Lack of floral nectar reduces self-pollination in a fly-pollinated orchid.
One explanation for the widespread absence of floral nectar in many orchids is that it causes pollinators to visit fewer flowers on a plant, and thus reduces self-pollination. This, in turn, could increase fitness by reducing inbreeding depression in progeny and promoting pollen export. The few previous investigations of this hypothesis have all involved bee-pollinated orchids and some have given contradictory results. We studied the effects of adding artificial nectar (sucrose solution) to the spurs of a non-rewarding long-proboscid fly-pollinated orchid, Disa pulchra. Addition of nectar significantly increased the number of flowers probed by flies (2.6-fold), the time spent on a flower (5.4-fold), the number of pollinia removed per inflorescence (4.8-fold) and the proportion of removed pollen involved in self-pollination (3.5-fold). The level of self-pollination increased dramatically with the number of flowers probed by flies. Experimental self-pollination resulted in fruits with only half as many viable seeds as those arising from cross-pollination. Pollinators were more likely to fly long distances (>40 cm) when departing from non-rewarding inflorescences than when departing from rewarding ones. These findings provide support for the idea that floral deception serves to reduce pollinator-mediated self-pollination.


In vitro drug sensitivity and clinical aspects of Plasmodium falciparum malaria in African children.
In vitro Plasmodium falciparum drug sensitivity was investigated in 115 brazzavillians children, between 1 year and 10 years of age. On the basis of clinical aspects, four groups were constituted: Group 1: 39 asymptomatic school children, Group 2: 16 children with uncomplicated malaria, Group 3: 40 with severe but not pernicious malaria and Group 4: 20 with pernicious malaria. The drugs tested were chloroquine (CQ), quinine (QN) and mefloquine (MQ). The sensitivity level was assessed by a 48-hour in vitro maturation test involving the uptake of tritiated hypoxanthine, the initial blood level of parasite being > or = 0.1% in all cases. For QN and MQ, the median IC50 values showed no significant difference related to clinical status, age or parasitaemia levels. For CQ, the proportion of resistant strains and the 50 inhibitory concentration (IC50) values were greater in the cases of children hospitalised for malaria but there were no differences related to clinical severity of these hospitalised children nor, within each group, to the age or parasitaemia levels. The percentage of subjects with an IC50 value greater than the 90 percentile of the IC50 of the asymptomatic group, which we propose as the severity index related to chemoresistance, was 15% for uncomplicated malaria, 38% for severe but non-pernicious forms and 35% for pernicious malaria. The IC50 for QN was significantly higher in CQ-resistant strains and there was a positive correlation for CQ vs QN and for QN vs MQ.


Charge compensation assisted enhancement of photoluminescence in combustion derived Li+ co-doped cubic ZrO2:Eu3+ nanophosphors.
Red light emitting cubic Zr0.99Eu0.01O2:Li+ (0-9 mol%) nanoparticles are synthesized by a low temperature, self-propagating solution combustion method using oxalyl di-hydrazide (ODH) as fuel. In this study, we report systematic investigation of the effect of lithium ion (Li+) concentration on the structural properties and the photoluminescence of zirconia. With increasing lithium concentration, the crystallinity of the samples increases and the lattice strain decreases. The higher crystallinity is likely due to charge compensation achieved by replacing one Zr4+ ion by a Eu3+ and a Li+ ion. Scanning electron micrographs (SEM) reveal a mesoporous structure characteristic of combustion derived nanomaterials. Photoluminescence (PL) spectra show that the intensity of the red emission (606 nm) is highly dependent on Li+ ion concentration. Furthermore there is a promising enhancement in the associated lifetime. Upon Li+ doping, the PL intensity of the samples is found to increase by two fold compared to the undoped sample. Variation of PL intensity with Li+ concentration is attributed to the differences in probability of non-radiative recombination (relaxing). Intensity parameters (Ω2, Ω) and radiative properties such as transition rates (A), branching ratios (β), stimulated emission cross-section (σe), gain bandwidth (σe × Δλeff) and optical gain (σe × τ) are calculated using the Judd-Ofelt theory. The calculated values suggest that in optimally co-doped samples, in addition to improved crystallinity and charge compensation, the lowering of Eu3+ site symmetry and the increase in the covalency of Eu-O bonding due to interstitial Li are responsible for the observed enhancement in PL intensity.


Functional dissection of the TBK1 molecular network.
TANK-binding kinase 1 (TBK1) and inducible IκB-kinase (IKK-i) are central regulators of type-I interferon induction. They are associated with three adaptor proteins called TANK, Sintbad (or TBKBP1) and NAP1 (or TBKBP2, AZI2) whose functional relationship to TBK1 and IKK-i is poorly understood. We performed a systematic affinity purification-mass spectrometry approach to derive a comprehensive TBK1/IKK-i molecular network. The most salient feature of the network is the mutual exclusive interaction of the adaptors with the kinases, suggesting distinct alternative complexes. Immunofluorescence data indicated that the individual adaptors reside in different subcellular locations. TANK, Sintbad and NAP1 competed for binding of TBK1. The binding site for all three adaptors was mapped to the C-terminal coiled-coil 2 region of TBK1. Point mutants that affect binding of individual adaptors were used to reconstitute TBK1/IKK-i-deficient cells and dissect the functional relevance of the individual kinase-adaptor edges within the network. Using a microarray-derived gene expression signature of TBK1 in response virus infection or poly(I∶C) stimulation, we found that TBK1 activation was strictly dependent on the integrity of the TBK1/TANK interaction.


Comprehensive survey of developmental genes in the pea aphid, Acyrthosiphon pisum: frequent lineage-specific duplications and losses of developmental genes.
Aphids exhibit unique attributes, such as polyphenisms and specialized cells to house endosymbionts, that make them an interesting system for studies at the interface of ecology, evolution and development. Here we present a comprehensive characterization of the developmental genes in the pea aphid, Acyrthosiphon pisum, and compare our results to other sequenced insects. We investigated genes involved in fundamental developmental processes such as establishment of the body plan and organogenesis, focusing on transcription factors and components of signalling pathways. We found that most developmental genes were well conserved in the pea aphid, although many lineage-specific gene duplications and gene losses have occurred in several gene families. In particular, genetic components of transforming growth factor beta (TGFbeta) Wnt, JAK/STAT (Janus kinase/signal transducer and activator of transcription) and EGF (Epidermal Growth Factor) pathways appear to have been significantly modified in the pea aphid.


Histone methylation in the nervous system: functions and dysfunctions.
Chromatin remodeling is a key epigenetic process controlling the regulation of gene transcription. Local changes of chromatin architecture can be achieved by post-translational modifications of histones such as methylation, acetylation, phosphorylation, ubiquitination, sumoylation, and ADP-ribosylation. These changes are dynamic and allow for rapid repression or de-repression of specific target genes. Chromatin remodeling enzymes are largely involved in the control of cellular differentiation, and loss or gain of function is often correlated with pathological events. For these reasons, research on chromatin remodeling enzymes is currently very active and rapidly expanding, these enzymes representing very promising targets for the design of novel therapeutics in different areas of medicine including oncology and neurology. In this review, we focus on histone methylation in the nervous system. We provide an overview on mammalian histone methyltransferases and demethylases and their mechanisms of action, and we discuss their roles in the development of the nervous system and their involvement in neurodevelopmental, neurodegenerative, and behavioral disorders.


Picobiliphytes: a marine picoplanktonic algal group with unknown affinities to other eukaryotes.
Environmental sequencing has revealed unimagined diversity among eukaryotic picoplankton. A distinct picoplanktonic algal group, initially detected from 18S ribosomal DNA (rDNA) sequences, was hybridized with rRNA-targeted probes, detected by tyramide signal amplification-fluorescent in situ hybridization, and showed an organelle-like body with orange fluorescence indicative of phycobilins. Using this fluorescence signal, cells were sorted by flow cytometry and probed. Hybridized cells contained a 4',6'-diamidino-2-phenylindole-stained organelle resembling a plastid with a nucleomorph. This suggests that they may be secondary endosymbiotic algae. Pending the isolation of living cells and their formal description, these algae have been termed picobiliphytes.


Effective electrocatalytic methanol oxidation of Pd-based metallic glass nanofilms.
Compared to their conventional polycrystalline Pd counterparts, Pd79Au9Si12 (at%) - metallic glass (MG) nanofilm (NF) electrocatalysts offer better methanol oxidation reaction (MOR) in alkaline medium, CO poisoning tolerance and catalyst stability even at high scan rates or high methanol concentrations owing to their amorphous structure without grain boundaries. This study evaluates the influence of scan rate and methanol concentration by cyclic voltammetry, frequency-dependent electrochemical impedance spectroscopy and a related equivalent circuit model at different potentials in Pd-Au-Si amorphous NFs. Structural and compositional differences for the NFs are assessed by high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), energy dispersive X-ray (EDX) mapping and X-ray diffraction (XRD). The ratio of the forward to reverse peak current density ipf/ipb for the MG NFs is ∼2.2 times higher than for polycrystalline Pd NFs, evidencing better oxidation of methanol to carbon dioxide in the forward scan and less poisoning of the electrocatalysts by carbonaceous (e.g. CO, HCO) species. Moreover, the electrochemical circuit model obtained from EIS measurements reveals that the MOR occurring around -100 mV increases the capacitance without any significant change in oxidation resistance, whereas CO2 formation towards lower potentials results in a sharp increase in the capacitance of the Faradaic MOR at the catalyst interface and a slight decrease in the corresponding resistance. These results, together with the high ipf/ipb = 3.37 yielding the minimum amount of carbonaceous species deposited on the thin film during cyclic voltammetry and stability in the alkaline environment, can potentially make these amorphous thin films potential candidates for fuel-cell applications.


