Awareness and impact of the 'Bubblewrap' advertising campaign among Aboriginal smokers in Western Australia.
Antismoking mass media campaigns have been shown to reduce smoking prevalence in the mainstream community, however there is little published research on their effect on Aboriginal Australian smokers. To evaluate the awareness and impact of a mainstream mass media advertising campaign (the 'Bubblewrap' campaign) on Aboriginal smokers in the state of Western Australia. A personal intercept survey was conducted in July 2008 across three sites (the Perth metropolitan area and the non-metropolitan towns of Kalgoorlie and Broome). An opportunity or convenience sampling strategy was used to recruit Aboriginal participants, and face-to-face interviews were conducted with 198 Aboriginal smokers to ascertain awareness of the campaign advertisements, whether they were seen as believable and relevant, and the impact the advertisements had on smoking behaviour. The majority of the participants interviewed had seen and/or heard the 'Bubblewrap' campaign advertisements, although there was considerably greater awareness of the television advertisement than the radio advertisements. Both forms of advertising were considered to be believable and relevant by the majority of Aboriginal smokers. Most of the smokers interviewed thought about cutting down and/or quitting after seeing or hearing the advertisements. Our findings suggest that mainstream antismoking mass media campaigns can positively influence the thoughts and behaviours that Aboriginal smokers have, and exhibit, towards quitting smoking. Notwithstanding this, advertisers should continue to look for better ways to incorporate Aboriginal themes in campaign messages. Future mainstream antismoking campaigns should source sufficient funds to ensure that advertising messages reach the large Aboriginal populations in regional and remote Australia.


Phenolic Profiles and Contribution of Individual Compounds to Antioxidant Activity of Apple Powders.
Apples (Malus domestica L.) are the most common source of phenolic compounds in northern European diet. Besides pectins, dietary fibers, vitamins, and oligosaccharides they contain phenolic compounds of different classes. Apple powders are convenient functional forms retaining significant amounts of phenolic antioxidants. In this study reducing and radical scavenging profiles of freeze-dried powders of "Aldas,ˮ "Auksis,ˮ "Connel Red,ˮ "Ligol,ˮ "Lodel,ˮ and "Rajkaˮ were determined and phenolic constituents were identified using ultra high-performance liquid chromatography coupled to quadrupole and time-of-flight mass spectrometers. A negative ionization mode was applied and seventeen compounds: phenolic acids (coumaroylquinic, chlorogenic), flavonoids (quercetin derivatives), and procyanidin derivatives (B1, B2, and C1) were identified in all tested apple samples. Total values of Trolox equivalents varied from 7.72 ± 0.32 up to 20.02 ± 0.52 and from 11.10 ± 0.57 up to 21.42 ± 0.75 μmol/g of dry weight of apple powder in FRAP (ferric reducing antioxidant power) and ABTS (2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) postcolumn assays, respectively. The greatest Trolox equivalent values were determined for apples of "Aldasˮ cultivar. Chlorogenic acid and procyanidin C1 were the most significant contributors to total reducing and radical scavenging activity in all apple cultivars tested, therefore they could be considered as markers of antioxidant activity.


Ferrocene-based supramolecular structures and their applications in electrochemical responsive systems.
Electrochemical stimuli have attracted much attention in recent years as they are simple, clean and can be widely applied in biological systems and material science. As one type of common guest molecules, ferrocene and its derivatives have been well studied with different host molecules, mainly including cyclodextrins, cucurbiturils, pillararenes and calixarenes. This article generally summarizes the recent work on the host-guest interactions between ferrocene derivatives and their host molecules, as well as various supramolecular systems based on these interactions. In addition, the development and outlook of electrochemical responsive systems are also discussed.


A PET study of brain 5-HT2 receptors and their correlation with platelet 5-HT2 receptors in healthy humans.
Platelets share many properties with brain serotonergic neurons such as active 5-hydroxytryptamine (5-HT) transport, 5-HT2 receptors, and mitochondrial monoamine oxidase. We measured brain 5-HT2 receptors and platelet 5-HT2 receptors in healthy volunteers to determine if there was any correlation between the two measures. Ten healthy volunteers with no lifetime history of psychiatric illness or family history in first-degree relatives were recruited. 5-HT2 receptor binding was determined for each subject with positron emission tomography and [18F]setoperone scan in the brain and with 3H-LSD binding in platelets. We found no significant correlation between 5-HT2 binding potential (BP) in platelets (Bmax/Kd) and a semiquantitative estimate of 5-HT2 BP in frontal, parietal, and temporal cortical regions. SPM voxel based analysis also showed no significant correlation between the 5-HT2 BP in platelets and in the brains of the study subjects. Brain 5-HT2 receptor binding was not significantly correlated to platelet 3H-LSD binding in healthy subjects. This raises questions about the validity of generalizing findings from platelet studies to 5-HT neurons in the brain.


Land use as a driver of soil fertility and biodiversity across an agricultural landscape in the Central Peruvian Andes.
Land use change and intensification in agricultural landscapes of the Andean highlands have resulted in widespread soil degradation and a loss in soil-based ecosystem services and biodiversity. This trend threatens the sustainability of farming communities in the Andes, with important implications for food security and biodiversity conservation throughout the region. Based on these challenges, we sought to understand the impact of current and future land use practices on soil fertility and biodiversity, so as to inform landscape planning and management decisions for sustainable agroecosystem management. We worked with local communities to identify and map dominant land uses in an agricultural landscape surrounding Quilcas, Peru. These land uses existed within two elevations zones (low-medium, 3200-3800 m, and high elevation, 3800-4300 m). They included three types of low-medium elevation forests (eucalyptus, alder, and mixed/native species), five pasture management types (permanent pasture, temporal pasture [in fallow stage], degraded pasture, high-altitude permanent pasture, and high-altitude temporal pasture [in fallow stage]) and six cropping systems (forage crops, maize/beans, and potato under four types of management). Soil fertility was evaluated in surface soils (0-20 cm) with soil physicochemical parameters (e.g., pH, soil organic matter, available nutrients, texture), while soil biological properties were assessed using the abundance and diversity of soil macrofauna and ground cover vegetation. Our results indicated clear impacts of land use on soil fertility and biological communities. Altitude demonstrated the strongest effect on soil physicochemical properties, but management systems within the low-mid elevation zone also showed important differences in soil biological communities. In general, the less-disturbed forest and pasture systems supported more diverse soil communities than the more intensively managed croplands. Degraded soils demonstrated the lowest overall soil fertility and abundance of soil macrofauna, but this may be reversible via the planting of alder forests. Our findings also indicated significant covariation between soil physicochemical parameters, soil macrofauna, and ground vegetation. This suggests that management for any one of these soil properties may yield unintended cascading effects throughout the soil subsystem. In summary, our findings suggest that shifts in land use across the landscape are likely to have important impacts on soil functioning and biodiversity.


Demonstration of a specific neutrophil receptor for a cell-derived chemotactic factor.
The crystal-induced chemotactic factor, a cell-derived chemoattractant for neutrophils, binds specifically to a site on human neutrophils but not to erythrocytes or lymphocytes, suggesting a relationship between the presence of specific binding sites on the neutrophils and the ability to be chemotactically activated. The Scatchard analysis revealed an equilibrium dissociation constant at 37 degrees C of 0.446 micrometer and the presence of approximately equal to 6.44 x 10(5) binding sites for 125I-crystal-induced chemotactic factor per cell. Binding was not displaced by the synthetic chemotactic factors F-Met-Leu-Phe and Gly-His-Gly or by complement-activated plasma providing evidence of the specificity of the receptor.


Atypical Clinical Presentations of TAZ Mutations: An Underdiagnosed Cause of Growth Retardation?
Barth syndrome is known as a highly recognizable X-linked disorder typically presenting with the three hallmarks: (left ventricular non-compaction) cardiomyopathy, neutropenia, and 3-methylglutaconic aciduria. Furthermore, growth retardation, mild skeletal myopathy, and specific facial features as well as mitochondrial dysfunction in muscle are frequently seen. Underlying mutations are found in TAZ and lead to defective cardiolipin remodeling.Here, we report atypical clinical manifestations of TAZ mutations in two male patients initially presenting with growth retardation and very mild skeletal myopathy. As other phenotypic hallmarks were missing, Barth syndrome had not been suspected in these patients. One of them has been incidentally diagnosed in the frame of an in-depth cardiolipin research analysis, while the underlying genetic defect was unexpectedly identified in the second one by exome sequencing. These cases underline that TAZ mutations might well be an underdiagnosed cause of skeletal myopathy and growth retardation and do not necessarily manifest with the full clinical picture of Barth syndrome.


Evolutionary structure prediction and electronic properties of indium oxide nanoclusters.
Indium sesquioxide is widely used as a transparent conducting oxide in modern optoelectronic devices; the rising cost of indium has generated interest in the nanoscale properties of In(2)O(3), and questions arise as to the nature of its physicochemical properties below the bulk regime. We report the stable and metastable stoichiometric clusters of (In(2)O(3))(n), where n = 1-10, as predicted from an evolutionary search within the classical interatomic potential and quantum density functional energy landscapes. In contrast to the paradigm set by ZnO, which favours high symmetry bubble-like structures, the In(2)O(3) nanoclusters are found to tend towards dense, low symmetry structures approaching the bulk system at remarkably small molecular masses. Electronic characterisation is performed at the hybrid density functional and many-body GW levels to obtain accurate predictions of the spectroscopic properties, with mean values of the ionisation potentials and electron affinities calculated as 7.7 and 1.7 eV, respectively.


Semantic based concept differential retrieval & equivalence detection in clinical terms version 3 (Read Codes).
Modern clinical terminologies are required to provide a large corpus of concepts to cover the complexity of medicine. It is well recognised that sufficient scalability is likely to be achieved only with those schemes that can build post-coordinated constructs compositionally. Clinical Terms Version 3 (Read Codes) uses a system of templates to both express the semantic definition (atoms) of concepts and to allow qualification of core concepts with additional detail. This common mechanism for expressing both intrinsic semantic information and additional information allows both pre- and post-coordinated concepts to be retrieved from different perspectives and to detect equivalence between alternative representations of the same concept. The practical application and experience of such an approach is described in relation to a live clinical database (Diabeta). The merits of such an approach are outlined and its relationship to other documented mechanisms outlined.


