioritising health equity and thus could lead to improved health outcomes.


Knee and hip arthroplasty infection rates in persons with haemophilia: a 27 year single center experience during the HIV epidemic.
Total joint replacement (TJR) is an option for the management of chronic haemophilic arthropathy. Because surgery is technically challenging, there is a high rate of deep prosthetic infections, particularly in human immunodeficiency virus (HIV)-infected individuals. We determined the incidence of deep infection rates following total knee and hip arthroplasties in HIV-seropositive and HIV-seronegative persons with haemophilia. Fifty-one primary joint replacements were performed on 32 patients seen at a regional comprehensive haemophilia care center from 1975 to 2002. Thirty prostheses were placed in patients who were HIV-seropositive prior to surgery (n = 14) or seroconverted later (n = 16). Median age at the time of surgery was 33 years (range: 20-61) among 19 HIV-seropositive patients and 35 years (range: 26-74) among 13 HIV-negative patients. Median duration of follow-up was 83 months (range: 2-323). Rate of primary joint infection per artificial joint-year by HIV status was compared by Poisson regression. Main outcome measures were the incidence of primary replacement joint infections by HIV status. Deep infections developed in five (9.8%) of 51 replacement joints. There were two infections during 204.15 joint-years without HIV infection and three infections during 205.28 joint-years with HIV infection. The incidence rate of joint infection (0.98 vs. 1.46 per 100 joint-years) was not increased with HIV (relative risk, RR: 1.49, 95% CI: 0.25-8.93, P = 0.66). We conclude that HIV infection is not a contraindication to knee or hip replacement arthroplasty in the appropriate clinical setting.


KIF5C: a new binding partner for protein kinase CK2 with a preference for the CK2alpha' subunit.
Protein kinase CK2 is a highly conserved serine/threonine kinase that is ubiquitously expressed in eukaryotic cells. CK2 is a constitutively active tetrameric enzyme composed of two catalytic alpha and/or alpha'-subunits and two regulatory beta-subunits. There is increasing evidence that the individual subunits may have independent functions and that they are asymmetrically distributed inside the cell. To gain a better understanding of the functions of the individual subunits, we employed a yeast-two-hybrid screen with CK2alpha and CK2alpha'. We identified the motor neuron protein KIF5C as a new binding partner for CK2. The interaction found in the yeast-two-hybrid screen was confirmed by co-sedimentation analysis on a sucrose density gradient and by co-immunoprecipitation analysis. Pull-down experiments and surface plasmon resonance spectrometry revealed a direct binding of KIF5C to CK2alpha'. Co-localization studies with neuroblastoma cells, bone marrow and with primary neurons confirmed the biochemical analysis that KIF5C preferentially bound to CK2alpha'.


Nas transgenic mouse line allows visualization of Notch pathway activity in vivo.
The Notch signaling pathway plays multiple and important roles in mammals. However, several aspects of its action, in particular, the precise mapping of its sites of activity, remain unclear. To address this issue, we generated a transgenic line carrying a construct consisting of a nls-lacZ reporter gene under the control of a minimal promoter and multiple RBP-Jkappa binding sites. Here we show that this transgenic line, which we termed NAS (for Notch Activity Sensor), displays an expression profile that is consistent with current knowledge on Notch activity sites in mice, even though it may not report on all these sites. Moreover, we observe that NAS transgene expression is abolished in a RBP-Jkappa-deficient background, indicating that it indeed requires Notch/RBP-Jkappa signaling pathway activity. Thus, the NAS transgenic line constitutes a valuable and versatile tool to gain further insights into the complex and various functions of the Notch signaling pathway.


Adding Biotin to Parenteral Nutrition Solutions Without Lipid Accelerates the Growth of Candida albicans.
We have previously demonstrated that Candida albicans requires multivitamins (MVs) or lipid to increase rapidly in parenteral nutrition (PN) solutions. In this study, in detail, the effects of vitamins on the growth of C. albicans in PN solutions without lipid were investigated. In the 1st experiment, a commercial PN solution without lipid was supplemented with water-soluble vitamins (SVs: vitamins B1, B2, B6, B12 and C, folic acid, nicotinamide, biotin and panthenol), water-insoluble vitamins (IVs: vitamins A, D, E and K) or both (MVs). In the 2nd experiment, the test solutions were prepared by supplementing the PN solution with one of each or all of the SVs. In the 3rd experiment, another commercial peripheral PN (PPN) solution without lipid was supplemented with SVs, nicotinic acid, biotin or both nicotinic acid and biotin. In each of the experiments, a specified number of C. albicans organisms was added to each test solution, and all of the test solutions were allowed to stand at room temperature (23-26ºC). The number of C. albicans was counted at 0, 24, 48 and 72 hours after the addition of the organism. In the 1st experiment, the C. albicans increased rapidly in the PN solution supplemented with the SVs, but increased slowly without the SVs, regardless of the addition of the IVs. In the 2nd experiment, the C. albicans increased rapidly in the PN solution supplemented with the SVs or biotin, but increased slowly with each of the other water-soluble vitamins. In the 3rd experiment, the C. albicans increased rapidly in the PPN solution supplemented with the SVs or biotin, but increased slowly with the addition of nicotinic acid. These results suggested that adding MVs or SVs to PN solutions without lipid promotes the growth of C. albicans, and that this effect is mostly attributable to biotin.


Inhibition of Breast Cancer Metastasis by Presurgical Treatment with an Oral Matrix Metalloproteinase Inhibitor: A Preclinical Proof-of-Principle Study.
Breast cancer has the second highest death toll in women worldwide, despite significant progress in early diagnosis and treatments. The main cause of death is metastatic disease. Matrix metalloproteinases (MMP) are required for the initial steps of metastasis, and have therefore been considered as ideal pharmacologic targets for antimetastatic therapy. However, clinical trials of MMP inhibitors were unsuccessful. These trials were conducted in patients with advanced disease, beyond the stage when these compounds could have been effective. We hypothesized that early treatment with a selective MMP inhibitor between the time of diagnosis and definitive surgery, the so-called "window-of-opportunity," can inhibit metastasis and thereby improve survival. To investigate our hypothesis, we used the 4T1 mouse model of aggressive mammary carcinoma. We treated the animals with SD-7300, an oral inhibitor of MMP-2, -9, and -13, starting after the initial detection of the primary tumor. Seven days later, the primary tumors were excised and analyzed for MMP activity, and the SD-7300 treatment was discontinued. After 4 weeks, the animals were sacrificed and their lungs analyzed histologically for number of metastases and metastatic burden (metastases' area/lung section area). SD-7300 treatment inhibited 70% to 80% of tumor-associated MMP activity (P = 0.0003), reduced metastasis number and metastatic burden by 50% to 60% (P = 0.002 and P = 0.0082, respectively), and increased survival (92% vs. 66.7%; P = 0.0409), relative to control vehicle. These results show that treatment of early invasive breast cancer with selective MMP inhibitors can lower the risk of recurrence and increase long-term disease-free survival. Mol Cancer Ther; 15(10); 2370-7. ©2016 AACR.