Control of out-of-focus light intensity in confocal raman microscopy using optical preprocessing.
Optical preprocessing, the manipulation of imaging-forming light prior to detection, is used in many forms of microscopy to enhance image information and interpretation. The rejection of out-of-focus light by a pinhole in confocal microscopy is an example of optical preprocessing, where spatial filtering is carried out in a plane conjugate to the object focal plane. The rejection efficiency afforded by this arrangement is, however, sometimes insufficient. Insufficient rejection of out-of-focus light intensity can lead to incorrect interpretations of confocal Raman depth and line maps. An alternative approach is to reject out-of-focus light by implementing spatial filtering in one of the several planes conjugate to the pupil plane. This paper shows that mapping enhanced by structured pupils (MESP) provides substantial additional rejection of out-of-focus intensity relative to traditional confocal microscopy, yielding a potential solution to the problem of misleading Raman maps. In addition, lossless MESP is proposed, wherein simple phase masks simultaneously direct in-focus and out-of-focus light intensity transmitted by confocal optics to different regions of a charge-coupled device (CCD) detector.


Organic Electroluminescent Devices
Electroluminescence from organic materials has the potential to enable low-cost, full-color flat-panel displays, as well as other emissive products. Some materials have now demonstrated adequate efficiencies (1 to 15 lumens/watt) and lifetimes (>5000 hours) for practical use; however, the factors that govern lifetime remain poorly understood. This article provides a brief review of device principles and applications requirements and focuses on the understanding of reliability issues.


Alternative splicing: a mechanism for phenotypic rescue of a common inherited defect.
Approximately 2% of Caucasians and African-Americans are homozygous for a nonsense mutation in exon 2 of the AMPD1 (AMP deaminase) gene. These individuals have a high grade deficiency of AMPD activity in their skeletal muscle. More than 100 patients with AMPD1 deficiency have been reported to have symptoms of a metabolic myopathy, but it is apparent many individuals with this inherited defect are asymptomatic given the prevalence of this mutant. Results of the present study provide a potential molecular explanation for "correction" of this genetic defect. Alternative splicing eliminates exon 2 in 0.6-2% of AMPD1 mRNA transcripts in adult skeletal muscle. Expression studies document that AMPD1 mRNA, which has exon 2 deleted, encodes a functional AMPD peptide. A much higher percentage of alternatively spliced transcripts are found during differentiation of human myocytes in vitro. Transfection studies with human minigene constructs demonstrate that alternative splicing of the primary transcript of human AMPD1 is controlled by tissue-specific and stage-specific signals. Alternative splicing of exon 2 in individuals who have inherited this defect provides a mechanism for phenotypic rescue and variations in splicing patterns may contribute to the variability in clinical symptoms.


Prescribed fire as a means of reducing forest carbon emissions in the western United States.
Carbon sequestration by forested ecosystems offers a potential climate change mitigation benefit. However, wildfire has the potential to reverse this benefit In the western United States, climate change and land management practices have led to increases in wildfire intensity and size. One potential means of reducing carbon emissions from wildfire is the use of prescribed burning,which consumes less biomass and therefore releases less carbon to the atmosphere. This study uses a regional fire emissions model to estimate the potential reduction in fire emissions when prescribed burning is applied in dry, temperate forested systems of the western U.S. Daily carbon dioxide (CO(2)) fire emissions for 2001-2008 were calculated for the western U.S. for two cases: a default wildfire case and one in which prescribed burning was applied. Wide-scale prescribed fire application can reduce CO(2) fire emissions for the western U.S. by 18-25%1 in the western U.S., and by as much as 60% in specific forest systems. Although this work does not address important considerations such as the feasibility of implementing wide-scale prescribed fire management or the cumulative emissions from repeated prescribed burning, it does provide constraints on potential carbon emission reductions when prescribed burning is used.


Skeletal muscle and plasma concentrations of cefazolin during complex paediatric spinal surgery.
Surgical site infections (SSIs) can have devastating consequences for children who undergo spinal instrumentation. Prospective evaluations of prophylactic cefazolin in this population are limited. The purpose of this study was to describe the pharmacokinetics and skeletal muscle disposition of prophylactic cefazolin in a paediatric population undergoing complex spinal surgery. This prospective pharmacokinetic study included 17 children with adolescent idiopathic scoliosis undergoing posterior spinal fusion, with a median age of 13.8 [interquartile range (IQR) 13.4-15.4] yr and a median weight of 60.6 (IQR 50.8-66.0) kg. A dosing strategy consistent with published guidelines was used. Serial plasma and skeletal muscle microdialysis samples were obtained during the operative procedure and unbound cefazolin concentrations measured. Non-compartmental pharmacokinetic analyses were performed. The amount of time that the concentration of unbound cefazolin exceeded the minimal inhibitory concentration for bacterial growth for selected SSI pathogens was calculated. Skeletal muscle concentrations peaked at a median of 37.6 (IQR 26.8-40.0) µg ml(-1) within 30-60 min after the first cefazolin 30 mg kg(-1) dose. For patients who received a second 30 mg kg(-1) dose, the peak concentrations reached a median of 40.5 (IQR 30.8-45.7) µg ml(-1) within 30-60 min. The target cefazolin concentrations for SSI prophylaxis for meticillin-sensitive Staphylococcus aureus (MSSA) and Gram-negative pathogens were exceeded in skeletal muscle 98.9 and 58.3% of the intraoperative time, respectively. For children with adolescent idiopathic scoliosis undergoing posterior spinal fusion, the cefazolin dosing strategy used in this study resulted in skeletal muscle concentrations that were likely not to be effective for intraoperative SSI prophylaxis against Gram-negative pathogens.


Routine daily chest radiography in patients with pulmonary artery catheters.
Pulmonary artery catheters are widely used invasive monitoring devices in critically ill patients. Clinicians disagree about whether daily chest radiographs are needed or clinical parameters alone are sufficient to verify catheter placement. To determine whether daily chest radiographs are needed to assess migration of pulmonary artery catheters. One hundred consecutive patients with pulmonary artery catheters were prospectively evaluated. Clinical criteria for optimal position of the pulmonary artery catheters and findings on chest radiographs were compared. Optimal clinical criteria were (1) amount of air required to measure pulmonary capillary wedge pressure: 1.25 to 1.5 mL and (2) pulmonary artery catheter migrated 1 cm or less from initial position. Three hundred ninety comparisons of clinical criteria and radiographic findings were done. Chest radiographs indicated the catheter required repositioning in 15 (4%) of 390 instances but in only 4 (1%) of 310 instances in which bedside clinical findings indicated adequate catheter position. In 69 (18%) of the 390 cases, the clinical criteria for adequate catheter position were not met, but radiographs showed the catheter in an appropriate position. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of abnormal clinical criteria were 73%, 82%, 81%, 14%, and 99%, respectively. Chest radiographs indicated that about 4% of catheters required repositioning. Catheter malposition can be reliably excluded (negative predictive value, 99%) by close observation of specific clinical criteria, so routine daily chest radiographs do not seem justified.


Multilocus coalescent analyses reveal the demographic history and speciation patterns of mouse lemur sister species.
Debate continues as to whether allopatric speciation or peripatric speciation through a founder effect is the predominant force driving evolution in vertebrates. The mouse lemurs of Madagascar are a system in which evolution has generated a large number of species over a relatively recent time frame. Here, we examine speciation patterns in a pair of sister species of mouse lemur, Microcebus murinus and M. griseorufus. These two species have ranges that are disparately proportioned in size, with M. murinus showing a much more extensive range that marginally overlaps that of M. griseorufus. Given that these two species are sister taxa, the asymmetric but overlapping geographic ranges are consistent with a model of peripatric speciation. To test this hypothesis, we analyze DNA sequence data from four molecular markers using coalescent methods. If the peripatric speciation model is supported, we predict substantially greater genetic diversity in M. murinus, relative to M. griseorufus. Further, we expect a larger effective population size in M. murinus and in the common ancestor of the two species than in M. griseorufus, with a concomitant decrease in gene tree/species tree incongruence in the latter and weak signs of demographic expansion in M. murinus. Our results reject a model of peripatric divergence. Coalescent effective population size estimates were similar for both extant species and larger than that estimated for their most recent common ancestor. Gene tree results show similar levels of incomplete lineage sorting within species with respect to the species tree, and locus-specific estimates of genetic diversity are concordant for both species. Multilocus demographic analyses suggest range expansions for M. murinus, with this species also experiencing more recent population declines over the past 160 thousand years. Results suggest that speciation occurred in allopatry from a common ancestor narrowly distributed throughout southwest Madagascar, with subsequent range expansion for M. murinus. Population decline in M. murinus is likely related to patterns of climate change in Madagascar throughout the Pleistocene, potentially exacerbated by continual anthropogenic perturbation. Genome-level data are needed to quantify the role of niche specialization and adaptation in shaping the current ranges of these species.


Policing men: militarised masculinity, youth livelihoods, and security in conflict-affected northern Uganda.
Relations between militaries and masculinities-and hegemonic masculinity and the state-are well-established in the literature on gender and development. However, there is less research on how militarised masculinities relate to state governance strategies. This paper, based on qualitative research conducted in northern Uganda between 2014 and 2017, offers a gender analysis of youths participating in informal security arrangements. Civilian male youths accept poorly paid or unpaid work in the informal security sector in the hope of gaining access to livelihoods that will enable them to fulfil masculine ideal-types. However, this arrangement denies them the resources necessary to achieve the ideal-type of civilian masculinity, as well as the state's military masculinity, which produces young men as subjects of the ruling regime. To reconfigure this relationship between civilian and militarised masculinities, one should understand informal security organisations in the context of alternative livelihood arrangements and take a long-term approach to the demilitarisation of the Ugandan state.


Individual differences and social influences on the neurobehavioral pharmacology of abused drugs.
The interaction of drugs with biologic targets is a critical area of research, particularly for the development of medications to treat substance use disorders. In addition to understanding these drug-target interactions, however, there is a need to understand more fully the psychosocial influences that moderate these interactions. The first section of this review introduces some examples from human behavioral pharmacology that illustrate the clinical importance of this research. The second section covers preclinical evidence to characterize some of the key individual differences that alter drug sensitivity and abuse vulnerability, related primarily to differences in response to novelty and impulsivity. Evidence is presented to indicate that critical neuropharmacological mechanisms associated with these individual differences involve integrated neurocircuits underlying stress, reward, and behavioral inhibitory processes. The third section covers social influences on drug abuse vulnerability, including effects experienced during infancy, adolescence, and young adulthood, such as maternal separation, housing conditions, and social interactions (defeat, play, and social rank). Some of the same neurocircuits involved in individual differences also are altered by social influences, although the precise neurochemical and cellular mechanisms involved remain to be elucidated fully. Finally, some speculation is offered about the implications of this research for the prevention and treatment of substance abuse.


