YfiO stabilizes the YaeT complex and is essential for outer membrane protein assembly in Escherichia coli.
Recent advances in the study of bacterial membranes have led to the identification of a multicomponent YaeT complex in the outer membrane (OM) of Gram-negative bacteria that is involved in the targeting and folding of beta-barrel outer membrane proteins (OMPs). In Escherichia coli, this complex consists of an essential OMP, YaeT, and three OM lipoproteins, YfgL, NlpB and YfiO. YfiO is the only essential lipoprotein component of the complex. We show that this lipoprotein is required for the proper assembly and/or targeting of OMPs to the OM but not the assembly of lipopolysaccharides (LPS). Depletion of YfiO causes similar phenotypes as does the depletion of YaeT, and we conclude that YfiO plays a critical role in YaeT-mediated OMP folding. We demonstrate that YfiO and YfgL directly interact with YaeT in vitro, while NlpB interacts directly with YfiO. Genetic analysis verifies the importance of YfiO and its interactions with NlpB in maintaining the functional integrity of the YaeT complex.


D-serine is distributed in neurons in the brain of the sea lamprey.
The amino acid D-serine is an endogenous coagonist of N-methyl-D-aspartate (NMDA) receptors in mammals that has been shown to play an important role in synaptic function, behavior, learning, and memory. The distribution and cellular location of D-serine in the brain of the sea lamprey was investigated by using immunofluorescence methods. One major finding of our study, unlike early studies of mammals, was the localization of D-serine immunoreactivity in perikarya and dendrites of neurons, whereas D-serine immunoreactivity was not generally observed in the lamprey glia. D-serine-immunoreactive neurons were observed in different brain regions, including the olfactory bulb, medial pallium, thalamus, torus semicircularis, isthmus, and reticular formation. The colocalization of D-serine with gamma-aminobutyric acid (GABA) was also studied with a double-immunofluorescence technique. The relationship between D-serine and glycine immunoreactivities was studied in alternate parallel series of sections stained for either D-serine/GABA or glycine/GABA. Colocalization with GABA was observed in various D-serine-immunoreactive populations, and codistribution and possible colocalization with glycine was also observed in some populations, mainly in the dorsal isthmic gray, medial octavolateral nucleus, dorsal column nucleus, interpeduncular nucleus, and reticular formation. Although numerous fibers were strongly GABA- and glycine-immunoreactive, D-serine immunoreactivity was observed mostly in cell perikarya and dendrites. The present results indicate that the D-serine immunoreactive cells are small to medium-sized neurons, some exhibiting classical inhibitory neurotransmitters, in which D-serine might be acting as a modulator. The neuronal distribution of D-serine and its frequent colocalization and/or codistribution with the two main inhibitory neurotransmitters appeared early in vertebrates.


Immune response in mice that lack the interferon-gamma receptor.
Interferon-gamma (IFN-gamma) exerts pleiotropic effects, including antiviral activity, stimulation of macrophages and natural killer cells, and increased expression of major histocompatibility complex antigens. Mice without the IFN-gamma receptor had no overt anomalies, and their immune system appeared to develop normally. However, mutant mice had a defective natural resistance, they had increased susceptibility to infection by Listeria monocytogenes and vaccinia virus despite normal cytotoxic and T helper cell responses. Immunoglobulin isotype analysis revealed that IFN-gamma is necessary for a normal antigen-specific immunoglobulin G2a response. These mutant mice offer the possibility for the further elucidation of IFN-gamma-mediated functions by transgenic cell- or tissue-specific reconstitution of a functional receptor.


[Trauma score and injury severity score in evaluation of the trauma patients: a preliminary report of 1000 cases].
It is important to evaluate trauma patients with a properly graded severity system in the emergency management of these patients. In this study the Trauma and the Injury Severity Scores based on the evaluation of trauma patients at the emergency services of Mackay Memorial Hospital and Taipei Medical College Hospital, and the mortality rate of these patients is analyzed. There was not a single mortality in patients with a Trauma Score of 15 or 16 and no survival in the patients with Trauma Scores under 11. Eighty-three of 1000 patients (8.3%) had a Trauma Score under 16, and hospitalization was necessary for most of them. All the 22 fatal cases had an Injury Severity Score greater than 24. The mortality rate was 70.6% for the patients with an Injury Severity Score greater than 30. This was the first trial in Taiwan to evaluate patients with the Trauma Score in the hope of aiding medical and paramedical staffs in the selection hospitals to which to transfer patients. All patients having a Trauma Score under 14 should be transferred to well-equipped trauma centers and those with a better score to other hospitals. The Injury Severity Score is nowadays used widely in the world to evaluate the severity and to predict the outcome of the patients. By comparing and utilizing these two grading systems, a more accurate evaluation of the trauma patients can be expected.


Effect of stem cell source on outcomes after unrelated donor transplantation in severe aplastic anemia.
Outcome after unrelated donor bone marrow (BM) transplantation for severe aplastic anemia (SAA) has improved, with survival rates now approximately 75%. Increasing use of peripheral blood stem and progenitor cells (PBPCs) instead of BM as a graft source prompted us to compare outcomes of PBPC and BM transplantation for SAA. We studied 296 patients receiving either BM (n = 225) or PBPC (n = 71) from unrelated donors matched at human leukocyte antigen-A, -B, -C, -DRB1. Hematopoietic recovery was similar after PBPC and BM transplantation. Grade 2 to 4 acute graft-versus-host disease risks were higher after transplantation of PBPC compared with BM (hazard ratio = 1.68, P = .02; 48% vs 31%). Chronic graft-versus-host disease risks were not significantly different after adjusting for age at transplantation (hazard ratio = 1.39, P = .14). Mortality risks, independent of age, were higher after PBPC compared with BM transplantation (hazard ratio = 1.62, P = .04; 76% vs 61%). These data indicate that BM is the preferred graft source for unrelated donor transplantation in SAA.


[Validation of an instrument for screening cases of type 2 diabetes and monitoring at-risk individuals in Mexico].
To validate a method for screening cases of type 2 diabetes and monitoring at-risk people in a community in northern Mexico. The screening instrument for type 2 diabetes (ITD, for its Spanish acronym) was developed using a multiple logistic regression analysis that made it possible to determine the association between a new diagnosis of diabetes (a dependent variable) and 11 known risk factors. Internal validations were performed (through v-fold cross-validation), together with external validations (through the monitoring of a cohort of healthy individuals). In order to estimate the relative risk (RR) of developing type 2 diabetes, the total ITD score is calculated on the basis of an individual's risk factors and compared against a curve that shows the probability of that individual developing the disease. Of the 525 people in the cohort, 438 (83.4%) were followed for an average of 7 years (4.5 to 10 years), for a total of 2 696 person-years; 62 (14.2%) people developed diabetes during the time they were followed. Individuals scoring 55 points based on their risk factors demonstrated a significantly higher risk of developing diabetes in 7 years (RR = 6.1; IC95%: 1.7 to 11.1); the risk was even higher for those with a score of 75 points (RR = 9.4; IC95%: 2.1 to 11.5). The ITD is easy to use and a valid screening alternative for type 2 diabetes. Its use will allow more individuals to benefit from disease prevention methods and early diagnosis without substantially increasing costs and with minimal use of laboratory resources.


Flexible motor adjustment of pecking with an artificially extended bill in crows but not in pigeons.
The dextrous foraging skills of primates, including humans, are underpinned by flexible vision-guided control of the arms/hands and even tools as body-part extensions. This capacity involves a visuomotor conversion process that transfers the locations of the hands/arms and a target in retinal coordinates into body coordinates to generate a reaching/grasping movement and to correct online. Similar capacities have evolved in birds, such as tool use in corvids and finches, which represents the flexible motor control of extended body parts. However, the flexibility of avian head-reaching and bill-grasping with body-part extensions remains poorly understood. This study comparatively investigated the flexibility of pecking with an artificially extended bill in crows and pigeons. Pecking performance and kinematics were examined when the bill extension was attached, and after its removal. The bill extension deteriorated pecking in pigeons in both performance and kinematics over 10 days. After the bill removal, pigeons started bill-grasping earlier, indicating motor adaptation to the bill extension. Contrastingly, pecking in crows was deteriorated transiently with the bill extension, but was recovered by adjusting pecking at closer distances, suggesting a quick adjustment to the bill extension. These results indicate flexible visuomotor control to extended body parts in crows but not in pigeons.


DNA Barcoding to Improve the Taxonomy of the Afrotropical Hoverflies (Insecta: Diptera: Syrphidae).
The identification of Afrotropical hoverflies is very difficult because of limited recent taxonomic revisions and the lack of comprehensive identification keys. In order to assist in their identification, and to improve the taxonomy of this group, we constructed a reference dataset of 513 COI barcodes of 90 of the more common nominal species from Ghana, Togo, Benin and Nigeria (W Africa) and added ten publically available COI barcodes from nine nominal Afrotropical species to this (total: 523 COI barcodes; 98 nominal species; 26 genera). The identification accuracy of this dataset was evaluated with three methods (K2P distance-based, Neighbor-Joining (NJ) / Maximum Likelihood (ML) analysis, and using SpeciesIdentifier). Results of the three methods were highly congruent and showed a high identification success. Nine species pairs showed a low (< 0.03) mean interspecific K2P distance that resulted in several incorrect identifications. A high (> 0.03) maximum intraspecific K2P distance was observed in eight species and barcodes of these species not always formed single clusters in the NJ / ML analayses which may indicate the occurrence of cryptic species. Optimal K2P thresholds to differentiate intra- from interspecific K2P divergence were highly different among the three subfamilies (Eristalinae: 0.037, Syrphinae: 0.06, Microdontinae: 0.007-0.02), and among the different general suggesting that optimal thresholds are better defined at the genus level. In addition to providing an alternative identification tool, our study indicates that DNA barcoding improves the taxonomy of Afrotropical hoverflies by selecting (groups of) taxa that deserve further taxonomic study, and by attributing the unknown sex to species for which only one of the sexes is known.