A universal and label-free impedimetric biosensing platform for discrimination of single nucleotide substitutions in long nucleic acid strands.
We report a label-free universal biosensing platform for highly selective detection of long nucleic acid strands. The sensor consists of an electrode-immobilized universal stem-loop (USL) probe and two adaptor strands that form a 4J structure in the presence of a specific DNA/RNA analyte. The sensor was characterized by electrochemical impedance spectroscopy (EIS) using K3[Fe(CN)6]/K4[Fe(CN)6] redox couple in solution. An increase in charge transfer resistance (RCT) was observed upon 4J structure formation, the value of which depends on the analyte length. Cyclic voltammetry (CV) was used to further characterize the sensor and monitor the electrochemical reaction in conjunction with thickness measurements of the mixed DNA monolayer obtained using spectroscopic ellipsometry. In addition, the electron transfer was calculated at the electrode/electrolyte interface using a rotating disk electrode. Limits of detection in the femtomolar range were achieved for nucleic acid targets of different lengths (22 nt, 60 nt, 200 nt). The sensor produced only a background signal in the presence of single base mismatched analytes, even in hundred times excess in concentration. This label-free and highly selective biosensing platform is versatile and can be used for universal detection of nucleic acids of varied lengths which could revolutionize point of care diagnostics for applications such as bacterial or cancer screening.


Lateral transfers of serine hydroxymethyltransferase (glyA) and UDP-N-acetylglucosamine enolpyruvyl transferase (murA) genes from free-living Actinobacteria to the parasitic chlamydiae.
The chlamydiae are important human and animal pathogens which form a phylogentically distinct lineage within the Bacteria. There is evidence that some genes in these obligate intracellular parasites have undergone lateral exchange with other free-living organisms. In the present work, we describe two interesting cases of lateral gene transfer between chlamydiae and actinobacteria, which have been identified based on the shared presence of conserved inserts in two important proteins. In the enzyme serine hydroxymethyltransferase (SHMT or GlyA protein), which links amino acid and nucleotide metabolisms by generating the key intermediate for one-carbon transfer reactions, two conserved inserts of 3 and 31 amino acids (aa) are uniquely present in various chlamydiae species as well as in a subset of Actinobacteria and in the Treponema species. Similarly, in the enzyme UDP-N-acetylglucosamine enolpyruvyl transferase (MurA), which is involved in the synthesis of cell wall peptidoglycan, a 16-aa conserved insert is specifically present in various sequenced chlamydiae and a subset of actinobacteria (i.e., Streptomyces, Actinomyces, Tropheryma, Bifidobacterium, Leifsonia, Arthrobacter, and Brevibacterium). To determine the phylogenetic depths of the GlyA and MurA inserts, the fragments of these genes from two chlamydiae-like species, Simkania negevensis and Waddlia chondrophila, were PCR amplified and sequenced. The presence of the corresponding inserts in both these species strongly indicates that these inserts are distinctive characteristics of the Chlamydiales order. In phylogenetic trees based on GlyA and MurA protein sequences, the chlamydiae species (and also the Treponema species in the case of GlyA) branched with a high affinity with various insert-containing actinobacteria within a clade of other actinobacteria. These results provide strong evidence that the shared presence of these indels in these bacteria is very likely a consequence of ancient lateral gene transfers from actinobacteria to chlamydiae. Pairwise sequence identity and the branching pattern of the GlyA homologues in the phylogenetic tree indicates that the glyA gene was initially transferred from an actinobacteria to an ancestor of the Treponema genus and from there it was acquired by the common ancestor of the Chlamydiales.


The NADPH-dependent oxidase of phagocytes.
Polymorphonuclear leukocytes (PMNs) represent a prominent cellular element in the innate immune system, serving to ingest exogenous particles and microbes and to kill phagocytosed microorganisms. The microbicidal activity of PMNs depends on the interactions of a broad array of potent systems, including relatively stable degradative proteins as well as labile reactive radicals. These systems can be categorized as oxygen-dependent and nonoxidative mechanisms, although the physiologically relative activity depends on the precisely orchestrated interplay between both systems. The enzyme complex responsible for the activity of the oxygen-dependent system is the respiratory burst oxidase and its important contribution to host defense is best illustrated by the frequent and severe infections seen in individuals whose PMNs lack oxidase activity, namely patients with chronic granulomatous disease (CGD). Multiple elements comprise the oxygen-dependent system, and significant advances have been made in the past decade in understanding the protein components of the respiratory burst oxidase, their subcellular distribution in resting PMNs, and their agonist-dependent assembly into a functional system at phagosomal and plasma membranes. In parallel, substantial insights into the molecular bases of CGD have likewise been made. Nonetheless there remain significant gaps in our understanding of the precise functional contributions of particular components of the system, the molecular mechanisms that regulate their coordinated assembly, and the role of related proteins in nonphagocytic cells.


Control of cell number in the bed nucleus of the stria terminalis of mice: role of testosterone metabolites and estrogen receptor subtypes.
The bed nucleus of the stria terminalis (BNST) exhibits several sex differences that may be related to male sexual behavior and gender identity. In mice and rats, sex differences in the principal nucleus of the BNST (BNSTp) are due to sexually dimorphic cell death during perinatal life. Although testosterone treatment of newborn female rats increases BNSTp cell number, the relevant hormone metabolite(s) are not known, and the effect of testosterone on the development of BNSTp cell number in mice has not been examined. To identify the sex hormone metabolites and receptors controlling cell number, volume, and cell size in the BNSTp of mice. In the first experiment, C57BL/6J male mice were injected on the day of birth with peanut oil; females were injected with testosterone propionate (TP), estradiol benzoate (EB), dihydrotestosterone propionate (DHTP), or oil alone, and the BNSTp of all animals was examined in adulthood. In the second experiment, to compare effects of EB to the effects of estrogen receptor subtype specific agonists, newborn female mice were injected with EB, propyl-pyrazole-triol (PPT, a selective estrogen receptor alpha [ERalpha] agonist), or diarylpropionitrile (DPN, a selective estrogen receptor beta [ERbeta] agonist). Nuclear volume measurements and stereological cell counts in the BNSTp in adulthood. TP treatment of newborn females completely masculinized both BNSTp volume and cell number. EB masculinized neuron number, whereas DHTP had no effect on volume or cell number. In the second experiment, EB again fully masculinized neuron number in the BNSTp and in this study also masculinized BNSTp volume. PPT and DPN each significantly increased cell number, but neither completely mimicked the effects of EB. We conclude that estrogenic metabolites of testosterone control sexually dimorphic cell survival in the BNSTp and that activation of both ERalpha and ERbeta may be required for complete masculinization of this brain region.


Automated counting of bacterial colony forming units on agar plates.
Manual counting of bacterial colony forming units (CFUs) on agar plates is laborious and error-prone. We therefore implemented a colony counting system with a novel segmentation algorithm to discriminate bacterial colonies from blood and other agar plates.A colony counter hardware was designed and a novel segmentation algorithm was written in MATLAB. In brief, pre-processing with Top-Hat-filtering to obtain a uniform background was followed by the segmentation step, during which the colony images were extracted from the blood agar and individual colonies were separated. A Bayes classifier was then applied to count the final number of bacterial colonies as some of the colonies could still be concatenated to form larger groups. To assess accuracy and performance of the colony counter, we tested automated colony counting of different agar plates with known CFU numbers of S. pneumoniae, P. aeruginosa and M. catarrhalis and showed excellent performance.


In silico-based vaccine design against Ebola virus glycoprotein.
Ebola virus (EBOV) is one of the lethal viruses, causing more than 24 epidemic outbreaks to date. Despite having available molecular knowledge of this virus, no definite vaccine or other remedial agents have been developed yet for the management and avoidance of EBOV infections in humans. Disclosing this, the present study described an epitope-based peptide vaccine against EBOV, using a combination of B-cell and T-cell epitope predictions, followed by molecular docking and molecular dynamics simulation approach. Here, protein sequences of all glycoproteins of EBOV were collected and examined via in silico methods to determine the most immunogenic protein. From the identified antigenic protein, the peptide region ranging from 186 to 220 and the sequence HKEGAFFLY from the positions of 154-162 were considered the most potential B-cell and T-cell epitopes, correspondingly. Moreover, this peptide (HKEGAFFLY) interacted with HLA-A*32:15 with the highest binding energy and stability, and also a good conservancy of 83.85% with maximum population coverage. The results imply that the designed epitopes could manifest vigorous enduring defensive immunity against EBOV.


Staged cardiac transplantation. Total artificial heart or ventricular-assist pump?
Because of donor organ unavailability, staged cardiac transplantation has been performed in eight patients with The Pennsylvania State University pneumatic total artificial heart (two patients) or with the Pierce-Donachy ventricular-assist pump (six patients). Of the six patients who received the ventricular-assist pump, four received cardiac allografts after 3, 11, 21, and 31 days of pump support, respectively. Two patients died before transplantation; the causes of death were non-device-related complications. One additional patient died of Pseudomonas sepsis after staged cardiac transplantation. The remaining three patients are alive and have been followed up for as long as 2 years after staged cardiac transplantation. Of the two patients who were supported with the total artificial heart, one underwent staged cardiac transplantation after 11 days of support. Unfortunately, this patient succumbed to fungal sepsis 17 days later. The remaining patient, who received the total artificial heart after rejection of a transplanted heart, expired 379 days later before a suitable donor organ could be located. These experiences indicate that 1) the ventricular-assist pump and total artificial heart can provide reasonably safe effective circulatory support until a patient's overall physiological status is optimal, until a donor organ can be located for transplantation, or both; 2) there is a need for short-, intermediate-, and long-term support system capabilities; and 3) regardless of the patients' underlying pathology (ischemic versus nonischemic cardiomyopathy), in most instances, the simpler external ventricular-assist pump is capable of satisfactory hemodynamic circulatory assistance.


