Combined GPS/GLONASS precise point positioning with fixed GPS ambiguities.
Precise point positioning (PPP) technology is mostly implemented with an ambiguity-float solution. Its performance may be further improved by performing ambiguity-fixed resolution. Currently, the PPP integer ambiguity resolutions (IARs) are mainly based on GPS-only measurements. The integration of GPS and GLONASS can speed up the convergence and increase the accuracy of float ambiguity estimates, which contributes to enhancing the success rate and reliability of fixing ambiguities. This paper presents an approach of combined GPS/GLONASS PPP with fixed GPS ambiguities (GGPPP-FGA) in which GPS ambiguities are fixed into integers, while all GLONASS ambiguities are kept as float values. An improved minimum constellation method (MCM) is proposed to enhance the efficiency of GPS ambiguity fixing. Datasets from 20 globally distributed stations on two consecutive days are employed to investigate the performance of the GGPPP-FGA, including the positioning accuracy, convergence time and the time to first fix (TTFF). All datasets are processed for a time span of three hours in three scenarios, i.e., the GPS ambiguity-float solution, the GPS ambiguity-fixed resolution and the GGPPP-FGA resolution. The results indicate that the performance of the GPS ambiguity-fixed resolutions is significantly better than that of the GPS ambiguity-float solutions. In addition, the GGPPP-FGA improves the positioning accuracy by 38%, 25% and 44% and reduces the convergence time by 36%, 36% and 29% in the east, north and up coordinate components over the GPS-only ambiguity-fixed resolutions, respectively. Moreover, the TTFF is reduced by 27% after adding GLONASS observations. Wilcoxon rank sum tests and chi-square two-sample tests are made to examine the significance of the improvement on the positioning accuracy, convergence time and TTFF.


Ancel Keys: The legacy of a giant in physiology, nutrition, and public health.
Ancel Keys, whose life spanned over 100 years (1904-2004), made a wealth of seminal scientific and public health contributions. As a physiologist, nutritionist, and public health scientist, he has left his mark on the 20th century by exploring different areas of physiology and nutrition, as well as by contributing to the understanding of basic public health issues. Among his major achievements one can mention in chronological order: studying adaptation to very high altitude, developing the K ration to enable the US military to survive with light but dense food, dissecting the physiology of starvation and nutritional rehabilitation to optimize recovery of functions, uncovering the link between serum cholesterol and heart disease, coordinating the first multi-country epidemiological longitudinal study in nutrition and health, coining the word "body mass index" (BMI), which he showed to be the best body weight index to predict body fat, and promoting the Mediterranean diet for a healthy life style. This review examines the historical events and scientific intrigues that have surrounded Ancel Keys's major classical studies that have ensured him a central place in the history of medical science.


Plate tectonics of virus shell assembly and reorganization in phage φ8, a distant relative of mammalian reoviruses.
The hallmark of a virus is its capsid, which harbors the viral genome and is formed from protein subunits, which assemble following precise geometric rules. dsRNA viruses use an unusual protein multiplicity (120 copies) to form their closed capsids. We have determined the atomic structure of the capsid protein (P1) from the dsRNA cystovirus Φ8. In the crystal P1 forms pentamers, very similar in shape to facets of empty procapsids, suggesting an unexpected assembly pathway that proceeds via a pentameric intermediate. Unlike the elongated proteins used by dsRNA mammalian reoviruses, P1 has a compact trapezoid-like shape and a distinct arrangement in the shell, with two near-identical conformers in nonequivalent structural environments. Nevertheless, structural similarity with the analogous protein from the mammalian viruses suggests a common ancestor. The unusual shape of the molecule may facilitate dramatic capsid expansion during phage maturation, allowing P1 to switch interaction interfaces to provide capsid plasticity.


Sequence of the peh gene of Erwinia carotovora: homology between Erwinia and plant enzymes.
Polygalacturonase (Peh) and other pectolytic enzymes play a crucial role in the maceration of vegetables by soft rot Erwinia spp. We have sequenced the peh gene of Erwinia carotovora subsp. carotovora, and identified its product as a precursor of molecular weight 42,639, and a mature protein of molecular weight 42,200. A putative KdgR-binding site was identified in the region 5' to the peh gene. The Peh protein showed significant homology with Peh from tomato. In addition, we have found homologies between pectin methylesterase and pectate lyase from Erwinia and their counterparts in tomato. These homologies are described, and their significance discussed.


Echocardiographic assessment of right ventricular systolic function.
Assessment of right chamber function has become increasingly popular and important in recent decades, complementing the evaluation of left chamber functional parameters. The late adoption and integration of right ventricular (RV) function into a complete evaluation of cardiac function could be due in part to the difficulty in visualization of the whole right ventricle, inconsistency in the analysis of RV parameters, and poor understanding of the impact of RV function on prognosis. From M-mode to 2-dimensional (2D) measurements of RV size and function, there have been arrays of parameters that provide important information of the right ventricle. However, there are limitations of using 2D echocardiography to quantify RV volume and ejection fraction (EF), and currently accurate measurements of RV volumes and EF can be obtained using cardiac magnetic resonance (CMR) imaging. Using 3-dimensional echocardiography (3DE), the measurements of RV volumes and EF have become feasible and reproducible. Importantly, 3D measurements have been validated against CMR with higher correlation compared to 2D measurements. With the establishment of reference values, 3D echocardiography determined RV volumes and EF have the potential for better understanding of RV function and exploration of its significance for outcome research in various clinical scenarios.


Relationships between reward sensitivity, risk-taking and family history of alcoholism during an interactive competitive fMRI task.
Individuals with a positive family history for alcoholism (FHP) have shown differences from family-history-negative (FHN) individuals in the neural correlates of reward processing. FHP, compared to FHN individuals, demonstrate relatively diminished ventral striatal activation during anticipation of monetary rewards, and the degree of ventral striatal activation shows an inverse correlation with specific impulsivity measures in alcohol-dependent individuals. Rewards in socially interactive contexts relate importantly to addictive propensities, yet have not been examined with respect to how their neural underpinnings relate to impulsivity-related measures. Here we describe impulsivity measures in FHN and FHP individuals as they relate to a socially interactive functional magnetic resonance imaging (fMRI) task. Forty FHP and 29 FHN subjects without histories of Axis-I disorders completed a socially interactive Domino task during functional magnetic resonance imaging and completed self-report and behavioral impulsivity-related assessments. FHP compared to FHN individuals showed higher scores (p = .004) on one impulsivity-related factor relating to both compulsivity (Padua Inventory) and reward/punishment sensitivity (Sensitivity to Punishment/Sensitivity to Reward Questionnaire). Multiple regression analysis within a reward-related network revealed a correlation between risk-taking (involving another impulsivity-related factor, the Balloon Analog Risk Task (BART)) and right ventral striatum activation under reward >punishment contrast (p<0.05 FWE corrected) in the social task. Behavioral risk-taking scores may be more closely associated with neural correlates of reward responsiveness in socially interactive contexts than are FH status or impulsivity-related self-report measures. These findings suggest that risk-taking assessments be examined further in socially interactive settings relevant to addictive behaviors.


Quality of survival among children treated for brain stem glioma.
In order to describe the status of long-term survivors of brain stem glioma, neuropsychological and behavioral measures were obtained a median of 2.5 (range 1.5-5.6) years after diagnosis from 16 survivors of 51 consecutively diagnosed children with brain stem glioma between 1983 and 1991. Among 11 children with dorsally exophytic tumors, 7 were treated with surgery alone (SRG) and 4 received conventionally fractionated local cranial radiation therapy (CFRT; 54-56 Gy) to the brain stem following surgery, 3 of these because of recurrent disease. Five others with diffusely infiltrative brain stem tumors received hyperfractionated radiation therapy (HFRT; 70.2 Gy) to the brain stem; 4 following biopsy or limited resection and 1 without prior surgery. IQs of children in the CFRT (mean 89, SD 24.4) and HFRT (mean 85, SD 12.7) groups were not significantly different. Children in the SRG group had significantly higher IQs (mean 100, SD 11.0) and fewer neurologic deficits than those who had received CFRT or HFRT. However, after statistically controlling for severity of neurologic deficits, treatment had no effect on IQ. The severity of residual neurologic deficits accounted for 42% of the variance in IQ scores; children with fewer neurologic problems scored higher. Additional studies are required to evaluate the potential neuropsychological benefits of equivalent total doses of HFRT compared to CFRT.


Evaluating mercury biomagnification in fish from a tropical marine environment using stable isotopes (delta13C and delta15N).
Concentrations of total mercury (T-Hg) and methylmercury (MeHg) were measured in zooplankton and 13 fish species from a coastal food web of the Gulf of Oman, an arm of the Arabian Sea between Oman and Iran. Stable isotope ratios (delta13C and delta15N) also were determined to track mercury biomagnification. The average concentration of T-Hg in zooplankton was 21 +/- 8.0 ng g(-1) with MeHg accounting 10% of T-Hg. Total mercury levels in fish species ranged from 3.0 ng g(-1) (Sardinella longiceps) to 760 ng g(-1) (Rhizoprionodon acutus) with relatively lower fraction of MeHg (72%) than that found in other studies. The average trophic difference (Deltadelta13C) between zooplankton and planktivorous fish (Selar crumenopthalmus, Rastrelliger kanagurta, and S. longiceps) was higher (3.4 per thousandth) than expected, suggesting that zooplankton may not be the main diet or direct carbon source for these fish species. However, further sampling would be required to compensate for temporal changes in zooplankton and the influence of their lipid content. Trophic position inferred by delta15N and and slopes of the regression equations (log10[T-Hg] = 0.13[delta15N] - 3.57 and log10[MeHg] = 0.14[delta15N] - 3.90) as estimates of biomagnification indicate that biomagnification of T-Hg and MeHg was lower in this tropical ocean compared to what has been observed in arctic and temperate ecosystems and tropical African lakes. The calculated daily intake of methylmercury in the diet of local people through fish consumption was well below the established World Health Organization (WHO) tolerable daily intake threshold for most of the fish species except Euthynnus affinis, Epinephelus epistictus, R. acutus, and Thunnus tonggol, illustrating safe consumption of the commonly consumed fish species.