Time series analyses of breathing patterns of lung cancer patients using nonlinear dynamical system theory.
The underlying requirements for successful implementation of any efficient tumour motion management strategy are regularity and reproducibility of a patient's breathing pattern. The physiological act of breathing is controlled by multiple nonlinear feedback and feed-forward couplings. It would therefore be appropriate to analyse the breathing pattern of lung cancer patients in the light of nonlinear dynamical system theory. The purpose of this paper is to analyse the one-dimensional respiratory time series of lung cancer patients based on nonlinear dynamics and delay coordinate state space embedding. It is very important to select a suitable pair of embedding dimension 'm' and time delay 'τ' when performing a state space reconstruction. Appropriate time delay and embedding dimension were obtained using well-established methods, namely mutual information and the false nearest neighbour method, respectively. Establishing stationarity and determinism in a given scalar time series is a prerequisite to demonstrating that the nonlinear dynamical system that gave rise to the scalar time series exhibits a sensitive dependence on initial conditions, i.e. is chaotic. Hence, once an appropriate state space embedding of the dynamical system has been reconstructed, we show that the time series of the nonlinear dynamical systems under study are both stationary and deterministic in nature. Once both criteria are established, we proceed to calculate the largest Lyapunov exponent (LLE), which is an invariant quantity under time delay embedding. The LLE for all 16 patients is positive, which along with stationarity and determinism establishes the fact that the time series of a lung cancer patient's breathing pattern is not random or irregular, but rather it is deterministic in nature albeit chaotic. These results indicate that chaotic characteristics exist in the respiratory waveform and techniques based on state space dynamics should be employed for tumour motion management.


Variability of peptidoglycan structural parameters in gram-negative bacteria.
Muropeptide composition of peptidoglycan from the Gram-negative bacteria Aeromonas sp., Acinetobacter acetoaceticus, Agrobacterium tumefaciens, Enterobacter cloacae, Proteus morganii, Pseudomonas aeruginosa, Pseudomonas putida, Vibrio parahaemolyticus Yersinia enterocolitica and Escherichia coli, was analyzed by HPLC. In all instances peptidoglycan was built up from the same subunits. A wide disparity in the relative abundance of muropeptides and all structural parameters was observed. The contribution of LD-A2pm-A2pm cross-linked muropeptides was extremely variable; from 1 to 45% of cross-linked muropeptides. Muropeptides with the dipeptides Lys-Lys or Arg-Lys, indicative of murein-bound (lipo)proteins, were detected in all instances although abundance was very variable.


Accounting for Sitting and Moving: An Analysis of Sedentary Behavior in Mass Media Campaigns.
Mass media campaigns are an important tool for promoting health-related physical activity. The relevance of sedentary behavior to public health has propelled it to feature prominently in health campaigns across the world. This study explored the use of messages regarding sedentary behavior in health campaigns within the context of current debates surrounding the association between sedentary behavior and health, and messaging strategies to promote moderate-to-vigorous physical activity (MVPA). A web-based search of major campaigns in the United Kingdom, United States, Canada, and Australia was performed to identify the main campaign from each country. A directed content analysis was then conducted to analyze the inclusion of messages regarding sedentary behavior in health campaigns and to elucidate key themes. Important areas for future research were illustrated. Four key themes from the campaigns emerged: clinging to sedentary behavior guidelines, advocating reducing sedentary behavior as a first step on the activity continuum and the importance of light activity, confusing the promotion of MVPA, and the demonization of sedentary behavior. Strategies for managing sedentary behavior as an additional complicating factor in health promotion are urgently required. Lessons learned from previous health communication campaigns should stimulate research to inform future messaging strategies.


Mutations in genes encoding the cadherin receptor-ligand pair DCHS1 and FAT4 disrupt cerebral cortical development.
The regulated proliferation and differentiation of neural stem cells before the generation and migration of neurons in the cerebral cortex are central aspects of mammalian development. Periventricular neuronal heterotopia, a specific form of mislocalization of cortical neurons, can arise from neuronal progenitors that fail to negotiate aspects of these developmental processes. Here we show that mutations in genes encoding the receptor-ligand cadherin pair DCHS1 and FAT4 lead to a recessive syndrome in humans that includes periventricular neuronal heterotopia. Reducing the expression of Dchs1 or Fat4 within mouse embryonic neuroepithelium increased progenitor cell numbers and reduced their differentiation into neurons, resulting in the heterotopic accumulation of cells below the neuronal layers in the neocortex, reminiscent of the human phenotype. These effects were countered by concurrent knockdown of Yap, a transcriptional effector of the Hippo signaling pathway. These findings implicate Dchs1 and Fat4 upstream of Yap as key regulators of mammalian neurogenesis.


Working memory plasticity in old age: practice gain, transfer, and maintenance.
Adult age differences in cognitive plasticity have been studied less often in working memory than in episodic memory. The authors investigated the effects of extensive working memory practice on performance improvement, transfer, and short-term maintenance of practice gains and transfer effects. Adults age 20-30 years and 70-80 years practiced a spatial working memory task with 2 levels of processing demands across 45 days for about 15 min per day. In both age groups and relative to age-matched, no-contact control groups, we found (a) substantial performance gains on the practiced task, (b) near transfer to a more demanding spatial n-back task and to numerical n-back tasks, and (c) 3-month maintenance of practice gains and near transfer effects, with decrements relative to postpractice performance among older but not younger adults. No evidence was found for far transfer to complex span tasks. The authors discuss neuronal mechanisms underlying adult age differences and similarities in patterns of plasticity and conclude that the potential of deliberate working memory practice as a tool for improving cognition in old age merits further exploration.


Is TWEAK a Biomarker for Autoimmune/Chronic Inflammatory Diseases?
The TWEAK/Fn14 pathway is now well-known for its involvement in the modulation of inflammation in various human autoimmune/chronic inflammatory diseases (AICID) including lupus, rheumatoid arthritis, and multiple sclerosis. A panel of data is now available concerning TWEAK expression in tissues or biological fluids of patients suffering from AICID, suggesting that it could be a promising biological marker in these diseases. Evidences from several teams support the hypothesis that blocking TWEAK/Fn14 pathway is an attractive new therapeutic lead in such diseases and clinical trials with anti-TWEAK-blocking antibodies are in progress. In this mini-review we discuss the potential use of TWEAK quantification in AICD management in routine practice and highlight the challenge of standardizing data collection to better estimate the clinical utility of such a biological parameter.


Anti-La antibody production by MRL-1pr/1pr mice. Analysis of fine specificity.
In evaluating the origin of autoantibodies, patterns of self-Ag recognition have been interpreted to reflect the relative role of Ag in stimulating a response. Few studies, however, have assessed whether human autoantibodies display patterns of autoantigen recognition similar to those of SLE-prone mice. In previous studies, anti-La antibodies from humans have been shown to bind multiple epitopes on recombinant human La Ag, including immunoreactivity with a large fragment, termed La C, representing the middle portion of the La sequence. We report herein for the first time that MRL-1pr mice also spontaneously produce antibodies to recombinant human La protein and resemble human autoantibodies in their reactivity with La C. To further investigate the fine specificity of this response, we tested for antibody binding to six synthetic La peptides representing sequences within La C. Whereas two of the synthetic La peptides reacted with MRL-1pr sera containing anti-La binding, low reactivity was observed with a large panel of human anti-La sera. Our results therefore show that patterns of La antigen recognition displayed by MRL-1pr antibodies differ from those of human autoantibodies, possibly reflecting differences between mouse and man in the induction of these responses.


Musculoskeletal disorders: does the osteopathic medical profession demonstrate its unique and distinctive characteristics?
The authors used the National Ambulatory Medical Care Survey: 1999 Summary to compare the practice patterns of osteopathic and allopathic physicians in the management of musculoskeletal disorders in family practice settings. Patient and physician characteristics, diagnostic test ordering patterns, treatments, and amount of time spent with patients during visits were compared. Patients who visited osteopathic physicians were more likely to be middle-aged and referred, with injury-related visits that were self-paid. Osteopathic physicians spent more time with patients, ordered a greater number of nontraditional diagnostic tests, and provided more manual and complementary modes of therapy. In contrast, although most of the patients seen by both osteopathic and allopathic physicians were white, allopathic physicians had a greater percentage of patients who were of an ethnic minority or under Medicaid or Medicare. Allopathic physicians ordered a greater number of traditional diagnostic tests and prescribed more medications. Based on the nationally representative data, osteopathic physicians used physiotherapy (including osteopathic manipulative treatment and physical modes of therapy) and complementary treatments to a greater degree in their physician-patient contacts. In contrast, allopathic physicians spent more resources on diagnosis versus treatment (eg, physiotherapy) and seemed to focus on the search for a nonstructural medical cause.


Complications of renal cryoablation: a single center experience.
We describe perioperative complications associated with renal cryoablation and identify potential risk factors for certain complications. We retrospectively analyzed the medical records of patients with unifocal renal masses treated with cryosurgery at a single center between 1997 and 2007. All complications associated with these procedures were documented and classified into grades 1 to 5 by the Clavien surgical complication classification. In-depth analysis was done to identify potential risk factors for the most common complications. We evaluated 101 percutaneous, 52 laparoscopic and 9 open procedures. Complications were noted in 38 procedures (23.5%), including grades 1 to 4 in 19 (11.7%), 8 (4.9%), 5 (3.1%) and 6 (3.7%), respectively, as the severest complication. The most common complication was flank pain (11 procedures), followed by perinephric hematoma and cardiovascular complications (10 each). Mass size (p = 0.001), number of cryoablation probes (p <0.001) and chronic anticoagulation (p <0.05) were associated with an increased incidence of significant hematoma. Cardiovascular complications were more common when upper pole lesions were treated, and when an open approach was used (each p <0.05). Respiratory complications occurred in 7 procedures and were associated with patient age (p <0.05) and mass size (p <0.01). Cryoablation is a relatively safe procedure with a low complications rate in properly selected patients. We identified potential risk factors that may help identify patients most at risk for certain complications and consequently assist in preprocedural planning and counseling.


A practical approach to evidence-based dentistry: How to search for evidence to inform clinical decisions.
Knowing how to search for evidence that can inform clinical decisions is a fundamental skill for the practice of evidence-based dentistry. There are many available types of evidence-based resources, characterized by their degrees of coverage of preappraised or summarized evidence at varying levels of processing, from primary studies to systematic reviews and clinical guidelines. The practice of evidence-based dentistry requires familiarity with these resources. In this article, the authors describe the process of searching for evidence: defining the question, identifying the question's nature and main components, and selecting the study design that best addresses the question.


