Perceived race discrimination moderates dietary beliefs' effects on dietary intake.
Despite the recognized role diet plays in disease, health, and longevity, less than half the US population consumes the desired 5 fruit/ vegetable servings a day. What accounts for the disjunction between cognition and behavior? Telephone survey data from a probability sample of 308 metropolitan Washington, DC, residents confirm the contingent consistency hypothesis as one explanation. The hypothesis suggests that optimal beliefs about health outcomes of dietary intake motivate optimal dietary intake, contingent on social structural experiences. The data show that experiences with racial discrimination can lessen the tendency for optimally healthy dietary intake to follow from belief in: 1) the benefit of eating healthy diets (or harm of unhealthy diets); and 2) self-control of health outcomes. Race (a proxy for assumed race-related social structural experiences, like race discrimination) does not demonstrate this moderating or contingency effect.


Voltage-dependent blockade of HERG channels expressed in Xenopus oocytes by external Ca2+ and Mg2+.
1. We expressed the human eag-related gene (HERG), which is known to encode the delayed rectifier K+ current (IKr) in cardiac muscle, in Xenopus oocytes. Using a two-microelectrode voltage clamp technique, the effect of external Ca2+ and Mg2+ on the HERG current (IHERG) was investigated. 2. When [Ca2+]o was increased, the amplitude of outward IHERG elicited by depolarization decreased, and the rate of current onset slowed. The rate of current decay observed on repolarization was greatly accelerated. The threshold and fully activated potential of IHERG shifted to a more positive potential. On the other hand, the inactivation property represented by the negative slope of the I-V curve and the instantaneous conductance of IHERG were little affected by [Ca2+]o. 3. The effect of [Ca2+]o on IHERG can be interpreted using the channel blockade model. The blockade is voltage dependent; smaller dissociation constants (KM) at more negative potentials indicate that block is facilitated by hyperpolarization. KM changes e-fold for 14.5 mV and the fractional electrical distance of the binding site calculated from this value is 0.86. 4. Blockade by a low concentration of Ca2+ (0.5 mM) was inhibited by increasing [K+]o (from 2 to 20 mM), whereas blockade by a high concentration of Ca2+ (5 mM) was not affected by varying [K+]o, indicating that there is competition between permeating ions and blocking ions. 5. The effect of [Mg2+]o on IHERG was qualitatively similar to that of [Ca2+]o, but the potency was lower. 6. These results suggest that external Ca2+ and Mg2+ block the HERG channel in a voltage- and time-dependent manner, resulting in a voltage dependence which has been regarded as a property of the activation gate.


The influence of droplet size on the stability, in vivo digestion, and oral bioavailability of vitamin E emulsions.
Vitamin E (α-tocopherol) is a nutraceutical compound, which has been shown to possess potent antioxidant and anticancer activity. However, its biological activity may be limited by its poor bioavailability. Colloidal delivery systems have shown wide applications in the food and pharmaceutical industries to deliver lipophilic bioactive compounds. In this study, we have developed conventional and nanoemulsions of vitamin E from food grade ingredients (sunflower oil, saponin, and water) and showed the nanoemulsion formulation increased the oral bioavailability when compared to the conventional emulsion. The mean droplet diameters in the nano and conventional emulsions were 0.277 and 1.285 μm, respectively. The stability of the emulsion formulation after thermal processing, long-term storage at different temperatures, mechanical stress and in plasma was determined. The results showed that the saponin coated nanoemulsion was stable to droplet coalescence during thermal processing (30-90 °C), long-term storage and mechanical stress when compared to the conventional emulsion. The biological fate of the emulsion formulations were studied using male Wistar rats as an animal model. The emulsion droplet stability during passage through the gastrointestinal tract was evaluated by their introduction into rat stomachs. Microscopy was used to investigate the structural changes that occurred during digestion. Both the conventional emulsion and nanoemulsion formulations showed strong evidence of droplet flocculation and coalescence during in vivo digestion. The in vivo oral bioavailability study revealed that vitamin E in a nanoemulsion form showed a 3-fold increase in the AUC when compared to the conventional emulsion. The information reported in this study will facilitate the design of colloidal delivery systems using nanoemulsion formulations.