A method for the calculation of rate constants from stochastic transition paths.
We present a novel and efficient method for computation of rate constants in the systems where two metastable states are separated by a high free energy barrier. Our approach is based on the thermodynamic integration applied to the grand canonical ensemble of the stochastic transition paths. As illustrated on a multidimensional model system, the required computational costs depend only weakly on the barrier height, which provides a speedup of orders of magnitude in comparison to direct simulations.


Disparity of reperfusion arrhythmias after reversible myocardial ischemia in open chest and conscious dogs.
Myocardial reperfusion after brief, reversible ischemia is frequently associated with malignant arrhythmias in experimental animals. These observations have been extrapolated to humans despite being restricted to anesthetized, open chest preparations. No data are available regarding the incidence of reperfusion arrhythmias after reversible (less than 20 minutes) ischemia in the conscious state. Thus, reperfusion arrhythmias after a 15 minute occlusion of the left anterior descending coronary artery were compared in 24 open chest dogs (17 anesthetized with pentobarbital and 7 with chloralose plus urethane) and 25 conscious, unsedated, trained dogs. The incidence of all rhythm disorders (single premature ventricular complexes, pairs, ventricular tachycardia and fibrillation) was markedly and significantly lower in conscious than in either pentobarbital- or chloralose-anesthetized dogs. The disparity was not accounted for by differences in coronary collateral flow, coronary reactive hyperemia or occluded bed size. The conscious animals, however, exhibited lower heart rates and arterial pressures during reperfusion than did the open chest dogs, suggesting a lower level of adrenergic stimulation, which might have contributed to the reduced incidence of reperfusion arrhythmias. Coronary reperfusion after 15 minutes of occlusion is unlikely to precipitate ventricular tachyarrhythmias in the conscious, trained dog, even after severe ischemia. The occurrence of these rhythm disorders in anesthetized models may reflect the influence of surgical trauma or excessive adrenergic activity, or both. Reperfusion arrhythmias after reversible ischemia may be considerably less common in the clinical setting than previously postulated on the basis of open chest animal experiments.


Forced residential mobility and social support: impacts on psychiatric disorders among Somali migrants.
Somali migrants fleeing the civil war in their country face punishing journeys, the loss of homes, possessions, and bereavement. On arrival in the host country they encounter poverty, hostility, and residential instability which may also undermine their mental health. An in-depth and semi-structured interview was used to gather detailed accommodation histories for a five year period from 142 Somali migrants recruited in community venues and primary care. Post-codes were verified and geo-mapped to calculate characteristics of residential location including deprivation indices, the number of moves and the distances between residential moves. We asked about the reasons for changing accommodation, perceived discrimination, asylum status, traumatic experiences, social support, employment and demographic factors. These factors were assessed alongside characteristics of residential mobility as correlates of ICD-10 psychiatric disorders. Those who were forced to move homes were more likely to have an ICD-10 psychiatric disorder (OR = 2.64, 1.16-5.98, p = 0.02) compared with those moving through their own choice. A lower risk of psychiatric disorders was found for people with larger friendship networks (0.35, 0.14-0.84, p = 0.02), for those with more confiding emotional support (0.42, 0.18-1.0, p = 0.05), and for those who had not moved during the study period (OR = 0.21, 0.07-0.62, p = 0.01). Forced residential mobility is a risk factor for psychiatric disorder; social support may contribute to resilience against psychiatric disorders associated with residential mobility.


Clinical and biochemical effects during treatment of depression with nortriptyline: the role of 10-hydroxynortriptyline.
Plasma concentrations of nortriptyline (NT) and its major metabolite 10-hydroxy-NT (10-OH-NT) were measured in 30 patients with depression, treated with NT for 3 weeks. Nine patients who recovered completely had plasma concentrations of NT and 10-OH-NT ranging from 358 to 728 nmol/L and from 428 to 688 nmol/L, respectively. Of the 21 patients who did not recover completely, only four had plasma concentrations within the window limited by these two plasma concentration ranges. A correlation was found between the degree of amelioration and the plasma concentration of NT (rs = 0.469; P less than 0.01). Lumbar punctures were performed in 26 patients before and after 3 weeks of NT treatment. During treatment there was a 30.9% mean decrease in the noradrenaline metabolite 4-hydroxy-3-methoxyphenylglycol (HMPG) in cerebrospinal fluid (CSF). We could not evaluate the extent to which this decrease was caused by NT or 10-OH-NT, respectively, because both are strong inhibitors of noradrenaline uptake. The ratio between the concentration of NT and 10-OH-NT in CSF correlated to the reduction of HMPG in CSF (r = 0.397; P less than 0.05) and to the amelioration of depression (rs = 0.623; P less than 0.001). This might indicate that NT and 10-OH-NT interact on the noradrenaline system in a nonadditive way. During treatment there was a 15.2% decrease in CSF concentration of the serotonin metabolite 5-hydroxyindoleacetic acid. The reduction was significantly correlated to the CSF concentration of NT but not to that of 10-OH-NT. This is in accordance with the fact that NT is a more potent inhibitor of serotonin uptake than is 10-OH-NT. The dopamine metabolite homovanillic acid in CSF decreased significantly by 10.0%. The biochemical data indicate that noradrenergic, serotoninergic, and dopaminergic systems are affected by NT treatment and that 10-OH-NT might be more selective on noradrenergic neurons than the parent drug.


Arginine deiminase pathway enzymes: evolutionary history in metamonads and other eukaryotes.
Multiple prokaryotic lineages use the arginine deiminase (ADI) pathway for anaerobic energy production by arginine degradation. The distribution of this pathway among eukaryotes has been thought to be very limited, with only two specialized groups living in low oxygen environments (Parabasalia and Diplomonadida) known to possess the complete set of all three enzymes. We have performed an extensive survey of available sequence data in order to map the distribution of these enzymes among eukaryotes and to reconstruct their phylogenies. We have found genes for the complete pathway in almost all examined representatives of Metamonada, the anaerobic protist group that includes parabasalids and diplomonads. Phylogenetic analyses indicate the presence of the complete pathway in the last common ancestor of metamonads and heterologous transformation experiments suggest its cytosolic localization in the metamonad ancestor. Outside Metamonada, the complete pathway occurs rarely, nevertheless, it was found in representatives of most major eukaryotic clades. Phylogenetic relationships of complete pathways are consistent with the presence of the Archaea-derived ADI pathway in the last common ancestor of all eukaryotes, although other evolutionary scenarios remain possible. The presence of the incomplete set of enzymes is relatively common among eukaryotes and it may be related to the fact that these enzymes are involved in other cellular processes, such as the ornithine-urea cycle. Single protein phylogenies suggest that the evolutionary history of all three enzymes has been shaped by frequent gene losses and horizontal transfers, which may sometimes be connected with their diverse roles in cellular metabolism.


Multiple intra-abdominal serosal myxosarcomas in two koalas (Phascolarctos cinereus).
Two adult koalas (Phascolarctos cinereus) were presented for necropsy examination without any clinical history. A diffuse, severe gelatinous effusion was found in the abdominal cavity, while numerous 1-3 mm diameter, round, well-demarcated, multifocal to coalescing, raised, firm nodules containing a clear gelatinous fluid were scattered on the surface of the parietal peritoneum, diaphragm, liver, gastrointestinal tract and mesentery. Microscopically, the nodular lesions consisted of spindle-shaped to stellate neoplastic cells, with scant eosinophilic cytoplasm and moderate anisocytosis and anisokaryosis. The neoplastic cells were admixed with and surrounded by abundant acellular pale eosinophilic material that was stained by Alcian blue and only weakly by the periodic acid-Schiff reaction. Serosal proliferations are described rarely in koalas and to the authors' knowledge this is the first reported case of serosal myxosarcoma. The significance and pathogenesis of this condition in the koala population is unknown.


Post-coupling strategy enables true receptor-targeted nanoparticles.
A key goal of our research is the targeted delivery of functional biopharmaceutical agents of interest, such as small interfering RNA (siRNA), to selected cells by means of receptor-mediated nanoparticle technologies. Recently, we described how pH-triggered, PEGylated siRNA-nanoparticles (pH triggered siRNA-ABC nanoparticles) were able to mediate the passive targeting of siRNA to liver cells in vivo. In addition, PEGylated siRNA nanoparticles enabled for long-term circulation (LTC siRNA-ABC nanoparticles, LEsiRNA nanoparticles) were shown to do the same to tumour cells in vivo. Further gains in the efficiency of siRNA delivery are expected to require active targeting with nanoparticles targeted for delivery and cellular uptake by means of attached biological ligands. Here we report on the development of a new synthetic chemistry and a bioconjugation methodology that allows for the controlled formulation of PEGylated nanoparticles which surface-present integrin-targeting peptides unambiguously and so enable integrin receptor-mediated cellular uptake. Furthermore, we present delivery data that provide a clear preliminary demonstration of physical principles that we propose should underpin successful, bonefide receptor-mediated targeted delivery of therapeutic and/or imaging agents to cells.


Different brain activities predict retrieval success during emotional and semantic encoding.
There is an increasing line of evidence supporting the idea that the formation of lasting memories involves neural activity preceding stimulus presentation. Following this line, we presented words in an incidental learning setting and manipulated the prestimulus state by asking the participants to perform either an emotional (neutral or emotional) or a semantic (animate or inanimate) decision task. Later, we tested the retrieval of each previously presented word with a recognition memory test. For both conditions, the subsequent memory effect (SME) was defined as ERP difference between subsequently remembered and forgotten words. Comparing the prestimulus SME between and within the two conditions yielded topographic differences in the time interval from -1300 to -700 msec before stimulus onset. This indicates that the activity of brain areas involved in incidental encoding of semantic information varied in the spatial distribution of ERPs, depending on the emotional and semantic requirements of the task. These findings provide evidence that there is a difference in semantic and emotional preparatory processes, which modulates successful encoding into episodic memory. This difference suggests that there are multiple task-specific functional neural systems that support memory formation. These systems differ in location and/or relative contribution of some of the brain structures that generate the measured scalp electric fields. Consequently, the cognitive processes that enable memory formation depend on the differential semantic nature of the study task and reflect differences in the preparatory processing of the multiple semantic components of a word's meaning.


