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• The background to 'Science as a Vocation' in Max Weber's own work. • Weber's rare yet highly perceptive statements on the origins of modern science • What made Weber so outstanding a scholar In his 1917 lecture for Munich students (most often entitled in English translation "Science as a Vocation"), Max Weber addressed numerous issues: not only how "profession" and "calling" are related in science and scholarship, but also Entzauberung ("disenchantment"); rationality and its limits; ultimate values; and the field of tension between science and religion. The present essay locates these themes in Weber's oeuvre from 1911 onward, and analyses how they resonate and culminate in Weber's address in 1917. It is in 1911 that he decided to engage with the problem that was to stand central in his thinking until his death in 1920: the nature and causes of certain specific turns in the course of European history which, so he argued, have proven to be of "universal significance." Special attention is given in the present essay to how Weber dealt in this connection with the rise of modern science and the rise of modern tonal harmony. A concluding section explains what, over a century later, makes reading Weber still so rewarding an experience. [ABSTRACT FROM AUTHOR]

Background: Walkway codes and standards are created through consensus by committees based on a number of factors, including historical precedence, common practice, cost, and, sometimes, empirical data. The authors maintain that codes and standards that can have an impact on human safety and welfare should give consideration in their formulation to the results of pertinent scientific research.Purpose: This article extends a companion one in examining many elements of common walkway codes and standards related specifically to lighting, warnings and markings. It indicates which elements are based on or supported by empirical data; and which elements could benefit from additional scientific research.Practical Applications: This article identifies areas in which additional research leading toward scientific based codes and standards may be beneficial in enhancing the safety of pedestrian walkway surfaces. [ABSTRACT FROM AUTHOR]

Abstract: Alterations of nitric oxide (NO) metabolism in the brain have been associated with modifications of stress-related behavior in animal models. It has been generally assumed that these behavioral changes are due to the neuronal nitrosative activity. On the other hand, glial NO production has been demonstrated mainly as a slow reaction to brain insults through the activity of an inducible nitric oxide synthase (NOS) isoform (NOS2). Recently we uncovered increased NOS activity in astrocytes of mice with a NOS2 mutation. Interestingly, these mice revealed a behavioral phenotype suggestive of increased susceptibility to stress. In the present study we investigated the responses of these mutants to stress by exposing them to predator scent. Seven days later, mutant mice exhibited significantly higher anxiety-like behavior in the elevated-plus maze, increased acoustic startle responses, and higher plasma corticosterone levels compared with their controls. Systemic administration of a NOS inhibitor prior to the stress exposure reversed these stress-related effects without affecting controls'' behavior. These findings are in agreement with previous studies showing an association between increased NO levels and enhanced anxiety-like responses. In addition, mutant mice performed better in the Morris water maze prior to stress exposure, but the two animal groups performed alike in an object-recognition test. Taken together, our results suggest the involvement of astrocytic-derived NO in modulating behavior. [Copyright &y& Elsevier]

Problem: Evidence exists to suggest that working with computer terminals and keyboards is associated with the development and exacerbation of a range of musculoskeletal disorders (MSDs). Research has suggested that psychosocial factors may be of more importance than computer use factors in the development of MSDs in the computing workplace. Method: A questionnaire-based study was undertaken to test this hypothesis in a sample of 67 call center workers. A Spearman''s rho was performed on the data, as well as χ2 tests on the individual variables. Results: It was found that overall, computer use factors were significantly associated with self-reporting of MSD symptoms, whereas psychosocial factors had no such association. However, certain individual psychosocial factors emerged as having a significant association with MSD symptoms. Discussion: The findings suggest that specific areas of call center work have associations with poor worker health and possible long-term MSD problems. These areas appear to be workload and particular management–worker relations, rather than computer use. Summary: This suggests that the relationship among computer use, psychosocial factors, and MSD is a complex area that would benefit from more research. Impact on industry: This study raises issues about the importance of psychosocial and organizational factors and employee welfare in the call center working environment. [Copyright &y& Elsevier]

It is known that CsxWO3, 0.3⩾x⩾0.19, is a 3D superconductor. Below x=0.19 a transition from a metal to an insulator occurs and for x=0.10, for example, no superconductivity is observed. We find, however, that for x⩽0.05 superconductivity reappears. For x=0.005 nominal concentration we observe a critical transition Tc to the superconducting state at 5.9 K. This is observed in magnetic measurements, where a pronounced Meissner effect is present. X-ray photoelectron spectroscopy and transport measurements indicate that the SC state is confined to mesoscopic islands, some 10 nm thick on the surface of the CsxWO3 doped crystals. The bulk of the crystal is practically pure WO3. Thus during the high temperature crystal growth process, there is a redistribution of the Cs dopant as it migrates to the surface of the WO3 crystals. From these observations, we conclude that upon reduction of the Cs nominal concentration below x=0.05, a 2D superconductor is formed, while for x⩾0.19, the CsxWO3 bronze is a 3D superconductor. [Copyright &y& Elsevier]

