Observed full blood count and lymphocyte subset values in a cohort of clinically healthy South African children from a semi-informal settlement in Cape Town.
The paediatric full blood count and lymphocyte subset reference intervals used by the National Health Laboratory Service (NHLS), South Africa (SA), are taken from two international reference interval publications. Differences in reference intervals suggest that international data sets may not be appropriate for use in SA. To study immunohaematological values of a group of clinically healthy children from an informal settlement in Cape Town, SA, to assess whether international paediatric reference intervals used by the NHLS are appropriate. A cross-sectional study of 207 female and 174 male HIV-uninfected children living in an informal settlement in Cape Town was performed. Full blood counts, automated differential counts and lymphocyte subset analysis were done using internationally accepted technologies. Data were categorised by age and reference intervals compiled using medians and 95% confidence intervals (CIs). Gender comparisons were calculated by non-parametric tests. Although median and 95% CI values differed slightly, physiological trends for red cell, platelet, white blood cell differential and lymphocyte subsets were similar to international reference intervals currently in use at the NHLS. Benign ethnic neutropenia was not a significant finding, and gender-specific intervals were not necessary until 12 years of age. Lower overall median values for haemoglobin and haematocrit, and higher median values for mean cell volume and red cell distribution width, were noted. Assessment of haemoglobin, red cell distribution width and calculated Mentzer ratios suggested underlying iron deficiency in 14.2% of participants. Paediatric immunohaematological reference intervals observed in this study are similar to, and support continued use of, international paediatric reference intervals. Underlying iron and related nutritional deficiencies may be contributing to lower haemoglobin levels noted in local children. A larger nationwide study, including all ethnic groups, is recommended.


Doxorubicin-induced oxidative stress: The protective effect of nicorandil on HL-1 cardiomyocytes.
The primary cardiotoxic action of doxorubicin when used as antitumor drug is attributed to the generation of reactive oxygen species (ROS) therefore effective cardioprotection therapies are needed. In this sense, the antianginal drug nicorandil has been shown to be effective in cardioprotection from ischemic conditions but the underlying molecular mechanism to cope with doxorubicin-induced ROS is unclear. Our in vitro study using the HL-1 cardiomyocyte cell line derived from mouse atria reveals that the endogenous nitric oxide (NO) production was stimulated by nicorandil and arrested by NO synthase inhibition. Moreover, while the NO synthase activity was inhibited by doxorubicin-induced ROS, the NO synthase inhibition did not affect doxorubicin-induced ROS. The inhibition of NO synthase activity by doxorubicin was totally prevented by preincubation with nicorandil. Nicorandil also concentration-dependently (10 to 100 μM) decreased doxorubicin-induced ROS and the effect was antagonized by 5-hydroxydecanoate. The inhibition profile of doxorubicin-induced ROS by nicorandil was unaltered when an L-arginine derivative or a protein kinase G inhibitor was present. Preincubation with pinacidil mimicked the effect of nicorandil and the protection was eliminated by glibenclamide. Quantitative colocalization of fluorescence indicated that the mitochondrion was the target organelle of nicorandil and the observed response was a decrease in the mitochondrial inner membrane potential. Interference with H+ movement across the mitochondrial inner membrane, leading to depolarization, also protected from doxorubicin-induced ROS. The data indicate that activation of the mitochondrial ATP-sensitive K+ channel by nicorandil causing mitochondrial depolarization, without participation of the NO donor activity, was responsible for inhibition of the mitochondrial NADPH oxidase that is the main contributor to ROS production in cardiomyocytes. Impairment of the cytosolic Ca2+ signal induced by caffeine and the increase in lipid peroxidation, both of which are indicators of doxorubicin-induced oxidative stress, were also prevented by nicorandil.


Image velocity sensing by optical correlation.
The technique of measuring the velocity of a moving image by means of a parallel-slit spatial filter is treated as continuous optical correlation processing. This technique is compared with other approaches to measuring image velocity by correlation and is shown to be a special case where the image displacement necessary for the correlation measurement is held constant and the time interval required to traverse this fixed distance is measured. The time measurement is accomplished inherently in terms of the frequency of the periodic signal generated by the image motion. Based on a derived mathematical model of the process and the characteristics of spatial filters, some conclusions are drawn about the way various parameters affect signal quality and continuity.


Individual genetic variations related to satiety and appetite control increase risk of obesity in preschool-age children in the STRONG kids program.
The burden of the childhood obesity epidemic is well recognized; nevertheless, the genetic markers and gene-environment interactions associated with the development of common obesity are still unknown. In this study, candidate genes associated to satiety and appetite control pathways with obesity-related traits were tested in Caucasian preschoolers from the STRONG Kids project. Eight genetic variants in genes related to obesity (BDNF, LEPR, FTO, PCSK1, POMC, TUB, LEP, and MC4R) were genotyped in 128 children from the STRONG Kids project (mean age 39.7 months). Data were analyzed for individual associations and to test for genetic predisposition scores (GPSs) with body mass index (BMI) and anthropometric traits (Z-scores, e.g. height-for-age Z-score, HAZ). Covariates included age, sex, and breastfeeding (BF) duration. Obesity and overweight prevalence was 6.3 and 19.5%, respectively, according to age- and sex-specific BMI percentiles. Individual genetic associations of MC4R and LEPR markers with HAZ were strengthened when BF duration was included as a covariate. Our GPSs show that, as the number of risk alleles increased, the risk of higher BMI and HAZ also increased. Overall, the GPSs assembled were able to explain 2-3% of the variability in BMI and HAZ phenotypes. Genetic associations with common obesity-related phenotypes were found in the STRONG Kids project. GPSs assembled for specific candidate genes were associated with BMI and HAZ phenotypes.


Photoinduced damage of AsLOV2 domain is accompanied by increased singlet oxygen production due to flavin dissociation.
Flavin mononucleotide (FMN) belongs to the group of very efficient endogenous photosensitizers producing singlet oxygen, 1O2, but with limited ability to be targeted. On the other hand, in genetically-encoded photosensitizers, which can be targeted by means of various tags, the efficiency of FMN to produce 1O2 is significantly diminished due to its interactions with surrounding amino acid residues. Recently, an increase of 1O2 production yield by FMN buried in a protein matrix was achieved by a decrease of quenching of the cofactor excited states by weakening of the protein-FMN interactions while still forming a complex. Here, we suggest an alternative approach which relies on the blue light irradiation-induced dissociation of FMN to solvent. This dissociation unlocks the full capacity of FMN as 1O2 producer. Our suggestion is based on the study of an irradiation effect on two variants of the LOV2 domain from Avena sativa; wild type, AsLOV2 wt, and the variant with a replaced cysteine residue, AsLOV2 C450A. We detected irradiation-induced conformational changes as well as oxidation of several amino acids in both AsLOV2 variants. Detailed analysis of these observations indicates that irradiation-induced increase in 1O2 production is caused by a release of FMN from the protein. Moreover, an increased FMN dissociation from AsLOV2 wt in comparison with AsLOV2 C450A points to a role of C450 oxidation in repelling the cofactor from the protein.


Functional validation of a human CAPN5 exome variant by lentiviral transduction into mouse retina.
Exome sequencing indicated that the gene encoding the calpain-5 protease, CAPN5, is the likely cause of retinal degeneration and autoimmune uveitis in human patients with autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV, OMIM #193235). To explore the mechanism of ADNIV, a human CAPN5 disease allele was expressed in mouse retinas with a lentiviral vector created to express either the wild-type human (h) CAPN5 or the ADNIV mutant hCAPN5-R243L allele under a rhodopsin promoter with tandem green fluorescent protein (GFP) expression. Vectors were injected into the subretinal space of perinatal mice. Mouse phenotypes were analyzed using electroretinography, histology and inflammatory gene expression profiling. Mouse calpain-5 showed high homology to its human ortholog with >98% sequence identity that includes the ADNIV mutant residue. Calpain-5 protein was expressed in the inner and outer segments of the photoreceptors and in the outer plexiform layer. Expression of the hCAPN5-R243L allele caused loss of the electroretinogram b-wave, photoreceptor degeneration and induction of immune cell infiltration and inflammatory genes in the retina, recapitulating major features of the ADNIV phenotype. Intraocular neovascularization and fibrosis were not observed during the study period. Our study shows that expression of the hCAPN5-R243L disease allele elicits an ADNIV-like disease in mice. It further suggests that ADNIV is due to CAPN5 gain-of-function rather than haploinsufficiency, and retinal expression may be sufficient to generate an autoimmune response. Genetic models of ADNIV in the mouse can be used to explore protease mechanisms in retinal degeneration and inflammation as well as preclinical therapeutic testing.


The direct magnetoelectric effect in ferroelectric-ferromagnetic epitaxial heterostructures.
Ferroelectric (FE) and ferromagnetic (FM) materials engineered in horizontal heterostructures allow interface-mediated magnetoelectric coupling. The so-called converse magnetoelectric effect (CME) has been already demonstrated by electric-field poling of the ferroelectric layers and subsequent modification of the magnetic state of adjacent ferromagnetic layers by strain effects and/or free-carrier density tuning. Here we focus on the direct magnetoelectric effect (DME) where the dielectric state of a ferroelectric thin film is modified by a magnetic field. Ferroelectric BaTiO3 (BTO) and ferromagnetic CoFe2O4 (CFO) oxide thin films have been used to create epitaxial FE/FM and FM/FE heterostructures on SrTiO3(001) substrates buffered with metallic SrRuO3. It will be shown that large ferroelectric polarization and DME can be obtained by appropriate selection of the stacking order of the FE and FM films and their relative thicknesses. The dielectric permittivity, at the structural transitions of BTO, is strongly modified (up to 36%) when measurements are performed under a magnetic field. Due to the insulating nature of the ferromagnetic layer and the concomitant absence of the electric-field effect, the observed DME effect solely results from the magnetostrictive response of CFO elastically coupled to the BTO layer. These findings show that appropriate architecture and materials selection allow overcoming substrate-induced clamping in multiferroic multi-layered films.