Effectiveness of Tailored Rehabilitation Education in Improving the Health Literacy and Health Status of Postoperative Patients With Breast Cancer: A Randomized Controlled Trial.
The improvement of breast cancer treatment and the extension of survivorship have led to the development of postoperative complications among cancer survivors. Health literacy (HL), defined as patients' capability of using health information to maintain their health status, can enable breast cancer patients to manage postoperative complications. The aims of this study were to develop a tailored rehabilitation education (TRE) program and examine the effectiveness of this program in improving the HL and health status with breast cancer. This randomized controlled trial recruited 99 breast cancer patients (49 and 50 in the intervention and control groups, respectively) within 1 week after surgery. Four-week individualized TRE programs were implemented to improve their HL and health status. Our results showed that the TRE program produced significant improvements in HL and health status in the components of the International Classification of Functioning, Disability and Health. However, no significant difference was observed in the activity scores obtained using the Barthel Index between the 2 groups. Our finding supports the effectiveness of 1-month TRE in improving HL and all components of the International Classification of Functioning, Disability and Health status, except the activity component among breast cancer in Taiwan. Clinicians could incorporate the TRE techniques in the rehabilitation sessions according to the healthcare, disease prevention, and health promotion domains to improve the clinical outcomes as well as change their health behaviors and attitudes of patients with breast cancer.


Comparison of clinical manifestations between patients with ocular myasthenia gravis and generalized myasthenia gravis.
To compare the clinical manifestations between patients with ocular myasthenia gravis and those with generalized myasthenia gravis (MG). The medical records of 71 patients diagnosed with MG between January 1995 and December 2007 were reviewed. Demographics, sensitivities of diagnostic methods, the presence of systemic autoimmune diseases, ophthalmic complications caused by MG, and treatments were evaluated and compared. Fourteen patients (20%) were diagnosed with ocular MG and 57 patients (80%) with generalized MG. Sensitivities of anti-acetylcholine receptor antibody and repetitive nerve stimulation tests were significantly higher in the generalized MG group (84%, 89%) compared to those in the ocular MG group (50%, 54%) (p = 0.011, p = 0.008). The sensitivity of the neostigmine test was the highest in both groups (98% of generalized MG, 79% of ocular MG), and the difference between the two groups was borderline significant (p = 0.058). The most common symptoms were ptosis and diplopia, and both groups presented with pain, blurred vision, and tearing. Systemic autoimmune disease was more prominent in the generalized MG group (21%) than in the ocular MG group (14%), and steroid therapy was used more frequently in the generalized MG group (82%) than in the ocular MG group (57%). Ophthalmic complications associated with long-term steroid treatment were more profound in the generalized MG (30%) compared to those of the ocular MG (21%). The generalized MG group was associated with higher sensitivities to diagnostic tests, more systemic steroid use, higher ophthalmic complications caused by systemic autoimmune disease, and long-term steroid treatment compared to those of the ocular MG group.


The representation and plasticity of body emotion expression.
Emotions are expressed by the face, the voice and the whole body. Research on the face and the voice has not only demonstrated that emotions are perceived categorically, but that this perception can be manipulated. The purpose of this study was to investigate, via two separate experiments using adaptation and multisensory techniques, whether the perception of body emotion expressions also shows categorical effects and plasticity. We used an approach developed for studies investigating both face and voice emotion perception and created novel morphed affective body stimuli, which varied in small incremental steps between emotions. Participants were instructed to perform an emotion categorisation of these morphed bodies after adaptation to bodies conveying different expressions (Experiment 1), or while simultaneously hearing affective voices (Experiment 2). We show that not only is body expression perceived categorically, but that both adaptation to affective body expressions and concurrent presentation of vocal affective information can shift the categorical boundary between body expressions, specifically for the angry body expressions. Overall, our findings provide significant new insights into emotional body categorisation, which may prove important in gaining a deeper understanding of body expression perception in everyday social situations.


The effect of literacy on oral language processing: Implications for aphasia tests.
Most studies investigating the impact of literacy on oral language processing have shown that literacy provides phonological awareness skills in the processing of oral language. The implications of these results on aphasia tests could be significant and pose questions on the adequacy of such tools for testing non-literate individuals. Aiming at examining the impact of literacy on oral language processing and its implication on aphasia tests, this study tested 12 non-literate and 12 literate individuals with a modified Amharic version of the Bilingual Aphasia Test (Paradis and Amberber, 1991, Bilingual Aphasia Test. Amharic version. Hillsdale, NJ: Lawrence Erlbaum.). The problems of phonological awareness skills in oral language processing in non-literates are substantiated. In addition, compared with literate participants, non-literate individuals demonstrated difficulties in the word/sentence-picture matching tasks. This study has also revealed that the Amharic version of the Bilingual Aphasia Test may be viable for testing Amharic-speaking non-literate individuals with aphasia when modifications are incorporated.


Dorsal Anterior Cingulate, Medial Superior Frontal Cortex, and Anterior Insula Show Performance Reporting-Related Late Task Control Signals.
The cingulo-opercular network (including the dorsal anterior cingulate and bilateral anterior insula) shows 3 distinct task-control signals across a wide variety of tasks, including trial-related signals that appear to come online at or near the end of the trial. Previous work suggests that there are separable responses in this network for errors and ambiguity, implicating multiple types of processing units within these regions. Using a unique paradigm, we directly show that these separable responses withhold activity to the end of the trial, in the service of reporting performance back into the task set. Participants performed a slow reveal task where images were presented behind a black mask which was gradually degraded, and they pressed a button when they could recognize the object that was being revealed. A behavioral pilot was used to identify ambiguous stimuli. We found interactive effects of accuracy and ambiguity, which suggests that these regions are computing and utilizing information, at one time, about both types of performance indices. Importantly, we showed a relationship between cingulo-opercular activity and behavioral performance, suggesting a role for these regions in performance reporting, per se. We discuss these results in the context of task control.


Optimization of soft x-ray amplifier by tailoring plasma hydrodynamics.
Plasma-based seeded soft x-ray lasers have the potential to generate a high-energy, highly coherent, short pulse beam. Owing to their high density, plasmas created by interaction of an intense laser with a solid target should store the highest amount of energy among all plasma amplifiers. However, to date output energy from seeded solid amplifiers remains as low as 60 nJ. We demonstrated that careful tailoring of the plasma shape is crucial for extracting energy stored in the plasma. With 1-mm-wide plasma, energy as high as 20 microJ in sub-ps pulses is achievable. With such tailored plasma, gain and pumping efficiency have been increased by nearly a factor of 10 as compared to the narrower plasma amplifiers studied here.