Phylogenetic relationships of necrogenic Erwinia and Brenneria species as revealed by glyceraldehyde-3-phosphate dehydrogenase gene sequences.
Recent examination of the relationships of the dry necrosis-inducing (necrogenic) erwinias using 16S rDNA sequences demonstrated that these bacteria comprise a polyphyletic group and, therefore, have been subdivided into three distinct genera, Erwinia, Brenneria and Pectobacterium, with the classical 'amylovora' group species now being distributed nearly evenly among the first two. To further assess the molecular evolutionary relationships between current necrogenic Erwinia and Brenneria species, as well as between these genera and the exclusively soft-rotting genus Pectobacterium, the glyceraldehyde-3-phosphate dehydrogenase (gapDH) genes from 57 Erwinia and Brenneria isolates along with Pectobacterium type strains were PCR-amplified, sequenced and subjected to phylogenetic analysis. Pairwise alignments of cloned gapDH genes revealed remarkably high interspecies genetic diversity among necrogenic isolates. Four evolutionary clades of necrogenic species were described that assorted more closely to known soft-rotting species than to each other. Interclade comparisons of gapDH nucleotide sequences revealed as much genetic divergence between these four necrogenic clades as existed between necrogenic and soft-rotting clades. An examination of the phylogenetic utility of the gapDH gene in light of current 16S rDNA clustering of these species revealed varying levels of taxonomic congruence between these genes for the structure of Erwinia, Brenneria and Pectobacterium. These analyses suggest that, while gapDH possesses sufficient genetic variation to fully differentiate Erwinia and Brenneria species, the gene may not accurately reflect interspecies taxonomic relatedness among all three phytopathogenic genera.


Perceived social support as a predictor of disease-specific quality of life in head-and-neck cancer patients.
Treatment for head-and-neck cancer (HNC) can lead to severe decrements in disease-specific quality of life (DSQOL) due to disfigurement and disability in speech, eating, and/or breathing. Psychosocial factors such as social support may explain individual variance in DSQOL outcomes. The researchers sought to evaluate changes in perceived availability of social support from pretreatment to posttreatment and to determine whether decreases in perceived social support predicted poorer posttreatment DSQOL among HNC patients, controlling for disease- and treatment-related factors. Participants (n = 32) were newly diagnosed with HNC and were awaiting surgery and/or radiation treatment. Measures included the ENRICHD Social Support instrument (ESSI) to assess perceived social support and the Functional Assessment of Cancer Therapy-Head & Neck (FACT-H&N) to assess DSQOL. Paired-samples t-tests and hierarchical regression analyses were conducted to determine relationships between pretreatment and posttreatment perceived social support and DSQOL. Perceived social support decreased significantly from pre- to posttreatment (F[31] = -2.71, P < .01). After adjusting for relevant covariates and pretreatment DSQOL, change in perceived social support remained a significant predictor of posttreatment DSQOL (β = .47, P < .01). This study included a relatively small sample of HNC patients, which limited power to evaluate mechanisms of observed relationships. Increased social isolation may be a risk factor for poorer physical recovery from, or adjustment to, treatment-related side effects. Social support may be an important target for psychosocial interventions for patients who face challenging treatment side effects.


3D polymer directional coupler for on-board optical interconnects at 1550 nm.
We propose three-dimensional (3D) polymer directional couplers operating at 1550 nm for on-board optical interconnects. The proposed directional coupler can realize free-position light coupling and splitting in three dimension and can be cascaded to serve as an effective and scalable device for multi-layer and multi-channel interconnects. The 3D directional coupler was fabricated with commercially available UV-curable epoxies by combining the use of a needle-type liquid micro-dispenser and a 3-axis robot stage. The main parameters of the 3D directional coupler such as the interaction length, coupling ratio, coupling position, and cascade numbers can be easily adjusted. In the experiment, single-mode two-dimensional (2D) polymer directional couplers in both horizontal and vertical directions operating at 1550 nm with different coupling ratios (CRs) were demonstrated at first. The experimental results agree with the simulated ones. A 3D directional coupler with coupling ratios of 58:23:19 at 1550 nm was then successfully fabricated using the mosquito method for the first time to the best of our knowledge. The CR varies with the wavelength as expected while the excess loss remains almost the same within C-band. The results imply that the proposed method may be applicable in the fabrication of functional devices in three dimension for high-density on-board optical interconnects with further improvement on fabrication process.


MondoA drives muscle lipid accumulation and insulin resistance.
Obesity-related insulin resistance is associated with intramyocellular lipid accumulation in skeletal muscle. We hypothesized that in contrast to current dogma, this linkage is related to an upstream mechanism that coordinately regulates both processes. We demonstrate that the muscle-enriched transcription factor MondoA is glucose/fructose responsive in human skeletal myotubes and directs the transcription of genes in cellular metabolic pathways involved in diversion of energy substrate from a catabolic fate into nutrient storage pathways including fatty acid desaturation and elongation, triacylglyeride (TAG) biosynthesis, glycogen storage, and hexosamine biosynthesis. MondoA also reduces myocyte glucose uptake by suppressing insulin signaling. Mice with muscle-specific MondoA deficiency were partially protected from insulin resistance and muscle TAG accumulation in the context of diet-induced obesity. These results identify MondoA as a nutrient-regulated transcription factor that under normal physiological conditions serves a dynamic checkpoint function to prevent excess energy substrate flux into muscle catabolic pathways when myocyte nutrient balance is positive. However, in conditions of chronic caloric excess, this mechanism becomes persistently activated leading to progressive myocyte lipid storage and insulin resistance.


Exploring patterns and pattern languages of medical education.
The practices and concepts of medical education are often treated as global constants even though they can take many forms depending on the contexts in which they are realised. This represents challenges in presenting and appraising medical education research, as well as in translating practices and concepts between different contexts. This paper explores the problem and seeks to respond to its challenges. This paper explores the application of architectural theorist Christopher Alexander's work on patterns and pattern languages to medical education. The authors review the underlying concepts of patterns and pattern language, they consider the development of pattern languages in medical education, they suggest possible applications of pattern languages for medical education and they discuss the implications of such use. Examples are drawn from across the field of medical education. The authors argue that the deliberate and systematic use of patterns and pattern languages in describing medical educational activities, systems and contexts can help us to make sense of the world, and the pattern languages of medical education have the potential to advance understanding and scholarship in medical education, to drive innovation and to enable critical engagement with many of the underlying issues in this field.


Population, development, and climate change: links and effects on human health.
Global health, population growth, economic development, environmental degradation, and climate change are the main challenges we face in the 21st century. However, because the academics, non-governmental organisations, and policy makers in these specialties work within separate communities, our understanding of the associations between them is restricted. We organised an international symposium in May, 2011 in London, UK, for academics and technical experts from population, developmental, and environmental science to encourage debate and collaboration between these disciplines. The conference provided the impetus for this Review, which describes, in historical context, key events and fundamental intercommunity debates from the perspectives of population, development, and climate change communities. We consider the interconnections between population, development, and climate change and their effects on health, including new analysis of longstanding debates, and identify opportunities for effective collaboration on shared goals.


Fish oil supplementation improves large arterial elasticity in overweight hypertensive patients.
To observe the effect of fish oil supplementation on arterial elasticity and blood pressure (BP) in overweight hypertensive patients. This was a double-blind, randomized and placebo-controlled clinical study, in which 52 overweight hypertensive patients from a community were selected and randomly allocated to two groups (26 in the fish oil group (3 g day(-1), fish oil capsules) and 26 in the placebo group (only capsules). All the subjects were follow-up for 8 weeks. The arterial elasticity was determined by CVProfilor DO-2020 and expressed as elasticity indexes (C(1)-large artery and C(2)-small artery). During the follow-up, totally nine cases were dropped out (three cases from the fish oil group and six cases from the placebo group). After 8 weeks follow-up, the large artery elasticity in the fish oil group, compared with its baseline, was significantly improved (C(1): 15.5+/-1.5 vs 12.8+/-3.7 ml mm Hg(-1) x 10), whereas no effects were found in the placebo group (C(1): 13.0+/-3.4 vs 13.4+/-3.8 ml mm Hg(-1) x 10), P=0.027, RM-ANOVA across the two groups. The small artery elasticity (C(2)), BP and pulse pressure were not found any changes, either in the fish oil group or in the placebo group. At same time, the serum soluble vascular cell adhesion molecule-1(sVCAM-1) and leptin levels, the lipid profile and insulin sensitivity index (ISI) as well, did not show significant differences between two groups. Fish oil supplementation certainly would improve large arterial elasticity but no effect on BP in overweight hypertensive patients. Further study is needed to confirm the benefits of fish oil supplementation on age-related increases in arterial stiffness.


The molecular pathology of urological malignancies.
Urological malignancies kill over 16,000 people annually in England and Wales. There have been exciting recent developments in our understanding of the molecular pathogenesis of these diseases, although many questions remain unanswered. Three separate genes (WT1, WT2, and WT3) have been implicated in Wilms' tumour development. Patients with von Hippel-Lindau (VHL) syndrome develop renal cell carcinoma and it has been shown that VHL protein inhibits elongin, a cellular transcription factor which controls RNA elongation. Use of molecular markers to identify superficial bladder tumours likely to progress to muscle invasive disease has met with some success. Increased epidermal growth factor receptor (EGFR) and p53 expression, and decreased E-cadherin expression all correlate with tumour progression. Tumours in patients with carcinoma in situ have distinct molecular features. Androgen ablation delays disease progression in men with prostate cancer, but relapse is inevitable. Research has been directed towards elucidating the mechanisms by which prostate cancer 'escapes' hormonal control. Mutations in the androgen receptor have been identified. It is apparent that locally produced growth factors mediate androgen-dependent processes and these too have been implicated in prostate carcinogenesis.