Actin Cytoskeleton Straddling the Immunological Synapse between Cytotoxic Lymphocytes and Cancer Cells.
The immune system is a fundamental part of the tumor microenvironment. In particular, cytotoxic lymphocytes, such as cytolytic T cells and natural killer cells, control tumor growth and disease progression by interacting and eliminating tumor cells. The actin cytoskeleton of cytotoxic lymphocytes engaged in an immunological synapse has received considerable research attention. It has been recognized as a central mediator of the formation and maturation of the immunological synapse, and its signaling and cytolytic activities. In comparison, fewer studies have explored the organization and function of actin filaments on the target cancer cell side of the immunological synapse. However, there is growing evidence that the actin cytoskeleton of cancer cells also undergoes extensive remodeling upon cytotoxic lymphocyte attack, and that such remodeling can alter physical and functional interactions at the immunological synapse. In this article, we review the current knowledge of actin organization and functions at both sides of the immunological synapse between cytotoxic lymphocytes and cancer cells, with particular focus on synapse formation, signaling and cytolytic activity, and immune evasion.


Wavefront analysis in post-LASIK eyes and its correlation with visual symptoms, refraction, and topography.
To evaluate the information assessed with the LADARWave wavefront measurement device and correlate it with visual symptoms, refraction, and corneal topography in previously LASIK-treated eyes. One hundred five eyes (58 patients) of individuals who underwent LASIK surgery were evaluated. Retrospective, noncomparative case series. Complete ophthalmologic examination, corneal topography, and wavefront measurements were performed. Correlations were made between the examinations and symptoms. Wavefront measurements were assessed with the LADARWave device. Manifest, cycloplegic refraction, and topographic data were compared with wavefront refraction and higher order aberrations. Visual symptoms were correlated to higher order aberrations in 3 different pupil sizes (5-mm, 7-mm, and scotopic pupil size). Pearson's correlation coefficient and generalized estimating equations were used for statistical analysis. In post-LASIK eyes, wavefront refraction components were poorly correlated to manifest and cycloplegic components. The comparison between manifest, cycloplegic, and wavefront refraction with total amount of higher order aberrations showed no strong correlation. The comparison between topography and manifest, cycloplegic, and wavefront refraction did not show strong correlation. Visual symptoms analysis showed correlation of double vision with total coma and with horizontal coma for the 5-mm and 7-mm pupil size; correlation between starburst and total coma for the 7-mm pupil size; and correlation of double vision with horizontal coma, glare with spherical aberrations and with total aberrations, and starburst with spherical aberrations for the scotopic pupil size. Scotopic pupil size had a positive association with starburst and a negative association with double vision. The LADARWave wavefront measurement device is a valuable diagnostic tool in measuring refractive error with ocular aberrations in post-LASIK eyes. A strong correlation between visual symptoms and ocular aberrations, such as monocular diplopia with coma and starburst and glare with spherical aberration, suggest this device is valuable in diagnosing symptomatic LASIK-induced aberrations. Horizontal coma was correlated with double vision, whereas vertical coma was not.


A neurogenetics approach to understanding individual differences in brain, behavior, and risk for psychopathology.
Neurogenetics research has begun to advance our understanding of how genetic variation gives rise to individual differences in brain function, which, in turn, shapes behavior and risk for psychopathology. Despite these advancements, neurogenetics research is currently confronted by three major challenges: (1) conducting research on individual variables with small effects, (2) absence of detailed mechanisms, and (3) a need to translate findings toward greater clinical relevance. In this review, we showcase techniques and developments that address these challenges and highlight the benefits of a neurogenetics approach to understanding brain, behavior and psychopathology. To address the challenge of small effects, we explore approaches including incorporating the environment, modeling epistatic relationships and using multilocus profiles. To address the challenge of mechanism, we explore how non-human animal research, epigenetics research and genome-wide association studies can inform our mechanistic understanding of behaviorally relevant brain function. Finally, to address the challenge of clinical relevance, we examine how neurogenetics research can identify novel therapeutic targets and for whom treatments work best. By addressing these challenges, neurogenetics research is poised to exponentially increase our understanding of how genetic variation interacts with the environment to shape the brain, behavior and risk for psychopathology.


Urokinase combination chemotherapy in small cell lung cancer. A phase II study.
Fifty-one patients with small cell lung cancer (SCLC) were treated with alternating urokinase (UK)-cyclophosphamide-doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH)-vincristine and cisplatin-etoposide-vincristine. UK was given as a loading dose of 3000 micrograms/kg body weight, followed by 3000 micrograms/kg/h for 6 hours. Thoracic irradiation with split technique (46 Gy) and prophylactic cranial irradiation (25 Gy) were administered to responding patients. A second staging was performed in patients exhibiting a clinical complete response (CR) after 1 year. In 27 patients with limited disease, there were 23 CR and 8 partial responses (PR) (CR, 85.1%; 66.2-95.8% at 95% confidence intervals); in 24 patients with extensive disease, there were 17 CR, 4 PR, and 3 cases with progression. Pathologically proven CR were observed in 59.2% patients with limited disease and 33.3% patients with extensive disease. Survival rates were as follows: in patients with limited disease, 1 year, 85.1%; 2 years, 55.5%; and 3 years, 25.9%; in patients with extensive disease, 1 year, 54.1; and 2 years, 16.9%. Median survival times were 26.3 months (patients with limited disease) and 13.3 months (patients with extensive disease). UK-related toxic effects included four episodes of mild to moderate bleeding, one allergic reaction, and one cerebrovascular accident. Myelotoxicity was severe, with a median of two episodes of Grade III-IV (World Health Organization classification) aplasia per patient. These results are consistent with a potential benefit of fibrinolytic therapy in combination with chemotherapy in patients with SCLC with limited disease. Additional trials are indicated.


Increased local recurrence and reduced survival from colorectal cancer following anastomotic leak: systematic review and meta-analysis.
To examine the long-term oncological impact of anastomotic leakage (AL) after restorative surgery for colorectal cancer using meta-analytical methods. Outcomes evaluated were local recurrence, distant recurrence, and survival. Recurrence after potentially curative surgery for colorectal cancer remains a significant clinical problem and has a poor prognosis. AL may be a risk factor for disease recurrence, however available studies have been conflicting. A meta-analysis was conducted to investigate the impact of AL on disease recurrence and long-term survival. Studies published between 1965 and 2009 evaluating the long-term oncological impact of AL were identified by an electronic literature search. Outcomes evaluated included local recurrence, distant recurrence, and cancer specific survival. Meta-analysis was performed using the DerSimonian-Laird random-effects model to compute odds ratio and 95% confidence intervals. Study heterogeneity was evaluated using Q statistics and I and publication bias assessed with funnel plots and Egger's test. Twenty-one studies comprising 13 prospective nonrandomized studies, 1 prospective randomized, and 7 retrospective studies met the inclusion criteria, yielding a total of 21,902 patients. For rectal anastomoses, the odd ratios (OR) of developing a local recurrence when there was AL was 2.05 (95% CI = 1.51-2.8; P = 0.0001). For studies describing both colon and rectal anastomoses, the OR of local recurrence when there was an AL was 2.9 (95% CI = 1.78-4.71; P < 0.001). The OR of developing a distant recurrence after AL was 1.38 (95% CI = 0.96-1.99; P = 0.083). Long term cancer specific mortality was significantly higher after AL with an OR of 1.75 (95% CI = 1.47-2.1; P = 0.0001). AL has a negative prognostic impact on local recurrence after restorative resection of rectal cancer. A significant association between colorectal AL and reduced long-term cancer specific survival was also noted. No association between AL and distant recurrence was found.


Plectranthus amboinicus attenuates inflammatory bone erosion in mice with collagen-induced arthritis by downregulation of RANKL-induced NFATc1 expression.
Plectranthus amboinicus has been known to treat inflammatory diseases or swelling symptoms. We investigated whether P. amboinicus exhibited an inhibitory effect on osteoclastogenesis in vitro and inflammatory bone erosion in collagen-induced arthritis (CIA) mice, an animal model of rheumatoid arthritis. We attempted to identify the active component of P. amboinicus involved in regulation of osteoclastogenesis. We treated M-CSF- and RANKL-stimulated murine bone marrow-derived macrophages (BMM) and RANKL-induced RAW264.7 cells with different concentrations of P. amboinicus or rosmarinic acid, a phytopolyphenol purified from P. amboinicus, to monitor osteoclast formation by TRAP staining. The mechanism of the inhibition was studied by biochemical analysis such as RT-PCR and immunoblotting. CIA mice were administered gavages of P. amboinicus (375 mg/kg) or placebo. Then clinical, histological, and biochemical measures were assessed to determine the effects of P. amboinicus on synovial inflammation and bone erosion by H&E staining of the inflamed joints and ELISA. Rosmarinic acid strongly inhibited RANKL-induced NF-κB activation and nuclear factor of activated T cells c1 (NFATc1) nuclear translocation in BMM, and also inhibited RANKL-induced formation of TRAP-positive multinucleated cells. A pit formation assay and the CIA animal model showed that P. amboinicus significantly inhibited the bone-resorbing activity of mature osteoclasts. We postulated that rosmarinic acid conferred the inhibitory activity on P. amboinicus for inhibition of osteoclastogenesis via downregulation of RANKL-induced NFATc1 expression. Our results indicated the possibility of P. amboinicus as a new remedy against inflammatory bone destruction.


D1-mGlu5 heteromers mediate noncanonical dopamine signaling in Parkinson's disease.
Dopamine receptor D1 modulates glutamatergic transmission in cortico-basal ganglia circuits and represents a major target of L-DOPA therapy in Parkinson's disease. Here we show that D1 and metabotropic glutamate type 5 (mGlu5) receptors can form previously unknown heteromeric entities with distinctive functional properties. Interacting with Gq proteins, cell-surface D1-mGlu5 heteromers exacerbated PLC signaling and intracellular calcium release in response to either glutamate or dopamine. In rodent models of Parkinson's disease, D1-mGlu5 nanocomplexes were strongly upregulated in the dopamine-denervated striatum, resulting in a synergistic activation of PLC signaling by D1 and mGlu5 receptor agonists. In turn, D1-mGlu5-dependent PLC signaling was causally linked with excessive activation of extracellular signal-regulated kinases in striatal neurons, leading to dyskinesia in animals treated with L-DOPA or D1 receptor agonists. The discovery of D1-mGlu5 functional heteromers mediating maladaptive molecular and motor responses in the dopamine-denervated striatum may prompt the development of new therapeutic principles for Parkinson's disease.


