[Therapy of synchronous multiple primary malignancies].
The data on 526 patients treated for primary multiple synchronous malignancies were evaluated. The total number of detected tumors was 1,069; concomitant pathology was identified in 377 out of 490 (76.9 +/- 1.9%). Removal of all synchronous tumors was considered radical--and palliative or symptomatic when, whatever the modality, two or at least one tumor was treated. Most of primary multiple synchronous tumors were removed radically (56.4 +/- 2.3%). The best results were obtained when combined therapy was used for early-stage tumors while surgical treatment of advanced cancer was complemented with radiochemotherapy. Radical treatment was contraindicated in 30.3 +/- 3.8% because of concomitant pathology.


Self-confirming "AND" logic nanoparticles for fault-free MRI.
Achieving high accuracy in the imaging of biological targets is a challenging issue. For MRI, to enhance imaging accuracy, two different imaging modes with specific contrast agents are used; one is a T1 type for a "positive" MRI signal and the other is a T2 type for a "negative" signal. Conventional contrast agents respond only in a single imaging mode and frequently encounter ambiguities in the MR images. Here, we propose a "magnetically decoupled" core-shell design concept to develop a dual mode nanoparticle contrast agent (DMCA). This DMCA not only possesses superior MR contrast effects but also has the unique capability of displaying "AND" logic signals in both the T1 and T2 modes. The latter enables self-confirmation of images and leads to greater diagnostic accuracy. A variety of novel DMCAs are possible, and the use of DMCAs can potentially bring the accuracy of MR imaging of diseases to a higher level.


Parameters of cardiac symptoms in young athletes using the Heartbytes database.
Introduction: To determine clinical parameters that are related to abnormal cardiac symptoms in physically active youth. Methods: We used Simon's Heart Heartbytes National Youth Cardiac Registry to collect data from adolescent athletes in southeastern Pennsylvania. We collected age, race/ethnicity, abnormal cardiac symptoms, medical history, medication use, caffeine intake, and family history. We obtained height, weight, blood pressure, cardiac murmur findings, and ECGs. Echocardiogram was obtained if necessary. Binary logistic regression analysis was performed to identify independent associations between abnormal cardiac symptoms and collected variables. The odds ratio (OR), 95% confidence interval (95% CI), and p-values were used as statistical values. Results: Of the 887 athletes (543 males and 344 females, age = 16.9 ± 2.1 years, height = 166.9 ± 11.4 cm, weight = 62.0 ± 16.0 kg), 186 (21%) had abnormal cardiac symptoms including chest pain, passing out, difficulty breathing, extreme fatigue, and heart race. There was an independent association between abnormal symptoms and a past medical history (OR: 4.77, 95%CI: 3.18, 7.17, p = 0.001) and medication use (OR: 1.74, 95%CI: 1.08, 2.79, p = 0.022). In medical history, young athletes with asthma showed a greater propensity of abnormal cardiac symptoms (48.9%) compared to young athletes without (14.0%, p = 0.001). Additionally, young athletes with anxiety or depression demonstrated a higher proportion of abnormal cardiac symptoms (48.9%) than those without (19.5%, p = 0.001). Although the association between the presence of abnormal symptoms and African-American race (OR: 2.04, 95%CI: 0.96, 4.35, p = 0.065) and average daily consumption of at least 2 caffeine drinks (OR: 2.08, 95%CI: 0.86, 5.02, p = 0.103) were not significant, there was a trend to reach the a priori significance level. Conclusions: This study identified several clinical parameters that are associated with symptoms suggestive of abnormal cardiac conditions. Larger studies need to be done to better sort out the clinical history that may contribute to false positives to further reduce false positives at heart screenings.


Tracing the genetic roots of the indigenous White Park Cattle.
The White Park Cattle (WPC) is an indigenous ancient breed from the British Isles which has a long-standing history in heroic sagas and documents. The WPC has retained many primitive traits, especially in their grazing behaviour and preferences. Altogether, the aura of this breed has led to much speculation surrounding its origin. In this study, we sequenced the mitogenomes from 27 WPC and three intronic fragments of genes from the Y chromosome of three bulls. We observed six novel mitogenomic lineages that have not been found in any other cattle breed so far. We found no evidence that the WPC is a descendant of a particular North or West European branch of aurochs. The WPC mitogenomes are grouped in the T3 cluster together with most other domestic breeds. Nevertheless, both molecular markers support the primitive position of the WPC within the taurine breeds.


Establishment of SLC7A11-knockout mouse and its preliminary investigation in melanoma.
Solute carrier family 7 member 11 (SLC7A11)/xCT is an amino acid transporter that mediates the cystine uptake and glutamate export, participates in several malignant tumors' progression. However, the role of SLC7A11 on the occurrence and development of melanoma still remains unclear. Here, the transcribed mRNA encoding for Cas9 and sgRNA targeting SLC7A11 in vitro were microinjected into zygotes, to establish the SLC7A11 knockout (KO) mice (SLC7A11-/-). Further, we conducted melanoma-bearing mice using the metastatic melanoma cell line (B16-F10) to observe the melanoma development. There was no off-target in KO mice detected by T7E1 cleavage assay. The results showed that the tumor volume of KO mice was significantly lower than that of SLC7A11+/+ (WT) mice at 8d, 10d, 12d, 14d, and 16d (P < 0.05). The tumors of WT appeared to more disorganized morphology, more unbalanced nuclear-cytoplasmic ratio, less defined boundary, and increased tumor necrosis. And after SLC7A11 deletion, the expression of CXCL9 and TLR6 were significantly up-regulated, and that of NOS2 and CCL8 were significantly down-regulated (P < 0.01). Additionally, Ki67 immunostaining revealed lower proliferating cells in the tumors of SLC7A11 KO mice compared to WT mice. In summary, the deletion of SLC7A11 significantly inhibited the development of melanoma. Our results provide direct evidence to identify SLC7A11 as a novel target for molecular therapy and prognosis judgment of melanoma.


Effect of age of red cells for transfusion on patient outcomes: a systematic review and meta-analysis.
Longer storage duration of red blood cell (RBC) units prior to transfusion has been associated with worse outcomes in observational studies. We performed a systematic review, including recently published randomized trials, to determine if storage age of RBCs is associated with mortality, morbidity or adverse events in patients. Searches were performed up to 21st July 2017 in Medline (OvidSP), 20 July in EMBASE (OvidSP) and June 2017 in Cochrane Library. Eligible studies were randomized controlled trials comparing transfusion of fresher or freshest available with older or standard issue RBCs. Human volunteer and autologous RBC transfusion studies were excluded. Data were extracted from published reports independently by 2 authors and strength of evidence assessed according to GRADE criteria. The primary outcome was latest-reported mortality. Sixteen trials randomizing 31,359 patients were identified. Transfusion with fresher compared with older RBC was not associated with risk of death (relative risk [RR] 1.04, 95% CI 0.98-1.09; P=.20, I2=0%, high quality evidence), but was associated with higher risk of transfusion reactions (RR 1.35, 95% CI 1.04-1.76; P=.02; I2=0%; high quality evidence) and infection (RR 1.08, 95% CI 1.00-1.17; P=.05; I2=0%, moderate evidence). Trial sequential analysis showed required information size has now been reached to exclude a 10% relative risk increase or decrease in mortality. Transfusion of fresher RBCs is not associated with decreased risk of death but is associated with higher rates of transfusion reactions and possibly infection. The current evidence does not support a change from current usual transfusion practice.


Influence of swimming strategy on microorganism separation by asymmetric obstacles.
It has been shown that a nanoliter chamber separated by a wall of asymmetric obstacles can lead to an inhomogeneous distribution of self-propelled microorganisms. Although it is well established that this rectification effect arises from the interaction between the swimmers and the noncentrosymmetric pillars, here we demonstrate numerically that its efficiency is strongly dependent on the detailed dynamics of the individual microorganism. In particular, for the case of run-and-tumble dynamics, the distribution of run lengths, the rotational diffusion, and the partial preservation of run orientation memory through a tumble are important factors when computing the rectification efficiency. In addition, we optimize the geometrical dimensions of the asymmetric pillars in order to maximize the swimmer concentration and we illustrate how it can be used for sorting by swimming strategy in a long array of parallel obstacles.


Primary hepatic gastrinoma: Report of a case and review of literature.
Primary hepatic gastrinoma is a very rare ectopic gastrinoma with less than 20 cases reported worldwide. We report the case of a patient with hypergastrinemia who was subjected to exhaustive preoperative and intraoperative imaging and also careful surgical exploration of the duodenum and pancreas which failed initially to identify the primary tumour. Eventually the patient was subjected to left liver lobectomy, as a small palpable lesion was noted intraoperatively. The diagnosis of gastrinoma requires a high index of clinical suspicion and the flawless cooperation of many specialties.


Donor Heart Preservation: Current Knowledge and the New Era of Machine Perfusion.
Heart transplantation remains the conventional treatment in end-stage heart failure, with static cold storage (SCS) being the standard technique used for donor preservation. Nevertheless, prolonged cold ischemic storage is associated with the increased risk of early graft dysfunction attributed to residual ischemia, reperfusion, and rewarming damage. In addition, the demand for the use of marginal grafts requires the development of new methods for organ preservation and repair. In this review, we focus on current knowledge and novel methods of donor preservation in heart transplantation. Hypothermic or normothermic machine perfusion may be a promising novel method of donor preservation based on the administration of cardioprotective agents. Machine perfusion seems to be comparable to cold cardioplegia regarding donor preservation and allows potential repair treatments to be employed and the assessment of graft function before implantation. It is also a promising platform for using marginal organs and increasing donor pool. New pharmacological cardiac repair treatments, as well as cardioprotective interventions have emerged and could allow for the optimization of this modality, making it more practical and cost-effective for the real world of transplantation. Recently, the use of triiodothyronine during normothermic perfusion has shown a favorable profile on cardiac function and microvascular dysfunction, likely by suppressing pro-apoptotic signaling and increasing the expression of cardioprotective molecules.