Energy compensation and adiposity in humans.
Understanding the impacts of activity on energy balance is crucial. Increasing levels of activity may bring diminishing returns in energy expenditure because of compensatory responses in non-activity energy expenditures.1-3 This suggestion has profound implications for both the evolution of metabolism and human health. It implies that a long-term increase in activity does not directly translate into an increase in total energy expenditure (TEE) because other components of TEE may decrease in response-energy compensation. We used the largest dataset compiled on adult TEE and basal energy expenditure (BEE) (n = 1,754) of people living normal lives to find that energy compensation by a typical human averages 28% due to reduced BEE; this suggests that only 72% of the extra calories we burn from additional activity translates into extra calories burned that day. Moreover, the degree of energy compensation varied considerably between people of different body compositions. This association between compensation and adiposity could be due to among-individual differences in compensation: people who compensate more may be more likely to accumulate body fat. Alternatively, the process might occur within individuals: as we get fatter, our body might compensate more strongly for the calories burned during activity, making losing fat progressively more difficult. Determining the causality of the relationship between energy compensation and adiposity will be key to improving public health strategies regarding obesity.


Internet treatment for depression: a randomized controlled trial comparing clinician vs. technician assistance.
Internet-based cognitive behavioural therapy (iCBT) for depression is effective when guided by a clinician, less so if unguided. Would guidance from a technician be as effective as guidance from a clinician? Randomized controlled non-inferiority trial comparing three groups: Clinician-assisted vs. technician-assisted vs. delayed treatment. Community-based volunteers applied to the VirtualClinic (www.virtualclinic.org.au) research program, and 141 participants with major depressive disorder were randomized. Participants in the clinician- and technician-assisted groups received access to an iCBT program for depression comprising 6 online lessons, weekly homework assignments, and weekly supportive contact over a treatment period of 8 weeks. Participants in the clinician-assisted group also received access to a moderated online discussion forum. The main outcome measures were the Beck Depression Inventory (BDI-II) and the Patient Health QUESTIONnaire-9 Item (PHQ-9). Completion rates were high, and at post-treatment, both treatment groups reduced scores on the BDI-II (p<0.001) and PHQ-9 (p<0.001) compared to the delayed treatment group but did not differ from each other. Within group effect sizes on the BDI-II were 1.27 and 1.20 for the clinician- and technician-assisted groups respectively, and on the PHQ-9, were 1.54 and 1.60 respectively. At 4-month follow-up participants in the technician group had made further improvements and had significantly lower scores on the PHQ-9 than those in the clinician group. A total of approximately 60 minutes of clinician or technician time was required per participant during the 8-week treatment program. Both clinician- and technician-assisted treatment resulted in large effect sizes and clinically significant improvements comparable to those associated with face-to-face treatment, while a delayed treatment control group did not improve. These results provide support for large scale trials to determine the clinical effectiveness and acceptability of technician-assisted iCBT programs for depression. This form of treatment has potential to increase the capacity of existing mental health services. Australian New Zealand Clinical Trials Registry ACTRN12609000559213.


[Coccidioidomycosis in Argentina, 1892-2009].
Clinical cases of coccidioidomycosis are rare in Argentina and are generally found in the large arid precordilleran area of the country. This study aims to perform a retrospective review of all coccidioidomycosis cases documented in the country from 1892 to 2009, and to describe those occurring in the last 4 years. One hundred and twenty eight cases were documented in the 117 year-period. Since the original description of the disease in 1892 until 1939, only 6 cases were registered; between 1940 and 1999, 59 (6-14/10 yrs) and the remaining 63 (49% of total cases) occurred in the last decade. The median age of 34 patients registered in 2006-2009 was 31 years (range: 7-89), male/female ratio was 1.3:1 and 12 patients were immunocompromised. Twenty-six cases were confirmed by direct microscopy and/or culture whereas the remaining ones by serology. All isolates were identified as Coccidioides posadasii. Thirty patients lived in a vast geographic region with epicenter in Catamarca Valley. Between 2006 and 2009, annual disease incidence rates in Catamarca Province increased from historical values below 0.5/100,000 to 2/100,000 inhabitants. Such increase suggests an emergency of coccidioidomycosis in that region.


Face and gaze perception in borderline personality disorder: An electrical neuroimaging study.
Humans are sensitive to gaze direction from early life, and gaze has social and affective values. Borderline personality disorder (BPD) is a clinical condition characterized by emotional dysregulation and enhanced sensitivity to affective and social cues. In this study we wanted to investigate the temporal-spatial dynamics of spontaneous gaze processing in BPD. We used a 2-back-working-memory task, in which neutral faces with direct and averted gaze were presented. Gaze was used as an emotional modulator of event-related-potentials to faces. High density EEG data were acquired in 19 females with BPD and 19 healthy women, and analyzed with a spatio-temporal microstates analysis approach. Independently of gaze direction, BPD patients showed altered N170 and P200 topographies for neutral faces. Source localization revealed that the anterior cingulate and other prefrontal regions were abnormally activated during the N170 component related to face encoding, while middle temporal deactivations were observed during the P200 component. Post-task affective ratings showed that BPD patients had difficulty to disambiguate neutral gaze. This study provides first evidence for an early neural bias toward neutral faces in BPD independent of gaze direction and also suggests the importance of considering basic aspects of social cognition in identifying biological risk factors of BPD.


Hospital efficiency: how to spend less maintaining quality?
The recent global economic crisis is pushing governments worldwide to obtain a more explicit and urgent rationing of resources. The purpose of this study is to provide, through Data Envelopment Analysis (DEA), a methodological framework useful for investigating technical efficiency of hospital care. To validate such framework, we compared 50 Italian public hospital trusts (AOs) to identify relative efficient using inputs and outputs from national databases. We also evaluated if, and how, efficiency is affected by various exogenous factors. On average, Italian AOs had an efficiency score of 77% (SD 0.12). Tobit regression model identified a positive association between efficiency and a lower case-mix index, being in the north of Italy, in a region with fiscal autonomy, with a higher public and a lower private expenditure on health as percentage of GDP. DEA may provide useful and especially objective information regarding the technical efficiency of hospital care and support hospital management and policy makers' decisions.


Effects of Tyrosine Kinase Inhibitor-masitinib Mesylate on Canine Mammary Tumour Cell Lines.
Masitinib mesylate, a selective tyrosine kinase inhibitor of the c-KIT receptor, is used for the treatment of mast cell tumours in dogs. Masitinib has previously been investigated in various cancers; however, its potential anticancer effect in canine mammary tumours (CMTs) is unknown. In the present paper, we investigated the antiproliferative effect of masitinib in CMT cells and its possible mechanisms of action. The effect of masitinib on the proliferation of CMT-U27 and CMT-U309 cells was assessed by MTT assay and DNA fragmentation. Flow cytometric analysis was used to measure the effect of masitinib on apoptosis and the cell cycle. Additionally, vascular endothelial growth factor levels (VEGF) were measured, and the proliferation marker Ki-67 was visualised in immunocytochemical stainings in CMT cells. Treatment with masitinib inhibited the proliferation of CMT cells in a concentration-dependent manner. Maximal apoptotic activity and DNA fragmentation were observed at approximately IC50 of masitinib in both cell lines. In addition, cell cycle distribution was altered and VEGF levels and Ki-67 proliferation indices were decreased in masitinib-treated cells in comparison with control cells. In this study, masitinib suppressed cell proliferation concomitantly via induction of apoptosis and cell cycle arrest by decreasing VEGF levels and the Ki-67 proliferation index in CMT-U27 and CMT-U309 cells in vitro, suggesting its potential as a therapeutic tool in the clinical setting of mammary cancer treatment in dogs.


Focal Adhesion Kinase (FAK) Over-Expression and Prognostic Implication in Pediatric Hepatocellular Carcinoma.
Focal adhesion kinase (FAK) is over-expressed and is correlated with aggressiveness in adult hepatocellular carcinoma (HCC). Inhibition of FAK decreases HCC invasiveness by down-regulating Enhancer of Zeste homolog 2 (EZH2), an epigenetic controller, that acts in transcriptional repression of a large number of genes via histone 3 methylation of lysine 27 (H3K27me3). Here, we investigated the hepatic expression of total FAK, EZH2, H3K27me3, and proliferating cell nuclear antigen (PCNA) in 17 pediatric HCCs and 8 healthy livers (CTRL). Quantitative imaging analysis showed that FAK gene/protein expression is up-regulated in HCCs compared to CTRL and, among tumor samples the levels of this gene/protein are significantly higher in cirrhotic HCCs than in a healthy milieu. Accordingly, the protein levels of EZH2 were also significantly increased in HCCs from a cirrhotic background. Intriguingly, the protein expression of FAK, EZH2, and PCNA significantly inversely correlated with tumor size. Finally, in HCC samples, mainly in cirrhotic background, the up-regulation of FAK gene positively correlated with that observed in β-Catenin gene. Conclusion: FAK gene/protein is over-expressed in pediatric HCCs concomitantly to EZH2 protein and β-Catenin gene, with a more significant up-regulation in a cirrhotic background. This triad of interactors deserves further investigations for translational application.


Model-based iterative reconstruction technique for ultralow-dose chest CT: comparison of pulmonary nodule detectability with the adaptive statistical iterative reconstruction technique.
The purpose of this study was to evaluate whether model-based iterative reconstruction (MBIR) enables dose reduction over adaptive iterative reconstruction (ASIR) while maintaining diagnostic performance. In this institutional review board-approved and Health Insurance Portability and Accountability Act-compliant study, 59 patients (mean [SD] age, 64.7 [13.4] years) gave informed consent to undergo reference-, low-, and ultralow-dose chest computed tomography (CT) with 64-row multidetector CT. The reference- and low-dose CT involved the use of automatic tube current modulation with fixed noise indices (31.5 and 70.44 at 0.625 mm, respectively) and were reconstructed with 50% ASIR-filtered back projection blending. The ultralow-dose CT was acquired with a fixed tube current-time product of 5 mA s and reconstructed with MBIR. Two radiologists evaluated 2.5- and 0.625-mm-slice-thick axial images from low-dose ASIR and ultralow-dose MBIR, recorded the pattern of each nodule candidate, and assigned each a confidence score. A reference standard was established by a consensus panel of 2 different radiologists, who identified 84 noncalcified nodules with diameters of 4 mm or greater on reference-dose ASIR (ground-glass opacity, n = 18; partly solid, n = 11; solid, n = 55). Sensitivity in nodule detection was assessed using the McNemar test. Jackknife alternative free-response receiver operating characteristic (JAFROC) analysis was applied to assess the results including confidence scores. Compared with the low-dose CT, a 78.1% decrease in dose-length product was seen with the ultralow-dose CT. No significant differences were observed between the low-dose ASIR and the ultralow-dose MBIR for overall nodule detection in sensitivity (P = 0.48-0.69) or the JAFROC analysis (P = 0.57). Likewise, no significant differences were seen for ground-glass opacity, partly solid, or solid nodule detection in sensitivity (P = 0.08-0.65) or the JAFROC analysis (P = 0.21-0.90). Model-based iterative reconstruction enables nearly an 80% reduction in radiation dose for chest CT from a low-dose level to an ultralow-dose level, without affecting nodule detectability.


