Bacterial Selection during the Formation of Early-Stage Aerobic Granules in Wastewater Treatment Systems Operated Under Wash-Out Dynamics.
Aerobic granular sludge is attractive for high-rate biological wastewater treatment. Biomass wash-out conditions stimulate the formation of aerobic granules. Deteriorated performances in biomass settling and nutrient removal during start-up have however often been reported. The effect of wash-out dynamics was investigated on bacterial selection, biomass settling behavior, and metabolic activities during the formation of early-stage granules from activated sludge of two wastewater treatment plants (WWTP) over start-up periods of maximum 60 days. Five bubble-column sequencing batch reactors were operated with feast-famine regimes consisting of rapid pulse or slow anaerobic feeding followed by aerobic starvation. Slow-settling fluffy granules were formed when an insufficient superficial air velocity (SAV; 1.8 cm s(-1)) was applied, when the inoculation sludge was taken from a WWTP removing organic matter only, or when reactors were operated at 30°C. Fast-settling dense granules were obtained with 4.0 cm s(-1) SAV, or when the inoculation sludge was taken from a WWTP removing all nutrients biologically. However, only carbon was aerobically removed during start-up. Fluffy granules and dense granules were displaying distinct predominant phylotypes, namely filamentous Burkholderiales affiliates and Zoogloea relatives, respectively. The latter were predominant in dense granules independently from the feeding regime. A combination of insufficient solid retention time and of leakage of acetate into the aeration phase during intensive biomass wash-out was the cause for the proliferation of Zoogloea spp. in dense granules, and for the deterioration of BNR performances. It is however not certain that Zoogloea-like organisms are essential in granule formation. Optimal operation conditions should be elucidated for maintaining a balance between organisms with granulation propensity and nutrient removing organisms in order to form granules with BNR activities in short start-up periods.


Limitations of the use of group-specific primers in real-time PCR as appear from quantitative analyses of closely related ammonia-oxidising species.
To study the ecology of ammonia-oxidising bacteria (AOB), quantitative techniques are essential. Real-time PCR assays based on the 16S rRNA or on the structural amoA gene are routinely used. The CTO primer set rooted on the 16S rRNA gene has a number of mismatches with some of the cultures of AOB. To examine if these mismatches have an effect on the outcome of real-time PCR assays, the assay was tested with DNA from a number of closely related isolates of AOB. Standard curves of known amounts of initial DNA were similar among most of the tested cultures of AOB, except for the standard curves of Nitrosomonas strain AL212 and Nitrosospira strain NpAV. Nitrosomonas strain AL212 had 3 mismatches with the CTO primer set. Adaptation of the CTO primer set in order to perfectly match the Nitrosomonas strain AL212 gave a standard curve similar to the majority of the AOB tested. As Nitrosospira strain NpAV has no mismatches with the original CTO primer set, there must be another reason for the less efficient amplification than the sequence itself. Application of an existing sigmoidal mathematical model gave no other results with respect to the standard curves of Nitrosomonas europaea and Nitrosomonas strain AL212, but also demonstrated that primer mismatches can seriously underestimate the initial target concentration. It was concluded that in general correct interpretation of real-time PCR results requires knowledge of the target community composition, in particular of the target sequences of the dominant community members.


Modeled response of the West Nile virus vector Culex quinquefasciatus to changing climate using the dynamic mosquito simulation model.
Climate can strongly influence the population dynamics of disease vectors and is consequently a key component of disease ecology. Future climate change and variability may alter the location and seasonality of many disease vectors, possibly increasing the risk of disease transmission to humans. The mosquito species Culex quinquefasciatus is a concern across the southern United States because of its role as a West Nile virus vector and its affinity for urban environments. Using established relationships between atmospheric variables (temperature and precipitation) and mosquito development, we have created the Dynamic Mosquito Simulation Model (DyMSiM) to simulate Cx. quinquefasciatus population dynamics. The model is driven with climate data and validated against mosquito count data from Pasco County, Florida and Coachella Valley, California. Using 1-week and 2-week filters, mosquito trap data are reproduced well by the model (P < 0.0001). Dry environments in southern California produce different mosquito population trends than moist locations in Florida. Florida and California mosquito populations are generally temperature-limited in winter. In California, locations are water-limited through much of the year. Using future climate projection data generated by the National Center for Atmospheric Research CCSM3 general circulation model, we applied temperature and precipitation offsets to the climate data at each location to evaluate mosquito population sensitivity to possible future climate conditions. We found that temperature and precipitation shifts act interdependently to cause remarkable changes in modeled mosquito population dynamics. Impacts include a summer population decline from drying in California due to loss of immature mosquito habitats, and in Florida a decrease in late-season mosquito populations due to drier late summer conditions.


Development and evaluation of the modiolar research array--multi-centre collaborative study in human temporal bones.
Multi-centre collaborative study to develop and refine the design of a prototype thin perimodiolar cochlear implant electrode array and to assess feasibility for use in human subjects. Multi-centre temporal bone insertion studies. The modiolar research array (MRA) is a thin pre-curved electrode that is held straight for initial insertion with an external sheath rather than an internal stylet. Between November 2006 and February 2009, six iterations of electrode design were studied in 21 separate insertion studies in which 140 electrode insertions were performed in 85 human temporal bones by 12 surgeons. These studies aimed at addressing four fundamental questions related to the electrode concept, being: (1) Could a sheath result in additional intra-cochlear trauma? (2) Could a sheath accommodate variations in cochlea size and anatomies? (3) Could a sheath be inserted via the round window? and (4) Could a sheath be safely removed once the electrode had been inserted? These questions were investigated within these studies using a number of evaluation techniques, including X-ray and microfluoroscopy, acrylic fixation and temporal bone histologic sectioning, temporal bone microdissection of cochlear structures with electrode visualization, rotational tomography, and insertion force analysis. Frequent examples of electrode rotation and tip fold-over were demonstrated with the initial designs. This was typically caused by excessive curvature of the electrode tip, and also difficulty in handling of the electrode and sheath. The degree of tip curvature was progressively relaxed in subsequent versions with a corresponding reduction in the frequency of tip fold-over. Modifications to the sheath facilitated electrode insertion and sheath removal. Insertion studies with the final MRA design demonstrated minimal trauma, excellent perimodiolar placement, and very small electrode dimensions within scala tympani. Force measurements in temporal bones demonstrated negligible force on cochlear structures with angular insertion depths of between 390 and 450°. The MRA is a novel, very thin perimodiolar prototype electrode array that has been developed using a systematic collaborative approach. The different evaluation techniques employed by the investigators contributed to the early identification of issues and generation of solutions. Regarding the four fundamental questions related to the electrode concept, the studies demonstrated that (1) the sheath did not result in additional intra-cochlear trauma; (2) the sheath could accommodate variations in cochlea size and anatomies; (3) the sheath was more successfully inserted via a cochleostomy than via the round window; and (4) the sheath could be safely removed once the electrode had been inserted.


Meals served to hypertensive and cardiac inpatients in Jordan: comparison with WHO and NIH dietary guidelines.
This study aimed to evaluate the compliance of daily meals served to hypertensive and cardiac inpatients in Jordan according to WHO guidelines and the Therapeutic Lifestyle Changes (TLC) and Dietary Approach to Stop Hypertension (DASH) diets plans. Weekly cycle menus from the food service department of major hospitals in Jordan (n = 16) were analysed using ESHA Food Processor software to obtain data about macroand micronutrient contents and food groups represented. The results showed inappropriate amounts of several nutrients in the menus provided, along with a general noncompliance with the DASH, TLC and WHO guidelines. Meals had higher than recommended sodium content coupled with low potassium content. Fatty acid profiles were often outside the recommended ranges. Meals provided to cardiac inpatients in Jordan need to be revised to meet the guidelines specified for the health conditions of these patients.


Vector Symbolic Spiking Neural Network Model of Hippocampal Subarea CA1 Novelty Detection Functionality.
A neural network model is presented of novelty detection in the CA1 subdomain of the hippocampal formation from the perspective of information flow. This computational model is restricted on several levels by both anatomical information about hippocampal circuitry and behavioral data from studies done in rats. Several studies report that the CA1 area broadcasts a generalized novelty signal in response to changes in the environment. Using the neural engineering framework developed by Eliasmith et al., a spiking neural network architecture is created that is able to compare high-dimensional vectors, symbolizing semantic information, according to the semantic pointer hypothesis. This model then computes the similarity between the vectors, as both direct inputs and a recalled memory from a long-term memory network by performing the dot-product operation in a novelty neural network architecture. The developed CA1 model agrees with available neuroanatomical data, as well as the presented behavioral data, and so it is a biologically realistic model of novelty detection in the hippocampus, which can provide a feasible explanation for experimentally observed dynamics.


Association mapping of complex diseases in linked regions: estimation of genetic effects and feasibility of testing rare variants.
Association mapping in linked regions is a current major approach for the identification of genes for complex diseases. Loci contributing to linkage, even with small values of sibling recurrence risk (lambda(s)), may be equivalent to substantial underlying genetic effects for association studies. For disease alleles with a frequency as low as 1%, highly reliable association studies (80% power for significance level alpha=10(-6)) require only 277, 781, and 1289 families or cases and controls for loci detected with lambda(s) of 1.5, 1.1, and 1.05, respectively, under a multiplicative genetic model. Under alternative models, provided epistatic effects are minor, larger achievable sample sizes will provide sufficient power to map almost any disease gene that may have initially contributed to linkage.


Mechanism of action of nikkomycin and the peptide transport system of Candida albicans.
Nikkomycin was found to be a potent growth inhibitor of Candida albicans through competitive inhibition of chitin synthase [Ki = 0.16 microM (0.1 microgram ml-1)]. The activity of the peptide-nucleoside drug was antagonized by both peptone and defined peptides. Transported dipeptides were effective antagonists while transported oligopeptides were not. A mutant of C. albicans resistant to the effects of nikkomycin through a transport defect was unable to transport dipeptides, while oligopeptide uptake was apparently unaffected. At least two peptide permeases are operational in this organism.