Stability of fathers' representations of their infants during the transition to parenthood.
Studies investigating fathers' roles in child development have focused on a range of different aspects. However, few studies have focused on the early father-infant relationship, which already emerges before the child is born. The aim of this study is to examine the concordance of fathers' representations of their children during the transition to parenthood. The influences of demographic variables, psychological wellbeing, and personality on the stability of these representations are investigated. At 26 weeks gestational age and when infants were six months old, fathers (N = 243) completed questionnaires and the Working Model of the Child Interview during a home visit. A strong association was found between fathers' prenatal and postnatal representations. First-time fathers more often had balanced representations than fathers who already had children. Furthermore, agreeable fathers were more likely to evolve from a non-balanced prenatal representation to a balanced postnatal representation.


Regulation of yeast pyruvate kinase by ultrasensitive allostery independent of phosphorylation.
Allostery and covalent modification are major means of fast-acting metabolic regulation. Their relative roles in responding to environmental changes remain, however, unclear. Here we examine this issue, using as a case study the rapid decrease in pyruvate kinase flux in yeast upon glucose removal. The main pyruvate kinase isozyme (Cdc19) is phosphorylated in response to environmental cues. It also exhibits positively cooperative (ultrasensitive) allosteric activation by fructose-1,6-bisphosphate (FBP). Glucose removal causes accumulation of Cdc19's substrate, phosphoenolpyruvate. This response is retained in strains with altered protein-kinase-A or AMP-activated-protein-kinase activity or with CDC19 carrying mutated phosphorylation sites. In contrast, yeast engineered with a CDC19 point mutation that ablates FBP-based regulation fail to accumulate phosphoenolpyruvate. They also fail to grow on ethanol and slowly resume growth upon glucose upshift. Thus, while yeast pyruvate kinase is covalently modified in response to glucose availability, its activity is controlled almost exclusively by ultrasensitive allostery.


The inability of human immunodeficiency virus to infect chimpanzee monocytes can be overcome by serial viral passage in vivo.
Studies of lentivirus infection in ruminants, nonhuman primates, and humans suggest that virus infection of macrophages plays a central role in the disease process. To investigate whether human immunodeficiency virus type 1 (HIV-1) can infect chimpanzee macrophages, we recovered monocytes from peripheral blood mononuclear cells of HIV-1-negative animals and inoculated these and control human monocytes with a panel of four human-passaged monocytotropic virus strains and one chimpanzee-passaged isolate. HIV-1 infected human monocytes synthesized proviral DNA, viral mRNA, p24 antigen, and progeny virions. In contrast, except for the chimpanzee-passaged HIV-1 isolate, chimpanzee monocytes failed to support HIV-1 replication when cultured under both identical and a variety of other conditions. Proviral DNA was demonstrated only at background levels in these cell cultures by polymerase chain reaction for gag- and env-related sequences. Interestingly, the chimpanzee-passaged HIV-1 isolate did not replicate in human monocytes; viral p24 antigens and progeny virions were not detected. The same monocytotropic panel of HIV-1 strains replicated in both human and chimpanzee CD4+ T lymphoblasts treated with phytohemagglutinin and interleukin-2. The failure of HIV-1 to infect chimpanzee monocytes, which can be overcome by serial in vivo viral passage, occurs through a block early in the viral life cycle.


The effect of shoe gear on human tibial strains recorded during dynamic loading: a pilot study.
The study was conducted to test the hypothesis that alterations in shoe gear can affect tibial strains in the human during dynamic loading. Rosette strain gauges were mounted on the medial border of the mid-diaphysis in two human subjects with a new strain gauge bonding technique using methyl methacrylate. Strain measurements were made at this site, the most frequent location for stress fractures in the Israeli Army during treadmill walking and free running while wearing various sport shoes (Rockport ProWalkers and New Balance NBX 900) and army boots (light Israeli infantry, double layered sole Israeli infantry, and Zohar infantry boots). Data were analyzed for only one of the subjects because strain gauge bonding was found to be inadequate at the time of surgical removal in the other subject. No single shoe lowered both the principal tibial compression and tensile strains, and the shear strains. The Zohar boot had the lowest principal compression strains during treadmill walking and mobile running, despite its relatively higher weight and sole durometry.


Electrocatalytic water oxidation over AlFe2B2.
We report excellent electrocatalytic performance by AlFe2B2 in the oxygen-evolution reaction (OER). The inexpensive catalytic material, prepared simply by arc-melting followed by ball-milling, exhibits high stability and sustained catalytic performance under alkaline conditions. The overpotential value of 0.24 V observed at the current density of 10 mA cm-2 remained constant for at least 10 days. Electron microscopy and electron energy loss spectroscopy performed on the initial ball-milled material and on the material activated under electrocatalytic conditions suggest that the catalytic mechanism involves partial leaching of Al from the layered structure of AlFe2B2 and the formation of Fe3O4 nanoclusters on the exposed [Fe2B2] layers. Thus, the AlFe2B2 structure serves as a robust supporting material and, more importantly, as a pre-catalyst to the in situ formed active electrocatalytic sites. Comparative electrochemical measurements demonstrate that the electrocatalytic performance of the AlFe2B2-supported Fe3O4 nanoclusters substantially exceeds the results obtained with unsupported nanoparticles of Fe3O4, FeB, or such benchmark OER catalysts as IrO2 or RuO2. The excellent catalytic performance and long-term stability of this system suggests that AlFe2B2 can serve as a promising and inexpensive OER electrocatalyst.


Highly similar microbial communities are shared among related and trophically similar ant species.
Ants dominate many terrestrial ecosystems, yet we know little about their nutritional physiology and ecology. While traditionally viewed as predators and scavengers, recent isotopic studies revealed that many dominant ant species are functional herbivores. As with other insects with nitrogen-poor diets, it is hypothesized that these ants rely on symbiotic bacteria for nutritional supplementation. In this study, we used cloning and 16S sequencing to further characterize the bacterial flora of several herbivorous ants, while also examining the beta diversity of bacterial communities within and between ant species from different trophic levels. Through estimating phylogenetic overlap between these communities, we tested the hypothesis that ecologically or phylogenetically similar groups of ants harbor similar microbial flora. Our findings reveal: (i) clear differences in bacterial communities harbored by predatory and herbivorous ants; (ii) notable similarities among communities from distantly related herbivorous ants and (iii) similar communities shared by different predatory army ant species. Focusing on one herbivorous ant tribe, the Cephalotini, we detected five major bacterial taxa that likely represent the core microbiota. Metabolic functions of bacterial relatives suggest that these microbes may play roles in fixing, recycling, or upgrading nitrogen. Overall, our findings reveal that similar microbial communities are harbored by ants from similar trophic niches and, to a greater extent, by related ants from the same colonies, species, genera, and tribes. These trends hint at coevolved histories between ants and microbes, suggesting new possibilities for roles of bacteria in the evolution of both herbivores and carnivores from the ant family Formicidae.


Examiner error in curriculum-based measurement of oral reading.
Although curriculum based measures of oral reading (CBM-R) have strong technical adequacy, there is still a reason to believe that student performance may be influenced by factors of the testing situation, such as errors examiners make in administering and scoring the test. This study examined the construct-irrelevant variance introduced by examiners using a cross-classified multilevel model. We sought to determine the extent of variance in student CBM-R scores attributable to examiners and, if present, the extent to which it was moderated by students' grade level and English learner (EL) status. Fit indices indicated that a cross-classified random effects model (CCREM) best fits the data with measures nested within students, students nested within schools, and examiners crossing schools. Intraclass correlations of the CCREM revealed that roughly 16% of the variance in student CBM-R scores was associated between examiners. The remaining variance was associated with the measurement level, 3.59%; between students, 75.23%; and between schools, 5.21%. Results were moderated by grade level but not by EL status. The discussion addresses the implications of this error for low-stakes and high-stakes decisions about students, teacher evaluation systems, and hypothesis testing in reading intervention research.


cADPR stimulates SERCA activity in Xenopus oocytes.
The intracellular second messenger cyclic ADP-ribose (cADPR) induces Ca(2+) release through the activation of ryanodine receptors (RyRs). Moreover, it has been suggested that cADPR may serve an additional role to modulate sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) pump activity, but studies have been complicated by concurrent actions on RyR. Here, we explore the actions of cADPR in Xenopus oocytes, which lack RyRs. We examined the effects of cADPR on the sequestration of cytosolic Ca(2+) following Ca(2+) transients evoked by photoreleased inositol 1,4,5-trisphosphate (InsP(3)), and by Ca(2+) influx through expressed nicotinic acetylcholine receptors (nAChR) in the oocytes membrane. In both cases the decay of the Ca(2+) transients was accelerated by intracellular injection of a non-metabolizable analogue of cADPR, 3-Deaza-cADPR, and photorelease of cADPR from a caged precursor demonstrated that this action is rapid (a few s). The acceleration was abolished by pre-treatment with thapsigargin to block SERCA activity, and was inhibited by two specific antagonists of cADPR, 8-NH(2)-cADPR and 8-br-cADPR. We conclude that cADPR serves to modulate Ca(2+) sequestration by enhancing SERCA pump activity, in addition to its well-established action on RyRs to liberate Ca(2+).


Probing spermatogenesis in Drosophila with P-element enhancer detectors.
Formation of motile sperm in Drosophila melanogaster requires the coordination of processes such as stem cell division, mitotic and meiotic control and structural reorganization of a cell. Proper execution of spermatogenesis entails the differentiation of cells derived from two distinct embryonic lineages, the germ line and the somatic mesoderm. Through an analysis of homozygous viable and fertile enhancer detector lines, we have identified molecular markers for the different cell types present in testes. Some lines label germ cells or somatic cyst cells in a stage-specific manner during their differentiation program. These expression patterns reveal transient identities for the cyst cells that had not been previously recognized by morphological criteria. A marker line labels early stages of male but not female germ cell differentiation and proves useful in the analysis of germ line sex-determination. Other lines label the hub of somatic cells around which germ line stem cells are anchored. By analyzing the fate of the somatic hub in an agametic background, we show that the germ line plays some role in directing its size and its position in the testis. We also describe how marker lines enable us to identify presumptive cells in the embryonic gonadal mesoderm before they give rise to morphologically distinct cell types. Finally, this collection of marker lines will allow the characterization of genes expressed either in the germ line or in the soma during spermatogenesis.