Evaluation of fasting plasma glucose as screening test for NIDDM in older adults. Rancho Bernardo Study.
To examine the efficiency of fasting plasma glucose (FPG) as a screening test for non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH AND METHODS DESIGN: A population-based evaluation was made of FPG as screening test for NIDDM in an upper middle-class white community of Rancho Bernardo, California. NIDDM was defined by 2-h postchallenge plasma glucose (PCPG) level greater than or equal to 11.1 mM, the cutoff point recommended by the World Health Organization. Participants comprised a population-based sample of 1851 men and women 50-79 yr of age that represented 80% of surviving participants surveyed between 1972 and 1974 for the Lipid Research Clinic Prevalence Study. Those with insulin-dependent diabetes were excluded. Analyses were stratified by age after logistic regression indicated that FPG and age (but not gender) were significantly related to probability of disease. As FPG cutoff points increased, sensitivity and percentage of the population to be recalled for confirmation decreased, whereas specificity and positive predictive value increased. Negative predictive value was consistently in the 90% range. Specificity did not change with age. In contrast, at virtually every FPG cutoff point, sensitivity decreased with increasing age. For example, at FPG greater than or equal to 6.7 mM, sensitivity was 65.6% for those 50-64 yr of age and 40.0% for those 65-79 yr of age. At FPG greater than or equal to 7.2 mM, these sensitivities were 46.9 and 28.5%, respectively. Positive predictive value increased with increasing age, reflecting the increasing prevalence of NIDDM with age. Poorer sensitivity with increasing age reflects the fact that the numerator of the sensitivity equation is not affected by age (mean FPG did not vary significantly between age-groups), whereas the denominator increases with age (mean PCPG increased from 6.6 mM for subjects 50-64 yr of age to 8.2 mM for subjects 65-79 yr of age). Nevertheless, because the clinical significance of increasing PCPG with age in older adults is unknown, age-specific screening criteria probably are not warranted.


13.1 W, high-beam-quality, narrow-linewidth continuous-wave fiber-based source at 970 nm.
We report an efficient fiber-laser-based source of high-power, continuous-wave (cw), linearly-polarized radiation at 970 nm in a simple, compact, and practical design. Using direct single-pass second-harmonic-generation (SP-SHG) of a cw thulium fiber laser at 1940 nm in a 40-mm-long periodically-poled LiNbO3 (PPLN) crystal, we have generated 13.1 W of output power at 970 nm for a fundamental power of 40 W at a conversion efficiency as high as 32.7%. The generated second-harmonic output exhibits a passive power stability better than 1.4% (1σ value) over 1 hour, has a linewidth better than 0.3 nm, and a TEM(00) spatial beam profile with M(2)<1.6. Relevant theoretical calculations for the characterization of SP-SHG in the crystal have also been performed.


Pre-stimulus functional networks modulate task performance in time-pressured evidence gathering and decision-making.
Rapid perceptual decision-making is believed to depend upon efficient allocation of neural resources to the processing of transient stimuli within task-relevant contexts. Given decision-making under severe time pressure, it is reasonable to posit that the brain configures itself, prior to processing stimulus information, in a way that depends upon prior beliefs and/or anticipation. However, relatively little is known about such configuration processes, how they might be manifested in the human brain, or ultimately how they mediate task performance. Here we show that network configuration, defined via pre-stimulus functional connectivity measures estimated from functional magnetic resonance imaging (fMRI) data, is predictive of performance in a time-pressured Go/No-Go task. Specifically, using connectivity measures to summarize network properties, we show that pre-stimulus brain state can be used to discriminate behaviorally correct and incorrect trials, as well as behaviorally correct commission and omission trial categories. More broadly, our results show that pre-stimulus functional configurations of cortical and sub-cortical networks can be a major determiner of task performance.


Nuclear and unclear functions of SUMO.
Post-translational modification by the ubiquitin-like SUMO protein is emerging as a defining feature of eukaryotic cells. Sumoylation has crucial roles in the regulatory challenges that face nucleate cells, including the control of nucleocytoplasmic signalling and transport and the faithful replication of a large and complex genome, as well as the regulation of gene expression.


Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial.
Patients with muscle-invasive urothelial carcinoma of the bladder have poor survival after cystectomy. The EORTC 30994 trial aimed to compare immediate versus deferred cisplatin-based combination chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder. This intergroup, open-label, randomised, phase 3 trial recruited patients from hospitals across Europe and Canada. Eligible patients had histologically proven urothelial carcinoma of the bladder, pT3-pT4 disease or node positive (pN1-3) M0 disease after radical cystectomy and bilateral lymphadenectomy, with no evidence of any microscopic residual disease. Within 90 days of cystectomy, patients were centrally randomly assigned (1:1) by minimisation to either immediate adjuvant chemotherapy (four cycles of gemcitabine plus cisplatin, high-dose methotrexate, vinblastine, doxorubicin, and cisplatin [high-dose MVAC], or MVAC) or six cycles of deferred chemotherapy at relapse, with stratification for institution, pT category, and lymph node status according to the number of nodes dissected. Neither patients nor investigators were masked. Overall survival was the primary endpoint; all analyses were by intention to treat. The trial was closed after recruitment of 284 of the planned 660 patients. This trial is registered with ClinicalTrials.gov, number NCT00028756. From April 29, 2002, to Aug 14, 2008, 284 patients were randomly assigned (141 to immediate treatment and 143 to deferred treatment), and followed up until the data cutoff of Aug 21, 2013. After a median follow-up of 7.0 years (IQR 5.2-8.7), 66 (47%) of 141 patients in the immediate treatment group had died compared with 82 (57%) of 143 in the deferred treatment group. No significant improvement in overall survival was noted with immediate treatment when compared with deferred treatment (adjusted HR 0.78, 95% CI 0.56-1.08; p=0.13). Immediate treatment significantly prolonged progression-free survival compared with deferred treatment (HR 0.54, 95% CI 0.4-0.73, p<0.0001), with 5-year progression-free survival of 47.6% (95% CI 38.8-55.9) in the immediate treatment group and 31.8% (24.2-39.6) in the deferred treatment group. Grade 3-4 myelosuppression was reported in 33 (26%) of 128 patients who received treatment in the immediate chemotherapy group versus 24 (35%) of 68 patients who received treatment in the deferred chemotherapy group, neutropenia occurred in 49 (38%) versus 36 (53%) patients, respectively, and thrombocytopenia in 36 (28%) versus 26 (38%). Two patients died due to toxicity, one in each group. Our data did not show a significant improvement in overall survival with immediate versus deferred chemotherapy after radical cystectomy and bilateral lymphadenectomy for patients with muscle-invasive urothelial carcinoma. However, the trial is limited in power, and it is possible that some subgroups of patients might still benefit from immediate chemotherapy. An updated individual patient data meta-analysis and biomarker research are needed to further elucidate the potential for survival benefit in subgroups of patients. Lilly, Canadian Cancer Society Research.


Reduced behavioral response to gonadal hormones in mice shipped during the peripubertal/adolescent period.
Animals shipped from commercial suppliers to laboratories are exposed to a wide variety of stressors. Female C57Bl6/J mice shipped during the peripubertal/adolescent period (6 wk old) display lower levels of female sexual behavior in response to estradiol and progesterone injections after ovariectomy when tested in adulthood than female mice shipped in adulthood (12 wk old). These shipping-induced reductions in female sexual behavior appear to be limited to a vulnerable period around the time of puberty. Likewise, male mice shipped at 6 wk of age express lower levels of masculine sexual behavior in response to testosterone treatment as adults than do mice shipped when 12 wk old. RIA of corticosterone levels in response to behavior testing revealed that, upon first exposure to testing, mice shipped at 6 wk of age have reduced corticosterone levels. These results suggest that during the peripubertal/adolescent period, mice of both sexes are susceptible to the effects of stressors associated with shipping. Furthermore, they suggest that stress during this period has enduring, negative influences on behavioral responses to estradiol and progesterone in females and to testosterone in males, and it induces changes in response of the hypothalamic-pituitary-adrenal axis. These results suggest that age at shipping is a critical variable that may influence many endocrinological studies, and they suggest that the peripubertal/adolescent period is a period of vulnerability to some stressors.


High sensitivity and specificity of the Pastorex latex agglutination test for Neisseria meningitidis serogroup A during a clinical trial in Niger.
There is a great need for a rapid diagnostic test to guide vaccine choice during outbreaks of meningococcal meningitis in resource-poor countries. During a randomised clinical trial conducted during an epidemic of Neisseria meningitidis serogroup A in Niger in 2003, the sensitivity and specificity of the Pastorex latex agglutination test for this serogroup under optimal field conditions were assessed, using culture and/or PCR as the gold standard. Results from 484 samples showed a sensitivity of 88% (95% CI 85-91%) and a specificity of 93% (95% CI 90-95%). Pastorex could be a good alternative to current methods, as it can be performed in a local laboratory with rapid results and is highly specific. Sensitivity can be improved with prior microscopy where feasible. A study specifically to evaluate the Pastorex test under epidemic conditions, using laboratories with limited resources, is recommended.


Validation of Biomarkers of CVD Risk from Dried Blood Spots in Community-Based Research: Methodologies and Study-Specific Serum Equivalencies.
Dried blood spot (DBS) methodology offers significant advantages over venipuncture in studies of vulnerable populations or large-scale studies, including reduced participant burden and higher response rates. Uncertainty about the validity of cardiovascular disease (CVD) risk biomarkers remains a barrier to wide-scale use. We determined the validity of DBS-derived biomarkers of CVD risk versus gold-standard assessments, and study-specific, serum-equivalency values for clinical relevance of DBS-derived values. Concurrent venipuncture serum and DBS samples (n = 150 adults) were assayed in Clinical Laboratory Improvement Amendments-certified and DBS laboratories, respectively. Time controls of DBS standard samples were assayed single-blind along with test samples. Linear regression analyses evaluated DBS-to-serum equivalency values; agreement and bias were assessed via Bland-Altman plots. Linear regressions of venipuncture values on DBS-to-serum equivalencies provided R(2) values for total cholesterol, high-density lipoprotein cholesterol (HDL-C), and C-reactive protein (CRP) of 0.484, 0.118, and 0.666, respectively. Bland-Altman plots revealed minimal systematic bias between DBS-to-serum and venipuncture values; precision worsened at higher mean values of CRP. Time controls revealed little degradation or change in analyte values for HDL-C and CRP over 30 weeks. We concluded that DBS-assessed biomarkers represent a valid alternative to venipuncture assessments. Large studies using DBS should include study-specific serum-equivalency determinations to optimize individual-level sensitivity, the viability of detecting intervention effects, and generalizability in community-level primary prevention interventions.