Disruption of retinoic acid receptor alpha reveals the growth promoter face of retinoic acid.
Retinoic acid (RA), the bioactive derivative of Vitamin A, by epigenetically controlling transcription through the RA-receptors (RARs), exerts a potent antiproliferative effect on human cells. However, a number of studies show that RA can also promote cell survival and growth. In the course of one of our studies we observed that disruption of RA-receptor alpha, RARalpha, abrogates the RA-mediated growth-inhibitory effects and unmasks the growth-promoting face of RA (Ren et al., Mol. Cell. Biol., 2005, 25:10591). The objective of this study was to investigate whether RA can differentially govern cell growth, in the presence and absence of RARalpha, through differential regulation of the "rheostat" comprising ceramide (CER), the sphingolipid with growth-inhibitory activity, and sphingosine-1-phosphate (S1P), the sphingolipid with prosurvival activity. We found that functional inhibition of endogenous RARalpha in breast cancer cells by using either RARalpha specific antagonists or a dominant negative RARalpha mutant hampers on one hand the RA-induced upregulation of neutral sphingomyelinase (nSMase)-mediated CER synthesis, and on the other hand the RA-induced downregulation of sphingosine kinase 1, SK1, pivotal for S1P synthesis. In association with RA inability to regulate the sphingolipid rheostat, cells not only survive, but also grow more in response to RA both in vitro and in vivo. By combining genetic, pharmacological and biochemical approaches, we mechanistically demonstrated that RA-induced growth is, at least in part, due to non-RAR-mediated activation of the SK1-S1P signaling. In the presence of functional RARalpha, RA inhibits cell growth by concertedly, and inversely, modulating the CER and S1P synthetic pathways. In the absence of a functional RARalpha, RA-in a non-RAR-mediated fashion-promotes cell growth by activating the prosurvival S1P signaling. These two distinct, yet integrated processes apparently concur to the growth-promoter effects of RA.


A quantitative association study of SLC25A12 and restricted repetitive behavior traits in autism spectrum disorders.
SLC25A12 was previously identified by a linkage-directed association analysis in autism. In this study, we investigated the relationship between three SLC25A12 single nucleotide polymorphisms (SNPs) (rs2056202, rs908670 and rs2292813) and restricted repetitive behavior (RRB) traits in autism spectrum disorders (ASDs), based on a positive correlation between the G allele of rs2056202 and an RRB subdomain score on the Autism Diagnostic Interview-Revised (ADI-R). We used the Repetitive Behavior Scale-Revised (RBS-R) as a quantitative RRB measure, and conducted linear regression analyses for individual SNPs and a previously identified haplotype (rs2056202-rs2292813). We examined associations in our University of Illinois at Chicago-University of Florida (UIC-UF) sample (179 unrelated individuals with an ASD), and then attempted to replicate our findings in the Simons Simplex Collection (SSC) sample (720 ASD families). In the UIC-UF sample, three RBS-R scores (ritualistic, sameness, sum) had positive associations with the A allele of rs2292813 (p = 0.006-0.012) and with the rs2056202-rs2292813 haplotype (omnibus test, p = 0.025-0.040). The SSC sample had positive associations between the A allele of rs2056202 and four RBS-R scores (stereotyped, sameness, restricted, sum) (p = 0.006-0.010), between the A allele of rs908670 and three RBS-R scores (stereotyped, self-injurious, sum) (p = 0.003-0.015), and between the rs2056202-rs2292813 haplotype and six RBS-R scores (stereotyped, self-injurious, compulsive, sameness, restricted, sum)(omnibus test, p = 0.002-0.028). Taken together, the A alleles of rs2056202 and rs2292813 were consistently and positively associated with RRB traits in both the UIC-UF and SSC samples, but the most significant SNP with phenotype association varied in each dataset. This study confirmed an association between SLC25A12 and RRB traits in ASDs, but the direction of the association was different from that in the initial study. This could be due to the examined SLC25A12 SNPs being in linkage disequilibrium with another risk allele, and/or genetic/phenotypic heterogeneity of the ASD samples across studies.


G3 PhyloChip Analysis Confirms the Promise of Plant-Based Culture Media for Unlocking the Composition and Diversity of the Maize Root Microbiome and for Recovering Unculturable Candidate Divisions/Phyla.
The rapid development of high-throughput techniques and expansion of bacterial databases have accelerated efforts to bring plant microbiomes into cultivation. We introduced plant-only-based culture media as a successful candidate to mimic the nutritional matrices of plant roots. We herein employed a G3 PhyloChip microarray to meticulously characterize the culture-dependent and -independent bacterial communities of the maize root compartments, the endo- and ecto-rhizospheres. An emphasis was placed on the preference of the growth of unculturable candidate divisions/phyla on plant-only-based culture media over standard culture media (nutrient agar). A total of 1,818 different operational taxonomic units (OTUs) were resolved representing 67 bacterial phyla. Plant-only-based culture media displayed particular affinity towards recovering endophytic over ectophytic rhizobacteria. This was shown by the slightly higher recovery of CFUs for endophytes on plant-only-based culture media (26%) than on standard culture media (10%) as well as the higher taxa richness and numbers of exclusive families of unculturable divisions/phyla. Out of 30 bacterial phyla (comprising >95% of the whole population), 13 were of a significantly higher incidence on plant-only-based culture media, 6 phyla of which were not-yet-cultured (Atribacteria, OP9; Dependentiae, TM6; Latescibacteria, WS3; Marinimicrobia, SAR406; Omnitrophica, OP3; BRC1). Furthermore, plant-only-based culture media significantly enriched less abundant and/or hard-to-culture bacterial phyla (Acidobacteria, Gemmatimonadetes, and Tenericutes). These results present conclusive evidence of the ability of plant-only-based culture media to bring the plant-fed in situ microbiome into the status of plant-fed in vitro cultures, and to widen the scope of cultivation of heretofore-unculturable bacterial divisions/phyla.


Treatment of antipsychotic-induced hyperprolactinemia: an update on the role of the dopaminergic receptors D2 partial agonist aripiprazole.
Hyperprolactinemia is an unwanted adverse effect present in several typical and atypical antipsychotics. Aripiprazole is a drug with partial agonist activity at the level of dopamine receptors D2, which may be effective for antipsychotic- induced hyperprolactinemia. Therefore, we analyzed the literature concerning the treatment of antipsychoticinduced hyperprolactinemia with aripiprazole by updating a previous paper written on the same topic. More recent studies were reviewed. They showed that there are two options for the treatment of antipsychotic-induced hyperprolactinemia with aripiprazole. The safest strategy may require the addition of aripiprazole to ongoing treatments, in the case patients had previously responded to antipsychotic drugs and then developed hyperprolactinemia. However, it is advisable to monitor the patients in case relapses and/or side effect, although rare, might occur. Switching drugs should be considered when a patient does not appear to be responding to the previous antipsychotic, thus developing hyperprolactinemia. A cross-taper switch should always be considered, but the risk of a relapse in the disorder may occur more frequently and the patients should be closely monitored. However, limitations must be considered and further studies are needed to definitely elucidate this important issue. Some relevant patents are also described in this review.


The Impact of Playworks on Students' Physical Activity by Race/Ethnicity: Findings from a Randomized Controlled Trial.
The Playworks program places coaches in low-income urban schools to engage students in physical activity during recess. The purpose of this study was to estimate the impact of Playworks on students' physical activity separately for Hispanic, non-Hispanic black, and non-Hispanic white students. Twenty-seven schools from 6 cities were randomly assigned to treatment and control groups. Accelerometers were used to measure the intensity of students' physical activity, the number of steps taken, and the percentage of time in moderate-to-vigorous physical activity (MVPA) during recess. The impact of Playworks was estimated by comparing average physical activity outcomes in treatment and control groups. Compared with non-Hispanic black students in control schools, non-Hispanic black students in Playworks schools recorded 338 more intensity counts per minute, 4.9 more steps per minute, and 6.3 percentage points more time in MVPA during recess. Playworks also had an impact on the number of steps per minute during recess for Hispanic students but no significant impact on the physical activity of non-Hispanic white students. The impact of Playworks was larger among minority students than among non-Hispanic white students. One possible explanation is that minority students in non-Playworks schools typically engaged in less physical activity, suggesting that there is more room for improvement.


Repeated Porphyromonas gingivalis W83 exposure leads to release pro-inflammatory cytokynes and angiotensin II in coronary artery endothelial cells.
The role of Porphyromonas gingivalis (P. gingivalis) or its virulence factors, including lipopolysaccharide (LPS) not only has been related with periodontitis but also with endothelial dysfunction, a key mechanism involved in the genesis of atherosclerosis and hypertension that involving systemic inflammatory markers as angiotensin II (Ang II) and cytokines. This study compares the effect of repeated and unique exposures of P. gingivalis W83 LPS and live bacteria on the production and expression of inflammatory mediators and vasoconstrictor molecules with Ang II. Human coronary artery endothelial cells (HCAEC) were stimulated with purified LPS of P. gingivalis (1.0, 3.5 or 7.0 μg/mL) or serial dilutions of live bacteria (MOI 1: 100 - 1:0,1) at a single or repeated exposure for a time of 24 h. mRNA expression levels of AGTR1, AGTR2, IL-8, IL-1β and MCP-1 were determined by RT-qPCR, and IL-6, MCP-1, IL-8, IL-1β and GM-CSF levels were measured by flow cytometry, ELISA determined Ang II levels. Live bacteria in a single dose increased mRNA levels of AGTR1, and repeated doses increased mRNA levels of IL-8 and IL-1β (p < 0.05). Repeated exposure of live-P. gingivalis induced significant production IL-6, MCP-1 and GM-CSF (p < 0.05). Moreover, these MCP-1, IL-6 and GM-CSF levels were greater than in cells treated with single exposure (p < 0.05), The expression of AGTR1 and production of Ang II induced by live-P. gingivalis W83 showed a vasomotor effect of whole bacteria in HCAEC more than LPS. In conclusion, the findings of this study suggest that repeated exposure of P. gingivalis in HCAEC induces the activation of proinflammatory and vasoconstrictor molecules that lead to endothelial dysfunction being a key mechanism of the onset and progression of arterial hypertension and atherosclerosis.