Feasibility of Dried Blood Spots in Children with Behavioral Problems.
Minimally invasive sampling methods are important to facilitate therapeutic drug monitoring and pharmacokinetic research in children with behavioral problems. This study assessed the feasibility and pain of dried blood spot (DBS) sampling in this population. Repeated DBS sampling was performed in children with autism spectrum disorder (ASD) and severe behavioral problems using antipsychotic drugs, aged between 6 and 18 years. The child, guardian, and DBS performer assessed pain using the numeric rating scale (NRS-11) or 5-face Faces Pain Scale. The influence of age, sex, and the fingerprick performer on the child's pain intensity was analyzed using linear mixed models. Overall, 247 fingerpricks were performed in 70 children. Seven children refused all DBS sampling. The median (interquartile range) NRS-11 pain scores were 2 (3) rated by children, 3 (2.5) by guardians, and 2 (2) by fingerprick performers. The child's age and sex, and fingerprick performer had no significant influence on pain intensity. DBS sampling could be performed in most children with ASD and severe behavioral problems. However, 1 in 5 children refused one or more DBS fingerpricks owing to distress. Most expressed minimal pain (NRS < 4). Repeated sampling with DBS is feasible in children with ASD and severe behavioral problems.


Two dynamin-like proteins stabilize FtsZ rings during Streptomyces sporulation.
During sporulation, the filamentous bacteria Streptomyces undergo a massive cell division event in which the synthesis of ladders of sporulation septa convert multigenomic hyphae into chains of unigenomic spores. This process requires cytokinetic Z-rings formed by the bacterial tubulin homolog FtsZ, and the stabilization of the newly formed Z-rings is crucial for completion of septum synthesis. Here we show that two dynamin-like proteins, DynA and DynB, play critical roles in this process. Dynamins are a family of large, multidomain GTPases involved in key cellular processes in eukaryotes, including vesicle trafficking and organelle division. Many bacterial genomes encode dynamin-like proteins, but the biological function of these proteins has remained largely enigmatic. Using a cell biological approach, we show that the two Streptomyces dynamins specifically localize to sporulation septa in an FtsZ-dependent manner. Moreover, dynamin mutants have a cell division defect due to the decreased stability of sporulation-specific Z-rings, as demonstrated by kymographs derived from time-lapse images of FtsZ ladder formation. This defect causes the premature disassembly of individual Z-rings, leading to the frequent abortion of septum synthesis, which in turn results in the production of long spore-like compartments with multiple chromosomes. Two-hybrid analysis revealed that the dynamins are part of the cell division machinery and that they mediate their effects on Z-ring stability during developmentally controlled cell division via a network of protein-protein interactions involving DynA, DynB, FtsZ, SepF, SepF2, and the FtsZ-positioning protein SsgB.


The role of Bcl-2 protein and autocrine growth factors in a human follicular lymphoma-derived B cell line.
We have shown that the ability of the human follicular lymphoma-derived cell line SU-DHL-6 to proliferate and survive in vitro depends on both Bcl-2 expression and multiple autocrine growth factors. Treatment with Bcl-2 antisense (AS Bcl-2) decreased Bcl-2 protein levels. However, a cytotoxic effect was seen only at very restricted cell densities. Below such densities cells underwent spontaneous death without any treatment, while above these cell densities no cytotoxic effect of AS Bcl-2 could be seen. The conditioned medium of SU-DHL cells supported the survival and growth of these cells cultivated at low cell densities and partially reversed the cytotoxicity associated with Bcl-2 depletion. RT/PCR analysis revealed autocrine expression of IL-1 beta, IL-2, IL-5 and TNF-beta in SU-DHL cells. Neutralizing antibodies against these cytokines inhibited SU-DHL proliferation. Thus, development of autocrine GF secretion may be the second step in the pathogenesis of follicular lymphomas.


Breast-conserving surgery for breast cancer.
Surgical treatment of breast cancer has changed significantly in recent years. Fine-needle aspirations or core-needle biopsies can be used in the diagnostic process, thus avoiding scarring incisions. The preferred method of treatment for many women with early breast cancer is conservative surgical therapy (principally lumpectomy and axillary dissection) followed by breast irradiation. Sentinel node biopsy is being investigated as an alternative to standard axillary node dissection. This could decrease morbidity following standard axillary dissection. These techniques allow women with different forms of breast cancer to conserve their breasts. For women who choose mastectomy, immediate reconstruction of the breast is now routinely performed with a prosthetic implant or autologous tissue. Clinical history, physical examination, and breast imaging are the most effective means of follow-up.


Ventromedial prefrontal cortex supports affective future simulation by integrating distributed knowledge.
Although the future often seems intangible, we can make it more concrete by imagining prospective events. Here, using functional MRI, we demonstrate a mechanism by which the ventromedial prefrontal cortex supports such episodic simulations, and thereby contributes to affective foresight: This region supports processes that (i) integrate knowledge related to the elements that constitute an episode and (ii) represent the episode's emergent affective quality. The ventromedial prefrontal cortex achieves such integration via interactions with distributed cortical regions that process the individual elements. Its activation then signals the affective quality of the ensuing episode, which goes beyond the combined affective quality of its constituting elements. The integrative process further augments long-term retention of the episode, making it available at later time points. This mechanism thus renders the future tangible, providing a basis for farsighted behavior.


On-Chip Chemical Self-Assembly of Semiconducting Single-Walled Carbon Nanotubes (SWNTs): Toward Robust and Scale Invariant SWNTs Transistors.
In this paper, the fabrication of carbon nanotubes field effect transistors by chemical self-assembly of semiconducting single walled carbon nanotubes (s-SWNTs) on prepatterned substrates is demonstrated. Polyfluorenes derivatives have been demonstrated to be effective in selecting s-SWNTs from raw mixtures. In this work the authors functionalized the polymer with side chains containing thiols, to obtain chemical self-assembly of the selected s-SWNTs on substrates with prepatterned gold electrodes. The authors show that the full side functionalization of the conjugated polymer with thiol groups partially disrupts the s-SWNTs selection, with the presence of metallic tubes in the dispersion. However, the authors determine that the selectivity can be recovered either by tuning the number of thiol groups in the polymer, or by modulating the polymer/SWNTs proportions. As demonstrated by optical and electrical measurements, the polymer containing 2.5% of thiol groups gives the best s-SWNT purity. Field-effect transistors with various channel lengths, using networks of SWNTs and individual tubes, are fabricated by direct chemical self-assembly of the SWNTs/thiolated-polyfluorenes on substrates with lithographically defined electrodes. The network devices show superior performance (mobility up to 24 cm2 V-1 s-1 ), while SWNTs devices based on individual tubes show an unprecedented (100%) yield for working devices. Importantly, the SWNTs assembled by mean of the thiol groups are stably anchored to the substrate and are resistant to external perturbation as sonication in organic solvents.


Effective prevention of pseudothrombocytopenia in feline blood samples with the prostaglandin I2 analogue Iloprost.
In vitro platelet aggregation in feline blood samples is a well-known phenomenon in veterinary clinical laboratories resulting in high numbers of pseudothrombocytopenia. Several attempts have been made to prevent or dissolve platelet aggregates in feline blood samples and to increase the reliability of feline platelet counts. Prostaglandin I2 (PGI2) is the most powerful endogenous inhibitor of platelet aggregation but unstable. Iloprost is a stable PGI2 analogue. The aims of the present study were (1) to evaluate the anti-aggregatory effect of Iloprost on feline platelet counts and to determine a useful concentration to inhibit platelet aggregation in EDTA samples from clinically healthy cats, (2) to investigate the effect of Iloprost on hematological blood parameters, and (3) to determine stability of Iloprost in K3-EDTA tubes for up to 16 weeks. From 20 clinically healthy cats blood was drawn from the jugular vein and immediately distributed in a 1.3 ml K3-EDTA tube, and two 1.3 ml K3-EDTA tubes containing 20 ng and 200 ng Iloprost, respectively. A complete blood cell count was performed on the Sysmex XT-2000iV and the Mythic 18 on eight consecutive time points after collection. Blood smears were evaluated for the presence of PLT aggregates. In the absence of Iloprost, pseudothrombocytopenia was observed in 50% of the investigated samples that led to significantly decreased optical PLT counts by a mean of 105 x10(3)/μl, which could be prevented by the addition of 1 μL (20 ng) Iloprost leading to an increase in PLT counts by a mean of 108 x10(3)/μl. This is the first study showing an anti-aggregatory effect of the PGI2-analogue Iloprost in feline EDTA blood. In all clinically healthy cats investigated, pseudothrombocytopenia was prevented by adding Iloprost to EDTA tubes prior to blood collection. Furthermore, Iloprost was very useful in preventing falsely increased WBC counts in samples with platelet aggregates analyzed on impedance-based hematological instruments. Iloprost is preferable to PGI2 or PGE1 due to its stability and easy and safe handling properties. Cytological evaluations of blood smears as well as other hematological parameters were not influenced to a clinically significant degree by the presence of Iloprost.


Healthcare provider and patient perspectives on diagnostic imaging investigations.
Much has been written about the patient-centred approach in doctor-patient consultations. Little is known about interactions and communication processes regarding healthcare providers' and patients' perspectives on expectations and experiences of diagnostic imaging investigations within the medical encounter. Patients journey through the health system from the point of referral to the imaging investigation itself and then to the post-imaging consultation. AIM AND SETTING: To explore healthcare provider and patient perspectives on interaction and communication processes during diagnostic imaging investigations as part of their clinical journey through a healthcare complex. A qualitative study was conducted, with two phases of data collection. Twenty-four patients were conveniently selected at a public district hospital complex and were followed throughout their journey in the hospital system, from admission to discharge. The second phase entailed focus group interviews conducted with providers in the district hospital and adjacent academic hospital (medical officers and family physicians, nurses, radiographers, radiology consultants and registrars). Two main themes guided our analysis: (1) provider perspectives; and (2) patient dispositions and reactions. Golden threads that cut across these themes are interactions and communication processes in the context of expectations, experiences of the imaging investigations and the outcomes thereof. Insights from this study provide a better understanding of the complexity of the processes and interactions between providers and patients during the imaging investigations conducted as part of their clinical pathway. The interactions and communication processes are provider-patient centred when a referral for a diagnostic imaging investigation is included.