Leukocytes derived from the peripheral blood of peripheral patients demonstrated an. enhanced chemotactic response compared with leukocytes from healthy subjects. No significant difference was detected between the chemotactic response of leukocytes from patients with minimal or no skin involvement and those from patients with extensive lesions. Psoriatic leukocytes also had a significantly higher capacity to engulf 125I labeled Shigella flexneri than control leukocytes. It is postulated that a decrease in the cyclic AMP/cyclic GMP ratio in psoriatic leukocytes, similar to the imbalance of these 2 cyclic nucleotides found in the lesional epidermis of psoriasis, might be the cause of their enhanced chemotactic and phagocytic activities. [ABSTRACT FROM AUTHOR]

Introduction Glucocorticoid (GC) hormones play a major role in orchestrating the physiological and behavioral reactions essential for homeostasis. As such, these hormones enable the organism to prepare for, respond to, and cope with the acute demands of physical and emotional stressors [1]. The secretion of GC hormones is a dynamic process which displays, in addition to a circadian pattern of release, an ultradian rhythmicity in the blood and in target tissues [2] Inadequate GC release following stress not only delays recovery but can also interfere with the processing or interpretation of stressful information, resulting in long-term disruptions of memory integration processes [3]. An example of such an impaired process is post-traumatic stress disorder (PTSD) [4]. In the rat, corticosterone ultradian pulses have a near-hourly frequency and changes in the amplitude of these pulses throughout the 24 h cycle determine the circadian variation in hormone secretion [2]. Aims We used an animal model of PTSD [5] in order to assess whether stress-induced impairment of behavioral responses is mediated by an aberrant secretion of corticosterone. Methods Serial blood samples were collected manually via the jugular vein cannula during the inactive phase in conscious male rats at 20-min intervals for a period of 5 h before and 6.5 h after exposure to predator scent stress (PSS). The outcome measures included behavior in an elevated plus-maze and acoustic startle response 7 days after exposure. Individual animals were retrospectively classified as having "extreme", "partial", and "minimal" behavioral responses according to pre-set cut-off criteria for behavioral response patterns [5] and blood samples were analyzed retrospectively for corticosterone secretion patterns. For the behavioral results and for serum corticosterone levels, the statistical analyses were performed using one-way analysis of variance (ANOVA), bonferroni tests were used to examine differences between individual groups. To gain additional understanding about the relationship between behavioral measures and corticosterone pulsatility parameters, two sets of regression analysis were conducted: Pearson's correlation analysis was used to describe the relationship between each behavioral variable and corticosterone pulsatility parameters across the entire sample. The contribution of each variable that exhibited a significant correlation (or trend) was then evaluated using a multiple stepwise-regression analysis. Results Under basal conditions, the amplitude of ultradian oscillations of corticosterone levels, rather than the mean corticosterone level or the frequency of corticosterone pulsatility, was significantly reduced in individuals who displayed PTSD-phenotype 8 days later. In addition, extreme disruption of behavior on day 8 post-exposure was also characterized by a blunting of corticosterone response to the stressor. Animals with behavior that was only partially affected or unaffected displayed none of the above changes. Conclusions Blunted basal corticosterone pulse amplitude is a pre-existing susceptibility or risk factor for PTSD, which originates from prior (life) experiences and may therefore predict post-exposure PTSD-phenotype in rats. Further studies confirming these findings in animals and in human subjects are required to ascertain whether dysregulation in pulsatility indeed predisposes individuals to, or in fact underlies, faults in the HPA-axis response to stress and renders them vulnerable to PTSD. [ABSTRACT FROM AUTHOR]