Celiac disease: a review.
Triggered by the ingestion of gluten in genetically predisposed individuals, celiac disease is the most common genetically based food intolerance in the world, with a prevalence among approximately 1% of the general population. This enteropathy may appear at any age and is characterized by a wide variety of clinical signs and symptoms that go well beyond the gastrointestinal tract. In young children, gastrointestinal presentations are common and include chronic diarrhea, failure to thrive, and abdominal distention; however, extraintestinal manifestations are becoming increasingly more common. They include numerous conditions such as dermatitis herpetiformis, anemia, dental enamel hypoplasia, recurrent oral aphthae, short stature, osteoporosis, arthritis, neurologic problems, unexplained elevation of transaminase levels, and female infertility. Therefore, diagnosing celiac disease requires a high degree of suspicion, followed by correct screening and a confirmatory test with an intestinal biopsy. After diagnosis, a strict gluten-free diet must be followed, which in most cases will bring a marked improvement of symptoms. However, there are important compliance and quality-of-life problems, especially in adolescents.


Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity.
The prevalence of mental illness, particularly depression and dementia, is increased by obesity. Here, we test the hypothesis that obesity-associated changes in gut microbiota are intrinsically able to impair neurocognitive behavior in mice. Conventionally housed, nonobese, adult male C57BL/6 mice maintained on a normal chow diet were subjected to a microbiome depletion/transplantation paradigm using microbiota isolated from donors on either a high-fat diet (HFD) or control diet. Following re-colonization, mice were subjected to comprehensive behavioral and biochemical analyses. The mice given HFD microbiota had significant and selective disruptions in exploratory, cognitive, and stereotypical behavior compared with mice with control diet microbiota in the absence of significant differences in body weight. Sequencing-based phylogenetic analysis confirmed the presence of distinct core microbiota between groups, with alterations in α- and β-diversity, modulation in taxonomic distribution, and statistically significant alterations to metabolically active taxa. HFD microbiota also disrupted markers of intestinal barrier function, increased circulating endotoxin, and increased lymphocyte expression of ionized calcium-binding adapter molecule 1, toll-like receptor 2, and toll-like receptor 4. Finally, evaluation of brain homogenates revealed that HFD-shaped microbiota increased neuroinflammation and disrupted cerebrovascular homeostasis. Collectively, these data reinforce the link between gut dysbiosis and neurologic dysfunction and suggest that dietary and/or pharmacologic manipulation of gut microbiota could attenuate the neurologic complications of obesity.


Culturally competent library services and related factors among health sciences librarians: an exploratory study.
This study investigated the current state of health sciences libraries' provision of culturally competent services to support health professions education and patient care and examined factors associated with cultural competency in relation to library services and professional development. This was a cross-sectional study. Data were collected with a survey questionnaire that was distributed via SurveyMonkey to several health sciences librarian email discussion lists. Out of 176 respondents, 163 reported serving clients from diverse cultural backgrounds. Various services were provided to develop or support initiatives in cultural competency in health professions education and patient care. A considerable number of respondents were unsure or reported no library services to support initiatives in cultural competency, although a majority of respondents perceived the importance of providing culturally competent library services (156, 89.1%) and cultural competency for health sciences librarians (162, 93.1%). Those who self-identified as nonwhites perceived culturally competent services to be more important than whites (p=0.04). Those who spoke another language in addition to English had higher self-rated cultural competency (p=0.01) than those who only spoke English. These findings contribute to our knowledge of the types of library services provided to support cultural competency initiatives and of health sciences librarians' perceived importance in providing culturally competent library services and cultural competency for health sciences librarians. The results suggest implications for health sciences libraries in fostering professional development in cultural competency and in providing culturally competent services to increase library use by people from a wide range of cultures and backgrounds.


Hyperandrogenemia predicts metabolic phenotype in polycystic ovary syndrome: the utility of serum androstenedione.
Polycystic ovary syndrome (PCOS) is a triad of anovulation, insulin resistance, and hyperandrogenism. Androgen excess may correlate with metabolic risk and PCOS consensus criteria define androgen excess on the basis of serum T. Here we studied the utility of the androgen precursor serum androstenedione (A) in conjunction with serum T for predicting metabolic dysfunction in PCOS. Eighty-six PCOS patients fulfilling Rotterdam diagnostic consensus criteria and 43 age- and body mass index-matched controls underwent measurement of serum androgens by tandem mass spectrometry and an oral glucose tolerance test with homeostatic model assessment of insulin resistance and insulin sensitivity index calculation. We analyzed 24-hour urine androgen excretion by gas chromatography/mass spectrometry. PCOS patients had higher levels of serum androgens and urinary androgen metabolites than controls (all P < .001). Within the PCOS cohort, both serum A and T were positively correlated with the free androgen index (T × 100/SHBG) and total androgen metabolite excretion (all P < .001). All subjects with T above the normal reference range [high T (HT)] also had high A (HA/HT group, n = 56). However, the remaining 30 patients had normal T levels, either in the presence of HA (HA/NT; n = 20) or normal A (NA/NT; n = 10). The groups did not differ in age or BMI. The HA/HT and HA/NT groups had higher total androgen excretion than NA/NT (P < .01 and P < .05, respectively). Multiple linear regression showed a strong negative association between serum androstenedione and insulin sensitivity. The incidence of dysglycemia according to an oral glucose tolerance test increased with the severity of androgen phenotype (NA/NT, 0%; HA/NT, 14%; HA/HT, 25%, P = .03). Simultaneous measurement of serum T and A represents a useful tool for predicting metabolic risk in PCOS women. HA levels are a sensitive indicator of PCOS-related androgen excess.


Structures of riboswitch RNA reaction states by mix-and-inject XFEL serial crystallography.
Riboswitches are structural RNA elements that are generally located in the 5' untranslated region of messenger RNA. During regulation of gene expression, ligand binding to the aptamer domain of a riboswitch triggers a signal to the downstream expression platform. A complete understanding of the structural basis of this mechanism requires the ability to study structural changes over time. Here we use femtosecond X-ray free electron laser (XFEL) pulses to obtain structural measurements from crystals so small that diffusion of a ligand can be timed to initiate a reaction before diffraction. We demonstrate this approach by determining four structures of the adenine riboswitch aptamer domain during the course of a reaction, involving two unbound apo structures, one ligand-bound intermediate, and the final ligand-bound conformation. These structures support a reaction mechanism model with at least four states and illustrate the structural basis of signal transmission. The three-way junction and the P1 switch helix of the two apo conformers are notably different from those in the ligand-bound conformation. Our time-resolved crystallographic measurements with a 10-second delay captured the structure of an intermediate with changes in the binding pocket that accommodate the ligand. With at least a 10-minute delay, the RNA molecules were fully converted to the ligand-bound state, in which the substantial conformational changes resulted in conversion of the space group. Such notable changes in crystallo highlight the important opportunities that micro- and nanocrystals may offer in these and similar time-resolved diffraction studies. Together, these results demonstrate the potential of 'mix-and-inject' time-resolved serial crystallography to study biochemically important interactions between biomacromolecules and ligands, including those that involve large conformational changes.


Sexual offending runs in families: A 37-year nationwide study.
Sexual crime is an important public health concern. The possible causes of sexual aggression, however, remain uncertain. We examined familial aggregation and the contribution of genetic and environmental factors to sexual crime by linking longitudinal, nationwide Swedish crime and multigenerational family registers. We included all men convicted of any sexual offence (N = 21,566), specifically rape of an adult (N = 6131) and child molestation (N = 4465), from 1973 to 2009. Sexual crime rates among fathers and brothers of sexual offenders were compared with corresponding rates in fathers and brothers of age-matched population control men without sexual crime convictions. We also modelled the relative influence of genetic and environmental factors to the liability of sexual offending. We found strong familial aggregation of sexual crime [odds ratio (OR) = 5.1, 95% confidence interval (CI) = 4.5-5.9] among full brothers of convicted sexual offenders. Familial aggregation was lower in father-son dyads (OR = 3.7, 95% CI = 3.2-4.4) among paternal half-brothers (OR = 2.1, 95% CI = 1.5-2.9) and maternal half-brothers (OR = 1.7, 95% CI = 1.2-2.4). Statistical modelling of the strength and patterns of familial aggregation suggested that genetic factors (40%) and non-shared environmental factors (58%) explained the liability to offend sexually more than shared environmental influences (2%). Further, genetic effects tended to be weaker for rape of an adult (19%) than for child molestation (46%). We report strong evidence of familial clustering of sexual offending, primarily accounted for by genes rather than shared environmental influences. Future research should possibly test the effectiveness of selective prevention efforts for male first-degree relatives of sexually aggressive individuals, and consider familial risk in sexual violence risk assessment.


Mechanisms of alcoholic pancreatitis.
Alcoholic pancreatitis is a major complication of alcohol abuse. The risk of developing pancreatitis increases with increasing doses of alcohol, suggesting that alcohol exerts dose-related toxic effects on the pancreas. However, it is also clear that only a minority of alcoholics develop the disease, indicating that an additional trigger may be required to initiate clinically evident pancreatic injury. It is now well established that alcohol is metabolized by the pancreas via both oxidative and non-oxidative metabolites. Alcohol and its metabolites produce changes in the acinar cells, which may promote premature intracellular digestive enzyme activation thereby predisposing the gland to autodigestive injury. Pancreatic stellate cells (PSCs) are activated directly by alcohol and its metabolites and also by cytokines and growth factors released during alcohol-induced pancreatic necroinflammation. Activated PSCs are the key cells responsible for producing the fibrosis of alcoholic chronic pancreatitis. Efforts to identify clinically relevant factors that may explain the susceptibility of some alcoholics to pancreatitis have been underway for several years. An unequivocal, functionally characterized, association is yet to be identified in clinical studies, although in the experimental setting, endotoxin has been shown to trigger overt pancreatic injury and to promote disease progression in alcohol-fed animals. Thus, while the molecular effects of alcohol on the pancreas have been increasingly clarified in recent years, identification of predisposing or triggering factors remains a challenge.