The Sources of Dual-task Costs in Multisensory Working Memory Tasks.
We investigated the sources of dual-task costs arising in multisensory working memory (WM) tasks, where stimuli from different modalities have to be simultaneously maintained. Performance decrements relative to unimodal single-task baselines have been attributed to a modality-unspecific central WM store, but such costs could also reflect increased demands on central executive processes involved in dual-task coordination. To compare these hypotheses, we asked participants to maintain two, three, or four visual items. Unimodal trials, where only this visual task was performed, and bimodal trials, where a concurrent tactile WM task required the additional maintenance of two tactile items, were randomly intermixed. We measured the visual and tactile contralateral delay activity (CDA/tCDA components) as markers of WM maintenance in visual and somatosensory areas. There were reliable dual-task costs, as visual CDA components were reduced in size and visual WM accuracy was impaired on bimodal relative to unimodal trials. However, these costs did not depend on visual load, which caused identical CDA modulations in unimodal and bimodal trials, suggesting that memorizing tactile items did not reduce the number of visual items that could be maintained. Visual load did not also affect tCDA amplitudes. These findings indicate that bimodal dual-task costs do not result from a competition between multisensory items for shared storage capacity. Instead, these costs reflect generic limitations of executive control mechanisms that coordinate multiple cognitive processes in dual tasks. Our results support hierarchical models of WM, where distributed maintenance processes with modality-specific capacity limitations are controlled by a central executive mechanism.


Identification of the in vivo phosphorylation sites for acidic-directed kinases in murine mdr1b P-glycoprotein.
P-glycoprotein, the multidrug resistance transporter, is phosphorylated in vivo and the major phosphorylation domain has been identified as the linker region (amino acids 629-686). The linker region is a highly charged segment of the transporter in which the negative and positive amino acid side chains are spatially segregated. Both of these charged domains contain several consensus phosphorylation sites for protein kinases. Three of the consensus phosphorylation sites for basic-directed kinases in murine mdr1b P-glycoprotein are utilized in vivo and have been identified as serines 665, 669, and 681. Mutagenesis of all the consensus basic-directed kinase phosphorylation sites in the linker region of human MDR1 P-glycoprotein did not alter the ability of the mutated transporter to confer the multidrug resistance phenotype in stably transfected cell lines. These studies would suggest that phosphorylation/dephosphorylation within the basic domain of the linker region is not directly involved in regulation of drug transporter activity. We now report that the linker region of mdr1b P-glycoprotein is also phosphorylated in vivo within the acidic domain (amino acids 631-658). These sites have been mapped using casein kinase II, a prototypic acidic-directed kinase, and a recombinant mdr1b linker region peptide (amino acids 621-687). Electrospray mass spectrometry demonstrated that casein kinase II could introduce up to five phosphates into the recombinant peptide. Two-dimensional phosphopeptide mapping indicated that all the phosphates were contained in a tryptic peptide consisting of amino acids 631-658. Phosphopeptide mapping of in vivo labeled P-glycoprotein, isolated from either J7.V1-1, a murine vinblastine-resistant cell line, or HeLa cells stably transfected with mdr1b P-glycoprotein cDNA, revealed that this tryptic peptide was phosphorylated in both proteins.


Walking motion generation, synthesis, and control for biped robot by using PGRL, LPI, and fuzzy logic.
This paper proposes the implementation of fuzzy motion control based on reinforcement learning (RL) and Lagrange polynomial interpolation (LPI) for gait synthesis of biped robots. First, the procedure of a walking gait is redefined into three states, and the parameters of this designed walking gait are determined. Then, the machine learning approach applied to adjusting the walking parameters is policy gradient RL (PGRL), which can execute real-time performance and directly modify the policy without calculating the dynamic function. Given a parameterized walking motion designed for biped robots, the PGRL algorithm automatically searches the set of possible parameters and finds the fastest possible walking motion. The reward function mainly considered is first the walking speed, which can be estimated from the vision system. However, the experiment illustrates that there are some stability problems in this kind of learning process. To solve these problems, the desired zero moment point trajectory is added to the reward function. The results show that the robot not only has more stable walking but also increases its walking speed after learning. This is more effective and attractive than manual trial-and-error tuning. LPI, moreover, is employed to transform the existing motions to the motion which has a revised angle determined by the fuzzy motion controller. Then, the biped robot can continuously walk in any desired direction through this fuzzy motion control. Finally, the fuzzy-based gait synthesis control is demonstrated by tasks and point- and line-target tracking. The experiments show the feasibility and effectiveness of gait learning with PGRL and the practicability of the proposed fuzzy motion control scheme.


Evidence-Based Practice Implementation in Stroke Rehabilitation: A Scoping Review of Barriers and Facilitators.
Despite advancements in stroke rehabilitation research, occupational therapy practitioners still face challenges with implementing research into routine practice. Although the development of evidence-based practices (EBPs) is one critical step along the knowledge translation continuum for the population of people with stroke, research is also needed to identify the most effective strategies for implementing EBPs with stroke survivors who are receiving occupational therapy services. To synthesize research related to occupational therapy practitioners' implementation of EBPs in adult stroke rehabilitation. We searched four electronic databases-CINAHL, MEDLINE, PubMed, and Academic Search Complete-and the peer-reviewed journal Implementation Science to identify relevant research studies. Studies that met the following inclusion criteria were included in the scoping review: published between January 2003 and January 2018, addressed the adult stroke population, and examined the implementation of occupational therapy interventions. Data were abstracted on the basis of recommendations from the seminal review framework established by Arksey and O'Malley (2005). Thematic analysis identified themes that emerged from the included studies. Twenty-five articles satisfied our inclusion parameters. Our analyses yielded three overarching themes: barriers to implementation, facilitators of implementation, and implementation strategies. Implementation strategies often consisted of multimodal knowledge translation training programs. Although the stroke rehabilitation literature appears to have established the barriers to and facilitators of EBP implementation, greater attention to the identification of effective implementation strategies that promote the uptake of EBPs by occupational therapy practitioners is needed. This article summarizes the contextual factors and effective strategies that may influence practitioners' implementation of stroke research findings in real-world practice.


Molecular basis for cytadsorption of Mycoplasma pneumoniae.
Hemadsorbing (HA+) virulent Mycoplasma pneumoniae and spontaneously derived nonhemadsorbing (HA-) avirulent mutants were compared by biochemical and ultrastructural techniques in an attempt to understand the molecular basis for cytadsorption. Lactoperoxidase-catalyzed iodination of intact mycoplasmas indicated that both virulent and avirulent mycoplasmas displayed similar surface protein patterns. A specific external protein, P1 (molecular weight, 165,000), previously implicated as a major ligand mediating attachment, was readily detected in HA+ and HA- mycoplasma strains. However, immunoferritin electron microscopy, with monospecific antibody against P1, revealed that differences in P1 topography existed among these strains. Only virulent mycoplasmas exhibited high concentrations of P1 at the terminal organelle. Avirulent mycoplasmas which possessed P1 showed no P1 clustering at the terminus. Both virulent M. pneumoniae and avirulent P1-containing mutants possessed numerous less dense P1 regions along the mycoplasma surface. Not surprisingly, an HA- mutant lacking P1 exhibited only background immunoferritin labeling. Negative staining of intact mycoplasmas revealed a well-defined, naplike terminus (associated with P1 clusters) confined at the tip of virulent M. pneumoniae. Previous characterization of HA+ virulent and HA- avirulent strains of M. pneumoniae by one- and two-dimensional polyacrylamide gel electrophoresis suggests that identified groups of mycoplasma proteins, lacking in specific HA- mycoplasmas, regulate the physical arrangement of P1 and the ultrastructure of the terminus, thus influencing adherence to the respiratory epithelium and virulence.


ACOX1, regulated by C/EBPα and miR-25-3p, promotes bovine preadipocyte adipogenesis.
Acyl-coenzyme A oxidase 1 (ACOX1) is the first and rate-limiting enzyme in peroxisomal fatty acid β-oxidation of fatty acids. Previous studies have reported that ACOX1 was correlated with the meat quality of livestock, while the role of ACOX1 in intramuscular adipogenesis of beef cattle and its transcriptional and post-transcriptional regulatory mechanisms remain unclear. In the present study, gain-of-function and loss-of-function assays demonstrated that ACOX1 positively regulated the adipogenesis of bovine intramuscular preadipocytes. The C/EBPα-binding sites in the bovine ACOX1 promoter region at -1142 to -1129 bp, -831 to -826 bp, and -303 to -298 bp were identified by promoter deletion analysis and site-directed mutagenesis. Electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) further showed that these three regions are C/EBPα-binding sites, both in vitro and in vivo, indicating that C/EBPα directly interacts with the bovine ACOX1 promoter and inhibits its transcription. Furthermore, the results from bioinformatics analysis, dual luciferase assay, site-directed mutagenesis, qRT-PCR, and Western blotting demonstrated that miR-25-3p directly targeted the ACOX1 3'UTR (3'UTR). Taken together, our findings suggest that ACOX1, regulated by transcription factor C/EBPα and miR-25-3p, promotes adipogenesis of bovine intramuscular preadipocytes via regulating peroxisomal fatty acid β-oxidation.


Factors associated with HIV testing among immigrants in Portugal.
This paper describes the uptake of HIV testing and its associated factors among a sample of immigrants in Portugal. A questionnaire was completed by 1,513 immigrants at the National Immigrant Support Centre, in Lisbon. The magnitude of the association between ever been HIV tested and socio-demographic variables was estimated by means of crude and adjusted odds ratios, and their 95% confidence intervals, using logistic regression. Approximately half of the participants reported having ever been HIV tested. Age, sex, educational level, region of origin, immigration status and knowing someone infected were independently associated with the HIV test uptake. Almost 90% of participants reported knowing where to obtain support on HIV-related issues. Most declared preferring doctors to get HIV information. However, only 9.2% had sought HIV information at the National Health Service. Our results suggest differences between migrant groups regarding HIV testing. Adopting more innovative approaches to HIV testing could improve the efficacy of HIV prevention strategies, especially among vulnerable groups within immigrant population as male and undocumented.


Transcriptional regulation of autophagy in RAS-driven cancers.
RAS-driven cancers exhibit variable dependency on autophagy for survival; however, it is not fully understood how. In this issue of the JCI, Cheong and colleagues demonstrate that RAS-dependent elevation of casein kinase 1α (CK1α) negatively regulates autophagy at the level of autophagy gene transcription. Moreover, combined inhibition of both CK1α and autophagy reduced proliferation of RAS-driven tumors. The results of this study provide insight into the connection between mutant RAS and autophagy, and suggest targeting CK1α as a potential therapeutic strategy to modulate autophagy in RAS-driven cancers.