The expression of self-incompatibility in angiosperms is bimodal.
Self-incompatibility is expressed by nearly one-half of all angiosperms. A large proportion of the remaining species are self-compatible, and they either outcross using various contrivances or self-fertilize to some extent. Because of the common occurrence of populations and individuals with intermediate levels of self-incompatibility, categorization of the expression of self-incompatibility as an approximately binary trait has become controversial. We collect a widely reported index (index of self-incompatibility [ISI]) used to asses the strength and variation of self-incompatibility from over 1200 angiosperm taxa. Its distribution is bimodal and positively associated with outcrossing rate, albeit with a weak relationship within self-compatible taxa. A substantial fraction of species has intermediate mean values of ISI. Their occurrence can be caused by segregating ephemeral self-compatible mutations, averaging artifacts, and experimental biases, in addition to the often invoked stabilizing selection acting on the expression of self-incompatibility. Selection may also generally favor taxa with high ISI values through increased lineage birth and death rates, and it may counter lower level selection advantages within taxa expressing intermediate and low values of ISI. Such a null hypothesis is nearly universally overlooked, despite the fact that it could adequately explain the observed distribution of mating and breeding systems.


Effects of hydroxyurea treatment for patients with hemoglobin SC disease.
Although hemoglobin SC (HbSC) disease is usually considered less severe than sickle cell anemia (SCA), which includes HbSS and HbS/β(0) -thalassemia genotypes, many patients with HbSC experience severe disease complications, including vaso-occlusive pain, acute chest syndrome, avascular necrosis, retinopathy, and poor quality of life. Fully 20 years after the clinical and laboratory efficacy of hydroxyurea was proven in adult SCA patients, the safety and utility of hydroxyurea treatment for HbSC patients remain unclear. Recent NHLBI evidence-based guidelines highlight this as a critical knowledge gap, noting HbSC accounts for ∼30% of sickle cell patients within the United States. To date, only 5 publications have reported short-term, incomplete, or conflicting laboratory and clinical outcomes of hydroxyurea treatment in a total of 71 adults and children with HbSC. We now report on a cohort of 133 adult and pediatric HbSC patients who received hydroxyurea, typically for recurrent vaso-occlusive pain. Hydroxyurea treatment was associated with a stable hemoglobin concentration; increased fetal hemoglobin (HbF) and mean corpuscular volume (MCV); and reduced white blood cell count (WBC), absolute neutrophil count (ANC), and absolute reticulocyte count (ARC). Reversible cytopenias occurred in 22% of patients, primarily neutropenia and thrombocytopenia. Painful events were reduced with hydroxyurea, more in patients >15 years old. These multicenter data support the safety and potentially salutary effects of hydroxyurea treatment for HbSC disease; however, a multicenter, placebo-controlled, Phase 3 clinical trial is needed to determine if hydroxyurea therapy has efficacy for patients with HbSC disease.


Temporal clustering analysis: what does it tell us about the resting state of the brain?
Several networks of synchronous blood oxygen level dependent (BOLD) oscillations have been identified in the brain during the resting state. The aim of this study was to further characterize the dynamic nature of the brain at rest by investigating the presence and distribution of coherent, transient BOLD activity in resting fMRI data using a novel method of fMRI data analysis--2dTCA. High-field fMRI data were acquired in 27 subjects. The temporal clustering analysis, 2dTCA, was implemented to determine the timing of significant, spatially coherent, transient BOLD signal changes. Group maps of positive and negative coherent BOLD changes from each timing profile were created. Spontaneous increases in BOLD activity at both 3T and 4T and decreases at 4T were found in regions of the alpha rhythm circuit including the thalamus, precuneus and the occipital cortex. Additional positive and negative oscillations at 4T and a small region of positive activity at 3T were identified in the area of the brain stem reticular formation, the control center for maintaining arousal and motivation. These results provide additional evidence for the presence of dynamic functional networks in the resting brain that are active while the subjects appear to be at rest and that are spatially distributed in areas responsible for maintaining consciousness and vigilance including brain stem. These findings should be considered in interpreting fMRI results which use resting baseline for comparisons.


The KREPA3 zinc finger motifs and OB-fold domain are essential for RNA editing and survival of Trypanosoma brucei.
Three types of editosomes, each with an identical core containing six related KREPA proteins, catalyze the U insertion and deletion RNA editing of mitochondrial mRNAs in trypanosomes. Repression of expression of one of these, KREPA3 (also known as TbMP42), shows that it is essential for growth and in vivo editing in both procyclic (PF) and bloodstream (BF) life cycle stages of Trypanosoma brucei. RNA interference knockdown results in editosome disruption and altered in vitro editing in PFs, while repression by regulatable double knockout results in almost complete loss of editosomes in BFs. Mutational analysis shows that the KREPA3 zinc fingers and OB-fold domain are each essential for growth and in vivo editing. Nevertheless, KREPA3 with mutated zinc fingers incorporates into editosomes that catalyze in vitro editing and thus is not essential for editosome integrity, although stability is affected. In contrast, the OB-fold domain is essential for editosome integrity. Overall, KREPA3, especially its OB-fold, functions in editosome integrity, and its zinc fingers are essential for editing in vivo but not for the central catalytic steps. KREPA3 may function in editosome organization and/or RNA positioning.


Nonspiro, Fluorene-Based, Amorphous Hole Transporting Materials for Efficient and Stable Perovskite Solar Cells.
Novel nonspiro, fluorene-based, small-molecule hole transporting materials (HTMs) V1050 and V1061 are designed and synthesized using a facile three-step synthetic route. The synthesized compounds exhibit amorphous nature with a high glass transition temperature, a good solubility, and decent thermal stability. The planar perovskite solar cells (PSCs) employing V1050 generated an excellent power conversion efficiency of 18.3%, which is comparable to 18.9% obtained with the state-of-the-art Spiro-OMeTAD. Importantly, the devices based on V1050 and V1061 show better stability compared to devices based on Spiro-OMeTAD when aged without any encapsulation under uncontrolled humidity conditions (relative humidity around 60%) in the dark and under continuous full sun illumination.


The nurse practitioner role in pain management in long-term care.
This paper is a report of a study exploring the perceptions of long-term care team members and nurse managers about barriers and facilitators to optimal use of nurse practitioners to manage residents' pain in long-term care settings. Considering the high rates of pain in long-term care, research is needed to explore innovations in health-services delivery, including the emerging nurse practitioner role. For this study, an exploratory descriptive design was used to collect data in spring 2007 from five focus groups of nurses and 14 individual interviews with other healthcare team members and nurse managers. Data were analysed using thematic content analysis. Five pain management activities performed by nurse practitioners were identified, including assessing pain, prescribing pain medications, monitoring pain levels and side effects of pain medications, consulting and advocating for staff and patients, and leading and educating staff related to pain management. Factors that influenced the implementation of the nurse practitioner role included the availability of the nurse practitioner, scope of practice, role clarity, perceived added value of nurse practitioner role, terms of employment, nurse practitioner-physician relationship. Perceived outcomes of the nurse practitioner role were also described. The findings from this study contribute to our understanding of how the nurse practitioner role is perceived by other healthcare professionals, particularly in pain management. Stronger interprofessional collaborative relationships need to be facilitated within a model of care that includes a nurse practitioner, with the ultimate goal of improving pain management services in long-term care.


Influence of bulky polynuclear carcinogen lesions in a TATA promoter sequence on TATA binding protein-DNA complex formation.
The TATA binding protein (TBP) is an essential component of the transcription initiation complex that recognizes and binds to the minor groove of the TATA DNA duplex consensus sequences. The objective of this study was to determine the effect of a carcinogen-modified adenine residue, positioned site-specifically within a regulatory TATA DNA sequence, on the binding of TBP. Two 25-mer oligonucleotides with stereoisomeric 10S (+)-trans-anti- or 10R (-)-trans-anti-BPDE-N(6)-dA residues at A(1) or A(2) within the TATA sequence element (5'-...TA(1)TAAA...-3')-(5'-...TTTA(2)TA...) were synthesized (anti-BPDE-N(6)-dA denotes an adduct formed from the reaction of r7,t8-dihydroxy-t9,10-epoxy-7,8,9,10-tetrahydobenzo[a]pyrene). The formation of complexes with TBP of these two sequences in the double-stranded forms (1 nM) were studied employing electrophoretic mobility shift assays (EMSA) at different TBP concentrations (0-70 nM). The overall affinity of TBP for the BPDE-modified target DNA sequences was weakly enhanced in the case of the (+)-trans or (-)-trans lesions positioned at site A(1) with K(d) approximately 8 and 6 nM, respectively (K(d) approximately 9 nM for the unmodified TATA DNA). Higher-order TBP-DNA complexes were observed at TBP concentrations in excess of approximately 15 nM. However, the stabilities of the biologically significant monomeric TBP-DNA complexes was dramatically increased or decreased, depending on the position of the lesion (A(1) or A(2)), or on its stereochemical and conformational characteristics. A molecular docking modeling approach was employed to insert the stereoisomeric BPDE residues into the known TATA box-TBP structure [Nikolov, D. B., et al. (1996) Proc. Natl. Acad. Sci. U.S.A. 4862-4867] to rationalize these observations. Native gel electrophoresis experiments with the same duplexes without TBP indicate that none of the modified sequences exhibit unusual bending induced by the lesions, nor that they differ from one another in this respect. These results suggest that the hydrophobic, bulky BPDE residues influence the binding of TBP by mechanisms other than prebending. The efficiency of RNA transcription of TBP-controlled promoters could be strongly influenced by the presence of such bulky lesions that could adversely affect the levels of gene expression.


Experimental and ab initio studies of Cd5(BO3)3Cl: the first cadmium borate chlorine NLO material with isolated BO3 groups.
A nonlinear optical crystal cadmium borate chlorine (Cd5(BO3)3Cl) has been successfully grown through a spontaneous crystallization method. Cd5(BO3)3Cl crystallizes in the noncentrosymmetric space group Cm with isolated BO3 and distorted CdOnClm (n = 4, 5, 7; m = 0, 1, 2) polyhedra. Powder second harmonic generation (SHG) measurements on polycrystalline Cd5(BO3)3Cl indicated that the title compound is phase-matchable in the visible region and exhibits a large SHG response of about 5 × KH2PO4 (KDP). Further optical characterization suggested that the compound has a wide transparent region ranging from UV to near IR with a UV cutoff edge at about 295 nm. In addition, first-principles electronic structure calculations revealed that the macroscopic SHG coefficients of Cd5(BO3)3Cl originate from the cooperative effects of the BO3 groups with asymmetric π-delocalization, the d10 cation Cd2+ with the polar displacement and the Cl- anions.