A Burgeoning Crisis? A Nationwide Assessment of the Geography of Water Affordability in the United States.
While basic access to clean water is critical, another important issue is the affordability of water access for people around the globe. Prior international work has highlighted that a large proportion of consumers could not afford water if priced at full cost recovery levels. Given growing concern about affordability issues due to rising water rates, and a comparative lack of work on affordability in the developed world, as compared to the developing world, more work is needed in developed countries to understand the extent of this issue in terms of the number of households and persons impacted. To address this need, this paper assesses potential affordability issues for households in the United States using the U.S. EPA's 4.5% affordability criteria for combined water and wastewater services. Analytical results from this paper highlight high-risk and at-risk households for water poverty or unaffordable water services. Many of these households are clustered in pockets of water poverty within counties, which is a concern for individual utility providers servicing a large proportion of customers with a financial inability to pay for water services. Results also highlight that while water rates remain comparatively affordable for many U.S. households, this trend will not continue in the future. If water rates rise at projected amounts over the next five years, conservative projections estimate that the percentage of U.S. households who will find water bills unaffordable could triple from 11.9% to 35.6%. This is a concern due to the cascading economic impacts associated with widespread affordability issues; these issues mean that utility providers could have fewer customers over which to spread the large fixed costs of water service. Unaffordable water bills also impact customers for whom water services are affordable via higher water rates to recover the costs of services that go unpaid by lower income households.


Covalent association of C3b with C4b within C5 convertase of the classical complement pathway.
The C5 convertase of the classical complement pathway is a complex enzyme consisting of three complement fragments, C4b, C2a, and C3b. Previous studies have elucidated functional roles of each subunit (4, 6, 7), but little is known about how the subunits associate with each other. In this investigation, we studied the nature of the classical C5 convertase that was assembled on sheep erythrocytes. We found that one of the nascent C3b molecules that had been generated by the C3 convertase directly bound covalently to C4b. C3b bound to the alpha' chain of C4b through an ester bond, which could be cleaved by treatment with hydroxylamine. The ester bond was rather unstable, with a half-life of 7.9 h at pH 7.4 and 37 degrees C. Formation of the C4b-C3b dimer is quite efficient; e.g., 54% of the cell-bound C3b was associated with C4b when 25,000 molecules of C4b and 12,000 molecules of C3b were present per cell. Kinetic analysis also showed the efficient formation of the C4b-C3b dimer; the rate of dimer formation was similar to or even faster than that of cell-bound monomeric C3b molecules. These results indicate that C4b is a highly reactive acceptor molecule for nascent C3b. High-affinity C5-binding sites with an association constant of 2.1 X 10(8) L/M were demonstrated on C4b-C3b dimer-bearing sheep erythrocytes, EAC43 cells. The number of high-affinity C5-binding sites coincided with the number of C4b-C3b dimers, but not with the total number of cell-bound C3b molecules. Anti-C4 antibodies caused 80% inhibition of the binding of C5 to EAC43 cells. These results suggest that only C4b-associated C3b serves as a high-affinity C5 binding site. EAC14 cells had a small amount of high-affinity C5 binding sites with an association constant of 8.1 X 10(7) L/M, 100 molecules of bound C4b being necessary for 1 binding site. In accordance with the hypothesis that C4b-associated C4b might also serve as a high-affinity C5-binding site, a small amount of C4b-C4b dimer was detected on EAC14 cells by SDS-PAGE analysis. Taken together, these observations indicate that the high-affinity binding of C5 is probably divalent, in that C5 recognizes both protomers in the dimers. The high-affinity binding may allow selective binding of C5 to the convertase in spite of surrounding monomeric C3b molecules.


Pretreatment seizure semiology in childhood absence epilepsy.
To determine seizure semiology in children with newly diagnosed childhood absence epilepsy and to evaluate associations with short-term treatment outcomes. For participants enrolled in a multicenter, randomized, double-blind, comparative-effectiveness trial, semiologic features of pretreatment seizures were analyzed as predictors of treatment outcome at the week 16 to 20 visit. Video of 1,932 electrographic absence seizures from 416 participants was evaluated. Median seizure duration was 10.2 seconds; median time between electrographic seizure onset and clinical manifestation onset was 1.5 seconds. For individual seizures and by participant, the most common semiology features were pause/stare (seizure 95.5%, participant 99.3%), motor automatisms (60.6%, 86.1%), and eye involvement (54.9%, 76.5%). The interrater agreement for motor automatisms and eye involvement was good (72%-84%). Variability of semiology features between seizures even within participants was high. Clustering analyses revealed 4 patterns (involving the presence/absence of eye involvement and motor automatisms superimposed on the nearly ubiquitous pause/stare). Most participants experienced more than one seizure cluster pattern. No individual semiologic feature was individually predictive of short-term outcome. Seizure freedom was half as likely in participants with one or more seizure having the pattern of eye involvement without motor automatisms than in participants without this pattern. Almost all absence seizures are characterized by a pause in activity or staring, but rarely is this the only feature. Semiologic features tend to cluster, resulting in identifiable absence seizure subtypes with significant intraparticipant seizure phenomenologic heterogeneity. One seizure subtype, pause/stare and eye involvement but no motor automatisms, is specifically associated with a worse treatment outcome.


Regulation of cAMP-mediated signal transduction via interaction of caveolins with the catalytic subunit of protein kinase A.
cAMP-dependent processes are essential for cell growth, differentiation, and homeostasis. The classic components of this system include the serpentine receptors, heterotrimeric G-proteins, adenylyl cyclase, protein kinase A (PKA), and numerous downstream target substrates. Evidence is accumulating that some members of this cascade are concentrated within membrane microdomains, termed caveolae and caveolae-related domains. In addition, the caveolin-1 protein has been shown to interact with some of these components, and this interaction inhibits their enzymatic activity. However, the functional effects of caveolins on cAMP-mediated signaling at the most pivotal step, PKA activation, remain unknown. Here, we show that caveolin-1 can dramatically inhibit cAMP-dependent signaling in vivo. We provide evidence for a direct interaction between caveolin-1 and the catalytic subunit of PKA both in vitro and in vivo. Caveolin-1 binding appears to be mediated both by the caveolin scaffolding domain (residues 82-101) and a portion of the C-terminal domain (residues 135-156). Further functional analysis indicates that caveolin-based peptides derived from these binding regions can inhibit the catalytic activity of purified PKA in vitro. Mutational analysis of the caveolin scaffolding domain reveals that a series of aromatic residues within the caveolin scaffolding domain are critical for mediating inhibition of PKA. In addition, co-expression of caveolin-1 and PKA in cultured cells results in their co-localization as seen by immunofluorescence microscopy. In cells co-expressing caveolin-1 and PKA, PKA assumed a punctate distribution that coincided with the distribution of caveolin-1. In contrast, in cells expressing PKA alone, PKA was localized throughout the cytoplasm and yielded a diffuse staining pattern. Taken together, our results suggest that the direct inhibition of PKA by caveolin-1 is an important and previously unrecognized mechanism for modulating cAMP-mediated signaling.