Disease modifying drugs in multiple sclerosis: mechanisms of action and new drugs in the horizon.
The term "disease modifying drugs" (DMD) is taken from rheumatologists who coined it after the use of immunosuppressive drugs and, more recently, the association of "biological drugs" that changed the degenerative course of rheumatic disease. In the treatment of multiple sclerosis (MS), the advent of interferon (IFN)-β, which caused a reduction in the number of relapses and possibly improvement in disability outcomes, was the first strategy to prevent inflammatory damage in the central nervous system (CNS). Soon after, glatiramer acetate showed similar results. It would be more than a decade before natalizumab was licensed, showing a much better efficiency in relapse reduction than was seen after first-line therapies failed. The pipeline is now much larger with several drugs on the horizon. Overall, the anti-inflammatory strategy has been mostly successful but drugs that have protection and repair mechanisms are still missing.


The role for protein tyrosine phosphatase non-receptor type 22 in regulating intestinal homeostasis.
Inflammatory bowel disease represents a chronic intestinal inflammation. Recent knowledge suggests a crucial role for genetic, immunological and bacterial factors in inflammatory bowel disease pathogenesis. Variations within the gene locus encoding PTPN22 have been associated with inflammatory bowel disease. PTPN22 is critically involved in controlling immune cell activation and thereby plays an important role in maintaining intestinal homeostasis. Although in B and T cells the mechanism showing how PTPN22 affects cell signalling pathways is well studied, its role in myeloid cells remains less defined. Regulation of the innate immune system plays an essential role in the intestine, and levels of PTPN22 in myeloid cells are drastically reduced in the intestine of inflammatory bowel disease patients. Therefore, additional studies to define the role of PTPN22 in myeloid cells might clearly enhance our understanding of how PTPN22 contributes to intestinal homeostasis.


Therapist-assisted online psychological therapies differing in trauma focus for post-traumatic stress disorder (STOP-PTSD): a UK-based, single-blind, randomised controlled trial.
Many patients are currently unable to access psychological treatments for post-traumatic stress disorder (PTSD), and it is unclear which types of therapist-assisted internet-based treatments work best. We aimed to investigate whether a novel internet-delivered cognitive therapy for PTSD (iCT-PTSD), which implements all procedures of a first-line, trauma-focused intervention recommended by the UK National Institute for Health and Care Excellence (NICE) for PTSD, is superior to internet-delivered stress management therapy for PTSD (iStress-PTSD), a comprehensive cognitive behavioural treatment programme focusing on a wide range of coping skills. We did a single-blind, randomised controlled trial in three locations in the UK. Participants (≥18 years) were recruited from UK National Health Service (NHS) Improving Access to Psychological Therapies (IAPT) services or by self-referral and met DSM-5 criteria for PTSD to single or multiple events. Participants were randomly allocated by a computer programme (3:3:1) to iCT-PTSD, iStress-PTSD, or a 3-month waiting list with usual NHS care, after which patients who still met PTSD criteria were randomly allocated (1:1) to iCT-PTSD or iStress-PTSD. Randomisation was stratified by location, duration of PTSD (<18 months or ≥18 months), and severity of PTSD symptoms (high vs low). iCT-PTSD and iStress-PTSD were delivered online with therapist support by messages and short weekly phone calls over the first 12 weeks (weekly treatment phase), and three phone calls over the next 3 months (booster phase). The primary outcome was the severity of PTSD symptoms at 13 weeks after random assignment, measured by self-report on the PTSD Checklist for DSM-5 (PCL-5), and analysed by intention-to-treat. Safety was assessed in all participants who started treatment. Process analyses investigated acceptability and compliance with treatment, and candidate moderators and mediators of outcome. The trial was prospectively registered with the ISRCTN registry, ISRCTN16806208. Of the 217 participants, 158 (73%) self-reported as female, 57 (26%) as male, and two (1%) as other; 170 (78%) were White British, 20 (9%) were other White, six (3%) were Asian, ten (5%) were Black, eight (4%) had a mixed ethnic background, and three (1%) had other ethnic backgrounds. Mean age was 36·36 years (SD 12·11; range 18-71 years). 52 (24%) participants met self-reported criteria for ICD-11 complex PTSD. Fewer than 10% of participants dropped out of each treatment group. iCT-PTSD was superior to iStress-PTSD in reducing PTSD symptoms, showing an adjusted difference on the PCL-5 of -4·92 (95% CI -8·92 to -0·92; p=0·016; standardised effect size d=0·38 [0·07 to 0·69]) for immediate allocations and -5·82 (-9·59 to -2·04; p=0·0027; d=0·44 [0·15 to 0·72]) for all treatment allocations. Both treatments were superior to the waiting list for PCL-5 at 13 weeks (d=1·67 [1·23 to 2·10] for iCT-PTSD and 1·29 [0·85 to 1·72] for iStress-PTSD). The advantages in outcome for iCT-PTSD were greater for participants with high dissociation or complex PTSD symptoms, and mediation analyses showed both treatments worked by changing negative meanings of the trauma, unhelpful coping, and flashback memories. No serious adverse events were reported. Trauma-focused iCT-PTSD is effective and acceptable to patients with PTSD, and superior to a non-trauma-focused cognitive behavioural stress management therapy, suggesting that iCT-PTSD is an effective way of delivering the contents of CT-PTSD, one of the NICE-recommended first-line treatments for PTSD, while reducing therapist time compared with face-to-face therapy. Wellcome Trust, UK National Institute for Health and Care Research Oxford Health Biomedical Research Centre.


Analysis of the mononuclear inflammatory cell infiltrate in the normal breast, benign proliferative breast disease, in situ and infiltrating ductal breast carcinomas: preliminary observations.
Mammary carcinogenesis is a multistep process entailing the transition from normal breast to benign proliferative breast disease (ductal hyperplasia) to ductal carcinoma in situ to infiltrating ductal carcinoma. These transitions are associated with changes in the mononuclear inflammatory cell infiltrate. A total of 53 mastectomy specimens of normal breast, benign proliferative breast disease, ductal carcinoma in situ and infiltrating ductal carcinoma were evaluated for mononuclear inflammatory cell infiltrate by using immunohistological methods and monoclonal antibodies including CD20, CD68, CD3 and granzyme B, histiocytes, T cells and cytotoxic T cells. Transitions from normal breast to the subsequent tissue with lesions (normal skin v benign proliferative breast disease v ductal carcinoma in situ v infiltrating ductal carcinoma) were associated with significantly (p<0.01) increased mean (SD) density of mononuclear inflammatory cell infiltrate at the parenchyma (3.2 (1.0) v 26.4 (7.8) v 33.6 (7.9) v 39.1 (4.7) for CD20+ B cells; 2.8 (1.0) v 81.5 (14.0) v 84.0 (14.9) v103.7 (3.9) for CD3; 1.3 (2.0) v 3.8 (4.0) v 12.7 (23) v 22.1 (25.0) for CD68+ macrophages; 2.0 (1.0) v 58.3 (5.0) v 60.0 (10.0) v 74.1 (28.0) for granzyme B+ cytotoxic T cells) and at the stroma (0.7 (1.0) v 3.0 (5.0) v 13.3 (20) v 16.7 (30.0) for CD20+ B cells; 1.0 (2.06) v 4.0 (2.5) v 16.7 (5.0) v 21.7 (15) for CD68+ macrophages; 1.4 (0.6) v 4.2 (1.2) v 46.6 (16.7) v 77.0 (5.0) for CD3+ cells and 0 (0) v 0.5 (1.0) v 0.7 (1.0) v 0.7 (1.0) for granzyme B+ cytotoxic T cells). The increased mononuclear inflammatory cell infiltrate during mammary carcinogenesis may reflect non-specific or specific immunological processes.


Fatherhood in the twenty-first century.
The twentieth century has been characterized by four important social trends that have fundamentally changed the social cultural context in which children develop: women's increased labor force participation, increased absence of nonresidential fathers in the lives of their children, increased involvement of fathers in intact families, and increased cultural diversity in the U.S.. In this essay, we discuss how these trends are changing the nature of father involvement and family life, and in turn affecting children's and fathers' developmental trajectories. We end with an eye toward the twenty-first century by examining how the children of today will construct their expectations about the roles of fathers and mothers as they become the parents of tomorrow. This life-span approach to fatherhood considers the broader sociohistorical context in which fatherhood develops, and emphasizes the urgent need to consider mothers, fathers, and family structure in future research as we seek to understand and model the effects of parenting on children's development.


Recent strategies to improve boron dipyrromethene (BODIPY) for photodynamic cancer therapy: an updated review.
BODIPYs are photosensitizers activatable by light to generate highly reactive singlet oxygen (1O2) from molecular oxygen, leading to tissue damage in the photoirradiated region. Despite their extraordinary photophysical characteristics, they are not featured in clinical photodynamic therapy. This review discusses the recent advances in the design and/or modifications of BODIPYs since 2013, to improve their potential in photodynamic cancer therapy and related areas.


Spoof-plasmon relevant one-way collimation and multiplexing at beaming from a slit in metallic grating.
Diode and collimator/multiplexer functions are suggested to be combined in one device that is based on a thin metallic grating with a single subwavelength slit. A proper choice of the structural (a)symmetry of the grating can result in obtaining one-way collimation and multiplexing with a single on-axis or off-axis, or two off-axis narrow outgoing beams. It is possible due to freedom in utilizing different combinations of the excitation conditions of the spoof surface plasmons at the four grating parts - right and left front-side and right and left back-side ones. Such a combining provides one with an efficient tool to engineer one-way collimators and multiplexers with the desired characteristics. Strong asymmetry in transmission with respect to the incidence direction (forward vs backward case) can be obtained within a wide range of variation of the incident beam parameters, i.e., angle of incidence and frequency, while the outgoing radiation is concentrated within a narrow range of the observation angle variation. Most of the observed asymmetric transmission features can be qualitatively explained using the concept of the equivalent source placed inside the slit.


Leveraging Neuroscience to Inform Adolescent Health: The Need for an Innovative Transdisciplinary Developmental Science of Adolescence.
In this article, we consider how to leverage some of the rapid advances in developmental neuroscience in ways that can improve adolescent health. We provide a brief overview of several key areas of scientific progress relevant to these issues. We then focus on two examples of important health problems that increase sharply during adolescence: sleep problems and affective disorders. These examples illustrate how an integrative, developmental science approach provides new insights into treatment and intervention. They also highlight a cornerstone principle: how a deeper understanding of potentially modifiable factors-at key developmental inflection points along the trajectory toward clinical disorders-is beginning to inform, and may eventually transform, a broad range of innovative early intervention strategies to improve adolescent health.


