Pornographic picture processing interferes with working memory performance.
Some individuals report problems during and after Internet sex engagement, such as missing sleep and forgetting appointments, which are associated with negative life consequences. One mechanism potentially leading to these kinds of problems is that sexual arousal during Internet sex might interfere with working memory (WM) capacity, resulting in a neglect of relevant environmental information and therefore disadvantageous decision making. In this study, 28 healthy individuals performed 4 experimental manipulations of a pictorial 4-back WM task with neutral, negative, positive, or pornographic stimuli. Participants also rated 100 pornographic pictures with respect to sexual arousal and indicated masturbation urges previous to and following pornographic picture presentation. Results revealed worse WM performance in the pornographic picture condition of the 4-back task compared with the three remaining picture conditions. Furthermore, hierarchical regression analysis indicated an explanation of variance of the sensitivity in the pornographic picture condition by the subjective rating of the pornographic pictures as well as by a moderation effect of masturbation urges. Results contribute to the view that indicators of sexual arousal due to pornographic picture processing interfere with WM performance. Findings are discussed with respect to Internet sex addiction because WM interference by addiction-related cues is well known from substance dependencies.


Comprehensive and Scalable Highly Automated MS-Based Proteomic Workflow for Clinical Biomarker Discovery in Human Plasma.
Over the past decade, mass spectrometric performance has greatly improved in terms of sensitivity, dynamic range, and speed. By contrast, only limited progress has been accomplished with regard to automation, throughput, and robustness of the proteomic sample preparation process upstream of mass spectrometry. The present work delivers an optimized analysis of human plasma samples in both small preclinical and large clinical studies, enabled by the development of a highly automated quantitative proteomic workflow. Several iterative evaluation and validation steps were performed before process "design freeze" and development completion. A robotic liquid handling workflow and platform (including reduction, alkylation, digestion, TMT labeling, pooling, and purification) were shown to provide better quantitative trueness and precision than manual operation at the bench. Depletion of the most abundant human plasma proteins and subsequent buffer exchange were also developed and integrated. Finally, 96 identical pooled human plasma samples were prepared in a 96-well plate format, and each sample was individually subjected to our developed workflow. This test revealed increased throughput and robustness compared with to-date published manual or less automated workflows. Our workflow is ready-to-use for future (pre-) clinical studies. We expect our work to facilitate, accelerate, and improve clinical proteomic discovery in human blood plasma.


Overweight and aerobic fitness in children in the United States/Mexico border region.
To study overweight and aerobic fitness among children in the third and fourth grades of elementary schools in a city in the United States of America (El Paso, Texas) and a city in Mexico (Chihuahua, Chihuahua) that are on or near the border between those two countries, and to compare the results from those two cities with earlier findings for other children in the United States. We followed the El Paso children (427 boys and 385 girls, 93% of them of Mexican descent) from third to fourth grade and assessed the change in their body mass index (BMI). In the city of Chihuahua we cross-sectionally measured the BMI of a sample of third grade children (221 boys and 237 girls) and a sample of fourth grade children (268 boys and 215 girls). BMI and triceps skinfolds were measured for all the children studied in the two cities. BMI was used to assess risk for overweight (at least the 85th percentile BMI for age and gender) and overweight (at least the 95th percentile BMI for age and gender) in all the children. The distance that El Paso children ran in nine minutes was used to assess their aerobic fitness (aerobic fitness was not measured in the Chihuahua children). The data from El Paso were collected in 1999, 2000, and 2001, and the Chihuahua data were collected in 2000 and 2001. In the El Paso boys, overweight significantly increased in the one year from third grade to fourth grade, from 22% to 28%, while risk for overweight significantly increased, from 37% to 44%. In the El Paso girls, risk for overweight significantly increased over the same one-year period, from 29% to 37%. The El Paso boys and girls were significantly less fit when compared to samples of children from throughout the United States. Third and fourth grade children from Chihuahua had similar rates of risk for overweight and of overweight when compared to the children from the same grades in El Paso. Children in both El Paso and Chihuahua were more overweight than were non-Hispanic white children throughout the United States. In addition, the children in El Paso were less aerobically fit than were non-Hispanic white children and than were other Mexican-American children in the United States. These results clearly show that efforts should be made in the border regions of both Mexico and the United States to develop physical activity and nutrition programs to help stem rising rates of overweight.


Best practices for the treatment of metastatic pancreatic adenocarcinoma: the therapeutic landscape in 2017.
The vast majority of patients diagnosed with pancreatic adenocarcinoma have inoperable, most commonly metastatic, disease at the time of initial presentation, at which point systemic therapy becomes the mainstay of treatment. Although survival rates remain very poor in this clinical setting, patients currently have a greater number of therapeutic options available to them than ever before, and consequently individuals are more frequently able to be sequenced through multiple lines of treatment. In this review, we will provide an overview of the current treatment landscape for metastatic pancreatic cancer in 2017, focusing on best practices and the various factors that should be considered in selecting the most appropriate regimen for a given individual. Options for front-line therapy include both infusional 5-fluorouracil, leucovorin, irinotecan, oxaliplatin (FOLFIRINOX) and the combination of gemcitabine plus nab-paclitaxel; however, how to choose between these two regimens can sometimes pose a challenging problem, and some patients may not be suitable candidates for either. For patients who are robust enough to receive second-line therapy (and beyond), the selection of treatment depends in part on their prior treatment exposure; newer drugs such as nanoliposomal irinotecan (nal-IRI) (in combination with infusional 5-fluorouracil and leucovorin) are now approved by the United States Food and Drug Administration (FDA) specifically for use following disease progression on first-line gemcitabine-based therapy. Despite these welcome advances in standard of care treatment, patients should still be encouraged to participate in clinical trials whenever possible.


Efficacy of integrated school based de-worming and prompt malaria treatment on helminths -Plasmodium falciparum co-infections: A 33 months follow up study.
The geographical congruency in distribution of helminths and Plasmodium falciparum makes polyparasitism a common phenomenon in Sub Saharan Africa. The devastating effects of helminths-Plasmodium co-infections on primary school health have raised global interest for integrated control. However little is known on the feasibility, timing and efficacy of integrated helminths-Plasmodium control strategies. A study was conducted in Zimbabwe to evaluate the efficacy of repeated combined school based antihelminthic and prompt malaria treatment. A cohort of primary schoolchildren (5-17 years) received combined Praziquantel, albendazole treatment at baseline, and again during 6, 12 and 33 months follow up surveys and sustained prompt malaria treatment. Sustained prompt malaria treatment was carried out throughout the study period. Children's infection status with helminths, Plasmodium and helminths-Plasmodium co-infections was determined by parasitological examinations at baseline and at each treatment point. The prevalence of S. haematobium, S. mansoni, STH, malaria, helminths-Plasmodium co-infections and helminths infection intensities before and after treatment were analysed. Longitudinal data showed that two rounds of combined Praziquantel and albendazole treatment for schistosomiasis and STHs at 6 monthly intervals and sustained prompt malaria treatment significantly reduced the overall prevalence of S. haematobium, S. mansoni, hookworms and P. falciparum infection in primary schoolchildren by 73.5%, 70.8%, 67.3% and 58.8% respectively (p < 0.001, p < 0.001, p < 0.001, p < 0.001 respectively). More importantly, the prevalence of STH + schistosomes, P. f + schistosomes, and P. f + STHs + schistosomes co-infections were reduced by 68.0%, 84.2%, and 90.7%, respectively. The absence of anti-helminthic treatment between the 12 mth and 33 mth follow-up surveys resulted in the sharp increase in STHs + schistosomes co-infection from 3.3% at 12 months follow up survey to 10.7%, slightly more than the baseline level (10.3%) while other co-infection combinations remained significantly low. The overall prevalence of heavy S. haematobium, S. mansoni and hookworms infection intensities were significantly reduced from: 17.9-22.4% to 2.6-5.1%, 1.6-3.3% to 0.0% and 0.0-0.7% to 0.0% respectively. Biannual Integrated school based antihelminthic and sustained prompt malaria treatment has a potential to reduce the burden of helminths-plasmodium co-infections in primary school children. In areas of stable malaria transmission, active case finding is recommended to track and treat asymptomatic malaria cases as these may sustain transmission in the community.


Population balance models: a useful complementary modelling framework for future WWTP modelling.
Population balance models (PBMs) represent a powerful modelling framework for the description of the dynamics of properties that are characterised by distributions. This distribution of properties under transient conditions has been demonstrated in many chemical engineering applications. Modelling efforts of several current and future unit processes in wastewater treatment plants could potentially benefit from this framework, especially when distributed dynamics have a significant impact on the overall unit process performance. In these cases, current models that rely on average properties cannot sufficiently capture the true behaviour and even lead to completely wrong conclusions. Examples of distributed properties are bubble size, floc size, crystal size or granule size. In these cases, PBMs can be used to develop new knowledge that can be embedded in our current models to improve their predictive capability. Hence, PBMs should be regarded as a complementary modelling framework to biokinetic models. This paper provides an overview of current applications, future potential and limitations of PBMs in the field of wastewater treatment modelling, thereby looking over the fence to other scientific disciplines.


Influence of graded dehydration on hyperthermia and cardiovascular drift during exercise.
This investigation determined the effect of different rates of dehydration, induced by ingesting different volumes of fluid during prolonged exercise, on hyperthermia, heart rate (HR), and stroke volume (SV). On four different occasions, eight endurance-trained cyclists [age 23 +/- 3 (SD) yr, body wt 71.9 +/- 11.6 kg, maximal O2 consumption 4.72 +/- 0.33 l/min] cycled at a power output equal to 62-67% maximal O2 consumption for 2 h in a warm environment (33 degrees C dry bulb, 50% relative humidity, wind speed 2.5 m/s). During exercise, they randomly received no fluid (NF) or ingested a small (SF), moderate (MF), or large (LF) volume of fluid that replaced 20 +/- 1, 48 +/- 1, and 81 +/- 2%, respectively, of the fluid lost in sweat during exercise. The protocol resulted in graded magnitudes of dehydration as body weight declined 4.2 +/- 0.1, 3.4 +/- 0.1, 2.3 +/- 0.1, and 1.1 +/- 0.1%, respectively, during NF, SF, MF, and LF. After 2 h of exercise, esophageal temperature (Tes), HR, and SV were significantly different among the four trials (P < 0.05), with the exception of NF and SF. The magnitude of dehydration accrued after 2 h of exercise in the four trials was linearly related with the increase in Tes (r = 0.98, P < 0.02), the increase in HR (r = 0.99, P < 0.01), and the decline in SV (r = 0.99, P < 0.01). LF attenuated hyperthermia, apparently because of higher skin blood flow, inasmuch as forearm blood flow was 20-22% higher than during SF and NF at 105 min (P < 0.05). There were no differences in sweat rate among the four trials. In each subject, the increase in Tes from 20 to 120 min of exercise was highly correlated to the increase in serum osmolality (r = 0.81-0.98, P < 0.02-0.19) and the increase in serum sodium concentration (r = 0.87-0.99, P < 0.01-0.13) from 5 to 120 min of exercise. In summary, the magnitude of increase in core temperature and HR and the decline in SV are graded in proportion to the amount of dehydration accrued during exercise.