Five-year clinical and radiological outcomes in 257 consecutive cementless Oxford medial unicompartmental knee arthroplasties.
Our aim was to examine the clinical and radiographic outcomes in 257 consecutive Oxford unicompartmental knee arthroplasties (OUKAs) (238 patients), five years post-operatively. A retrospective evaluation was undertaken of patients treated between April 2008 and October 2010 in a regional centre by two non-designing surgeons with no previous experience of UKAs. The Oxford Knee Scores (OKSs) were recorded and fluoroscopically aligned radiographs were assessed post-operatively at one and five years. The median age of the 238 patients was 65.0 years (interquartile range (IQR) 59.0 to 73.0), the median body mas index was 30.0 (IQR 27.5 to 33.0) and 51.7% were male. There were no intra-operative complications. There was a significant improvement in the median OKS at six weeks (34, IQR 31.0 to 37.0), one year (38, IQR 29.0 to 43.0) and five years (37, IQR 27.0 to 42.0) when compared with the pre-operative scores (16, IQR 13.0 to 19.0) (all p = < 0.01). No patient had progressive radiolucent lines or loosening. A total of 16 patients had died by five years. The cumulative survival at five years was 98.8% and the mean survival time was 5.8 years (95% confidence interval 5.6 to 5.9). A total of seven OUKAs (2.7%) were revised; three within five years and four thereafter, between 5.1 and 5.7 years post-operatively. Five (1.9%) had re-operations within five years. The proportion of patients requiring revision at five years is lower than that generally reported for UKA. These findings add support for the use of the cementless OUKA outside the design centre. Longer follow-up is required. Cite this article: Bone Joint J 2017;99-B:623-31.


Trifluoperazine versus placebo for schizophrenia.
Trifluoperazine is a long-established high potency typical antipsychotic drug used in the treatment of schizophrenia and schizophrenia-like illnesses. To determine absolute effects of trifluoperazine for schizophrenia and schizophrenia-like illnesses compared with placebo.To critically appraise and summarise current evidence on the resource use, cost and economic evaluation of trifluoperazine compared with placebo for schizophrenia. Searches of the Cochrane Schizophrenia Group's register of trials (July 2012), supplemented with handsearching, reference searching, personal communication and contact with industry. Two review authors undertook a search for economic studies using the Cochrane Schizophrenia Group's Health Economic Database (CSzGHED) on the 9th April 2013. All available clinical randomised trials involving people with schizophrenia and schizophrenia-like illnesses that compare trifluoperazine with placebo. Studies for the effects of interventions were reliably selected by a review team and data were doubly independently extracted to reduce bias. We only used dichotomous data, using intention-to-treat analysis when possible. Data were estimated using risk ratio (RR) with 95% confidence intervals (CI). A 'Summary of findings' table was produced, where possible, for each primary outcome using GRADE. Economic studies were searched and reliably selected by review authors (VF and SS) to provide an economic summary of available data. Where no relevant economic studies were eligible for inclusion, the economic review team valued the already-included effectiveness outcome data to provide a rudimentary economic summary. This review included 10 studies with a total number of 686 participants featuring in 20 different outcomes of interest. Overall, there was significant clinical improvement in clinical global state at medium term amongst people receiving trifluoperazine (3 RCTs, n = 417, RR 4.61, CI 1.54 to 13.84, low quality evidence) and significantly fewer people receiving trifluoperazine left the studies early due to relapse or worsening at medium term (2 RCTs, n = 381, RR 0.34, CI 0.23 to 0.49, low quality evidence). However, results were equivocal for leaving the study early at medium term for any reason (2 RCTs, n = 391, RR 0.80, CI 0.17 to 3.81, very low quality evidence) and due to severe adverse effects (2 RCTs, n = 391, RR 1.54, CI 0.56 to 4.24, very low quality evidence). Equivocal data were also found for intensified symptoms at medium term (2 RCTs, n = 80, RR 1.05, CI 0.54 to 2.05, very low quality evidence) and rates of agitation or distress again at medium term (1 RCT, n = 52, RR 2.00, CI 0.19 to 20.72, very low quality evidence). Comparison between low and high-dose trifluoperazine with placebo from a single study provided equivocal evidence of effects. For economic outcomes, we valued outcomes in GBP terms and presented them in additional tables; there was an estimated saving of £3488.3 in favour of trifluoperazine. However, numerous assumptions were made and these savings need to be interpreted in light of those assumptions. Our results agree with existing evidence that compared to placebo, trifluoperazine is an effective antipsychotic for people with schizophrenia. Furthermore, our review provides supportive evidence that trifluoperazine increases the risk of extrapyramidal adverse effects. Although the effect sizes against placebo are similar to those observed with other agents, they are based on data from many small, pre-CONSORT trials with generally either a low or very low GRADE evidence that has limited implication for clinical practice. Large, independent trials are needed that adhere to the CONSORT statement to compare trifluoperazine with placebo used in the treatment of schizophrenia and schizophrenia-like illnesses.