Fusidic acid-resistant Staphylococcus aureus in impetigo contagiosa and secondarily infected atopic dermatitis.
Fusidic acid-resistant Staphylococcus aureus (FRSA) has been identified as a causative agent in outbreaks of impetigo and its emergence has been associated with increased use of topical fusidic acid. The frequency of FRSA in atopic dermatitis (AD) has been less extensively investigated. The aim of this study was to investigate the bacterial spectrum and frequency of FRSA in patients with impetigo or secondarily infected AD. A prospective study in our clinic in 2004 to 2008 included 38 patients with impetigo and 37 with secondarily infected AD. S. aureus was the predominant finding in all groups (bullous impetigo 92% (12/13), impetigo 76% (19/25) and secondarily infected AD 89% (33/37)). Seventy-five percent of S. aureus were fusidic acid resistant in bullous impetigo, 32% in impetigo and 6.1% in secondarily infected AD (bullous impetigo vs. AD p < 0.0001, impetigo vs. AD p < 0.05). We then performed a retrospective patient record review including all patients with impetigo or secondarily infected AD seen at the clinic during the first and last year of the prospective study. In the first year 33% (19/58) of the S. aureus isolates were fusidic acid-resistant in impetigo and 12% (5/43) in secondarily infected AD (p < 0.05). In the last year corresponding values were 24% (6/25) for impetigo and 2.2% (1/45) for AD (p < 0.01). In summary, the prospective study and the patient record review both showed higher FRSA levels in impetigo than in AD. FRSA levels were persistently low in AD. Continued restrictive use of topical fusidic acid is advised to limit an increase in FRSA levels in dermatology patients.


Preliminary visual field preservation after staged CyberKnife radiosurgery for perioptic lesions.
The limited radiation tolerance of the optic nerves and the optic chiasm makes it a challenge to treat immediately adjacent lesions with radiosurgery. Staged or hypofractionated radiosurgery has the virtue of combining the accuracy and conformality of radiosurgery with the normal tissue-sparing benefits of fractionation. We describe a consecutive series of patients with meningiomas and pituitary adenomas abutting the anterior visual pathways who were treated with staged, image-guided radiosurgery. Thirty-four patients with either meningiomas (20 patients) or pituitary adenomas (14 patients) within 2 mm of the optic apparatus were treated. Several patients had previously been treated with conventional fractionated radiotherapy (5 patients) or subtotal surgical resection (23 patients). Radiosurgery was delivered in two to five stages to a cumulative average marginal dose of 20.0 Gy. Visual testing and clinical examinations were performed before treatment and at follow-up intervals beginning at 6 months after treatment. The mean follow-up period was 29 months (range, 15-62 mo). Pre- and posttreatment vision was unchanged in 20 patients, improved in 10, and worse in 3. One patient died during follow-up as a result of an unrelated cardiac event. Visual loss was accompanied by tumor progression in two cases. In a third patient with a multiply recurrent adrenocorticotropic hormone-secreting pituitary adenoma, injury to one optic nerve occurred after both a prior course of radiotherapy and three separate sessions of radiosurgery. Staged radiosurgery resulted in high rates of tumor control and preservation of visual function. Ninety-one percent of patients retained their presurgical vision. Staged radiosurgery may be a safe and effective alternative to either surgery or fractionated radiotherapy for selected lesions adjacent to the optic apparatus.


Localizing matrix metalloproteinase activities in the pericellular environment.
Matrix metalloproteinases (MMPs) are a group of structurally related proteolytic enzymes containing a zinc ion in the active site. They are secreted from cells or bound to the plasma membrane and hydrolyze extracellular matrix (ECM) and cell surface-bound molecules. They therefore play key roles in morphogenesis, wound healing, tissue repair and remodeling in diseases such as cancer and arthritis. Although the cell anchored membrane-type MMPs (MT-MMPs) function pericellularly, the secreted MMPs have been considered to act within the ECM, away from the cells from which they are synthesized. However, recent studies have shown that secreted MMPs bind to specific cell surface receptors, membrane-anchored proteins or cell-associated ECM molecules and function pericellularly at focussed locations. This minireview describes examples of cell surface and pericellular partners of MMPs, as well as how they alter enzyme function and cellular behaviour.


Dose-dependent cigarette smoking-related inflammatory responses in healthy adults.
The aim of this study was to determine the dose-response relationship between cigarette smoke exposure and pulmonary cell and cytokine concentrations in bronchoalveolar lavage (BAL). BAL cells and BAL supernatant concentrations of tumour necrosis factor-alpha (TNF alpha), interleukin (IL)-1 beta, IL-6, IL-8, and monocyte chemoattractant protein (MCP)-1 from 14 healthy smokers and 16 healthy nonsmokers were quantified. Statistically greater concentrations of neutrophils, macrophages, IL-1 beta, IL-6, IL-8 and MCP-1 were observed among smokers compared with nonsmokers (p < or = 0.0007 in all cases). Cigarette smoking, categorized ordinally as: less than one pack, one pack, or greater than one pack per day, was predictive of BAL macrophages (p < 0.0001), neutrophils (p = 0.015), IL-1 beta (p < 0.001) and IL-8 (p = 0.02). We conclude that concentrations of macrophages, neutrophils, IL-1 beta and IL-8 are elevated in the pulmonary microenvironment of smokers in a cigarette dose-dependent manner. Based on the present findings, we would caution against simple analyses that treat current smokers as a homogeneous group and which do not account for smoking intensity.


Study of RP HPLC Retention Behaviours in Analysis of Carotenoids.
For determination of selected carotenoids, various types of columns for high-performance liquid chromatography (HPLC) with different properties have been used. The characteristics of the laboratory-used packing material containing monomeric alkyl-bonded phases (C18, C30) and phenyl as well as phenyl-hexyl stationary phases were studied. The retention data of the examined compounds were used to determine the hydrophobicity and silanol activity of stationary phases applied in the study. The presence of the polar and carboxyl groups in the structure of the bonded ligand strongly influences the polarity of the stationary phase. Columns were compared according to methylene selectivity using a series of benzene homologues. The measurements were done using a methanol-water mobile phase. Knowledge of the properties of the applied stationary phase provided the possibility to predict the RP HPLC retention behaviours in analysis of carotenoids including lutein, lycopene and β-carotene. The composition of the mobile phase, the addition of triethylamine and the type of stationary phase had been taken into account in designing the method of carotenoid identification. Also a monolithic column characterised by low hydrodynamic resistance, high porosity and high permeability was applied. The presented results show that the coverage density of the bonded ligands on silica gel packings and length of the linkage strongly influence the carotenoid retention behaviours. In our study, the highest retention parameters for lutein, lycopene and β-carotene were observed for C30 and C18 stationary phase. This effect corresponds with pore size of column packing greater than 100 Å and carbon content higher than 11 %.


A Wearable Microwave Antenna Array for Time-Domain Breast Tumor Screening.
In this work, we present a clinical prototype with a wearable patient interface for microwave breast cancer detection. The long-term aim of the prototype is a breast health monitoring application. The system operates using multistatic time-domain pulsed radar, with 16 flexible antennas embedded into a bra. Unlike the previously reported, table-based prototype with a rigid cup-like holder, the wearable one requires no immersion medium and enables simple localization of breast surface. In comparison with the table-based prototype, the wearable one is also significantly more cost-effective and has a smaller footprint. To demonstrate the improved functionality of the wearable prototype, we here report the outcome of daily testing of the new, wearable prototype on a healthy volunteer over a 28-day period. The resulting data (both signals and reconstructed images) is compared to that obtained with our table-based prototype. We show that the use of the wearable prototype has improved the quality of collected volunteer data by every investigated measure. This work demonstrates the proof-of-concept for a wearable breast health monitoring array, which can be further optimized in the future for use with patients with various breast sizes and tissue densities.


Managing health research capacity strengthening consortia: a systematised review of the published literature.
Locally relevant research is considered critical for advancing health and development in low- and middle-income countries (LMICs). Accordingly, health research capacity strengthening (HRCS) efforts have intensified, increasingly through consortia. Yet, the knowledge base for managing such consortia is not well defined. This review aimed to ascertain the scope and quality of published literature on HRCS consortium management processes, management-related factors influencing consortium operations and outcomes, and the knowledge gaps. Given the paucity of published HRCS literature, a 'systematised review' as outlined by Grant and Booth was conducted, modelling the systematic review process without restriction to research-based publications. A systematic search in PubMed and Scopus was carried out coupled with a manual search for papers using reference checking and citation searching. A quality appraisal of eligible articles using the Mixed Method Appraisal Tool was undertaken. Thematic synthesis was used to analyse the extracted data. The search identified 55 papers, made up of 18 empirical papers and 37 commentaries focusing on consortium-based HRCS initiatives involving LMICs and reporting management-related data. The review indicates increasing efforts being made in the HRCS field in reporting consortia outcomes. However, it highlights the dearth of high-quality empirical research on HRCS consortium management and the nascent nature of the field with most papers published after 2010. The available literature highlights the importance of relational management factors such as equity and power relations in influencing consortium success, though these factors were not explored in depth. Operational management processes and their role in the capacity strengthening pathway were rarely examined. Findings indicate a weak evidence base for HRCS consortium management both in terms of quantity and conceptual depth, demonstrating the need for an expanded research effort to inform HRCS practice.


Impacts of air cleaners on indoor air quality in residences impacted by wood smoke.
Residential wood combustion is an important source of ambient air pollution, accounting for over 25% of fine particulate matter (PM2.5) emissions in Canada. In addition to these ambient contributions, wood smoke pollutants can enter the indoor environment directly when loading or stoking stoves, resulting in a high potential for human exposure. A study of the effectiveness of air cleaners at reducing wood smoke-associated PM2.5 of indoor and outdoor origin was conducted in 31 homes during winter 2009-10. Day 1, the residents' wood burning appliance operated as usual with no air cleaner. Days 2 and 3, the wood burning appliance was not operational and the air cleaner was randomly chosen to operate in "filtration" or "placebo filtration" mode. When the air cleaner was operating, total indoor PM2.5 levels were significantly lower than on placebo filtration days (p = 0.0001) resulting in a median reduction of 52%. There was also a reduction in the median PM2.5 infiltration factor from 0.56 to 0.26 between these 2 days, suggesting the air cleaner was responsible for increased PM2.5 deposition on filtration days. Our findings suggest that the use of an air cleaner reduces exposure to indoor PM2.5 resulting from both indoor and ambient wood smoke sources.