Social grants for people living with HIV and on antiretroviral therapy in KwaZulu-Natal, South Africa: a longitudinal study.
The aim of this study was to assess the predictors of the receipt of a disability grant (DG) status and the impact of the DG on health outcomes of HIV patients and on antiretroviral therapy (ART) in a longitudinal study over 20 months in KwaZulu-Natal, South Africa. Consecutive patients, 735 (29.8% males and 70.2% females), who attended three HIV clinics completed the assessments (with a structured questionnaire and medical file review) prior to antiretroviral initiation, 519 after 6 months, 557 after 12 months and 499 after 20 months on ART. The results indicate that a large number of HIV or ART patients were found to be in receipt of a DG, which declined significantly over the time of being on ART (from 52.3% at 6 months on ART to 9.8% at 20 months on ART). At various stages, being in receipt of a DG was found to be associated with not being employed, higher quality of life (QoL), older age, higher alcohol use score, no formal salary as household income and higher subjective health status in multivariable analyses. A significant number of patients lost their DG status over the assessment period, which was not found to be associated with major health outcomes (CD4 cell counts, adherence to ART and HIV symptoms). In a multiple regression generalized estimating equation model, not being in receipt of a DG, health-related QoL, lower HIV symptoms and lower depression scores were associated with CD4 counts. HIV patients who no longer qualify for the DG and yet do not have adequate financial means to meet basic necessities should be put on a nutritional support programme.


Non-invasive diagnosis of esophageal varices after Baveno VI.
A major complication of portal hypertension in patients with cirrhosis is the development of esophageal varices with the associated risk of variceal bleeding. Hence, the Baveno consensus on portal hypertension in its first five editions had recommended surveillance with periodic upper endoscopies in these patients to identify in a timely fashion the development of esophageal varices and initiate a primary prophylaxis strategy in those at a high risk of bleeding. For the first time, the Sixth Baveno Consensus on Portal Hypertension (Baveno VI) recommended using non-invasive tools to rule out the presence of varices with a high risk of bleeding. According to Baveno VI, surveillance endoscopy is not necessary for patients with "compensated advanced chronic liver disease" (cACLD) who have normal platelets (>150×109/L) and a liver stiffness measure (LSM) <20 kPa. In this review, we will briefly describe the currently available non-invasive methods to predict the presence of varices, such as serum tests, imaging, and elastography. We will also discuss the rationale that led to Baveno VI recommendation and describe the studies that have validated Baveno VI criteria after its publication. Finally, we will mention some potential caveats and suggest some areas for future research.


Potential of alfalfa as an alternative molt induction diet for laying hens: egg quality and consumer acceptability.
Dietary molt induction to initiate additional egg laying cycles in commercial laying hen flocks is a wide spread practice in the United States. Feed deprivation is the most commonly used method but this practice has generated several concerns which has lead to research for viable alternative approaches. From a management standpoint a single ingredient molting diet consisting of high fiber-low energy represents an easily adaptable diet for large laying hen production units. Alfalfa meal is readily available in most commercial locations and possesses many of the desirable properties of an ideal laying hen molt diet. In the current study hens at a commercial laying facility were molted by both alfalfa and feed deprivation. After the hens had reentered post-molt commercial egg production, eggs were examined for egg quality performance. Egg shell strength, albumen height, yolk height, weight, length, and yolk color were all tested using various mechanical techniques. The eggs were also sampled for testing by consumer sensory panels that assessed the desirability of the eggs' color and flavor/texture. Eggs laid by hens molted by alfalfa had a significantly lower (p<0.05) "a*" level of colorimetry. Eggs laid by hens molted with alfalfa also exhibited significantly higher (p<0.05) egg weights and length. In the consumer sensory test, there was no significant difference (p>0.05) in color or flavor/texture scores in eggs from either feed deprived or alfalfa molted hens. The consumer sensory and mechanical quality attributes indicates that alfalfa shows promise as an alternative molt induction diet by providing a single diet option for extending egg production into a second egg laying cycle.


Effect of human immunodeficiency virus-1 envelope glycoprotein on in vitro hematopoiesis of umbilical cord blood.
Although hypercellularity is a common bone marrow finding in patients with human immunodeficiency virus type 1 (HIV-1) infection, the effect of HIV-1 on the hematopoietic system, which has been investigated in in vitro studies, is still controversial. In this study, we have investigated the effects of HIV-1 envelope glycoprotein, gp160, on the differentiation of hematopoietic progenitor cells derived from cord blood. Culture of cord blood mononuclear cells with gp160 resulted in enhancement of the in vitro growth of myeloid hematopoietic progenitors. To investigate the mechanism of the enhancement, adherent cells, T cells, or CD34-bearing hematopoietic progenitors were isolated and cultivated with gp160 in a variety of culture conditions. We have shown that gp160 had no direct effect on highly purified hematopoietic progenitors but exerted its enhancing effect indirectly via T cells, by induction of a humoral colony-stimulating factor(s). The activity of gp160 on T cells was abrogated by preincubation of gp160 with recombinant CD4 molecule and goat anti-gp120 antibody. These data provide evidence for a novel biological activity of HIV envelope glycoprotein, that of T-cell-mediated stimulation of myelopoiesis. Binding of gp160 with the cell surface CD4 molecule appears to be necessary for secretion of the colony-stimulating factor(s).


Simultaneous detection of cell-secreted TNF-α and IFN-γ using micropatterned aptamer-modified electrodes.
Cellular production of such cytokines as interferon (IFN)-γ and tumor necrosis factor (TNF)-α is used to determine disease-specific immune responses and may be used to diagnose infectious diseases such as tuberculosis. In this paper, we describe the development of micropatterned electrodes functionalized with electroactive aptamers for multiplexed detection of immune-cell-produced cytokines. A sequence of electrode deprotection and aptamer incubation steps were used to assemble anti-IFN-γ DNA aptamers and anti-TNF-α RNA aptamers on individually addressable half-ring electrodes. Aptamer molecules were thiolated for assembly on gold and were functionalized with methylene blue redox reporter for electrochemical signal transduction. Specificity of individual sensors to the correct cytokine species was confirmed by exposure to recombinant cytokines. For cell detection experiments, electrode arrays were integrated into microfluidic devices and incubated with immune cells. Design of the surface was such that a small group of ~400 cells attached in the circular adhesion sites surrounded by half-ring electrodes sensing IFN-γ and TNF-α. The microdevice consisted of two parallel microfluidic channels, each channel containing four cell capture/sensing sites. Upon mitogenic activation, secreted IFN-γ and TNF-α molecules were monitored by performing square wave voltammetry (SWV) at different time points at individually addressable electrodes. This biosensing platform was used to analyze the quantity and rate of cytokine release from primary T cells and a monocyte cell line. Upon further development of this platform may be enhanced to enable detection of larger number of cytokines and used to correlate the levels and dynamics of cytokine release in immune cells to diagnosis and treatment of infectious diseases.


Fluorophotometric Determination of Riboflavin Concentrations in a Human Artificial Anterior Chamber Model.
Corneal cross-linking (CXL) requires an adequate corneal riboflavin impregnation, which is clinically assessed by verification of a riboflavin "flare" in the anterior chamber. We set out to replace this subjective assessment with an objective measurement method and evaluated fluorophotometry as an apparatus-based technique for riboflavin detection in the anterior chamber. In an artificial anterior chamber model using human corneas and a modified Fluorotron fluorophotometer, we determined the detection limits of riboflavin concentrations across native corneas by comparison measurements of the same concentrations in glass cuvettes. Subsequently, standard CXL procedures with corneal application of riboflavin were simulated and the proportions of riboflavin entering the anterior chamber were measured fluorophotometrically. The measurement results of the riboflavin dilution series in the artificial anterior chamber showed a very high concordance with the results obtained in a glass cuvette (Pitman test P = 0.329). In the CXL simulation, the mean riboflavin concentration measured in the anterior chamber increased within 15 minutes from 5 (±1) to 903 (±204) ng/mL and stood at 1089 (±56) ng/mL after 30 minutes. Fluorophotometry is able to measure riboflavin in an artificial anterior chamber across human corneas over a wide range of concentrations and it reliably detects the increasing riboflavin signal in simulated CXL procedures. The replacement of the subjective riboflavin detection by a technically straightforward, objective detection method might increase patient safety and treatment efficiency in CXL.


Changes in HIV prevalence among differently educated groups in Tanzania between 2003 and 2007.
HIV prevalence trends suggest that the epidemic is stable or declining in many sub-Saharan African countries. However, trends might differ between socioeconomic groups. Educational attainment is a common measure of socioeconomic position in HIV datasets from Africa. Several studies have shown higher HIV prevalence among more educated groups, but this may change over time. We describe changes in HIV prevalence by educational attainment in Tanzania from 2003 to 2007. Analysis of data from two large, nationally representative HIV prevalence surveys conducted among adults aged 15-49 years in Tanzania in 2003-2004 (10 934 participants) and 2007-2008 (15 542 participants). We explored whether changes in HIV prevalence differed between groups with different levels of educational attainment after adjustment for potential confounding factors (sex, age, urban/rural residence and household wealth). Changes in HIV prevalence differed by educational attainment level (interaction test P value = 0.07). HIV prevalence was stable among those with no education (adjusted odds ratio 2007-2008 vs. 2003-2004 1.03, 95% confidence interval 0.72-1.47), whereas showing a small but borderline significant decline among those with primary education (adjusted odds ratio 0.85, 95% confidence interval 0.69-1.03) and a larger statistically significant decline among those with secondary education (adjusted odds ratio 0.53, 95% confidence interval 0.34-0.84). Prevalent HIV infections are now concentrating among those with the lowest levels of education in Tanzania. Although HIV-related mortality, migration and cohort effects might contribute to this, different HIV incidence by educational level between the surveys provides the most likely explanation. Urgent measures to improve HIV prevention among those with limited education and of low socioeconomic position are necessary in Tanzania.