Shape variation in Aterian tanged tools and the origins of projectile technology: a morphometric perspective on stone tool function.
Recent findings suggest that the North African Middle Stone Age technocomplex known as the Aterian is both much older than previously assumed, and certainly associated with fossils exhibiting anatomically modern human morphology and behavior. The Aterian is defined by the presence of 'tanged' or 'stemmed' tools, which have been widely assumed to be among the earliest projectile weapon tips. The present study systematically investigates morphological variation in a large sample of Aterian tools to test the hypothesis that these tools were hafted and/or used as projectile weapons. Both classical morphometrics and Elliptical Fourier Analysis of tool outlines are used to show that the shape variation in the sample exhibits size-dependent patterns consistent with a reduction of the tools from the tip down, with the tang remaining intact. Additionally, the process of reduction led to increasing side-to-side asymmetries as the tools got smaller. Finally, a comparison of shape-change trajectories between Aterian tools and Late Paleolithic arrowheads from the North German site of Stellmoor reveal significant differences in terms of the amount and location of the variation. The patterns of size-dependent shape variation strongly support the functional hypothesis of Aterian tools as hafted knives or scrapers with alternating active edges, rather than as weapon tips. Nevertheless, the same morphological patterns are interpreted as one of the earliest evidences for a hafting modification, and for the successful combination of different raw materials (haft and stone tip) into one implement, in itself an important achievement in the evolution of hominin technologies.


Regulation of mouse glutathione S-transferases by chemoprotectors. Molecular evidence for the existence of three distinct alpha-class glutathione S-transferase subunits, Ya1, Ya2, and Ya3, in mouse liver.
Liver cytosol from mice fed on a normal diet contains Alpha-class glutathione S-transferase (GST) subunits of Mr 25,800, Mu-class GST subunits of Mr 26,400 and Pi-class GST subunits of Mr 24,800. Feeding female mice with a diet containing the anticarcinogenic antioxidant butylated hydroxyanisole (BHA) causes induction of the constitutively expressed Mu-class and Pi-class subunits. BHA also induces an Alpha-class GST comprising subunits of Mr 25,600, which is not expressed at detectable levels in normal mouse liver [McLellan & Hayes (1989) Biochem. J. 263, 393-402]. Data are now presented that show that administration of the anticarcinogen beta-naphthoflavone (BNF), like BHA, induces the Alpha-class 25,600-Mr subunits but not the constitutive Alpha-class GST with subunits of Mr 25,800. The effects of BNF on expression of hepatic GST were studied in both DBA/2 and C57BL/6 mice; these studies revealed a preferential induction of the Alpha-class 25,600-Mr subunits and of the Pi-class 24,800-Mr subunits in those mice in possession of a functional Ah receptor. The BHA/BNF-inducible Alpha-class GST can be resolved into two separate, non-interconvertible peaks by reverse-phase h.p.l.c. Automated amino acid sequence analysis of CNBr-derived peptides from each of these h.p.l.c.-purified peaks showed that the peaks contained at least two very similar subunits. These have been named Ya1 and Ya2. The amino acid sequence of the Ya1 subunit was compared with sequences deduced from a genomic clone, lambda mYa1 (Daniel, Sharon, Tichauer & Sarid (1987) DNA 6, 317-324], and a cDNA clone, pGT41 [Pearson, Reinhart, Sisk, Anderson & Adler (1988) J. Biol. Chem. 263, 13324-13332]. Our data suggest that the Ya1 subunit represents the subunit encoded by the genomic clone, lambda mYa1. Sequence analysis of the constitutive Alpha-class Ya3 subunit (Mr 25,800) shows that, although it is a member of the same gene family as the Ya1 and Ya2 subunits, it represents a distinct sub-family of Alpha-class GST, containing subunits that are more similar to rat Yc. Our data indicate that, of these Alpha-class GST subunits, the two with Mr 25,600 (Ya1 and Ya2) are selectively induced by BHA or BNF in mouse liver; neither BHA nor BNF induces significantly the GST subunit with Mr 25,800 (Ya3).


"The social advantage of miscalibrated individuals: The relationship between social class and overconfidence and its implications for class-based inequality": Correction to Belmi et al. (2019).
Reports an error in "The social advantage of miscalibrated individuals: The relationship between social class and overconfidence and its implications for class-based inequality" by Peter Belmi, Margaret A. Neale, David Reiff and Rosemary Ulfe (Journal of Personality and Social Psychology, Advanced Online Publication, May 20, 2019, np). In the article, the first sentence in the Social class, perceived competence, and status attainment section is incorrect due to a printer error and should read instead as follows: Hypothesis 4 predicted that relative to individuals with lower social class, individuals with relatively high social class would be more overconfident, which in turn, would be associated with higher competence ratings, and ultimately, higher hiring ratings. All versions of this article have been corrected. (The following abstract of the original article appeared in record 2019-25778-001.) Understanding how socioeconomic inequalities perpetuate is a central concern among social and organizational psychologists. Drawing on a collection of findings suggesting that different social class contexts have powerful effects on people's sense of self, we propose that social class shapes the beliefs that people hold about their abilities, and that this, in turn, has important implications for how status hierarchies perpetuate. We first hypothesize that compared with individuals with relatively low social class, individuals with relatively high social class are more overconfident. Then, drawing on research suggesting that overconfidence can confer social advantages, we further hypothesize that the overconfidence of higher class individuals can help perpetuate the existing class hierarchy: It can provide them a path to social advantage by making them appear more competent in the eyes of others. We test these ideas in four large studies with a combined sample of 152,661 individuals. Study 1, a large field study featuring small-business owners from Mexico, found evidence that individuals with relatively high social class are more overconfident compared with their lower-class counterparts. Study 2, a multiwave study in the United States, replicated this result and further shed light on the underlying mechanism: Individuals with relatively high (vs. low) social class tend to be more overconfident because they have a stronger desire to achieve high social rank. Study 3 replicated these findings in a high-powered, preregistered study and found that individuals with relatively high social class were more overconfident, even in a task in which they had no performance advantages. Study 4, a multiphase study that featured a mock job interview in the laboratory, found that compared with their lower-class counterparts, higher-class individuals were more overconfident; overconfidence, in turn, made them appear more competent and more likely to attain social rank. (PsycINFO Database Record (c) 2020 APA, all rights reserved).


Elucidation of the cross-reactive immunoglobulin M response to human herpesviruses 6 and 7 on the basis of neutralizing antibodies.
Human herpesvirus 6 (HHV-6) is closely related to HHV-7 in terms of genome organization and sequence. The cross-reactive responses between HHV-6 and HHV-7 have been reported by using immunofluorescent techniques. Recently we have shown that neutralizing (NT) antibody responses are specific to each virus and do not cross-react. We took advantage of this and used the NT antibody response to estimate the time of seroconversion to each virus and examined the pattern of humoral immune response, especially the immunoglobulin M (IgM) response, against each virus antigen in the natural course of infection with HHV-6 and HHV-7. In children who experienced HHV-6 infection first, followed by HHV-7 infection, the IgM response at the first HHV-6 infection was directed only against HHV-6, while no IgM response was directed against HHV-7 at the second HHV-7 infection. In contrast, in children who experienced HHV-7 infection first, followed by HHV-6 infection, the IgM response at the first HHV-7 infection was directed not only against HHV-7 but also against HHV-6. These data suggest that cross-reactive responses to heterologous viruses should be taken into consideration when making a diagnosis based on IgM antibody.