GLP-1 Receptor Agonists and Kidney Protection.
Type 2 diabetes mellitus (T2DM) is the leading cause of chronic kidney disease (CKD). Diabetic nephropathy (DN) is determined by specific pathological structural and functional alterations of the kidneys in patients with diabetes, and its clinical manifestations are albuminuria and decline of glomerular filtration rate (GFR). Apart from renin-angiotensin-aldosterone system (RAAS) inhibitors, no other drugs are currently available as therapy for diabetic kidney disease (DKD). Glucagon-like peptide-1 receptor (GLP-1R) agonists are a new class of anti-hyperglycemic drugs which have been demonstrated to prevent the onset of macroalbuminuria and reduce the decline of GFR in diabetic patients. These drugs may exert their beneficial actions on the kidneys through blood glucose- and blood pressure (BP)-lowering effects, reduction of insulin levels and weight loss. Clinical benefits of GLP-1R agonists were acknowledged due to data from large randomized phase III clinical trials conducted to assess their cardiovascular(CV) safety. These drugs improved renal biomarkers in placebo-controlled clinical studies, with effects supposed to be independent of the actions on glycemic control. In this review, we will focus on the actions of GLP-1R agonists on glucose metabolism and kidney physiology, and evaluate direct and indirect mechanisms through which these drugs may confer renal protection.


Socioeconomic status and smokers' number of smoking friends: findings from the International Tobacco Control (ITC) Four Country Survey.
Smoking rates are higher among low socioeconomic (SES) groups, and there is evidence that inequalities in smoking are widening over time in many countries. Low SES smokers may be more likely to smoke and less likely to quit because smoking is heavily concentrated in their social contexts. This study investigated whether low SES smokers (1) have more smoking friends, and (2) are more likely to gain and less likely to lose smoking friends over time. Correlates of having more smoking friends and gaining or losing smoking friends were also considered. Respondents included 6321 adult current smokers (at recruitment) from Wave 1 (2002) and Wave 2 (2003) of the International Tobacco Control Project (ITC) Four Country Survey, a nationally representative longitudinal cohort survey of smokers in Australia, Canada, UK, and US. Low SES smokers reported more smoking friends than moderate and high SES smokers. Low SES smokers were also more likely to gain smoking friends over time compared with high SES smokers. Smokers who were male, younger, and lived with other smokers reported more smoking friends, and were also more likely to gain and less likely to lose smoking friends. Smoking behaviours, such as higher nicotine dependence were related to reporting more smoking friends, but not to losing or gain smoking friends. Smoking is highly concentrated in the social networks of lower SES smokers and this concentration may be increasing over time. Cessation interventions should consider how the structure of low SES smokers' social networks affects quitting.


Contribution to Family, Friends, School, and Community Is Associated With Fewer Depression Symptoms in Adolescents - Mediated by Self-Regulation and Academic Performance.
The tendency to get involved in helping one's family, friends, school, and community has many potential benefits such as greater compassion, concern for others, and social responsibility. Research interest in the benefits of contribution in adolescents has increased recently, but there are not many studies examining the effect of contribution on adolescents' mental health. The present study focused on whether the contribution is associated with fewer self-rated depression symptoms in adolescents. We further tested whether self-regulation and academic performance can have a mediating role in this association. A total of 423 secondary school students (233 female) from eastern Croatia participated in the study. Mean age was 16.78 (SD = 1.21). Students completed measures of self-regulation, depression symptoms, and contribution (helping one's family, friends, or neighbors, mentoring peers, volunteering in one's community, and participating in school organizations or boards), and gave information about age, gender, and academic performance. A hierarchical regression analysis revealed that contribution, self-regulation, and academic performance were related with lower levels of self-rated depression symptoms. Furthermore, mediation analysis indicated a significant indirect effect through two mediators, self-regulation and academic performance, which was stronger than a path containing only self-regulation. Academic performance alone was not a significant mediator. Our findings suggest that contribution could protect against depression by promoting self-regulation, leading to higher academic performance, and consequently fewer depression symptoms.


Potent stimulation of transcription-coupled DNA supercoiling by sequence-specific DNA-binding proteins.
Transcription by RNA polymerase can stimulate localized DNA supercoiling in Escherichia coli. In vivo, there is extensive experimental support for a "twin-domain" model in which positive DNA supercoils are generated ahead of a translocating RNA polymerase complex and negative supercoils are formed behind it. Negative supercoils accumulate in the template DNA because the positive supercoils are preferentially removed by cellular topoisomerase action. Yet, in vitro, clear and convincing support for the twin-domain mechanism has been lacking. In this article, we reconcile this inconsistency by showing that, in a defined in vitro system with plasmid DNA templates, a variety of sequence-specific DNA-binding proteins, such as the bacteriophage lambda O replication initiator or the E. coli lactose or galactose repressors, strikingly stimulate transcription-coupled DNA supercoiling. We demonstrate further that this stimulation requires the presence in the DNA template of a recognition sequence for the relevant DNA-binding protein and depends on the production of long RNA chains by an RNA polymerase. Our data are most consistent with a model in which specific DNA-binding proteins facilitate a twin-domain mechanism to enhance DNA supercoiling during transcription. More precisely, we suggest that some nucleoprotein complexes, perhaps those that contain sharply bent DNA, can form barriers that impede the diffusion and merger of independent chromosomal supercoil domains. Localization of DNA supercoils by nucleoprotein complexes may serve as a general mechanism for modulating DNA transactions that are sensitive to DNA superhelicity.


In vitro analysis of oocyte cumulus complex pickup rate in the hamster Mesocricetus auratus.
In mammals, the oocyte and its surrounding cumulus cells constitute on oocyte cumulus complex (OCC). During ovulation, OCCs are extruded into the peritoneal or bursal cavity, depending on the species, and are then rapidly picked up by the fimbria on the outer surface of the oviductal infundibulum and transported to the ampulla, where fertilization occurs. We developed a method to measure OCC pickup rates quantitatively in vitro, and we used this method to evaluate the effects of viscosity and temperature on pickup rates. Hamster infundibula are placed in a holding pipette in a chamber modified to study OCC pickup. Ciliary beat frequencies (CBF) can be measured in the same preparation. Pickup rates vary depending on the pathway on which the OCC travels over the surface of the infundibulum; however, rates for a given pathway are very consistent. The average pickup rate at room temperature calculated from three different pathways/infundibulum was 55.2 +/- 10.6 microns/sec. Both rates between infundibula from the same female and rates among infundibula from different females were in most cases similar. Preparations preincubated in vitro for 2.75 hr produced rates similar to nonpreincubated samples, while longer preincubation resulted in decreased rates. Inclusion of Ficoll in culture medium to increase viscosity caused a concentration-dependent decrease in both OCC pickup rate and in CBF. However, a significant decrease in OCC pickup rate was only observed at viscosities higher than those found in bursal fluid. When trials were run at physiological temperature (36.4 degrees C) rather ambient temperature, rates increased to 136.7 +/- 29.9 (SD) microns/sec. Linear regression analysis demonstrated a strong positive correlation (r = 0.94) between OCC pickup rate and temperature. The OCC pickup rate assay can be used experimentally, and should be valuable in evaluating factors that affect rate and in studies dealing with the mechanism of OCC pickup.


Sir Ludwig Guttmann: his neurology research and his role in the treatment of peripheral nerve injuries, 1939-1944.
Ludwig Guttmann spent five crucial years in Oxford between 1939 and 1944, carrying out fundamental research in peripheral nerve regeneration and the rehabilitation of patients with peripheral nerve injuries. He worked with Peter Medawar, John Zachary Young, Graham Weddell, Ernst Gutmann and others. He dismissed this period of his life, but the experience he gained was critical for his subsequent career in rehabilitating spinal injury patients.


Digital Natives' Preferences on Mobile Artificial Intelligence Apps for Skin Cancer Diagnostics: Survey Study.
Artificial intelligence (AI) has shown potential to improve diagnostics of various diseases, especially for early detection of skin cancer. Studies have yet to investigate the clear application of AI technology in clinical practice or determine the added value for younger user groups. Translation of AI-based diagnostic tools can only be successful if they are accepted by potential users. Young adults as digital natives may offer the greatest potential for successful implementation of AI into clinical practice, while at the same time, representing the future generation of skin cancer screening participants. We conducted an anonymous online survey to examine how and to what extent individuals are willing to accept AI-based mobile apps for skin cancer diagnostics. We evaluated preferences and relative influences of concerns, with a focus on younger age groups. We recruited participants below 35 years of age using three social media channels-Facebook, LinkedIn, and Xing. Descriptive analysis and statistical tests were performed to evaluate participants' attitudes toward mobile apps for skin examination. We integrated an adaptive choice-based conjoint to assess participants' preferences. We evaluated potential concerns using maximum difference scaling. We included 728 participants in the analysis. The majority of participants (66.5%, 484/728; 95% CI 0.631-0.699) expressed a positive attitude toward the use of AI-based apps. In particular, participants residing in big cities or small towns (P=.02) and individuals that were familiar with the use of health or fitness apps (P=.02) were significantly more open to mobile diagnostic systems. Hierarchical Bayes estimation of the preferences of participants with a positive attitude (n=484) revealed that the use of mobile apps as an assistance system was preferred. Participants ruled out app versions with an accuracy of ≤65%, apps using data storage without encryption, and systems that did not provide background information about the decision-making process. However, participants did not mind their data being used anonymously for research purposes, nor did they object to the inclusion of clinical patient information in the decision-making process. Maximum difference scaling analysis for the negative-minded participant group (n=244) showed that data security, insufficient trust in the app, and lack of personal interaction represented the dominant concerns with respect to app use. The majority of potential future users below 35 years of age were ready to accept AI-based diagnostic solutions for early detection of skin cancer. However, for translation into clinical practice, the participants' demands for increased transparency and explainability of AI-based tools seem to be critical. Altogether, digital natives between 18 and 24 years and between 25 and 34 years of age expressed similar preferences and concerns when compared both to each other and to results obtained by previous studies that included other age groups.