A method for an approximate determination of a polymer-rich-domain concentration in phase-separated poly(N-isopropylacrylamide) aqueous solution by means of confocal Raman microspectroscopy combined with optical tweezers.
The paper demonstrates that a confocal Raman microspectroscope combined with optical tweezers is a promising technique to estimate polymer concentration in polymer-rich domain in phase-separated-aqueous polymer solution. The sample polymer is poly-(N-isopropylacrylamide) (PNIPAM) that is well-known as a representative thermo-responsive polymer. Optical tweezers can selectively trap the polymer-rich domain at the focal point in non-contact and non-intrusive modes. Such situation allows us to determine polymer concentration in the domain, which has been unclear due to a lack of appropriate analytical technique. It is applicable for a variety of other thermo-responsive polymers.


Relevance of the deletion of the Tatri4 gene in the secondary metabolome of Trichoderma arundinaceum.
The fungus Trichoderma arundinaceum (Ta37) has a significant biocontrol application which has been related to the production of the trichothecene, harzianum A (2). Previous studies with a strain of T. arundinaceum which was blocked for the production of 2, revealed the existence of a chemical cross-regulation between the biocontrol fungus and its target organism. A study of the secondary metabolome of a single culture of a mutant of T. arundinaceum TaΔTri4 which produces trichothecene biosynthetic intermediates, has now been carried out. The production of secondary metabolites in a co-culture with the phytopathogen, Botrytis cinerea, was then analyzed. The mutant produced a larger quantity of the aspinolides B (6) and C (7) and other derivatives when compared to the wild type Ta37. Ten new metabolites were isolated: three aspinolides 12-14, the γ-lactones 15 and 16, two hemi-ketals 17 and 18 and three aspinolide degradation products, 19, 21 and 22. In the confrontation cultures involving the TaΔTri4 and the B. cinerea B05.10 strains, there was a higher production of the aspinolides B and C by the TaΔTri4 mutant while the production of the botryanes and botcinins by B. cinerea was reduced in the area of interaction between the cultures. These results shed light on the chemical cross-talk and ecological interactions between these fungi.


Review: The variability of the eating quality of beef can be reduced by predicting consumer satisfaction.
The Meat Standards Australia (MSA) grading scheme has the ability to predict beef eating quality for each 'cut×cooking method combination' from animal and carcass traits such as sex, age, breed, marbling, hot carcass weight and fatness, ageing time, etc. Following MSA testing protocols, a total of 22 different muscles, cooked by four different cooking methods and to three different degrees of doneness, were tasted by over 19 000 consumers from Northern Ireland, Poland, Ireland, France and Australia. Consumers scored the sensory characteristics (tenderness, flavor liking, juiciness and overall liking) and then allocated samples to one of four quality grades: unsatisfactory, good-every-day, better-than-every-day and premium. We observed that 26% of the beef was unsatisfactory. As previously reported, 68% of samples were allocated to the correct quality grades using the MSA grading scheme. Furthermore, only 7% of the beef unsatisfactory to consumers was misclassified as acceptable. Overall, we concluded that an MSA-like grading scheme could be used to predict beef eating quality and hence underpin commercial brands or labels in a number of European countries, and possibly the whole of Europe. In addition, such an eating quality guarantee system may allow the implementation of an MSA genetic index to improve eating quality through genetics as well as through management. Finally, such an eating quality guarantee system is likely to generate economic benefits to be shared along the beef supply chain from farmers to retailors, as consumers are willing to pay more for a better quality product.


Kinetics of the formation and removal of cisplatin-DNA adducts in blood cells and tumor tissue of cancer patients receiving chemotherapy: comparison with in vitro adduct formation.
During chemotherapy with a cisplatin-containing combination of drugs, 217 blood samples from 30 cancer patients were analyzed for the presence of the main cisplatin-DNA adduct cis-Pt(NH3)2d(pGpG) (Pt-GG). Cisplatin was administered during 3-h infusions on each of 5 consecutive days, resulting in increasing adduct levels which, on the average, were about twice as high after the fifth as after the first infusion. Higher levels were found in blood samples of patients who received the same total amount of cisplatin in one single 3-h infusion. No significant differences in adduct levels were found during first and repeated courses. The nonlinear dependence of adduct levels on total dose can be attributed to removal of adducts. At 21 h after a very first cisplatin infusion 76% of the adducts were removed. Lower percentages of removal were observed over the 21-h periods following the fourth and fifth infusions of 5-day courses (49 and 53%, respectively). After the initial 21 h the removal of adducts continued, albeit at a slower rate. Substantial interindividual variation was found in the adduct levels, which did correlate with the levels obtained after in vitro cisplatin treatment of blood samples from the same patients but not with their age or gender. Testicular cancer patients with complete tumor response showed higher adduct levels in their blood than those with partial response or progressive disease. When blood samples from 8 healthy volunteers were treated with cisplatin in vitro, the person-to-person variation in adduct levels and the intraindividual variation observed over a 2-year period were found to be in the same range, which was narrower than that observed with samples from treated patients. In vitro studies with human blood showed that the formation of the Pt-GG adduct is proportional to cisplatin concentration and complete after about 1 hour. In some of the in vivo and in vitro cisplatin-treated blood samples, all 4 known platinum-DNA adducts were determined. In all cases Pt-GG was by far the major adduct, and no significant differences were observed with respect to the relative amounts of the 4 adducts. Similar adduct ratios were found in DNA from a testicular tumor obtained from a patient who underwent orchidectomy; the Pt-GG adduct level was about 10-fold higher than that in his blood cells.


Oxygen isotopes in refractory stratospheric dust particles: proof of extraterrestrial origin.
The oxygen and magnesium isotopic compositions of five individual particles that were collected from the stratosphere and that bear refractory minerals were measured by secondary ion mass spectrometry. Four of the particles exhibit excesses of oxygen-16 similar to those observed in anhydrous mineral phases of carbonaceous chondrites and thus are extraterrestrial. The oxygen and magnesium isotopic abundances of one corundum-rich particle are consistent with a terrestrial origin. Magnesium in the four extraterrestrial particles is isotopically normal. It is unlikely that these particles are derived from carbonaceous chondrites and thus such particles probably represent a new type of collected extraterrestrial material.


Parameter-free methods distinguish Wnt pathway models and guide design of experiments.
The canonical Wnt signaling pathway, mediated by β-catenin, is crucially involved in development, adult stem cell tissue maintenance, and a host of diseases including cancer. We analyze existing mathematical models of Wnt and compare them to a new Wnt signaling model that targets spatial localization; our aim is to distinguish between the models and distill biological insight from them. Using Bayesian methods we infer parameters for each model from mammalian Wnt signaling data and find that all models can fit this time course. We appeal to algebraic methods (concepts from chemical reaction network theory and matroid theory) to analyze the models without recourse to specific parameter values. These approaches provide insight into aspects of Wnt regulation: the new model, via control of shuttling and degradation parameters, permits multiple stable steady states corresponding to stem-like vs. committed cell states in the differentiation hierarchy. Our analysis also identifies groups of variables that should be measured to fully characterize and discriminate between competing models, and thus serves as a guide for performing minimal experiments for model comparison.


Current treatments and preventive strategies for radiation retinopathy.
Radiation retinopathy remains a devastating cause of visual morbidity in patients undergoing radiation for globe, orbit, and head and neck malignancies. This review discusses the recent efforts of several authors to treat radiation retinopathy once it has developed and efforts to prevent its development with early aggressive management. Intravitreal anti-vascular endothelial growth factor agents and intravitreal steroid agents have been used to successfully treat radiation-induced macular edema and neovascular events secondary to radiation retinopathy. The visual outcomes, however, have varied. Recent work has been directed towards prevention of radiation retinopathy prior to its development. This has been done with preventive scatter laser and intravitreal bevacizumab therapy. Effective customization of radiation dose to the tumor has also reduced some collateral radiation damage. Preventive vitrectomy and silicone oil placement at the time of plaque brachytherapy may shield normal ocular structures from radiation injury. Radiation retinopathy remains a major source of visual morbidity following radiotherapy for malignancies. Promising, albeit unproven, new therapies and preventive efforts may ameliorate the negative visual outcomes.


Toward development of a fibromyalgia responder index and disease activity score: OMERACT module update.
Following development of the core domain set for fibromyalgia (FM) in Outcome Measures in Rheumatology Clinical Trials (OMERACT) meetings 7 to 9, the FM working group has progressed toward the development of an FM responder index and a disease activity score based on these domains, utilizing outcome indices of these domains from archived randomized clinical trials in FM. Possible clinical domains that could be included in a responder index and disease activity score include pain, fatigue, sleep disturbance, cognitive dysfunction, mood disturbance, tenderness, stiffness, and functional impairment. Outcome measures for these domains demonstrate good to adequate psychometric properties, although measures of cognitive dysfunction need to be further developed. The approach used in the development of responder indices and disease activity scores for rheumatoid arthritis and ankylosing spondylitis represents heuristic models for our work, but FM is challenging in that there is no clear algorithm of treatment that defines disease activity based on treatment decisions, nor are there objective markers that define thresholds of severity or response to treatment. The process of developing candidate dichotomous responder definitions and continuous quantitative disease activity measures is described, along with participant discussions from OMERACT 10. Final results of this work will be published in a separate report pending completion of analyses.