Action to address the household economic burden of non-communicable diseases.
The economic burden on households of non-communicable diseases (NCDs), including cardiovascular diseases, cancer, respiratory diseases, and diabetes, poses major challenges to global poverty alleviation efforts. For patients with NCDs, being uninsured is associated with 2-7-fold higher odds of catastrophic levels of out-of-pocket costs; however, the protection offered by health insurance is often incomplete. To enable coverage of the predictable and long-term costs of treatment, national programmes to extend financial protection should be based on schemes that entail compulsory enrolment or be financed through taxation. Priority should be given to eliminating financial barriers to the uptake of and adherence to interventions that are cost-effective and are designed to help the poor. In concert with programmes to strengthen national health systems and governance arrangements, comprehensive financial protection against the growing burden of NCDs is crucial in meeting the UN's Sustainable Development Goals.


VivaScope® 1500 and 3000 systems for detecting and monitoring skin lesions: a systematic review and economic evaluation.
Skin cancer is one of the most common cancers in the UK. The main risk factor is exposure to ultraviolet radiation from sunlight or the use of sunbeds. Patients with suspicious skin lesions are first examined with a dermoscope. After examination, those with non-cancerous lesions are discharged, but lesions that are still considered clinically suspicious are surgically removed. VivaScope(®) is a non-invasive technology designed to be used in conjunction with dermoscopy to provide a more accurate diagnosis, leading to fewer biopsies of benign lesions or to provide more accurate presurgical margins reducing the risk of cancer recurrence. To evaluate the clinical effectiveness and cost-effectiveness of VivaScope(®) 1500 (Caliber Imaging and Diagnostics, Rochester, NY, USA; Lucid Inc., Rochester, NY, USA; or Lucid Inc., MAVIG GmbH, Munich, Germany) and VivaScope(®) 3000 (Caliber Imaging and Diagnostics, Rochester, NY, USA) in the diagnosis of equivocal skin lesions, and VivaScope 3000 in lesion margin delineation prior to surgical excision of lesions. Databases (MEDLINE, EMBASE and The Cochrane Library) were searched on 14 October 2014, reference lists of included papers were assessed and clinical experts were contacted for additional information on published and unpublished studies. A systematic review was carried out to identify randomised controlled trials (RCTs) or observational studies evaluating dermoscopy plus VivaScope, or VivaScope alone, with histopathology as the reference test. A probabilistic de novo economic model was developed to synthesise the available data on costs and clinical outcomes from the UK NHS perspective. All costs were expressed as 2014 prices. Sixteen studies were included in the review, but they were too heterogeneous to be combined in a meta-analysis. One of two diagnostic studies that were deemed most representative of UK clinical practice reported that dermoscopy plus VivaScope 1500 was significantly more sensitive than dermoscopy alone in the diagnosis of melanoma (97.8% vs. 94.6%; p = 0.043) and significantly more specific than dermoscopy alone in the diagnosis of non-melanoma (92.4% vs. 26.74%; p < 0.000001). The results of another study suggest 100% [95% confidence interval (CI) 86.16% to 100%] sensitivity for dermoscopy plus VivaScope 1500 versus 100% (95% CI 91.51% to 100%) for dermoscopy alone. Specificity varied from 51.77% to 80.2% depending on the analysis set used. In terms of margin delineation with VivaScope, one study found that 17 out of 29 patients with visible lentigo maligna (LM) had subclinical disease of > 5 mm beyond the dermoscopically identified margin. Using 'optimistic' diagnostic data, the economic model resulted in an incremental cost-effectiveness ratio (ICER) of £8877 per quality-adjusted life-year (QALY) (£9362 per QALY), while the 'less favourable' diagnostic data resulted in an ICER of £19,095 per QALY (£25,453 per QALY) in the diagnosis of suspected melanomas. VivaScope was also shown to be a dominant strategy when used for the diagnostic assessment of suspected basal cell carcinoma (BCC). Regarding margin delineation of LM, mapping with VivaScope was cost-effective, with an ICER of £10,241 per QALY (£11,651 per QALY). However, when VivaScope was used for diagnosis as well as mapping of LM, then the intervention cost was reduced and VivaScope became a dominant strategy. There is an absence of UK data in the included studies and, therefore, generalisability of the results to the UK population is unclear. The use of VivaScope appears to be a cost-effective strategy in the diagnostic assessment of equivocal melanomas and BCCs, and in margin delineation of LM prior to surgical treatment. High-quality RCTs are required in a UK population to assess the diagnostic accuracy of VivaScope in people with equivocal lesions. This study is registered as PROSPERO CRD42014014433. The National Institute for Health Research Health Technology Assessment programme.


SUMO-1 is associated with a subset of lysosomes in glial protein aggregate diseases.
Oligodendroglial inclusion bodies characterize a subset of neurodegenerative diseases. Multiple system atrophy (MSA) is characterized by α-synuclein glial cytoplasmic inclusions and progressive supranuclear palsy (PSP) is associated with glial tau inclusions. The ubiquitin homologue, SUMO-1, has been identified in inclusion bodies in MSA, located in discrete sub-domains in α-synuclein-positive inclusions. We investigated SUMO-1 associated with oligodendroglial inclusion bodies in brain tissue from MSA and PSP and in glial cell models. We examined MSA and PSP cases and compared to age-matched normal controls. Fluorescence immunohistochemistry revealed frequent SUMO-1 sub-domains within and surrounding inclusions bodies in both diseases and showed punctate co-localization of SUMO-1 and the lysosomal marker, cathepsin D, in affected brain regions. Cell counting data revealed that 70-75 % of lysosomes in inclusion body-positive oligodendrocytes were SUMO-1-positive consistently across MSA and PSP cases, compared to 20 % in neighbouring inclusion body negative oligodendrocytes and 10 % in normal brain tissue. Hsp90 co-localized with some SUMO-1 puncta. We examined the SUMO-1 status of lysosomes in 1321N1 human glioma cells over-expressing α-synuclein and in immortalized rat oligodendrocyte cells over-expressing the four repeat form of tau following treatment with the proteasome inhibitor, MG132. We also transfected 1321N1 cells with the inherently aggregation-prone huntingtin exon 1 mutant, HttQ74-GFP. Each cell model showed the association of SUMO-1-positive lysosomes around focal cytoplasmic accumulations of α-synuclein, tau or HttQ74-GFP, respectively. Association of SUMO-1 with lysosomes was also detected in glial cells bearing α-synuclein aggregates in a rotenone-lesioned rat model. SUMO-1 labelling of lysosomes showed a major increase between 24 and 48 h post-incubation of 1321N1 cells with MG132 resulting in an increase in a 90 kDa SUMO-1-positive band that was immunopositive for Hsp90 and immunoprecipitated with an anti-SUMO-1 antibody. That SUMO-1 co-localizes with a subset of lysosomes in neurodegenerative diseases with glial protein aggregates and in glial cell culture models of protein aggregation suggests a role for SUMO-1 in lysosome function.


21-Aminosteroid lipid peroxidation inhibitor U74006F protects against cerebral ischemia in gerbils.
U74006F (21-[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-16 alpha-methylpregna-1,4,9(11)-triene-3,20-dione, monomethane sulfonate) is a novel and potent inhibitor of central nervous system tissue lipid peroxidation that is devoid of classical steroid hormonal activities. Its possible efficacy in attenuating postischemic mortality and neuronal necrosis was examined in gerbils following 3-hour unilateral carotid artery occlusion. Male Mongolian gerbils received two intraperitoneal injections of either vehicle or U74006F (3 or 10 mg/kg), the first injection 10 minutes before and the second injection at the end of the 3-hour ischemic episode. In an initial series of experiments, vehicle-treated gerbils displayed 60.9% (14 of 23) survival 24 hours after ischemia, which decreased to 34.8% (8 of 23) at 48 hours. In contrast, the 10 mg/kg U74006F-treated group showed 86.7% (13 of 15) survival at 24 hours (p less than 0.15 vs. vehicle) and 80.0% (12 of 15) survival at 48 hours (p less than 0.02). In a second series, neurons in the hippocampal CA1 subfield and the medial and lateral cerebral cortex were counted in gerbils surviving 24 hours after unilateral carotid artery occlusion. Comparison of neuronal densities in the ischemic hemisphere with those in the contralateral nonischemic hemisphere revealed significant neuronal preservation in all three brain regions of 10 mg/kg i.p. x 2 U74006F-treated gerbils. Our results show that U74006F can improve survival and attenuate neuronal necrosis in a severe brain ischemia model.(ABSTRACT TRUNCATED AT 250 WORDS)


Electronics and optoelectronics of two-dimensional transition metal dichalcogenides.
The remarkable properties of graphene have renewed interest in inorganic, two-dimensional materials with unique electronic and optical attributes. Transition metal dichalcogenides (TMDCs) are layered materials with strong in-plane bonding and weak out-of-plane interactions enabling exfoliation into two-dimensional layers of single unit cell thickness. Although TMDCs have been studied for decades, recent advances in nanoscale materials characterization and device fabrication have opened up new opportunities for two-dimensional layers of thin TMDCs in nanoelectronics and optoelectronics. TMDCs such as MoS(2), MoSe(2), WS(2) and WSe(2) have sizable bandgaps that change from indirect to direct in single layers, allowing applications such as transistors, photodetectors and electroluminescent devices. We review the historical development of TMDCs, methods for preparing atomically thin layers, their electronic and optical properties, and prospects for future advances in electronics and optoelectronics.


Time-dependent vibrational spectral analysis of first principles trajectory of methylamine with wavelet transform.
The fluctuation dynamics of amine stretching frequencies, hydrogen bonds, dangling N-D bonds, and the orientation profile of the amine group of methylamine (MA) were investigated under ambient conditions by means of dispersion-corrected density functional theory-based first principles molecular dynamics (FPMD) simulations. Along with the dynamical properties, various equilibrium properties such as radial distribution function, spatial distribution function, combined radial and angular distribution functions and hydrogen bonding were also calculated. The instantaneous stretching frequencies of amine groups were obtained by wavelet transform of the trajectory obtained from FPMD simulations. The frequency-structure correlation reveals that the amine stretching frequency is weakly correlated with the nearest nitrogen-deuterium distance. The frequency-frequency correlation function has a short time scale of around 110 fs and a longer time scale of about 1.15 ps. It was found that the short time scale originates from the underdamped motion of intact hydrogen bonds of MA pairs. However, the long time scale of the vibrational spectral diffusion of N-D modes is determined by the overall dynamics of hydrogen bonds as well as the dangling ND groups and the inertial rotation of the amine group of the molecule.