Outpatient waiting time in health services and teaching hospitals: a case study in Iran.
One of the most important indexes of the health care quality is patient's satisfaction and it takes place only when there is a process based on management. One of these processes in the health care organizations is the appropriate management of the waiting time process. The aim of this study is the systematic analyzing of the outpatient waiting time. This descriptive cross sectional study conducted in 2011 is an applicable study performed in the educational and health care hospitals of one of the medical universities located in the north west of Iran. Since the distributions of outpatients in all the months were equal, sampling stage was used. 160 outpatients were studied and the data was analyzed by using SPSS software. Results of the study showed that the waiting time for the outpatients of ophthalmology clinic with an average of 245 minutes for each patient allocated the maximum time among the other clinics for itself. Orthopedic clinic had the minimal waiting time including an average of 77 minutes per patient. The total average waiting time for each patient in the educational hospitals under this study was about 161 minutes. by applying some models, we can reduce the waiting time especially in the realm of time and space before the admission to the examination room. Utilizing the models including the one before admission, electronic visit systems via internet, a process model, six sigma model, queuing theory model and FIFO model, are the components of the intervention that reduces the outpatient waiting time.


A 17-year experience with mitral valve repair with artificial chordae in infants and children.
We sought to examine our long-term results of mitral valve (MV) repair with expanded polytetrafluoroethylene (ePTFE) sutures and to determine the predictors for the outcome of this procedure. Between 1995 and 2011, MV repair with chordal reconstruction by artificial chordae was achieved in 78 patients (34 males and 44 females). Median age at repair was 1.5 years (range 3.6 months-13.4) and weight was 9.1 kg (2.5-31.4). The mean follow-up was 8.3 years. A Cox proportional hazards model was used to analyse the risk factors for a composite outcome of death, conversion to other MV repair techniques or MV replacement, reoperation on MV and recurrent mitral regurgitation (MR). According to Carpentier classification, 65 (83.3%) patients were Type 2 and 13 (16.7%) were Type 3. Mitral annuloplasty was performed in all cases, except 2. During MV repair, 8 (10.3%) patients were ineffective with artificial chordae and converted to other techniques. Six (7.7%) patients underwent MV reoperation (three repairs and three replacements). Freedom from MV reoperation was 92.5 and 90.4% at 5 and 10 years, respectively. There was 1 in-hospital death. At the latest follow-up, moderate or more MR was observed in 3 (3.8%) patients. Risks for the composite outcome were low body weight at operation and Carpentier classification Type 3. MV repair with artificial chordae in infants and children is safe and effective and associated with a low reoperation rate. Further investigation into the long-term durability and biological adaptation of ePTFE sutures after patient growth is mandatory.


Modification of a direct enzyme-linked immunosorbent assay for the detection of immunoglobulin G and M antibodies to pneumococcal capsular polysaccharide.
In contrast to the usual indirect enzyme-linked immunosorbent assay (ELISA) method for detection of antibody responses, a modified direct ELISA technique was used to measure immunoglobulin G (IgG) and IgM responses to pneumococcal capsular types 1, 3, 9N, and 23F in humans. Individual capsular polysaccharides were covalently bound to poly-L-lysine before adsorption to the solid phase. The coupling reaction was enhanced by maintenance of a constant pH of 8.2 after the addition of all reactants. The evaluation of four diluents (phosphate-buffered saline [PBS]-Tween; PBS-Tween plus 10% fetal calf serum; PBS-Tween plus 10% bovine serum albumin; and PBS-Tween plus 20% normal goat serum) showed that the sensitivity and specificity of the assay was increased with normal goat serum (10-fold). Serum samples from 10 subjects immunized with polyvalent pneumococcal vaccine were tested by direct ELISA and by radioimmunoassay. At 4 weeks postimmunization, the ELISA method showed that IgG was the predominant antibody and that IgM responses were lower or had diminished. Isotype shifts during this period would have been undetected by the radioimmunoassay method. The changes in antibody response measured by ELISA were comparable to the radioimmunoassay results. The direct ELISA method for the detection of antipneumococcal capsular antibody has been found to be a sensitive and reproducible assay for the detection of IgG and IgM antibodies.


Co-ordinated structural and functional covariance in the adolescent brain underlies face processing performance.
Our ability to process complex social cues presented by faces improves during adolescence. Using multivariate analyses of neuroimaging data collected longitudinally from a sample of 38 adolescents (17 males) when they were 10, 11.5, 13 and 15 years old, we tested the possibility that there exists parallel variations in the structural and functional development of neural systems supporting face processing. By combining measures of task-related functional connectivity and brain morphology, we reveal that both the structural covariance and functional connectivity among 'distal' nodes of the face-processing network engaged by ambiguous faces increase during this age range. Furthermore, we show that the trajectory of increasing functional connectivity between the distal nodes occurs in tandem with the development of their structural covariance. This demonstrates a tight coupling between functional and structural maturation within the face-processing network. Finally, we demonstrate that increased functional connectivity is associated with age-related improvements of face-processing performance, particularly in females. We suggest that our findings reflect greater integration among distal elements of the neural systems supporting the processing of facial expressions. This, in turn, might facilitate an enhanced extraction of social information from faces during a time when greater importance is placed on social interactions.


Current transcatheter devices to treat functional tricuspid regurgitation with discussion of issues relevant to clinical trial design.
Functional or secondary tricuspid regurgitation (TR) has seen increased attention in recent times as relationships with clinically-relevant outcomes have come to light. Despite the association of increased mortality with significant TR, the disease remains under-recognized and thus relatively untreated. In addition, the disease itself has not been extensively studied and the interactions between annular dilatation, right heart disease and pulmonary hypertension are poorly understood. However, the high mortality and recurrence rate with current surgical replacement or repair techniques is well recognised, opening the door to transcatheter therapies for functional TR. The current perspective reviews the rationale for transcatheter solutions, describes some of the current approaches and discusses the ongoing questions of a poorly-studied condition which may limit the design of clinical trials for this disease.


Simulating the Genetics Clinic of the Future - whether undergoing whole-genome sequencing shapes professional attitudes.
Whole-genome sequencing (WGS) can provide valuable health insight for research participants or patients. Opportunities to be sequenced are increasing as direct-to-consumer (DTC) testing becomes more prevalent, but it is still fairly unusual to have been sequenced. We offered WGS to fourteen professionals with pre-existing familiarity with an interest in human genetics - healthcare, science, policy and art. Participants received a hard drive containing their personal sequence data files (.BAM,.gvcf), without further explanation or obligation, to consider how experiencing WGS firsthand might influence their professional attitudes. We performed semi-structured pre- and post-sequencing interviews with each participant to identify key themes that they raised after being sequenced. To evaluate how their experience of the procedure evolved over time, we also conducted a questionnaire to gather their views 3 years after receiving their genomic data. Participants were generally satisfied with the experience (all 14 participants would choose to participate again). They mostly decided to participate out of curiosity (personal) and to learn from the experience (professional). Whereas most participants slightly developed their original perspective on genetic data, a small selection of them radically changed their views over the course of the project. We conclude that personal experience of sequencing provides an interesting alternative perspective for experts involved in leading, planning, implementing or researching genome sequencing services. Moreover, the personal experience may provide professionals with a better understanding of the challenges visitors of the Genetics Clinic of the Future may face.


Telephone Intervention to Improve Diabetes Control: A Randomized Trial in the New York City A1c Registry.
Scalable self-management interventions are necessary to address suboptimal diabetes control, especially among minority populations. The study tested the effectiveness of a telephone behavioral intervention in improving glycemic control among adults with diabetes in the New York City A1c Registry. RCT comparing a telephone intervention to print-only intervention in the context of the A1c Registry program. Nine hundred forty-one adults with diabetes and hemoglobin A1c (A1c) >7% from a low-income, predominantly Latino population in the South Bronx were recruited from the A1c Registry. All study participants were mailed print diabetes self-management materials at baseline and modest lifestyle incentives quarterly. Only the telephone participants received four calls from health educators evenly spaced over 1 year if baseline A1c was >7%-9%, or eight calls if baseline A1c was >9%. Medication adherence was the main behavioral focus and, secondarily, nutrition and exercise. Primary outcome was difference between two study arms in change in A1c from baseline to 1 year. Secondary outcomes included diabetes self-care activities, including self-reported medication adherence. Data were collected in 2008-2012 and analyzed in 2012-2014. Participants were predominantly Latino (67.7%) or non-Latino black (28%), with 69.7% foreign-born and 55.1% Spanish-speaking. Among 694 (74%) participants with follow-up A1c, mean A1c decreased by 0.9 (SD=0.1) among the telephone group compared with 0.5 (SD=0.1) among the print-only group, a difference of 0.4 (95% CI=0.09, 0.74, p=0.01). The intervention had significant effect when baseline A1c was >9%. Both groups experienced similar improvements in self-care activities, medication adherence, and intensification. A telephone intervention delivered by health educators can be a clinically effective tool to improve diabetes control in diverse populations, specifically for those with worse metabolic control identified using a registry. This public health approach could be adopted by health systems supported by electronic record capabilities. CLINICALTRIALS. NCT00797888.


Clinical features of active tuberculosis that developed during anti-tumor necrosis factor therapy in patients with inflammatory bowel disease.
Anti-tumor necrosis factor (TNF) therapy for active ulcerative colitis (UC) and Crohn's disease (CD) is associated with increased risks of tuberculosis (TB) infection. We analyzed the incidence and clinical features of Korean patients with inflammatory bowel disease (IBD) who developed active TB during anti-TNF therapy. Ten cases of active TB developed in patients treated with infliximab (n=592) or adalimumab (n=229) for UC (n=160) or CD (n=661) were reviewed. We analyzed demographics, interval between start of anti-TNF therapy and active TB development, tests for latent TB infection (LTBI), concomitant medications, and the details of diagnosis and treatments for TB. The incidence of active TB was 1.2% (10/821): 1.5% (9/592) and 0.4% (1/229) in patients receiving infliximab and adalimumab, respectively. The median time to the development of active TB after initiation of anti-TNF therapy was three months (range: 2-36). Three patients had past histories of treatment for TB. Positive findings in a TB skin test (TST) and/or interferon gamma releasing assay (IGRA) were observed in three patients, and two of them received anti-TB prophylaxis. Two patients were negative by both TST and IGRA. The most common site of active TB was the lungs, and the active TB was cured in all patients. Active TB can develop during anti-TNF therapy in IBD patients without LTBI, and even in those with histories of TB treatment or LTBI prophylaxis. Physicians should be aware of the potential for TB development during anti-TNF therapy, especially in countries with a high prevalence of TB.