Exploring the Chemical Space of Benzothiazole-Based DNA Gyrase B Inhibitors.
We designed and synthesized a series of inhibitors of the bacterial enzymes DNA gyrase and DNA topoisomerase IV, based on our recently published benzothiazole-based inhibitor bearing an oxalyl moiety. To improve the antibacterial activity and retain potent enzymatic activity, we systematically explored the chemical space. Several strategies of modification were followed: varying substituents on the pyrrole carboxamide moiety, alteration of the central scaffold, including variation of substitution position and, most importantly, modification of the oxalyl moiety. Compounds with acidic, basic, and neutral properties were synthesized. To understand the mechanism of action and binding mode, we have obtained a crystal structure of compound 16a, bearing a primary amino group, in complex with the N-terminal domain of E. coli gyrase B (24 kDa) (PDB: 6YD9). Compound 15a, with a low molecular weight of 383 Da, potent inhibitory activity on E. coli gyrase (IC50 = 9.5 nM), potent antibacterial activity on E. faecalis (MIC = 3.13 μM), and efflux impaired E. coli strain (MIC = 0.78 μM), is an important contribution for the development of novel gyrase and topoisomerase IV inhibitors in Gram-negative bacteria.


Theoretical Migration Model for Micellar Capillary Electrophoresis and Its Application to the Separation of Anionic Metal Complexes of HEDTC and CDTA.
A mathematical model relating the effective mobility of an analyte in micellar capillary electrophoresis (MCE) to the concentration of surfactant and organic modifier in the background electrolyte (BGE) was derived. Effective mobility is expressed in terms of the electrophoretic mobility of the analyte, the partition coefficient of the analyte into the micelle, and the influence of organic modifier on these two factors. The performance of the model was evaluated using Cd(II), Pb(II), Co(II), Ni(II), Bi(III), Cu(II), and Hg(II) complexes of bis(2-hydroxyethyl)dithiocarbamate, all of which carry a partial negative charge, and Cd(II), Pb(II), Co(II), Ni(II), Bi(III), Cu(II), Hg(II), Fe(III), Ag(I), Tl(I), and Mn(II) complexes of trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid, all of which are anionic having charges in the range -1 to -3. These analytes were separated in borate BGEs containing 10-50 mM sodium dodecyl sulfate and 0-20% (v/v) methanol. Nonlinear regression was used to derive parameters for the model from experimental data and these parameters were used to predict effective mobilities of the analytes. Predicted values of effective mobilties agreed with experimental values to within 3.1%. Values of parameters from the model equation are used to explain changes in separation selectivity observed at different BGE compositions and the model equation is shown to be applicable to computer-assisted optimization of the BGE composition, in MCE using a limited number of experiments.


Bacterial expression strategies for several Sus scrofa diacylglycerol kinase alpha constructs: solubility challenges.
We pursued several strategies for expressing either full-length Sus scrofa diacylglycerol kinase (DGK) alpha or the catalytic domain (alphacat) in Escherichia coli. Alphacat could be extracted, refolded, and purified from inclusion bodies, but when subjected to analytical gel filtration chromatography, it elutes in the void volume, in what we conclude are microscopic aggregates unsuitable for x-ray crystallography. Adding glutathione S-transferase, thioredoxin, or maltose binding protein as N-terminal fusion tags did not improve alphacat's solubility. Coexpressing with bacterial chaperones increased the yield of alphacat in the supernatant after high-speed centrifugation, but the protein still elutes in the void upon analytical gel filtration chromatography. We believe our work will be of interest to those interested in the structure of eukaryotic DGKs, so that they know which expression strategies have already been tried, as well as to those interested in protein folding and those interested in chaperone/target-protein interactions.


Youth advocacy as a tool for environmental and policy changes that support physical activity and nutrition: an evaluation study in San Diego County.
As evidence grows about the benefits of policy and environmental changes to support active living and healthy eating, effective tools for implementing change must be developed. Youth advocacy, a successful strategy in the field of tobacco control, should be evaluated for its potential in the field of obesity prevention. San Diego State University collaborated with the San Diego County Childhood Obesity Initiative to evaluate Youth Engagement and Action for Health! (YEAH!), a youth advocacy project to engage youth and adult mentors in advocating for neighborhood improvements in physical activity and healthy eating opportunities. Study objectives included documenting group process and success of groups in engaging in community advocacy with decision makers. In 2011 and 2012, YEAH! group leaders were recruited from the San Diego County Childhood Obesity Initiative's half-day train-the-trainer seminars for adult leaders. Evaluators collected baseline and postproject survey data from youth participants and adult group leaders and interviewed decision makers. Of the 21 groups formed, 20 completed the evaluation, conducted community assessments, and advocated with decision makers. Various types of decision makers were engaged, including school principals, food service personnel, city council members, and parks and recreation officials. Eleven groups reported change(s) implemented as a result of their advocacy, 4 groups reported changes pending, and 5 groups reported no change as a result of their efforts. Even a brief training session, paired with a practical manual, technical assistance, and commitment of adult leaders and youth may successfully engage decision makers and, ultimately, bring about change.


Unconscious effects of language-specific terminology on preattentive color perception.
It is now established that native language affects one's perception of the world. However, it is unknown whether this effect is merely driven by conscious, language-based evaluation of the environment or whether it reflects fundamental differences in perceptual processing between individuals speaking different languages. Using brain potentials, we demonstrate that the existence in Greek of 2 color terms--ghalazio and ble--distinguishing light and dark blue leads to greater and faster perceptual discrimination of these colors in native speakers of Greek than in native speakers of English. The visual mismatch negativity, an index of automatic and preattentive change detection, was similar for blue and green deviant stimuli during a color oddball detection task in English participants, but it was significantly larger for blue than green deviant stimuli in native speakers of Greek. These findings establish an implicit effect of language-specific terminology on human color perception.


An integrated process and management tools for ranking multiple emerging threats to animal health.
The UK's Department for Environment, Food and Rural Affairs supports the use of systematic tools for the prioritisation of known and well defined animal diseases to facilitate long and medium term planning of surveillance and disease control activities. The recognition that emerging events were not covered by the existing disease-specific approaches led to the establishment of the Veterinary Risk Group (VRG), constituted of government officials, and supporting structures such as the Risk Management Cycle and the Emerging Threat Highlight Report (ETHiR), to facilitate the identification, reporting and assessment of emerging threats to UK's animal health. Since its inception in November 2009 to the end of February 2011, the VRG reviewed 111 threats and vulnerabilities (T&V) reported through ETHiR. In July 2010 a decision support system (DSS) based on multi-criteria-decision-analysis (MCDA) improved ETHiR to allow the systematic prioritisation of emerging T&V. The DSS allows the regular ranking of emerging T&V by calculating a set of measurement indices related to the actual impact, possible impact on public perception and level of available capabilities associated with every T&V. The systematic characterisation of the processes leading to the assessment of T&V by the VRG has led to a consistent, auditable and transparent approach to the identification and assessment of emerging risks. The regular use of MCDA to manage a portfolio of emerging risks represents a different and novel application of MCDA in a health related context.


The Importance of Iron Status for Young Children in Low- and Middle-Income Countries: A Narrative Review.
Early childhood is characterised by high physiological iron demand to support processes including blood volume expansion, brain development and tissue growth. Iron is also required for other essential functions including the generation of effective immune responses. Adequate iron status is therefore a prerequisite for optimal child development, yet nutritional iron deficiency and inflammation-related iron restriction are widespread amongst young children in low- and middle-income countries (LMICs), meaning iron demands are frequently not met. Consequently, therapeutic iron interventions are commonly recommended. However, iron also influences infection pathogenesis: iron deficiency reduces the risk of malaria, while therapeutic iron may increase susceptibility to malaria, respiratory and gastrointestinal infections, besides reshaping the intestinal microbiome. This means caution should be employed in administering iron interventions to young children in LMIC settings with high infection burdens. In this narrative review, we first examine demand and supply of iron during early childhood, in relation to the molecular understanding of systemic iron control. We then evaluate the importance of iron for distinct aspects of physiology and development, particularly focusing on young LMIC children. We finally discuss the implications and potential for interventions aimed at improving iron status whilst minimising infection-related risks in such settings. Optimal iron intervention strategies will likely need to be individually or setting-specifically adapted according to iron deficiency, inflammation status and infection risk, while maximising iron bioavailability and considering the trade-offs between benefits and risks for different aspects of physiology. The effectiveness of alternative approaches not centred around nutritional iron interventions for children should also be thoroughly evaluated: these include direct targeting of common causes of infection/inflammation, and maternal iron administration during pregnancy.


Intrapartum asphyxia and hypoxic ischaemic encephalopathy in a public hospital: Incidence and predictors of poor outcome.
To determine the incidence of asphyxia and hypoxic ischaemic encephalopathy (HIE) and predictors of poor outcome in a hospital in a developing country. Neonates of birth weight ≥ 2,000 g who required bag-and-mask ventilation and were admitted with a primary diagnosis of asphyxia from January to December 2011 were included. Medical records were retrieved and maternal and infant data collected and analysed. Infants who had severe HIE and/or died were compared with those who survived to hospital discharge with no or mild to moderate HIE. There were 21 086 liveborn infants with a birth weight of 2 000 g over the study period. The incidence of asphyxia ranged from 8.7 to 15.2/1 000 live births and that of HIE from 8.5 to 13.3/1 000, based on the definition of asphyxia used. In 60% of patients with HIE it was moderate to severe. The overall mortality rate was 7.8%. The mortality rate in infants with moderate and severe HIE was 7.1% and 62.5%, respectively. The odds of severe HIE and/or death were high if the Apgar score was <5 at 10 minutes (odds ratio (OR) 19.1; 95% confidence interval (CI) 5.7-66.9) and if there was no spontaneous respiration at 20 minutes (OR 27.2; 95% CI 6.9-117.4), a need for adrenaline (OR 81.2; 95% CI 13.2-647.7) and a pH of < 7 (OR 5.33; 95% CI 1.31-25.16). Predictors of poor outcome were Apgar score at 10 minutes (p = 0.004), need for adrenaline (p = 0.034) and low serum bicarbonate (p = 0.028). The incidence of asphyxia in term and near-term infants is higher than that reported in developed countries. Apgar score at 10 minutes and need for adrenaline remain important factors in predicting poor outcome in infants with asphyxia.