The main objective of this study was to assess the seasonal nutrients requirement of ‘Hass’ avocado trees grown in lysimeters, especially during flowering and the early period of fruit development that may affect later on the fruitlet abscission and determine crop yield. The experimental design included three fertigation treatments applying a fixed nutrient solution at three different starting dates of fertigation: (a) T1 – continuous fertigation, including macro nutrients (N-P -K) and micronutrients application, all over the year; (b) T2 – no fertilization (only irrigation) until 15 March, and fertigation as T1 since then; (c) T3 - no fertilization (only irrigation) until 15 May, and fertigation as T1 since then. Absence of fertilization during the winter period induced leaf-chlorosis while healthy, dense and plenteously green leaves characterized the fertilized trees (T1). The beneficial effect of early fertigation on fruit yield was statistically significant, mostly because of higher fruit number. Leaf analyses are commonly used in the avocado industry as a guide for fertilization yet; fruits rather than leaves are the main products of avocado orchards. Consequently, fruit rather than leaf analyses should determine fertilization management. Based on fruit growth data and nutrient concentration in the fruit, the N, P and K quantities removed by ‘Hass’ avocado fruit yield of 30 t ha −1 were 120, 25 and 240 kg ha −1 . Taking into account common efficiency consideration (nutrient quantities removed by fruit yield divided by quantities added), the annual quantities of N, P and K required for attaining high quality avocado yield are 250–300, 80–120 and 500–600 kg ha −1 , respectively. Thus, fertilization rate together with nutrient combination should be modified in order to insure optimal fruit development. [ABSTRACT FROM AUTHOR]

Little is known about wombat diseases in general, and about their congenital diseases in particular. In the current study, the skeleton of a common wombat (Vombatus ursinus) that exhibited generalized hyperostosis is analyzed, and possible diagnoses are reviewed. Macromorphological analyses revealed that the diaphyses of the long bones manifested an increased diameter with extensive diaphyseal new-bone formation (periosteal and endosteal). Cross-sections of the diaphyses showed that the corticalmedullary demarcation was indistinct. The calvarial bones were thickened. Radiographs showed uniform sclerosis of the long bones with loss of trabecular pattern. Microradiography showed extensive bone remodeling, a hyper-vascularized lamellated layer of bone and numerous linear formation defects. Possible causes for the lesions, including sclerosing bone dysplasia disorders, acquired syndromes causing hyperostosis, and metabolic diseases typical of animals in captivity, are discussed. [ABSTRACT FROM AUTHOR]

Abstract: A novel method for preparation of durable standards of biological samples for quantitative analysis by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) has been developed. Rat brain tissue samples were ground and then spiked by aqueous solutions containing controlled amounts of trace metals of interest. The spiked rat brain samples were then encapsulated in a sol–gel matrix produced by tetraethyl orthosilicate (TEOS). The spiked standards were prepared by addition of 0–50μgg−1 of eight elements (Li, Co, Cr, Cu, Fe, Mn, Pb and Zn) to the biological samples. The correlation coefficients of the calibration curves for all elements tested were better than 0.97. Carbon-13, found in all biological samples, was used as an internal standard to correct for variations in the amount of material ablated and carried to the ICP-MS plasma torch, a common problem in LA-ICP-MS analysis. The results of analysis of the standards showed very good repeatability and homogeneity as well as long room temperature shelf life. [Copyright &y& Elsevier]

Abstract: General slowing of performance speed is a common finding associated with normal aging. However, which aspects of information processing are playing a major role in this decline are not well understood. Impairment in maze learning has been shown in patients with neurological disorders. Hippocampal bilateral lesions are associated mith larger deficits and interfere with both storage and retrieval of spatial information. Frontal lesions also produce similar effects and are characterized by perseverative errors. Reduced working memory has also been implicated in cognitive aging and is reflected in difficulties encountered in the execution of a task in real time when alterning between encoding and retrieval of information. A computerized maze learning task (Groton Maze Learning Task, GMLT) was developed specifically to determine the extent to which perseverative behaviors, working memory difficulties or other factors are implicated in the cognitive slowing generally observed in aging. Two groups of right-handed subjects (20 young adults: M=22.6; SD=1.54; 19 older adults: M=64; SD3=0.93) were compared looking at speed of learning and perseverative errors. Subjects were also assessed on tasks of procedural learning (Tower of Toronto), working memory (Paced Auditory Serial Addition Test; PASAT), and four subtests of the Wechsler Memory Scale-III (logical memory, faces, paired associates, family pictures) with immediate and delayed recall. With respect to the GMLT, subjects were required to find the correct path through a hidden maze by pressing on the computer’s touchscreen to move to the location of their choice. After practice trials, all subjects underwent ten consecutive trials followed, ten minutes later, by one last trial. Results of interest showed significant differences between the two groups in the time needed to complete all trials and in the number of perseverative errors. More specifically, the older subjects made more perseverative errors and were slower in learning the maze. In addition, a canonical correlation analysis was performed to determine the relationship between maze learning and the cognitive systems involved (executive function, working memory, procedural learning). The analysis revealed a canonical variate explaining 49% of the total variance, showing that the number of perseverative errors and number of moves on the Tower of Toronto test are the main components principally implicated in the performance of subjects on the GMLT. We conclude that the tendency for healthy elderly adults to make perseverative errors while completing the learning trials, often related to frontal-lobe dysexecutive syndromes, may also be associated with normal aging. It is suggested that the poorer monitoring of errors and/or the inhibition of a choice in response to new information observed in the elderly accounts, at least in part, for the overall finding of slowed information processing speed. [Copyright &y& Elsevier]