Effective treatment of single-stage revision using intra-articular antibiotic infusion for culture-negative prosthetic joint infection.
In the absence of an identified organism, single-stage revision is contraindicated in prosthetic joint infection (PJI). However, no studies have examined the use of intra-articular antibiotics in combination with single-stage revision in these cases. In this study, we present the results of single-stage revision using intra-articular antibiotic infusion for treating culture-negative (CN) PJI. A retrospective analysis between 2009 and 2016 included 51 patients with CN PJI who underwent single-stage revision using intra-articular antibiotic infusion; these were compared with 192 culture-positive (CP) patients. CN patients were treated according to a protocol including intravenous vancomycin and a direct intra-articular infusion of imipenem and vancomycin alternately used in the morning and afternoon. In the CP patients, pathogen-sensitive intravenous (IV) antibiotics were administered for a mean of 16 days (12 to 21), and for resistant cases, additional intra-articular antibiotics were used. The infection healing rate, Harris Hip Score (HHS), and Hospital for Special Surgery (HSS) knee score were compared between CN and CP groups. Of 51 CN patients, 46 (90.2%) required no additional medical treatment for recurrent infection at a mean of 53.2 months (24 to 72) of follow-up. Impaired kidney function occurred in two patients, and one patient had a local skin rash. No significant difference in the infection control rate was observed between CN and CP PJIs (90.2% (46/51) versus 94.3% (181/192); p = 0.297). The HHS of the CN group showed no substantial difference from that of CP cases (79 versus 81; p = 0.359). However, the CN group showed a mean HSS inferior to that of the CP group (76 versus 80; p = 0.027). Single-stage revision with direct intra-articular antibiotic infusion can be effective in treating CN PJI, and can achieve an infection control rate similar to that in CP patients. However, in view of systemic toxicity, local adverse reactions, and higher costs, additional strong evidence is needed to verify these treatment regimens. Cite this article: Bone Joint J 2020;102-B(3):336-344.


Language-general biases and language-specific experience contribute to phonological detail in toddlers' word representations.
Although toddlers in their 2nd year of life generally have phonologically detailed representations of words, a consistent lack of sensitivity to certain kinds of phonological changes has been reported. The origin of these insensitivities is poorly understood, and uncovering their cause is crucial for obtaining a complete picture of early phonological development. The present study explored the origins of the insensitivity to the change from coronal to labial consonants. In cross-linguistic research, we assessed to what extent this insensitivity is language-specific (or would show both in learners of Dutch and a very different language like Japanese), and contrast/direction-specific to the coronal-to-labial change (or would also extend to the coronal-to-dorsal change). We measured Dutch and Japanese 18-month-old toddlers' sensitivity to labial and dorsal mispronunciations of newly learned coronal-initial words. Both Dutch and Japanese toddlers showed reduced sensitivity to the coronal-to-labial change, although this effect was more pronounced in Dutch toddlers. The lack of sensitivity was also specific to the coronal-to-labial change because toddlers from both language backgrounds were highly sensitive to dorsal mispronunciations. Combined with results from previous studies, the present outcomes are most consistent with an early, language-general bias specific to the coronal-to-labial change, which is modified by the properties of toddlers' early, language-specific lexicon.


Cultural Differences in Stress-Related Psychological, Nutrition, Physical Activity and Oral Health Factors of Professors.
With the aim to explore cultural differences in stress-related psychological, nutrition, physical activity, and oral health factors between Spanish and Latin American professors, we analysed stress-related factors in 598 professors (39.9% male, 60.1% female, 41.3 ± 9.8 years) by a collection of questionnaires, which involved psychological, nutritional, physical activity and oral health items. Results showed how Spanish professors presented significantly (p ≤ 0.05) higher scores than Latin American professors in perceived stress (Spanish: 21.40 ± 4.32 vs. Latin American: 20.36 ± 4.31), teaching stress (Spanish: 6.59 ± 2.28 vs. Latin American: 6.00 ± 2.99) and neuroticism (Spanish: 5.40 ± 2.10 vs. Latin American: 4.58 ± 1.72). Spanish professors also showed healthier nutritional and physical activity habits than their Latin American counterparts, presenting higher consumption of milk products and a higher numbers of meals per day, greater weekly meat and fish consumption and higher weekly resistance training, as well as less eating between hours and snacking consumption. Nevertheless, Spanish professors brushed their teeth less and showed a higher smoking habit than Latin American professors. We concluded that there were cultural differences between Spanish and Latin American professors. In the present research, Spanish professors showed significantly higher burnout levels, teaching stress, perceived stress, and neuroticism than Latin American professors, and several differences were also found around health behaviours. These differences in perceived stress, teaching stress and burnout syndrome may be due to the habituation process of Latin American professors, and probably are associated with a higher stressful and demanding socio-cultural context.


The deaf mouse mutant whirler suggests a role for whirlin in actin filament dynamics and stereocilia development.
Stereocilia, finger-like projections forming the hair bundle on the apical surface of sensory hair cells in the cochlea, are responsible for mechanosensation and ultimately the perception of sound. The actin cytoskeleton of the stereocilia contains hundreds of tightly cross-linked parallel actin filaments in a paracrystalline array and it is vital for their function. Although several genes have been identified and associated with stereocilia development, the molecular mechanisms responsible for stereocilia growth, maintenance and organisation of the hair bundle have not been fully resolved. Here we provide further characterisation of the stereocilia of the whirler mouse mutant. We found that a lack of whirlin protein in whirler mutants results in short stereocilia with larger diameters without a corresponding increase in the number of actin filaments in inner hair cells. However, a decrease in the actin filament packing density was evident in the whirler mutant. The electron-density at the tip of each stereocilium was markedly patchy and irregular in the whirler mutants compared with a uniform band in controls. The outer hair cell stereocilia of the whirler homozygote also showed an increase in diameter and variable heights within bundles. The number of outer hair cell stereocilia was significantly reduced and the centre-to-centre spacing between the stereocilia was greater than in the wildtype. Our findings suggest that whirlin plays an important role in actin filament packing and dynamics during postnatal stereocilium elongation.


Revision of the taxonomic status of type strains of Mesorhizobium loti and reclassification of strain USDA 3471T as the type strain of Mesorhizobiumerdmanii sp. nov. and ATCC 33669T as the type strain of Mesorhizobiumjarvisii sp. nov.
The species Mesorhizobim loti was isolated from nodules of Lotus corniculatus and its type strain deposited in several collections. Some of these type strains, such as those deposited in the USDA and ATCC collections before 1990, are not coincident with the original strain, NZP 2213T, deposited in the NZP culture collection. The analysis of the 16S rRNA gene showed that strains USDA 3471T and ATCC 33669T formed independent branches from that occupied by Mesorhizobium loti NZP 2213T and related to those occupied by Mesorhizobium opportunistum WSM2075T and Mesorhizobium huakuii IFO 15243T, respectively, with 99.9 % similarity in both cases. However, the analysis of concatenated recA, atpD and glnII genes with similarities lower than 96, 98 and 94 %, respectively, between strains USDA 3471T and M. opportunistum WSM2075T and between strains ATCC 33669T and M. huakuii IFO 15243T, indicated that the strains USDA 3471T and ATCC 33669T represent different species of the genus Mesorhizobium. These results were confirmed by DNA-DNA hybridization experiments and phenotypic characterization. Therefore, the two strains were reclassified as representatives of the two species Mesorhizobium erdmanii sp. nov. (type strain USDA 3471T = CECT 8631T = LMG 17826t2T) and Mesorhizobium jarvisii sp. nov. (type strain ATCC 33669T = CECT 8632T = LMG 28313T).


A test of the differential accuracy of the maxillary versus the mandibular dentition in age estimations of immature skeletal remains based on developing tooth length.
Liversidge and colleagues developed a method for predicting the age of immature skeletal remains based on the length of developing teeth. This quantitative method combines dental data from both jaws, except for the permanent lateral incisor, and because there are reasons to suspect that these two types of data are not identical and should not be combined, it raises concerns regarding the accuracy of the technique when applied differently to each jaw. In this study, the differential accuracy of the method was test when applied to the maxillary and mandibular dentition. The test sample is comprised of 57 Portuguese subadult skeletons of known age at death. Results suggest an overall high consistency between estimates obtained from both jaws, but for the permanent dentition only. In the deciduous dentition the age estimates obtained from the maxillary teeth tend to be greater than the age estimates obtained from the mandibular pair, and the differences are significant for the incisors and canine. Additionally, ages obtained from the maxillary deciduous canine also differ significantly from true chronological age. In the permanent dentition there were no differences between the ages provided by both jaws but both the maxillary and mandibular second molars show a significant tendency to underestimate true chronological age. Although this study cannot validate completely the method presented by Liversidge and colleagues, it does provide an important test to its accuracy and calls for further research into its overall performance, particularly with respect to the results obtained from both jaws.


Importance of the number of acid molecules and the strength of the base for double-ion formation in (H2SO4)m x base x (H2O)6 clusters.
Sulfuric acid and water clusters are important for new particle formation in the atmosphere. Recent experimental studies demonstrate that critical clusters in diverse atmospheric environments contain two acid molecules and may also include additional N-containing molecules (i.e., a base). We use first-principles molecular dynamics simulations to show that the presence of two sulfuric acid molecules in (H2SO4)m x base x (H2O)6 clusters is always sufficient to form a double ion, whereas a single acid molecule, even in the presence of a base, is not.