Opaque optics thickness measurement using a cyclic path optical configuration setup and polarization phase shifting interferometry.
Thickness measurement of an opaque optics using a cyclic path optical configuration (CPOC) setup and polarization phase shifting interferometry (PPSI) is presented. The CPOC setup is used to simultaneously focus two orthogonally polarized counterpropagating converging beams at its hypotenuse arm. The opaque optics is placed at the hypotenuse arm of the CPOC setup such that one of its surfaces reflects back one of the counterpropagating focusing beams. Because of the thickness of the opaque optics, the other focusing beam suffers a longitudinal shift in the beam focus. Applying PPSI, the longitudinal shift in the beam focus which is twice the thickness of the opaque optics is determined. The results obtained for a silicon plate of thickness 0.660 mm with a measurement uncertainty of 0.013 mm are presented.


[Cloning of vertebrates: successes and problems].
Cloning of vertebrates, in particular, amphibians and mammals, is discussed. In the last decade, significant progress was made cloning mammals, while cloning of adult amphibians remained problematical. Low-traumatic methods of enucleation of recipient oocytes and transplantation of donor nuclei were worked out. In 1997, an adult sheep was cloned in Great Britain, thus demonstrating the possibility of cloning adult mammals. However, methods of cloning mammals need improvement because of the high lethality of reconstructed embryos (nuclear transplants). The use of in vitro cultured low-differentiated stem cells to obtain donor nuclei seems promising. Works on human cloning are not expedient in the near future because of technical and ethical aspects.


Bacteriophage Mu Mor protein requires sigma 70 to activate the Mu middle promoter.
Transcription during the bacteriophage Mu lytic cycle occurs in three phases: early, middle, and late. Middle transcription requires the early gene product Mor for its activation. Mor protein overproduction was accomplished by fusing the mor gene to an efficient phage T7 promoter and translation initiation region. A protein fraction highly enriched for Escherichia coli RNA polymerase (E sigma 70) from the Mor-overproducing strain was able to activate transcription from both the tac promoter (Ptac) and the Mu middle promoter (Pm) in vitro. Transcription initiation from Pm was Mor dependent, and the RNA 5' end was identical to that of in vivo RNA. Addition of anti-sigma 70 antibody to transcription reactions containing Ptac and Pm resulted in inhibition of transcription from both promoters; addition of purified sigma 70 restored transcription. These results indicate that Mor-dependent activation requires sigma 70 and therefore imply that Mor is not an alternate sigma factor. This conclusion was further substantiated by a reconstitution experiment with purified proteins in which all three components, Mor, sigma 70, and core RNA polymerase, were required for Pm-dependent transcription in vitro. The sigma 70 dependence of Mor-specific transcription and the amino acid sequence similarity between Mor and C (an activator for Mu late transcription) both support the hypothesis that Mor functions mechanistically as an activator protein.