Abstract: Background: The bipolar affective disorder is long been speculated to have an autonomic involvement. Nonlinear analysis of heart rate variability has recently been shown to be a reliable noninvasive test for quantitative assessment of the central sympathovagal interaction that modulates cardiovascular autonomic function. Methods: We studied 32 euthymic bipolar patients and 24 controls. A high-resolution electrocardiogram was obtained during complete rest. Nonlinear analysis (Poincare plot, largest Lyaponuv exponent, minimal embedding dimension, symbolic dynamic) was used. Results: There wasn''t a statistically significant difference in the nonlinear analysis of the heart rate variability, between the euthymic bipolar patients and controls, in the rest situation. Conclusion: The nonlinear analysis of heart rate variability didn''t support the notation that there is a disturbance in the autonomic nerves system of bipolar patients in the euthymic state. [Copyright &y& Elsevier]

Abstract Background Tissue factor pathway inhibitor (TFPI) antibodies, which have been reported in patients with antiphospholipid syndrome (APS), may impair TFPI activity and contribute to hypercoagulability, but their role in APS and in thrombosis remains undefined. Objective/methods We assessed the presence and avidity of TFPI IgG antibodies, associations with protein C IgG antibodies and associations with clinical disease severity, in 50 patients with thrombotic APS and 50 thrombotic control patients, on long term anticoagulation with warfarin. Results Thrombotic APS patients had a significantly higher prevalence of TFPI IgG antibodies (40%; 20/50) compared to thrombotic controls (18%; 9/50). TFPI antibodies were predominantly high avidity in APS (50%, 10/20 of positive patients) and strongly associated with a severe thrombotic phenotype (venous and arterial thromboembolism or recurrent thromboembolic episodes despite therapeutic anticoagulation) (odds ratio (OR): 12.0, 95%CI: 2.2–66.1, p = 0.004), while thrombotic control patients mainly showed low avidity antibodies (78%, 7/9 of positive patients). Coexistence of TFPI and protein C IgG antibodies, regardless of their avidity, was strongly associated with a more severe thrombotic phenotype in APS patients (OR: 20.2, 95%CI: 2.0–47.0, p < 0.0001) and also in thrombotic controls (OR: 75.0, 95%CI 1.2–195, p = 0.02). Conclusions Coexistent TFPI and protein C IgG antibodies, irrespective of their avidity, may be a useful marker for a severe thrombotic phenotype in thrombotic patients. This suggests a possibly pathophysiological relationship between the two antibodies, predisposing to thrombosis with a possibly more general role in the development of thrombotic complications. Highlights • TFPI and protein C (PC) antibodies (abs) have been reported in APS. • We examined prevalence and avidity and associations with severity of clinical phenotype in APS. • TFPI abs show high prevalence in APS (40%); and thrombotic controls (18%). • Mostly high/intermediate avidity in APS, associated with severe thrombotic phenotype • Coexistent with PC abs, regardless of avidity, may be a marker for a severe thrombotic phenotype in thrombotic patients. [ABSTRACT FROM AUTHOR]

The instantaneous luminosity of the Large Hadron Collider at CERN will be increased up to a factor of five with respect to the present design value by undergoing an extensive upgrade program over the coming decade. The most important upgrade project for the ATLAS Muon System is the replacement of the present first station in the forward regions with the so-called New Small Wheels (NSWs). The NSWs will be installed during the LHC long shutdown in 2019/2020. Small-Strip Thin Gap Chamber (sTGC) detectors are designed to provide fast trigger and high precision muon tracking under the high luminosity LHC conditions. To validate the design, a full-size prototype sTGC detector of approximately 1.2 × 1.0 m 2 consisting of four gaps has been constructed. Each gap provides pad, strip and wire readouts. The sTGC intrinsic spatial resolution has been measured in a 32 GeV pion beam test at Fermilab. At perpendicular incidence angle, single gap position resolutions of about 50 μm have been obtained, uniform along the sTGC strip and perpendicular wire directions, well within design requirements. Pad readout measurements have been performed in a 130 GeV muon beam test at CERN. The transition region between readout pads has been found to be 4 mm, and the pads have been found to be fully efficient. [ABSTRACT FROM AUTHOR]