The associations between personality traits, education, occupation and the occurrence of eczema in adulthood.
There were 5834 participants with complete data on parental social class at birth, childhood cognitive ability tests scores at 11 years, educational qualifications at 33 years, the Big Five-Factor personality traits, occupational levels and eczema (measured at age 50 years). Results showed that eczema in childhood, educational achievement and occupational levels were significantly associated with the occurrence of reported eczema in adulthood. Emotionally Stable people (non-neurotic) were less likely to have eczema, but those with high Agreeableness and Openness more likely to have eczema. Childhood cognitive ability was significantly and positively associated with eczema in adulthood.


Systematic Transcriptional Profiling of Responses to STAT1- and STAT3-Activating Cytokines in Different Cancer Types.
Cytokines orchestrate responses to pathogens and in inflammatory processes, but they also play an important role in cancer by shaping the expression levels of cytokine response genes. Here, we conducted a large profiling study comparing miRNome and mRNA transcriptome data generated following different cytokine stimulations. Transcriptomic responses to STAT1- (IFNγ, IL-27) and STAT3-activating cytokines (IL6, OSM) were systematically compared in nine cancerous and non-neoplastic cell lines of different tissue origins (skin, liver and colon). The largest variation in our datasets was seen between cell lines of the three different tissues rather than stimuli. Notably, the variability in miRNome datasets was a lot more pronounced than in mRNA data. Our data also revealed that cells of skin, liver and colon tissues respond very differently to cytokines and that the cell signaling networks activated or silenced in response to STAT1- or STAT3-activating cytokines are specific to the tissue and the type of cytokine. However, globally, STAT1-activating cytokines had stronger effects than STAT3-inducing cytokines with most significant responses in liver cells, showing more genes upregulated and with higher fold change. A more detailed analysis of gene regulations upon cytokine stimulation in these cells provided insights into STAT1- versus STAT3-driven processes in hepatocarcinogenesis. Finally, independent component analysis revealed interconnected transcriptional networks distinct between cancer cells and their healthy counterparts.


Approach to outcome measurement in the prevention of thrombosis in surgical and medical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.
This article provides the rationale for the approach to making recommendations primarily used in four articles of the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines: orthopedic surgery, nonorthopedic surgery, nonsurgical patients, and stroke. Some of the early clinical trials of antithrombotic prophylaxis with a placebo or no treatment group used symptomatic VTE and fatal PE to measure efficacy of the treatment. These trials suggest a benefit of thromboprophylaxis in reducing fatal PE. In contrast, most of the recent clinical trials comparing the efficacy of alternative anticoagulants used a surrogate outcome, asymptomatic DVT detected at mandatory venography. This outcome is fundamentally unsatisfactory because it does not allow a trade-off with serious bleeding; that trade-off requires knowledge of the number of symptomatic events that thromboprophylaxis prevents. In this article, we review the merits and limitations of four approaches to estimating reduction in symptomatic thrombosis: (1) direct measurement of symptomatic thrombosis, (2) use of asymptomatic events for relative risks and symptomatic events from randomized controlled trials for baseline risk, (3) use of baseline risk estimates from studies that did not perform surveillance and relative effect from asymptomatic events in randomized controlled trials, and (4) use of available data to estimate the proportion of asymptomatic events that will become symptomatic. All approaches have their limitations. The optimal choice of approach depends on the nature of the evidence available.


Cognitive decline after carotid endarterectomy: Systematic review and meta-analysis.
Postoperative cognitive decline (pCD) occurs frequently (6 to 30%) after carotid endarterectomy (CEA), although there are no exact estimates and risk factors are still unclear. The objective of this study was to determine pCD incidence and risk factors in CEA patients. We performed a systematic review and meta-analysis of both randomised and nonrandomised trials following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched Cochrane, PubMed/Medline and Embase databases from the date of database inception to 1 December 2018. We selected longitudinal studies including CEA patients with both pre-operative and postoperative cognitive assessments. Primary outcome was pCD incidence, differentiating delayed neurocognitive recovery (dNCR) and postoperative neurocognitive disorder (pNCD). dNCR and pNCD incidences were expressed as proportions of cases on total CEA sample and pooled as weighted estimates from proportions. Postoperative delirium was excluded from the study design. Secondary outcomes were patient-related (i.e. age, sex, diabetes, hypertension, contralateral stenosis, pre-operative symptoms, dyslipidaemia and statin use) and procedure-related (i.e. hyperperfusion, cross-clamping duration and shunting placement) risk factors for pCD. We estimated odds ratios (ORs) and mean differences through a random effects model by using STATA 13.1 and RevMan 5.3. Our search identified 5311 publications and 60 studies met inclusion criteria reporting a total of 4823 CEA patients. dNCR and pNCD incidence were 20.5% [95% confidence interval (CI), 17.1 to 24.0] and 14.1% (95% CI, 9.5 to 18.6), respectively. pCD risk was higher in patients experiencing hyperperfusion during surgery (OR, 35.68; 95% CI, 16.64 to 76.51; P < 0.00001; I = 0%), whereas dNCR risk was lower in patients taking statins before surgery (OR, 0.56; 95% CI, 0.41 to 0.77; P = 0.0004; I = 19%). Sensitivity analysis revealed that longer cross-clamping duration was a predictor for dNCR (mean difference, 5.25 min; 95% CI, 0.87 to 9.63; P = 0.02; I = 49%). We found high incidences of dNCR (20.5%) and pNCD (14.1%) after CEA. Hyperperfusion seems to be a risk factor for pCD, whereas the use of statins is associated with a lower risk of dNCR. An increased cross-clamping duration could be a risk factor for dNCR. This systematic review was registered in the International Prospective Register of Systematic Reviews (CDR42017073633).


A proposed panel of biomarkers of healthy ageing.
There is no criterion reference for assessing healthy ageing and this creates difficulties when conducting and comparing research on ageing across studies. A cardinal feature of ageing is loss of function which translates into wide-ranging consequences for the individual and for family, carers and society. We undertook comprehensive reviews of the literature searching for biomarkers of ageing on five ageing-related domains including physical capability and cognitive, physiological and musculoskeletal, endocrine and immune functions. Where available, we used existing systematic reviews, meta-analyses and other authoritative reports such as the recently launched NIH Toolbox for assessment of neurological and behavioural function, which includes test batteries for cognitive and motor function (the latter described here as physical capability). We invited international experts to comment on our draft recommendations. In addition, we hosted an experts workshop in Newcastle, UK, on 22-23 October 2012, aiming to help capture the state-of-the-art in this complex area and to provide an opportunity for the wider ageing research community to critique the proposed panel of biomarkers. Here we have identified important biomarkers of healthy ageing classified as subdomains of the main areas proposed. Cardiovascular and lung function, glucose metabolism and musculoskeletal function are key subdomains of physiological function. Strength, locomotion, balance and dexterity are key physical capability subdomains. Memory, processing speed and executive function emerged as key subdomains of cognitive function. Markers of the HPA-axis, sex hormones and growth hormones were important biomarkers of endocrine function. Finally, inflammatory factors were identified as important biomarkers of immune function. We present recommendations for a panel of biomarkers that address these major areas of function which decline during ageing. This biomarker panel may have utility in epidemiological studies of human ageing, in health surveys of older people and as outcomes in intervention studies that aim to promote healthy ageing. Further, the inclusion of the same common panel of measures of healthy ageing in diverse study designs and populations may enhance the value of those studies by allowing the harmonisation of surrogate endpoints or outcome measures, thus facilitating less equivocal comparisons between studies and the pooling of data across studies.


Respiratory infections and the autumn increase in asthma morbidity.
Unexplained autumn increases in hospital admissions for asthma have been reported in many countries, including the United States, Canada, England and Wales. To investigate the role of infection, the association was tested between hospital admissions for asthma and respiratory infections among preschool children in Metropolitan Toronto, Canada during the period 1981 to 1989. The seasonal pattern in overall hospital utilization was assessed by admissions for nonrespiratory diseases. Time series analysis was used to remove potentially confounding temporal trends and the influence of correlated errors. A fourfold increase in asthma admissions occurred between July and October unaccompanied by similar increases in nonrespiratory admissions. Admissions began increasing during the third week of August, peaked during the third week in September, and slowly decreased during November and December. After adjusting for serial correlation, trends, climate, ambient air pollution and aeroallergens, the seasonal pattern of respiratory infection explained 14% of the variance in asthma admissions. Based on seasonal patterns, respiratory infection is the major identifiable risk factor for the large autumnal increase in asthma admissions.


FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer.
Data are lacking on the efficacy and safety of a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) as compared with gemcitabine as first-line therapy in patients with metastatic pancreatic cancer. We randomly assigned 342 patients with an Eastern Cooperative Oncology Group performance status score of 0 or 1 (on a scale of 0 to 5, with higher scores indicating a greater severity of illness) to receive FOLFIRINOX (oxaliplatin, 85 mg per square meter of body-surface area; irinotecan, 180 mg per square meter; leucovorin, 400 mg per square meter; and fluorouracil, 400 mg per square meter given as a bolus followed by 2400 mg per square meter given as a 46-hour continuous infusion, every 2 weeks) or gemcitabine at a dose of 1000 mg per square meter weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. Six months of chemotherapy were recommended in both groups in patients who had a response. The primary end point was overall survival. The median overall survival was 11.1 months in the FOLFIRINOX group as compared with 6.8 months in the gemcitabine group (hazard ratio for death, 0.57; 95% confidence interval [CI], 0.45 to 0.73; P<0.001). Median progression-free survival was 6.4 months in the FOLFIRINOX group and 3.3 months in the gemcitabine group (hazard ratio for disease progression, 0.47; 95% CI, 0.37 to 0.59; P<0.001). The objective response rate was 31.6% in the FOLFIRINOX group versus 9.4% in the gemcitabine group (P<0.001). More adverse events were noted in the FOLFIRINOX group; 5.4% of patients in this group had febrile neutropenia. At 6 months, 31% of the patients in the FOLFIRINOX group had a definitive degradation of the quality of life versus 66% in the gemcitabine group (hazard ratio, 0.47; 95% CI, 0.30 to 0.70; P<0.001). As compared with gemcitabine, FOLFIRINOX was associated with a survival advantage and had increased toxicity. FOLFIRINOX is an option for the treatment of patients with metastatic pancreatic cancer and good performance status. (Funded by the French government and others; ClinicalTrials.gov number, NCT00112658.).