Fixed green and brown color morphs and a novel color-changing morph of the Pacific tree frog Hyla regilla.
Pacific tree frogs Hyla regilla are typically either green or brown in dorsal coloration. The frequency of green and brown individuals is known to fluctuate seasonally. Previous investigators have generally assumed that the green and brown body colors represent a "fixed" polymorphism and that seasonal changes in the proportion of the two body colors are a consequence of differential survival of the two color morphs. Here we report that, in addition to the "fixed" (i.e., non-color-changing) green and brown morphs of H. regilla, there are some individuals that can change hue between green and brown. The distribution of color-change ability in our study population is bimodal, suggesting that "color changers" are a distinct morph rather than one extreme of a continuous distribution of color-change ability. Our findings suggest that background brightness, not hue, triggers color change in the newly discovered morph and that this change requires days to weeks to occur. Such slow color change is not well suited for making short-term changes in color as a frog moves between differently colored substrates. Rather, seasonal changes in habitat characteristics and/or microhabitat use are likely to maintain color-change ability. Color polymorphism and color-change ability appear to represent alternative responses to divergent selection for crypsis in a heterogeneous, seasonally variable environment.


WD repeat-containing protein 5, a ubiquitously expressed histone methyltransferase adaptor protein, regulates smooth muscle cell-selective gene activation through interaction with pituitary homeobox 2.
WD repeat-containing protein 5 (WDR5) is a common component of mammalian mixed lineage leukemia methyltransferase family members and is important for histone H3 lysine 4 methylation (H3K4me), which has been implicated in control of activation of cell lineage genes during embryogenesis. However, WDR5 has not been considered to play a specific regulatory role in epigenetic programming of cell lineage because it is ubiquitously expressed. Previous work from our laboratory showed the appearance of histone H3K4me within smooth muscle cell (SMC)-marker gene promoters during the early stages of development of SMC from multipotential embryonic cells but did not elucidate the underlying mechanisms that mediate SMC-specific and locus-selective H3K4me. Results presented herein show that knockdown of WDR5 significantly decreased SMC-marker gene expression in cultured SMC differentiation systems and in Xenopus laevis embryos in vivo. In addition, we showed that WDR5 complexes within SMC progenitor cells contained H3K4 methyltransferase enzymatic activity and that knockdown of WDR5 selectively decreased H3K4me1 and H3K4me3 enrichment within SMC-marker gene promoter loci. Moreover, we present evidence that it is recruited to these gene promoter loci through interaction with a SMC-selective pituitary homeobox 2 (Pitx2). Taken together, studies provide evidence for a novel mechanism for epigenetic control of SMC-marker gene expression during development through interaction of WDR5, homeodomain proteins, and chromatin remodeling enzymes.


The polyamines: past, present and future.
The polyamines, spermidine and spermine, were first discovered in 1678 by Antonie van Leeuwenhoek. In the early part of the 20th century their structure was determined and their pathway of biosynthesis established. The polyamines are essential elements of cells from all species. They are required for optimum cell growth, and cells where polyamine production has been prevented by mutation, or blocked by inhibitors, require exogenous provision of at least one polyamine for continued survival. Despite this critical function, the polyamines have not attracted as much attention as they deserve in the wider field of biochemistry and cell biology. They are rarely mentioned in standard textbooks, despite over 75000 research papers having been written on the subject since 1900, and more than half (54%) were published after 1990. There have been a number of books dedicated to the polyamines published and "The Guide to the Polyamines" by Seymour Cohen deserves mention as a work of outstanding scholarship describing "everything you ever wanted to know about the polyamines" in exquisite detail. The current volume of Essays in Biochemistry has a much humbler aim: to introduce the polyamines to interested researchers and students, and to describe how they are associated with, and might be utilized as a target for intervention in major diseases such as cancer.


Two fractions required for cell-free protein synthesis with components from rabbit reticulocytes.
An extract was prepared from rabbit reticulocyte ribosomes after treatment with potassium chloride as described by Miller, Hamada, Yang, Cohen & Schweet (1967). This extract has been shown to convert monoribosomes into polyribosomes during protein synthesis in vitro (Cohen, 1968). The nature of this extract was studied in greater detail. Centrifugation of the extract through a sucrose density gradient separated the activity into a fast-sedimenting fraction. The two fractions were shown to have different functions in stimulating cell-free protein synthesis and their active components were shown to be protein or partly protein in nature. Each fraction was analysed by electrophoresis and in the analytical ultracentrifuge. It was concluded that the active component in the fast-sedimenting fraction had a sedimentation coefficient of 15.5s and that of the slow-sedimenting fraction 10.5s.


[Constipation in children].
Chronic constipation (HZ) in children remains one of the most urgent and complex problems of pediatric gastroenterology and form a wide range of health and social and psychological problems. Due to the lack of clear understanding of the pathogenesis, classification, diagnosis and treatment of constipation are complicated. A significant role belongs to the nervous system and in the development of other forms of HZ, which should be considered during diagnostics and treatment.


Predicting how environmental conditions and smolt body length when entering the marine environment impact individual Atlantic salmon Salmo salar adult return rates.
Populations of Atlantic salmon Salmo salar have experienced precipitous declines in abundance since the 1970s. This decline has been associated with reduced numbers of adult salmon returning to fresh water from their marine migration, i.e., their marine return rates (MRR). Thus, understanding the factors that affect MRR is of crucial conservation importance. The authors used a state-space model with a 13-year time series of individually tagged salmon mark-recapture histories on the River Frome, southern England, to test the effect of smolt body length on their MRR. In addition to smolt length, the model tested for the influence of environmental covariates that were representative of the conditions experienced by the smolts in the early stages of their seaward migration, i.e., from the lower river to the estuary exit. The model indicated that, even when accounting for environmental covariates, smolt body length was an important predictor of MRR. Although larger smolts have a higher probability of returning to their natal river as adults than smaller smolts, and one-sea-winter salmon have a survival rate twice as high as multi-sea-winter salmon, the actual biological mechanisms underpinning this phenomenon remain uncertain. These results have important applications for salmon conservation, as efforts to bolster salmon populations in the freshwater environment should consider methods to improve smolt quality (i.e., body size) as well as smolt quantity.


Perceived tiredness and heart rate variability in relation to overload during a field hockey World Cup.
The aim of the study was to examine the utility of perceived tiredness to predict cardiac autonomic response to overload among field hockey players during the 2006 World Cup. The French Society for Sports Medicine (SFMS) questionnaire was administered at the start of the Cup to evaluate perception of tiredness. Autonomic function was assessed nine days later at the semifinal match by time and frequency domain analysis of heart rate variability. An anxiety questionnaire was administered so that the effect of precompetitive anxiety on heart rate variability could be controlled. Results showed a negative correlation between perceived tiredness scores and time domain indexes, and a positive correlation of perceived tiredness scores and the high frequency component ratio (LF/HF ratio) of heart rate variability. Anxiety did not influence the precompetitive cardiac response despite somatic anxiety's correlation with sympathetic response (LF/HF ratio) and tiredness scores. Perceived tiredness predicted the autonomic cardiac response to competitive overload. Thus, the perceived tiredness assessment would be a good early marker of fatigue and overload states during competition.


The presence of hydrogenotrophic methanogens in the inoculum improves methane gas production in microbial electrolysis cells.
High current densities in microbial electrolysis cells (MECs) result from the predominance of various Geobacter species on the anode, but it is not known if archaeal communities similarly converge to one specific genus. MECs were examined here on the basis of maximum methane production and current density relative to the inoculum community structure. We used anaerobic digester (AD) sludge dominated by acetoclastic Methanosaeta, and an anaerobic bog sediment where hydrogenotrophic methanogens were detected. Inoculation using solids to medium ratio of 25% (w/v) resulted in the highest methane production rates (0.27 mL mL(-1) cm(-2), gas volume normalized by liquid volume and cathode projected area) and highest peak current densities (0.5 mA cm(-2)) for the bog sample. Methane production was independent of solid to medium ratio when AD sludge was used as the inoculum. 16S rRNA gene community analysis using pyrosequencing and quantitative PCR confirmed the convergence of Archaea to Methanobacterium and Methanobrevibacter, and of Bacteria to Geobacter, despite their absence in AD sludge. Combined with other studies, these findings suggest that Archaea of the hydrogenotrophic genera Methanobacterium and Methanobrevibacter are the most important microorganisms for methane production in MECs and that their presence in the inoculum improves the performance.


Effect of collateral circulation in patients with multiple craniocervical artery stenoses.
Based on previous findings, collateral circulation in the brain is vital in mitigating cerebral ischemia's effects and influencing stroke risk. This retrospective study examined collateral circulation, admission ischemic stroke status, and long-term recurrence in patients with multiple craniocervical artery stenoses. Consecutive symptomatic internal carotid artery (ICA) stenosis patients from the First Affiliated Hospital of Soochow University were recruited. Baseline data including medical histories and neurological function at admission were collected. Imaging techniques assessed collateral compensative capacity. Multivariate logistic regression analysis was used to investigate the association between collateral circulation and case status. A total of 559 patients with symptomatic ICA stenosis were included, among whom 153 (27.4%) had concurrent moderate to severe vertebro-basilar artery (VBA) stenosis. Dizziness, weakness/numbness, and slurring of speech were the primary symptoms in all patients. Over 36 months, 71 (12.7%) patients experienced a recurrence of acute ischemic stroke (AIS). In multivariate analysis, collateral circulation was found to be negatively associated with AIS (regional leptomeningeal collateral [rLMC] scores: OR: 0.798, 95% CI: 0.743-0.857, p < 0.001; Tan scores: OR: 0.478, 95% CI: 0.336-0.679, p < 0.001). Meanwhile, the collateral circulation scores were significantly associated with the recurrence of AIS within 3 years (rLMC scores: OR: 0.926, 95% CI: 0.860-0.997, p = 0.042; Tan scores: OR: 0.467, 95% CI: 0.306-0.712, p < 0.001). Most associations remained significant in the subgroup of patients with VBA stenosis. Favorable collateral circulation in multiple craniocervical artery stenosis patients reduced long-term ischemic event recurrence. Stratifying treatment risks is essential for optimizing outcomes.


Evaluation of emergency extracorporeal shock wave lithotripsy for obstructing ureteral stones.
To assess the efficacy of extracorporeal shockwave lithotripsy (ESWL) for ureteral calculi during acute renal colic. From January 2002 to March 2007, 108 patients were treated by ESWL for obstructing ureteral stones causing acute renal colic. ESWL was performed within 24 hours of the onset of renal colic. The mean age of the patients was 39.5 years (11-72 years). Male/female ratio was 85/23. Mean stone size was 8.45 mm (4-20 mm). They were located in the pelvic (n = 53), iliac (n = 28) or lumbar (n = 27) region. Fragmentation after a single session was complete in 56 patients (52%), incomplete in 28 (26%), and absent in 24 (22%). Patients presenting incomplete fragmentation underwent a second (n = 28) or even a third session (n = 11). Of the 24 patients in whom ESWL had no impact on the stone, 21 underwent ureteroscopy, and in one case open ureterolithotomy for a patient with a hard 17 mm stone, while spontaneous passage occurred in two patients with small stones. Emergency ESWL for obstructing ureteral stones has a satisfactory success rate and very low morbidity. The stone-free rate of retreating ureteral calculi with ESWL decreases significantly after failed initial treatment. Stone size may be the main predictive factor for retreatment. We suggest that no more than 3 treatments should be given for a particular stone due to minimal improvement in the subsequent cumulative treatment success rate.