Rivaroxaban is non-inferior to warfarin for the treatment of venous thromboembolism, with regard to clinical efficacy and safety. The ex-vivo effects of warfarin versus therapeutic dose rivaroxaban on in-vivo markers of coagulation activation and thrombin generation remain undefined. The aim of this study was to compare the effects of warfarin and therapeutic dose rivaroxaban on ex-vivo thrombin generation (TG), and the in-vivo markers of coagulation activation, prothrombin fragment 1.2 (F1.2), thrombin-antithrombin complex (TAT), and D-dimer. Methods Eighty-five patients with venous thromboembolism were studied, 45 on warfarin, target INR 2.5 and 40 on rivaroxaban 20mg once daily. Results Anticoagulation was in therapeutic range in 71% (32/45) warfarin and 65% (26/40) rivaroxaban treated patients. 8 patients on warfarin and 9 patients on rivaroxaban had subtherapeutic INR and rivaroxaban levels respectively. Both rivaroxaban and warfarin reduced endogenous thrombin potential (ETP) and peak thrombin, and prolonged lag time and time to peak, compared to normal controls (p<0.0001). The lag time and time to peak TG were longer, and peak thrombin was lower in patients receiving rivaroxaban (p<0.0001) compared with warfarin, although warfarin-treated patients had lower ETP (p=0.0008). In-vivo coagulation activation markers were within the normal ranges in all rivaroxaban-treated patients (including those with levels considered to be subtherapeutic) and in 37/45 warfarin-treated patients who had an INR ≥ 2.0. The warfarin-treated patients with subtherapeutic INRs exhibited slightly raised F1.2 and/or TAT. Conclusion In conclusion, both rivaroxaban and warfarin provided effective anticoagulation, as assessed by inhibition of TG and makers of in-vivo coagulation activation. [ABSTRACT FROM AUTHOR]

Background Cyclophosphamide-methotrexate-5-fluorouracil (CMF) is often selected as adjuvant chemotherapy for older patients with early-stage breast cancer due to perceived superior tolerability. We sought to measure persistence with CMF, adherence to oral cyclophosphamide, and the association of these with toxic effects. Patients and methods CALGB 49907 was a randomized trial comparing standard chemotherapy (CMF or AC, provider/patient choice) with capecitabine in patients aged ≥65 with stage I–IIIB breast cancer. Those randomized to standard therapy and choosing CMF were prescribed oral cyclophosphamide 100 mg/m2 for 14 consecutive days in six 28-day cycles. Persistence was defined as being prescribed six cycles of at least one of the three CMF drugs. Adherence was the number of cyclophosphamide doses that women reported they had taken divided by the number prescribed. Persistence and adherence were based on case report forms and medication calendars. Results Of 317 randomized to standard chemotherapy, 133 received CMF. Median age was 73 (range 65–88). Seventy-one percent submitted at least one medication calendar; 65% persisted with CMF. Non-persistence was associated with node negativity (P = 0.019), febrile neutropenia (P = 0.002), and fatigue (P = 0.044). Average adherence was 97% during prescribed cycles. Conclusions Self-reported adherence to cyclophosphamide was high, but persistence was lower, which may be attributable to toxic effects. [ABSTRACT FROM PUBLISHER]

Abstract: Introduction: Patients receiving warfarin are at increased risk of bleeding when their International Normalised Ratio (INR) >4.5. Although not standardised above 4.5 the INR is measured in over-anticoagulated patients, consequently we have examined the reliability of INR results ≥4.5. We assessed: the relationship between different prothrombin time systems for INRs >4.5; the relationships between the INR and levels of vitamin K-dependent coagulation factors (VKD-CF) and thrombin generation test (TGT) parameters; and the impact that variation in results would have on warfarin dosing. Methods: INRs were performed using a CoaguChek XS Plus point-of-care (POC) device (measuring range 0.6-8.0). For POC INRs ≥4.5, laboratory INRs were also measured using a recombinant tissue factor (rTF) and a rabbit brain (RBT) thromboplastin. Results: There was good correlation between POC (INR ≥4.5, <8.0) and Lab INRs (rTF n=154, rs=0.87, p<0.0001; RBT n=102, rs=0.76, p<0.0001); and significant correlations between each of the VKD-CF and the INR, the strongest being with FVII (POC INR rs=-0.53 p<0.0001; Lab rTF-INR rs=-0.70 p<0.0001). TGT peak thrombin and ETP also showed good correlations with INR values (R2 >0.71). Using POC and Lab rTF-INR, 109/154 (71%), or POC and Lab RBT-INR 75/102 (74%) results exhibited dosage concordance and/or were within 0.5 INR units. In the remaining patients variation in warfarin dosing was generally slight. Conclusions: Our data suggest that CoaguChek XS Plus INRs >4.5 and <8.0 are comparable to laboratory INRs (both methods) and it is probably unnecessary to perform laboratory INRs for clinical management of patients with INRs >4.5 including those >8.0. [Copyright &y& Elsevier]