Predicting food waste in households with children: socio-economic and food-related behavior factors.
The consumption phase accounts for approximately half of the food waste generated within the food system. Numerous studies have identified families with children as the primary contributors to food waste. The aims of this paper is to enhance the comprehension of food waste behaviors in households with children by characterizing it and studying how socioeconomic characteristics and food-related behaviors can predict it. A survey was conducted among 806 families with children, categorized by the child's age and family structure. The study utilized descriptive statistics to summarize the food waste behaviors and binary regression to evaluate the predictive abilities of 12 variable related to the socio-economic characteristic, purchase, and preparation behaviors and diet quality factors. Perishable food items, such as fruits, vegetables, cereal-based product, and dairy products, were the primary items wasted in households with children. Two patterns of food waste were identified: inadequate food management leading to small amounts of waste in families with young and middle-aged children, and over-purchasing perishable items leading to waste in other households with children. Household type and purchasing habits were significant predictors, while the purchaser's age and buying channel showed lower predictive capacity. Policies to reduce food waste should prioritize raising awareness among children, promoting good practices at the household level, and creating favorable conditions during purchases. Strategies include enlisting children's participation in meal planning and food preparation as well as limiting the promotion of ultra-processed products and incentivizing the sale of bulk products at supermarket.


Evaluating practice patterns in postnatal management of antenatal hydronephrosis: a national survey of Canadian pediatric urologists and nephrologists.
To ascertain practice patterns of prescribing continuous antibiotic prophylaxis (CAP) and obtaining a voiding cystourethrogram for infants with antenatal hydronephrosis (AHN) by pediatric nephrologists and urologists across Canada. A previously piloted online survey was distributed to members of the Canadian pediatric nephrology and urology associations. Summarized confidential responses were stratified by specialty, AHN grade, and laterality. A total of 88 of 139 responses were received (response rate, 63.3%; 95% confidence interval, 55.0%-71.0%): 46 nephrologists, 39 urologists, and 3 undisclosed. Only 17 of 88 (19.32%; 95% confidence interval, 12.4%-28.8%) reported following standardized AHN protocols. Concern surrounding the development of urinary tract infections was the main deciding factor for prescribing CAP (nephrology, 65.4%; urology, 71.4%). Almost a third of nephrologists (29.6%) recommend CAP for bilateral low-grade AHN compared with 11.4% of urologists (P = .02); in contrast, 73% of nephrologists and 38.2% of urologists (P = .02) offer CAP in the presence of isolated high-grade AHN. In regards to indications for voiding cystourethrogram, 31% of pediatric nephrologists would recommend this test for patients with unilateral low-grade AHN compared with 7.7% of urologists (P < .01), although almost all nephrologists (96.6%) and 69.2% of urologists (P = .02) would obtain this test for patients with unilateral high-grade isolated AHN. Our results show important practice variability between pediatric nephrologists and urologists in the management of children with AHN, which are partially explained by laterality and degree of dilation. This survey reflects the lack of treatment guidelines and supports efforts to obtain high-level evidence to develop management protocols for this common condition.


Suitability evaluation of new endogenous biomarkers for the identification of nitrite-based urine adulteration in mass spectrometry methods.
Urine adulteration to circumvent positive drug testing is a fundamental challenge for toxicological laboratories all over the world. Untargeted mass spectrometry (MS) methods used in metabolomics had previously revealed uric acid (UA), histidine, methylhistidine, and their oxidation products, for example 5-hydroxyisourate (HIU) as potential biomarkers for urine adulteration using potassium nitrite (KNO2 ). These markers should be further evaluated for their reliability, stability, and routine applicability. Influence of KNO2 concentration, urinary pH, reaction time, and stability at room temperature, 4°C, and - 20°C was determined in urine under varying conditions. Analysis was performed after protein precipitation with acetonitrile by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Receiver operating characteristics (ROC) analysis was applied for cut-off evaluation after biomarker quantification (n = 100 per group). Blinded measurements (n = 50) were performed to check the general applicability to identify adulterated samples under routine conditions. The higher the adulterant concentration, the lower the concentrations of histidine, methylhistidine, and UA. In return, amounts of their oxidation products increased. Highest changes were observed under weak acid conditions (pH 4-5). Storage at -20°C ensured sufficient stability for all oxidative markers over one month. ROC evaluated biomarker performance and application to unknown samples revealed satisfying results, with HIU as the most suitable biomarker (positive predictive value (PPV) 100%), followed by UA (PPV 93%). HIU and UA proved suitable markers to identify urine adulteration using KNO2 and are ready for implementation into routine MS procedures.


Relation of plasma β-amyloid, clusterin, and tau with cerebral microbleeds: Framingham Heart Study.
Cerebral microbleeds (CMBs) are associated with higher risk of stroke and dementia, predating clinical diagnosis by several years. CMB are considered markers of cerebral small vessel disease (CSVD): hypertensive (deep CMB) and cerebral amyloid angiopathy (lobar CMB). We related plasma β-Amyloid (40, 42 and their ratio), clusterin, and tau levels to CMB to elucidate their role as biomarkers for the angiopathies represented by CMB. Dementia, stroke, and other neurological disease-free Framingham Heart Study participants with available CMB and biomarker measurements were included. We related biomarker levels (standardized for analyses) to CMB presence overall and stratified by brain topography (any, lobar, deep), using multivariable logistic regression analyses. CMB were observed in 208 (5.7%) participants (mean age 57 years, 54% women). After multivariable adjustment, Aβ1-40 was associated with any CMB (OR (95%CI) 1.20 (0.99, 1.45) P = 0.062)) and lobar CMB (OR (95%CI) 1.33 (1.05, 1.68) P = 0.019), but not with deep CMB. Log-Aβ1-42 levels were not associated with CMB overall. Clusterin was related to mixed CMB (1.70 [1.05, 2.74], P = 0.031). Tau levels were associated with any CMB (OR (95%CI) 1.26 (1.07, 1.49) P = 0.006), lobar CMB (OR (95%CI) 1.26 (1.05, 1.52) P = 0.013), and with deep CMB (OR (95% CI) 1.46 (1.13, 1.89) P = 0.004). We found that plasma Aβ1-40 and Tau are associated with CMB but further studies are needed to confirm their role in hemorrhage prone CSVD represented by CMB and as indicators of ongoing subclinical neuronal injury.


Inhibition of cis-diamminedichloroplatinum secretion by the human kidney with probenecid.
The renal handling of cis-diamminedichloroplatinum (CP) was investigated by measuring the renal clearance of creatinine, inulin, and free platinum in ten cancer patients. Free platinum clearances exceeded the glomerular filtration rate in all time periods. For example, at 1 to 2 hr, the mean clearance of free platinum was 224 +/- 32 (S.E.) ml/min compared to a mean creatinine clearance of 94 +/- 15 ml/min or a mean inulin clearance of 94 +/- 17 ml/min (p less than 0.01), indicating secretion of CP or a metabolite. Seven additional cancer patients were treated with probenecid prior to CP. Fractional platinum clearances, calculated as a ratio of free platinum clearance to creatinine clearance, were reduced significantly in the probenecid-treated group (158 +/- 17%) compared to controls (270 +/- 57%) (p less than 0.03). Fractional platinum clearances, calculated as a ratio of free platinum clearance to inulin clearance, were also significantly reduced in the treated group (154 +/- 14%) compared to controls (271 +/- 47%) (p = 0.04). These results suggest that cisplatin is secreted by the human kidney, and this can be inhibited by probenecid. Such maneuvers may be helpful in improving the therapeutic index of this important chemotherapeutic agent.


Complete genome sequence and transcription profiles of the rock bream iridovirus RBIV-C1.
The family Iridoviridae consists of 5 genera of double-stranded DNA viruses, including the genus Megalocytivirus, which contains species that are important fish pathogens. In a previous study, we isolated the first rock bream iridovirus from China (RBIV-C1) and identified it as a member of the genus Megalocytivirus. In this report, we determined the complete genomic sequence of RBIV-C1 and examined its in vivo expression profiles. The genome of RBIV-C1 is 112333 bp in length, with a GC content of 55% and a coding density of 92%. RBIV-C1 contains 4584 simple sequence repeats, 89.8% of which are distributed among coding regions. A total of 119 potential open reading frames (ORFs) were identified in RBIV-C1, including the 26 core iridovirus genes; 41 ORFs encode proteins that are predicted to be associated with essential biological functions. RBIV-C1 exhibits the highest degree of sequence conservation and colinear arrangement of genes with orange-spotted grouper iridovirus (OSGIV) and rock bream iridovirus (RBIV). The pairwise nucleotide identities are 99.49% between RBIV-C1 and OSGIV and 98.69% between RBIV-C1 and RBIV. Compared to OSGIV, RBIV-C1 contains 11 insertions, 13 deletions, and 103 single nucleotide mutations. Whole-genome transcription analysis showed that following experimental infection of rock bream with RBIV-C1, all but 1 of the 119 ORFs were expressed at different time points and clustered into 3 hierarchical groups based on their expression patterns. These results provide new insights into the genetic nature and gene expression features of megalocytiviruses.


Curcumin as a Therapeutic Agent for Sarcopenia.
Sarcopenia is the progressive loss of muscle mass, strength, and functions as we age. The pathogenesis of sarcopenia is underlined by oxidative stress and inflammation. As such, it is reasonable to suggest that a natural compound with both antioxidant and anti-inflammatory activities could prevent sarcopenia. Curcumin, a natural compound derived from turmeric with both properties, could benefit muscle health. This review aims to summarise the therapeutic effects of curcumin on cellular, animal, and human studies. The available evidence found in the literature showed that curcumin prevents muscle degeneration by upregulating the expression of genes related to protein synthesis and suppressing genes related to muscle degradation. It also protects muscle health by maintaining satellite cell number and function, protecting the mitochondrial function of muscle cells, and suppressing inflammation and oxidative stress. However, it is noted that most studies are preclinical. Evidence from randomised control trials in humans is lacking. In conclusion, curcumin has the potential to be utilised to manage muscle wasting and injury, pending more evidence from carefully planned human clinical trials.