Somatic FGFR and TWIST mutations are not a common cause of isolated nonsyndromic single suture craniosynostosis.
Pathogenic mutations in FGFR2 and TWIST genes are detected in the majority of individuals with Crouzon, Pfeiffer, Apert, and Saethre-Chotzen syndromes. In contrast, mutations have been identified rarely in cases of nonsyndromic, single suture craniosynostosis. Recently, two studies confirming somatic mosaicism with local expression of an FGFR mutation have been reported. This study investigates whether somatic mosaicism could account for nonsyndromic, single suture craniosynostosis. Eight individuals with single suture craniosynostosis who were negative for known mutations in FGFR1-3 and TWIST after screening in their leucocyte DNA were tested for the presence of pathogenic mutations in suture cell-derived DNA. Five had sagittal synostosis, two had metopic synostosis, and the other unicoronal synostosis. Osteoprogenitor cells from surgically excised fusing sutures and an adjacent open suture were cultured. DNA from the cultured cells grown to passage 3 was then examined for underlying FGFR and TWIST mutations. No mutations within the exons of the FGFR or TWIST genes studied were identified in any suture cells. This study found no evidence to support the notion that mosaicism for FGFR or TWIST mutations, normally associated with syndromal forms of craniosynostosis, occur in single suture craniosynostosis. Thus, any underlying genetic defects must occur in regions outside those normally implicated in syndromal craniosynostosis, or this disorder could arise as a consequence of some other epigenetic modification.


A depth refugium from catastrophic coral bleaching prevents regional extinction.
Species intolerant of changing climate might avoid extinction within refugia buffered from extreme conditions. Refugia have been observed in the fossil record but are not well documented or understood on ecological time scales. Using a 37-year record from the eastern Pacific across the two most severe El Niño events on record (1982-1983 and 1997 1998) we show how an exceptionally thermally sensitive reef-building hydrocoral, Millepora intricata, twice survived catastrophic bleaching in a deeper-water refuge (> 11 m depth). During both events, M. intricata was extirpated across its range in shallow water, but showed recovery within several years, while two other hydrocorals without deep-water populations were driven to regional extinction. Evidence from the subfossil record in the same area showed shallow-water persistence of abundant M. intricata populations from 5000 years ago, through severe El Niño-Southern Oscillation cycles, suggesting a potential depth refugium on a millennial timescale. Our data confirm the deep refuge hypothesis for corals under thermal stress.


Protein localization in living cells and tissues using FRET and FLIM.
Interacting proteins assemble into molecular machines that control cellular homeostasis in living cells. While the in vitro screening methods have the advantage of providing direct access to the genetic information encoding unknown protein partners, they do not allow direct access to interactions of these protein partners in their natural environment inside the living cell. Using wide-field, confocal, or two-photon (2p) fluorescence resonance energy transfer (FRET) microscopy, this information can be obtained from living cells and tissues with nanometer resolution. One of the important conditions for FRET to occur is the overlap of the emission spectrum of the donor with the absorption spectrum of the acceptor. As a result of spectral overlap, the FRET signal is always contaminated by donor emission into the acceptor channel and by the excitation of acceptor molecules by the donor excitation wavelength. Mathematical algorithms are required to correct the spectral bleed-through signal in wide-field, confocal, and two-photon FRET microscopy. In contrast, spectral bleed-through is not an issue in FRET/FLIM imaging because only the donor fluorophore lifetime is measured; also, fluorescence lifetime imaging microscopy (FLIM) measurements are independent of excitation intensity or fluorophore concentration. The combination of FRET and FLIM provides high spatial (nanometer) and temporal (nanosecond) resolution when compared to intensity-based FRET imaging. In this paper, we describe various FRET microscopy techniques and its application to protein-protein interactions.


Clinical characteristics and outcomes in patients with traumatic brain injury in China: a prospective, multicentre, longitudinal, observational study.
Large-scale studies are required to better characterise traumatic brain injury (TBI) and to identify the most effective treatment approaches for TBI. However, evidence is scarce and mostly originates from high-income countries. We aimed to describe the existing care for patients with TBI and the outcomes in China. The Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) China registry is a prospective, multicentre, longitudinal, observational study done in 56 neurosurgical centres across China. We collected data of patients who were admitted to hospital with a clinical diagnosis of TBI and an indication for CT. Patients who were discharged directly from the emergency room were excluded. The primary endpoint was survival on discharge. Prognostic analyses were applied to identify predictors of mortality. Variations in mortality were compared between centres and provinces within China. Mortality was compared with expected mortality, estimated using the CRASH basic model. This study was registered with ClinicalTrials.gov, NCT02210221. From Dec 22, 2014, to Aug 1, 2017, 13 627 patients with TBI from 56 centres were enrolled in the registry. Data from 13 138 patients from 52 hospitals in 22 provinces of China were analysed. Most patients were male (9782 [74%]), with a median age of 48 years (IQR 33-61). The median Glasgow Coma Scale (GCS) score was 13 (IQR 9-15), and the leading cause of injury was road-traffic incident (6548 [50%]). Overall, 637 (5%) patients died, including 552 (20%) patients with severe TBI. Age, GCS score, injury severity score, pupillary light reflex, CT findings (compressed basal cistern and midline shift ≥5 mm), presence of hypoxia, systemic hypotension, altitude higher than >500 m, and GDP per capita were significantly associated with survival in all patients with TBI. Variation in mortality existed between centres and regions. The expected 14-day mortality was 1116 (13%), but 544 (7%) deaths within 14 days were observed (observed to expected ratio 0·49 [95% CI 0·45-0·53]). The results show differences in mortality between centres and regions across China, which indicates potential for identifying best practices through comparative effectiveness research. The risk factors identified in prognostic analyses might contribute to developing benchmarks for assessing quality of care. None.


A new home-based mental health program for older adults: description of the first 100 cases.
The Geriatric Psychiatry Outreach (GO) Program began in 2005 and provides in-home psychiatric evaluation and treatment for older adults who have difficulty getting to an office-based setting. An initial assessment was conducted on the first 100 patients seen by the program and follow-up treatment was provided as clinically indicated. The mean age of patients seen was 79.7 (SD: 8.2), 74% were women, and the most common psychiatric diagnoses were depression (50%) and dementia (45%), with a mean of 1.4 (SD: 0.6) psychiatric diagnoses per patient. The patients had a mean of 4.8 (SD: 2.9) medical diagnoses and were on a mean of 6.8 (SD: 4.0) prescription and 2.2 (SD: 1.2) nonprescription medications. Patients received a mean of 4.2 (SD: 4.2) in-person visits and a mean of 30.2 (SD: 36.5) additional contacts related to their care, such as phone calls, e-mails, and faxes. Providing psychiatric services at home for older adults with mental illness is a much needed but rarely available service. Such patients typically have a complex combination of medical and psychiatric diagnoses and benefit from contacts in addition to the face-to-face visits.


Regulation of APC/C activity in oocytes by a Bub1-dependent spindle assembly checkpoint.
Missegregation of chromosomes during meiosis in human females causes aneuploidy, including trisomy 21, and is thought also to be the major cause of age-related infertility. Most errors are thought to occur at the first meiotic division. The high frequency of errors raises questions as to whether the surveillance mechanism known as the spindle assembly checkpoint (SAC) that controls the anaphase-promoting complex or cyclosome (APC/C) operates effectively in oocytes. Experimental approaches hitherto used to inactivate the SAC in oocytes suffer from a number of drawbacks. Bub1 protein was depleted specifically in oocytes with a Zp3-Cre transgene to delete exons 7 and 8 from a floxed BUB1(F) allele. Loss of Bub1 greatly accelerates resolution of chiasmata and extrusion of polar bodies. It also causes defective biorientation of bivalents, massive chromosome missegregation at meiosis I, and precocious loss of cohesion between sister centromeres. By using a quantitative assay for APC/C-mediated securin destruction, we show that the APC/C is activated in an exponential fashion, with activity peaking 12-13 hr after GVBD, and that this process is advanced by 5 hr in oocytes lacking Bub1. Importantly, premature chiasmata resolution does not occur in Bub1-deficient oocytes also lacking either the APC/C's Apc2 subunit or separase. Finally, we show that Bub1's kinase domain is not required to delay APC/C activation. We conclude that far from being absent or ineffective, the SAC largely determines the timing of APC/C and hence separase activation in oocytes, delaying it for about 5 hr.


The Twisted gastrulation family of proteins, together with the IGFBP and CCN families, comprise the TIC superfamily of cysteine rich secreted factors.
To analyse the similarities between the Twisted gastrulation (TSG) proteins known to date; in addition, to determine phylogenetic relations among the TSG proteins, and between the TSGs and other protein families--the CCN (for example, CCN2 (CTGF), CCN1 (CYR61), and CCN3 (NOV)) and IGFBP (insulin-like growth factor binding protein) families. TBLASTN and FASTA3 were used to identify new tsg genes and relatives of the TSG family. The sequences were aligned with ClustalW. The predictions of sites for signal peptide cleavage, post-translational modifications, and putative protein domains were carried out with software available at various databases. Unrooted phylogenetic trees were calculated using the UPGMA method. Several tsg genes from vertebrates and invertebrates were compared. Alignment of protein sequences revealed a highly conserved family of TSG proteins present in both vertebrates and invertebrates, whereas the slightly less well conserved IGFBP and CCN proteins are apparently present only in vertebrates. The TSG proteins display strong homology among themselves and they are composed of a putative signal peptide at the N-terminus followed by a cysteine rich (CR) region, a conserved domain devoid of cysteines, a variable midregion, and a C-terminal CR region. The most striking similarity between the TSGs and the IGFBP and CCN proteins occurs in the N-terminal conserved cysteine rich domain and the characteristic 5' cysteine rich domain(s), spacer region, and 3' cysteine rich domain structure. The family of highly conserved TSG proteins, together with the IGFBP and CCN families, constitute an emerging multigene superfamily of secreted cysteine rich factors. The TSG branch of the superfamily appears to pre-date the others because it is present in all species examined, whereas the CCN and IGFBP genes are found only in vertebrates.