Background: Two Cancer and Leukemia Group B (CALGB) studies were utilized to determine the efficacy and tolerability of paclitaxel (Taxol) in older patients with metastatic breast cancer. Patients and methods: CALGB 9840 evaluated weekly paclitaxel (80 mg/m2) versus paclitaxel every 3 weeks (175 mg/m2); CALGB 9342 evaluated three doses of paclitaxel as follows: 175, 210 and 250 mg/m2 each over 3 h every 3 weeks. Of the 1048 patients, paclitaxel was used first line in 57%. The groups: (i) <55 years (45%), (ii) 55–64 years (29%), and (iii) ≥65 years (26%). Results: Tumor response was also similar among age groups. First-line therapy (P = 0.0001) and better performance status (PS) (P = 0.018) were significantly related to higher response. Age did not significantly relate to overall survival (OS) or progression-free survival (PFS). First-line therapy, better PS, estrogen receptor positive status and a fewer number of metastatic sites were significantly related to improved OS and PFS. The grade ≥3 toxic effects that increased linearly with age were leucopenia (P = 0.0099), granulocytopenia (P = 0.022), anorexia (P = 0.028), bilirubin elevation (P = 0.0035) and neurotoxicity (P < 0.0001). Patients over 65 years receiving second-line therapy had the shortest time to neurotoxicity. Conclusions: Older women with breast cancer derive similar efficacy from treatment with paclitaxel as younger women. Older women are at increased risk for specific toxic effects. [ABSTRACT FROM PUBLISHER]

Abstract: While modern neurobiology methods are necessary they are not sufficient to elucidate etiology and pathophysiology of affective disorders and develop new treatments. Achievement of these goals is contingent on applying cutting edge methods on appropriate disease models. In this review, the authors present four rodent models with good face-, construct-, and predictive-validity: the Flinders Sensitive rat line (FSL); the genetically “anxious” High Anxiety-like Behavior (HAB) line; the serotonin transporter knockout 5-HTT−/− rat and mouse lines; and the post-traumatic stress disorder (PTSD) model induced by exposure to predator scent, that they have employed to investigate the nature of depression and anxiety. [Copyright &y& Elsevier]

Our aim was to study the effect of 9-cis beta-carotene-rich powder of the alga Dunaliella bardawil on lipid profile, atherogenesis, and liver steatosis in high-fat diet-fed LDL receptor knockout mice. In 4 sets of experiments, mice were distributed into the following groups: control, fed an unfortified diet; Dunaliella 50, fed a diet composed of 50% 9-cis and 50% all-trans beta-carotene; Dunaliella 25, fed a diet containing 25% 9-cis and 75% all-trans beta-carotene; beta-carotene-deficient Dunaliella, fed beta-carotene-deficient Dunaliella powder; and all-trans beta-carotene, fed a synthetic all-trans beta-carotene. All fortified diets contained 0.6% total beta-carotene. Algal 9-cis beta-carotene was absorbed by the mice and accumulated in the liver. Synthetic all-trans beta-carotene was not converted to 9-cis beta-carotene. Dunaliella 50 inhibited high-fat diet-induced plasma cholesterol elevation by 40-63% and reduced cholesterol concentrations in the atherogenic VLDL and LDL. Atherosclerotic lesion area in mice treated with Dunaliella 50 was 60-83% lower compared with mice fed the high-fat diet alone. beta-Carotene-deficient Dunaliella did not influence plasma cholesterol and atherogenesis, suggesting that beta-carotene is essential for a Dunaliella protective effect. Moreover, by administrating Dunaliella powder containing different levels of 9-cis and all-trans beta-carotene isomers, we found that the effect on plasma cholesterol concentration and atherogenesis is 9-cis-dependent. Dunaliella 50 also inhibited fat accumulation and inflammation in the livers of mice fed a high-fat diet, which was accompanied by reduced mRNA levels of inflammatory genes. These results in mice suggest that 9-cis beta-carotene may have the potential to inhibit atherogenesis in humans. [ABSTRACT FROM AUTHOR]

Abstract: In vivo rodent models of focal cerebral ischemia have been developed to investigate stroke therapy. Typically these models require rapid quantification of cerebral infarct volumes using vital stains with tetrazolium salts to delineate the extent of neuronal death. To avoid animal sacrifice, we sought a study with MR acquired volumetric rat data where surrogate of ground truth is obtained by repeated manual delineation by experts, and an automated hybrid segmentation is evaluated for accuracy. We propose a rating system for the expert delineations that captures intra- and inter-expert discrepancy. Our preliminary results show that surrogate ground truth derived from MR data is at least as good as the one derived from histologic stained slices. Hence animal sacrifice is not necessary to evaluate ischemic stroke automated segmentation in a rat model of temporary middle cerebral artery occlusion. [Copyright &y& Elsevier]