Who participates in internet-based worksite weight loss programs?
The reach and representativeness are seldom examined in worksite weight loss studies. This paper describes and illustrates a method for directly assessing the reach and representativeness of a internet-based worksite weight loss program. A brief health survey (BHS) was administered, between January 2008 and November 2009, to employees at 19 worksites in Southwest Virginia. The BHS included demographic, behavioral, and health questions. All employees were blinded to the existence of a future weight loss program until the completion of the BHS. The BHS has a participation rate of 66 percent and the subsequent weight loss program has a participation rate of 30 percent. Employees from higher income households, with higher education levels and health literacy proficiency were significantly more likely to participate in the program (p's < .01). Worksite weight loss programs should include targeted marketing strategies to engage employees with lower income, education, and health literacy.


Differences in early and late mild cognitive impairment tractography using a diffusion tensor MRI.
Diffusion tensor MRI tractography is an imaging tool that can provide information of in-vivo neuronal fiber tracts to assess progress for Alzheimer's disease (AD). In an effort to detect early AD progression, we focused on distinguishing subgroups within mild cognitive impairment (MCI): early MCI and late MCI. Tractography was applied not only to white matter regions but also neighboring gray matter regions known to be affected by AD. Nerve fibers touching the hippocampus, thalamus, and amygdala in both hemispheres were extracted to quantify limbic system fiber connectivity. Two fiber extraction algorithms, fiber assignment by continuous tracking and the Runge Kutta approach, were applied to an AD imaging database. We computed the number of fibers touching regions of interest as the imaging feature. The imaging feature could distinguish between the MCI subgroups. It was also significantly correlated with a known genetic marker for AD, the apolipoprotein E epsilon 4 allele. The number of fibers might be a useful imaging biomarker to complement conventional region of interest-based biomarkers for AD research.


Metabolic risk factors and the impact of medical therapy on the management of nephrolithiasis in obese patients.
Previous studies have demonstrated that obesity can increase the risk of stone formation as well as recurrence rates of stone disease. Yet appropriate medical management can significantly decrease the risk of recurrent stone disease. Therefore, we analyzed our obese patient population, assessing the risk factors for stone formation and the impact of selective medical therapy on recurrent stone formation. A retrospective chart review was performed to identify obese patients with stone disease from our Stone Center. Metabolic risk factors for stones were identified as well as patient response to medical therapy. A similar analysis was performed on a group of age and sex matched nonobese stone formers. Of 1,021 patients 140 (14%) were identified as obese (body mass index greater than 30). Of these patients complete metabolic evaluations were available in 83 with an average followup of 2.3 years. The most common presenting metabolic abnormalities among these obese patients included gouty diathesis (54%), hypocitraturia (54%) and hyperuricosuria (43%), which presented at levels that were significantly higher than those of the nonobese stone formers (p <0.05). Stone analysis was available in 32 obese patients with 63% having uric acid calculi. After initiating treatment with selective medical therapy obese and nonobese patients demonstrated normalization of metabolic abnormalities, resulting in an average decrease in new stone formation from 1.75 to 0.15 new stones formed per patient per year in both groups. Obesity, as a result of dietary indiscretion, probable purine gluttony and possible type II diabetes, appears to have a significant role in recurrent stone formation. Appropriate metabolic evaluation, institution of medical therapy and dietary recommendations to decrease animal protein intake can significantly improve the risk of recurrent stone formation in these often difficult to treat patients.


Poaching empties critical Central African wilderness of forest elephants.
Elephant populations are in peril everywhere, but forest elephants in Central Africa have sustained alarming losses in the last decade [1]. Large, remote protected areas are thought to best safeguard forest elephants by supporting large populations buffered from habitat fragmentation, edge effects and human pressures. One such area, the Minkébé National Park (MNP), Gabon, was created chiefly for its reputation of harboring a large elephant population. MNP held the highest densities of elephants in Central Africa at the turn of the century, and was considered a critical sanctuary for forest elephants because of its relatively large size and isolation. We assessed population change in the park and its surroundings between 2004 and 2014. Using two independent modeling approaches, we estimated a 78-81% decline in elephant numbers over ten years - a loss of more than 25,000 elephants. While poaching occurs from within Gabon, cross-border poaching largely drove the precipitous drop in elephant numbers. With nearly 50% of forest elephants in Central Africa thought to reside in Gabon [1], their loss from the park is a considerable setback for the preservation of the species.


Superoxide radical production stimulates retroocular fibroblast proliferation in Graves' ophthalmopathy.
Retroocular fibroblast proliferation is believed to be a key component in the pathogenesis of Graves' ophthalmopathy. In the present study, we assessed the ability of superoxide radicals, generated using the xanthine oxidase/hypoxanthine system to induce cellular proliferation in cultured human retroocular fibroblasts obtained from two patients with severe Graves' ophthalmopathy and two control patients undergoing corrective eye surgery. In tissue obtained from patients with Graves' ophthalmopathy, fibroblast proliferation, as assessed by [3H]-thymidine incorporation, was induced by superoxide radicals in a dose-dependent manner. Xanthine oxidase or hypoxanthine alone had no proliferative effect, and control retroocular fibroblasts showed no proliferation in response to superoxide generation. Preincubation with the antithyroid drug methimazole, at concentrations ranging from 0-25 microM, prevented superoxide-induced fibroblast proliferation in a dose-response pattern. Preincubation with the xanthine oxidase inhibitor, allopurinol (1.0 mM) or the antioxidant nicotinamide (10 microM) also inhibited superoxide-induced fibroblast proliferation, whereas propylthiouracil (10 microM) had little effect. These studies suggest a pathway through which oxygen free radicals may contribute to the retroocular fibroblast proliferation observed in patients with Graves' ophthalmopathy.


Effect of intensive diabetes treatment on carotid artery wall thickness in the epidemiology of diabetes interventions and complications. Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group.
The Epidemiology of Diabetes Interventions and Complications (EDIC) is a multicenter longitudinal observational study of the Diabetes Control and Complications Trial (DCCT) cohort. One of the major objectives of EDIC is to study the development and progression of atherosclerotic cardiovascular disease in type 1 diabetes. In this study, we evaluated the role of cardiovascular risk factors and antecedent therapy in the DCCT on carotid intima-media wall thickness (IMT) in type 1 diabetes. At approximately 18 months after the end of the DCCT, high-resolution B-mode ultrasonography was used to assess the carotid arteries of 1,325 patients with type 1 diabetes, 19-51 years of age, with duration of diabetes ranging from 6.3 to 26.1 years. An age- and sex-matched nondiabetic population (n = 153) was studied with the same protocol. The ultrasound protocol was carried out in 28 EDIC clinics by centrally trained and certified sonographers using one of three scanning systems. Determination of IMT from videotaped images was performed by a single reader at the Central Ultrasound Reading Unit. Univariate associations with greater IMT were strongest for older age and longer diabetes duration, greater waist-to-hip ratio (men only), higher blood pressure, higher LDL cholesterol, and smoking. The DCCT therapy group (intensive versus conventional) and HbA1c, measured at the time of the ultrasound or the mean HbA1c during the DCCT, were not significantly related to IMT. Multivariate analyses suggest that age, height, smoking, and BMI were the major predictors of common carotid IMT, whereas age, smoking, and LDL cholesterol predicted internal carotid IMT. There were significant differences between the IMT values of the internal carotid artery in the EDIC male cohort and similarly aged male nondiabetic control subjects. There were no significant differences between the IMT values in the EDIC female cohort and similarly aged female nondiabetic control subjects. At this point in the planned 10-year follow-up of the DCCT cohort, neither intensive therapy nor HbA1c level appears to influence the early signs of atherosclerosis. Traditional risk factors, including age, smoking, and LDL cholesterol, were related to IMT. As the cohort is only now entering the age interval during which rapid progression and clinical expression of atherosclerosis are expected, further follow-up will help to determine the role of hyperglycemia, and its interaction with other risk factors, on the development of atherosclerosis.


Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients.
To describe the prevalence of, risk factors for, and prognostic importance of gastrointestinal (GI) bleeding and use of acid suppressants in acutely ill adult intensive care patients. We included adults without GI bleeding who were acutely admitted to the intensive care unit (ICU) during a 7-day period. The primary outcome was clinically important GI bleeding in ICU, and the analyses included estimations of baseline risk factors and potential associations with 90-day mortality. A total of 1,034 patients in 97 ICUs in 11 countries were included. Clinically important GI bleeding occurred in 2.6 % (95 % confidence interval 1.6-3.6 %) of patients. The following variables at ICU admission were independently associated with clinically important GI bleeding: three or more co-existing diseases (odds ratio 8.9, 2.7-28.8), co-existing liver disease (7.6, 3.3-17.6), use of renal replacement therapy (6.9, 2.7-17.5), co-existing coagulopathy (5.2, 2.3-11.8), acute coagulopathy (4.2, 1.7-10.2), use of acid suppressants (3.6, 1.3-10.2) and higher organ failure score (1.4, 1.2-1.5). In ICU, 73 % (71-76 %) of patients received acid suppressants; most received proton pump inhibitors. In patients with clinically important GI bleeding, crude and adjusted odds for mortality were 3.7 (1.7-8.0) and 1.7 (0.7-4.3), respectively. In ICU patients clinically important GI bleeding is rare, and acid suppressants are frequently used. Co-existing diseases, liver failure, coagulopathy and organ failures are the main risk factors for GI bleeding. Clinically important GI bleeding was not associated with increased adjusted 90-day mortality, which largely can be explained by severity of comorbidity, other organ failures and age.