Collagen, convulxin, and thrombin stimulate aggregation-independent tyrosine phosphorylation of CD31 in platelets. Evidence for the involvement of Src family kinases.
Platelet endothelial cell adhesion molecule-1 (CD31) is a 130-kDa glycoprotein receptor present on the surface of platelets, neutrophils, monocytes, certain T-lymphocytes, and vascular endothelial cells. CD31 is involved in adhesion and signal transduction and is implicated in the regulation of a number of cellular processes. These include transendothelial migration of leukocytes, integrin regulation, and T-cell function, although its function in platelets remains unclear. In this study, we demonstrate the ability of the platelet agonists collagen, convulxin, and thrombin to induce tyrosine phosphorylation of CD31. Furthermore, we show that this event is independent of platelet aggregation and secretion and is accompanied by an increase in surface expression of CD31. A kinase capable of phosphorylating CD31 was detected in CD31 immunoprecipitates, and its activity was increased following activation of platelets. CD31 tyrosine phosphorylation was reduced or abolished by the Src family kinase inhibitor PP2, suggesting a role for these enzymes. In accordance with this, each of the Src family members expressed in platelets, namely Fyn, Lyn, Src, Yes, and Hck, was shown to co-immunoprecipitate with CD31. The involvement of Src family kinases in this process was confirmed through the study of mouse platelets deficient in Fyn.


Tenofovir disoproxil fumarate (TDF), emtricitabine/TDF, and entecavir in patients with decompensated chronic hepatitis B liver disease.
Data are limited on the safety and effectiveness of oral antivirals other than lamivudine and adefovir dipivoxil for treatment of chronic hepatitis B (CHB) in patients with decompensated liver disease. This Phase 2, double-blind study randomized 112 patients with CHB and decompensated liver disease to receive either tenofovir disoproxil fumarate (TDF; n = 45), emtricitabine (FTC)/TDF (fixed-dose combination; n = 45), or entecavir (ETV; n = 22). The primary endpoint was safety; more specifically, tolerability failure (adverse events resulting in permanent treatment discontinuation) and confirmed serum creatinine increase ≥ 0.5 mg/dL from baseline or confirmed serum phosphorus <2 mg/dL. Patients with insufficient viral suppression (e.g., confirmed HBV DNA ≥ 400 copies/mL at week 8 or 24) could begin open-label FTC/TDF but were considered failures in this interim week 48 analysis for efficacy endpoints. Tolerability failure was infrequent across arms: 6.7% TDF, 4.4% FTC/TDF, and 9.1% ETV (P = 0.622) as were confirmed renal parameters meeting threshold 8.9%, 6.7%, and 4.5% (P = 1.000), respectively. Six patients died (none considered related to study drug) and six received liver transplants (none had HBV recurrence). The adverse event and laboratory profiles were consistent with advanced liver disease and complications, with no unexpected safety signals. At week 48, HBV DNA was <400 copies/mL (69 IU/mL) in 70.5% (TDF), 87.8% (FTC/TDF), and 72.7% (ETV) of patients. Proportions with normal alanine aminotransferase were: 57% (TDF), 76% (FTC/TDF), and 55% (ETV). Hepatitis B e antigen (HBeAg) loss/seroconversion occurred in 21%/21% (TDF), 27%/13% (FTC/TDF), and 0%/0% (ETV). Child-Turcotte-Pugh and Modification for End-stage Liver Disease scores improved in all groups. All treatments were well tolerated in patients with decompensated liver disease due to CHB with improvement in virologic, biochemical, and clinical parameters.


Improving Nurses' Knowledge About Older Adults With Cancer.
To assess nurses' knowledge, attitudes, and perceptions of caring for older adults and to use that assessment data to develop a training program to improve skills in caring for older adults with cancer. . Survey of oncology nursing staff conducted pre- and posteducation regarding geriatric care. . City of Hope, a comprehensive cancer center in southern California. . 422 (baseline) and 375 (postintervention) nursing staff in adult care areas. . The primary endpoint was the difference between baseline and postintervention knowledge. Secondary endpoints included differences in attitudes and perceptions of caring for older adults in an oncology setting. A two-sample t test was performed to compare the mean results between baseline and follow-up surveys. . Knowledge, attitudes, and perceptions of caring for older adults. . Survey comparisons from baseline to postintervention demonstrated statistically significant increases in nurses' knowledge of geriatric care after the implementation of an educational program targeted at oncology nurses. Nurses' attitudes remained the same pre- versus posteducation. A significant change reflecting a better perception was noted in the burden of behavioral problems; however, a worsening was noted in disagreements among staff; disagreements involving staff, patients, and families; and limited access to geriatric services. Both surveys highlighted the need to provide more education for staff about geriatric care issues and to make available more geriatric-specific resources. . Knowledge about caring for older adults is needed for oncology nurses, and a geriatric education program for oncology nurses can result in improved knowledge in a variety of domains. Surveying staff highlighted the positive attitude of nurses toward caring for older adults at the study institution. The use of this survey identified key issues facing older adults and ways to improve care. . Additional knowledge about caring for older adults for oncology nurses and assistive staff is needed to prepare for the increasing population of older adults with cancer. Continuous learning is key to professional development, and more research is needed on how to best continue to integrate knowledge of geriatric concepts into oncology care.


Proyecto Interconexiones: a pilot test of a community-based depression care program for Latina violence survivors.
Latina intimate partner violence (IPV) survivors often face great barriers to depression care. We sought to use a community-based participatory research (CBPR) approach to create and evaluate a community-based depression care program for Latina IPV survivors. We created a multifaceted, culturally tailored intervention, based on principles of chronic illness management. A promotora provided case management services and led 12 weekly group sessions. Participants completed surveys at baseline and 6 months and participated in open-ended exit interviews. Ten Spanish-speaking Latina women participated in the intervention. The program had excellent attendance, with 100% of women attending at least 10 group sessions, and high satisfaction. We found a large decrease in depression severity (Patient Health Questionnaire [PHQ]-9, 17.3-7.2; p = .001), as well as improvements in depression self-efficacy, self-esteem, and stress. This study offers promising preliminary data to support the use of community-based approaches to reducing depression disparities in Latina IPV survivors.


A comparison of longitudinal and transverse approaches to ultrasound-guided axillary vein cannulation by experienced operators.
The axillary vein is an easily accessible vessel that can be used for ultrasound-guided central vascular access and offers an alternative to the internal jugular and subclavian veins. The objective of this study was to identify which transducer orientation, longitudinal or transverse, is better for imaging the axillary vein with ultrasound. We analyzed 236 patients who had undergone central venous cannulation of axillary vein in this retrospective study. Patients were divided into two groups, the longitudinal approach group (n=120) and transverse approach group (n=116). Recorded the one-attempt success rate, operation time, arterial puncture rate and pneumothorax rate. We perform chest radiography to confirm pneumothorax on all patients. We compared the one-attempt success rate, operation time, arterial puncture rate and pneumothorax rate between the two groups. The two groups were comparable with clinical characters of patients. The overall success rates of the longitudinal group and the transverse group were both 100%. The rate of one-attempt success in the longitudinal approach group is higher than the transverse approach group (91.7% vs. 82.8%, P=0.040). The transverse approach group had shorter operation time than the longitudinal group (184.7±8.1 vs. 287.5±19.6 seconds, P=0.000). The two groups had lower postoperative complications. Arterial puncture occurred in 1 of 120 longitudinal and 2 of 116 transverse attempts and this difference was no significant (P=0.541). No pneumothorax occurred in the two groups. The longitudinal approach during ultrasound-guided axillary vein cannulation is associated with greater one-attempt success rate compared with the transverse approach by experienced operators. The transverse approach has shorter operation time. The two groups have lower postoperative complications and are comparable with pneumothorax and arterial puncture.


Optical methods of temperature measurement.
The history of the laws of thermal radiation is briefly reviewed, and the theoretical relations basic to some of the optical methods of temperature measurement are given. Comments on a number of optical methods are presented, as well as a selected reference with each method where more detail is available. In conclusion, several problems, in areas of uncertainty in the field of optical methods of temperature measurement, are suggested in the belief that a solution to these problems will greatly enhance the technical value of this field.


Virtual reality for stroke rehabilitation: an abridged version of a Cochrane review.
Virtual reality and interactive video gaming have emerged as new treatment approaches in stroke rehabilitation settings over the last ten years. The primary objective of this review was to determine the effectiveness of virtual reality on upper limb function and activity after stroke. The impact on secondary outcomes including gait, cognitive function and activities of daily living was also assessed. Randomized and quasi-randomized controlled trials comparing virtual reality with an alternative intervention or no intervention were eligible to be included in the review. The authors searched a number of electronic databases including: the Cochrane Stroke Group Trials Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, AMED, CINAHL, PsycINFO, clinical trial registers, reference lists, Dissertation Abstracts and contacted key researchers in the field. Search results were independently examined by two review authors to identify studies meeting the inclusion criteria. A total of 37 randomized or quasi randomized controlled trials with a total of 1019 participants were included in the review. Virtual reality was found to be significantly more effective than conventional therapy in improving upper limb function (standardized mean difference [SMD] 0.28, 95% confidence intervals [CI] 0.08 to 0.49) based on 12 studies and significantly more effective than no therapy in improving upper limber function (SMD 0.44 [95% CI 0.15 to 0.73]) based on nine studies. The use of virtual reality also significantly improved activities of daily living function when compared to more conventional therapy approaches (SMD 0.43 [95% CI 0.18 to 0.69]) based on eight studies. While there are a large number of studies assessing the efficacy of virtual reality they tend to be small and many are at risk of bias. While there is evidence to support the use of virtual reality intervention as part of upper limb training programs, more research is required to determine whether it is beneficial in terms of improving lower limb function and gait and cognitive function.