Variable etiology, limited testing of emotions and inclusion of patients in acute and chronic phases have made it difficult to specify the extent of right hemisphere involvement in the processing of emotional material. In addition, there is an absence of data concerning CVA patients’ long-term abilities to process emotional information. Two groups of subjects with unilateral brain damage (15 RBD, 17 LBD), matched for chronicity (minimum 12 months post-CVA), etiology (ischemic CVA), duration of hospitalization and other variables, and an appropriate control group participated in two experiments to address these concerns. In the first experiment, subjects were given a series of tasks (discrimination, identification, imitation, production on request) to assess their processing of facial expressions of the six universal emotions [P. Ekman, W. Friesen, Unmasking the face, Prentice-Hall, Englewood Cliffs, 1975]. The results showed that three emotions (surprise, happiness, fear) discriminate between RBD and LBD patients and controls, with RBD subjects performing worse than the other groups on the identification task only. Using tasks of the same nature, the second experiment investigated the processing of emotional prosody. The results showed that three emotions (fear, sadness, anger) discriminate between RBD and LBD patients and controls, with RBD subjects again performing worse than the others on the discrimination, imitation and production on request tasks. LBD subjects performed as well as normal controls on almost all tasks. The RBD subjects were the only ones who showed relatively consistent impairment in the processing of both facial and prosodic emotional information. Taken together, these data strongly suggest that the right hemisphere is preferentially involved in processing emotional information in the chronic phase of brain damage. [Copyright &y& Elsevier]

Balloon angioplasty of bifurcation lesions has been associated with lower success and higher complication rates than most other lesion types. The development of alternative strategies such as debulking and stenting, either alone or in combination, are currently used relatively often. The relative role of these newer approaches in improving acute or long-term outcome, however, remains uncertain. Of the total of 2,436 patients treated between July 1997 to February 1998 in the National Heart, Lung, and Blood Institute Dynamic Registry, there were 321 patients (group 1) with bifurcation lesions and 2,115 patients without any bifurcation lesions attempted (group 2). Treatment strategies in terms of major devices used were significantly different between the 2 groups (group 1 vs 2): balloon angioplasty alone (23.1% vs 26.5%), balloon angioplasty and rotational atherectomy (6.9% vs 4.4%), balloon angioplasty and stent (55.8% vs 59.9%), and balloon angioplasty, rotational atherectomy, and stent (10.3% vs 7%) with p <0.01. There were no significant differences between the groups in terms of age, gender, and frequency of prior myocardial infarction (MI) or coronary artery bypass graft surgery (CABG). Complete angiographic success was achieved in only 86% of bifurcation lesions versus 93.5% of nonbifurcation lesions (p <0.001). In-hospital complication rates were increased in patients with bifurcation lesions compared with the nonbifurcation group: MI, 3.7% versus 2.6%; CABG, 2.2% versus 1.1%; side branch occlusion, 7.3% versus 2.3% (p <0.001); and the composite of death, MI, and any CABG, 7.2% versus 5.0%. At 1-year follow-up, major adverse cardiac events were 25% higher in group 1 than in group 2 (32.1% vs 25.7%, p <0.05). We conclude that despite the widespread use of newer percutaneous devices, treatment of bifurcation lesions remains difficult and is associated with decreased success and increased complication rates compared with nonbifurcation lesions. [ABSTRACT FROM AUTHOR]

The National Heart, Lung, and Blood Institute Dynamic Registry includes 15 clinical sites in wave 1, and 16 sites in wave 2 as well as a data-coordinating center. The first wave of enrollment began in July 1997 and was completed in February 1998. The second wave began in February 1999 and ended in June 1999. There were a total of 2,526 patients in wave 1 and 2,109 patients in wave 2. Comprehensive pre-, intra-, and postprocedure (in-hospital) data were analyzed for changes between recruitment waves. Patients in wave 2 were more frequently nonwhite (p < or = 0.001), hypertensive by history (p < or = 0.001), had more significant noncardiac comorbidity (p < or = 0.01), and had more frequently undergone prior percutaneous coronary intervention (p < 0.05). Patients in wave 2 underwent percutaneous coronary intervention in a setting of acute coronary syndromes more frequently than wave 1 patients (p < or = 0.001). However, most interventions in both waves were performed on 1 vessel, irrespective of the extent of disease. Attempted lesions in wave 2 were longer (p < or = 0.001), less frequently totally occluded (p < or = 0.001), and more frequently in vessels with a prior stent (p < or = 0.01). Using the American Heart Association/American College of Cardiology lesion classification scheme, attempted lesions in wave 2 were less complex than those in wave 1 (p < or = 0.001). Stent use increased significantly from wave 1 (67%) to wave 2 (79%, p < or = 0.001) as did the use of platelet glycoprotein IIb/IIIa antagonists (wave 1, 24%; wave 2, 32%: p < 0.001). Procedural outcomes (angiographic success without major in-hospital adverse events) were excellent in both waves 1 (94.6%) and 2 (95.6%) and were not significantly different. However, the frequency of significant procedural coronary dissection and in- and out-of-laboratory abrupt closure were significantly less in wave 2 (p < or = 0.001) Discharge medications were more likely to include angiotensin-converting enzyme inhibitors, beta-adrenergic blocking agents, and hypolipidemic treatment in wave 2 than in wave 1 (p < or = 0.001). These data indicate a continuing aggressive approach to patient care over the time interval analyzed. Although overall procedural outcomes are excellent, procedural safety has been further enhanced. There is also a growing awareness of the importance of secondary prevention among interventional cardiologists. [ABSTRACT FROM AUTHOR]