Prevalence and predictors of highly active antiretroviral therapy use in patients with HIV infection in the united states. HCSUS Consortium. HIV Cost and Services Utilization.
Highly active antiretroviral therapy (HAART) became standard for HIV in 1996. Studies at that time showed that most people infected with HIV had initiated HAART, but that members of minority groups and poor people had lower HAART use. It is not known whether high levels of HAART use have been sustained or whether socioeconomic and racial disparities have diminished over time. To determine the proportion of patients who had received and were receiving HAART by January 1998, and to evaluate predictors of HAART receipt. Prospective cohort study of a national probability sample of 2267 adults receiving HIV care who completed baseline, first follow-up, and second follow-up interviews from January 1996 to January 1998. Proportion currently using HAART at second follow-up (August 1997 to January 1998), contrasted with the cumulative proportions using HAART at any time before January 1998 and before December 1996. Bivariate and multiple logistic regression analysis of population characteristics predicting current use of HAART at the time of the second follow-up interview. The proportion of patients ever having received HAART increased from 37% in December 1996 to 71% by January 1998, but only 53% of people were receiving HAART at the time of the second follow-up interview. Differences between sociodemographic groups in ever using HAART narrowed after 1996. In bivariate analysis, several groups remained significantly less likely to be using HAART at the time of the second follow-up interview: blacks, male and female drug users, female heterosexuals, people with less education, those uninsured and insured by Medicaid, those in the Northeast, and those with CD4 counts of >/=500 cells/microl (all p <.05). Using multiple logistic regression analysis, low CD4 count (for CD4 <50 cells/microl: odds ratio [OR], 3.20; p <.001) remained a significant predictor of current HAART use at the time of the second follow-up interview, but lack of insurance (OR, 0.71; p <.05) predicted not receiving HAART. The proportion of persons under HIV care in the United States who had ever received HAART increased to over 70% of the affected population by January 1998 and the disparities in use between groups narrowed but did not disappear. However, nearly half of those eligible for HAART according to the U.S. Department of Health and Human Services guidelines were not actually receiving it nearly 2 years after these medications were first introduced. Strategies to promote the initiation and continuation of HAART are needed for those without contraindications and those who can tolerate it.


Development of quinone analogues as dynamin GTPase inhibitors.
Virtual screening of the ChemDiversity and ChemBridge compound databases against dynamin I (dynI) GTPase activity identified 2,5-bis-(benzylamino)-1,4-benzoquinone 1 as a 273 ± 106 μM inhibitor. In silico lead optimization and focused library-led synthesis resulted in the development of four discrete benzoquinone/naphthoquinone based compound libraries comprising 54 compounds in total. Sixteen analogues were more potent than lead 1, with 2,5-bis-(4-hydroxyanilino)-1,4-benzoquinone (45) and 2,5-bis(4-carboxyanilino)-1,4-benzoquinone (49) the most active with IC50 values of 11.1 ± 3.6 and 10.6 ± 1.6 μM respectively. Molecular modelling suggested a number of hydrogen bonding and hydrophobic interactions were involved in stabilization of 49 within the dynI GTP binding site. Six of the most active inhibitors were evaluated for potential inhibition of clathrin-mediated endocytosis (CME). Quinone 45 was the most effective CME inhibitor with an IC50(CME) of 36 ± 16 μM.


Mechanisms of genetic resistance to Friend virus leukemia. III. Susceptibility of mitogen-responsive lymphocytes mediated by T cells.
Friend leukemia virus (FV) suppressed the proliferative responses of spleen, lymph node, marrow, and thymus cell populations to various T- and B-cell mitogens. Cells taken from mice, e.g. BALB/c genetically susceptible to leukemogenesis in vivo were much more susceptible to suppression of mitogenesis in vitro than similar cells from genetically resistant mice, e.g., C57BL/6. Nylon wool-purified splenic T cells from BALB/c and C3H mice lost susceptibility to FV-induced suppression of mitogenesis but became suppressible by addition of 10% unfiltered spleen cell. Thus, FV mediates in vitro suppression of lymphocyte proliferation indirectly by "activating" a suppressor cell. The suppressor cell adhered to nylon wool but not to glass wool or rayon wool columns. Pretreatment of spleen cells with carbonyl iron and a magnet did not abrogate the suppressor cell function. Suppressor cells were not eliminated by treatment with rabbit antimouse immunoglobulin (7S) and complement (C). However, high concentrations of anti-Thy-1 plus C destroyed suppressor cells of the spleen; thymic suppressor cells were much more susceptible to anti-Thy-1 serum. Nude athymic mice were devoid of suppressor cells and their B-cell proliferation was relatively resistant to FV-induced suppression in vitro. The suppressor cells in the thymus (but not in the spleen) were eliminated by treatment of mice with cortisol. Thus, FV appears to mediate its suppressive effect on mitogen-responsive lymphocytes by affecting "T-suppressor cells." Spleen cells from C57BL/6 mice treated with 89Sr to destroy marrow-dependent (M) cells were much more suppressible by FV in virto than normal C57BL/6 spleen cells. However, nylon-filtered spleen cells of 89Sr-treated C57BL/6 mice were resistant to FV-induced suppression in vitro, indicating that the susceptibility of spleen cells from 89Sr-treated B6 mice is also mediated by suppressor cells. Normal B6 splenic T cells were rendered susceptible to FV-induced suppression of mitogenesis by addition of 10% spleen cells from 89Sr-treated B6 mice. Thus, M cells appear to regulate the numbers and/or functions of T-suppressor cells which in turn mediate the immunosuppressive effects of FV in vitro. Neither mitogen-responsive lymphocytes nor T-suppressor cells are genetically resistant or susceptible to FV. The genetic resistance to FV is apparently a function of M cells, both in vitro as well as in vivo.


Keep talking about it: HIV/AIDS-related communication and prior HIV testing in Tanzania, Zimbabwe, South Africa, and Thailand.
Informal, interpersonal communication within a community about HIV and AIDS, or lack of such communication, may influence community members' uptake of voluntary counseling and testing. Drawing from Noelle-Neumann's spiral of silence theory, this study examined the association between communication about HIV/AIDS and prior HIV testing in communities in Tanzania, Zimbabwe, South Africa, and Thailand. Participants (N = 14,818) in 48 communities across five sites throughout the four countries completed a behavioral survey assessing communication, prior voluntary counseling and testing (VCT) uptake, social norms, stigma, and sexual risk. Site-specific logistic regression models demonstrated that frequent conversations about HIV were significantly associated with prior HIV testing at every site. Odds ratios for each site ranged from 1.885 to 3.085, indicating a roughly doubled or tripled chance of past VCT uptake. Results indicate that verbal communication may be an important mechanism for increasing health behaviors and inclusion in future interventions should be considered.


Quantum phase transition and emergent symmetry in a quadruple quantum dot system.
We propose a system of four quantum dots designed to study the competition between three types of interactions: Heisenberg, Kondo, and Ising. We find a rich phase diagram containing two sharp features: a quantum phase transition (QPT) between charge-ordered and charge-liquid phases and a dramatic resonance in the charge liquid visible in the conductance. The QPT is of the Kosterlitz-Thouless type with a discontinuous jump in the conductance at the transition. We connect the resonance phenomenon with the degeneracy of three levels in the isolated quadruple dot and argue that this leads to a Kondo-like emergent symmetry from left-right Z2 to U(1).


Anti-biofilm Agents against Pseudomonas aeruginosa: A Structure-Activity Relationship Study of C-Glycosidic LecB Inhibitors.
Biofilm formation is a key mechanism of antimicrobial resistance. We have recently reported two classes of orally bioavailable C-glycosidic inhibitors of the Pseudomonas aeruginosa lectin LecB with antibiofilm activity. They proved efficient in target binding, were metabolically stable, nontoxic, selective, and potent in inhibiting formation of bacterial biofilm. Here, we designed and synthesized six new carboxamides and 24 new sulfonamides for a detailed structure-activity relationship for two clinically representative LecB variants. Sulfonamides generally showed higher inhibition compared to carboxamides, which was rationalized based on crystal structure analyses. Substitutions at the thiophenesulfonamide increased binding through extensive contacts with a lipophilic protein patch. These metabolically stable compounds showed a further increase in potency toward the target and in biofilm inhibition assays. In general, we established the structure-activity relationship for these promising antibiofilm agents and showed that modification of the sulfonamide residue bears future optimization potential.


There might be blood: a scoping review on women's responses to contraceptive-induced menstrual bleeding changes.
Concern about side effects and health issues are common reasons for contraceptive non-use or discontinuation. Contraceptive-induced menstrual bleeding changes (CIMBCs) are linked to these concerns. Research on women's responses to CIMBCs has not been mapped or summarized in a systematic scoping review. We conducted a systematic scoping review of data on women's responses to CIMBCs in peer-reviewed, English-language publications in the last 15 years. Investigator dyads abstracted information from relevant studies on pre-specified and emergent themes using a standardized form. We held an expert consultation to obtain critical input. We provide recommendations for researchers, contraceptive counselors, and product developers. We identified 100 relevant studies. All world regions were represented (except Antarctica), including Africa (11%), the Americas (32%), Asia (7%), Europe (20%), and Oceania (6%). We summarize findings pertinent to five thematic areas: women's responses to contraceptive-induced non-standard bleeding patterns; CIMBCs influence on non-use, dissatisfaction or discontinuation; conceptual linkages between CIMBCs and health; women's responses to menstrual suppression; and other emergent themes. Women's preferences for non-monthly bleeding patterns ranged widely, though amenorrhea appears most acceptable in the Americas and Europe. Multiple studies reported CIMBCs as top reasons for contraceptive dissatisfaction and discontinuation; others suggested disruption of regular bleeding patterns was associated with non-use. CIMBCs in some contexts were perceived as linked with a wide range of health concerns; e.g., some women perceived amenorrhea to cause a buildup of "dirty" or "blocked" blood, in turn perceived as causing blood clots, fibroids, emotional disturbances, weight gain, infertility, or death. Multiple studies addressed how CIMBCs (or menstruation) impacted daily activities, including participation in domestic, work, school, sports, or religious life; sexual or emotional relationships; and other domains. Substantial variability exists around how women respond to CIMBCs; these responses are shaped by individual and social influences. Despite variation in responses across contexts and sub-populations, CIMBCs can impact multiple aspects of women's lives. Women's responses to CIMBCs should be recognized as a key issue in contraceptive research, counseling, and product development, but may be underappreciated, despite likely - and potentially substantial - impacts on contraceptive discontinuation and unmet need for modern contraception.