Pricing Policies And Control of Tobacco in Europe (PPACTE) project: cross-national comparison of smoking prevalence in 18 European countries.
Limited data on smoking prevalence allowing valid between-country comparison are available in Europe. The aim of this study is to provide data on smoking prevalence and its determinants in 18 European countries. In 2010, within the Pricing Policies And Control of Tobacco in Europe (PPACTE) project, we conducted a face-to-face survey on smoking in 18 European countries (Albania, Austria, Bulgaria, Czech Republic, Croatia, England, Finland, France, Greece, Hungary, Ireland, Italy, Latvia, Poland, Portugal, Romania, Spain and Sweden) on a total of 18 056 participants, representative for each country of the population aged 15 years or older. Overall, 27.2% of the participants were current smokers (30.6% of men and 24.1% of women). Smoking prevalence was highest in Bulgaria (40.9%) and Greece (38.9%) and lowest in Italy (22.0%) and Sweden (16.3%). Smoking prevalence ranged between 15.7% (Sweden) and 44.3% (Bulgaria) for men and between 11.6% (Albania) and 38.1% (Ireland) for women. Multivariate analysis showed a significant inverse trend between smoking prevalence and the level of education in both sexes. Male-to-female smoking prevalence ratios ranged from 0.85 in Spain to 3.47 in Albania and current-to-ex prevalence ratios ranged from 0.68 in Sweden to 4.28 in Albania. There are considerable differences across Europe in smoking prevalence, and male-to-female and current-to-ex smoking prevalence ratios. Eastern European countries, lower income countries and those with less advanced tobacco control policies have less favourable smoking patterns and are at an earlier stage of the tobacco epidemic.


Integrating Morphological and Physiological Responses of Tomato Plants to Light Quality to the Crop Level by 3D Modeling.
Next to its intensity, the spectral composition of light is one of the most important factors affecting plant growth and morphology. The introduction of light emitting diodes (LEDs) offers perspectives to design optimal light spectra for plant production systems. However, knowledge on the effects of light quality on physiological plant processes is still limited. The aim of this study is to determine the effects of six light qualities on growth and plant architecture of young tomato plants, and to upscale these effects to the crop level using a multispectral, functional-structural plant model. Young tomato plants were grown under 210 μmol m-2 s-1 blue, green, amber, red, white or red/blue (92%/8%) LED light with a low intensity of sunlight as background. Plants grown under blue light were shorter and developed smaller leaves which were obliquely oriented upward. Leaves grown under blue light contained the highest levels of light harvesting pigments, but when exposed to blue light only, they had the lowest rate of leaf photosynthesis. However, when exposed to white light these leaves had the highest rate of photosynthesis. Under green light, tomato plants were taller and leaves were nearly horizontally oriented, with a high specific leaf area. The open plant structure combined with a high light transmission and reflection at the leaf level allowed green light to penetrate deeper into the canopy. Plants grown under red, amber and white light were comparable with respect to height, leaf area and biomass production. The 3D model simulations indicated that the observed changes in plant architecture had a significant impact on light absorbance at the leaf and crop level. The combination of plant architecture and spectrum dependent photosynthesis was found to result in the highest rate of crop photosynthesis under red light in plants initially grown under green light. These results suggest that dynamic light spectra may offer perspectives to increase growth and production in high value production systems such as greenhouse horticulture and vertical farming.


Semiconductor-based sequencing of genome-wide DNA methylation states.
Methylated DNA immunoprecipitation sequencing (MeDIP-Seq) is a widely used approach to study DNA methylation genome-wide. Here, we developed a MeDIP-Seq protocol compatible with the Ion Torrent semiconductor-based sequencing platform that is low cost, rapid, and scalable. We applied this protocol to demonstrate MeDIP-Seq on the Ion Torrent platform provides adequate coverage of CpG cytosines, the methylation states of which we validated at single-base resolution on the Infinium HumanMethylation450 BeadChip array, and accurately identifies sites of differential DNA methylation. Furthermore, we applied an integrative approach to further investigate and confirm the role of DNA methylation in alternative splicing and to profile 5mC and 5hmC variants of DNA methylation in normal human brain tissue that is localized over distinct genomic regions. These applications of MeDIP-Seq on the Ion Torrent platform have broad utility and add to the current methodologies for profiling genome-wide DNA methylation states in normal and disease conditions.


Efficacy of scheduled time ketorolac administration compared to continuous infusion for post-operative pain after abdominal surgery.
Ketorolac tromethanime is a non steroidal anti inflammatory drug and its efficacy on acute pain control after abdominal surgery has been well documented. It has a rapid onset and it can be given both for intra operative and for post operative pain management. In this study we aimed to evaluate if there were any differences in relieving post operative pain when Ketorolac was administered with continuous infusion or if it was given at prearranged times. 80 ASA I patients, scheduled for major gynecological surgery, were randomly assigned to 2 groups: group A patients were connected after surgical incision with a 24h analgesic infusor (2 ml/h) containing morphine (0.02 mg/kg/h) and Ketorolac (90 mg). Group B patients were connected after surgical incision with a 24h analgesic infusor (2 ml/h) containing morphine (0.02 mg/kg/h) at first and Ketorolac was then given in bolus after surgical incision and then every 8 hours for the first 24 hours. Post-operative pain scores were assessed using the Visual Analogue Scale (VAS) every 8 hours for 24 h. For a VAS value greater than 6, patients received Tramadol 100 mg. Post-operative pain scores showed a better pain relief for patients in the group B. Furthermore, the requirements of rescue analgesic were less in the group B [Tramadol was used for only 8 patients] than in the group A [Tramadol was used for 31 patients]. No adverse effects were registered in both groups. <strong> </strong> For post-operative pain Ketorolac administration at prearranged times, every 8 hours, offers greater benefits in respect to its continuous infusion.


ChartStory: Automated Partitioning, Layout, and Captioning of Charts into Comic-Style Narratives.
Visual data storytelling is gaining importance as a means of presenting data-driven information or analysis results, especially to the general public. This has resulted in design principles being proposed for data-driven storytelling, and new authoring tools being created to aid such storytelling. However, data analysts typically lack sufficient background in design and storytelling to make effective use of these principles and authoring tools. To assist this process, we present ChartStory for crafting data stories from a collection of user-created charts, using a style akin to comic panels to imply the underlying sequence and logic of data-driven narratives. Our approach is to operationalize established design principles into an advanced pipeline that characterizes charts by their properties and similarities to each other, and recommends ways to partition, layout, and caption story pieces to serve a narrative. ChartStory also augments this pipeline with intuitive user interactions for visual refinement of generated data comics. We extensively and holistically evaluate ChartStory via a trio of studies. We first assess how the tool supports data comic creation in comparison to a manual baseline tool. Data comics from this study are subsequently compared and evaluated to ChartStory's automated recommendations by a team of narrative visualization practitioners. This is followed by a pair of interview studies with data scientists using their own datasets and charts who provide an additional assessment of the system. We find that ChartStory provides cogent recommendations for narrative generation, resulting in data comics that compare favorably to manually-created ones.


Some remarks on the relevance of basic research in nursing inquiry.
The aim of this article was to illuminate the issue of basic research in nursing and to problematize its relevance for our discipline. First, we asked leading nursing scholars in the Nordic countries to share their views on basic research in nursing. Thereafter, the ideas, views and suggestions of the scholars were amalgamated with insights from the literature and from the discussions in our project team. Our two guiding questions were: What role can basic research be assigned? Which, if any, forms of basic research can be identified? We found that basic nursing research may be seen as a necessary basis for applied research, as a contribution to applied research, or that the whole issue is seen as a pseudo-issue. We further found that basic nursing research can be seen as either contextual or general as well as either intradisciplinary or multidisciplinary in form. We conclude by the following three succinct remarks or assertions: that basic nursing research is not to be equated with biomedical conceptions of basic research; that basic nursing research may take place on several theoretical levels; and finally, that an indiscriminate dismissal of basic research in nursing may affect the cognitive autonomy of our discipline.


Deliberate self harm patients with depressive disorders: treatment and outcome.
Depression is the most common psychiatric disorder in deliberate self-harm (DSH) patients and in those who commit suicide. The aim of this study was to examine the treatment received by DSH patients with depression and their progress following DSH. A representative sample of 106 patients with an ICD-10 depressive episode who presented to a general hospital following an episode of DSH were investigated in terms of their treatment before and after the episode and their outcome at follow-up. Prior to the index episode of DSH, 39 patients (36.8%) were receiving treatment from the psychiatric services and a further 35 (33.0%) were receiving treatment for mental health problems from their general practitioner. Fifty-two patients (49.1%) were receiving antidepressants (in therapeutic dosages in 93.6%). After the episode of DSH 94 patients (88.7%) were offered treatment with the psychiatric services, either as a new referral or continuation of treatment they were receiving prior to DSH. Of the patients who were followed-up, 36.3% remained in contact with the psychiatric services, 52.3% showed poor compliance with recommended treatment and 60.2% no longer fulfilled the diagnostic criteria for depression. Almost one-third reported a further episode of DSH during the follow-up period. The nature and quality of non-physical treatments provided by the psychiatric services was not investigated. Reports of the treatment provided by general practitioners, the timing of improvement in symptoms and compliance with treatment largely relied on patients' self report. All patients presenting following DSH need to be carefully screened for depressive illness. Randomised controlled studies need to be conducted on DSH patients with depression to determine which treatments are effective.


Sigma-1 (σ1) receptor activity is necessary for physiological brain plasticity in mice.
The sigma-1 receptor (S1R) is a membrane-associated protein expressed in neurons and glia at mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs). S1R interacts with different partners to regulate cellular responses, including ER stress, mitochondrial physiology and Ca2+ fluxes. S1R shapes cellular plasticity by directly modulating signaling pathways involved in inflammatory responses, cell survival and death. We here analyzed its impact on brain plasticity in vivo, in mice trained in a complex maze, the Hamlet test. The device, providing strong enriched environment (EE) conditions, mimics a small village. It has a central agora and streets expanding from it, leading to functionalized houses where animals can Drink, Eat, Hide, Run, or Interact. Animals were trained in groups, 4 h/day for two weeks, and their maze exploration and topographic memory could be analyzed. Several groups of mice were considered: non-trained vs. trained; repeatedly administered with saline vs. NE-100, a selective S1R antagonist; and wildtype vs. S1R KO mice. S1R inactivation altered maze exploration and prevented topographic learning. EE induced a strong plasticity measured through resilience to behavioral despair or to the amnesic effects of scopolamine, and increases in S1R expression and bdnf mRNA levels in the hippocampus; increases in neurogenesis (proliferation and maturation); and increases of histone acetylation in the hippocampus and cortex. S1R inactivation altered all these parameters significantly, showing that S1R activity plays a major role in physiological brain plasticity. As S1R is a major resident protein in MAMs, modulating ER responses and mitochondrial homeostasy, MAM physiology appeared impacted by enriched environment.