Self-Assembly of Mesoscale Objects into Ordered Two-Dimensional Arrays
Regular arrays of topologically complex, millimeter-scale objects were prepared by self-assembly, with the shapes of the assembling objects and the wettability of their surfaces determining the structure of the arrays. The system was composed of solid objects floating at the interface between perfluorodecalin and water and interacting by lateral capillary forces; patterning of the wettability of the surfaces of the objects directs these forces. Self-assembly results from minimization of the interfacial free energy of the liquid-liquid interface. Calculations suggest that this strategy for self-assembly can be applied to objects on a micrometer scale.


Habitat Use and Spatial Variability of Hawkfishes with a Focus on Colour Polymorphism in Paracirrhites forsteri.
Identifying relationships between fishes and their environment is an integral part of understanding coral reef ecosystems. However, this information is lacking for many species, particularly in understudied and remote regions. With coral reefs continuing to face environmental pressures, insight into abundance and distribution patterns along with resource use of fish communities will aid in advancing our ecological understanding and management processes. Based on ecological surveys of hawkfish assemblages (Family: Cirrhitidae) in the Red Sea, we reveal distinct patterns in the distribution and abundance across the continental shelf, wave exposure, and with depth, particularly in the four colour morphs of Paracirrhites forsteri. Distinct patterns were observed among hawkfishes, with higher abundance of all species recorded on reefs farther from shore and on wave exposed reef zones. Cirrhitus spilotoceps was only recorded on the exposed crest, but unlike the other species, did not associate with live coral colonies. Overall, the most abundant species was P. forsteri. This species exploited a variety of habitats but showed an affinity for complex habitats provided by live and dead coral colonies. No difference in habitat use was observed among the four colour morphs, but distinct patterns were apparent in distribution and abundance with depth. This study suggests that in addition to P. forsteri exhibiting diverse colour morphologies, these various morphotypes appear to have corresponding ecological differences in the Red Sea. To better understand this, further studies are needed to identify what these differences extend to and the mechanisms involved.


1.4 A structure of photoactive yellow protein, a cytosolic photoreceptor: unusual fold, active site, and chromophore.
A photosensing protein directs light energy captured by its chromophore into a photocycle. The protein's structure must accommodate the photocycle and promote the resulting chemical or conformational changes that lead to signal transduction. The 1.4 A crystallographic structure of photoactive yellow protein, determined by multiple isomorphous replacement methods, provides the first view at atomic resolution of a protein with a photocycle. The alpha/beta fold, which differs from the original chain tracing, shows striking similarity to distinct parts of the signal transduction proteins profilin and the SH2 domain. In the dark state structure of photoactive yellow protein, the novel 4-hydroxycinnamyl chromophore, covalently attached to Cys69, is buried within the major hydrophobic core of the protein and is tethered at both ends by hydrogen bonds. In the active site, the yellow anionic form of the chromophore is stabilized by hydrogen bonds from the side chains of Tyr42 and buried Glu46 to the phenolic oxygen atom and by electrostatic complementarity with the positively charged guanidinium group of Arg52. Thr50 further interlocks Tyr42, Glu46, and Arg52 through a network of active site hydrogen bonds. Arg52, located in a concavity of the protein surface adjacent to the dominant patch of negative electrostatic potential, shields the chromophore from solvent and is positioned to form a gateway for the phototactic signal. Overall, the high-resolution structure of photoactive yellow protein supports a mechanism whereby electrostatic interactions create an active site poised for photon-induced rearrangements and efficient protein-mediated signal transduction.


Self-organization of intertidal snails facilitates evolution of aggregation behavior.
Many intertidal snails form aggregations during emersion to minimize desiccation stress. Here we investigate possible mechanisms for the evolution of such behavior. Two behavioral traits (following of mucus trails, and crevice occupation), which both provide selective advantages to individuals that possess the traits over individuals that do not, result in self-organization of aggregations in crevices in the rock surface. We suggest that the existence of self-organizing aggregations provides a mechanism by which aggregation behavior can evolve. The inclusion of an explicitly coded third behavior, aggregation, in a simulated population produces patterns statistically similar to those found on real rocky shores. Allowing these three behaviors to evolve using an evolutionary algorithm, however, results in aggregation behavior being selected against on shores with high crevice density. The inclusion of broadcast spawning dispersal mechanisms in the simulation, however, results in aggregation behavior evolving as predicted on shores with both high crevice density and low crevice density (evolving in crevices first, and then both in crevices and on flat rock), indicating the importance of environmental interactions in understanding evolutionary processes. We propose that self-organization can be an important factor in the evolution of group behaviors.


Querying large read collections in main memory: a versatile data structure.
High Throughput Sequencing (HTS) is now heavily exploited for genome (re-) sequencing, metagenomics, epigenomics, and transcriptomics and requires different, but computer intensive bioinformatic analyses. When a reference genome is available, mapping reads on it is the first step of this analysis. Read mapping programs owe their efficiency to the use of involved genome indexing data structures, like the Burrows-Wheeler transform. Recent solutions index both the genome, and the k-mers of the reads using hash-tables to further increase efficiency and accuracy. In various contexts (e.g. assembly or transcriptome analysis), read processing requires to determine the sub-collection of reads that are related to a given sequence, which is done by searching for some k-mers in the reads. Currently, many developments have focused on genome indexing structures for read mapping, but the question of read indexing remains broadly unexplored. However, the increase in sequence throughput urges for new algorithmic solutions to query large read collections efficiently. Here, we present a solution, named Gk arrays, to index large collections of reads, an algorithm to build the structure, and procedures to query it. Once constructed, the index structure is kept in main memory and is repeatedly accessed to answer queries like "given a k-mer, get the reads containing this k-mer (once/at least once)". We compared our structure to other solutions that adapt uncompressed indexing structures designed for long texts and show that it processes queries fast, while requiring much less memory. Our structure can thus handle larger read collections. We provide examples where such queries are adapted to different types of read analysis (SNP detection, assembly, RNA-Seq). Gk arrays constitute a versatile data structure that enables fast and more accurate read analysis in various contexts. The Gk arrays provide a flexible brick to design innovative programs that mine efficiently genomics, epigenomics, metagenomics, or transcriptomics reads. The Gk arrays library is available under Cecill (GPL compliant) license from http://www.atgc-montpellier.fr/ngs/.


Analysis of bacterial biofilms using NMR-based metabolomics.
Infectious diseases can be difficult to cure, especially if the pathogen forms a biofilm. After decades of extensive research into the morphology, physiology and genomics of biofilm formation, attention has recently been directed toward the analysis of the cellular metabolome in order to understand the transformation of a planktonic cell to a biofilm. Metabolomics can play an invaluable role in enhancing our understanding of the underlying biological processes related to the structure, formation and antibiotic resistance of biofilms. A systematic view of metabolic pathways or processes responsible for regulating this 'social structure' of microorganisms may provide critical insights into biofilm-related drug resistance and lead to novel treatments. This review will discuss the development of NMR-based metabolomics as a technology to study medically relevant biofilms. Recent advancements from case studies reviewed in this manuscript have shown the potential of metabolomics to shed light on numerous biological problems related to biofilms.


Canopy position has a profound effect on soybean seed composition.
Although soybean seeds appear homogeneous, their composition (protein, oil and mineral concentrations) can vary significantly with the canopy position where they were produced. In studies with 10 cultivars grown over a 3-yr period, we found that seeds produced at the top of the canopy have higher concentrations of protein but less oil and lower concentrations of minerals such as Mg, Fe, and Cu compared to seeds produced at the bottom of the canopy. Among cultivars, mean protein concentration (average of different positions) correlated positively with mean concentrations of S, Zn and Fe, but not other minerals. Therefore, on a whole plant basis, the uptake and allocation of S, Zn and Fe to seeds correlated with the production and allocation of reduced N to seed protein; however, the reduced N and correlated minerals (S, Zn and Fe) showed different patterns of allocation among node positions. For example, while mean concentrations of protein and Fe correlated positively, the two parameters correlated negatively in terms of variation with canopy position. Altering the microenvironment within the soybean canopy by removing neighboring plants at flowering increased protein concentration in particular at lower node positions and thus altered the node-position gradient in protein (and oil) without altering the distribution of Mg, Fe and Cu, suggesting different underlying control mechanisms. Metabolomic analysis of developing seeds at different positions in the canopy suggests that availability of free asparagine may be a positive determinant of storage protein accumulation in seeds and may explain the increased protein accumulation in seeds produced at the top of the canopy. Our results establish node-position variation in seed constituents and provide a new experimental system to identify genes controlling key aspects of seed composition. In addition, our results provide an unexpected and simple approach to link agronomic practices to improve human nutrition and health in developing countries because food products produced from seeds at the bottom of the canopy contained higher Fe concentrations than products from the top of the canopy. Therefore, using seeds produced in the lower canopy for production of iron-rich soy foods for human consumption could be important when plants are the major source of protein and human diets can be chronically deficient in Fe and other minerals.