Withdrawing treatment from patients with prolonged disorders of consciousness: the wrong answer is what the wrong question begets.
In a recent paper, Charles Foster argued that the epistemic uncertainties surrounding prolonged disorders of consciousness (PDOC) make it impossible to prove that the withdrawal of life-sustaining treatment can be in a patient's best interests and, therefore, the presumption in favour of the maintenance of life cannot be rebutted. In the present response, I argue that, from a legal perspective, Foster has reached the wrong conclusion because he is asking the wrong question. According to the reasoning in two leading cases-Bland and James-the principle of respect for autonomy creates a persuasive presumption against treatment without consent. Therefore, it is the continuation of treatment that requires justification, rather than its withdrawal. This presumption also works as the tiebreaker determining that treatment should stop if there is no persuasive evidence that its continuation is in the best interests of the patient. The presumption in favour of the maintenance of life, on the other hand, should be understood as an evidential presumption on a factual issue that is assumed to be true if unchallenged. However, the uncertainties regarding PDOC actually give reasons for displacing this evidential presumption. Consequently, decision-makers will have to weigh up the pros and cons of treatment having the presumption against treatment without consent as the tiebreaker if the evidence is inconclusive. In conclusion, when the right question is asked, Foster's argument can be turned on its head and uncertainties surrounding PDOC weigh in to justify the interruption of treatment in the absence of compelling contrary evidence.


Dietary intake of heme iron is associated with ferritin and hemoglobin levels in Dutch blood donors: results from Donor InSight.
Whole blood donors, especially frequently donating donors, have a risk of iron deficiency and low hemoglobin levels, which may affect their health and eligibility to donate. Lifestyle behaviors, such as dietary iron intake and physical activity, may influence iron stores and thereby hemoglobin levels. We aimed to investigate whether dietary iron intake and questionnaire-based moderate-to-vigorous physical activity were associated with hemoglobin levels, and whether ferritin levels mediated these associations. In Donor InSight-III, a Dutch cohort study of blood and plasma donors, data on heme and non-heme iron intake (mg/day), moderate-to-vigorous physical activity (10 minutes/day), hemoglobin levels (mmol/L) and ferritin levels (μg/L) were available in 2,323 donors (1,074 male). Donors with higher heme iron intakes (regression coefficients (β) in men and women: 0.160 and 0.065 mmol/L higher hemoglobin per 1 mg of heme iron, respectively) and lower non-heme iron intakes (β: -0.014 and -0.017, respectively) had higher hemoglobin levels, adjusted for relevant confounders. Ferritin levels mediated these associations (indirect effect (95% confidence interval) in men and women respectively: 0.074 (0.045; 0.111) and 0.061 (0.030; 0.096) for heme and -0.003 (-0.008;0.001) and -0.008 (-0.013;-0.003) for non-heme). Moderate-to-vigorous physical activity was negatively associated with hemoglobin levels in men only (β: -0.005), but not mediated by ferritin levels. In conclusion, higher heme and lower non-heme iron intake were associated with higher hemoglobin levels in donors, via higher ferritin levels. This indicates that donors with high heme iron intake may be more capable of maintaining iron stores to recover hemoglobin levels after blood donation.


Associations between migraine, celiac disease, non-celiac gluten sensitivity and activity of diamine oxidase.
Recent reports reveal a close relationship between migraine and gastrointestinal disorders (GI), such as celiac disease (CD) and non-celiac gluten sensitivity (NCGS). CD is a genetic autoimmune disorder, which affects the mucosa of the small intestine. Gluten, found in various grains, not only plays a major role in the pathophysiology of CD and NCGS, but also aggravates migraine attacks. Another common food component, which can induce migraine headaches, is histamine. Diamine oxidase (DAO) is an enzyme, which degrades histamine. Reduced activity of DAO means reduced histamine degradation, which can cause histamine build-up and lead to various symptoms, including headaches and migraine. In this paper we propose a hypothesis, that in pathogenesis of migraine, low serum DAO activity is related to CD and NCGS. We also conducted our own pilot study of 44 patients with severe migraine in efforts to evaluate the co-presence of decreased serum DAO activity and celiac disease/NCGS in patients. 44 consecutive migraine patients were divided into 2 groups: decreased DAO activity (group 1; n = 26) and normal DAO activity (group 2; n = 18). All patients were screened for celiac disease. The diagnosis of NCGS was made after exclusion of CD, food allergies and other GI disorders in the presence of gluten sensitivity symptoms. Furthermore, dietary recommendations were given to all participants and their effects were assessed 3 months after the initial evaluation via the MIDAS (Migraine Disability Assessment) questionnaire. Only 1 patient fit the criteria for celiac disease, rendering this result inconclusive. Pathological findings of the remainder of patients were attributed to NCGS (n = 10). 9 of 10 patients with NCGS belonged to the decreased serum DAO activity group (group 1; n = 26), suggesting a strong relationship between reduced serum DAO activity and NCGS. MIDAS questionnaire revealed, that patients with decreased serum DAO activity were more severely impacted by migraine than those with normal DAO activity, and this remained so after our interventions. Dietary adjustments significantly reduced the impact of migraine on patients' daily activities after 3 months in both groups. We argue, that migraine, celiac disease and NCGS may benefit from treatment with a multidisciplinary approach, involving neurologists, gastroenterologists and dietitians.


CCL20 mediates lipopolysaccharide induced liver injury and is a potential driver of inflammation and fibrosis in alcoholic hepatitis.
Chemokines are known to play an important role in the pathophysiology of alcoholic hepatitis (AH), a form of acute-on-chronic liver injury frequently mediated by gut derived lipopolysaccharide (LPS). In our study, we hypothesise that chemokine CCL20, one of the most upregulated chemokines in patients with AH, is implicated in the pathogenesis of AH by mediating LPS induced liver injury. CCL20 gene expression and serum levels and their correlation with disease severity were assessed in patients with AH. Cellular sources of CCL20 and its biological effects were evaluated in vitro and in vivo in chronic, acute and acute-on-chronic experimental models of carbon tetrachloride and LPS induced liver injury. RNA interference technology was used to knockdown CCL20 in vivo. CCL20 hepatic and serum levels were increased in patients with AH and correlated with the degree of fibrosis, portal hypertension, endotoxaemia, disease severity scores and short term mortality. Moreover, CCL20 expression was increased in animal models of liver injury and particularly under acute-on-chronic conditions. Macrophages and hepatic stellate cells (HSCs) were identified as the main CCL20 producing cell types. Silencing CCL20 in vivo reduced LPS induced aspartate aminotransferase and lactate dehydrogenase serum levels and hepatic proinflammatory and profibrogenic genes. CCL20 induced proinflammatory and profibrogenic effects in cultured primary HSCs. Our results suggest that CCL20 upregulation is strongly associated with LPS and may not only represent a new potential biomarker to predict outcome in patients with AH but also an important mediator linking hepatic inflammation, injury and fibrosis in AH.


Discovery of a new Mycobacterium tuberculosis thymidylate synthase X inhibitor with a unique inhibition profile.
Tuberculosis (TB), mainly caused by Mycobacterium tuberculosis (Mtb), is an infection that is responsible for roughly 1.5 million deaths per year. The situation is further complicated by the wide-spread resistance to the existing first- and second-line drugs. As a result of this, it is urgent to develop new drugs to combat the resistant bacteria as well as have lower side effects, which can promote adherence to the treatment regimens. Targeting the de novo synthesis of thymidylate (dTMP) is an important pathway to develop drugs for TB. Although Mtb carries genes for two families of thymidylate synthases (TS), ThyA and ThyX, only ThyX is essential for its normal growth. Both enzymes catalyze the conversion of uridylate (dUMP) to dTMP but employ a different catalytic approach and have different structures. Also, ThyA is the only TS found in humans. This is the rationale for identifying selective inhibitors against ThyX. We exploited the NADPH oxidation to NADP+ step, catalyzed by ThyX, to develop a spectrophotometric biochemical assay. Success of the assay was demonstrated by its effectiveness (average Z'=0.77) and identification of selective ThyX inhibitors. The most potent compound is a tight-binding inhibitor with an IC50 of 710nM. Its mechanism of inhibition is analyzed in relation to the latest findings of ThyX mechanism and substrate and cofactor binding order.


Evaluation of informative materials on leishmaniasis distributed in Brazil: criteria and basis for the production and improvement of health education materials.
Based on categories related to structure, content, language, and illustrations, the present study provides an evaluation of the quality of educational materials on leishmaniasis available to health services in Brazil. The 18 publications evaluated consisted of four handbooks, four guided studies, four booklets, and six leaflets. Of the total publications assessed, nine were produced by the Brazilian National Health Foundation (FUNASA), five by State and Municipal Health Departments jointly with FUNASA, and one by the Pan-American Health Organization. The evaluations were also performed by three professionals: a physician specialized in leishmaniasis, a parasitologist, and an information/communications expert. The publications failed to specify key items such as target public, objective, and bibliography. The illustrations, especially in the booklets and leaflets, failed to clarify the text, portrayed biased concepts, and omitted credits and scale. According to this study, informative materials on leishmaniasis distributed in Brazil present major limitations which jeopardize the quality of information they contain.


Meaningful inclusion of consumers in research and service delivery.
Although participatory methods have become increasingly popular, people with lived experience of mental illness and homelessness have been historically excluded from service planning and research. To better plan for meaningful inclusion of consumers, this study examines lessons learned from the People with Lived Experience Caucus in the Toronto Site of the At Home/Chez Soi Research Demonstration Project on Homelessness and Mental Health. The inclusion of the People with Lived Experience Caucus was evaluated using qualitative methods and multiple data sources, including review of 42 documents, 11 individual interviews, and three focus groups. Caucus members were included in the study team. Transcripts were analyzed using grounded theory methodology. Findings revealed a complex story of Caucus engagement: Facing time constraints and given little direction, the Caucus developed through a tumultuous process related to both internal and external barriers to meaningful inclusion. Despite the challenges, the Caucus contributed meaningfully to various aspects of the research demonstration project. It is possible to successfully integrate psychiatric consumers with experience of homelessness in many aspects of research and service planning. Suggestions for future initiatives hoping to engage consumers include: early involvement, purposeful selection of members, clear communication of roles and responsibilities, a consumer coordinating group, and space for critical dialog throughout the process. Lessons learned can inform the inclusion of consumers in similar endeavors in other jurisdictions.