Tacit and encoded knowledge in the use of standardised outcome measures in multidisciplinary team decision making: a case study of in-patient neurorehabilitation.
This paper explores how multidisciplinary teams (MDTs) balance encoded knowledge, in the form of standardised outcome measurement, with tacit knowledge, in the form of intuitive judgement, clinical experience and expertise, in the process of clinical decision making. The paper is based on findings from a qualitative case study of a multidisciplinary in-patient neurorehabilitation team in one UK NHS trust who routinely collected standardised outcome measures. Data were collected using non-participant observation of 16 MDT meetings and semi-structured interviews with 11 practitioners representing different professional groups. Our analysis suggests that clinicians drew on tacit knowledge to supplement, adjust or dismiss 'the scores' in making judgements about a patients' likely progress in rehabilitation, their change (or lack of) during therapy and their need for support on discharge. In many cases, the scores accorded with clinicians' tacit knowledge of the patient, and were used to reinforce this opinion, rather than determine it. In other cases, the scores, in particular the Barthel Index, provided a partial picture of the patient and in these circumstances, clinicians employed tacit knowledge to fill in the gaps. In some cases, the scores and tacit knowledge diverged and clinicians preferred to rely on their clinical experience and intuition and adjusted or downplayed the accuracy of the scores. We conclude that there are limits to the advantages of quantifying and standardising assessments of health within routine clinical practice and that standardised outcome measures can support, rather than determine clinical judgement. Tacit knowledge is essential to produce and interpret this form of encoded knowledge and to balance its significance against other information about the patient in making decisions about patient care.


DaVinci's Mona Lisa entering the next dimension.
For several of Leonardo da Vinci's paintings, such as The Virgin and Child with St Anne or the Mona Lisa, there exist copies produced by his own studio. In case of the Mona Lisa, a quite exceptional, rediscovered studio copy was presented to the public in 2012 by the Prado Museum in Madrid. Not only does it mirror its famous counterpart superficially; it also features the very same corrections to the lower layers, which indicates that da Vinci and the 'copyist' must have elaborated their panels simultaneously. On the basis of subjective (thirty-two participants estimated painter-model constellations) as well as objective data (analysis of trajectories between landmarks of both paintings), we revealed that both versions differ slightly in perspective. We reconstructed the original studio setting and found evidence that the disparity between both paintings mimics human binocular disparity. This points to the possibility that the two Giocondas together might represent the first stereoscopic image in world history.


Managing Cancer And Living Meaningfully (CALM): randomised feasibility trial in patients with advanced cancer.
Managing Cancer And Living Meaningfully (CALM) is a brief individual psychotherapy for patients with advanced cancer. In an intervention-only phase 2a trial, CALM showed promising results, leading to the present 2b pilot, which introduces procedures for randomisation and improved rigour in preparation for a phase 3 randomised controlled trial (RCT). To test trial methodology and assess feasibility of a confirmatory RCT. A parallel-arm RCT (intervention vs usual care) with 3 and 6-month follow-ups. Assessment of feasibility included rates of consent, randomisation, attrition, intervention non-compliance and usual care contamination. depressive symptoms (Patient Health Questionnaire-9; PHQ-9). major depressive disorder (MDD), generalised anxiety, death anxiety, spiritual well-being, attachment anxiety and avoidance, self-esteem, experiential avoidance, quality of life and post-traumatic growth. Bayesian conjugate analysis was used in this low-powered setting. 60 adult patients with advanced cancer from the Princess Margaret Cancer Centre. Rate of consent was 32%, randomisation 78%, attrition 25%, non-compliance 37% and contamination 17%. There was support for potential treatment effects on: PHQ-9, OR=1.48, 95% Credible Interval (CRI.95) (0.65, 3.38); MDD, OR=1.56, CRI.95 (0.50, 4.84); attachment anxiety, OR=1.72, CRI.95 (0.73, 4.03); and attachment avoidance, OR=1.58, CRI.95 (0.67, 3.71). There was no support for effects on the seven remaining secondary outcomes. A phase 3 CALM RCT is feasible and should aim to detect effect sizes of d=0.40, with greater attention to issues of compliance and contamination. NCT02353546.


Covalent labelling of the NADPH: protochlorophyllide oxidoreductase from etioplast membranes with [3H]N-phenylmaleimide.
[3H]N-Phenylmaleimide has been used to covalently label in a specific manner the substrate-protected thiol groups of the enzyme protochlorophyllide reductase. In membrane preparations from oat (Avena sativa) and runner-bean (Phaseolus vulgaris) seedlings, two related peptides of mol.wts. 35000/37000 and 34000/35000 respectively and showing properties expected of the reductase have been identified, whereas the same technique with barley (Hordeum vulgare) extracts resulted in labelling a single peptide of mol.wt. 38000. Evidence is presented that both NADPH and protochlorophyllide are required for protection of the essential thiol groups on the reductase in oat extracts, a situation favouring a ternary complex as the structure for the photoactive enzyme--substrates intermediate.


Cgnl1, an endothelial junction complex protein, regulates GTPase mediated angiogenesis.
The formation of cell-cell and cell-extra cellular matrix (ECM) contacts by endothelial cells (ECs) is crucial for the stability and integrity of a vascular network. We previously identified cingulin-like 1 (Cgnl1) in a transcriptomic screen for new angiogenic modulators. Here we aim to study the function of the cell-cell junction associated protein Cgnl1 during vessel formation. Unlike family member cingulin, Cgnl1 expression is enriched in ECs during vascular growth. Cgnl1 is important for the formation of multicellular tubule structures, as shown in vitro using loss-of function assays in a 3D matrix co-culture system that uses primary human ECs and supporting mural cells. Further studies revealed that Cgnl1 regulates vascular growth by promoting Ve-cadherin association with the actin cytoskeleton, thereby stabilizing adherens junctions. Cgnl1 also regulates focal adhesion assembly in response to ECM contact, promoting vinculin and paxillin recruitment and focal adhesion kinase signalling. In vivo, we demonstrate in a postnatal retinal vascular development model in mice that Cgnl1 function is crucial for sustaining neovascular growth and stability. Our data demonstrate a functional relevance for Cgnl1 as a defining factor in new vessel formation both in vitro and in vivo.


Hunting down the chimera of multiple disciplinarity in conservation science.
The consensus is that both ecological and social factors are essential dimensions of conservation research and practice. However, much of the literature on multiple disciplinary collaboration focuses on the difficulties of undertaking it. This review of the challenges of conducting multiple disciplinary collaboration offers a framework for thinking about the diversity and complexity of this endeavor. We focused on conceptual challenges, of which 5 main categories emerged: methodological challenges, value judgments, theories of knowledge, disciplinary prejudices, and interdisciplinary communication. The major problems identified in these areas have proved remarkably persistent in the literature surveyed (c.1960-2012). Reasons for these failures to learn from past experience include the pressure to produce positive outcomes and gloss over disagreements, the ephemeral nature of many such projects and resulting lack of institutional memory, and the apparent complexity and incoherence of the endeavor. We suggest that multiple disciplinary collaboration requires conceptual integration among carefully selected multiple disciplinary team members united in investigating a shared problem or question. We outline a 9-point sequence of steps for setting up a successful multiple disciplinary project. This encompasses points on recruitment, involving stakeholders, developing research questions, negotiating power dynamics and hidden values and conceptual differences, explaining and choosing appropriate methods, developing a shared language, facilitating on-going communications, and discussing data integration and project outcomes. Although numerous solutions to the challenges of multiple disciplinary research have been proposed, lessons learned are often lost when projects end or experienced individuals move on. We urge multiple disciplinary teams to capture the challenges recognized, and solutions proposed, by their researchers while projects are in process. A database of well-documented case studies would showcase theories and methods from a variety of disciplines and their interactions, enable better comparative study and evaluation, and provide a useful resource for developing future projects and training multiple disciplinary researchers.


Health service resilience in Yobe state, Nigeria in the context of the Boko Haram insurgency: a systems dynamics analysis using group model building.
Yobe State has faced severe disruption of its health service as a result of the Boko Haram insurgency. A systems dynamics analysis was conducted to identify key pathways of threat to provision and emerging pathways of response and adaptation. Structured interviews were conducted with 39 stakeholders from three local government areas selected to represent the diversity of conflict experience across the state: Damaturu, Fune and Nguru, and with four officers of the PRRINN-MNCH program providing technical assistance for primary care development in the state. A group model building session was convened with 11 senior stakeholders, which used participatory scripts to review thematic analysis of interviews and develop a preliminary systems model linking identified variables. Population migration and transport restrictions have substantially impacted access to health provision. The human resource for health capability of the state has been severely diminished through the outward migration of (especially non-indigenous) health workers and the suspension of programmes providing external technical assistance. The political will of the Yobe State government to strengthen health provision - through lifting a moratorium on recruitment and providing incentives for retention and support of staff - has supported a recovery of health systems functioning. Policies of free-drug provision and decentralized drug supply appear to have been protective of the operation of the health system. Community resources and cohesion have been significant assets in combatting the impacts of the insurgency on service utilization and quality. Staff commitment and motivation - particularly amongst staff indigenous to the state - has protected health care quality and enabled flexibility of human resource deployment. A systems analysis using participatory group model building provided a mechanism to identify key pathways of threat and adaptation with regard to health service functioning. Generalizable systems characteristics supportive of resilience are suggested, and linked to wider discussion of the role of factors such as diversity, self-regulation and integration.