Probing the dynamics of N-methylacetamide in methanol via ab initio molecular dynamics.
Two-dimensional infrared (2D IR) spectroscopy of amide 1 vibrational bands provides a valuable probe of proteins as well as molecules such as N-methylacetamide (NMA), which present peptide-like H-bonding possibilities to a solvent. To assist in rationalizing a large body of experimental 2D IR data on NMA in both aqueous and non-aqueous solvents, we have performed an ab initio molecular dynamics simulation of NMA in methanol. Our study enables us to compare and contrast our findings with earlier calculations on NMA in water, and thereby explore the effect of solvent on the structural and dynamical properties of the NMA solute. We explicitly focus on the dynamics associated with the amide mode I (mainly C[double bond, length as m-dash]O stretch) and amide mode A (mainly N-H stretch) and its interaction with solvent through hydrogen bonding. Our results show that NMA exhibits faster hydrogen bond dynamics in methanol than in water, with an accompanying blue shift of the vibrational frequencies with respect to water. The observed faster diffusion of NMA in methanol signifies a weakening of hydrogen bonding between solute and solvent compared with water.


The Short-Form 36 and older people: some problems encountered when using postal administration.
To explore some of the problems encountered in the postal administration of the Short-Form 36 (SF-36). Questions that seem to present particular difficulties for the group are identified. In addition some of the written comments from the questionnaires and people's responses to questions on how difficult they found the SF-36 are discussed. The study group were asked to complete a health questionnaire containing the SF-36 on three separate occasions (at zero, three, and six months). The first and final questionnaires were interviewer administered during a face to face interview. A shorter questionnaire containing only the SF-36 and another health status measure was sent by post to each patient in the interim. People aged 65 years or above who were new referrals to community based occupational therapy or physiotherapy services in three areas in north west England. Response and completion rates for the postal questionnaire were lower than expected, even though all the patients had already had a face to face interview and had therefore completed the SF-36 once. Only 34 of 56 respondents (60.7%) completed all the items on the SF-36. All those planning to use the SF-36 (and similar measures) with older populations should be sensitive to the problems of postal administration. Non-return of questionnaires, high levels of missing data on those that are received, and ambiguities in response may mean that other measures, or perhaps alternative research methods, are more appropriate.


Review of issues concerning the use of reproductive inhibitors, with particular emphasis on resolving human-wildlife conflicts in North America.
This manuscript provides an overview of past wildlife contraception efforts and discusses the current state of research. Two fertility control agents, an avian reproductive inhibitor containing the active ingredient nicarbazin and an immunocontraceptive vaccine, have received regulatory approval with the Environmental Protection Agency and are commercially available in the USA. OvoControl G Contraceptive Bait for Canada Geese and Ovo Control for pigeons are delivered as oral baits. An injectable immunocontraceptive vaccine (GonaCon Immunocontraceptive Vaccine) was registered with the Environmental Protection Agency for use in female white-tailed deer in September 2009. An injectable product (GonaCon Immunocontraceptive Vaccine) is registered for use in female white-tailed deer. Both products are labeled for use in urban/suburban areas where these species are overabundant. Several other compounds are currently being tested for use in wildlife in the USA, Europe, Australia and New Zealand that could have promise in the future. The development and use of reproductive inhibitors for resolving human-wildlife conflicts will depend on a number of factors, including meeting the requirements of regulatory agencies for use in the environment and on the biological and economical feasibility of their use. Use will also be dependent on health and safety issues and on public acceptance of the techniques.


Therapeutic Endoscopic Retrograde Cholangiopancreatography in Pediatric Patients With Acute Recurrent and Chronic Pancreatitis: Data From the INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) Study.
The aim of this study was to characterize utilization and benefit of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in children with acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP). From August 2012 to February 2015, 301 children with ARP or CP were enrolled in the INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) study. Physicians reported utilization and benefit of therapeutic ERCP at enrollment. Differences were analyzed using appropriate statistical methods. One hundred seventeen children (38.9%) underwent at least 1 therapeutic ERCP. The procedure was more commonly performed in children with CP compared with those with ARP (65.8% vs 13.5%, P < 0.0001). Utility of therapeutic ERCP was reported to be similar between ARP and CP (53% vs 56%, P = 0.81) and was found to be helpful for at least 1 indication in both groups (53/99 patients [53.5%]). Predictors for undergoing therapeutic ERCP were presence of obstructive factors in ARP and CP, Hispanic ethnicity, or white race in CP. Therapeutic ERCP is frequently utilized in children with ARP or CP and may offer benefit in selected cases, specifically if ductal obstruction is present. Longitudinal studies are needed to clarify the efficacy of therapeutic ERCP and to explore subgroups that might have increased benefit from such intervention.


Agreement and Discrepancy on Emotional and Behavioral Problems Between Caregivers and HIV-Infected Children and Adolescents From Uganda.
Background: HIV-infected children and adolescents (CA-HIV) face significant mental health challenges related to a broad range of biological and psychosocial factors. Data are scarce on the agreement and discrepancy between caregivers and CA-HIV regarding emotional and behavioral problems (EBPs) in CA-HIV. Objectives: We determined agreement between self- versus caregiver- reported EBPs and describe factors associated with informant discrepancy among caregiver-youth dyads who participated in the "Mental health among HIV-infected CHildren and Adolescents in KAmpala and Masaka, Uganda" (CHAKA) study. Methods: In a cross-sectional sample, caregiver-reported EBPs were assessed with the Child and Adolescent Symptom Inventory-5 (CASI-5), and self-reported problems were evaluated with the Youth Inventory-4 (YI-4) in 469 adolescents aged 12-17 years and the Child Inventory-4 (CI-4) in 493 children aged 8-11 years. Adolescents were questioned about experiences of HIV stigma. Caregiver psychological distress was assessed with the Self-Reporting Questionnaire (SRQ-20). Linear regression models were applied to identify variables associated with discrepancy scores. Results: Self-reported emotional problems (EPs) were present in 28.8% of adolescents and 36.9% of children, and 14.5% of adolescents self-reported behavioral problems (BPs). There was only a modest correlation (r ≤ 0.29) between caregiver- and CA-HIV-reported EBPs, with caregivers reporting more EPs whereas adolescents reported more BPs. Informant discrepancy between adolescents and caregivers for BPs was associated with adolescent age and caregiver's employment and HIV status. Among adolescents, EP discrepancy scores were associated with adolescent's WHO HIV clinical stage, caregiver level of education, and caregivers caring for other children. Among children, EP discrepancy scores were associated with child and caregiver age, caregiver level of education, and caregiver self-rated health status. HIV stigma and caregiver psychological distress were also associated with discrepancy, such that adolescents who experienced HIV stigma rated their EPs as more severe than their caregivers did and caregivers with increased psychological distress rated EBPs as more severe than CA-HIV self-rated. Conclusions: EBPs are frequently endorsed by CA-HIV, and agreement between informants is modest. Informant discrepancy is related to unique psychosocial and HIV-related factors. Multi-informant reports enhance the evaluation of CA-HIV and informant discrepancies can provide additional insights into the mental health of CA-HIV.


Costs of remission and recovery using family therapy for adolescent anorexia nervosa: a descriptive report.
This paper reports on the costs of overall treatment for a cohort of adolescent patients with AN treated with a similar regimen consisting of inpatient medical stabilization, outpatient family therapy, and psychiatric medications for co-morbid psychiatric conditions. Most of the costs associated with outcome were secondary to medical hospitalization. However, the overall costs per remission varied widely depending on the threshold used. However, compared to costs described for adults with AN, adolescent treatment costs appear to be lower when families are used effectively to aid in treatment.


Strongly enhanced charge-density-wave order in monolayer NbSe2.
Two-dimensional materials possess very different properties from their bulk counterparts. While changes in single-particle electronic properties have been investigated extensively, modifications in the many-body collective phenomena in the exact two-dimensional limit remain relatively unexplored. Here, we report a combined optical and electrical transport study on the many-body collective-order phase diagram of NbSe2 down to a thickness of one monolayer. Both the charge density wave and the superconducting phase have been observed down to the monolayer limit. The superconducting transition temperature decreases on lowering the layer thickness, but the newly observed charge-density-wave transition temperature increases from 33 K in the bulk to 145 K in the monolayer. Such highly unusual enhancement of charge density waves in atomically thin samples can be understood to be a result of significantly enhanced electron-phonon interactions in two-dimensional NbSe2 (ref. 4) and is supported by the large blueshift of the collective amplitude vibration observed in our experiment. Our results open up a new window for search and control of collective phases of two-dimensional matter, as well as expanding the functionalities of these materials for electronic applications.


Implicit alcohol-aggression scripts and alcohol-related aggression on a laboratory task in 11- to 14-year-old adolescents.
Social scripts are commonly shared representations of behavior in social contexts, which are seen to be partly transmitted through social and cultural media. Research suggests that people hold scripts associated with alcohol-related aggression, but, unlike general aggression scripts, there is little evidence of social transmission. To demonstrate social transmission of alcohol-related aggression scripts, learning mechanisms based on personal experience should be minimized. We used a lexical decision task to examine implicit links between alcohol and aggression in alcohol-naïve adolescents who have limited personal or vicarious experience of alcohol-related aggression. One hundred and four 11-14 year old adolescents made lexical decisions on aggressive or nonaggressive words preceded by 40-ms alcohol or nonalcohol word primes. Repeated measures analyses of group data showed that alcohol word primes did not lead to faster responses to aggressive words than to nonaggressive words, nor were responses to aggressive words faster when they were preceded by alcohol word primes than by nonalcohol word primes. However, at an individual level, faster recognition times to the alcohol prime/aggression target word combination predicted aggression on a competitive laboratory task in 14 year olds only. This occurred only when the competitive aggression task was preceded by a visual presentation of alcoholic, but not nonalcoholic beverage, images. We concluded that alcohol-related aggression scripts are not strongly developed in this age group, but individual differences in script strength are linked to alcohol-related laboratory aggression.