Treatment Approach to Sleep Terror: Two Case Reports.
Parasomnias are a group of disorders characterized by abnormal behaviors, physical activities, and autonomic arousal symptoms while transition to sleep or continuation of sleep. Sleep terror (ST) is classified under parasomnias characterized by sudden fear attacks beginning with crying attacks or high-frequency screams and continuing with increased autonomic symptoms. ST occurs in the first few hours of sleep during the delta phase. Further, the lifetime prevalence of ST in adults is less than 1%. It is important to obtain; anamnesis from patients' bed partner for a clinical evaluation of ST. Methods, such as evaluating sleep diaries and video recordings, can help ST diagnosis. It is also important to evaluate patients' medical history, history of substance or alcohol abuse, psychological traumatic experiences, primary or secondary incomes, and detailed neurological aspects. Physician can select some serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCADs) as medical treatment if patients have a high frequency of attacks. Because of addiction and relapse of ST episodes, benzodiazepines are not preferred as the first-line treatment. In this study, we will discuss ST, which is rare in adulthood, and use of long-acting benzodiazepine based on two cases.


On faculty development of STEM inclusive teaching practices.
Faculty development of inclusive teaching practices has become more common in response to significant differences in STEM student retention between underrepresented minorities in the USA and students from other ethnic groups. Approaches to solve this have shifted from focusing on student deficits to changing campus culture, including the mindsets of instructors who teach STEM courses. In this article, I argue that based on the literature informing the conceptual frameworks used for faculty development in inclusive teaching, faculty developers should reframe the message of their workshops to focus participants more on the scope of the journey, and shift the direction of overall efforts some to redevelop pedagogical training at the graduate and postdoc levels. Informed by historical as well as recent theories on the role of higher education to society, I highlight the areas of the literature that can effectively inform our current approaches to inclusion. I also briefly review the reasons why this approach is needed, and include suggestions for new faculty development approaches for long-term sustainable change in STEM inclusive education at the postsecondary level.


Under-nutrition among adolescents: a survey in five secondary schools in rural Goa.
This study was done in 2008-09 to assess the nutritional status among adolescents (10-19 years of age, Classes V-XII) in 5 schools in rural Goa to inform the content of a health promotion intervention in these schools. Three methods were used. First, nutritional status was measured by assessing body mass index among 1015 students during a health camp in each school. Second, a diet analysis was done to measure energy and protein Intake of 76 randomly selected underweight students. Third, a self-report questionnaire survey measured the prevalence of hunger among 684 students. One-third of students (338; 37.8% boys and 27.5% girls) who attended the health camps were underweight and 59.2% of the 684 students who completed the survey reported experiencing hunger due to inadequate food consumption. More boys were underweight than girls (p<0.001) and under-nutrition was uniform across all the years of schooling. Energy intake of underweight students was significantly lower than the recommended daily allowance. The results were shared with the School Health Promotion Advisory Boards to generate information on the stakeholders' perception about the issue and ways to address it. There is an immediate need to address the high burden of hunger and under-nutrition in adolescents of both sexes in schools by instituting routine annual monitoring of nutritional status, extending the mid-day meal programme to all school-going adolescents, providing nutritional counselling for underweight adolescents and expanding research on the causes and impact of under-nutrition and evaluation of the impact of the enhanced mid-day meal programme.


Effects of clinical parameters on patient-reported outcome in cataract patients: a multicentre study.
Ophthalmologists tend to evaluate the results of cataract surgery by focusing on the clinical visual and refractive outcomes and the incidence of complications, where patients' main interest might be their ability to perform daily activities. Therefore, there appears to be a need for optimizing effective communication between patients and ophthalmologist about the outcome of cataract surgery. The aim of this multicentre study was to determine the effects of whether the surgery was performed in one or two eyes, ocular comorbidity and per- and postoperative complications on visual function experienced by patients measured with the Catquest-9SF. To measure patient-reported outcomes, Catquest-9SF data were collected between 2014 and 2015 in five Dutch hospitals. Data from 870 pairs of questionnaires - completed before and after cataract surgery - were compared with clinical data. Clinical data, retrieved from patients' medical files, consisted of one or two eye surgery, ocular comorbidity and per- and postoperative complications. Quality of vision improved more in patients who had surgery in both eyes and had fewer postoperative complications (both p < 0.001). We found a nonsignificant trend that quality of vision was worse when ocular comorbidity was present. No significant effect of peroperative complications was observed. Our results emphasize the added value of the Catquest-9SF as a tool for visual function experienced by patients; the additional information can complement clinical parameters to improve patient-centred approaches in clinical practice.


Is there a change of corneal thickness in uveitis with Behçet disease?
To report the measurements of central corneal thickness (CCT) in uveitic eyes with Behçet disease (BD) and compare it with age- and sex-matched healthy controls. This study included 69 eyes with ocular BD with no history of corneal disease, glaucoma, or ocular surgery and 50 eyes of healthy controls. Eyes with ocular BD were subdivided into active and inactive groups. Active group was defined as the presence of anterior uveitis or panuveitis, whereas inactive group was defined as having had at least 1 previous attack and absence of any active inflammation in the eye within the last 3 months. CCT was measured with ultrasonic pachymeter. Statistical analyses were performed, and P < 0.05 was considered statistically significant. Active group had 24 patients and inactive group had 45 patients. Demographic characteristics of patients with ocular BD and control subjects were similar (P > 0.05). There was no significant difference in respect to the disease duration between active and inactive groups (P = 0.160). The mean CCT was significantly greater in active group (584.75 ± 20.94 μm) than in inactive group (540.55 ± 36.16 μm) and control group (543.04 ± 25.35 μm) (P = 0.0001). We found that eyes with active BD had increased CCT because of active inflammation when compared with inactive and control groups, and mean CCT of inactive BD was normal. Therefore, we assume that CCT is in normal range in the inactive phase, and recurrent uveitis does not lead to a permanent change in CCT in BD.


Neural elements in dental pulp and dentin.
This article addresses the structural and quantitative aspects of human tooth innervation and briefly considers the functions and clinical relevance of tooth axons. The classification of peripheral axons, the pulpal and dentinal innervation, and the theories of dentin sensitivity are discussed. Quantitative studies on tooth innervation are also reviewed. Human premolars receive about 2300 axons at the root-apex of which about 13% are myelinated and 87% are nonmyelinated fibers. Most apical myelinated axons are fast-conducting A delta-fibers with their receptive fields located at the pulpal periphery and inner dentin. These fibers are probably activated by a hydrodynamic mechanism and conduct impulses that are perceived as a short well-localized sharp pain. Most C-fibers are slow-conducting fine sensory afferents with their receptive fields located in the pulp and transmit impulses that are experienced as dull poorly localized and lingering pain. In addition to the nociceptive alarm signaling, the intradental sensory axons may play a regulatory role in the maintenance and repair of the pulpodentinal complex.


Investigation of rhodopsin dynamics in its signaling state by solid-state deuterium NMR spectroscopy.
Site-directed deuterium NMR spectroscopy is a valuable tool to study the structural dynamics of biomolecules in cases where solution NMR is inapplicable. Solid-state (2)H NMR spectral studies of aligned membrane samples of rhodopsin with selectively labeled retinal provide information on structural changes of the chromophore in different protein states. Moreover (2)H NMR relaxation time measurements allow one to study the dynamics of the ligand during the transition from the inactive to the active state. Here we describe the methodological aspects of solid-state (2)H NMR spectroscopy for functional studies of rhodopsin, with an emphasis on the dynamics of the retinal cofactor. We provide complete protocols for the preparation of NMR samples of rhodopsin with 11-cis-retinal selectively deuterated at the methyl groups in aligned membranes. In addition we review optimized conditions for trapping the rhodopsin photointermediates; and we address the challenging problem of trapping the signaling state of rhodopsin in aligned membrane films.


Soliton compression to few-cycle pulses with a high quality factor by engineering cascaded quadratic nonlinearities.
We propose an efficient approach to improve few-cycle soliton compression with cascaded quadratic nonlinearities by using an engineered multi-section structure of the nonlinear crystal. By exploiting engineering of the cascaded quadratic nonlinearities, in each section soliton compression with a low effective order is realized, and high-quality few-cycle pulses with large compression factors are feasible. Each subsequent section is designed so that the compressed pulse exiting the previous section experiences an overall effective self-defocusing cubic nonlinearity corresponding to a modest soliton order, which is kept larger than unity to ensure further compression. This is done by increasing the cascaded quadratic nonlinearity in the new section with an engineered reduced residual phase mismatch. The low soliton orders in each section ensure excellent pulse quality and high efficiency. Numerical results show that compressed pulses with less than three-cycle duration can be achieved even when the compression factor is very large, and in contrast to standard soliton compression, these compressed pulses have minimal pedestal and high quality factor.


Survival among Veterans Obtaining Dialysis in VA and Non-VA Settings.
Outcomes of veterans with ESRD may differ depending on where they receive dialysis and who finances this care, but little is known about variation in outcomes across different dialysis settings and financial arrangements. We examined survival among 27,241 Veterans Affairs (VA)-enrolled veterans who initiated chronic dialysis in 2008-2011 at (1) VA-based units, (2) community-based clinics through the Veterans Affairs Purchased Care program (VA-PC), (3) community-based clinics under Medicare, or (4) more than one of these settings ("dual" care). Using a Cox proportional hazards model, we compared all-cause mortality across dialysis settings during the 2-year period after dialysis initiation, adjusting for demographic and clinical characteristics. Overall, 4% of patients received dialysis in VA, 11% under VA-PC, 67% under Medicare, and 18% in dual settings (nearly half receiving dual VA and VA-PC dialysis). Crude 2-year mortality was 25% for veterans receiving dialysis in the VA, 30% under VA-PC, 42% under Medicare, and 23% in dual settings. After adjustment, dialysis patients in VA or in dual settings had significantly lower 2-year mortality than those under Medicare; mortality did not differ in VA-PC and Medicare dialysis settings. Mortality rates were highest for veterans receiving dialysis in Medicare or VA-PC settings and lowest for veterans receiving dialysis in the VA or dual settings. These findings inform institutional decisions about provision of dialysis for veterans. Further research identifying processes associated with improved survival for patients receiving VA-based dialysis may be useful in establishing best practices for outsourced veteran care.