Polygraphical sleep recordings in insomniac patients under zopiclone or nitrazepam.
Zopiclone, a new hypnotic with an original chemical structure, was compared in a sleep laboratory study with nitrazepam according to a double-blind, parallel group randomized design. Zopiclone (7.5 mg) and nitrazepam (5 mg) were each given for 14 nights to 5 insomniacs; a placebo washout period of 4 nights and a placebo withdrawal period of 10 nights were included in the design. Both drugs were found to be immediately and lastingly effective. Some slight insomnia rebound was found with nitrazepam, but not with zopiclone. Stage 2 was decreased, slow wave sleep (SWS) increased, and rapid eye movement unchanged by both drugs: however, only nitrazepam increased rapid eye movement latency. The differences between the effects of the drugs were quite limited. However, 3 out of 50 comparisons favoured zopiclone and none nitrazepam.


Prolactin increases ATP-dependent taurocholate transport in canalicular plasma membrane from rat liver.
The taurocholate (TC) maximal secretory rate (SRm) in the isolated perfused liver is increased in postpartum rats and ovariectomized rats treated with ovine prolactin (oPRL). The present studies were designed to characterize the mechanism(s) by which oPRL increases TC transport in the liver. oPRL (300 micrograms/day i.v. for 7 days) increased the SRm 1.6-fold from 185 to 364 nmol.min-1.mg protein-1 in the perfused rat liver and the maximal rate of transport for ATP-dependent transport 1.7-fold from 66 to 109 nmol.min-1.mg protein-1 in canalicular liver plasma membrane (cLPM) vesicles without changing the Michaelis constant (5-6 microM). The oPRL-mediated increases in biliary excretion in the perfused liver and ATP-dependent TC transport in cLPM vesicles were significantly inhibited by cycloheximide treatment (2 mg/kg). oPRL (300 micrograms/day iv for 7 days) increased expression of Ca(2+)-Mg(2+)-ecto-adenosinetriphosphatase mRNA sixfold and increased protein expression two- to threefold, but had no effect on the expression of P-glycoprotein (mdr1b and mdr2) mRNA. Thus the increase in ATP-dependent transport in cLPM vesicles due to oPRL treatment accounts for the increased TC SRm in the perfused liver. The oPRL-mediated increased TC transport may be associated with increased expression of proteins related to bile acid transport.


Anisotropic particle synthesis inside droplet templates on superhydrophobic surfaces.
We demonstrate how droplet templates dispensed on superhydrophobic substrates can be used to fabricate both shape-anisotropic ("doughnut") and composition-anisotropic ("patchy magnetic") supraparticles. The macroscopic shape of the closely-packed particle assemblies is guided by the droplet meniscus. Aqueous droplets of monodisperse microsphere suspensions dispensed on the substrates initially acquire near-spherical shape due to a high contact angle. During the solvent evaporation, however, silica suspension droplets undergo shape transitions (concaving) guiding the structure of the final assemblies into doughnut supraparticles. Composition anisotropy is achieved by drying a droplet containing a mixed suspension of latex and magnetic nanoparticles, while exposing it to magnetic field gradients. Depending on the pattern of the magnetic fields, the magnetic nanoparticles segregate into single, bilateral, or trilateral, patched spherical supraparticles. The physical effects leading to the development of anisotropy are discussed. Unlike the conventional wet self-assembly (WSA) methods where the final structures need to be extracted from the liquid environment, this efficient one-step procedure produces ready to use "dry" supraparticles.


Delay discounting predicts adolescent substance abuse treatment outcome.
The purpose of the current study was to identify predictors of delay discounting among adolescents receiving treatment for marijuana abuse or dependence, and to test delay discounting as a predictor of treatment outcome. Participants for this study were 165 adolescents (88% male) between the ages of 12 and 18 (mean age = 15.8 years; standard deviation = 1.3 years) who enrolled in a clinical trial comparing three behavioral treatments for adolescent marijuana abuse or dependence. Participants completed a delay discounting task at treatment onset for $100 and $1,000 of hypothetical money and marijuana. Overall, smaller magnitude rewards were discounted more than larger magnitude rewards. Delay discounting rates were concurrently related to demographic variables (socioeconomic status, race). Delay discounting of $1,000 of money predicted during treatment abstinence outcomes among adolescent marijuana abusers, over and above the effects of type of treatment received. Teens who show higher levels of discounting of the future may be an important subgroup to identify at treatment onset. Youth with a greater tendency to discount the future may require different intervention strategies that address their impulsivity (e.g., targeting executive function or inhibitory control) and/or different schedules of reinforcement to address their degree of preference for immediate rewards.


Effect of physical activity goals on aerobic physical activity: testing the mediating role of external and internal motivation.
Prior work has shown that primary care patients endorse one or more of the following PA goals, weight maintenance, overall benefits, stress reduction, weight loss, tone/body shape, overall well-being, cardiovascular fitness, and increased energy. Using self-determination theory as a guide, the present study tested whether these eight goals had indirect effects on likelihood of meeting aerobic PA guidelines through internal motivation, external motivation or both. Patients (N = 642; 60.7% female; 44.5% Black; Mage = 50.26 years) were recruited from the waiting room of a primary care clinic to complete a questionnaire. Results showed that PA goals of tone/shape, weight maintenance, and stress reduction had dual, opposing influences on likelihood of meeting aerobic PA guidelines via internal and external motivation. The goal of weight loss had a negative indirect effect on likelihood of meeting guidelines via external motivation. The PA goals of overall health benefits and cardiovascular health had singular, positive indirect effects on PA via internal motivation. Well-being had a direct positive effect on PA and a negative indirect effect via external motivation. Finally, the goal of improved energy had a direct positive effect on likelihood to meet PA guidelines. Implications for clinical practice and theory development are discussed.


Clinical and experimental experience with factor Xa inhibitors.
Cardiovascular disease is the major cause of mortality in the industrial world today. We are constantly moving towards new and better ways of fighting this epidemic. Advances have been made in various fields such as patient education, imaging techniques, interventional cardiology, and novel therapeutic agents. In particular, antithrombotics are being studied with great interest and hope. Amid this class of agents, factor Xa inhibitors have already begun to show promising results in trials involving patients with acute coronary syndromes. Whereas DX-9065a is in late stage clinical trials, fondaparinux sodium is available for clinical use. Promising results have been obtained with fondaparinux sodium in patients with coronary artery disease in the PENTUA (Pentasaccharide in Unstable Angina) and PENTALYSE (Pentasaccharide as an Adjunct to Fibrinolysis in ST-Elevation Acute Myocardial Infarction) trials. Besides having a direct effect on the coagulation cascade, they have shown properties that indirectly influence the remodeling of plaques in the coronary circulation. Available evidence on factor Xa inhibitors does not ensure a remedy to acute coronary syndromes but it gives hope of improving current treatments and reducing the morbidity and mortality of cardiovascular disease. The efficacy and tolerability of fondaparinux sodium in the prevention and treatment of deep vein thrombosis (with or without pulmonary embolism) has been established in several large trials such as PENTATHLON (Pentasaccharide in Total Hip Replacement Surgery), PENTAMAKS (Pentasaccharide in Major Knee Surgery), EPHESUS (European Pentasaccharide Hip Elective Surgery), PENTHIFRA (Pentasaccharide in Hip-Fracture Surgery), and PENTHIFRA-Plus. Whereas fondaparinux sodium offers benefits over low molecular weight heparins and unfractionated heparin, the incidence of bleeding complications was greater with fondaparinux sodium than with unfractionated heparin. Treatment with factor VIIa can reverse the anticoagulant effect of fondaparinux sodium and this may be particularly important in patients who need to undergo emergency surgical procedures. Fondaparinux sodium has been recently approved for use, in conjunction with warfarin, in patients with symptomatic deep vein thrombosis or acute pulmonary embolism based on the results of two large trials conducted by the Matisse investigators. In conclusion, these observations strongly suggest the clinical potential of this class of agents in preventing arterial and venous thrombosis.


System for stable β-estradiol-inducible gene expression in the moss Physcomitrella patens.
Inducible transgene expression provides a useful tool to analyze gene function. The moss Physcomitrellapatens is a model basal land plant with well-developed research tools, including a high efficiency of gene targeting and substantial genomics resources. However, current systems for controlled transgene expression remain limited. Here we report the development of an estrogen receptor mediated inducible gene expression system, based on the system used in flowering plants. After identifying the appropriate promoters to drive the chimeric transducer, we succeeded in inducing transcription over 1,000-fold after 24 h incubation with β-estradiol. The P. patens system was also effective for high-level long-term induction of gene expression; transcript levels of the activated gene were maintained for at least seven days on medium containing β-estradiol. We also established two potentially neutral targeting sites and a set of vectors for reproducible expression of two transgenes. This β-estradiol-dependent system will be useful to test genes individually or in combination, allowing stable, inducible transgenic expression in P. patens.


Cost effectiveness of memantine in Alzheimer's disease in the UK.
This analysis assesses the cost-effectiveness of memantine for the treatment of moderate-to-severe Alzheimer's disease (AD) in the UK. This cost-utility analysis was based on a Markov model. The model simulated 5-year progress of patients with AD until they need full-time care (FTC), defined as a patient becoming either dependent or institutionalised. Transition probabilities were based on a predictive equation, derived from the London and South-East Region epidemiological study. Resource use, utilities and mortality were obtained from the same study. Memantine efficacy was based on a meta-analysis of six large trials. The model compared memantine to its alternative in the UK, i.e. no pharmacological treatment or background therapy with acetylcholinesterase inhibitors. Memantine was found to delay the need to FTC by 6 weeks compared with current practice in the UK. It was associated with increased quality-adjusted life-years and cost savings to the healthcare system (probability of this outcome was 96%). The projections were made assuming that benefits from the 6-month treatment were sustained over time, which is regarded as the main limitation. The model underwent extensive sensitivity analyses, which confirmed the base-case findings. The model suggests that memantine delays the need for FTC and decreases cost. It can be regarded as a cost-effective choice in the management of moderate and severe AD.