Control of hyperuricemia in subjects with refractory gout, and induction of antibody against poly(ethylene glycol) (PEG), in a phase I trial of subcutaneous PEGylated urate oxidase.
PEG-modified recombinant mammalian urate oxidase (PEG-uricase) is being developed as a treatment for patients with chronic gout who are intolerant of, or refractory to, available therapy for controlling hyperuricemia. In an open-label phase I trial, single subcutaneous injections of PEG-uricase (4 to 24 mg) were administered to 13 such subjects (11 had tophaceous gout), whose plasma uric acid concentration (pUAc) was 11.3 +/- 2.1 mg/dl (mean +/- SD). By day seven after injection of PEG-uricase, pUAc had declined by an average of 7.9 mg/dl and had normalized in 11 subjects, whose mean pUAc decreased to 2.8 +/- 2.2 mg/dl. At doses of 8, 12, and 24 mg, the mean pUAc at 21 days after injection remained no more than 6 mg/dl. In eight subjects, plasma uricase activity was still measurable at 21 days after injection (half-life 10.5 to 19.9 days). In the other five subjects, plasma uricase activity could not be detected beyond ten days after injection; this was associated with the appearance of relatively low-titer IgM and IgG antibodies against PEG-uricase. Unexpectedly, these antibodies were directed against PEG itself rather than the uricase protein. Three PEG antibody-positive subjects had injection-site reactions at 8 to 9 days after injection. Gout flares in six subjects were the only other significant adverse reactions, and PEG-uricase was otherwise well tolerated. A prolonged circulating life and the ability to normalize plasma uric acid in markedly hyperuricemic subjects suggest that PEG-uricase could be effective in depleting expanded tissue stores of uric acid in subjects with chronic or tophaceous gout. The development of anti-PEG antibodies, which may limit efficacy in some patients, is contrary to the general assumption that PEG is non-immunogenic. PEG immunogenicity deserves further investigation, because it has potential implications for other PEGylated therapeutic agents in clinical use.


Loss of Nix in Pdx1-deficient mice prevents apoptotic and necrotic β cell death and diabetes.
Mutations in pancreatic duodenal homeobox (PDX1) are linked to human type 2 diabetes and maturity-onset diabetes of the young type 4. Consistent with this, Pdx1-haploinsufficient mice develop diabetes. Both apoptosis and necrosis of β cells are mechanistically implicated in diabetes in these mice, but a molecular link between Pdx1 and these 2 forms of cell death has not been defined. In this study, we introduced an shRNA into mouse insulinoma MIN6 cells to deplete Pdx1 and found that expression of proapoptotic genes, including NIP3-like protein X (Nix), was increased. Forced Nix expression in MIN6 and pancreatic islet β cells induced programmed cell death by simultaneously activating apoptotic and mitochondrial permeability transition-dependent necrotic pathways. Preventing Nix upregulation during Pdx1 suppression abrogated apoptotic and necrotic β cell death in vitro. In Pdx1-haploinsufficient mice, Nix ablation normalized pancreatic islet architecture, β cell mass, and insulin secretion and eliminated reactive hyperglycemia after glucose challenge. These results establish Nix as a critical mediator of β cell apoptosis and programmed necrosis in Pdx1-deficient diabetes.


Disparities in mental health among adolescents with and without impairments.
To analyse whether there are differences in mental health among adolescents with and without various kinds of impairments, taking into account the number of impairments and gender. Data from the study Life & Health - Young People conducted in a Swedish county in 2011 was used. The survey included all students in grades 7 (13-14 years) and 9 (15-16 years) in compulsory school and grade 2 (17-18 years) in upper secondary school; there were 7793 respondents (81.0%). The students answered a questionnaire anonymously during school hours. Various measures of mental health were assessed in the groups: hard of hearing, visual impairment, motor impairment, difficulties in reading/writing/dyslexia, attention deficit hyperactive disorder/attention deficit disorder, other impairment, no impairment. Of the studied impairments, difficulties in reading/writing/dyslexia are the most common (6.3%), followed by hard of hearing (5.4%). To have at least one impairment is more common among boys (18.2%) than girls (15.4%). In the impairment group, 21.5% have multiple impairments. Adolescents with impairments have worse mental health than those without, and those with multiple impairments have particularly higher odds ratio to have worse mental health. There are also differences in mental health between number and various kinds of impairments and between girls and boys. Adolescents with impairments, particularly girls and those with multiple impairments, have considerably worse mental health than others. These inequalities in health are an immense challenge, not only for those directly involved with the impaired: they affect everyone involved with the goal health equity for the whole population.


Factors that may Facilitate or Hinder a Family-Focus in the Treatment of Parents with a Mental Illness.
Children with mentally ill parents are at risk of developing mental health problems themselves. To enhance early support for these children may prevent mental health problems from being transmitted from one generation to the next. The sample (N = 219) included health professionals in a large university hospital, who responded to a web-based survey on the routines of the mental health services, attitudes within the workforce capacity, worker's knowledge on the impact of parental mental illness on children, knowledge on legislation concerning children of patients, experience, expectations for possible outcomes of change in current clinical practice and demographic variables. A total of 56 % reported that they did not identify whether or not patients had children. There were no significant differences between the groups (identifiers and non-identifiers) except for the two scales measuring aspects of knowledge, i.e., Knowledge Children and Knowledge Legislation where workers who identified children had higher scores. The results also showed that younger workers with a medium level of education scored higher on Positive Attitudes. Furthermore, workers who reported to have more knowledge about children and the impact of mental illness on the parenting role were less concerned about a child-focussed approach interfering with the patient-therapist relation.


Therapy with the elderly: introducing psychodynamic psychotherapy to the multi-disciplinary team.
Psychotherapy with the elderly has tended to be restricted to family or behavioural paradigms with some contribution from cognitive approaches, but at least until recently, very little input from psychodynamic therapy. The reasons for this are discussed and include both patient and therapist factors. Freud himself was pessimistic regarding the prospects of working with the elderly, a viewpoint he changed as he aged. As the discipline of old age psychiatry also matures there may be increasing scope for collaboration between the mental health of the elderly teams and psychodynamically orientated therapists. We describe here one model of such collaboration, a weekly case discussion seminar, conducted in an acute admission old age psychiatry in-patient unit. The role of the seminar in discussing difficult cases will be described and a case will be discussed to illustrate the work. Finally, recommendations for broadening the scope of the work are advanced.


Classification and treatment follow-up of a juxtapapillary retinal hemangioblastoma with optical coherence tomography angiography.
Only an endophytic growth pattern in juxtapapillary retinal hemangioblastoma (JRH) is an indication for surgical treatment, but classification of growth types is difficult using conventional imaging techniques. This case report describes the use of optical coherence tomography angiography (OCT-A) features for classification and treatment follow-up in a case with JRH. The JRH of this patient was easily detected with two different OCT-A methods in both en-face and cross-sectional B-scan images, and was classified as a sessile growth type. This growth type excluded the treatment option of vitreoretinal surgery with excision of the lesion or ligation of the feeder vessels. The patient was treated multiple times with intravitreal bevacizumab. Treatment follow-up with OCT-A initially revealed a stable extent of the JRH, with some slight flow deviations in en-face visualization, followed by a period of progressive growth of the lesion. OCT-A revealed the depth localization of the JRH and seems to be a valuable tool for JRH classification. Detailed classification may be useful when surgery is considered as a treatment strategy. Furthermore, treatment follow-up is possible with OCT-A, although imaging artifacts should be taken into account.


5-Nitroindole oligonucleotides with alkynyl side chains: universal base pairing, triple bond hydration and properties of pyrene "click" adducts.
Oligonucleotides with 3-ethynyl-5-nitroindole and 3-octadiynyl-5-nitroindole 2'-deoxyribonucleosides were prepared by solid-phase synthesis. To this end, nucleoside phosphoramidites with clickable side chains were synthesized. The 3-ethynylated 5-nitroindole nucleoside was hydrated during automatized DNA synthesis to 3-acetyl-5-nitroindole 2'-deoxyribonucleoside. Side product formation was circumvented by triisopropylsilyl protection of the ethynyl side chain and was removed with TBAF after oligonucleotide synthesis. All compounds with a clickable 5-nitroindole skeleton show universal base pairing and can be functionalized with almost any azide in any position of the DNA chain. Functionalization of the side chain with 1-azidomethylpyrene afforded click adducts in which the fluorescence was quenched by the 5-nitroindole moieties. However, fluorescence was slightly recovered during duplex formation. Oligonucleotides with a pyrene residue and a long linker arm are stabilized over those with non-functionalized side chains. From the UV red shift of the pyrene residue in oligonucleotides and modelling studies, pyrene intercalation was established for the long linker adduct showing increased duplex stability over those with a short side chain.


Insulin Phosphorylates Tyrosine Residue 464 of Tub and Translocates Tubby into the Nucleus in HIRcB Cells.
The tubby protein has a motif that might be relevant for its action in the insulin signaling pathway. Previous studies have indicated that tubby undergoes phosphorylation on tyrosine residues in response to several stimuli and is known to localize in the nucleus as well as in the plasma membrane. However, the relationship between phosphorylation and nuclear translocation is not well understood. Here, we report that insulin directly phosphorylates tubby, which translocates into the nucleus. The effects of insulin on Tubby were performed with Western blot. The immunoprecipitation and confocal microscopy were performed to prove phosphorylation and nuclear translocation. Mutation study reveals that tyrosine residue 464 of tubby gene (Tub) is a phosphorylation site activated by insulin. In addition, major portions of tubby protein in the plasma membrane are translocated into the nucleus after insulin treatment. Tyrosine kinase inhibitor pretreatment blocked insulin-induced tubby translocation, suggesting that phosphorylation is important for nuclear translocation. Moreover, mutant tyrosine residue 464 did not translocate into the nucleus in respond to insulin. These findings demonstrate that insulin phosphorylates tyrosine residue 464 of Tub, and this event is important for insulin-induced tubby nuclear translocation. Insulin phosphorylates tyrosine residue 464 of Tub and translocates tubby into the nuclei of HIRcB cells.


Immobilization of histidine-tagged proteins by magnetic nanoparticles encapsulated with nitrilotriacetic acid (NTA)-phospholipids micelle.
We described the development of functionalized magnetic nanoparticles (MNPs) with PEG-modification, a phospholipids micelle coating, and their use in manipulating histidine-tagged proteins. Highly monodisperse MNPs were synthesized in an organic solvent and could be phase-transferred into an aqueous solution by encapsulating the nanoparticles with a phospholipids micelle. The phospholipids micelle coating rendered the nanoparticles highly water-soluble, and the functional groups of the phospholipids coating allowed for the bioconjugation of various moieties, such as fluorescent molecules and engineered proteins. Functionalized phospholipids, such as nitrilotriacetic acid (NTA)-phospholipids, caused the MNPs to bind and allowed for manipulation of histidine-tagged proteins. Due to their high surface/volume ratio, the MNPs showed better performance (about 100 times higher) in immobilizing engineered proteins than conventional micrometer-sized beads. This demonstrates that MNPs coated with phospholipids micelle can be a versatile platform for the effective manipulation of various kinds of engineered proteins, which is very important in the field of proteomics. It is expected that a combination of MNPs with optical fluorescent molecules can find applications in bimodal (magnetic and optical) molecular imaging nanoprobes.