How primary healthcare in Iceland swiftly changed its strategy in response to the COVID-19 pandemic.
To describe how the primary healthcare (PHC) in Iceland changed its strategy to handle the COVID-19 pandemic. Descriptive observational study. Reykjavik, the capital of Iceland. The Reykjavik area has a total of 233 000 inhabitants. The number and the mode of consultations carried out. Drug prescriptions and changes in the 10 most common diagnoses made in PHC. Laboratory tests including COVID-19 tests. Average numbers in March and April 2020 compared with the same months in 2018 and 2019. Pragmatic strategies and new tasks were rapidly applied to the clinical work to meet the foreseen healthcare needs caused by the pandemic. The number of daytime consultations increased by 35% or from 780 to 1051/1000 inhabitants (p<0.001) during the study period. Telephone and web-based consultations increased by 127% (p<0.001). The same tendency was observed in out-of-hours services. The number of consultations in maternity and well-child care decreased only by 4% (p=0.003). Changes were seen in the 10 most common diagnoses. Most noteworthy, apart from a high number of COVID-19 suspected disease, was that immunisation, depression, hypothyroidism and lumbago were not among the top 10 diagnoses during the epidemic period. The number of drug prescriptions increased by 10.3% (from 494 to 545 per 1000 inhabitants, p<0.001). The number of prescriptions from telephone and web-based consultations rose by 55.6%. No changes were observed in antibiotics prescriptions. As the first point of contact in the COVID-19 pandemic, the PHC in Iceland managed to change its strategy swiftly while preserving traditional maternity and well-child care, indicating a very solid PHC with substantial flexibility in its organisation.


Socioeconomic status and orofacial clefts in Scotland, 1989 to 1998.
The purpose of this study was to investigate the association between socioeconomic status and orofacial clefts (OFC) in Scotland. Study of prevalence at birth over a 10-year period using an area-based measure of material deprivation. Population-based study throughout Scotland. Eight hundred thirty-four live births with OFC born between January 1, 1989, and December 31, 1998, ascertained from the nationwide register of the Cleft Service in Scotland, compared with the total 603,825 live births in Scotland in this period. There was a strong positive relationship whereby the prevalence of OFC at birth increased with increasing deprivation. This trend was statistically significant for cleft lip and/or palate (CL[P]: p =.016) but not for cleft palate (CP; p =.078). For each type of cleft, the relative risk among those resident in the most deprived areas, compared with those resident in the least deprived areas, was 2.33. The association between OFC and socioeconomic status is consistent with a report for an earlier period in a smaller part of Scotland. Unlike the earlier study, this pattern appears to be stronger for CL(P) than for CP. These observations do not appear to be an artifact of recording. It is possible that they reflect the association between deprivation and risk factors for OFC, most likely tobacco smoking during pregnancy. Because the relationship between OFC and socioeconomic status appears to have been virtually unstudied in other populations, it would be valuable to investigate this relationship elsewhere and determine whether known risk factors account for the relationship.


Do flowers wave to attract pollinators? A case study with Silene maritima.
To answer the question whether flowers wave to attract pollinators, we determine: (1) the heritability of floral mobility; (2) whether wavy flowers attract more insects; (3) does the duration of pollination affect seed set; and (4) the relationship between seed set and floral mobility. The pollination ecology of Silene maritima was investigated. Flowers on stalks of different waviness were used to investigate the effect of floral movement on pollinator visits. There is heritable variation in both direct and indirect estimates of floral mobility. The highest insect total visitation times were associated with medium length thin stalks that were visited more frequently and by more insect species. Although mean individual visit durations were less than those of less mobile flowers, this was compensated for by increased visits. Observations of controlled pollinations show that when the visit times are low, so is seed set and therefore low and high mobility flowers might suffer from reduced fitness. Combining these observations provides a mechanism that could be driving stabilizing selection for flower stalk traits, with a trade-off applying between waving to attract pollinators and not being too mobile as to prevent effective pollination. Further evidence for stabilizing selection is provided by the relationship observed in the field between seed set and floral mobility where the highest levels of fitness was associated with intermediate levels of floral waving.


Two-parameter Fisher criterion.
This paper proposes further generalization of a multiclass Fisher's criterion. A formula describing the dependence between the generalized multiclass Fisher's criterion F(Theta) and the variance criterion F(v)Theta has been obtained. Using this formula, it has been shown that the feature extraction methods based on the Karhunen-Loeve (K-L) expansions are special cases of the discriminant method. A full evaluation of heuristic methods for feature extraction based on the K-L expansion with regard to discriminant methods has been presented. A new algorithm for sequential feature extraction has been proposed and is illustrated with an example.