The influence of depression on sexual risk reduction and STD infection in a controlled, randomized intervention trial.
A randomized controlled trial of SAFE, a cognitive/behavioral intervention, revealed that it significantly reduces reinfection and behavioral risks among participants compared with controls. However, studies suggest that depression may moderate intervention efficacy among affected persons because of impaired information processing, failure to recognize risk, or inability to change behavior. We evaluated SAFE efficacy among depressed and nondepressed Mexican- and African American women after comparing initial risk factors by depression status. We further explored intervention effects in moderately and severely depressed women. We stratified 477 participants (249 intervention, 228 controls) according to their depression status at baseline determined by CES-D scores. Using chi and multivariate logistic regression, we evaluated differences in reinfection and behavioral risk at 6-month, 12-month, and 1-year cumulative follow-ups between groups within baseline depression strata. : At baseline, 74.4% of women were depressed and had significantly greater levels of behavioral risks than nondepressed women. At follow-up intervals, behavioral risks and reinfection rates were lower among intervention women compared with controls regardless of depression status. For example, at 1-year follow-up reinfection rates were 15.2% in nondepressed intervention women versus 21.4% in nondepressed controls (AOR = 0.6), and 18.6% in depressed intervention women versus 27.3% in depressed controls (AOR = 0.6). Moreover, reinfection was consistently lower among moderately and severely depressed intervention women than controls (moderately depressed: 19.3% vs. 27.2%, AOR = 0.6; severely depressed: 17.9% vs. 27.5%, AOR = 0.6). Despite significantly greater behavioral risk among depressed women at baseline, SAFE was equally successful in reducing reinfection and high-risk behavior among depressed and nondepressed participants.


Monitoring changes in rugby league players' perceived stress and recovery during intensified training.
This study assessed whether the Recovery-Stress Questionnaire for Athletes (RESTQ-Sport) could be used to monitor changes in perceived stress and recovery during intensified training of rugby league players. 20 semiprofessional rugby league players were divided into two equal groups randomly assigned to complete 6 wk. of Normal Training or Intensified Training, each followed with a 7-day taper. Multistage Fitness Test performance and RESTQ-Sport measures were taken at the beginning, at 2-wk. intervals, and at the end of the training period. Endurance significantly decreased with Intensified Training and returned to baseline levels following the taper, while remaining unchanged in the Normal Training group. The RESTQ-Sport scores with training were positively related to stress subscale scores (Fatigue, Disturbed Breaks, and General Stress) and recovery subscale measures (Success, Physical Recovery, Being in Shape, Self-efficacy, Social Relaxation, General Well-being, and Sleep Quality) decreasing in the Intensified Training group and then normalising following the taper (Stress subscales: Fatigue and General Stress, and Recovery subscales: Physical Recovery and General Well-being). The RESTQ-Sport is a practical psychometric tool for monitoring responses to training in team-sport athletes.


Reinvestigation of the taxonomy of Clostridium bifermentans and Clostridium sordellii.
The taxonomic relationships between Clostridium bifermentans and C. sordellii were reinvestigated by numerical taxonomy, studies of DNA-DNA homology and DNA duplex thermal stability, and by analysis of cell-wall sugar components. Although the results indicate that both species may be grouped into one geno-species, C. sordellii strains could be differentiated from C. bifermentans strains on the basis of a few phenetic criteria that include the inability to ferment mannose and sorbitol, the absence of mannose in the cell wall, the production of urease, the absence of arginine deaminase activity, and susceptibility to inhibition of growth by mannose.


GenNet: A Platform for Hybrid Network Experiments.
We describe General Network (GenNet), a software plugin for the real time experimental interface (RTXI) dynamic clamp system that allows for straightforward and flexible implementation of hybrid network experiments. This extension to RTXI allows for hybrid networks that contain an arbitrary number of simulated and real neurons, significantly improving upon previous solutions that were limited, particularly by the number of cells supported. The benefits of this system include the ability to rapidly and easily set up and perform scalable experiments with hybrid networks and the ability to scan through ranges of parameters. We present instructions for installing, running and using GenNet for hybrid network experiments and provide several example uses of the system.


Malignant melanoma of the skin - not a sunshine story!
In an earlier study on malignant melanoma incidence in Sweden, Norway, Denmark and the USA, we found a strong association between the introduction of FM radio broadcasting at full-body resonant frequencies and increasing melanoma incidence. The purpose of the current study was to review mortality and incidence data for malignant melanoma of the skin in Sweden and its temporal relation to increased "sun-traveling", and to the introduction of FM and TV broadcasting net-works. Official, published information was collected and displayed graphically. These data included incidence rates of malignant melanoma, death numbers, charter travel statistics, and data on the expansion of the FM broadcasting network in all counties of Sweden. A good correlation in time was found for the rollout of FM/TV broadcasting networks while the increased amount of "sun travel" by air (charter) did not start until 7 years after the melanoma trend break in 1955. Counties that did not roll out their FM-broadcasting network until several years after 1955 continued to have a stable melanoma mortality during the intervening years. The increased incidence and mortality of melanoma of skin cannot solely be explained by increased exposure to UV-radiation from the sun. We conclude that continuous disturbance of cell repair mechanisms by body-resonant electromagnetic fields seems to amplify the carcinogenic effects resulting from cell damage caused e.g. by UV-radiation.


Individual and climate factors associated with acute respiratory infection in Colombian children.
The objective of this study was to examine the association between acute respiratory infection recall (ARI-recall) and individual and environmental factors such as climate, precipitation, and altitude above sea level in Colombian children. A secondary analysis of 11,483 Colombian children, whose mothers were interviewed in the 2010 National Demographic and Health Survey, was carried out. The outcome variable was the mother's or caregiver's ARI-recall. The independent variables were expressed at individual, cluster, and municipal levels. At the individual level, we considered health and individual characteristics of the children; at cluster level, we incorporated the altitude above sea level; and at the municipal level, we included precipitation and annual average climate. The association between ARI-recall and independent variables was assessed using a multilevel logistic regression model. ARI-recall was significantly associated with age (OR = 0.61; 95%CI: 0.48-0.79), belonging to an indigenous group (OR = 1.51; 95%CI: 1.16-1.96), and a medium or very poor wealth index (OR = 2.03; 95%CI: 1.25-3.30 and OR = 1.75; 95%CI: 1.08-2.84, respectively). We found interaction between acute child malnutrition and average annual precipitation. Children with acute malnutrition and from municipalities with high annual precipitation had significantly 3.6-fold increased risk of ARI-recall (OR = 3.6; 95%CI: 1.3-10.1). Individual conditions and precipitation are risk factors for ARI-recall in Colombian children. These results could be useful to understand ARI occurrence in children living in tropical countries with similar characteristics.


Nanogranular origin of concrete creep.
Concrete, the solid that forms at room temperature from mixing Portland cement with water, sand, and aggregates, suffers from time-dependent deformation under load. This creep occurs at a rate that deteriorates the durability and truncates the lifespan of concrete structures. However, despite decades of research, the origin of concrete creep remains unknown. Here, we measure the in situ creep behavior of calcium-silicate-hydrates (C-S-H), the nano-meter sized particles that form the fundamental building block of Portland cement concrete. We show that C-S-H exhibits a logarithmic creep that depends only on the packing of 3 structurally distinct but compositionally similar C-S-H forms: low density, high density, ultra-high density. We demonstrate that the creep rate ( approximately 1/t) is likely due to the rearrangement of nanoscale particles around limit packing densities following the free-volume dynamics theory of granular physics. These findings could lead to a new basis for nanoengineering concrete materials and structures with minimal creep rates monitored by packing density distributions of nanoscale particles, and predicted by nanoscale creep measurements in some minute time, which are as exact as macroscopic creep tests carried out over years.


Post-colonoscopy rectal cancer in Swedish patients with Crohn's disease 2001-2015: a population-based case review study.
Post-colonoscopy colorectal cancer (PCCRC) is a key quality indicator of colonoscopy, and PCCRC rates are high in the IBD population. Rectal cancer, an important risk factor for PCCRC among patients with Crohn's disease (CD), has not previously been examined. Swedish adult patients with CD who underwent a colonoscopy within 36 months before a rectal cancer diagnosis between 2001 and 2015 were identified through the National Patient and Cancer registers. Their medical records were reviewed and a root-cause analysis and a sub-categorization according to the World Endoscopic Organization (WEO) were performed. Of 24 patients with CD and PCCRC in the rectum, 79% were men and the median age was 50 (IQR 45-59) years. The median disease duration was 21.5 (IQR 19-30) years. The cancer was located in the distal 5 cm of the rectum in 63% of the cases. Retroversion in the rectum was reported in only one case. The most common plausible explanation for PCCRC was 'possible missed lesion, prior examination adequate' (63%); when adding retroversion in the rectum, instead 77% of examinations were considered negative but deemed as inadequate. The most common PCCRC sub-category was non-interval type C (54%) and B (37%). Among those with type C, 38% should have been included in surveillance according to present guidelines. Better adherence to surveillance guidelines and more meticulous follow-up is warranted. The importance of performing rectal palpation and retroversion in the rectum is underscored and we suggest that this is included in the WEO algorithm.


Associations between the atrial electromechanical interval, atrial remodelling and outcome of catheter ablation in paroxysmal atrial fibrillation.
The atrial electromechanical (PA-PDI) interval was reported to be a useful predictor of new-onset atrial fibrillation (AF) and the occurrence of AF after coronary artery bypass surgery. The aim of this study was to investigate the associations of the electromechanical interval with atrial substrate properties and the outcome of catheter ablation in paroxysmal AF patients. 132 paroxysmal AF patients who had received catheter ablation were enrolled. The electromechanical interval was determined as the time interval from the initiation of P-wave deflection to the peak of the mitral inflow A-wave on pulse-wave Doppler imaging. The left atrial voltage and total activation time were collected before pulmonary vein isolation. Every patient underwent standard follow-up after catheter ablation. The PA-PDI interval was significantly correlated with the left atrial dimension (r=0.419, p=0.003), left atrial volume (r=0.827, p<0.001), left atrial voltage (r=-0.451, p<0.001) and left atrial activation time (r=0.547, p<0.001). During a follow-up of 23 ± 13 months, 36 patients (27% of the study population) had AF recurrence. The PA-PDI interval and left atrial volume were independent predictors of AF recurrence. At a cut-point of 160 ms, the Kaplan-Meier survival analysis showed that a long PA-PDI interval significantly predicted AF recurrence. The PA-PDI interval can reflect the process of left atrial remodelling, such as a left atrial enlargement, prolonged activation time and decreased voltage. It was a convenient parameter for predicting recurrence after catheter ablation of paroxysmal AF.