Pharmacokinetics of table and Port red wine anthocyanins: a crossover trial in healthy men.
This study was designed to evaluate the pharmacokinetics of Port and table red wine anthocyanins in healthy men. Volunteers were recruited to drink 250 mL of a table red wine (221 mg of anthocyanins) and 150 mL of young Port red wine (49 mg of anthocyanins). Venous blood was collected from participants at 0, 15, 30, 60 and 120 min after wine ingestion. Urine samples were collected at baseline and at 120 min. Anthocyanins and anthocyanin metabolites in plasma and urine samples were quantified by HPLC-DAD and tentatively identified by LC-MS. Red wine anthocyanins were detected in their intact forms in both plasma and urine samples, but the glucuronylated metabolites of peonidin and malvidin (PnGlucr and MvGlucr) were the two main derivatives detected after both red wine consumptions. For the first time, and supported by the synthesis of Mv3Glucr, the main pathway followed by Mv3glc after absorption was described and involves anthocyanidin conjugation with glucuronic acid after glucose removal. Despite the lower total content of anthocyanins ingested when volunteers drank Port wine, no differences were observed in the plasma Cmax of MvGlucr and PnGlucr after table and Port red wine consumption. The relative bioavailability of anthocyanins in Port wine was 96.58 ± 5.74%, compared to the anthocyanins present in red wine. In conclusion, both Port and table red wines are good sources of bioavailable anthocyanins.


Role of sulfhydryl groups in Y2 neuropeptide Y receptor binding activity.
Benextramine, a tetramine disulfide, irreversibly inhibits neuropeptide Y (NPY) binding to the 50-kDa Y2 NPY receptor in bovine hippocampus (Li, W., MacDonald, R. G., and Hexum, T. D. (1991) Eur. J. Pharmacol. 207, 89-91). Evidence is presented that this inhibition occurs through a thiol-disulfide exchange. Treatment of bovine hippocampal membranes with benextramine inhibited NPY affinity cross-linking to the 50-kDa receptor. This inhibition of labeling was not affected by washing the membranes, but could be completely reversed by the addition of several thiol reducing reagents, including reduced glutathione, beta-mercaptoethanol, and cysteine. Benextramine inhibited 70% of NPY-specific labeling and was much more effective than other sulfhydryl reactive agents, such as oxidized glutathione, cystamine, and 5,5'-dithio-bis(2-nitrobenzoic acid). Furthermore, the sulfhydryl-modifying agents N-ethylmaleimide and p-chloromercuriphenyl-sulfonic acid specifically decreased NPY affinity labeling. Finally, NPY labeling of the 50-kDa receptor was reduced by the heavy metal ions Zn2+, Cu2+, and Hg2+. Preincubation with NPY prevented Y2 receptors from being inactivated by either 400 microM N-ethylmaleimide or 1 mM benextramine. These results suggest that one or more benextramine-sensitive sulfhydryl groups on the Y2 receptor are important for NPY binding activity.


Expression signature developed from a complex series of mouse models accurately predicts human breast cancer survival.
The capability of microarray platform to interrogate thousands of genes has led to the development of molecular diagnostic tools for cancer patients. Although large-scale comparative studies on clinical samples are often limited by the access of human tissues, expression profiling databases of various human cancer types are publicly available for researchers. Given that mouse models have been instrumental to our current understanding of cancer progression, we aimed to test the hypothesis that novel gene signatures possessing predictability in clinical outcome can be derived by coupling genomic analyses in mouse models of cancer with publicly available human cancer data sets. We established a complex series of syngeneic metastatic animal models using a murine breast cancer cell line. Tumor RNA was hybridized on Affymetrix MouseGenome-430A2.0 GeneChips. With the use of Venn logic, gene signatures that represent metastatic competency were derived and tested against publicly available human breast and lung cancer data sets. Survival analyses showed that the spontaneous metastasis gene signature was significantly associated with metastasis-free and overall survival (P < 0.0005). Consequently, the six-gene model was determined and showed statistical predictability in predicting survival in breast cancer patients. In addition, the model was able to stratify poor from good prognosis for lung cancer patients in most data sets analyzed. Together, our data support that novel gene signature derived from mouse models of cancer can be used for predicting human cancer outcome. Our approaches set precedence that similar strategies may be used to decipher novel gene signatures for clinical utility.


Avoiding Optimal Mean ℓ2,1-Norm Maximization-Based Robust PCA for Reconstruction.
Robust principal component analysis (PCA) is one of the most important dimension-reduction techniques for handling high-dimensional data with outliers. However, most of the existing robust PCA presupposes that the mean of the data is zero and incorrectly utilizes the average of data as the optimal mean of robust PCA. In fact, this assumption holds only for the squared [Formula: see text]-norm-based traditional PCA. In this letter, we equivalently reformulate the objective of conventional PCA and learn the optimal projection directions by maximizing the sum of projected difference between each pair of instances based on [Formula: see text]-norm. The proposed method is robust to outliers and also invariant to rotation. More important, the reformulated objective not only automatically avoids the calculation of optimal mean and makes the assumption of centered data unnecessary, but also theoretically connects to the minimization of reconstruction error. To solve the proposed nonsmooth problem, we exploit an efficient optimization algorithm to soften the contributions from outliers by reweighting each data point iteratively. We theoretically analyze the convergence and computational complexity of the proposed algorithm. Extensive experimental results on several benchmark data sets illustrate the effectiveness and superiority of the proposed method.


Biocompatibility and mineralized nodule formation of Neo MTA Plus and an experimental tricalcium silicate cement containing tantalum oxide.
To evaluate the biocompatibility and mineralized nodule formation of an experimental tricalcium silicate cement with tantalum oxide (TSC/Ta2 O5 ) as radiopacifier, Neo MTA Plus (Avalon Biomed Inc., Bradenton, FL, USA) and MTA (Angelus, Londrina, PR, Brazil) on human osteoblast-like cells (Saos-2). Biocompatibility was evaluated by 3-(4,5-dimethyl-thiazoyl)-2,5-diphenyl-tetrazolium bromide (MTT) and neutral red (NR) assays, after exposure of Saos-2 to cement extracts at 1 : 1, 1 : 2, 1 : 4 and 1 : 8 dilutions for 24 h. Bioactivity was evaluated by alkaline phosphatase (ALP) activity, and calcium deposits were detected with alizarin red staining (ARS). Statistical analysis was performed with analysis of variance and Bonferroni or Tukey post-test (α = 0.05). The MTT assay revealed lower cytotoxicity for NEO and MTA (P < 0.05), and higher for TSC/Ta2 O5 at 1 : 1 and 1 : 2 dilutions when compared to serum-free medium - control (P > 0.05). At 1 : 4 dilution, the TSC/Ta2 O5 cytotoxicity was similar to the control (P > 0.05). At 1 : 8 dilution, cell viability was significantly greater than the control (P < 0.05). Saos-2 cell viability performed using the NR assay at all dilutions revealed no cytotoxic effect of MTA, NEO and TSC/Ta2 O5 . ALP activity at 1 and 3 days was similar to the control (P > 0.05). TSC/Ta2 O5 had significantly greater ALP activity at 7 days when compared with the control (P < 0.05). All materials induced the production of mineralized nodules, and NEO produced significantly more mineralized nodules than MTA and TSC/Ta2 O5 (P < 0.05). Neo MTA Plus and TSC/Ta2 O5 were biocompatible and induced ALP activity in Saos-2 cells. Both materials induced mineralized nodule formation by Saos-2 with Neo MTA Plus producing significantly more.


Therapeutic potential of endothelial progenitor cells in cardiovascular diseases.
Endothelial dysfunction and cell loss are prominent features in cardiovascular disease. Endothelial progenitor cells (EPCs) originating from the bone marrow play a significant role in neovascularization of ischemic tissues and in re-endothelialization of injured blood vessels. Several studies have shown the therapeutic potential of EPC transplantation in rescue of tissue ischemia and in repair of blood vessels and bioengineering of prosthetic grafts. Recent small-scale trials have provided preliminary evidence of feasibility, safety, and efficacy in patients with myocardial and critical limb ischemia. However, several studies have shown that age and cardiovascular disease risk factors reduce the availability of circulating EPCs (CEPCs) and impair their function to varying degrees. In addition, the relative scarcity of CEPCs limits the ability to expand these cells in sufficient numbers for some therapeutic applications. Priority must be given to the development of strategies to enhance the number and improve the function of CEPCs. Furthermore, alternative sources of EPC such as chord blood need to be explored. Strategies for improvement of cell adhesion, survival, and prevention of cell senescence are also essential to ensure therapeutic viability. Genetic engineering of EPCs may be a useful approach to developing these cells into efficient therapeutic tools. In the clinical arena there is pressing need to standardize the protocols for isolation, culture, and therapeutic application of EPC. Large-scale multi-center randomized trials are required to evaluate the long-term safety and efficacy of EPC therapy. Despite these hurdles, the outlook for EPC-based therapy for cardiovascular disease is promising.


"Supersaturated" self-assembled charge-selective interfacial layers for organic solar cells.
To achieve densely packed charge-selective organosilane-based interfacial layers (IFLs) on the tin-doped indium oxide (ITO) anodes of organic photovoltaic (OPV) cells, a series of Ar2N-(CH2)n-SiCl3 precursors with Ar = 3,4-difluorophenyl, n = 3, 6, 10, and 18, was synthesized, characterized, and chemisorbed on OPV anodes to serve as IFLs. To minimize lateral nonbonded -NAr2···Ar2N- repulsions which likely limit IFL packing densities in the resulting self-assembled monolayers (SAMs), precursor mixtures having both small and large n values are simultaneously deposited. These "heterogeneous" SAMs are characterized by a battery of techniques: contact angle measurements, X-ray reflectivity, X-ray photoelectron spectroscopy, ultraviolet photoelectron spectroscopy (UPS), cyclic voltammetry, and DFT computation. It is found that the headgroup densities of these "supersaturated" heterogeneous SAMs (SHSAMs) are enhanced by as much as 17% versus their homogeneous counterparts. Supersaturation significantly modifies the IFL properties including the work function (as much as 16%) and areal dipole moment (as much as 49%). Bulk-heterojunction OPV devices are fabricated with these SHSAMs: ITO/IFL/poly[[4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5-b']dithiophene-2,6-diyl][2-[[(2-ethylhexyl)oxy]carbonyl]-3-fluorothieno[3,4-b]thiophenediyl]]:phenyl-C71-butyric acid methyl ester (PTB7:PC71BM)/LiF/Al. OPVs having SHSAM IFLs exhibit significantly enhanced performance (PCE by 54%; Voc by 35%) due to enhanced charge selectivity and collection, with the PCE rivaling or exceeding that of PEDOT:PSS IFL devices -7.62%. The mechanism underlying the enhanced performance involves modified hole collection and selectivity efficiency inferred from the UPS data. The ITO/SAM/SHSAM surface potential imposed by the dipolar SAMs causes band bending and favorably alters the Schottky barrier height. Thus, interfacial charge selectivity and collection are enhanced as evident in the greater OPV Voc.