Prevalence of tick-borne pathogens in Ixodes ricinus and Dermacentor reticulatus ticks from different geographical locations in Belarus.
Worldwide, ticks are important vectors of human and animal pathogens. Besides Lyme Borreliosis, a variety of other bacterial and protozoal tick-borne infections are of medical interest in Europe. In this study, 553 questing and feeding Ixodes ricinus (n = 327) and Dermacentor reticulatus ticks (n = 226) were analysed by PCR for Borrelia, Rickettsia, Anaplasma, Coxiella, Francisella and Babesia species. Overall, the pathogen prevalence in ticks was 30.6% for I. ricinus and 45.6% for D. reticulatus. The majority of infections were caused by members of the spotted-fever group rickettsiae (24.4%), 9.4% of ticks were positive for Borrelia burgdorferi sensu lato, with Borrelia afzelii being the most frequently detected species (40.4%). Pathogens with low prevalence rates in ticks were Anaplasma phagocytophilum (2.2%), Coxiella burnetii (0.9%), Francisella tularensis subspecies (0.7%), Bartonella henselae (0.7%), Babesia microti (0.5%) and Babesia venatorum (0.4%). On a regional level, hotspots of pathogens were identified for A. phagocytophilum (12.5-17.2%), F. tularensis ssp. (5.5%) and C. burnetii (9.1%), suggesting established zoonotic cycles of these pathogens at least at these sites. Our survey revealed a high burden of tick-borne pathogens in questing and feeding I. ricinus and D. reticulatus ticks collected in different regions in Belarus, indicating a potential risk for humans and animals. Identified hotspots of infected ticks should be included in future surveillance studies, especially when F. tularensis ssp. and C. burnetii are involved.


Signaling and ligand binding by recombinant neuromedin U receptors: evidence for dual coupling to Galphaq/11 and Galphai and an irreversible ligand-receptor interaction.
The neuropeptide neuromedin U (NmU) shows considerable structural conservation across species. Within the body, it is widely distributed and in mammals has been implicated in physiological roles, including the regulation of feeding, anxiety, pain, blood flow, and smooth muscle contraction. Human NmU-25 (hNmU-25) and other NmU analogs were recently identified as ligands for two human orphan G protein-coupled receptors, subsequently named hNmU-R1 and hNmU-R2. These receptors have approximately 50% amino acid homology, and, at least in mammalian species, NmU-R1 and NmU-R2 are expressed predominantly in the periphery and central nervous system, respectively. Here, we have characterized signaling mediated by hNmU-R1 and hNmU-R2 expressed as recombinant proteins in human embryonic kidney 293 cells, particularly to define their G protein coupling and the activation and regulation of signal transduction pathways. We show that these receptors couple to both Galpha(q/11) and Galpha(i). Activation of either receptor type causes a pertussis toxin-insensitive activation of both phospholipase C and mitogen activated-protein kinase and a pertussis toxin-sensitive inhibition of adenylyl cyclase with subnanomolar potency for each. Activation of phospholipase C is sustained, but despite this capacity for prolonged receptor activation, repetitive application of hNmU-25 does not cause repetitive intracellular Ca2+ signaling by either recombinant receptors or those expressed endogenously in isolated smooth muscle cells from rat fundus. Using several strategies, we show this to be a consequence of essentially irreversible binding of hNmU-25 to its receptors and that this is followed by ligand internalization. Despite structural differences between receptors, there were no apparent differences in their activation, coupling, or regulation.


Respiratory capacities of mitochondria of Saccharomyces cerevisiae CBS 8066 and Candida utilis CBS 621 grown under glucose limitation.
A comparative study was made of the in vitro respiratory capacity of mitochondria isolated from Saccharomyces cerevisiae and Candida utilis grown in glucose-limited chemostat cultures. An electron-microscopic analysis of whole cells revealed that the volume density of mitochondria was the same in both yeasts. Mitochondria from both organisms exhibited respiratory control with NADH, pyruvate + malate, 2-oxoglutarate + acetate or malate, and ethanol. The rate of oxidation of these compounds by isolated mitochondria was the same in both yeasts. The rate of oxidation of NADPH by mitochondria from S. cerevisiae was 10 times lower than by those from C. utilis. However, this low rate probably has no influence on the overall in vivo respiratory capacity of S. cerevisiae. The results are discussed in relation to the differences in metabolic behaviour between S. cerevisiae and C. utilis upon transition of cultures from glucose limitation to glucose excess. It is concluded that the occurrence of alcoholic fermentation in S. cerevisiae under these conditions does not result from a bottleneck in the respiratory capacity of the mitochondria.


Bone marrow transplantation for feline mucopolysaccharidosis I.
Severe mucopolysaccharidosis type I (MPS I) is a fatal neuropathic lysosomal storage disorder with significant skeletal involvement. Treatment involves bone marrow transplantation (BMT), and although effective, is suboptimal, due to treatment sequelae and residual disease. Improved approaches will need to be tested in animal models and compared to BMT. Herein we report on bone marrow transplantation to treat feline mucopolysaccharidosis I (MPS I). Five MPS I stably engrafted kittens, transplanted with unfractionated bone marrow (6.3x10(7)-1.1x10(9) nucleated bone marrow cells per kilogram) were monitored for 13-37 months post-engraftment. The tissue total glycosaminoglycan (GAG) content was reduced to normal levels in liver, spleen, kidney, heart muscle, lung, and thyroid. Aorta GAG content was between normal and affected levels. Treated cats had a significant decrease in the brain GAG levels relative to untreated MPS I cats and a paradoxical decrease relative to normal cats. The alpha-l-iduronidase (IDUA) activity in the livers and spleens of transplanted MPS I cats approached heterozygote levels. In kidney cortex, aorta, heart muscle, and cerebrum, there were decreases in GAG without significant increases in detectable IDUA activity. Treated animals had improved mobility and decreased radiographic signs of disease. However, significant pathology remained, especially in the cervical spine. Corneal clouding appeared improved in some animals. Immunohistochemical and biochemical analysis documented decreased central nervous system ganglioside storage. This large animal MPS I study will serve as a benchmark of future therapies designed to improve on BMT.


A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins.
A 73-kilodalton (kD) intracellular protein was found to bind to peptide regions that target intracellular proteins for lysosomal degradation in response to serum withdrawal. This protein cross-reacted with a monoclonal antibody raised to a member of the 70-kD heat shock protein (hsp70) family, and sequences of two internal peptides of the 73-kD protein confirm that it is a member of this family. In response to serum withdrawal, the intracellular concentration of the 73-kD protein increased severalfold. In the presence of adenosine 5'-triphosphate (ATP) and MgCl2, the 73-kD protein enhanced protein degradation in two different cell-free assays for lysosomal proteolysis.


You say you want a revolution: An empirical study of community-based participatory research with people with developmental disabilities.
Community-based participatory research (CBPR) seeks to improve the responsiveness of science to community priorities and foster positive community change through equitable research collaborations between scientists and community members. CBPR resonates with disability rights principles, and is increasingly being used in disability research, though there are few studies of its use with people with developmental disabilities. We conducted a prospective qualitative study to explore the experiences of scientists and community members in a multi-year CBPR project with people with developmental disabilities. Over the four project years, we conducted periodic individual interviews and focus groups with members of the CBPR project, and used an inductive thematic analysis to identify and develop relational themes. We identified factors that contributed to the success of the CBPR project and factors that presented challenges to the CBPR project. We also identified potential individual, project, and societal level impacts of the CBPR project. CBPR with people with developmental disabilities is possible and fruitful, and can serve as an effective model for the full inclusion of people with developmental disabilities in science and society at large.


Newspaper coverage of water issues in Australia.
The media has been found to have an impact on public debate, public opinion, and public policy agendas. Public debate, and public opinion about water conservation and water supply management projects matter because they can influence specific outcomes. For example, public opinion can potentially lead to positive behaviour, like increased water conservation, or potentially negative behaviours such as public opposition to developments such as dams or water recycling plants, which may be necessary under changing climatic conditions. It is therefore critical to understand how the media reports on water-related topics. Results from a content analysis of 1253 newspaper articles published in Australia in 2008 indicate that water-related reports are characterised by lack of inclusion of views held by various stakeholders, a low level of support of statements with scientific evidence, a low level of impartiality in the sense of reporting on opposing views and a relatively high level of hedging, meaning that the author signals that there is some uncertainly about the reported information. In sum these tendencies could theoretically culminate to work against public engagement in water issues and undermine the public's understanding of and confidence in water management measures. Proactive measures of media management are recommended.


Family structure, family functioning and adolescent well-being: the transcendent influence of parental style.
This study assessed the association between parental style, family functioning and adolescent well being, contrasting intact families with those of changed configuration. Eight hundred and one grade 10 general level teenagers in 11 high schools of a single educational system were the subjects. Results indicated that the configuration of the family was not the key determinant of effectiveness of family functioning. Instead the style of parenting turned out to be the main determinant of both family functioning and well being of the adolescents. While both "parents" were judged to have contributed to these outcomes cross gender effects were found.


Mobility and maternal position during childbirth in Tanzania: an exploratory study at four government hospitals.
BACKGROUND: Emerging research evidence suggests a potential benefit in being upright in the first stage of labour and a systematic review of trials suggests both benefits and harmful effects associated with being upright in the second stage of labour. Implementing evidence-based obstetric care in African countries with scarce resources is particularly challenging, and requires an understanding of the cumulative nature of science and commitment to applying the most up to date evidence to clinical decisions. In this study, we documented current practice rates, explored the barriers and opportunities to implementing these procedures from the provider perspective, and documented women's preferences and satisfaction with care. METHODS: This was an exploratory study using quantitative and qualitative methods. Practice rates were determined by exit interviews with a consecutive sample of postnatal women. Provider views were explored using semi-structured interviews (with doctors and traditional birth attendants) and focus group discussions (with midwives). The study was conducted at four government hospitals, two in Dar es Salaam and two in the neighbouring Coast region, Tanzania. MAIN OUTCOME MEASURES: Practice rates for mobility during labour and delivery position; women's experiences, preferences and views about the care provided; and provider views of current practice and barriers and opportunities to evidence-based obstetric practice. RESULTS: Across all study sites more women were mobile at home (15.0%) than in the labour ward (2.9%), but movement was quite restricted at home before women were admitted to labour ward (51.6% chose to rest with little movement). Supine position for delivery was used routinely at all four hospitals; this was consistent with women's preferred choice of position, although very few women are aware of other positions. Qualitative findings suggest obstetricians and midwives favoured confining to bed during the first stage of labour, and supine position for delivery. CONCLUSIONS: The barriers to change appear to be complicated and require providers to want to change, and women to be informed of alternative positions during the first stage of labour and delivery. We believe that highlighting the gap between actual practice and current evidence provides a platform for dialogue with providers to evaluate the threats and opportunities for changing practice.