The isolation and properties of the specific cytoplasmic granules of rabbit polymorphonuclear leucocytes.
A method has been described for isolation of the specific cytoplasmic granules of rabbit polymorphonuclear leucocytes. Homogeneous suspensions of leucocytes were disrupted by lysis in 0.34 M sucrose. This procedure liberated the cytoplasmic contents of the cell and dissolved a considerable proportion of the nuclei. Following disruption, the sucrose lysate was separated into three fractions by differential centrifugation, i.e. 400 g or nuclear pellet, 8,200 g or granule pellet and the postgranule supernate. Microscopic examination revealed that the 8,200 g pellet was composed of intact granules as well as occasional mitochondria. The other two fractions were morphologically heterogeneous. Studies with isolated granules demonstrated their lysis by a variety of weak acids and surface-active agents. When buffered solutions were employed between the ranges of pH 2.0 and 9.0, granule lysis began at pH 5.5 and was complete at pH 4.0. Chemical analysis disclosed that the granule pellet contained protein and phospholipid with only traces of nucleic acids. Approximately 70 to 80 per cent of the total cellular antimicrobial agent phagocytin was present in the granule fraction. This material was liberated from the granules by acid (pH 5.0 or lower). Studies on selected enzymes showed that acid phosphatase, alkaline phosphatase, nucleotidase, ribonuclease, deoxyribonuclease, and beta glucuronidase were predominantly localized in the granule fraction. Approximately 50 per cent of total cellular lysozyme and cathepsin were also present in the 8,200 g pellet. Disruption of the granules was associated with the release of the majority of granule protein and enzymes in a non-sedimentable form. The properties and composition of rabbit polymorphonuclear leucocyte granules seem to be analogous to those of liver lysosomes.


Expression of transient receptor potential C6 and related transient receptor potential family members in human airway smooth muscle and lung tissue.
Elevation of the intracellular free Ca(2+) concentration regulates many functional responses in airway smooth muscle, including contraction, proliferation, adhesion, and cell survival. This increase in calcium can be achieved by a release from internal stores (sarcoplasmic reticulum) and/or entry across the cell membrane from the extracellular environment. The molecular identity of this calcium influx pathway in human airway smooth muscle (HASM) remains unclear. Functional studies using Fluo 4-loaded HASM suggest the presence of a histamine H(1) receptor-activated Ca(2+) entry pathway with characteristics similar to those seen with transient receptor potential (TRP) family homologs. Using a range of molecular and cell biological approaches we defined the expression pattern of transient receptor potential classics (TRPC) homologs in airway cells and tissue. Here we show that HASM and human bronchial epithelial cells both express TRPC1, -4, and -6, with HASM also expressing TRPC3 at the mRNA level. Identification of TRPC6 protein by western blot and confocal microscopy indicated that the protein is localized in specific cell types, suggesting that it plays an important role in regulating key functions in airway cells. These data demonstrate the expression of a range of TRPC homologs in the airway and the presence of a functional Ca(2+) entry pathway with characteristics typical of TRPC family members. TRPC homologs may provide an important novel target for the treatment of airway disease.