Molecular characterization of Xenopus laevis DP proteins.
It is widely believed that in mammalian cells the cellular transcription factor (DRTF1/E2F integrates cell-cycle events with the transcription apparatus by interacting with important regulators of the cell cycle, such as the retinoblastoma gene product (pRb) and related proteins, cyclins, and cyclin-dependent kinases. Here, we have defined DRTF1/E2F in Xenopus laevis that, like its mammalian counterpart, specifically binds to the E2F site, is regulated during development, and interacts with pRb and related proteins. We have isolated cDNAs that encode the functional homologue of mammalian DP-1, X1 DP-1, together with a close relative, X1 DP-2. X1 DP-1, which is highly conserved with murine DP-1, is a major DNA binding component of X1 DRTF1/E2F. Both DP-1 and DP-2 synergistically interact with members of the E2F family of proteins, E2F-1, E2F-2, and E2F-3, to generate DNA binding complexes that specifically recognize the E2F site and functionally interact with E2F-1 in E2F site-dependent transcriptional activation of cellular genes. DP-1 and DP-2 encode maternally stored transcripts that are expressed during early development. In the adult however, the expression of DP-1 and DP-2 is tissue restricted. This study therefore defines a new family of transcription factors, the DP proteins, members of which can interact combinatorially with E2F proteins to generate an array of DNA binding complexes that integrate cell-cycle progression with the transcription apparatus through the E2F binding site. The tissue-specific expression of DP family members suggests that the combination of DP/E2F heterodimers that constitute DRTF1/E2F is influenced by the phenotype of the cell.


Structure and action of a C-C bond cleaving alpha/beta-hydrolase involved in nicotine degradation.
The enzyme 2,6-dihydroxy-pseudo-oxynicotine hydrolase from the nicotine-degradation pathway of Arthrobacter nicotinovorans was crystallized and the structure was determined by an X-ray diffraction analysis at 2.1 A resolution. The enzyme belongs to the alpha/beta-hydrolase family as derived from the chain-fold and from the presence of a catalytic triad with its oxyanion hole at the common position. This relationship assigns a pocket lined by the catalytic triad as the active center. The asymmetric unit contains two C(2)-symmetric dimer molecules, each adopting a specific conformation. One dimer forms a more spacious active center pocket and the other a smaller one, suggesting an induced-fit. All of the currently established C-C bond cleaving alpha/beta-hydrolases are from bacterial meta-cleavage pathways for the degradation of aromatic compounds and cover their active center with a 40 residue lid placed between two adjacent strands of the beta-sheet. In contrast, the reported enzyme shields its active center with a 110 residue N-terminal domain, which is absent in the meta-cleavage hydrolases. Since neither the substrate nor an analogue could be bound in the crystals, the substrate was modeled into the active center using the oxyanion hole as a geometric constraint. The model was supported by enzymatic activity data of 11 point mutants and by the two dimer conformations suggesting an induced-fit. Moreover, the model assigned a major role for the large N-terminal domain that is specific to the reported enzyme. The proposal is consistent with the known data for the meta-cleavage hydrolases although it differs in that the reaction does not release alkenes but a hetero-aromatic compound in a retro-Friedel-Crafts acylation. Because the hydrolytic water molecule can be assigned to a geometrically suitable site that can be occupied in the presence of the substrate, the catalytic triad may not form a covalent acyl-enzyme intermediate but merely support a direct hydrolysis.


DNA rearrangements associated with multiple consecutive directed antigenic switches in Trypanosoma brucei.
Changes in variant surface glycoprotein (Vsg) expression allow Trypanosoma brucei to elude the immune response. The expressed vsg is always located at the telomeric end of a polycistronic transcription unit known as an expression site (ES). Although there are many ESs, only one is active at any particular time. The mechanisms regulating ES transcription and switching are unknown. Chromosome rearrangements within or upstream of the ES have been described to occur in occasional switch events, but no changes have been consistently associated with switching. We inserted the drug resistance genes neo and ble, conferring resistance to G418 and phleomycin, respectively, 1 kb downstream of "silent" ES promoters. This demonstrated that short-range transcription could be achieved from a silent ES promoter. From one initial transformant clone, panels of independent consecutive on-off-on switch clones were generated and analyzed. The first activation of the neo-targeted ES was always associated with deletion of the upstream tandem promoter in this ES, but no further rearrangements were detected in consecutive off-on switches of this ES. On the other hand, direct analysis of ES promoters showed that deletions and duplications occurred elsewhere. Activation of a ble-tagged 300-kb chromosome could not be achieved, but phleomycin-resistant clones could be obtained. One such clone arose from recombination between three ESs. Taken together, our experiments suggest that ES switching may occur after a period of chromosomal interactivity that may or may not leave tangible evidence in the form of detectable sequence changes.


Robust Classification of Intramuscular EMG Signals to Aid the Diagnosis of Neuromuscular Disorders.
Goal: This article presents the design and validation of an accurate automatic diagnostic system to classify intramuscular EMG (iEMG) signals into healthy, myopathy, or neuropathy categories to aid the diagnosis of neuromuscular diseases. Methods: First, an iEMG signal is decimated to produce a set of "disjoint" downsampled signals, which are decomposed by the lifting wavelet transform (LWT). The Higuchi's fractal dimensions (FDs) of LWT coefficients in the subbands are computed. The FDs of LWT subband coefficients are fused with one-dimensional local binary pattern derived from each downsampled signal. Next, a multilayer perceptron neural network (MLPNN) determines the class labels of downsampled signals. Finally, the sequence of class labels is fed to the Boyer-Moore majority vote (BMMV) algorithm, which assigns a class to every iEMG signal. Results: The MLPNN-BMMV classifier was experimented with 250 iEMG signals belonging to three categories. The performance of the classifier was validated in comparison with state-of-the-art approaches. The MLPNN-BMMV has resulted in impressive performance measures (%) using a 10-fold cross-validation-accuracy = [Formula: see text], sensitivity (normal) = [Formula: see text], sensitivity (myopathy) = [Formula: see text], sensitivity (neuropathy) = [Formula: see text], specificity (normal) = [Formula: see text], specificity (myopathy) = [Formula: see text], and specificity (neuropathy) = [Formula: see text]-surpassing the existing approaches. Conclusions: A future research direction is to validate the classifier performance with diverse iEMG datasets, which would lead to the design of an affordable real-time expert system for neuromuscular disorder diagnosis.


Independent and additive effects of glutamic acid and methionine on yeast longevity.
It is established that glucose restriction extends yeast chronological and replicative lifespan, but little is known about the influence of amino acids on yeast lifespan, although some amino acids were reported to delay aging in rodents. Here we show that amino acid composition greatly alters yeast chronological lifespan. We found that non-essential amino acids (to yeast) methionine and glutamic acid had the most significant impact on yeast chronological lifespan extension, restriction of methionine and/or increase of glutamic acid led to longevity that was not the result of low acetic acid production and acidification in aging media. Remarkably, low methionine, high glutamic acid and glucose restriction additively and independently extended yeast lifespan, which could not be further extended by buffering the medium (pH 6.0). Our preliminary findings using yeasts with gene deletion demonstrate that glutamic acid addition, methionine and glucose restriction prompt yeast longevity through distinct mechanisms. This study may help to fill a gap in yeast model for the fast developing view that nutrient balance is a critical factor to extend lifespan.


Quantitative techniques for musculoskeletal MRI at 7 Tesla.
Whole-body 7 Tesla MRI scanners have been approved solely for research since they appeared on the market over 10 years ago, but may soon be approved for selected clinical neurological and musculoskeletal applications in both the EU and the United States. There has been considerable research work on musculoskeletal applications at 7 Tesla over the past decade, including techniques for ultra-high resolution morphological imaging, 3D T2 and T2* mapping, ultra-short TE applications, diffusion tensor imaging of cartilage, and several techniques for assessing proteoglycan content in cartilage. Most of this work has been done in the knee or other extremities, due to technical difficulties associated with scanning areas such as the hip and torso at 7 Tesla. In this manuscript, we first provide some technical context for 7 Tesla imaging, including challenges and potential advantages. We then review the major quantitative MRI techniques being applied to musculoskeletal applications on 7 Tesla whole-body systems.


Improved dual-energy material discrimination for dual-source CT by means of additional spectral filtration.
The use of additional spectral filtration for dual-energy (DE) imaging using a dual-source CT (DSCT) system was investigated and its effect on the material-specific DE(ratio) was evaluated for several clinically relevant materials. The x-ray spectra, data acquisition, and reconstruction processes for a DSCT system (Siemens Definition) were simulated using information provided by the system manufacturer, resulting in virtual DE images. The factory-installed filtration for the 80 kV spectrum was left unchanged to avoid any further reductions in tube output, and only the filtration for the high-energy spectrum was modified. Only practical single-element filter materials within the atomic number range of 40 < or = Z < or = 83 were evaluated, with the aim of maximizing the separation between the two spectra, while maintaining similar noise levels for high- and low-energy images acquired at the same tube current. The differences between mean energies and the ratio of the 140 and 80 kV detector signals, each integrated below 80 keV, were evaluated. The simulations were performed for three attenuation scenarios: Head, body, and large body. The large body scenario was evaluated for the DE acquisition mode using the 100 and 140 kV spectra. The DE(ratio) for calcium hydroxyapatite (simulating bone or calcifications), iodine, and iron were determined for CT images simulated using the modified and factory-installed filtration. Several filter materials were found to perform well at proper thicknesses, with tin being a good practical choice. When image noise was matched between the low- and high-energy images, the spectral difference in mean absorbed energy using tin was increased from 25.7 to 42.7 keV (head), from 28.6 to 44.1 keV (body), and from 20.2 to 30.2 keV (large body). The overlap of the signal spectra for energies below 80 keV was reduced from 78% to 31% (head), from 93% to 27% (body), and from 106% to 79% (large body). The DE(ratio) for the body attenuation scenario increased from 1.45 to 1.91 (calcium), from 1.84 to 3.39 (iodine), and from 1.73 to 2.93 (iron) with the additional tin filtration compared to the factory filtration. This use of additional filtration for one of the x-ray tubes used in dual-source DECT dramatically increased the difference between material-specific DE ratios, e.g., from 0.39 to 1.48 for calcium and iodine or from 0.28 to 1.02 for calcium and iron. Because the ability to discriminate between different materials in DE imaging depends primarily on the differences in DE ratios, this increase is expected to improve the performance of any material-specific DECT imaging task. Furthermore, for the large patient size and in conjunction with a 100/140 kV acquisition, the use of additional filtration decreased noise in the low-energy images and increased contrast in the DE image relative to that obtained with 80/140 kV and no additional filtration.