CSF Proteomics Identifies Specific and Shared Pathways for Multiple Sclerosis Clinical Subtypes.
Multiple sclerosis (MS) is an immune-mediated, neuro-inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS) with a heterogeneous clinical presentation and course. There is a remarkable phenotypic heterogeneity in MS, and the molecular mechanisms underlying it remain unknown. We aimed to investigate further the etiopathogenesis related molecular pathways in subclinical types of MS using proteomic and bioinformatics approaches in cerebrospinal fluids of patients with clinically isolated syndrome, relapsing remitting MS and progressive MS (n=179). Comparison of disease groups with controls revealed a total of 151 proteins that are differentially expressed in clinically different MS subtypes. KEGG analysis using PANOGA tool revealed the disease related pathways including aldosterone-regulated sodium reabsorption (p=8.02x10-5) which is important in the immune cell migration, renin-angiotensin (p=6.88x10-5) system that induces Th17 dependent immunity, notch signaling (p=1.83x10-10) pathway indicating the activated remyelination and vitamin digestion and absorption pathways (p=1.73x10-5). An emerging theme from our studies is that whilst all MS clinical forms share common biological pathways, there are also clinical subtypes specific and pathophysiology related pathways which may have further therapeutic implications.


Psychosis in an adolescent patient with Wilson's disease: effects of chelation therapy.
Wilson's disease is a rare genetic disorder involving the liver and brain, with onset frequently in adolescence. Psychiatric symptoms are often the first manifestation of the disease and can obscure the diagnosis. Chelation therapy can reverse the fatal outcome of untreated patients, so early detection is critically important. This paper describes an adolescent with Wilson's disease who, after initiation of penicillamine therapy, developed florid psychosis that improved as copper levels were decreased and that did not require use of neuroleptic medication.


Why is the change of the Johari-Goldstein β-relaxation time by densification in ultrastable glass minor?
Ultrastable glasses (USG) formed by vapor deposition are considerably denser. The onset temperature of devitrification, Ton, is significantly higher than Ton or Tg of ordinary glass (OG) formed by cooling, which implies an increase of the structural α-relaxation time by many orders of magnitude in USG compared to that in OG at the same temperature. However, for a special type of secondary relaxation having properties strongly connected to those of the α-relaxation, called the Johari-Goldstein β-relaxation, its relaxation time in USG is about an order of magnitude slower than that in OG and it has nearly the same activation energy, Eβ. The much smaller change in τβ and practically no change in Eβ by densification in USG are in stark contrast to the behavior of the α-relaxation. This cannot be explained by asserting that the Johari-Goldstein (JG) β-relaxation is insensitive to densification in USG, since the JG β-relaxation strength is significantly reduced in USG to such a level that it would require several thousands of years of aging for an OG to reach the same state, and therefore the JG β-relaxation does respond to densification in USG like the α-relaxation. Here, we provide an explanation based on two general properties established from the studies of glasses and liquids at elevated pressures and applied to USG. The increase in density of the glasses formed under high pressure can be even larger than that in USG. One property is the approximate invariance of the ratio τα(Ton)/τβ(Ton) to density change at constant τα(Ton), and the other is the same ργ/T-dependence of τβ in USG and OG where ρ is the density and γ is a material constant. These two properties are derived using the Coupling Model, giving a theoretical explanation of the phenomena. The explanation is also relevant for a full understanding of the experimental result that approximately the same surface diffusion coefficient is found in USG and OG with and without physical aging, and ultrathin films of a molecular glass-former.


Evaluation of patulin toxicity in the thymus of growing male rats.
Patulin is a mycotoxin produced by several Penicillium, Aspergillus, and Byssachlamys species growing on food products. In this study, we investigated the effects of patulin on the thymus of growing male rats aged five to six weeks. The rats were receiving it orally at a dose of 0.1 mg kg-1 bw a day for either 60 or 90 days. At the end of the experiment, the thymus was examined for histopathology by light microscopy and for epidermal growth factor (EGF) and its receptor (EGFR) by immunolocalisation. For morphometry we used the Bs200prop program to analyse images obtained with the Olympus BX51 light microscope. Cell ultrastructure was studied by electron microscopy. In rats treated with patulin, the thymus showed haemorrhage, plasma cell hyperplasia, a dilation and fibrosis in the cortex, enlarged interstitial tissue between the thymic lobules, enlarged fat tissue, thinning of the cortex, and blurring of the cortico-medullary demarcation. Electron microscopy showed signs of cell destruction, abnormalities of the nucleus and organelles, and loss of mitochondrial cristae. However, no differences were observed in thymus EGF and EGFR immunoreactivity between treated and control rats.


Dyslexia and Substance Use in a University Undergraduate Population.
A number of cognitive deficits are associated with dyslexia. However, only a limited amount of research has been performed exploring a putative link between dyslexia and substance use. As substance use is thought to involve a cognitive component, it is possible that the pattern of substance use would be different for dyslexic participants, when compared to nondyslexic controls. During the current study, a guiding hypothesis was that people with dyslexia would demonstrate less substance use than nondyslexic controls. Theories of memory activation, automaticity, and attentional bias in substance use suggest that cognitive components of substance use are important in the development and maintenance of continued substance use and it is thought that, at least some of these components, would be impaired in a dyslexic population. If the cognitive deficits displayed by dyslexics somehow impair the development of cognitive components of substance use, substance use for dyslexic participants may be less pronounced. This paper therefore examines this hypothesis by comparing substance use within dyslexic and nondyslexic participants, from an undergraduate population. This was an exploratory questionnaire-based study. Dyslexic participants (n = 35) were compared to control participants (n = 62) on a series of questions designed to measure their substance use history. The results provided preliminary evidence of a difference between dyslexic and nondyslexic substance use. Dyslexics reported a substance use history that was significantly lower than nondyslexic controls. These results are interpreted in terms of cognitive deficits within dyslexia and with reference to the cognitive model of substance use.


The slipping slipper sign: a marker of severe peripheral diabetic neuropathy and foot sepsis.
Peripheral neuropathy is a major contributor to diabetic foot complications including ulceration, sepsis and limb loss. The aim of this study was to document the frequency of this previously undocumented clinical marker of peripheral neuropathy, the "slipping slipper sign" (SSS), characterised by unrecognised loss of slippers from one's feet while walking, and to compare it with traditional clinical tests for peripheral neuropathy. To evaluate the relationship between a positive SSS and diabetic peripheral neuropathy. The study included 105 diabetic outpatients without active foot problems, 40 diabetic inpatients with active foot sepsis, and 69 other patients with neither diabetes nor active foot sepsis as negative controls. Demographic data, clinical neuropathy scores and the presence or absence of the SSS were obtained. No control subjects had a positive SSS. In contrast, 64 of 145 diabetic patients had severe neuropathy of whom 53 had a positive SSS (83% sensitivity) and 74 of 81 without severe neuropathy had a negative SSS (91% specificity). Diabetic patients with concurrent foot sepsis had a higher frequency of severe neuropathy (70%) and positive SSS (65%) compared with those without (36% and 35%, respectively, p<0.001). Multivariate analysis showed that a positive SSS was strongly related to severity of neuropathy independent of duration of diabetes. The SSS reflects severe peripheral neuropathy and is particularly prevalent among those with active foot disease. Patients who have experienced the SSS should be encouraged to seek attention and preventive action taken.


Generalist palliative care in hospital - Cultural and organisational interactions. Results of a mixed-methods study.
It can be challenging to provide generalist palliative care in hospitals, owing to difficulties in integrating disease-oriented treatment with palliative care and the influences of cultural and organisational conditions. However, knowledge on the interactions that occur is sparse. To investigate the interactions between organisation and culture as conditions for integrated palliative care in hospital and, if possible, to suggest workable solutions for the provision of generalist palliative care. A convergent parallel mixed-methods design was chosen using two independent studies: a quantitative study, in which three independent datasets were triangulated to study the organisation and evaluation of generalist palliative care, and a qualitative, ethnographic study exploring the culture of generalist palliative nursing care in medical departments. A Danish regional hospital with 29 department managements and one hospital management. Two overall themes emerged: (1) 'generalist palliative care as a priority at the hospital', suggesting contrasting issues regarding prioritisation of palliative care at different organisational levels, and (2) 'knowledge and use of generalist palliative care clinical guideline', suggesting that the guideline had not reached all levels of the organisation. Contrasting issues in the hospital's provision of generalist palliative care at different organisational levels seem to hamper the interactions between organisation and culture - interactions that appear to be necessary for the provision of integrated palliative care in the hospital. The implementation of palliative care is also hindered by the main focus being on disease-oriented treatment, which is reflected at all the organisational levels.


The DNA sequence and biology of human chromosome 19.
Chromosome 19 has the highest gene density of all human chromosomes, more than double the genome-wide average. The large clustered gene families, corresponding high G + C content, CpG islands and density of repetitive DNA indicate a chromosome rich in biological and evolutionary significance. Here we describe 55.8 million base pairs of highly accurate finished sequence representing 99.9% of the euchromatin portion of the chromosome. Manual curation of gene loci reveals 1,461 protein-coding genes and 321 pseudogenes. Among these are genes directly implicated in mendelian disorders, including familial hypercholesterolaemia and insulin-resistant diabetes. Nearly one-quarter of these genes belong to tandemly arranged families, encompassing more than 25% of the chromosome. Comparative analyses show a fascinating picture of conservation and divergence, revealing large blocks of gene orthology with rodents, scattered regions with more recent gene family expansions and deletions, and segments of coding and non-coding conservation with the distant fish species Takifugu.


The discovery of integrated gene networks for autism and related disorders.
Despite considerable genetic heterogeneity underlying neurodevelopmental diseases, there is compelling evidence that many disease genes will map to a much smaller number of biological subnetworks. We developed a computational method, termed MAGI (merging affected genes into integrated networks), that simultaneously integrates protein-protein interactions and RNA-seq expression profiles during brain development to discover "modules" enriched for de novo mutations in probands. We applied this method to recent exome sequencing of 1116 patients with autism and intellectual disability, discovering two distinct modules that differ in their properties and associated phenotypes. The first module consists of 80 genes associated with Wnt, Notch, SWI/SNF, and NCOR complexes and shows the highest expression early during embryonic development (8-16 post-conception weeks [pcw]). The second module consists of 24 genes associated with synaptic function, including long-term potentiation and calcium signaling with higher levels of postnatal expression. Patients with de novo mutations in these modules are more significantly intellectually impaired and carry more severe missense mutations when compared to probands with de novo mutations outside of these modules. We used our approach to define subsets of the network associated with higher functioning autism as well as greater severity with respect to IQ. Finally, we applied MAGI independently to epilepsy and schizophrenia exome sequencing cohorts and found significant overlap as well as expansion of these modules, suggesting a core set of integrated neurodevelopmental networks common to seemingly diverse human diseases.