[The mechanisms of the impact of preliminary immunization with staphylococcus anatoxin on postresuscitation pathology of the myocardium].
Chronic experiments lasting for 5 weeks were carried out in 40 nonpedigree mature dogs. It has been detected that preliminary immunization with staphylococcus anatoxin potentiates the compensation mechanisms in the course of postresuscitation period, stimulates cell proliferation by increasing cardiac output that is an adaptive reaction of the cardiovascular system in postresuscitation period and provides optimal metabolism of the organism.


Development of a Quality of Meals and Meal Service Set of Indicators for Residential Facilities for Elderly.
To develop a content validated set of indicators to evaluate the quality of meals and meal service in residential facilities for elderly. Inadequate food intake is an important risk factor for malnutrition in residential facilities for elderly. Through better meeting the needs and preferences of residents and optimization of meals and meal service, residents' food intake can improve. No indicators were available which could help to guide strategies to improve the quality of meals and meal service. The indicator set was developed according to the Indicator Development Manual of the Dutch Institute for Health Care Improvement (CBO). The working group consisted of three nurse researchers and one expert in gastrology and had expertise in elderly care, malnutrition, indicator development, and food quality. A preliminary list of potential indicators was compiled using the literature and the working group's expertise. Criteria necessary to measure the indicator in practice were developed for each potential indicator. In a double Delphi procedure, the list of potential indicators and respective criteria were analyzed for content validity, using a multidisciplinary expert panel of 11 experts in elderly meal care. A preliminary list of 20 quality indicators, including 45 criteria, was submitted to the expert panel in a double Delphi procedure. After the second Delphi round, 13 indicators and 25 criteria were accepted as having content validity. The content validity index (CVI) ranged from 0.83 to 1. The indicator set consisted of six structural, four result, and three outcome indicators covering the quality domains food, service and choice, as well as nutritional screening. The criteria measure diverse aspects of meal care which are part of the responsibility of kitchen staff and health care professionals. The 'quality of meals and meal service' set of indicators is a resource to map meal quality in residential facilities for elderly. As soon as feasibility tests in practice are completed, the indicator set can be used to guide meal and meal service quality improvement projects in collaboration with kitchen staff and health care professionals. These improvement projects will help to improve food intake and reduce the risk of malnutrition among elders living in residential facilities.


Tuberculosis and COVID-19 co-infection: description of the global cohort.
Information on tuberculosis (TB) and coronavirus disease 2019 (COVID-19) is still limited. The aim of this study was to describe the features of the TB/COVID-19 co-infected individuals from a prospective, anonymised, multicountry register-based cohort with special focus on the determinants of mortality and other outcomes. We enrolled all patients of any age with either active TB or previous TB and COVID-19. 172 centres from 34 countries provided individual data on 767 TB-COVID-19 co-infected patients, (>50% population-based). Of 767 patients, 553 (74.0%) out of 747 had TB before COVID-19 (including 234 out of 747 with previous TB), 71 (9.5%) out of 747 had COVID-19 first and 123 (16.5%) out of 747 had both diseases diagnosed within the same week (n=35 (4.6%) on the same day). 85 (11.08%) out of 767 patients died (41 (14.2%) out of 289 in Europe and 44 (9.2%) out of 478 outside Europe; p=0.03): 42 (49.4%) from COVID-19, 31 (36.5%) from COVID-19 and TB, one (1.2%) from TB and 11 from other causes. In the univariate analysis on mortality the following variables reached statistical significance: age, male gender, having more than one comorbidity, diabetes mellitus, cardiovascular disease, chronic respiratory disease, chronic renal disease, presence of key symptoms, invasive ventilation and hospitalisation due to COVID-19. The final multivariable logistic regression model included age, male gender and invasive ventilation as independent contributors to mortality. The data suggest that TB and COVID-19 are a "cursed duet" and need immediate attention. TB should be considered a risk factor for severe COVID disease and patients with TB should be prioritised for COVID-19 preventative efforts, including vaccination.


[Results of the treatment of cardiac surgery patients with postoperative acute respiratory distress syndrome by prone-position pulmonary ventilation].
Prone position ventilation (PPV) became an effective method of management of ARDS since 1974. Its positive effects on arterial oxygenation have been amply described, but its impact on the results of treatment and hospital mortality remains a disputable point. We observed 2 groups of patients, 36 pts. each, with ARDS after cardiovascular surgery. The main causes of ARDS were shock syndrome, massive blood loss and transfusion, previous COPD, and postcardiopulmonary bypass ALI. Because of impaired lung function (PaO2/FiO2 < 200), all patients were supported by special methods of ventilation including PEEP, high FiO2, and PCV with inverse I:E ratio. In the main group, PPV was started on days 3.6 +/- 1.2 postoperation. Daily duration of PPV was 4-12 h, after which the patients were turned into a supine position. Controls were treated in a supine position. The groups were identical by age, sex, types of surgery, severity of ARF, and manifestations of MOSF. PPV improved lung function and arterial oxygenation. Clinical outcomes were better in the PPV group than in the controls: a lower frequency of threatening arrhythmia, better results of MOSF treatment, and lower mortality (69 and 33.4%, respectively). Prone position is an effective measure improving arterial oxygenation in patients with ARDS after cardiovascular surgery. The main results of PPV are decrease in complications induced by hypoxia and higher survival rate.


Disposition and metabolism of [2-14C]epichlorohydrin after oral administration to rats.
A comprehensive disposition and metabolism study of epichlorohydrin (ECH) has not been previously reported. In this study, male Fischer 344 rats were dosed (6 mg/kg) orally with [2-14C]ECH (98% radiochemically pure) as an aqueous solution and killed after 3 days. Approximately 38% of the radioactive dose was exhaled as CO2, 50% was excreted as metabolites in the urine, and 3% was present in the feces. Radioactivity in tissues accounted for the remainder of the administered dose. When expressed per gram of tissue, radioactivity was highest in liver, kidney, and forestomach. The half-life of initial elimination of radioactivity in both the urine and exhaled air was about 2 hr, indicating that ECH was rapidly absorbed and metabolized. The major metabolites in the urine were identified as N-acetyl-S-(3-chloro-2-hydroxypropyl)-L-cysteine and alpha-chlorohydrin, about 36 and 4% of the administered dose, respectively. Finding these metabolites, which have not been previously reported, is consistent with the initial metabolic reactions being conjugation of the epoxide with glutathione and hydration of the epoxide.


Clinical parameters of concern in the pathology and treatment of hypertension.
To sum up, the endocrine analysis of human hypertension, tracing the renin system patterns, has provided a convincing body of data revealing and defining the biochemical heterogeneity of human hypertension. The heterogeneity, and the ability to differentiate it by the study of renin, embraces the major category that we call essential hypertension, which brackets at least 85% of all hypertension patients. This spectrum of biochemical heterogeneity is manifested physiologically by two different forms of vasoconstriction. One form is renin-mediated vasoconstriction, signified by the finding of a medium or high plasma renin activity and corrected by antirenin surgical or pharmacologic means. Toward the other end of the spectrum, revealed by the finding of low plasma renin, a sodium-volume-induced form of vasoconstriction operates. This appears to involve abnormal calcium metabolism and can also be characterized by measurable changes in serum ionized calcium values. With the development of newer and more specific antihypertensive agents with actions that appear to be rather specific against a particular vasoconstriction mechanism, new patterns of treatment are emerging that are preferable to the undiscriminating protocols of diuretic-oriented stepped care. The beta blockers or the CEIs can now be considered as the first pharmacological step against high- or medium-renin hypertensive states. The prescription of diuretics as the first step against the low-renin state can now be weighed against a more rational physiologic attack involving the probably safer, less troublesome, and more specific calcium-channel blocking drugs and also by the less potent alpha-adrenergic blockers. These latter two types of agents may exhibit finer marksmanship than do diuretics in opposing the etiology of low-renin hypertension, for there is growing reason to believe that sodium-volume-mediated vasoconstriction is related to abnormal calcium influx and possibly to abnormal alpha-adrenergic traffic.


[False positive with Tl-201 in the study of Ewing's sarcoma of the astragalus caused by reflex sympathetic dystrophy].
We describe a 14 year old male, diagnosed of Ewing sarcoma in left astragalus. We performed two 201-Thallium scan for evaluating the response to chemotherapy (before and after the treatment). The scan performed after chemotherapy showed patchy uptake in astragalus, calcaneus and some joints of the foot. The following radiology and scintigraphy diagnosed a reflex sympathetic dystrophy in the left foot due to disuse of the limb. The 201-Thallium overestimated viability of the tumour for this reason. We must discard the presence of this kind of associated pathology in order that they could be cause of false positives.


Congenitally corrected transposition of the great arteries.
Congenitally corrected transposition of the great arteries (CCTGA) is a rare congenital heart lesion with varied morphological presentation and can often by asymptomatic. A failing systemic right ventricle (RV) or increasing tricuspid regurgitation are generally indications for surgical intervention. The surgical approach depends upon the age of the patient and morphology of the lesion. Anatomical correction is associated with satisfactory long-term results.


Immunosignaturing can detect products from molecular markers in brain cancer.
Immunosignaturing shows promise as a general approach to diagnosis. It has been shown to detect immunological signs of infection early during the course of disease and to distinguish Alzheimer's disease from healthy controls. Here we test whether immunosignatures correspond to clinical classifications of disease using samples from people with brain tumors. Blood samples from patients undergoing craniotomies for therapeutically naïve brain tumors with diagnoses of astrocytoma (23 samples), Glioblastoma multiforme (22 samples), mixed oligodendroglioma/astrocytoma (16 samples), oligodendroglioma (18 samples), and 34 otherwise healthy controls were tested by immunosignature. Because samples were taken prior to adjuvant therapy, they are unlikely to be perturbed by non-cancer related affects. The immunosignaturing platform distinguished not only brain cancer from controls, but also pathologically important features about the tumor including type, grade, and the presence or absence of O(6)-methyl-guanine-DNA methyltransferase methylation promoter (MGMT), an important biomarker that predicts response to temozolomide in Glioblastoma multiformae patients.