DNA technology.
Scientific developments in molecular biology enable clinical laboratory testing to directly examine genetic information coded in biologic specimens. These efforts, accomplished by the use of DNA probe technology in the in situ hybridization and other tests will allow for the specific identification of pathogens; recognition of genetic diseases; and the critical evaluation of the genetic basis of cancer. The authors discuss the concepts and uses of DNA testing.


Piezoelectric bimorph optical-fiber sensor.
We propose and demonstrate a novel high-voltage optical-fiber sensor. This sensor consists of an emitting fiber, a receiving fiber, and a piezoelectric bimorph transducer. The emitting fiber is fixed in a base, whereas the receiving fiber is mounted on the free end of the piezoelectric bimorph transducer. When a voltage is applied to the piezoelectric bimorph transducer, its free end is displaced over a distance delta. The displacement induces a loss in the optical coupling between the emitting and the receiving fiber. The voltage can be measured by monitoring the coupling loss.


The unique social sense of puerperium: Increased empathy and Schadenfreude in parents of newborns.
Pregnancy and puerperium are typified by marked biobehavioral changes. These changes, which are traceable in both mothers and fathers, play an important role in parenthood and may modulate social cognition abilities. However, the latter effects remain notably unexplored in parents of newborns (PNs). To bridge this gap, we assessed empathy and social emotions (envy and Schadenfreude) in 55 PNs and 60 controls (childless healthy participants without a romantic relationship or sexual intercourse in the previous 48 hours). We used facial electromyography to detect physiological signatures of social emotion processing. Results revealed higher levels of affective empathy and Schadenfreude in PNs, the latter pattern being accompanied by increased activity of the corrugator suppercilii region. These effects were not explained by potential confounding variables (educational level, executive functioning, depression, stress levels, hours of sleep). Our novel findings suggest that PNs might show social cognition changes crucial for parental bonding and newborn care.


Defining the three cell lineages of the human blastocyst by single-cell RNA-seq.
Here, we provide fundamental insights into early human development by single-cell RNA-sequencing of human and mouse preimplantation embryos. We elucidate conserved transcriptional programs along with those that are human specific. Importantly, we validate our RNA-sequencing findings at the protein level, which further reveals differences in human and mouse embryo gene expression. For example, we identify several genes exclusively expressed in the human pluripotent epiblast, including the transcription factor KLF17. Key components of the TGF-β signalling pathway, including NODAL, GDF3, TGFBR1/ALK5, LEFTY1, SMAD2, SMAD4 and TDGF1, are also enriched in the human epiblast. Intriguingly, inhibition of TGF-β signalling abrogates NANOG expression in human epiblast cells, consistent with a requirement for this pathway in pluripotency. Although the key trophectoderm factors Id2, Elf5 and Eomes are exclusively localized to this lineage in the mouse, the human orthologues are either absent or expressed in alternative lineages. Importantly, we also identify genes with conserved expression dynamics, including Foxa2/FOXA2, which we show is restricted to the primitive endoderm in both human and mouse embryos. Comparison of the human epiblast to existing embryonic stem cells (hESCs) reveals conservation of pluripotency but also additional pathways more enriched in hESCs. Our analysis highlights significant differences in human preimplantation development compared with mouse and provides a molecular blueprint to understand human embryogenesis and its relationship to stem cells.


Thoracoscopic talc poudrage pleurodesis for chronic recurrent pleural effusions.
To assess the effectiveness of thoracoscopic talc poudrage for the treatment of chronic pleural effusions. Prospective evaluation. Kaiser-Permanente Hospital. Forty-seven consecutive patients with recalcitrant pleural effusions, referred for thoracoscopy. Patients received general or local anesthesia; 42 had a 7-mm rigid thoracoscopic examination followed by insufflation of 5 mL of talc. Patients then had chest-tube drainage. We recorded clinical characteristics, final diagnosis, procedure-related pain and morbidity, days of hospitalization, patient-reported degree of symptom relief, and chest roentgenographic results at 1, 3, and 12 months. All patients were followed for 16 months or until death. Of 39 evaluable patients, all reported prolonged relief of effusion-related dyspnea. Radiographic results confirmed the elimination of pleural effusions in 34 patients (87%), including all 11 with benign conditions and 23 of 28 (82%) with malignancies. Treatment failed in three patients because of entrapped lung and in two patients with mesotheliomas whose effusions recurred more than a year after treatment. No procedure-related mortality or morbidity was found. Ambulatory patients required hospitalization for a mean of 3.9 days (range, 2 to 11 days). Mild pain was reported by some patients. The mean duration of chest-tube drainage was 2.7 days (range, 1 to 9 days). Patients with malignant disease lived an average of 12.4 months (range, 1 to 61 months) after the procedure. Thoracoscopic talc poudrage is an effective pleural sclerosing technique and is relatively painless.


Dynamic plantar loading index: understanding the benefit of custom foot orthoses for painful pes cavus.
The purpose of this study was to evaluate a new method showing how custom foot orthoses (CFO) improve dynamics of plantar loading. The method is based on the probability distribution of peak pressure time series and is quantified using the Regression Factor (RF). RF is a least square regression slope between the experimentally observed plantar pressure magnitude probability distribution and a modeled Gaussian shape. Plantar pressure data from a randomized controlled trial of 154 participants with painful Pes Cavus were retrospectively re-analyzed. The participants were randomized to an active treatment group given CFO or a control group given sham orthoses. The location of 2(nd) Peak pressure as a percentage of stance time (P(Loc2)) and its magnitude (P(M2)) was also calculated. In addition, plantar pressure data were collected on 23 healthy volunteers with normal foot alignment and no foot pain. Results demonstrated Pes Cavus had a significantly lower RF than healthy participants (0.30 v. 0.51; p<10(-7)). P(M2) was reduced in both active and control groups. However, RF and the P(Loc2) were only changed in the active group (p<0.005) without any significant change in the control group (p>0.5). This study suggests that painful Pes Cavus alters the shape of probability distribution of plantar loading during walking and CFO are an effective therapeutic solution that can significantly improve it. Further use of the RF index and 2(nd) peak pressure location as an outcome measure for treatment of foot and ankle deformities is suggested.


A Bayesian approach to estimate changes in condom use from limited human immunodeficiency virus prevalence data.
Evaluation of large-scale intervention programmes against human immunodeficiency virus (HIV) is becoming increasingly important, but impact estimates frequently hinge on knowledge of changes in behaviour such as the frequency of condom use over time, or other self-reported behaviour changes, for which we generally have limited or potentially biased data. We employ a Bayesian inference methodology that incorporates an HIV transmission dynamics model to estimate condom use time trends from HIV prevalence data. Estimation is implemented via particle Markov chain Monte Carlo methods, applied for the first time in this context. The preliminary choice of the formulation for the time varying parameter reflecting the proportion of condom use is critical in the context studied, because of the very limited amount of condom use and HIV data available. We consider various novel formulations to explore the trajectory of condom use over time, based on diffusion-driven trajectories and smooth sigmoid curves. Numerical simulations indicate that informative results can be obtained regarding the amplitude of the increase in condom use during an intervention, with good levels of sensitivity and specificity performance in effectively detecting changes. The application of this method to a real life problem demonstrates how it can help in evaluating HIV interventions based on a small number of prevalence estimates, and it opens the way to similar applications in different contexts.


Temporary atrial pacing for cardiac output after pediatric cardiac surgery.
Pediatric cardiothoracic surgery is often associated with low cardiac output in the postoperative period. This study sought to determine whether increasing heart rate via temporary atrial pacing is beneficial in augmenting cardiac output. Patients younger than 18 years who underwent cardiothoracic surgery and had no perioperative arrhythmias were eligible for the study. Patients not paced postoperatively were atrial paced at a rate of 15 % above the intrinsic sinus rate (not to exceed 170 beats per minute, less for older patients) for 15 min. Patients paced for cardiac output postoperatively had their pacemakers paused for 15 min. Markers of cardiac output were measured before and after the intervention. Of the 60 patients who consented to participate, 30 completed the study. Failure to complete the study was due to tachycardia (n = 13), lack of pacing wires (n = 7), junctional rhythm (n = 4), advanced atrioventricular block (n = 3), and other cause (n = 3). Three patients were paced at baseline. There was no change in arteriovenous oxygen saturation difference, mean arterial blood pressure, central venous pressure, toe temperature, or lactate with atrial pacing. Atrial pacing was associated with a decrease in head and flank near-infrared spectroscopy (p = 0.01 and <0.01 respectively). Secondary analysis found an inverse relationship between mean arterial pressure response to pacing and bypass time. Temporary atrial pacing does not improve cardiac output after pediatric cardiac surgery and may be deleterious. Future research may identify subsets of patients who benefit from this strategy. Practitioners considering this strategy should carefully evaluate each patient's response to atrial pacing before its implementation.


Thinking beyond rupture: continuity and relationality in everyday illness and dying experience.
This article challenges the dominance of a rupture model for understanding how we live day-to-day with life-threatening illness and the prospect of death. It argues that this model acts as a key interpretive framework for understanding dying and its related experiences. As a result, a rupture model upholds a normative and inherently crisis-based view of severe ill-health that reifies dying as an experience which exists outside of, and somehow transformatively beyond, everyday matters of ordinary life. These matters include the minutiae of daily experience which inform and shape our lived identities - as individuals and as relational selves. Drawing primarily on interview data from two family case studies that have contributed to an ethnographic project exploring family experiences of living with life-threatening illness, it will show how mundane, daily life is integral to understanding the ways in which families are produced and able to maintain a sense of continuity during circumstances of impending death. The analysis presented here moves analytical understanding of dying experience towards a theory of how individuals and families 'know' and engage with so-called 'big' life events and experiences. In this way, my study helps generate a novel and more inclusive way of understanding living with life-threatening/limiting illness.