Transcription factor TFIIH and DNA endonuclease Rad2 constitute yeast nucleotide excision repair factor 3: implications for nucleotide excision repair and Cockayne syndrome.
Nucleotide excision repair (NER) of ultraviolet light-damaged DNA in eukaryotes requires a large number of highly conserved protein factors. Recent studies in yeast have suggested that NER involves the action of distinct protein subassemblies at the damage site rather than the placement there of a "preformed repairosome" containing all the essential NER factors. Neither of the two endonucleases, Rad1-Rad10 and Rad2, required for dual incision, shows any affinity for ultraviolet-damaged DNA. Rad1-Rad10 forms a ternary complex with the DNA damage recognition protein Rad14, providing a means for targeting this nuclease to the damage site. It has remained unclear how the Rad2 nuclease is targeted to the DNA damage site and why mutations in the human RAD2 counterpart, XPG, result in Cockayne syndrome. Here we examine whether Rad2 is part of a higher order subassembly. Interestingly, we find copurification of Rad2 protein with TFIIH, such that TFIIH purified from a strain that overexpresses Rad2 contains a stoichiometric amount of Rad2. By several independent criteria, we establish that Rad2 is tightly associated with TFIIH, exhibiting an apparent dissociation constant < 3.3 x 10(-9) M. These results identify a novel subassembly consisting of TFIIH and Rad2, which we have designated as nucleotide excision repair factor 3. Association with TFIIH provides a means of targeting Rad2 to the damage site, where its endonuclease activity would mediate the 3' incision. Our findings are important for understanding the manner of assembly of the NER machinery and they have implications for Cockayne syndrome.


Surgery for gallstone ileus: a nationwide comparison of trends and outcomes.
Gallstone ileus is a mechanical bowel obstruction caused by a biliary calculus originating from a bilioenteric fistula. Because of the limited number of reported cases, the optimal surgical method of treatment has been the subject of ongoing debate. A retrospective review of the Nationwide Inpatient Sample from 2004 to 2009 was performed for gallstone ileus cases treated surgically by enterotomy with stone extraction alone (ES), enterotomy and cholecystectomy with fistula closure (EF), bowel resection alone (BR), and bowel resection with fistula closure (BF). Patient demographics, hospital factors, comorbidities, and postoperative outcomes were reported. Multivariate analysis was performed comparing mortality, morbidity, length of stay, and total cost for the different procedure types. Of the estimated 3,452,536 cases of mechanical bowel obstruction from 2004 to 2009, 3268 (0.095%) were due to gallstone ileus-an incidence lower than previously reported. The majority of patients were elderly women (>70%). ES was the most commonly performed procedure (62% of patients) followed by EF (19% of cases). In 19%, a bowel resection was required. The most common complication was acute renal failure (30.44% of cases). In-hospital mortality was 6.67%. On multivariate analysis, EF and BR were independently associated with higher mortality than ES [(odds ratio [OR] = 2.86; confidence interval [CI]: 1.16-7.07) and (OR = 2.96; CI: 1.26-6.96) respectively]. BR was also associated with a higher complication rate, OR = 1.98 (CI: 1.13-3.46). Gallstone ileus is a rare surgical disease affecting mainly the elderly female population. Mortality rates appear to be lower than previously reported in the literature. Enterotomy with stone extraction alone appears to be associated with better outcomes than more invasive techniques.


Does neoadjuvant doxorubicin drug-eluting bead transarterial chemoembolization improve survival in patients undergoing liver transplant for hepatocellular carcinoma?
We aimed to compare the overall (OS) and disease-free survival (DFS) of patients undergoing orthotopic liver transplant (OLT) for hepatocellular carcinoma who did and did not have neoadjuvant doxorubicin drug-eluting bead transarterial chemoembolization (DEB-TACE). This is a retrospective study of 94 patients with HCC transplanted between 2000 and 2014 in a single tertiary center. Pre- and postoperative features, DFS and OS were compared between patients who received pre-OLT DEB-TACE (n=34, DEB-TACE group) and those who did not (n=60, non-TACE group). Radiologic and histologic response to neoadjuvant treatment as well as its complications were also studied. There were no significant differences in post-transplantation DFS and OS rates between groups (5-year DFS: 70% in DEB-TACE group vs. 63% in non-TACE group, P = 0.454; 5-year OS: 70% in DEB-TACE group vs. 65% in non-TACE group, P = 0.532). The DEB-TACE group had longer OLT waiting time compared with the non-TACE group (110 vs. 72 days; P = 0.01). On univariate and multivariate analyses, alpha-fetoprotein (AFP) levels >500 ng/mL prior to OLT were associated with decreased OS and DFS regardless of neoadjuvant approach (hazard ratio of 6, P = 0.001 and 5.5, P = 0.002, respectively). Patients who underwent neoadjuvant DEB-TACE and OLT for hepatocellular carcinoma had no statistically different OS or DFS at 3 and 5 years from patients undergoing OLT alone.


A semi-quantitative GeLC-MS analysis of temporal proteome expression in the emerging nosocomial pathogen Ochrobactrum anthropi.
The alpha-Proteobacteria are capable of interaction with eukaryotic cells, with some members, such as Ochrobactrum anthropi, capable of acting as human pathogens. O. anthropi has been the cause of a growing number of hospital-acquired infections; however, little is known about its growth, physiology and metabolism. We used proteomics to investigate how protein expression of this organism changes with time during growth. This first gel-based liquid chromatography-mass spectrometry (GeLC-MS) temporal proteomic analysis of O. anthropi led to the positive identification of 131 proteins. These were functionally classified and physiochemically characterized. Utilizing the emPAI protocol to estimate protein abundance, we assigned molar concentrations to all proteins, and thus were able to identify 19 with significant changes in their expression. Pathway reconstruction led to the identification of a variety of central metabolic pathways, including nucleotide biosynthesis, fatty acid anabolism, glycolysis, TCA cycle and amino acid metabolism. In late phase growth we identified a number of gene products under the control of the oxyR regulon, which is induced in response to oxidative stress and whose protein products have been linked with pathogen survival in response to host immunity reactions. This study identified distinct proteomic profiles associated with specific growth points for O. anthropi, while the use of emPAI allowed semi-quantitative analyses of protein expression. It was possible to reconstruct central metabolic pathways and infer unique functional and adaptive processes associated with specific growth phases, thereby resulting in a deeper understanding of the physiology and metabolism of this emerging pathogenic bacterium.