Joint effect of white matter lesions and hippocampal volumes on severity of cognitive decline: the 3C-Dijon MRI study.
Several brain magnetic resonance imaging (MRI) changes are observed in older individuals including white matter lesions (WML), silent brain infarcts (SBI), and cerebral atrophy. Few studies, however, have assessed the combined association of these changes on the severity of future cognitive decline. In the prospective population-based 3C-Dijon MRI study, 1701 non-demented participants aged 65 to 80 years at entry had a brain MRI. Information on WML, hippocampal volumes, SBI presence, and brain parenchymal fraction were obtained. At 4-year follow-up, participants were screened for cognitive decline and dementia. Severity of cognitive decline was defined as none, moderate, or severe calculated from neuropsychological test performance change. The relation between brain MRI markers and longitudinal change in cognition was studied using polytomous logistic regression and multiple linear regression models controlling for potential confounders. Two-by-two interactions were tested including with the apolipoprotein E genotype. At follow-up, 46 participants showed severe cognitive deterioration and 224 participants showed moderate cognitive deterioration. In multivariable analyses, risk of severe cognitive deterioration as well as the cognitive decline rate were significantly increased in participants with higher WML volume (p< 0.01) and smaller hippocampal volume (p< 0.01). The results suggested that WML and hippocampal volumes had a cumulative effect on the future level of cognitive decline. The APOE genotype was found to be an effect modifier of this association. Vascular brain changes and degenerative processes coexist in normal older individuals. The co-occurrence of degenerative and non-degenerative pathologies could strongly affect the course of dementia expression.


Loci associated with ischaemic stroke and its subtypes (SiGN): a genome-wide association study.
The discovery of disease-associated loci through genome-wide association studies (GWAS) is the leading genetic approach to the identification of novel biological pathways underlying diseases in humans. Until recently, GWAS in ischaemic stroke have been limited by small sample sizes and have yielded few loci associated with ischaemic stroke. We did a large-scale GWAS to identify additional susceptibility genes for stroke and its subtypes. To identify genetic loci associated with ischaemic stroke, we did a two-stage GWAS. In the first stage, we included 16 851 cases with state-of-the-art phenotyping data and 32 473 stroke-free controls. Cases were aged 16 to 104 years, recruited between 1989 and 2012, and subtypes of ischaemic stroke were recorded by centrally trained and certified investigators who used the web-based protocol, Causative Classification of Stroke (CCS). We constructed case-control strata by identifying samples that were genotyped on nearly identical arrays and were of similar genetic ancestral background. We cleaned and imputed data by use of dense imputation reference panels generated from whole-genome sequence data. We did genome-wide testing to identify stroke-associated loci within each stratum for each available phenotype, and we combined summary-level results using inverse variance-weighted fixed-effects meta-analysis. In the second stage, we did in-silico lookups of 1372 single nucleotide polymorphisms identified from the first stage GWAS in 20 941 cases and 364 736 unique stroke-free controls. The ischaemic stroke subtypes of these cases had previously been established with the Trial of Org 10 172 in Acute Stroke Treatment (TOAST) classification system, in accordance with local standards. Results from the two stages were then jointly analysed in a final meta-analysis. We identified a novel locus (G allele at rs12122341) at 1p13.2 near TSPAN2 that was associated with large artery atherosclerosis-related stroke (first stage odds ratio [OR] 1·21, 95% CI 1·13-1·30, p=4·50 × 10-8; joint OR 1·19, 1·12-1·26, p=1·30 × 10-9). Our results also supported robust associations with ischaemic stroke for four other loci that have been reported in previous studies, including PITX2 (first stage OR 1·39, 1·29-1·49, p=3·26 × 10-19; joint OR 1·37, 1·30-1·45, p=2·79 × 10-32) and ZFHX3 (first stage OR 1·19, 1·11-1·27, p=2·93 × 10-7; joint OR 1·17, 1·11-1·23, p=2·29 × 10-10) for cardioembolic stroke, and HDAC9 (first stage OR 1·29, 1·18-1·42, p=3·50 × 10-8; joint OR 1·24, 1·15-1·33, p=4·52 × 10-9) for large artery atherosclerosis stroke. The 12q24 locus near ALDH2, which has previously been associated with all ischaemic stroke but not with any specific subtype, exceeded genome-wide significance in the meta-analysis of small artery stroke (first stage OR 1·20, 1·12-1·28, p=6·82 × 10-8; joint OR 1·17, 1·11-1·23, p=2·92 × 10-9). Other loci associated with stroke in previous studies, including NINJ2, were not confirmed. Our results suggest that all ischaemic stroke-related loci previously implicated by GWAS are subtype specific. We identified a novel gene associated with large artery atherosclerosis stroke susceptibility. Follow-up studies will be necessary to establish whether the locus near TSPAN2 can be a target for a novel therapeutic approach to stroke prevention. In view of the subtype-specificity of the associations detected, the rich phenotyping data available in the Stroke Genetics Network (SiGN) are likely to be crucial for further genetic discoveries related to ischaemic stroke. US National Institute of Neurological Disorders and Stroke, National Institutes of Health.


Understanding airborne contaminants produced by different fuel packages during training fires.
Fire training may expose firefighters and instructors to hazardous airborne chemicals that vary by the training fuel. We conducted area and personal air sampling during three instructional scenarios per day involving the burning of two types (designated as alpha and bravo) of oriented strand board (OSB), pallet and straw, or the use of simulated smoke, over a period of 5 days. Twenty-four firefighters and ten instructors participated. Firefighters participated in each scenario once (separated by about 48 hr) and instructors supervised three training exercise per scenarios (completed in 1 day). Personal air samples were analyzed for polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs), and hydrogen cyanide during live-fire scenarios (excluding simulated smoke). Area air samples were analyzed for acid gases, aldehydes, isocyanates, and VOCs for all scenarios. For the live-fire scenarios, median personal air concentrations of benzene and PAHs exceeded applicable short-term exposure limits and were higher among firefighters than instructors. When comparing results by type of fuel, personal air concentrations of benzene and PAHs were higher for bravo OSB compared to other fuels. Median area air concentrations of aldehydes and isocyanates were also highest during the bravo OSB scenario, while pallet and straw produced the highest median concentrations of certain VOCs and acid gases. These results suggest usage of self-contained breathing apparatus (SCBA) by both instructors and firefighters is essential during training fires to reduce potential inhalation exposure. Efforts should be taken to clean skin and clothing as soon as possible after live-fire training to limit dermal absorption as well.


Strategy to effect change in pharmacy practice.
The formulation of a strategy for change in pharmacy practice is described. Pharmacy has focused more on improving efficiency for existing functions than on identifying and adapting to the changing needs of society. The survival of the profession will depend on its ability to meet the present and future needs of society. Structural and procedural aspects of strategy formulation should focus on building a consensus within the profession. Interests of professional leaders, educators, practitioners, and the public should be incorporated into the profession's strategy. A center for strategic planning, supported by national pharmacy organizations, is suggested. Formulation of a strategy for pharmacy should involve: (1) an assessment of health-care needs relevant to pharmacy; (2) comparative evaluations of methods for delivering needed services; (3) integration with other health-care services; (4) organization and management of pharmacy practice; (5) financing considerations; and (6) legislative and regulatory changes. Planned strategic change will provide pharmacy with a mechanism for channeling its future activity in a direction that can effectively and efficiently meet the needs of society.


Variation of blood transfusion in patients undergoing major noncardiac surgery.
To examine the hospital variability in use of red blood cells (RBCs), fresh-frozen plasma (FFP), and platelet transfusions in patients undergoing major noncardiac surgery. Blood transfusion is commonly used in surgical procedures in the United States. Little is known about the hospital variability in perioperative transfusion rates for noncardiac surgery. We used the University HealthSystem Consortium database (2006-2010) to examine hospital variability in use of allogeneic RBC, FFP, and platelet transfusions in patients undergoing major noncardiac surgery. We used regression-based techniques to quantify the variability in hospital transfusion practices and to study the association between hospital characteristics and the likelihood of transfusion. After adjusting for patient risk factors, hospital transfusion rates varied widely for patients undergoing total hip replacement (THR), colectomy, and pancreaticoduodenectomy. Compared with patients undergoing THR in average-transfusion hospitals, patients treated in high-transfusion hospitals have a greater than twofold higher odds of being transfused with RBCs [adjusted odds ratio (AOR) = 2.41; 95% confidence interval (CI), 1.89-3.09], FFP (AOR = 2.81; 95% CI, 2.02-3.91), and platelets (AOR = 2.52; 95% CI, 1.95-3.25), whereas patients in low-transfusion hospitals have an approximately 50% lower odds of receiving RBCs (AOR = 0.45; 95% CI, 0.35-0.57), FFP (AOR = 0.37; 95% CI, 0.27-0.51), and platelets (AOR = 0.42; 95% CI, 0.29-0.62). Similar results were obtained for colectomy and pancreaticoduodenectomy. There was dramatic hospital variability in perioperative transfusion rates among patients undergoing major noncardiac surgery at academic medical centers. In light of the potential complications of transfusion therapy, reducing this variability in hospital transfusion practices may result in improved surgical outcomes.


Long Term and Spillover Effects of Health Shocks on Employment and Income.
We use matching combined with difference-in-differences to identify the causal effects of sudden illness, represented by acute hospitalizations, on employment and income up to six years after the health shock using linked Dutch hospital and tax register data. An acute hospital admission lowers the employment probability by seven percentage points and results in a five percent loss of personal income two years after the shock. There is no subsequent recovery in either employment or income. There are large spillover effects: household income falls by 50 percent more than the income of the disabled person.


Epidemiology of adolescent spinal pain: a systematic overview of the research literature.
Systematic literature review. To explore the available research literature, and provide an up-to-date synthesis of the epidemiology of idiopathic adolescent spinal pain (IASP). IASP and its potential causes have been a concern to researchers for over 2 decades. Because it has been suggested that IASP is related to the incidence of adult spinal pain, it appears important to synthesize what is currently known about IASP. A systematic meta-synthesis approach was used to identify secondary review articles and primary epidemiological studies regarding any type of IASP (neck, upper back, or low back). A total of 56 primary epidemiological (cross-sectional or longitudinal) studies were identified. Spinal or back pain was the most commonly reported measure, with the lifetime prevalence figures ranging from 4.7% to 74.4%. The lifetime prevalence of low back pain had a similar range, 7% to 72%. The prevalence of pain in other areas of the spine (i.e., thoracic spine and neck) was variably reported, as were incidence rates for all areas of the adolescent spine. IASP is thus a significant problem, and the prevalence figures approach those of adults. There is some evidence that IASP is a risk factor for spinal pain in adulthood. However, there was considerable variation in how back pain was defined, the areas of the spine that were reported on, the manner in which data were collected and reported, thus preventing any significant comparisons of prevalence or incidence rates across studies. Although there is wide discrepancy in the manner in which adolescent spinal pain is reported, it is evident that lifetime prevalence rates increase steadily with age and approximate adult levels by around the age of 18 years. There is an opportunity for further longitudinal research, with standardized methodology, to be undertaken that builds on the findings from this large group of studies.