Prevalence of respiratory conditions among schoolchildren exposed to different levels of air pollutants in the Haifa Bay area, Israel.
During spring 1984, 2334 second and 2000 fifth-grade schoolchildren living in three Haifa Bay areas on the eastern Mediterranean coast with different levels of air pollution were studied. The parents of these children filled out American Thoracic Society and National Heart and Lung Institute health questionnaires, and the children performed the following pulmonary function tests (PFT); FVC, FEV1, FEV1/FEV, PEF, FEF50, and FEF75. A trend of higher prevalence of most reported respiratory symptoms was found for schoolchildren growing up in the medium and high pollution areas as compared with the low pollution area. Part of the reported respiratory diseases were significantly more common among children from the high pollution area. Models fitted for the respiratory conditions that differed significantly among the three areas of residence also included background variables that could be responsible for these differences. Relative risk values, which were calculated from the logistic models, were in the range of 1.38 for sputum with cold and 1.81 for sputum without cold for children from the high pollution area as compared with 1.00 for children from the low pollution area. All the measured values of PFT were within the normal range. There was no consistent trend of reduced pulmonary function that characterized any residential area.


Central noradrenergic system modulates plasma interleukin-6 production by peripheral interleukin-1.
The role of the central noradrenergic system in systemic interleukin-6 (IL-6) production induced by intravenously administered recombinant human interleukin-1 beta (IL-1 beta) was examined in rats. Pretreatment of rats intracerebroventricularly with 6-hydroxydopamine (6-OHDA, 100 or 200 micrograms/rat) significantly attenuated the increase in plasma IL-6 levels caused by IL-1 beta (2 micrograms/kg i.v.). A modest inhibition of the IL-1 beta-induced plasma IL-6 production was observed following pretreatment with prazosin (20 micrograms/rat i.c.v.) but not after administration of idazoxan or propranolol. There were no significant increases in the IL-6 content in the hypothalamus, medulla oblongata, and cortex of the brain after intravenous IL-1 beta. Adrenalectomy produced an augmented plasma IL-6 response to intravenous IL-1 beta, whereas chemical sympathectomy with intraperitoneal injection of 6-OHDA (50 or 100 mg/kg) decreased the IL-1 beta-induced plasma IL-6 levels. Nor-epinephrine (NE), in the dose range 10(-6)-10(-4) M, significantly increased the IL-6 levels in the rat spleen lymphocyte culture media. At doses of 10(-9)-10(-7) M, NE enhanced the effect of IL-1 beta on the IL-6 release by spleen lymphocytes in a dose-dependent manner. These findings suggest that the plasma IL-6 response to intravenous IL-1 beta is partially mediated through the activation of the central noradrenergic system and a consequent increase in the sympathetic outflow to the peripheral tissues and that the NE released from the sympathetic terminals may function as a mediator and/or modulator to facilitate the synthesis/release of IL-6 in the sympathetic nerve-innervated organs.


Effect of monosodium n-alkylsalicylates on spores of Bacillus subtilis.
The effects of several monosodium n-alkylsalicylates on washed spores of Bacillus subtilis have been examined. None of the compounds was sporicidal, but in general they prevented dormancy induced by incubating the spores in water. This effect was related to the position in the ring and size of the alkyl groups substituted on the salicylic acid nucleus.


[Symptomatic management of brain metastasis].
Indications and choice of antiepileptic drugs (AED), treatments for cerebral edema and prophylactic and curative treatments of thromboembolic complications of brain metastasis are discussed.


Analytic Black Hole Perturbation Approach to Gravitational Radiation.
We review the analytic methods used to perform the post-Newtonian expansion of gravitational waves induced by a particle orbiting a massive, compact body, based on black hole perturbation theory. There exist two different methods of performing the post-Newtonian expansion. Both are based on the Teukolsky equation. In one method, the Teukolsky equation is transformed into a Regge-Wheeler type equation that reduces to the standard Klein Gordon equation in the flat-space limit, while in the other method (which was introduced by Mano, Suzuki, and Takasugi relatively recently, the Teukolsky equation is used directly in its original form. The former's advantage is that it is intuitively easy to understand how various curved space effects come into play. However, it becomes increasingly complicated when one goes to higher and higher post-Newtonian orders. In contrast, the latter's advantage is that a systematic calculation to higher post-Newtonian orders can be implemented relatively easily, but otherwise, it is so mathematical that it is hard to understand the interplay of higher order terms. In this paper, we review both methods so that their pros and cons may be seen clearly. We also review some results of calculations of gravitational radiation emitted by a particle orbiting a black hole.


Factors predictive of malignancy and endoscopic resectability in ampullary neoplasia.
Endoscopic treatment of ampullary lesions has been well described, though it remains uncertain if specific features predict malignancy, and whether identifiable factors are associated with successful endoscopic resection of benign lesions. Fifty-six consecutive patients undergoing endoscopic evaluation of ampullary neoplasia between March 2000 and May 2004 were included in the study. Clinical presentation, underlying medical conditions, endoscopic treatment, endoscopic ultrasound (EUS) to define extent of local involvement, pathology results, and outcome were documented. Data elements for analysis included EUS findings, lesion lifting with submucosal injection, age, gender, tumor size, and endoscopic intervention. Analyses were performed to determine the ability to predict malignancy and the ability to extirpate benign lesions. Thirty-one males and 25 females were included; mean age was 62 yr. Final diagnoses included 29 adenomas, 20 adenocarcinomas, 4 adenomyomas, 2 paragangliomas, and 1 neuroendocrine tumor. Thirty of 35 patients with benign lesions had extirpation with a mean of two endoscopic procedures. Complications of endoscopic resection included cholangitis (1), bleeding (2), and pancreatitis (4). The presence of malignancy was associated by multivariate analysis with the inability to obtain a cleavage plane with saline injection. Univariate analysis also identified EUS T stage as a predictor of malignancy. In benign lesions, none of the analyzed variables predicted successful endoscopic resection. In ampullary lesions, failure to achieve a cleavage plane with submucosal injection is the strongest predictor of malignancy followed by EUS T stage. Endoscopic treatment of benign ampullary neoplasia is effective; no factor was predictive of successful extirpation.


ELK4 neutralization sensitizes glioblastoma to apoptosis through downregulation of the anti-apoptotic protein Mcl-1.
Glioma is the most common adult primary brain tumor. Its most malignant form, glioblastoma multiforme (GBM), is almost invariably fatal, due in part to the intrinsic resistance of GBM to radiation- and chemotherapy-induced apoptosis. We analyzed B-cell leukemia-2 (Bcl-2) anti-apoptotic proteins in GBM and found myeloid cell leukemia-1 (Mcl-1) to be the highest expressed in the majority of malignant gliomas. Mcl-1 was functionally important, as neutralization of Mcl-1 induced apoptosis and increased chemotherapy-induced apoptosis. To determine how Mcl-1 was regulated in glioma, we analyzed the promoter and identified a novel functional single nucleotide polymorphism in an uncharacterized E26 transformation-specific (ETS) binding site. We identified the ETS transcription factor ELK4 as a critical regulator of Mcl-1 in glioma, since ELK4 downregulation was shown to reduce Mcl-1 and increase sensitivity to apoptosis. Importantly the presence of the single nucleotide polymorphism, which ablated ELK4 binding in gliomas, was associated with lower Mcl-1 levels and a greater dependence on Bcl-xL. Furthermore, in vivo, ELK4 downregulation reduced tumor formation in glioblastoma xenograft models. The critical role of ELK4 in Mcl-1 expression and protection from apoptosis in glioma defines ELK4 as a novel potential therapeutic target for GBM.


Molecular and cellular events linking variants in the histone demethylase KDM5C to the intellectual disability disorder Claes-Jensen syndrome.
The widespread availability of genetic testing for those with neurodevelopmental disorders has highlighted the importance of many genes necessary for the proper development and function of the nervous system. One gene found to be genetically altered in the X-linked intellectual disability disorder Claes-Jensen syndrome is KDM5C, which encodes a histone demethylase that regulates transcription by altering chromatin. While the genetic link between KDM5C and cognitive (dys)function is clear, how KDM5C functions to control transcriptional programs within neurons to impact their growth and activity remains the subject of ongoing research. Here, we review our current knowledge of Claes-Jensen syndrome and discuss important new data using model organisms that have revealed the importance of KDM5C in regulating aspects of neuronal development and function. Continued research into the molecular and cellular activities regulated by KDM5C is expected to provide critical etiological insights into Claes-Jensen syndrome and highlight potential targets for developing therapies to improve the quality of life of those affected.


[Relation between the changes in the structure and synthesis of DNA in the cells of mouse leukemia L1210 induced by 1-methyl-1-nitrosourea and 1,3-bis(2-chloroethyl)-1-nitrosourea].
The damage of DNA structure and synthesis in murine leukemia L1210 cells upon single administration in therapeutic doses of antitumour agents of N-nitrosourea type, such as 1-methyl-1-nitrosourea (MNU) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) was studied. MNU and BCNU were characterized by stronger inhibitory effects on de novo DNA synthesis compared to additional pathway of DNA synthesis in leukemia L1210 cells in vivo. Centrifugation in alkaline sucrose density gradients of L1210 cell lysates has revealed persistent single-strand breaks and alkaline-labile sites in newly replicated DNA. Parental DNA structure was more stable to damaging drug effects than that of newly replicated DNA. The results are consistent with our previous data on the differences in the mechanisms of MNU and BCNU action and the absence of complete cross resistance between the drugs.


Applying different independent component analysis algorithms and support vector regression for IT chain store sales forecasting.
Sales forecasting is one of the most important issues in managing information technology (IT) chain store sales since an IT chain store has many branches. Integrating feature extraction method and prediction tool, such as support vector regression (SVR), is a useful method for constructing an effective sales forecasting scheme. Independent component analysis (ICA) is a novel feature extraction technique and has been widely applied to deal with various forecasting problems. But, up to now, only the basic ICA method (i.e., temporal ICA model) was applied to sale forecasting problem. In this paper, we utilize three different ICA methods including spatial ICA (sICA), temporal ICA (tICA), and spatiotemporal ICA (stICA) to extract features from the sales data and compare their performance in sales forecasting of IT chain store. Experimental results from a real sales data show that the sales forecasting scheme by integrating stICA and SVR outperforms the comparison models in terms of forecasting error. The stICA is a promising tool for extracting effective features from branch sales data and the extracted features can improve the prediction performance of SVR for sales forecasting.