Capillary Assembly of Liquid Particles.
Capillary assembly is a versatile method for depositing colloidal particles within templates, resulting in nano/microarrays and colloidal superstructures for optical, plasmonic, and sensory applications. Liquid particles (LPs), comprised of oligomerized 3-(trimethoxysilyl)propyl methacrylate, are herein shown to deposit into patterned cavities via capillary assembly. In contrast to solid colloids, LPs coalesce upon solvent evaporation and assume the geometry of the template. Incorporating small molecules such as dyes followed by LP solidification generates fluorescent polymer microarrays of any geometry. The LP size is inversely proportional to the quantity of deposited material and the convexity of the final polymer array. Cavity filling can be tuned by increasing the assembly temperature. Extraction of the polymerized regions produces solidified particles with faceted shapes including square prisms, trapezoids, and ellipsoids with sizes up to 14 µm that retain the shape of the cavity in which they are initially held. LP deposition thus presents a highly controllable fabrication scheme for geometrically diverse polymer microarrays and anisotropic colloids of any conceivable polygonal shape due to space filling of the template. The extension of capillary assembly to LPs that can be doped with small molecule dyes and analytes invaluably expands the synthetic toolbox for top-down, scalable, hierarchically engineered materials.


A dual colour fluorescence in situ hybridization (FISH) assay for identifying the zoonotic malaria parasite Plasmodium knowlesi with a potential application for the specific diagnosis of knowlesi malaria in peripheral-level laboratories of Southeast Asia.
Plasmodium knowlesi is primarily responsible for zoonotic malaria in several Southeast Asian countries. Precise identification of the parasite in the blood of patients presently relies on an expensive and elaborate PCR procedure because microscopic examination of blood and other available field identification techniques lack adequate specificity. Therefore, the use of a simple and inexpensive dual-colour fluorescence in situ hybridization (FISH) assay, analogous to FISH assays recently described for Plasmodium falciparum and Plasmodium vivax, was investigated as a potential tool for identifying P. knowlesi. A P. knowlesi 18S rDNA sequence-based DNA probe was used to test thin blood smears of P. knowlesi by FISH, and fluorescence viewed in a light microscope fitted with a light emitting diode light source and appropriate emission and barrier filters. The limit of detection in the P. knowlesi FISH assay was 84 parasites per μl in infected monkey blood and 61 parasites per μl for P. knowlesi cultured in human blood. The P. knowlesi-specific FISH probe detected only P. knowlesi and not P. falciparum, Plasmodium malariae, Plasmodium ovale, P. vivax or a panel of other human blood-borne pathogens. A previously described Plasmodium genus-specific probe used simultaneously in the P. knowlesi FISH assay reacted with all tested Plasmodium species. To our knowledge, this is the first description of a FISH assay for P. knowlesi that is potentially useful for diagnosing infections in remote laboratories in endemic countries.


Relative roles of plaques and tangles in the dementia of Alzheimer's disease: correlations using three sets of neuropathological criteria.
We have performed a quantitative analysis of the amyloid load (plaques), neuritic plaques and neurofibrillary tangles (NFT) in the frontal, temporal and parietal association cortices of autopsied brains from 49 prospectively evaluated patients with Alzheimer's disease (AD) diagnosed according to three sets of published pathological criteria. These patients had been assessed clinically with psychological testing of cognitive abilities within 6 months of death. Correlations were sought between severity of pathological change and cognitive status before death, duration of disease and age at death. Using Khachaturian and CERAD criteria highly positive correlations were obtained between the extent of cognitive deficit and the density of NFT in frontal and parietal lobes. The percentage area of cortex occupied by amyloid in the parietal lobe was correlated to the cognitive deficit only in the CERAD-diagnosed cases. The density of all amyloid plaques (AP) showed no correlation with the extent of cognitive deficit, but the densities of neuritic plaques did correlate with cognitive deficit. Both amyloid load and tangle densities were positively correlated with disease duration. All these correlations were reduced or absent in a subgroup of cases fulfilling the Tierney et al. A3 diagnostic criteria for AD. We found no pathological measure that correlated with the age of patients at death. Amyloid loads and NFT densities showed highly significant but selective positive correlations, the most striking being between temporal lobe NFT density and frontal and parietal lobe amyloid load and between temporal lobe NFT density and frontal and parietal lobe NFT densities. Correlations involving AP density as a measure of amyloid load were almost always less significant than those involving the percentage area of cortex occupied by amyloid, suggesting that the latter measures amyloid load more accurately. However, the highest correlations of NFT densities were with neuritic plaque densities. Overall this study highlights the relevance of neuritic changes (revealed by NFT and neuritic plaques) and the irrelevance of amyloid plaques to the dementia of AD.


Left atrial volume: a powerful predictor of survival after acute myocardial infarction.
After acute myocardial infarction (AMI), diastolic function assessed by Doppler echocardiography provides important prognostic information that is incremental to systolic function. However, Doppler variables are affected by multiple factors and may change rapidly. In contrast, left atrial (LA) volume is less influenced by acute changes and reflects subacute or chronic diastolic function. This may be of importance when one assesses risk in patients with AMI. Three hundred fourteen patients with AMI who had a transthoracic echocardiogram with assessment of left ventricular (LV) systolic and diastolic function and measurement of LA volume during admission were identified. The LA volume was corrected for body surface area, and the population was divided according to LA volume index of 32 mL/m2 (2 SDs above normal). LA volume index was >32 mL/m2 in 142 (45%). The primary study end point was all-cause mortality. During follow-up of 15 (range 0 to 33) months, 46 patients (15%) died. LA volume index was a powerful predictor of mortality and remained an independent predictor (hazard ratio 1.05 per 1-mL/m2 change, 95% CI 1.03 to 1.06, P<0.001) after adjustment for clinical factors, LV systolic function, and Doppler-derived parameters of diastolic function. Increased LA volume index is a powerful predictor of mortality after AMI and provides prognostic information incremental to clinical data and conventional measures of LV systolic and diastolic function.


Early exposure to general anesthesia impairs social and emotional development in rats.
Several animal and emerging human studies suggest an association between an early exposure to general anesthesia (GA) and long-lasting problems with complex social and emotional behaviors such as inattentiveness, impulsivity, anxiogenic tendencies, as well as difficulties engaging in proper social intercourse, with significant increase in attention deficit and hyperactivity-type behaviors. To further investigate these behaviors, and to examine the potential of presently available rodent behavioral models to guide future assessments of long-term socio-emotional impairments in humans, we examined the long-term effects of GA on anxiety/fear and social behaviors. We exposed male and female Sprague-Dawley infant rats at the peak of their synaptogenesis to either GA containing midazolam (9 mg/kg, i.p.), 70% nitrous oxide (N2O) and 0.75% isoflurane (Iso) administered in 29-30% oxygen (experimental), or air (with 30% oxygen) plus the vehicle, 0.1% dimethyl sulfoxide (Sham) for 6 h. Behavioral experiments were conducted at adolescence (the open-field test) and young adulthood (the open-field test, the elevated plus-maze and the social novelty test). We report that an early exposure to GA during critical stages of brain development results in long-lasting increase in risk-taking tendencies and significant changes in the anxiety-related behaviors when tested in young adult rats. In addition, we noted novelty-seeking tendencies/less guarded behavior with changes in social discrimination. We conclude that early exposure to anesthesia may have lasting influences on emotional and social development. Importantly, our results show that currently used rodent behavioral models could be a good correlate to assess long-term socio-emotional GA-induced impairments observed in humans.