An open label, pilot, randomized controlled trial of noradrenaline versus terlipressin in the treatment of type 1 hepatorenal syndrome and predictors of response.
Hepatorenal syndrome (HRS) is characterized by functional renal failure in end-stage liver disease. Terlipressin is the drug of choice for treating type 1 HRS (HRS-1). It is expensive and often not readily available. We, in an open label, randomized, pilot trial, compared the efficacy of terlipressin and noradrenaline on the renal functions and clinical outcome of patients with HRS-1 and also sought predictors of response. PATIENTS AND Forty consecutive patients with HRS-1 were randomized to receive noradrenaline 0.5-3.0 mg/h and albumin (group A, N = 20) or terlipressin 0.5-2 mg, 6 hourly and albumin (group B, N = 20), until reversal of HRS (primary end point) or completion of 15 days of therapy (secondary end point). Systemic and renal parameters were monitored. Baseline parameters and delta creatinine at day 4 (DCD4) were used to predict response. The two groups were comparable at baseline. At similar time points, 10 (50%) patients in each group achieved primary end points. Patients in both groups had a significant (P < 0.05) decrease in serum creatinine from baseline (group A day 4 2.4 +/- 1.2 mg/dL, day 8 1.6 +/- 1.2 mg/dL, and day 15 1.0 +/- 0.4 mg/dL; group B day 4 2.5 +/- 1.5 mg/dL, day 8 1.8 +/- 0.9 mg/dL, and day 15 1.2 +/- 0.5 mg/dL) and progressive increase in creatinine clearance (group A day 4 26.5 +/- 12.8 mL/min and day 15 59.8 +/- 14.2 mL/min; group B day 4 31.4 +/- 21.4 mL/min and day 15 54.9 +/- 27.5 mL/min, P < 0.05). Median baseline plasma renin activity was reduced from 38.0 and 42.0 ng/mL/h to 3.0 and 8.0 ng/mL/h (P= 0.08) in groups A and B, respectively. Mean arterial BP and urine output significantly increased in both groups with therapy. Eleven (55%) patients in group A (10 responders) and an equal number in group B (8 responders) survived until day 15 (P= 0.798). Reversible cardiac ischemia was seen in one patient in each group. Noradrenaline therapy was significantly less expensive than terlipressin. On univariate analysis, the following baseline parameters predicted response to therapy: lower grade of encephalopathy, lower MELD score, higher creatinine clearance, higher mean arterial pressure (MAP), and lower plasma renin activity. However, on multivariate analysis only baseline creatinine clearance, MAP, and plasma renin activity were independent predictors of response. At day 4 of therapy, DCD4 was computed and a value of 0.15 mg/dL/day or more accurately predicted response. The sensitivity, specificity, positive predictive value, and negative predictive value for DCD4 0.15 mg/dL/day for predicting response to therapy were 90%, 75%, 78%, and 88%, respectively. Noradrenaline may be an effective and safe alternative to terlipressin in improving renal functions. Various baseline parameters and DCD4 can be used to predict response to therapy.


Discontinuation of antiepileptic drugs after successful surgery: who and when?
Surgery is a highly effective treatment for some specific types of refractory epilepsy and once seizure freedom is achieved many patients and clinicians have to ponder whether to taper or discontinue antiepileptic drugs (AEDs). However, there is no standard practice or guidelines and practices vary widely. The few studies that have addressed this question are retrospective and lack randomised, controlled comparisons, making it difficult to draw any solid inferences. This review examines this topic by analysing key data based on the following: controlled studies which compare outcomes in patients with either withdrawn or unmodified AEDs after epilepsy surgery, non-controlled studies, information from meta-analyses and systematic reviews, surveys of clinical practice, and other relevant reviews. Between 12 and 32% of patients had seizure relapse following tapering or discontinuation of AEDs, which was not significantly different from 7 to 45% in patients without AED modification. In the event of seizure relapse upon tapering of AEDs, 45-92.3% restarted AED treatment and regained seizure freedom. The most consistent risk factors for seizure relapse were: age older than 30 years at the time of surgery, persistent auras, early drug tapering, seizure recurrence before a reduction of drugs, normal MRI, a longer period with epilepsy, absence of hippocampal sclerosis, and the presence of interictal discharges on EEG after surgery.


Structure-function correlations in mononuclear manganese(iii) spin crossover systems with a big conjugated hexadentate Schiff-base ligand.
This paper reports the syntheses, crystal structures and magnetic properties of spin crossover (SCO) salts of formulae [Mn(naphth-sal-N-1,5,8,12)]SbF6 (1), [Mn(naphth-sal-N-1,5,8,12)]AsF6 (2), [Mn(naphth-sal-N-1,5,8,12)]PF6·1/2CH3OH (3) and [Mn(naphth-sal-N-1,5,8,12)]ClO4 (4), where (naphth-sal-N-1,5,8,12)2- (2,2'-((1E,14E)-2,6,10,14-tetraazapentadeca-1,14-diene-1,15-diyl)diphenolate) is a big conjugated hexadentate Schiff-base ligand. Magnetic susceptibility measurements demonstrated that complexes 1 and 2 showed a gradual one-step SCO between the high-spin (HS, S = 2) and low-spin (LS, S = 1) states without thermal hysteresis. The transition temperatures T1/2 of the SbF6 (1) and AsF6 (2) salts estimated from the magnetic susceptibility measurements are 164 and 171 K, respectively. The existence of the crystal solvent of complex 3 changes the supramolecular packing, leading to close ππ stacking interactions between the phenyl groups of the ligands. These close stacking interactions hinder the flexibility of the whole ligand, precluding the spin transformation of complex 3 and leading to its stabilization in the HS state in the temperature range of 2-300 K. For 4, crystal structure analysis indicates that the reduction in the anion size leads to close contacts between the naphthalene rings. These C-Hπ interactions provide a means for preventing the spin crossover occurring at low temperatures.


Comment on "Helical magnetorotational instability in magnetized Taylor-Couette flow".
Liu [Phys. Rev. E 74, 056302 (2006)] have presented a WKB analysis of the helical magnetorotational instability (HMRI), and claim that it does not exist for Keplerian rotation profiles. We show that, if radial boundary conditions are included, the HMRI can exist even for rotation profiles as flat as Keplerian, provided only that at least one of the boundaries is sufficiently conducting.


Ytterbium-doped large-mode-area all-solid photonic bandgap fiber lasers.
Single-mode operation in a large-mode-area fiber laser is highly desired for power scaling. We have, for the first time, demonstrated a 50μm-core-diameter Yb-doped all-solid photonic bandgap fiber laser with a mode area over 4 times that of the previous demonstration. 75W output power has been generated with a diffraction-limited beam and an efficiency of 70% relative to the launched pump power. We have also experimentally confirmed that a robust single-mode regime exists near the high frequency edge of the bandgap. These fibers only guide light within the bandgap over a narrow spectral range, which is essential for lasing far from the gain peak and suppression of stimulated Raman scattering. This work demonstrates the strong potential for mode area scaling of in single-mode all-solid photonic bandgap fibers.


HIF-prolyl hydroxylases as therapeutic targets in erythropoiesis and iron metabolism.
A classic response to systemic hypoxia is the increase in red blood cell production. This response is controlled by the prolyl hydroxylase domain/hypoxia-inducible factor (HIF) pathway, which regulates a broad spectrum of cellular functions. The discovery of this pathway as a key regulator of erythropoiesis has led to the development of small molecules that stimulate the production of endogenous erythropoietin and enhance iron metabolism. This review provides a concise overview of the cellular and molecular mechanisms that govern HIF-induced erythropoietic responses and provides an update on clinical experience with compounds that target HIF-prolyl hydroxylases for anemia therapy.


Dissipative open systems theory as a foundation for the thermodynamics of linear systems.
In this paper, we advocate the use of open dynamical systems, i.e. systems sharing input and output variables with their environment, and the dissipativity theory initiated by Jan Willems as models of thermodynamical systems, at the microscopic and macroscopic level alike. We take linear systems as a study case, where we show how to derive a global Lyapunov function to analyse networks of interconnected systems. We define a suitable notion of dynamic non-equilibrium temperature that allows us to derive a discrete Fourier law ruling the exchange of heat between lumped, discrete-space systems, enriched with the Maxwell-Cattaneo correction. We complete these results by a brief recall of the steps that allow complete derivation of the dissipation and fluctuation in macroscopic systems (i.e. at the level of probability distributions) from lossless and deterministic systems.This article is part of the themed issue 'Horizons of cybernetical physics'.


Radiation Engineering of Multifunctional Nanogels.
Nanogels combine the favourable properties of hydrogels with those of colloids. They can be soft and conformable, stimuli-responsive and highly permeable, and can expose a large surface with functional groups for conjugation to small and large molecules, and even macromolecules. They are among the very few systems that can be generated and used as aqueous dispersions. Nanogels are emerging materials for targeted drug delivery and bio-imaging, but they have also shown potential for water purification and in catalysis. The possibility of manufacturing nanogels with a simple process and at relatively low cost is a key criterion for their continued development and successful application. This paper highlights the most important structural features of nanogels related to their distinctive properties, and briefly presents the most common manufacturing strategies. It then focuses on synthetic approaches that are based on the irradiation of dilute aqueous polymer solutions using high-energy photons or electron beams. The reactions constituting the basis for nanogel formation and the approaches for controlling particle size and functionality are discussed in the context of a qualitative analysis of the kinetics of the various reactions.