Spectral analysis of canine epicardial electrogram. Short-term variations in the frequency content induced by myocardial ischemia.
Power spectra of epicardial electrograms were studied in 13 anesthetized dogs subjected to occlusion of the left anterior descending coronary artery. Electrograms were obtained from a bipolar electrode placed on the epicardial surface of the left ventricle and recorded before and after coronary occlusion. After digitization, power spectra of the first and every 50th subsequent waveform were evaluated and compared with the power spectrum of the average waveform obtained from the baseline recording. In particular, we examined variations in relative power content in three frequency ranges: 150-250 Hz, previously shown to be directly affected by myocardial ischemia; 40-150 Hz, presumably corresponding to the fine notches and slurs on the body surface QRS; and 2-40 Hz, the low-frequency range. Apart from a mild initial rise during the first 50 heart beats, the power in the high-frequency range gradually decreased, reaching 5% of the control value at wave 500. The power in the mid-frequency range showed a monotonous decrease after the occlusion and reached 16% of the control. The power in the low-frequency range showed a gradual buildup to 140% of the control after 500 heart beats. Therefore, ischemia causes a shift of the high-frequency spectral components of the local electrographic waveform to lower frequencies. Our findings and the fact that body surface ECG is produced by spatial summation of local electric potentials over the different regions of the myocardial tissue may explain two previously described effects of acute myocardial ischemia on the body surface ECG complex. First, local loss of spectral components in the range 150-250 Hz may produce a zone of reduced amplitude within a QRS complex band-pass filtered in this range. Second, displacement of power in the frequency domain may suggest an explanation to the increased incidence of visible notches and slurs on the surface QRS complex, characteristic to various myocardial pathologies.


Assessment of non-motor hearing symptoms in hemifacial spasm using magnetoencephalography.
Hemifacial spasm patients often suffer from non-motor symptoms such as tinnitus. These non-motor symptoms are known to be associated with changes in cortical activity. Magnetoencephalography (MEG) is a technique that can record brain activity noninvasively. To determine the usefulness of MEG in assessing changes in cortical activity associated with non-motor hearing symptoms in hemifacial spasm patients. We used MEG to evaluate the reactivity of the auditory cortex in 26 hemifacial spasm patients. We divided patients into a subjective tinnitus group (n = 10) and a non-tinnitus group (n = 16). The latency and amplitude of the most prominent deflection, N100m, was compared between the two groups. There was a significant difference in the pure tone audiogram on the spasm side compared with the non-spasm side. After stimulation on the spasm side, the amplitude of the N100m peak in the contralateral hemisphere was lower in the subjective tinnitus group than in the non-tinnitus group. Our results indicate that MEG can detect differences in cortical activity between hemifacial spasm patients with and without tinnitus. This suggests that MEG can identify changes in cortical activity associated with non-motor symptoms.


A solid-state (11)b NMR and computational study of boron electric field gradient and chemical shift tensors in boronic acids and boronic esters.
The results of a solid-state (11)B NMR study of a series of 10 boronic acids and boronic esters with aromatic substituents are reported. Boron-11 electric field gradient (EFG) and chemical shift (CS) tensors obtained from analyses of spectra acquired in magnetic fields of 9.4 and 21.1 T are demonstrated to be useful for gaining insight into the molecular and electronic structure about the boron nucleus. Data collected at 21.1 T clearly show the effects of chemical shift anisotropy (CSA), with tensor spans (Omega) on the order of 10-40 ppm. Signal enhancements of up to 2.95 were achieved with a DFS-modified QCPMG pulse sequence. To understand the relationship between the measured tensors and the local structure better, calculations of the (11)B EFG and magnetic shielding tensors for these compounds were conducted. The best agreement was found between experimental results and those obtained from GGA revPBE DFT calculations. A positive correlation was found between Omega and the dihedral angle (phi(CCBO)), which describes the orientation of the boronic acid/ester functional group relative to an aromatic system bound to boron. The small boron CSA is discussed in terms of paramagnetic shielding contributions as well as diamagnetic shielding contributions. Although there is a region of overlap, both Omega and the (11)B quadrupolar coupling constants tend to be larger for boronic acids than for the esters. We conclude that the span is generally the most characteristic boron NMR parameter of the molecular and electronic environment for boronic acids and esters, and show that the values result from a delicate interplay of several competing factors, including hydrogen bonding, the value of phi(CCBO), and the electron-donating or withdrawing substituents bound to the aromatic ring.


Dysphagia, stricture, and pneumonia in head and neck cancer patients: does treatment modality matter?
Dysphagia-related sequelae are common after head and neck cancer treatment. Our aims were 1) to document overall and site-specific dysphagia, stricture, and pneumonia rates in a Medicare population, 2) to calculate treatment-specific rates and adjusted odds of developing these complications, and 3) to track changes in rates between 1992 and 1999. Head and neck cancer patients between 1992 and 1999 were identified in combined Surveillance Epidemiology and End Results (SEER) registry and Medicare databases. Multivariate analyses determined odds of dysphagia, stricture, and pneumonia based on modality. Of 8,002 patients, 40% of experienced dysphagia, 7% stricture, and 10% pneumonia within 3 years of treatment. In adjusted analyses, patients treated with chemoradiation had more than 2.5-times-greater odds of dysphagia than did those treated with surgery alone. Combined therapy was associated with increased odds of stricture (p<0.05). The odds of pneumonia were increased in patients treated with radiation with or without chemotherapy. Temporally, the dysphagia rates increased 10% during this period (p<0.05). Sequelae of head and neck cancer treatment are common and differ by treatment regimen. Those treated with chemoradiation had higher odds of experiencing dysphagia and pneumonia, whereas patients treated with any combined therapy more commonly experienced stricture. These sequelae represent major sources of morbidity and mortality in this population.


Successful hemodialysis in a phenytoin overdose: case report and review of the literature.
We describe the case of a 42-year-old female who presented to our care 1 hour after ingesting 3.6 g of phenytoin. She was stuporous 48 hours after admission despite supportive therapy. She was treated with hemodialysis (HD) for nearly 6 hours in order to remove phenytoin. Her level of consciousness improved markedly during the procedure. During HD, phenytoin levels decreased by 47% and measured half-life was 6.8 hours as compared to 116 hours when not on HD. Finally, we were able to remove 547 mg of phenytoin (directly measured from the dialysate), representing approximately a third of estimated body stores. The use of extracorporeal therapy in phenytoin overdose is reviewed here. We believe that in severe cases of phenytoin intoxication, hemodialysis can be used to accelerate total body burden of the drug, even if protein binding is significant.


SU-E-J-209: A Simple Method to Minimize Uncertainty in ITV Delineation: Phantom Verification.
Irregular breathing causes variation in delineation of internal target volume (ITV), which is typically generated in the maximum intensity projection (MIP) images [1]. Previous studies have shown that MIP-based ITV can underestimate true tumor range [2]. This study examines a simple method to reduce such errors by combining the GTV of 3D-CT with the ITV of MIP. The Computerized Imaging Reference Systems (CIRS) Dynamic Thorax Phantom Model 008A (CIRS, Norfolk, VA) with CIRS motion control software was used to model 4 irregular patient respiratory profiles and one regular respiratory profile (sine wave). A 3 cm tumor insert was used as target. For each breathing profile, a 3D-CT and 3 repeated 4D-CT scans with random intervals within the breathing profile were performed on a 4-slice clinical scanner (Lightspeed, GE, WI). The RPM system (Varian, Palo Alto, CA) was used to track the respiratory profiles. GTV was contoured on 3D-CT, and ITV was contoured on each MIP (ITVMIP) using a consistent lung window by the same person. The new method of creating ITV was to combine the GTV and ITVMIP, namely ITVCOMB. To evaluate which ITV is more accurate, ITVCOMB and ITVMIP were compared to a 'ground truth' ITV (ITVGT) which was generated by combining the three ITVMIPs. For the regular profile, both ITVMIP (27.25 cm3 ) and ITVCOMB (28.12 cm3 ) were comparable to ITVGT (27.25 cm3 ). For irregular profiles, the mean absolute difference between ITVCOMB and ITVGT (6.3%±4.9) was significantly (p-value=0.0078) smaller than that between ITVMIP and ITVGT (18.1%±12.3). The results suggest that combining GTV of the 3D-CT with the ITV of the MIP is more accurate than the ITV of the MIP alone, and thus would be a simple method to reduce breathing irregularity induced errors in ITV delineation for treatment planning of lung cancer.


Measurement of T-kinin in rat plasma using a specific radioimmunoassay.
T-kinin (Ile-Ser-Bradykinin) has been isolated only from the plasma of the rat and it is unclear whether the peptide, or its biosynthetic precursor, T-kininogen, circulates in the human. An NH2-terminally directed antiserum to T-kinin was raised in rabbits using an immunogen prepared by coupling the free -SH group of T-kinin extended from its COOH-terminus by a cysteinyl residue to an -NH2 group on human serum albumin. A radioimmunoassay was developed using this antiserum and 125I-labelled [Tyr10]T-kinin as tracer that was sensitive (least-detectable concentration 3 fmol/tube) and relatively specific for T-kinin (cross-reactivity with bradykinin and kallidin less than 1%). Treatment of rat plasma with an excess of trypsin in the presence of a kininase inhibitor generated T-kinin immunoreactivity equivalent to 455 +/- 71 pmol/ml (mean +/- S.E.M.; n = 9) and this immunoreactivity was eluted from a reversed-phase HPLC column as a single peak with the same retention time as synthetic T-kinin. In contrast, treatment of plasma from healthy human subjects (n = 8) and from patients (n = 8) with inflammation due to acute or chronic gastrointestinal disease under the same conditions did not generate any detectable T-kinin immunoreactivity. It is concluded, therefore, that T-kininogen, the biosynthetic precursor of T-kinin in the rat, is either absent from the plasma of human subjects or is present in a concentration less than 30 fmol/ml. Similarly, T-kininogen is probably not an acute phase reactant in humans.