Receptor for activated C kinase 1 (RACK1) inhibits function of transient receptor potential (TRP)-type channel Pkd2L1 through physical interaction.
Pkd2L1 (also called TRPP3) is a non-selective cation channel permeable to Ca(2+), Na(+), and K(+) and is activated by Ca(2+). It is also part of an acid-triggered off-response cation channel complex. We previously reported roles of the Pkd2L1 C-terminal fragments in its channel function, but the role of the N terminus remains unclear. Using a yeast two-hybrid screening, we found that the Pkd2L1 N terminus interacts with the receptor for activated C kinase 1 (RACK1), a scaffolding/anchoring protein implicated in various cellular functions. This interaction requires the last two Trp-Asp (WD) motifs of RACK1 and fragment Ala(19)-Pro(45) of Pkd2L1. The interaction was confirmed by GST pulldown, blot overlay, and co-immunoprecipitation assays. By (45)Ca tracer uptake and two-microelectrode voltage clamp electrophysiology, we found that in Xenopus oocytes with RACK1 overexpression Pkd2L1 channel activity is abolished or substantially reduced. Combining with oocyte surface biotinylation experiments, we demonstrated that RACK1 inhibits the function of Pkd2L1 channel on the plasma membrane in addition to reducing its total and plasma membrane expression. Overexpressing Pkd2L1 N- or C-terminal fragments as potential blocking peptides for the Pkd2L1-RACK1 interaction, we found that Pkd2L1 N-terminal fragment Met(1)-Pro(45), but not Ile(40)-Ile(97) or C-terminal fragments, abolishes the inhibition of Pkd2L1 channel by overexpressed and oocyte-native RACK1 likely through disrupting the Pkd2L1-RACK1 association. Taken together, our study demonstrated that RACK1 inhibits Pkd2L1 channel function through binding to domain Met(1)-Pro(45) of Pkd2L1. Thus, Pkd2L1 is a novel target channel whose function is regulated by the versatile scaffolding protein RACK1.


Constitutive activity of the human TRPML2 channel induces cell degeneration.
The mucolipin (TRPML) ion channel proteins represent a distinct subfamily of channel proteins within the transient receptor potential (TRP) superfamily of cation channels. Mucolipin 1, 2, and 3 (TRPML1, -2, and -3, respectively) are channel proteins that share high sequence homology with each other and homology in the transmembrane domain with other TRPs. Mutations in the TRPML1 protein are implicated in mucolipidosis type IV, whereas mutations in TRPML3 are found in the varitint-waddler mouse. The properties of the wild type TRPML2 channel are not well known. Here we show functional expression of the wild type human TRPML2 channel (h-TRPML2). The channel is functional at the plasma membrane and characterized by a significant inward rectification similar to other constitutively active TRPML mutant isoforms. The h-TRPML2 channel displays nonselective cation permeability, which is Ca(2+)-permeable and inhibited by low extracytosolic pH but not Ca(2+) regulated. In addition, constitutively active h-TRPML2 leads to cell death by causing Ca(2+) overload. Furthermore, we demonstrate by functional mutation analysis that h-TRPML2 shares similar characteristics and structural similarities with other TRPML channels that regulate the channel in a similar manner. Hence, in addition to overall structure, all three TRPML channels also share common modes of regulation.


The role of steric and electronic interactions in the stereocontrol of the asymmetric 1,3-dipolar reactions of 5-ethoxy-3-p-(S)-tolylsulfinylfuran-2(5H)-ones with diazoalkanes: theoretical calculations and experimental evidences.
The addition of diazomethane and diazoethane to (5S,SS)- and (5R,SS)-5-ethoxy-3-p-tolylsulfinylfuran-2(5H)-ones (1a and 1b) and their 4-methylderivatives (2a and 2b) proceeded in almost quantitative yields and complete regioselectivity. The observed pi-facial selectivity is determined by the configurations at both C-5 and the sulfinyl group, the later being the most important. The syn adducts were almost exclusively obtained from 1a and 2a in apolar solvents but the pi-facial selectivity was strongly decreased in more polar solvents. On the other hand, the major adducts from 1b and 2b were the anti ones and such predominance was slightly increased with solvent polarity. The exo-selectivity was complete in all the cases except for the anti approach to compounds 2a (in polar solvents) and 2b. The role of the sulfinyl group in this behavior was inferred by comparison of these results with those obtained in reactions of diazoalkanes with 5-methoxyfuran-2(5H)-one (3). Steric interactions seem to be the main ones responsible for the observed exo selectivity of reactions with diazoethane, but electronic factors, which can be modulated by the solvent, are also significant in the pi-facial selectivity control. DFT computational methods are able to correctly predict the reactivity, regioselectivity, and pi-facial selectivity exhibited by 5-alkoxyfuranones as well as their changes with the solvent polarity. A C-H.O hydrogen bond, involving the oxygen atom of the 5-alkoxy group at dipolarophiles and the endo-hydrogen atom at dipoles, seems to play a key role in the electronic interactions influencing the stereochemical course of these reactions.