Effects of ectopic expression of NGAL on doxorubicin sensitivity.
Neutrophil gelatinase-associated lipocalin (NGAL, a.k.a Lnc2) is a member of the lipocalin family which has diverse roles including stabilizing matrix metalloproteinase-9 from auto-degradation and as siderocalins which are important in the transport of iron. NGAL also has important biological functions involved in immunity and inflammation as well as responses to kidney damage. NGAL expression has also been associated with certain neoplasia and is important in the metastasis of breast cancer. Many advanced cancer patients have elevated levels of NGAL in their urine and it has been proposed that NGAL may be a prognostic indicator for certain cancers (e.g. breast, brain, and others). NGAL expression is detected in response to various chemotherapeutic drugs including doxorubicin and docetaxel. We were interested in the roles of NGAL expression in cancer and whether it is associated with chemotherapeutic drug resistance. In the present study, we investigated whether increased NGAL expression led to resistance to the chemotherapeutic drug doxorubicin in normal breast epithelial cells (MCF-10A), breast cancer cells (MCF-7), and colorectal cancer cells (HT-29). We infected the various cell lines with a retrovirus encoding NGAL which we constructed. Increased NGAL expression was readily detected in the NGAL-infected cells but not the empty vector-infected cells. However, increased NGAL expression did not alter the sensitivity of the cells to the chemotherapeutic drug doxorubicin. Thus, although NGAL expression is often detected after chemotherapeutic drug treatment, it by itself, does not lead to doxorubicin resistance.


Lifetime risk of melanoma in CDKN2A mutation carriers in a population-based sample.
Germline mutations in the CDKN2A gene have been linked to melanoma incidence in many families with multiple cases of the disease. Previous studies of multiple-case families have indicated that the lifetime risk (i.e., penetrance) of melanoma in CDKN2A mutation carriers is very high, ranging from 58% in Europe to 91% in Australia by age 80 years. In this study, we examined lifetime melanoma risk among CDKN2A mutation carriers using carriers who were identified in a population-based study of melanoma. Probands for the study were incident case patients with either first or subsequent melanoma who were identified in nine geographic regions in Australia, Canada, the United States, and Italy. A total of 3626 probands (53% participation rate) with adequate DNA for analysis were recruited and genotyped for CDKN2A mutations. From the 3550 probands whose DNA could be amplified by polymerase chain reaction of CDKN2A exons 1alpha, 2, and 3 and surrounding regions, 65 mutation carriers were identified. Melanoma histories in first-degree relatives of these probands were used to calculate the lifetime risk in CDKN2A mutation carriers using the kin-cohort method. The risk of melanoma in CDKN2A mutation carriers was approximately 14% (95% CI = 8% to 22%) by age 50 years, 24% (95% CI = 15% to 34%) by age 70 years, and 28% (95% CI = 18% to 40%) by age 80 years. Eighteen probands had three or more first-degree relatives with melanoma, but only one was a carrier of a CDKN2A mutation. CDKN2A mutation carriers in the general population have a much lower risk of melanoma than that suggested by estimates obtained from multiple-case families. The preponderance of familial clustering of melanoma occurs in families without identifiable mutations in CDKN2A.


Treatment effects on serum lipoprotein lipids, apolipoproteins and low density lipoprotein particle size and relationships of lipoprotein variables to progression of coronary artery disease in the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT).
To investigate the mechanisms by which bezafibrate retarded the progression of coronary lesions in the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT), we examined the relationships of on-trial lipoproteins and lipoprotein subfractions to the angiographic outcome measurements. BECAIT, the first double-blind, placebo-controlled, randomized serial angiographic trial of a fibrate compound, showed that progression of focal coronary atherosclerosis in young survivors of myocardial infarction could be retarded by bezafibrate treatment. A total of 92 dyslipoproteinemic men who had survived a first myocardial infarction before the age of 45 years were randomly assigned to treatment for 5 years with bezafibrate (200 mg three times daily) or placebo; 81 patients underwent baseline and at least one post-treatment coronary angiography. In addition to the decrease in very low density lipoprotein (VLDL) cholesterol (-53%) and triglyceride (-46%) and plasma apolipoprotein (apo) B (-9%) levels, bezafibrate treatment resulted in a significant increase in high density lipoprotein-3 (HDL3) cholesterol (+9%) level and a shift in the low density lipoprotein (LDL) subclass distribution toward larger particle species (peak particle diameter +032 nm). The on-trial HDL3 cholesterol and plasma apo B concentrations were found to be independent predictors of the changes in mean minimum lumen diameter (r=-0.23, p < 0.05), and percent (%) stenosis (r = 0.30, p < 0.01), respectively. Decreases in small dense LDL and/or VLDL lipid concentrations were unrelated to disease progression. Our results suggest that the effect of bezafibrate on progression of focal coronary atherosclerosis could be at least partly attributed to a rise in HDL3 cholesterol and a decrease in the total number of apo B-containing lipoproteins.


Cryptic paraflagellar rod in endosymbiont-containing kinetoplastid protozoa.
Cilia and flagella are central to many biological processes in a diverse range of organisms. The kinetoplastid protozoa are very appealing models for the study of flagellar function, particularly in the light of the availability of extensive trypanosomatid genome information. In addition to the highly conserved 9 + 2 axoneme, the kinetoplastid flagellum contains a characteristic paraflagellar rod structure (PFR). The PFR is necessary for full motility and provides support for metabolic regulators that may influence flagellar beating. However, there is an intriguing puzzle: one clade of endosymbiont-containing kinetoplastids apparently lack a PFR yet are as motile as species that possess a PFR and are able to attach to the invertebrate host epithelia. We investigated how these organisms are able to locomote despite the apparent lack of PFR. Here we have identified a PFR1 gene in the endosymbiont-bearing trypanosome Crithidia deanei. This gene is expressed in C. deanei and is able to partially complement a pfr1 null mutation in Leishmania mexicana cells, demonstrating that the encoded protein is functional. Careful reexamination of C. deanei flagellar ultrastructure revealed a greatly reduced PFR missed by many previous analyses. This affirms the PFR as a canonical organelle of kinetoplastids. Moreover, although PFR proteins have been conserved in evolution, primary sequence differences contribute to particular PFR morphotypes characteristic of different kinetoplastid species.


Patient Decision Aids to Engage Adults in Treatment or Screening Decisions.
Are patient decision aids (PtDAs) associated with (1) improved decision quality defined as a decision informed by the evidence and a value-based decision; (2) improved decision-making processes defined as feeling informed, defining clear values related to the decision, and active participation in making the decision; and (3) better patient and health system outcomes compared with either usual care or a non-PtDA intervention? Patient decision aids are associated with improved decision quality and decision-making processes without worse patient or health system outcomes.