Balloon angioplasty of small coronary artery lesions has been associated with lower success and higher complication rates than large coronary artery lesions. This study evaluates the in-hospital and 1-year outcome of the treatment of small coronary artery lesions in the modern era of interventional cardiology and compares it with the outcome of treating large coronary artery lesions. Of 1,658 patients with a single lesion treated from July 1997 to February 1998 in the National Heart, Lung, and Blood Institute (NHLBI) Dynamic Registry, there were 587 patients with small coronary artery lesions (<3 mm) and 1,071 patients with large coronary artery lesions (> or =3 mm). Success, in-hospital, and 1-year outcomes between both groups were compared. Patients with lesions in small coronary arteries were more often women, insulin-treated diabetics, and had undergone more prior coronary bypass graft surgery. Conventional angioplasty alone was performed more often and angioplasty with stents was performed less often in the small coronary artery than in the large coronary artery group. Angiographic success was slightly lower in the small coronary artery group (94.2% vs 96.9%, p <0.05). Periprocedural and in-hospital complication rates were similar in both groups. Likewise, at 1-year follow-up, major adverse cardiac events including death, myocardial infarction, and coronary artery bypass graft surgery were relatively low and comparable between the 2 groups, although patients with small coronary arteries were more likely to undergo repeat revascularization (17.4% vs 13.6%, p <0.05). Treatment of lesions in small coronary arteries in the modern era is associated with high success and low complication rates, comparable to the treatment of large coronary artery lesions, although the incidence of repeat revascularization was significantly greater at follow-up even if stents were used. [ABSTRACT FROM AUTHOR]

Despite its merits, minimally invasive direct coronary artery bypass surgery (MIDCAB) has been criticized for variable left internal mammary artery (LIMA) graft patency rates, prompting the frequent use of postoperative LIMA angiography. Noninvasive transthoracic Doppler interrogation of LIMA grafts has recently been shown to have utility for assessing patency and flow reserve after conventional bypass surgery, but data after MIDCAB has been limited. The objective of this study was to assess LIMA graft anatomy and physiology in 54 patients after MIDCAB using angiography and noninvasive LIMA Doppler imaging. The right internal mammary artery (RIMA) was studied as a control. LIMA flow reserve in response to adenosine was evaluated in a subgroup of 18 randomly chosen patients with patent grafts. LIMA angiographic patency was 93%. Forty-four patients (81%) had obtainable LIMA Doppler data. Patent grafts had a diastolic dominant flow pattern with a peak diastolic/systolic velocity ratio of 1.3 +/- 0.6 and a percent diastolic time-velocity integral (TVI) of 70 +/- 11%. These data were significantly different than the RIMA control values of 0.2 +/- 0.1 and 30 +/- 10%, respectively (p <0.05). Occluded grafts had absent flow or a systolic dominant pattern. Adenosine-induced increases in LIMA peak diastolic velocity from 48 +/- 20 to 105 +/-28 cm/s (p <0.05 vs baseline) and diastolic TVI from 21 +/- 10 to 37 +/- 19 cm (p <0.05 vs baseline), yielding adenosine/baseline ratios of 2.4 +/- 0.9 and 2.0 +/- 0.7, respectively, which was consistent with normal flow reserve. The diastolic flow velocity reserve response was inversely related to baseline diastolic flow (r = -0.69). In conclusion, MIDCAB can be associated with a high rate of LIMA potency and favorable physiologic Doppler flow patterns. Correlation of these findings to long-term patient outcome after MIDCAB is warranted. [ABSTRACT FROM AUTHOR]