Evaluation of the sustainability of deep groundwater as an arsenic-safe resource in the Bengal Basin.
Tens of millions of people in the Bengal Basin region of Bangladesh and India drink groundwater containing unsafe concentrations of arsenic. This high-arsenic groundwater is produced from shallow (<100 m) depths by domestic and irrigation wells in the Bengal Basin aquifer system. The government of Bangladesh has begun to install wells to depths of >150 m where groundwater arsenic concentrations are nearly uniformly low, and many more wells are needed, however, the sustainability of deep, arsenic-safe groundwater has not been previously assessed. Deeper pumping could induce downward migration of dissolved arsenic, permanently destroying the deep resource. Here, it is shown, through quantitative, large-scale hydrogeologic analysis and simulation of the entire basin, that the deeper part of the aquifer system may provide a sustainable source of arsenic-safe water if its utilization is limited to domestic supply. Simulations provide two explanations for this result: deep domestic pumping only slightly perturbs the deep groundwater flow system, and substantial shallow pumping for irrigation forms a hydraulic barrier that protects deeper resources from shallow arsenic sources. Additional analysis indicates that this simple management approach could provide arsenic-safe drinking water to >90% of the arsenic-impacted region over a 1,000-year timescale. This insight may assist water-resources managers in alleviating one of the world's largest groundwater contamination problems.


Long-term Outcome of Argon Laser Peripheral Iridoplasty in the Management of Plateau Iris Syndrome Eyes.
To report long-term (>5 y) outcomes of plateau iris syndrome patients treated with argon laser peripheral iridoplasty (ALPI). A retrospective chart review was performed on all patients with plateau iris syndrome treated with ALPI from 1996 to 2007. The study included 22 eyes from 22 patients with plateau iris after peripheral iridotomy that were followed for at least 1 year after ALPI. The primary outcome was incidence of needing any intraocular pressure (IOP)-lowering medications or surgery (either a filtering procedure or phacoemulsification). Demographic and baseline clinical data were summarized by mean (±SD) or frequency (percentage). Snellen best-corrected visual acuity was converted to logMAR. The paired t test was used to compare IOP changes, number of IOP-lowering medications, and best-corrected visual acuity from baseline to annual follow-up. Mean follow-up was 76 months. Only 2 (9%) eyes maintained an IOP<21 mm Hg without requiring medication or surgery. Seventeen (77%) eyes underwent surgery at an average of 49.1±7.9 months after ALPI. Eight (36%) eyes underwent filtering surgery, and 9 (41%) eyes underwent phacoemulsification. Three months after cataract extraction, no eyes required IOP-lowering medication. The beneficial effects of ALPI last for <4 years, with the majority of patients (77%) requiring surgery. Phacoemulsification alone was a successful treatment for plateau iris in our patient population.


Tuning the electronic structure of Pd by the surface configuration of Al2O3 for hydrogenation reactions.
The electronic interaction between a metal and a support modulates the electronic structures of supported metals and plays an important role in manipulating their catalytic performance. However, this interaction is mainly realized in heterogeneous catalysts composed of reducible oxides. Herein, we demonstrate the electronic interaction between γ-Al2O3 and η-Al2O3 with varying acid-base properties and supported Pd nanoparticles (NPs) of 2 nm in size. The strength and number of acid-base sites on the supports and catalysts were systemically characterized by FT-IR spectroscopy and TPD. The supported Pd NPs exhibit electron-rich surface properties by receiving electrons from the electron-donating basic sites on γ-Al2O3, which are beneficial for catalyzing the hydrogenation of nitrobenzene. In contrast, Pd NPs loaded on η-Al2O3 are electron-deficient because of the rich electron-withdrawing acid sites of η-Al2O3. As a result, Pd/η-Al2O3 exhibits higher catalytic activity in phenylacetylene hydrogenation than Pd/γ-Al2O3. Our results suggest a promising route for designing high-performance catalysts by adjusting the acid-base properties of Al2O3 supports to maneuver the electronic structures of metals.


Intraocular large B-cell lymphoma. A case report.
Large cell lymphoma involving the vitreous humor is uncommon, and its diagnosis in the absence of central nervous system disease can be difficult. The major diagnostic difficulties with vitreous washings in the absence of ancillary studies are in the distinction of inflammatory lymphoid infiltrate from intraocular lymphoma or diagnosing lymphoma when only very few neoplastic cells are present. A 75-year-old, white male sought medical attention for bilateral blurred vision and decreased visual acuity of recent onset. A clinical diagnosis of bilateral uveitis to rule out primary intraocular lymphoma or an infectious process was made, and a right vitrectomy was performed. An unequivocal diagnosis of lymphoma could not be made due to the paucity of neoplastic cells on that specimen. Two months later smears from the Cytospin (Thermo Shandon, Pittsburgh, Pennsylvania, U.S.A.) prepared on the specimen from a left vitrectomy showed a greater number of large, pleomorphic cells. In addition, immunocytochemical staining confirmed the B-cell lineage of the neoplastic cells. Immunoglobulin gene rearrangement analysis performed by the polymerase chain reaction method on the frozen cell pellet from the left vitrectomy demonstrated the presence of a monoclonal B-cell population, confirming the diagnosis of large B-cell lymphoma. Vitreous cytology in conjunction with ancillary studies is a sensitive procedure in the diagnosis of intraocular lymphoma.


A Burkholderia pseudomallei deltapurM mutant is avirulent in immunocompetent and immunodeficient animals: candidate strain for exclusion from select-agent lists.
Burkholderia pseudomallei causes the disease melioidosis in humans and is classified as a category B select agent. Research utilizing this pathogen is highly regulated in the United States, and even basic studies must be conducted in biosafety level 3 (BSL-3) facilities. There is currently no attenuated B. pseudomallei strain available that is excluded from select-agent regulations and can be safely handled at BSL-2 facilities. To address this need, we created Bp82 and Bp190, which are DeltapurM derivatives of B. pseudomallei strains 1026b and K96243 that are deficient in adenine and thiamine biosynthesis but replication competent in vitro in rich medium. A series of animal challenge studies was conducted to ensure that these strains were fully attenuated. Whereas the parental strains 1026b and K96243 and the complemented mutants Bp410 and Bp454 were virulent in BALB/c mice following intranasal inoculation, the DeltapurM mutants Bp82 and Bp190 were avirulent even when they were administered at doses 4 logs higher than the doses used for the parental strains. Animals challenged with high doses of the DeltapurM mutants rapidly cleared the bacterium from tissues (lung, liver, and spleen) and remained free of culturable bacteria for the duration of the experiments (up to 60 days postinfection). Moreover, highly susceptible 129/SvEv mice and immune incompetent mice (IFN-gamma-/-, SCID) were resistant to challenges with DeltapurM mutant Bp82. This strain was also avirulent in the Syrian hamster challenge model. We concluded that DeltapurM mutant Bp82 is fully attenuated and safe for use under BSL-2 laboratory conditions and thus is a candidate for exclusion from the select-agent list.


[Pharmacokinetics of ketoprofen in the synovial fluid].
Serum and synovial fluid concentrations of ketoprofen were studied after administration of 50 or 100 mg in a single oral dose to patients with rheumatoid arthritis. Results show that ketoprofen is rapidly absorbed. Serum concentrations are similar in patients and healthy subjects. During the initial phase, plasma half-life, which averaged 1.5 to 2 hours in study patients, was similar to that recorded in controls. Significant accumulation of ketoprofen in synovial fluid of patients was demonstrated.


Search for Higgs and Z Boson Decays to J/ψγ and ϒ(nS)γ with the ATLAS Detector.
A search for the decays of the Higgs and Z bosons to J/ψγ and ϒ(nS)γ (n=1,2,3) is performed with pp collision data samples corresponding to integrated luminosities of up to 20.3 fb^{-1} collected at sqrt[s]=8 TeV with the ATLAS detector at the CERN Large Hadron Collider. No significant excess of events is observed above expected backgrounds and 95% C.L. upper limits are placed on the branching fractions. In the J/ψγ final state the limits are 1.5×10^{-3} and 2.6×10^{-6} for the Higgs and Z boson decays, respectively, while in the ϒ(1S,2S,3S)γ final states the limits are (1.3,1.9,1.3)×10^{-3} and (3.4,6.5,5.4)×10^{-6}, respectively.


A role of the -35 element in the initiation of transcription at psbA promoter in tobacco plastids.
Most plastid promoters recognized by bacteria-like plastid RNA polymerase (PEP) are similar to E. coli sigma(70)-type promoters comprising "-35" and "-10" elements. Among them, psbA promoter is unique in bearing additional elements between the conserved -35 and -10 elements. The psbA promoter activity is differentially maintained in the mature chloroplasts where the activity of most PEP promoters declines. Previously, we identified two types of PEP activities in wheat seedlings [Satoh et al. (1999) Plant J. 18: 407]; PEP present in the mature chloroplasts of the leaf tip (tip-type PEP) can initiate transcription from the -35-destructed psbA promoter, but the -35 element is essential for transcription by PEP present in immature chloroplasts of the leaf base (base-type PEP). To reveal which type of PEP functions in various types of plastids in tobacco, we analyzed the tobacco psbA promoter by means of a transplastomic approach. The promoter core context (-42 to +9) was sufficient for developmental regulation of the psbA promoter activity. The -35 promoter element was important for transcription initiation at the psbA promoter in all types of plastids, including chloroplasts in mature leaves, leucoplasts in roots, etioplasts in etiolated cotyledons. The conclusion is that the PEP bearing a promoter preference, similar to the wheat base-type PEP, functions dominantly in tobacco chloroplasts.


Genome-wide pleiotropy and shared biological pathways for resistance to bovine pathogens.
Host genetic architecture is a major factor in resistance to pathogens and parasites. The collection and analysis of sufficient data on both disease resistance and host genetics has, however, been a major obstacle to dissection the genetics of resistance to single or multiple pathogens. A severe challenge in the estimation of heritabilities and genetic correlations from pedigree-based studies has been the confounding effects of the common environment shared among relatives which are difficult to model in pedigree analyses, especially for health traits with low incidence rates. To circumvent this problem we used genome-wide single-nucleotide polymorphism data and implemented the Genomic-Restricted Maximum Likelihood (G-REML) method to estimate the heritabilities and genetic correlations for resistance to 23 different infectious pathogens in calves and cows in populations undergoing natural pathogen challenge. Furthermore, we conducted gene-based analysis and generalized gene-set analysis to understand the biological background of resistance to infectious diseases. The results showed relatively higher heritabilities of resistance in calves than in cows and significant pleiotropy (both positive and negative) among some calf and cow resistance traits. We also found significant pleiotropy between resistance and performance in both calves and cows. Finally, we confirmed the role of the B-lymphocyte pathway as one of the most important biological pathways associated with resistance to all pathogens. These results both illustrate the potential power of these approaches to illuminate the genetics of pathogen resistance in cattle and provide foundational information for future genomic selection aimed at improving the overall production fitness of cattle.