Acute myocardial infarction with a non-diagnostic electrocardiogram. Case presentation and overview.
The clinical presentation of a young hypertensive White man with acute high lateral non-transmural myocardial infarction (MI) is documented. This diagnosis was established on the grounds of a history of chest pain, elevated serial serum enzyme levels, technetium-99m pyrophosphate ('hot-spot') scintigraphy, exercise thallium-201 ('cold-spot') scanning, left ventricular cine angiography and selective coronary arteriography. Daily resting 12-lead ECGs failed to demonstrate unequivocal features of acute non-transmural subendocardial MI. The diagnostic difficulties facing the clinician in a case of acute MI associated with a non-diagnostic ECG are stressed, and the ECG features of acute subendocardial MI are reviewed.


Social protection for all ages? Impacts of Ethiopia's Productive Safety Net Program on child nutrition.
We investigate the impact of a large-scale social protection scheme, the Productive Safety Net Program (PSNP) in Ethiopia, on child nutritional outcomes. Children living in households that receive cash transfers should experience improved child nutrition. However, in the case of the PSNP, which for the majority of participants is a public works program, there are several potential threats to finding effects: first, without conditionality on child inputs, increased household income may not be translated into improved child nutrition. Second, the work requirement may impact on parental time, child time use and calories burned. Third, if there is a critical period for child human capital investment that closes before the age of 5 then children above this age may not see any improvement in medium-term nutritional outcomes, measured here as height-for-age. Using a cohort study that collected data both pre-and post-program implementation in 2002, 2006 and 2009, we exploit several novel aspects of the survey design to find estimates that can deal with non-random program placement. We present both matching and difference-in-differences estimates for the index children, as well as sibling-differences. Our estimates show an important positive medium-term nutritional impact of the program for children aged 5-15 that are comparable in size to Conditional Cash Transfer program impacts for much younger children. We show indicative evidence that the program impact on improved nutrition is associated with improved food security and reduced child working hours. Our robustness checks restrict the comparison group, by including only households who were shortlisted, but never received PSNP, and also exclude those who never received aid, thus identifying impact based on timing alone. We cannot rule out that the nutritional impact of the program is the same for younger and older children.


Positron emission tomography with 2-[18F]Fluoro-2-deoxy-D-glucose and 16alpha-[18F]fluoro-17beta-estradiol in breast cancer: correlation with estrogen receptor status and response to systemic therapy.
We assessed the value of positron emission tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) and 16alpha-[18F]fluoro-17beta-estradiol (FES) in women with breast cancer for predicting response to systemic therapy. Results of FES-PET were correlated with estrogen receptor (ER) status. Forty-three women with locally advanced or metastatic breast cancer underwent FDG-PET and FES-PET prior to institution of systemic therapy. All patients had measurable disease and had tumors submitted for ER determination. Cancers were considered functionally hormone sensitive if the standardized uptake value of the lesion on FES-PET was >/=1.0 (FES+) and hormone resistant if the standardized uptake value was <1.0 (FES-). Information obtained by FES-PET was compared with the results of ER assays. The tumor response to chemotherapy and hormonal therapy was correlated with intensity of uptake by both FDG-PET and FES-PET. The ER status of the breast cancers was negative (ER-) in 20 patients, positive (ER+) in 21 patients, and unknown in 2 patients. All 20 of the ER- tumors were also FES-. However, of the 21 ER+ tumors, 16 were FES+ and 5 were FES-. Thirty patients were treated initially with chemotherapy, and 21 (70%) demonstrated objective responses. We were unable to correlate the response to chemotherapy with information obtained by FDG-PET or FES-PET. Thirteen patients were treated with hormone therapy, and 8 (61%) responded to that therapy. Only 1 of the 5 patients whose tumors were ER+ but FES- received hormone therapy, and this treatment resulted in disease stabilization only. Multiple sites of disease were assessed by FES-PET in 17 patients with metastatic breast cancer. Functional hormone sensitivity, defined by FES-PET, was concordant with multiple lesions in 13 (76%). Ten patients with locally advanced breast cancer developed recurrent disease. The initial site of recurrence was the breast in 5 patients. Of the 5 patients with systemic recurrence, 4 had disease detected at the site of recurrence on the pretreatment FDG-PET study but not detected on pretreatment computed tomography. In our experience, FDG-PET imaging is more sensitive than conventional imaging methods, including computed tomography, in staging women with breast cancer. When compared with the in vitro assay of ER status, FES-PET has an apparent sensitivity of 76% and specificity of 100%. Our finding of a subset of patients who have tumors that are ER+ and FES- suggests that the functional assessment of hormone sensitivity by PET imaging can identify patients with ER+ disease whose tumors are likely to be hormone refractory.


Tin(ii) oxide carbodiimide and its relationship to SnO.
The compound Sn2O(CN2) was obtained as a brick-red crystalline powder from a solid-state reaction of equimolar amounts of SnCl2, SnO and Li2(CN2). Thermal analysis of the reaction indicates the formation of two intermediate compounds until Sn2O(CN2) is formed at 400 °C. The crystal structure of Sn2O(CN2) was determined in the space group Pccn (a = 13.3949(7) Å, b = 5.2954(3) Å, c = 5.5369(2) Å, Z = 4) from single-crystal X-ray diffraction data. The structure contains a Sn2+ ion with a 5s2 lone pair, situated in a fourfold, mixed O-/N-coordination environment. The crystal structure of Sn2O(CN2) is analyzed and discussed in relation to that of SnO, namely by electronic-structure calculations and a COHP bonding analysis of Sn2O(CN2).


Context consistency and seasonal variation in boldness of male two-spotted gobies.
In order to attribute the behaviour of an animal to its personality it is important to study whether certain behavioural traits show up consistently across a variety of contexts. The aim of this study was to investigate whether breeding state males of the two-spotted goby, Gobiusculus flavescens, showed consistent degree of boldness when tested in four different behaviour assays. We also wanted to investigate whether boldness varied over the breeding season in accordance with changes in male-male competition for matings. We used two standard assays (the emergence test and the open field test), and two simple assays related to threat response. Repeated runs of each of the tests were highly correlated, and we found significant correlations between all four assays. Thus, we have documented both a within and a between-context consistency in risk-taking behaviour. Furthermore, we found that goby males studied during the middle of the breeding season were bolder than males studied at the end of the season. Since male two-spotted gobies face strongly decreasing male-male competition as the season progresses, the benefit of being bold for the mating success of the males may differ over the time of the breeding season. The difference in behaviour found over the season thus corresponds well with the sexual dynamics of this model species.


Magnesium Stable Isotope Fractionation on a Cellular Level Explored by Cyanobacteria and Black Fungi with Implications for Higher Plants.
In a controlled growth experiment we found that the cyanobacterium Nostoc punctiforme has a bulk cell 26Mg/24Mg ratio (expressed as δ26Mg) that is -0.27‰ lower than the growth solution at a pH of ca. 5.9. This contrasts with a recently published δ26Mg value that was 0.65‰ higher than growth solution for the black fungus Knufia petricola at similar laboratory conditions, interpreted to reflect loss of 24Mg during cell growth. By a mass balance model constrained by δ26Mg in chlorophyll extract we inferred the δ26 Mg value of the main Mg compartments in a cyanobacteria cell: free cytosolic Mg (-2.64‰), chlorophyll (1.85‰), and the nonchlorophyll-bonded Mg compartments like ATP and ribosomes (-0.64‰). The lower δ26Mg found in Nostoc punctiforme would thus result from the absence of significant Mg efflux during cell growth in combination with either (a) discrimination against 26Mg during uptake by desolvation of Mg or transport across protein channels or (b) discrimination against 24Mg in the membrane transporter during efflux. The model predicts the preferential incorporation of 26Mg in cells and plant organs low in Mg and the absence of isotope fractionation in those high in Mg, corroborated by a compilation of Mg isotope ratios from fungi, bacteria, and higher plants.


Spline- and wavelet-based models of neural activity in response to natural visual stimulation.
We present a comparative study of the performance of different basis functions for the nonparametric modeling of neural activity in response to natural stimuli. Based on naturalistic video sequences, a generative model of neural activity was created using a stochastic linear-nonlinear-spiking cascade. The temporal dynamics of the spiking response is well captured with cubic splines with equidistant knot spacings. Whereas a sym4-wavelet decomposition performs competitively or only slightly worse than the spline basis, Haar wavelets (or histogram-based models) seem unsuitable for faithfully describing the temporal dynamics of the sensory neurons. This tendency was confirmed with an application to a real data set of spike trains recorded from visual cortex of the awake monkey.


Is task-shifting a solution to the health workers' shortage in Northern Ghana?
To explore the experiences and perceptions of health workers and implementers of task-shifting in rural health facilities in Upper East Region, Ghana. Data was collected through field interviews. A total of sixty eight (68) in-depth interviews were conducted with health workers' in primary health care facilities (health centres); Four in-depth interviews with key persons involved in staff management was conducted to understand how task-shifting is organised including its strengths and challenges. The health workers interview guide was designed with the aim of getting data on official tasks of health workers, additional tasks assigned to them, how they perceive these tasks, and the challenges associated with the practice of task-shifting. Task-shifting is a practice being used across the health facilities in the study area to help reduce the impact of insufficient health workers. Generally, health workers had a comprehensive training that supported the organisation of task-shifting. However, staff members' are sometimes engaged in tasks above their level of training and beyond their actual job descriptions. Adequate training is usually not provided before additional tasks are assigned to staff members. Whilst some health workers perceived the additional tasks they performed as an opportunity to learn new skills, others described these as stressful and overburdening. Task-shifting has the potential to contribute to addressing the insufficient health workforce, and thereby improving health delivery system where the procedures are well defined and staff members work in a coordinated and organised manner. The provision of adequate training and supervision for health workers is important in order to improve their expertise before additional tasks are assigned to them so that the quality of care would not be compromised.