Subsethood-product fuzzy neural inference system (SuPFuNIS).
A new subsethood-product fuzzy neural inference system (SuPFuNIS) is presented in this paper. It has the flexibility to handle both numeric and linguistic inputs simultaneously. Numeric inputs are fuzzified by input nodes which act as tunable feature fuzzifiers. Rule based knowledge is easily translated directly into a network architecture. Connections in the network are represented by Gaussian fuzzy sets. The novelty of the model lies in a combination of tunable input feature fuzzifiers; fuzzy mutual subsethood-based activation spread in the network; use of the product operator to compute the extent of firing of a rule; and a volume-defuzzification process to produce a numeric output. Supervised gradient descent is employed to train the centers and spreads of individual fuzzy connections. A subsethood-based method for rule generation from the trained network is also suggested. SuPFuNIS can be applied in a variety of application domains. The model has been tested on Mackey-Glass time series prediction, Iris data classification, Hepatitis medical diagnosis, and function approximation benchmark problems. We also use a standard truck backer-upper control problem to demonstrate how expert knowledge can be used to augment the network. The performance of SuPFuNIS compares excellently with other various existing models.


Sustained deviation of torsional eye position associated with transient semicircular canal stimulation.
Vestibular stimulation causes postural unsteadiness accompanied by a sensation of tilt. The mechanism of the sensation of tilt needs to be assessed by accurate calculation of the rotational axis of torsional eye position under various vestibular stimulations. Twenty-two healthy subjects participated in the study. Thirteen subjects underwent bilateral vestibular stimulation by on-axis yaw rotation under various head positions, and eighteen subjects underwent unilateral vestibular stimulation by caloric irrigation under various head positions. Listing's Plane was plotted for the eye movement data obtained by three-dimensional video-oculography. The offset of Listing's Plane showed sustained deviation of torsional eye position that was more prominent in head positions that stimulated lateral semicircular canals more than vertical semicircular canals. There was a less prominent and directionally reversed offset in head positions that stimulated vertical canals more than lateral semicircular canals. The sustained torsional eye position was validated by accurate assessment using Listing's Plane. The mechanism behind the deviation may be due to a combination of multiple anatomical components within the vestibular apparatus, with potentially stronger influence from lateral semicircular canals.


Reclassification of Desulfobacterium phenolicum as Desulfobacula phenolica comb. nov. and description of strain SaxT as Desulfotignum balticum gen. nov., sp. nov.
A mesophilic, sulfate-reducing bacterium (strain SaxT) was isolated from marine coastal sediment in the Baltic Sea and originally described as a 'Desulfoarculus' sp. It used a large variety of substrates, ranging from simple organic compounds and fatty acids to aromatic compounds as electron donors. Autotrophic growth was possible with H2, CO2 and formate in the presence of sulfate. Sulfate, thiosulfate and sulfite were used as electron acceptors. Sulfur and nitrate were not reduced. Fermentative growth was obtained with pyruvate, but not with fumarate or malate. Substrate oxidation was usually complete leading to CO2, but at high substrate concentrations acetate accumulated. CO dehydrogenase activity was observed, indicating the operation of the CO dehydrogenase pathway (reverse Wood pathway) for CO2 fixation and complete oxidation of acetyl-CoA. The rod-shaped cells were 0.8-1.0 microm wide and 1.5-2.5 microm long. Spores were not produced and cells stained Gram-negative. The temperature limits for growth were between 10 and 42 degrees C (optimum growth at 28-32 degrees C). Growth was observed at salinities ranging from 5 to 110 g NaCl l(-1), with an optimum at 10-25 g NaCl l(-1). The G+C content of the DNA was 62.4 mol%. Vitamins were required for growth. Based on the 16S rRNA gene sequence, strain SaxT represents a new genus within the delta-subclass of the Proteobacteria. The name Desulfotignum balticum gen. nov., sp. nov. is proposed. After the 16S rDNA sequences of all members of the genus Desulfobacterium were published (GenBank accession nos. AJ237601-AJ237604, AJ237606, AJ237607), the need to reclassify most members of the genus Desulfobacterium became obvious due to their strong phylogenetic affiliation to other genera. Here, we propose to reclassify Desulfobacterium phenolicum as Desulfobacula phenolica comb. nov. Desulfotignum balticum, Desulfobacterium phenolicum and Desulfobacula toluolica contain cellular fatty acids which have so far only been found in members of the genus Desulfobacter.