Altered zinc balance in the Atp7b-/- mouse reveals a mechanism of copper toxicity in Wilson disease.
Wilson disease (WD) is an autosomal recessive disorder caused by mutation in the ATP7B gene that affects copper transport in the body. ATP7B mutation damages copper transporter function, ultimately resulting in excessive copper accumulation and subsequent toxicity in both the liver and brain. Mechanisms of copper toxicity, however, are not well defined. The Atp7b-/- mouse model is well-characterized and presents a hepatic phenotype consistent with WD. In this study, we found that the untreated Atp7b-/- mice accumulate approximately 2-fold excess hepatic zinc compared to the wild type. We used targeted transcriptomics and proteomics to analyze the molecular events associated with zinc and copper accumulation in the Atp7b-/- mouse liver. Altered gene expression of Zip5 and ZnT1 zinc transporters indicated a transcriptional homeostatic response, while increased copper/zinc ratios associated with high levels of metallothioneins 1 and 2, indicated altered Zn availability in cells. These data suggest that copper toxicity in Wilson disease includes effects on zinc-dependent proteins. Transcriptional network analysis of RNA-seq data reveals an interconnected network of transcriptional activators with over-representation of zinc-dependent and zinc-responsive transcription factors. In the context of previous research, these observations support the hypothesis that mechanisms of copper toxicity include disruption of intracellular zinc distribution in liver cells. The translational significance of this work lies in oral zinc supplementation in treatment for WD, which is thought to mediate protective effects through the induction of metallothionein synthesis in the intestine. This work indicates broader impacts of altered zinc-copper balance in WD, including global transcriptional responses and altered zinc balance in the liver.


Personal values, beliefs, and ecological risk perception.
A mail survey on ecological risk perception was administered in the summer of 2002 to a randomized sample of the lay public and to selected risk professionals at the U.S. Environmental Protection Agency (US EPA). The ranking of 24 ecological risk items, from global climate change to commercial fishing, reveals that the lay public is more concerned about low-probability, high-consequence risks whereas the risk professionals are more concerned about risks that pose long-term, ecosystem-level impacts. To test the explanatory power of the value-belief-norm (VBN) theory for risk perception, respondents were questioned about their personal values, spiritual beliefs, and worldviews. The most consistent predictors of the risk rankings are belief in the new ecological paradigm (NEP) and Schwartz's altruism. The NEP and Schwartz's altruism explain from 19% to 46% of the variance in the risk rankings. Religious beliefs account for less than 6% of the variance and do not show a consistent pattern in predicting risk perception although religious fundamentalists are generally less concerned about the risk items. While not exerting as strong an impact, social-structural variables do have some influence on risk perception. Ethnicities show no effect on the risk scales but the more educated and financially well-off are less concerned about the risk items. Political leanings have no direct influence on risk rankings, but indirectly affect rankings through the NEP. These results reveal that the VBN theory is a plausible explanation for the differences measured in the respondents' perception of ecological risk.


Interactions between Neisseria meningitidis and human cells that promote colonisation and disease.
Neisseria meningitidis is the leading cause of bacterial meningitis, a potentially fatal condition that particularly affects children. Multiple steps are involved during the pathogenesis of infection, including the colonisation of healthy individuals and invasion of the bacterium into the cerebrospinal fluid. The bacterium is capable of adhering to, and entering into, a range of human cell types, which facilitates its ability to cause disease. This article summarises the molecular basis of host-pathogen interactions at the cellular level during meningococcal carriage and disease.


Adjusting health care: practicing care for socially vulnerable type 2 diabetes patients.
Type 2 diabetes cluster in lower social groups and people with type 2 diabetes from lower social groups experience more complications, benefit less from health services and live shorter lives than people with type 2 diabetes from higher social groups. Different logics govern diabetes care and potentially influence the possibility of socially vulnerable type 2 diabetes patients to access and benefit from health services. In order to understand which practice and underlying logic enable socially vulnerable type 2 diabetes patients to access and benefit from diabetes care we aim to describe what professionals at a specialized diabetes clinic do to adjust services to patient's needs and make the tasks involved in diabetes care doable for socially vulnerable patients and how this work is embedded in an organizational and moral context. Ethnographic fieldwork combining participant observation and interviews was carried out between February 2017 and March 2018 in a specialized diabetes clinic located in a socially deprived area in the capital region of Denmark. Sixteen patients (9 male, 7 female, aged 35-73 years) and 12 professionals (7 doctors, 4 nurses, 1 secretary) participated in the study. We used Annemarie Mol's concept of "the logic of care" to guide our analysis. Our analysis shows that the logic of care and the care practices in this clinic are characterized by a needs-based approach to treatment involving adjustment of services (permeability, timing, and content) and seeing the patient as a person with many needs. Throughout our description of selected care practices, we both characterize how health professionals practice this particular logic of care and the organizational and normative conditions that this logic is entangled with. Practicing diabetes care based on patients' needs involves individualization, something often described as an element of patient centred care. Our study shows that this ideal of individualization and adjustment of treatment is possible in practice. Organizational flexibility and an organizational culture that values patient needs enable needs-based care. In order for socially vulnerable type 2 diabetes patients to benefit from health services it is necessary to create conditions under which professionals can attend to these patients' multiple and complex needs. Adjusting care to these needs demand a variety of professional efforts some of which are hardly predictable or standardisable.


Hexosamines and insulin resistance.
Glucose is an important regulator of cell growth and metabolism. Thus, it is likely that some of the adverse effects of hyperglycemia are reflections of normal regulation by abnormal concentrations of glucose. How the cell senses glucose, however, is still incompletely understood. Evidence has been presented that the hexosamine biosynthesis pathway serves this function for regulation of aspects of glucose uptake, glycogen synthesis, glycolysis, and synthesis of growth factors. Excess hexosamine flux causes insulin resistance in cultured cells, tissues, and intact animals. Further evidence for the possible role of this pathway in normal glucose homeostasis and disease is that the level of activity of the rate-limiting enzyme in hexosamine synthesis, glutamine:fructose-6-phosphate amidotransferase, is correlated with glucose disposal rates (GDRs) in normal humans and transgenic mice.


Sick leave among native and immigrant workers in Spain--a 6-month follow-up study.
The incidence and the duration of sick leave were studied among immigrants and the native-born population in Spain. This observational follow-up study included 1427 immigrants and 2793 Spanish natives treated at five primary care centers in Lleida in 2005 and followed for 6 months. The sick leave causes were coded according to the International Classification of Diseases (10th revision). Multivariate Poisson regressions estimated the rate ratio (RR) for sick leave adjusted for age, and linear regressions evaluated the effect of age, gender, and region of origin on the total number of sick-leave days. Altogether 19.5% of the natives and 12.7% of the immigrants had at least one sick-leave episode. The incidence of new episodes per 100 person-years was lower for the immigrants than for the natives (32.5 versus 43.3 for the men and 18.6 versus 35.6 for the women, respectively). The mean duration of sick leave in the 6-month period was 19.4 (SD 29.4) days for the immigrants and 33.5 (SD 39.2) days for the natives. For the men, the risk of sick leave was greater for the natives than for the immigrants (adjusted RR 1.70, 95% confidence interval 1.43-2.02). After adjustment for age, the duration of sick leave for the native workers was 1.5 times greater than for the immigrants. Even though sick leave was less frequent among the immigrants than among the natives and the immigrant sick-leave periods were of shorter duration, the two study populations did not show differences in the causes of disability.


Confounding of Cerebral Blood Flow Velocity by Blood Pressure During Breath Holding or Hyperventilation in Transient Ischemic Attack or Stroke.
Background and Purpose- Breath holding (BH) and hyperventilation are used to assess abnormal cerebrovascular reactivity, often in relation to severity of small vessel disease and risk of stroke with carotid stenosis, but responses may be confounded by blood pressure (BP) changes. We compared effects of BP and end-tidal carbon dioxide (etCO2) on middle cerebral artery mean flow velocity (MFV) in consecutive transient ischemic attack and minor stroke patients. Methods- In the population-based, prospective OXVASC (Oxford Vascular Study) phenotyped cohort, change in MFV on transcranial Doppler ultrasound (ΔMFV, DWL-DopplerBox), beat-to-beat BP (Finometer), and etCO2 was measured during 30 seconds of BH or hyperventilation. Two blinded reviewers independently assessed recording quality. Dependence of ΔMFV on ΔBP and ΔetCO2 was determined by general linear models, stratified by quartiles. Results- Four hundred eighty-eight of 602 (81%) patients with adequate bone windows had high-quality recordings, more often in younger participants (64.6 versus 68.7 years; P<0.01), whereas 426 had hyperventilation tests (70.7%). During BH, ΔMFV was correlated with a rise in mean blood pressure (MBP; r2=0.15, P<0.001) but not ΔCO2 (r2=0.002, P=0.32), except in patients with ΔMBP <10% (r2=0.13, P<0.001). In contrast during hyperventilation, the fall in MFV was similarly correlated with reduction in CO2 and reduction in MBP (ΔCO2: r2=0.13, P<0.001; ΔMBP: r2=0.12, P<0.001), with a slightly greater effect of ΔCO2 when ΔMBP was <10% (r2=0.15). Stratifying by quartile, MFV increased linearly during BH across quartiles of ΔMBP, with no increase with ΔetCO2. In contrast, during hyperventilation, MFV decreased linearly with ΔetCO2, independent of ΔMBP. Conclusions- In older patients with recent transient ischemic attack or minor stroke, cerebral blood flow responses to BH were confounded by BP changes but reflected etCO2 change during hyperventilation. Correct interpretation of cerebrovascular reactivity responses to etCO2, including in small vessel disease and carotid stenosis, requires concurrent BP measurement.