Peculiar electrolytic and hormonal abnormalities in acute renal failure due to leptospirosis.
Hypokalemia in leptospirosis acute renal failure (ARF) was studied in nine patients with severe leptospirosis ARF and five patients with moderate leptospirosis ARF and compared with five patients with severe acute tubular necrosis (ATN) and eight healthy individuals. Urinary volumes of both the severe and moderate leptospirosis groups were higher than those of the severe ATN group. Leptospirosis groups had serum potassium levels lower than those found in the healthy and severe ATN groups. Serum sodium levels were lower in the severe leptospirosis group than in the moderate leptospirosis, the severe ATN, and the healthy groups. There was a positive correlation between the fractional excretion of sodium and potassium in the severe leptospirosis group as well as between serum creatinine and potassium levels in the pooled leptospirosis groups. Urinary pH in the severe and moderate leptospirosis groups was lower than in the severe ATN group. Aldosterone levels were higher in the severe leptospirosis group than in the healthy individuals. Cortisol levels were higher in the leptospirosis groups than in the healthy subjects. These results strongly suggest that hypokalemia in leptospirosis ARF is due to renal potassium wasting potentialized by aldosterone and cortisol, requiring that special attention is given to potassium replacement as well as to volume repletion in the treatment of leptospirosis ARF.


Characteristics associated with older adolescents who have a television in their bedrooms.
The goals were to examine the prevalence of adolescents having a television in their bedroom and to describe associated personal, social, and behavioral characteristics. Participants included 781 adolescents (mean age: 17.2 years) who completed a mailed Project Eating Among Teens II questionnaire. The relationships between adolescents having a television in their bedroom and sociodemographic, behavioral, and personal characteristics were examined. Nearly two thirds (62%) of participants had a bedroom television. Gender, race/ethnicity, socioeconomic status, and age were associated with the presence of a bedroom television. Compared with girls without a bedroom television, girls with a bedroom television reported less time spent in vigorous activity (1.8 vs 2.5 hours/week), more time spent watching television (20.7 vs 15.2 hours/week), lower vegetable intake (1.7 vs 2.0 servings per day), greater sweetened beverage consumption (1.2 vs 1.0 servings per day), and fewer family meals (2.9 vs 3.7 meals per week). Compared with boys without a bedroom television, boys with a bedroom television reported more time spent watching television (22.2 vs 18.2 hours/week), lower fruit intake (1.7 vs 2.2 servings per day), fewer family meals (2.9 vs 3.6 meals per week), and lower grade point average (2.6 vs 2.9). Twice as many youths with a television in their bedroom were heavy television users (watched >5 hours/day), compared with youths without a television in their bedroom (16% vs 8%). Adolescents with a bedroom television reported more television viewing time, less physical activity, poorer dietary habits, fewer family meals, and poorer school performance. Refraining from placing a television in teenagers' rooms may be a first step in helping to decrease screen time and subsequent poor behaviors associated with increased television watching.


Monitoring sintering burn-through point using infrared thermography.
Sintering is a complex industrial process that applies heat to fine particles of iron ore and other materials to produce sinter, a solidified porous material used in blast furnaces. The sintering process needs to be carefully adjusted, so that the combustion zone reaches the bottom of the material just before the discharge end. This is known as the burn-through point. Many different parameters need to be finely tuned, including the speed and the quantities of the materials mixed. However, in order to achieve good results, sintering control requires precise feedback to adjust these parameters. This work presents a sensor to monitor the sintering burn-through point based on infrared thermography. The proposed procedure is based on the acquisition of infrared images at the end of the sintering process. At this position, infrared images contain the cross-section temperatures of the mixture. The objective of this work is to process this information to extract relevant features about the sintering process. The proposed procedure is based on four steps: key frame detection, region of interest detection, segmentation and feature extraction. The results indicate that the proposed procedure is very robust and reliable, providing features that can be used effectively to control the sintering process.


Oestradiol and sex hormone-binding globulin in premenopausal and post-menopausal meat-eaters, vegetarians and vegans.
Endogenous oestradiol is strongly associated with breast cancer risk but its determinants are poorly understood. To test the hypothesis that vegetarians have lower plasma oestradiol and higher sex hormone-binding globulin (SHBG) than meat-eaters we assayed samples from 640 premenopausal women (153 meat-eaters, 382 vegetarians, 105 vegans) and 457 post-menopausal women (223 meat-eaters, 196 vegetarians, 38 vegans). Vegetarians and vegans had lower mean body mass indices (BMI) and lower plasma cholesterol concentrations than meat-eaters, but there were no statistically significant differences between meat-eaters, vegetarians and vegans in pre- or post-menopausal plasma concentrations of oestradiol or SHBG. Before adjusting for BMI there were small differences in the direction expected, with the vegetarians and vegans having higher SHBG and lower oestradiol (more noticeable amongst post-menopausal women) than the meat-eaters. These small differences were essentially eliminated by adjusting for BMI. Thus this study implies that the relatively low BMI of vegetarians and vegans does cause small changes in SHBG and in post-menopausal oestradiol, but that the composition of vegetarian diets may not have any additional effects on these hormones.


Maximising Refractive Outcomes with an Extended Depth of Focus IOL.
To assess the impact of the magnitude of preoperative and postoperative corneal astigmatism on refractive outcomes in patients undergoing cataract surgery or lens exchange with an extended depth of focus intraocular lens. To compare visual outcomes of steep and temporal on-axis corneal incisions. Department of Ophthalmology, Blackrock Clinic, Dublin, Ireland. Prospective cohort analysis. Fifty-three consecutive adult patients (94 eyes) undergoing routine phacoemulsification with Symfony IOL implantation were analysed. Exclusion criteria: targets for mini-monovision, incomplete data, other ocular pathology. Data were prospectively collected on pre- and postoperative refraction, keratometry, distance vision, near vision, surgical wound site and Surgically Induced Astigmatism (SIA). The average postoperative monocular Uncorrected Distance and Near visual acuities (UDVA and UNVA) were 0.12 LogMAR (± 0.1) (6/7.5+1) and 0.34 LogMAR (± 0.09) respectively. The average binocular UDVA and UNVA were 0.05 (± 0.07) and 0.29 LogMAR (± 0.06) respectively. Low levels of preoperative corneal astigmatism (0-0.99 D) were associated with better LogMAR UDVA and UNVA when compared with higher levels (> 0.99 D): 0.11 (CI 0.103-0.107) vs. 0.206 (CI 0.122-0.290) (p =0.015, CI 95%) and 0.33 (CI 0.316 - 0.356) vs. 0.39 (CI 0.34-0.43) (p =0.034, CI 95%) respectively. When patients with steep on-axis corneal incisions were compared with temporal on-axis corneal incisions, no difference was detected in visual outcome or SIA. The Symfony IOL is an effective surgical means of addressing presbyopia and reducing postoperative spectacle dependence. We stress caution when offering potential spectacle independence for patients with over 1D of preoperative corneal astigmatism as these patients achieve statistically significantly inferior and less predictable visual results.


The Well-Being Benefits of Person-Culture Match Are Contingent on Basic Personality Traits.
People enjoy well-being benefits if their personal characteristics match those of their culture. This person-culture match effect is integral to many psychological theories and-as a driver of migration-carries much societal relevance. But do people differ in the degree to which person-culture match confers well-being benefits? In the first-ever empirical test of that question, we examined whether the person-culture match effect is moderated by basic personality traits-the Big Two and Big Five. We relied on self-reports from 2,672,820 people across 102 countries and informant reports from 850,877 people across 61 countries. Communion, agreeableness, and neuroticism exacerbated the person-culture match effect, whereas agency, openness, extraversion, and conscientiousness diminished it. People who possessed low levels of communion coupled with high levels of agency evidenced no well-being benefits from person-culture match, and people who possessed low levels of agreeableness and neuroticism coupled with high levels of openness, extraversion, and conscientiousness even evidenced well-being costs. Those results have implications for theories building on the person-culture match effect, illuminate the mechanisms driving that effect, and help explain failures to replicate it.


Empirical analysis of locality, heritability and heuristic bias in evolutionary algorithms: a case study for the multidimensional knapsack problem.
Our main aim is to provide guidelines and practical help for the design of appropriate representations and operators for evolutionary algorithms (EAs). For this purpose, we propose techniques to obtain a better understanding of various effects in the interplay of the representation and the operators. We study six different representations and associated variation operators in the context of a steady-state evolutionary algorithm for the multidimensional knapsack problem. Four of them are indirect decoder-based techniques, and two are direct encodings combined with different initialization, repair, and local improvement strategies. The complex decoders and the local improvement and repair strategies make it practically impossible to completely analyze such EAs in a fully theoretical way. After comparing the general performance of the chosen EA variants for the multidimensional knapsack problem on two benchmark suites, we present a hands-on approach for empirically analyzing important aspects of initialization, mutation, and crossover in an isolated fashion. Static, inexpensive measurements based on randomly created solutions are performed in order to quantify and visualize specific properties with respect to heuristic bias, locality, and heritability. These tests shed light onto the complex behavior of such EAs and point out reasons for good or bad performance. In addition, the proposed measures are also examined during actual EA runs, which gives further insight into dynamic aspects of evolutionary search and verifies the validity of the isolated static measurements. All measurements are described in a general way, allowing for an easy adaption to other representations and problems.