[Effects of a palliative care program based on home care nursing].
This study was done to develop and test a palliative care program based on home care nursing. A quasi-experimental design was employed. Changes in the variables were evaluated to test effects of the developed program. Participants were patients with terminal cancer and their families receiving home care nursing from six hospitals (experimental group: 24 and control group: 22). Data collection was conducted from February to October, 2006. chi-square test, Fisher's exact test, t-test, Mann-Whitney U test and repeated measures ANOVA were used to analyse the data. Hypothesis 1, the experimental group receiving this program will experience less pain (severe, average, weak pain) than the control group, was supported. Hypothesis 2, the experimental group will have less symptom experience than the control group, was supported. Hypothesis 3, the experimental group will have higher QOL than the control group, was supported and the last hypothesis 4, family burden in the experimental group will be less than the control group, was supported. The home care nursing based palliative program developed in this study was found to be an effective program to reduce patient pain and symptom experience, to improve patient QOL and to decrease family burden.


Gaussian filters and filter synthesis using a Hermite/Laguerre neural network.
A neural network for calculating the correlation of a signal with a Gaussian function is described. The network behaves as a Gaussian filter and has two outputs: the first approximates the noisy signal and the second represents the filtered signal. The filtered output provides improvement by a factor of ten in the signal-to-noise ratio. A higher order Gaussian filter was synthesized by combining several Hermite functions together.


Development of a practical approach to expert elicitation for randomised controlled trials with missing health outcomes: Application to the IMPROVE trial.
The analyses of randomised controlled trials with missing data typically assume that, after conditioning on the observed data, the probability of missing data does not depend on the patient's outcome, and so the data are 'missing at random' . This assumption is usually implausible, for example, because patients in relatively poor health may be more likely to drop out. Methodological guidelines recommend that trials require sensitivity analysis, which is best informed by elicited expert opinion, to assess whether conclusions are robust to alternative assumptions about the missing data. A major barrier to implementing these methods in practice is the lack of relevant practical tools for eliciting expert opinion. We develop a new practical tool for eliciting expert opinion and demonstrate its use for randomised controlled trials with missing data. We develop and illustrate our approach for eliciting expert opinion with the IMPROVE trial (ISRCTN 48334791), an ongoing multi-centre randomised controlled trial which compares an emergency endovascular strategy versus open repair for patients with ruptured abdominal aortic aneurysm. In the IMPROVE trial at 3 months post-randomisation, 21% of surviving patients did not complete health-related quality of life questionnaires (assessed by EQ-5D-3L). We address this problem by developing a web-based tool that provides a practical approach for eliciting expert opinion about quality of life differences between patients with missing versus complete data. We show how this expert opinion can define informative priors within a fully Bayesian framework to perform sensitivity analyses that allow the missing data to depend upon unobserved patient characteristics. A total of 26 experts, of 46 asked to participate, completed the elicitation exercise. The elicited quality of life scores were lower on average for the patients with missing versus complete data, but there was considerable uncertainty in these elicited values. The missing at random analysis found that patients randomised to the emergency endovascular strategy versus open repair had higher average (95% credible interval) quality of life scores of 0.062 (-0.005 to 0.130). Our sensitivity analysis that used the elicited expert information as pooled priors found that the gain in average quality of life for the emergency endovascular strategy versus open repair was 0.076 (-0.054 to 0.198). We provide and exemplify a practical tool for eliciting the expert opinion required by recommended approaches to the sensitivity analyses of randomised controlled trials. We show how this approach allows the trial analysis to fully recognise the uncertainty that arises from making alternative, plausible assumptions about the reasons for missing data. This tool can be widely used in the design, analysis and interpretation of future trials, and to facilitate this, materials are available for download.


Periodontal status and self-reported systemic health of periodontal patients regularly visiting dental clinics in the 8020 Promotion Foundation Study of Japanese Dental Patients.
This nationwide cross-sectional survey investigated the association between periodontal disease and self-reported systemic health in periodontal patients who regularly visited private dental clinics in Japan. Data from 999 patients of 444 dental clinics were analyzed; the patients were aged 40 years or older, regularly visited dentists, and had diagnosed periodontal disease (defined as two or more teeth with a clinical attachment level ≥6 mm). Medical history was collected with a self-reported questionnaire. Number of teeth with a probing pocket depth (PPD) ≥5 mm was used to define periodontal status, and the highest quartile was used as the dependent variable. A Poisson regression model showed that histories of diabetes and hypertension were associated with a larger number of teeth with a PPD ≥5 mm (diabetes: prevalence rate ratio [PRR] 1.36, 95% confidence interval [CI] 1.00-1.85; hypertension: PRR 1.27, 95% CI 1.02-1.58) after adjusting for potential periodontal risk factors. These findings suggest that diabetes and hypertension are associated with worse periodontal disease. Dentists should confirm the diabetes and hypertension status of patients who receive maintenance care, because these conditions could affect periodontal management of patients.


Nocardia crassostreae sp. nov., the causal agent of nocardiosis in Pacific oysters.
Seven strains of bacteria were isolated from Pacific oysters, Crassostrea gigas, with a focal or systemic disease. The strains were aerobic, Gram-positive, acid-fast, produced a mycelium which fragmented into irregular rod-like elements, had a peptidoglycan containing meso-diaminopimelic acid, arabinose and galactose as major sugars, mycolic acids with 46-58 carbon atoms and G + C-rich DNA. All of these properties are consistent with the classification of the organisms in the genus Nocardia. A partial sequence of the 16S rRNA gene of isolate NB4H was determined following isolation and cloning of the PCR-amplified gene. The sequence was aligned with those of representative mycolic-acid-containing taxa and a phylogenetic tree was generated using the neighbour-joining method. It was evident from the phylogenetic tree that the three strains tested, RB1, OB3P and NB4H, were identical and belonged to the Nocardia otitidiscaviarum rRNA sub-group. The biochemical, chemical, morphological and physiological properties of the isolates were also essentially identical and served to distinguish them from representative nocardiae. It is, therefore, proposed that the strains isolated from the diseased Pacific oysters be assigned to a new species, Nocardia crassostreae. The type strain is NB4H (= ATCC 700418).


Two lives intertwined: pregnancy-associated breast cancer.
The incidence of concurrent breast cancer and pregnancy (also known as pregnancy-associated breast cancer [PABC]) may increase as women delay child bearing. Because of the physiologic changes associated with pregnancy, diagnosis often is delayed, lending to poorer prognostic factors on presentation. Therefore, the clinical challenge in managing PABC involves controlling the cancer while maximizing survival outcomes for the expectant mother without compromising the health and safety of the fetus. Collaboration and communication between multidisciplinary team members are crucial. Education is key in providing a general overview of available diagnostic modalities, endorsing the multidisciplinary approach to care and treatment for the mother and fetus, and identifying the oncology nursing role specific to this patient population. Women with PABC must be kept informed of all aspects of care to ensure active participation in the decision-making process, as they are not only concerned for their own well-being but also that of their unborn child. Anxiety levels often run high and steady communication offers a modicum of control to this already-stressed patient population.