Japanese medaka: a non-mammalian vertebrate model for studying sex and age-related bone metabolism in vivo.
In human, a reduction in estrogen has been proposed as one of the key contributing factors for postmenopausal osteoporosis. Rodents are conventional models for studying postmenopausal osteoporosis, but the major limitation is that ovariectomy is needed to mimic the estrogen decline after menopause. Interestingly, in medaka fish (Oryzias latipes), we observed a natural drop in plasma estrogen profile in females during aging and abnormal spinal curvature was apparent in old fish, which are similar to postmenopausal women. It is hypothesized that estrogen associated disorders in bone metabolism might be predicted and prevented by estrogen supplement in aging O. latipes, which could be corresponding to postmenopausal osteoporosis in women. In O. latipes, plasma estrogen was peaked at 8 months old and significantly declined after 10, 11 and 22 months in females. Spinal bone mineral density (BMD) and micro-architecture by microCT measurement progressively decreased and deteriorated from 8 to 10, 12 and 14 months old, which was more apparent in females than the male counterparts. After 10 months old, O. latipes were supplemented with 17α-ethinylestradiol (EE2, a potent estrogen mimic) at 6 and 60 ng/mg fish weight/day for 4 weeks, both reduction in spinal BMD and deterioration in bone micro-architecture were significantly prevented. The estrogenic effect of EE2 in O. latipes was confirmed by significant up-regulation of four key estrogen responsive genes in the liver. In general, bone histomorphometric analyses indicated significantly lowered osteoblasts and osteoclasts numbers and surfaces on vertebrae of EE2-fed medaka. We demonstrate osteoporosis development associated with natural drop in estrogen level during aging in female medaka, which could be attenuated by estrogen treatment. This small size fish is a unique alternative non-mammalian vertebrate model for studying estrogen-related molecular regulation in postmenopausal skeletal disorders in vivo without ovariectomy.


The importance of stroke as a risk factor of cognitive decline in community dwelling older and oldest peoples: the SONIC study.
Cognitive impairment is a major health concern among older and oldest people. Moreover, stroke is a relevant contributor for cognitive decline and development of dementia. The study of cognitive decline focused on stroke as the important risk factor by recruiting older and oldest is still lagging behind. Therefore, the aim of this study was to investigate the importance of stroke as a risk factor of cognitive decline during 3 years in community dwelling older and oldest people. This study was longitudinal study with a 3-year follow-up in Japan. The participants were 1333 community dwelling older and oldest people (70 years old = 675, 80 years old = 589, and 90 years old = 69). Data collected included basic data (age, sex, and history of stroke), vascular risk factors (hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, and current smoking), and social factors (educational level, frequency of going outdoors, long-term care (LTC) service used, and residential area). The Japanese version of the Montreal Cognitive Assessment (MoCA-J) was decline of ≥2 points was defined as cognitive decline. Multiple logistic regression analysis was used to investigate the association between stroke and other risk factors with cognitive decline during a 3-year follow-up. The fit of the hypothesized model by multiple logistic regression showed that a history of stroke, advanced age, and greater MoCA-J score at the baseline were important risk factors, while the presence of dyslipidemia and a higher educational level were protective factors that were significantly correlated with cognitive decline during the 3-year follow-up. The cognitive decline after the 3-year follow-up was influenced by the history of stroke and advanced age, while greater MoCA-J score at the baseline was positively associated with subsequent 3 years cognitive decline. The protective factors were the presence of dyslipidemia and a higher educational level. Therefore, these factors are considered important and should be taken into consideration when searching for creative solutions to prevent cognitive decline after stroke in community dwelling older and oldest people.


Benazepril-Induced Agranulocytosis: A Case Report and Review of the Literature.
Angiotensin-converting enzyme inhibitors are widely used drugs, and in appropriately selected patients, serious side effects are infrequent. Commonly seen side effects include cough, rash, hyperkalemia, renal dysfunction, and angioedema. Historically, dose-related agranulocytosis has been associated with captopril. Benazepril, a relatively more potent angiotensin-converting enzyme inhibitor, is rarely associated with agranulocytosis. Here, we report a case of drug-induced agranulocytosis due to benazepril, with complete recovery of white blood cell count upon discontinuation of the drug. All tests for other causes of agranulocytosis were unremarkable. This report highlights a serious and rare side effect associated with benazepril. Benazepril is a commonly employed anti-hypertensive medication, and we report an unusual condition associated with this medication in order to increase vigilance among caregivers. In such cases, prompt recognition and discontinuation of the causative drug can make the difference between a recovery and a fatal outcome associated with drug-induced agranulocytosis.


Silent research vessels are not quiet.
Behavior of herring (Clupea harengus) is stimulated by two ocean-going research vessels; respectively designed with and without regard to radiated-noise-standards. Both vessels generate a reaction pattern, but, contrary to expectations, the reaction initiated by the silent vessel is stronger and more prolonged than the one initiated by the conventional vessel. The recommendations from the scientific community on noise-reduced designs were motivated by the expectation of minimizing bias on survey results caused by vessel-induced fish behavior. In conclusion, the candidate stimuli for vessel avoidance remain obscure. Noise reduction might be necessary but is insufficient to obtain stealth vessel assets during surveys.


High-Throughput Chip Assay for Investigating Escherichia coli Interaction with the Blood-Brain Barrier Using Microbial and Human Proteome Microarrays (Dual-Microarray Technology).
Bacterial meningitis in neonates and infants is an acute lethal disease and occurs in response to microbial exploitation of the blood-brain barrier (BBB), resulting in the intracranial inflammation. Several pathogens, such as Escherichia coli ( E. coli), can cause this devastating disease; however, the underlying molecular mechanisms by which these pathogens exploit the BBB remain incompletely understood. To identify important players on both the pathogen and host sides that govern the E. coli-BBB cell interactions, we took advantage of the E. coli and human proteome microarrays (i.e., HuProt) as an unbiased, proteome-wide tool for identification of important players on both sides. Using the E. coli proteome microarrays, we developed a unique high throughput chip-based cell probing assay to probe with fluorescent live human brain microvascular endothelial cells (HBMEC, which constitute the BBB). We identified several transmembrane proteins, which effectively bound to live HBMEC. We focused on YojI protein for further study. By probing the HuProt arrays with YojI, interferon-alpha receptor (IFNAR2) was identified as one of its binding proteins. The importance of YojI and IFNAR2 involved in E. coli-HBMEC interactions was characterized using the YojI knockout bacteria and IFNAR2-knock down HBMEC and further confirmed by E. coli binding assay in HBMEC. This study represents a new paradigm (dual-microarray technology) that enables rapid, unbiased discovery of both pathogen and host players that are involved in pathogen-host interactions for human infectious diseases in a high throughput manner.


Deconvoluting lung evolution: from phenotypes to gene regulatory networks.
Speakers in this symposium presented examples of respiratory regulation that broadly illustrate principles of evolution from whole organ to genes. The swim bladder and lungs of aquatic and terrestrial organisms arose independently from a common primordial "respiratory pharynx" but not from each other. Pathways of lung evolution are similar between crocodiles and birds but a low compliance of mammalian lung may have driven the development of the diaphragm to permit lung inflation during inspiration. To meet the high oxygen demands of flight, bird lungs have evolved separate gas exchange and pump components to achieve unidirectional ventilation and minimize dead space. The process of "screening" (removal of oxygen from inspired air prior to entering the terminal units) reduces effective alveolar oxygen tension and potentially explains why nonathletic large mammals possess greater pulmonary diffusing capacities than required by their oxygen consumption. The "primitive" central admixture of oxygenated and deoxygenated blood in the incompletely divided reptilian heart is actually co-regulated with other autonomic cardiopulmonary responses to provide flexible control of arterial oxygen tension independent of ventilation as well as a unique mechanism for adjusting metabolic rate. Some of the most ancient oxygen-sensing molecules, i.e., hypoxia-inducible factor-1alpha and erythropoietin, are up-regulated during mammalian lung development and growth under apparently normoxic conditions, suggesting functional evolution. Normal alveolarization requires pleiotropic growth factors acting via highly conserved cell-cell signal transduction, e.g., parathyroid hormone-related protein transducing at least partly through the Wingless/int pathway. The latter regulates morphogenesis from nematode to mammal. If there is commonality among these diverse respiratory processes, it is that all levels of organization, from molecular signaling to structure to function, co-evolve progressively, and optimize an existing gas-exchange framework.


An integrated organisation-wide data quality management and information governance framework: theoretical underpinnings.
Increasing investment in eHealth aims to improve cost effectiveness and safety of care. Data extraction and aggregation can create new data products to improve professional practice and provide feedback to improve the quality of source data. A previous systematic review concluded that locally relevant clinical indicators and use of clinical record systems could support clinical governance. We aimed to extend and update the review with a theoretical framework. We searched PubMed, Medline, Web of Science, ABI Inform (Proquest) and Business Source Premier (EBSCO) using the terms curation, information ecosystem, data quality management (DQM), data governance, information governance (IG) and data stewardship. We focused on and analysed the scope of DQM and IG processes, theoretical frameworks, and determinants of the processing, quality assurance, presentation and sharing of data across the enterprise. There are good theoretical reasons for integrated governance, but there is variable alignment of DQM, IG and health system objectives across the health enterprise. Ethical constraints exist that require health information ecosystems to process data in ways that are aligned with improving health and system efficiency and ensuring patient safety. Despite an increasingly 'big-data' environment, DQM and IG in health services are still fragmented across the data production cycle. We extend current work on DQM and IG with a theoretical framework for integrated IG across the data cycle. The dimensions of this theory-based framework would require testing with qualitative and quantitative studies to examine the applicability and utility, along with an evaluation of its impact on data quality across the health enterprise.


Dietary intervention in chronic fatigue syndrome.
Anecdotal reports and books have been published linking an over growth of Candida Albicans with chronic fatigue syndrome (CFS), suggesting dietary change as a treatment option. Little scientific data has been published to validate this controversial theory. This study aims to determine the efficacy of dietary intervention on level of fatigue and quality of life (QoL) in individuals with CFS. A 24-week randomized intervention study was conducted with 52 individuals diagnosed with CFS. Patients were randomized to either a low sugar low yeast (LSLY) or healthy eating (HE) dietary interventions. Primary outcome measures were fatigue as measured by the Chalder Fatigue Score and QoL measured by Medical Outcomes Survey Short Form-36. A high drop out rate occurred with 13 participants not completing the final evaluation (7HE/6LSLY). Intention to treat analysis showed no statistically significant differences on primary outcome measurements. In this randomized control trial, a LSLY diet appeared to be no more efficacious on levels of fatigue or QoL compared to HE. Given the difficulty with dietary compliance experienced by participants, especially in the LSLY group, it would appear HE guidance is a more pragmatic approach than advocating a complicated dietary regime.