Effects of an exercise adherence intervention on outcomes in patients with heart failure.
The purpose of this study was to determine how an exercise adherence intervention affects the physiological, functional, and quality of life outcomes of patients with heart failure (HF). Sixteen HF patients were randomly assigned to an exercise-only group (n = 8) or to an exercise-with-adherence group (n = 8). Two of the 16 people died from nonexercise related causes during the study and were not included in the analysis. The intervention was tested over a 24-week period in which patients participated in a 12-week supervised exercise program (Phase 1) followed by 12 weeks of unsupervised home exercise (Phase 2). The intervention format was one of individualized graphic feedback on exercise goals and participation and problem-solving support by nurses. Results indicate that patients who received the intervention exercised more frequently and experienced improved outcomes during both phases. The adherence intervention may encourage HF patients to continue to exercise and thereby maintain the health benefits gained in both phases of an exercise program.


A mathematical model of kinetochore-microtubule attachment regulated by Aurora A activity gradient describes chromosome oscillation and correction of erroneous attachments.
Chromosome oscillation during metaphase is attenuated in cancer cell lines, concomitant with the reduction of Aurora A activity on kinetochores, which results in reduced mitotic fidelity. To verify the correlation between Aurora A activity, chromosome oscillation, and error correction efficiency, we developed a mathematical model of kinetochore-microtubule dynamics, based on stochastic attachment/detachment events regulated by Aurora A activity gradient centered at spindle poles. The model accurately reproduced the oscillatory movements of chromosomes, which were suppressed not only when Aurora A activity was inhibited, but also when it was upregulated, mimicking the situation in cancer cells. Our simulation also predicted efficient correction of erroneous attachments through chromosome oscillation, which was hampered by both inhibition and upregulation of Aurora A activity. Our model provides a framework to understand the physiological role of chromosome oscillation in the correction of erroneous attachments that is intrinsically related to Aurora A activity.


Effect anticipation and action control.
According to the authors' 2-phase model of action control, people first incidentally acquire bidirectional associations between motor patterns and movement-contingent events and then intentionally use these associations for goal-directed action. The authors tested the model in 4 experiments, each comprising an acquisition phase, in which participants experienced co-occurrences between left and right keypresses and low- and high-pitched tones, and a test phase, in which the tones preceded the responses in forced- and free-choice designs. Both reaction time and response frequency in the test phase depended on the learned associations, indicating that presenting a tone activated the associated response. Results are interpreted as evidence for automatic action-outcome integration and automatic response priming through learned action effects. These processes may be basic for the control of voluntary action by the anticipation of action goals.


Localized surface plasmon resonance effects on the magneto-optical activity of continuous Au/Co/Au trilayers.
We study how the magneto-optical activity in polar configuration of continuous Au/Co/Au trilayers is affected by the excitation of localized plasmon resonances of an array of Au nanodiscs fabricated on top of them over a dielectric SiO(2) spacer. We show that the effect of the nanodiscs array is twofold. First, it optimizes the absorption of light at specific photon energies corresponding to the localized surface plasmon excitation of the array, modifying the reflectivity of the system (we define this effect as the purely optical contribution). Second, upon localized plasmon resonance excitation, the electromagnetic field in the whole system is redistributed, and an enhanced magneto-optical activity occurs at those energies where the electromagnetic field in the magnetic layer is increased (this effect is identified as the purely magneto-optical contribution of the nanodiscs array).


[Problem of clinico-pathogenetic analysis and correction of behavior disorders in adolescents].
On the basis of integrated clinical, dynamic, and neurophysiological examinations of 542 children and adolescents with behaviour deviations a high (54.05%) percentage of psychic anomalies (primarily, characterological ones) was discovered. The structure of the delinquent behaviour was found to be the most complicated in children and adolescents taught at special schools for juvenile offenders. In adolescents registered at the Inspection on Minors' Affairs this structure was of a more isolated character. An important role of combinations of constitutional-biological, exogenous-organic, and negative microsocial factors in the genesis of the juvenile delinquency is demonstrated. Clinical and laboratory examinations of "difficult" adolescents with distinct neuropsychic disturbances revealed substantial shifts in their cortical neurodynamics and the functioning of chemoreactive systems. On the basis of the data obtained a complex of differentiated therapeutic and hygienic measures aimed at attaining a regression of the borderline personality pathologies has been developed.


The conserved structure of snake venom toxins confers extensive immunological cross-reactivity to toxin-specific antibody.
We have demonstrated previously that antisera from mice immunised with DNA encoding the carboxy-terminal domain (JD9) of a potent haemorrhagic metalloproteinase, jararhagin, neutralised over 70% of the haemorrhagic activity of the whole Bothrops jararaca venom. Here, we demonstrate that the JD9-specific antibody possesses extensive immunological reactivity to venom components in snakes of distinct species and genera. The polyspecific immunological reactivity of the antibody showed a correlation with amino acid sequence identity and with predicted antigenic domains of JD9-analogues in venoms of snakes with closest phylogenetic links to B. jararaca. This study further promotes the potential of DNA immunisation to generate toxin-specific antibodies with polyspecific cover. An analysis of the reactivity of the JD9-specific antisera to B. atrox complex venoms that exhibited intraspecific variation in the venom proteome revealed, however, that the toxin-specific approach to antivenom development requires a more in-depth knowledge of the target molecules than is required for conventional antivenoms.


The role of depth and 1/f dynamics in perceiving reversible figures.
When confronted with a reversible figure, such as the Necker Cube, viewers experience a spontaneously changing percept. We assess the dynamic of how the human visual system resolves perceptual ambiguity in stimuli that offer multiple interpretations. Subjects observed the Necker cube for one of three viewing durations during which they pressed a key each time they perceived a change in the orientation of the cube. Manipulations of binocular disparity served as a parameter to control perceptual stability. Low-depth conditions yielded more perceptual reversals than high-depth conditions. A Fourier analysis performed on the time series of reversals show 1/f (pink) noise was evident in their power spectra. These results together with theoretical models of complex systems (e.g., Bak, Tang, and Wiesenfeld, 1987) suggest that depth information may guide our perceptual system into a self-organized state to assist us in resolving ambiguous information. Moreover, slopes of the spectra were steeper in high-depth and brief viewing conditions, suggesting that the visual system relies more on previous perceptual states and filters more white noise in these conditions.


Membrane-mediated assembly of filamentous bacteriophage Pf1 coat protein.
Filamentous bacteriophage Pf1 assembles by a membrane-mediated process during which the viral DNA is secreted through the membrane while being encapsulated by the major coat protein. Neutron diffraction studies showed that in the virus most of the coat protein consists of two alpha-helical segments arranged end-to-end with an intervening mobile surface loop. Nuclear magnetic resonance studies of the coat protein in the membrane-bound form have shown that the secondary structure is essentially identical to that in the intact virus. A comparison indicates that during membrane-mediated viral assembly, while the secondary structure of the coat protein is largely conserved, its tertiary structure changes substantially.


Defective canalicular transport and toxicity of dietary ursodeoxycholic acid in the abcb11-/- mouse: transport and gene expression studies.
The bile salt export pump (BSEP), encoded by the abcb11 gene, is the major canalicular transporter of bile acids from the hepatocyte. BSEP malfunction in humans causes bile acid retention and progressive liver injury, ultimately leading to end-stage liver failure. The natural, hydrophilic, bile acid ursodeoxycholic acid (UDCA) is efficacious in the treatment of cholestatic conditions, such as primary biliary cirrhosis and cholestasis of pregnancy. The beneficial effects of UDCA include promoting bile flow, reducing hepatic inflammation, preventing apoptosis, and maintaining mitochondrial integrity in hepatocytes. However, the role of BSEP in mediating UDCA efficacy is not known. Here, we used abcb11 knockout mice (abcb11-/-) to test the effects of acute and chronic UDCA administration on biliary secretion, bile acid composition, liver histology, and liver gene expression. Acutely infused UDCA, or its taurine conjugate (TUDC), was taken up by the liver but retained, with negligible biliary output, in abcb11-/- mice. Feeding UDCA to abcb11-/- mice led to weight loss, retention of bile acids, elevated liver enzymes, and histological damage to the liver. Semiquantitative RT-PCR showed that genes encoding Mdr1a and Mdr1b (canalicular) as well as Mrp4 (basolateral) transporters were upregulated in abcb11-/- mice. We concluded that infusion of UDCA and TUDC failed to induce bile flow in abcb11-/- mice. UDCA fed to abcb11-/- mice caused liver damage and the appearance of biliary tetra- and penta-hydroxy bile acids. Supplementation with UDCA in the absence of Bsep caused adverse effects in abcb11-/- mice.


The influence of gradient and statistical arrangements of guanidinium or primary amine groups in poly(methacrylate) copolymers on their DNA binding affinity.
Herein, we report the first gradient guanidinium containing cationic copolymers and investigate their binding ability to plasmid DNA (pDNA). To understand the effect of different charge distributions and cationic charge sources (primary amines vs. guanidinium group) on (pDNA) binding affinity, we synthesized a library of well-defined statistical cationic copolymers comprising N-(2-hydroxy-propyl)methacrylamide (HPMA) and N-(3-aminopropyl)methacrylamide (APMA) or N-(3-guanidinopropyl)methacrylamide (GPMA) and compared them with gradient polymers containing the same monomers of similar composition. All copolymers were synthesized through aqueous reversible addition-fragmentation chain transfer (aRAFT) polymerization at various monomer ratios by aiming at similar molar masses with low dispersity indices. For the molar mass characterization, in addition to size exclusion chromatography with two different systems, hydrodynamic characterization utilizing analytical ultracentrifugation, viscometry, and accompanied density measurements was conducted. pDNA was used as a model drug to demonstrate the impact of copolymer architecture on binding efficiency. For both HPMA-APMA and HPMA-GPMA copolymers, the gradient distribution demonstrated superior binding and denser packing of pDNA than their statistical counterparts at 20% and lower cationic charge contents. With respect to charge origin, the guanidinium group represented a higher binding efficiency than primary amines with the same nitrogen to phosphate ratio (N/P ratio). Our study demonstrates the profound effect of gradient monomer arrangement on the ability of polyplex formation and reveals the potential for further investigation in gene delivery applications. Gradient guanidinium containing copolymers have great promise for gene delivery applications due to their high affinity toward pDNA even at very low degrees (<20%) of charged monomer content.