Shiga Toxin-Producing Serogroup O91 Escherichia coli Strains Isolated from Food and Environmental Samples.
Shiga toxin-producing Escherichia coli (STEC) strains of the O91:H21 serotype have caused severe infections, including hemolytic-uremic syndrome. Strains of the O91 serogroup have been isolated from food, animals, and the environment worldwide but are not well characterized. We used a microarray and other molecular assays to examine 49 serogroup O91 strains (environmental, food, and clinical strains) for their virulence potential and phylogenetic relationships. Most of the isolates were identified to be strains of the O91:H21 and O91:H14 serotypes, with a few O91:H10 strains and one O91:H9 strain being identified. None of the strains had the eae gene, which codes for the intimin adherence protein, and many did not have some of the genetic markers that are common in other STEC strains. The genetic profiles of the strains within each serotype were similar but differed greatly between strains of different serotypes. The genetic profiles of the O91:H21 strains that we tested were identical or nearly identical to those of the clinical O91:H21 strains that have caused severe diseases. Multilocus sequence typing and clustered regularly interspaced short palindromic repeat analyses showed that the O91:H21 strains clustered within the STEC 1 clonal group but the other O91 serotype strains were phylogenetically diverse.IMPORTANCE This study showed that food and environmental O91:H21 strains have similar genotypic profiles and Shiga toxin subtypes and are phylogenetically related to the O91:H21 strains that have caused hemolytic-uremic syndrome, suggesting that these strains may also have the potential to cause severe illness.


Nerve growth factor uses Ras/ERK and phosphatidylinositol 3-kinase cascades to up-regulate the N-methyl-D-aspartate receptor 1 promoter.
We reported previously that nerve growth factor (NGF) up-regulates activity of the N-methyl-D-aspartate receptor 1 (NR1) promoter. We have explored the pathways and nuclear targets of NGF signaling in regulating the NR1 promoter. PD98059 and wortmannin, but not rapamycin, significantly attenuated NGF-induced transcriptional activity from an NR1 promoter-luciferase construct. Coexpressing constitutively active forms of Ras, Raf, or MAPK/ERK kinase 1 (MEK1) increased promoter activity dramatically. The MEK1-induced increase was largely prevented by mutations of the tandem GC boxes in the promoter. Promoter activity was also increased significantly by coexpressed GC box-binding proteins (Sp1, 3, or 4) in nonstimulated PC12 cells. Either an extracellular signal-regulated kinase-1 (ERK1)- or Sp1-specific antibody coprecipitated Sp1 with ERKs, and the coprecipitation was enhanced significantly by NGF treatment of PC12 cells. ERK2 also incorporated radioactivity of [gamma(32)P]ATP into recombinant Sp1. However, ERK2-treated Sp1 and PC12 nuclear extracts or nuclear extracts from NGF-treated cells exhibited reduced binding to the promoter or a consensus GC box. Our results suggest that NGF utilizes both the Ras/ERK and phosphatidylinositol 3-kinase pathways to up-regulate NR1 promoter activity and that Sp1 is a novel substrate of NGF-activated ERKs. NGF-increased NR1 promoter activity may involve a complicated mechanism of Sp1 phosphorylation and possible transcription factor exchange.


[Tuberculosis and HIV - features of the co-infection].
The human immunodeficiency virus (HIV) epidemic has allowed the incidence of tuberculosis to rise globally and particularly in sub-Saharan Africa. Diagnosis and treatment of tuberculosis is more complex in patients with HIV/AIDS. Sputum smear microscopy is performing poorly in HIV-infected individuals, who are often started on antituberculosis treatment on clinical grounds. The treatment of coinfected patients requires antituberculosis and antiretroviral drugs to be administered concomittantly; challenges include pill burden and patient compliance, drug interactions, overlapping toxic effects, and immune reconstitution inflammatory syndrome. Current guidelines recommend starting antiretroviral treatment within a few weeks of antituberculosis therapy for patients with CD4 cell counts < 350 cells/ul.


An innovative approach to develop highly performant chalcogenide glasses and glass-ceramics transparent in the infrared range.
An innovative way to produce chalcogenide glasses and glass-ceramics for infrared devices is reported. This new method of synthesis at low temperature combining ball-milling and sintering by SPS (Spark Plasma Sintering) is a technological breakthrough to produce efficient infrared chalcogenide glasses and glass-ceramics. This technique will offer the possibility to strongly decrease the cost of infrared devices and to produce new chalcogenide glasses. It will also permit to increase the potential of some glass compositions by allowing their shaping at desired dimensions.


Surgical management of dysphagia and airway obstruction in patients with prominent ventral cervical osteophytes.
Large projecting ventral cervical osteophytes are associated with senile degenerative skeletal disease, post-traumatic osteophytogenesis, and diffuse idiopathic skeletal hyperostosis (DISH). The vast majority of patients with cervical osteophytes are asymptomatic. However, in a small subset this condition may lead to upper aerodigestive compromise manifesting as dysphagia and/or airway obstruction. Conservative medical therapy is usually sufficient, but patients with intractable disease may require surgical intervention, including tracheostomy, feeding tube placement, or osteophytectomy. A retrospective chart review was performed on all patients who presented to a tertiary referral center over a decade (1998-2008) with complaints of dysphagia and/or respiratory compromise and underwent osteophytectomy for treatment of recalcitrant symptoms. A total of nine patients met criteria. Six patients were diagnosed with DISH, two with trauma-associated osteophytogenesis, and one with senile degenerative vertebral disease. The mean age was 68 years and included seven males and two females. All patients had symptoms of dysphagia and two had simultaneous airway complaints. All patients underwent an anterolateral approach for osteophyte decompression, one of which required concurrent tracheostomy. Following surgery, 100% of patients had significant improvement in dysphagia and respiratory complaints. Eight of nine patients returned to an unrestricted diet and only one required postoperative abstinence from bulky foods; both patients with additional airway complaints were successfully decannulated after surgery. Degenerative conditions and DISH may lead to osteophyte-associated dysphagia and/or airway complaints. Surgical decompression through osteophytectomy is an effective alternative to tracheostomy and feeding tube in carefully selected patients and should be considered for surgically fit patients who fail conservative medical management.


Effect of Abdominal Lymphatic Pump Treatment on Disease Activity in a Rat Model of Inflammatory Bowel Disease.
Inflammatory bowel disease (IBD), such as ulcerative colitis and Crohn disease, are chronic relapsing inflammatory diseases that affect 1.5 million people in the United States. Lymphatic pump treatment (LPT) techniques were designed to enhance the movement of lymph and can be used to relieve symptoms in patients with IBD and other gastrointestinal disorders. To determine whether LPT would decrease gastrointestinal inflammation and reduce disease severity in rats with acute IBD. On day 0, rats were randomized into control or experimental groups. Control rats received normal drinking water for days 0 to 9. On days 0 to 9, rats in the experimental groups received drinking water containing 3.5% dextran sodium sulfate (DSS). On day 3, experimental rats were randomized into 3 groups. On days 3 to 8, experimental rats received either (1) no treatment or anesthesia (DSS alone); (2) 4 minutes of LPT with anesthesia administration (DSS+LPT); or (3) 4 minutes of sham treatment (ie, light touch) and anesthesia (DSS+sham). On day 9, colons and gastrointestinal lymphoid tissue were collected. Colon weight, histologic changes, disease activity index (DAI) score, and the concentration of leukocytes were measured. At day 9, the mean (SD) DAI score in the DSS+LPT group (1.0 [0.1]) was significantly decreased (P<.01) compared with the DAI score of DSS-alone rats (1.5 [0.1]). While the DAI in DSS+LPT rats was reduced on days 8 to 9, this difference was not statistically different (P>.05) compared with DSS+sham (1.3 [0.1]). No significant differences were found in colon weight, histopathologic findings, or the concentration of gastrointestinal leukocytes between DSS alone, DSS+sham, or DSS+LPT (P>.05). While DSS+LPT reduced IBD compared with DSS+sham, the decrease was not statistically significant. Considering the growing use of adjunctive treatment for the management of IBD, it is important to identify the effect of osteopathic manipulative medicine on IBD progression.


An immersive virtual peer for studying social influences on child cyclists' road-crossing behavior.
The goal of our work is to develop a programmatically controlled peer to bicycle with a human subject for the purpose of studying how social interactions influence road-crossing behavior. The peer is controlled through a combination of reactive controllers that determine the gross motion of the virtual bicycle, action-based controllers that animate the virtual bicyclist and generate verbal behaviors, and a keyboard interface that allows an experimenter to initiate the virtual bicyclist's actions during the course of an experiment. The virtual bicyclist's repertoire of behaviors includes road following, riding alongside the human rider, stopping at intersections, and crossing intersections through specified gaps in traffic. The virtual cyclist engages the human subject through gaze, gesture, and verbal interactions. We describe the structure of the behavior code and report the results of a study examining how 10- and 12-year-old children interact with a peer cyclist that makes either risky or safe choices in selecting gaps in traffic. Results of our study revealed that children who rode with a risky peer were more likely to cross intermediate-sized gaps than children who rode with a safe peer. In addition, children were significantly less likely to stop at the last six intersections after the experience of riding with the risky than the safe peer during the first six intersections. The results of the study and children's reactions to the virtual peer indicate that our virtual peer framework is a promising platform for future behavioral studies of peer influences on children's bicycle riding behavior.


RecA acts in trans to allow replication of damaged DNA by DNA polymerase V.
The DNA polymerase V (pol V) and RecA proteins are essential components of a mutagenic translesion synthesis pathway in Escherichia coli designed to cope with DNA damage. Previously, it has been assumed that RecA binds to the DNA template strand being copied. Here we show, however, that pol-V-catalysed translesion synthesis, in the presence or absence of the beta-processivity-clamp, occurs only when RecA nucleoprotein filaments assemble or RecA protomers bind on separate single-stranded (ss)DNA molecules in trans. A 3'-proximal RecA filament end on trans DNA is essential for stimulation; however, synthesis is strengthened by further pol V-RecA interactions occurring elsewhere along a trans nucleoprotein filament. We suggest that trans-stimulation of pol V by RecA bound to ssDNA reflects a distinctive regulatory mechanism of mutation that resolves the paradox of RecA filaments assembled in cis on a damaged template strand obstructing translesion DNA synthesis despite the absolute requirement of RecA for SOS mutagenesis.