Role of mucins in the skin during benign and malignant conditions.
Skin-related diseases comprise a major health challenge to the practicing physician, and constitute a significant psychological, social and financial burden to the society. Further, skin cancer, especially non-melanoma skin cancer is currently the leading type of malignancy in the Western world. Given the huge burden of skin diseases, there is growing emphasis on understanding their pathophysiology, and towards their early detection. Mucins are high-molecular weight O- and N-linked glycoproteins that have emerged in recent years as important molecules in maintaining health and in promoting or protecting against inflammation and cancer. They have also begun to emerge as highly specific diagnostic and prognostic markers and novel therapeutic targets in several malignant disorders. However, their role in cutaneous pathologies has remained largely obscured. The present review provides the expression patterns and proposed role of mucins in the healthy skin and various benign and malignant skin diseases. The review has immense clinical significance as the availability of highly specific reagents including monoclonal antibodies against mucins makes them extremely attractive targets for specific diagnosis and/or immunotherapy of benign and malignant cutaneous diseases.


Remodeling natural products: chemistry and serine hydrolase activity of a rocaglate-derived β-lactone.
Flavaglines are a class of natural products with potent insecticidal and anticancer activities. β-Lactones are a privileged structural motif found in both therapeutic agents and chemical probes. Herein, we report the synthesis, unexpected light-driven di-epimerization, and activity-based protein profiling of a novel rocaglate-derived β-lactone. In addition to in vitro inhibition of the serine hydrolases ABHD10 and ACOT1/2, the most potent β-lactone enantiomer was also found to inhibit these enzymes, as well as the serine peptidases CTSA and SCPEP1, in PC3 cells.


Rhizomic learning: How environmental non-governmental organizations (ENGOs) acquire and assemble knowledge.
It has been a common assumption that the knowledge practices of environmental organisations (ENGOs) is largely based on interaction with environmental research. Implied in such assumptions is the idea that ENGOs are so-called boundary organizations brokering knowledge between science and environmental policy decision-making. In this article, we challenge this belief. Through interviews, we have investigated the practices of ENGO employees as they acquire and assemble knowledge they need in their involvement with environmental policymakers. From their accounts, these ENGOs are not boundary organizations. Science is important but such knowledge was usually acquired indirectly and appeared to be seen as ubiquitous in the environmental policy community. We found that the knowledge practices were based on what we call rhizomic learning. We introduce this concept to highlight the complexity, opacity and non-linearity of the ways in which ENGO actors acquire and assemble environmental knowledge. We found that this rhizomic learning is characterized by five main features: 1) diversity of sources and the importance of networks, 2) pragmatism, 3) opacity of the process, 4) community among involved actors, and 5) mediation. ENGO actors expected that their capacity for rhizomic learning - not the least the purposeful mediation and assembly of knowledge from a multitude of sources - would make them appear to policymakers as competent, relevant and reliable.


Identification of Vibrio metschnikovii and Vibrio injensis Isolated from Leachate Ponds: Characterization of Their Antibiotic Resistance and Virulence-Associated Genes.
This study aimed to evaluate the antibiotic resistance of 22 environmental Vibrio metschnikovii isolates and 1 Vibrio injensis isolate from landfill leachates in southwestern Colombia. Isolates were identified by Matrix-Assisted Laser Desorption/Ionization-Time-Of-Flight (MALDI-TOF), and 16S ribosomal RNA gene sequencing. Analysis of the susceptibility to six antibacterial agents by the Kirby-Bauer method showed susceptibility of all the isolates to ciprofloxacin and imipenem. We recorded resistance to beta-lactams and aminoglycosides, but no multidrug resistance was observed. The genome of one of the isolates was sequenced to determine the pathogenic potential of V. injensis. Genes associated with virulence were identified, including for flagellar synthesis, biofilm formation, and hemolysins, among others. These results demonstrate that landfill leachates are potential reservoirs of antibiotic-resistant and pathogenic bacteria and highlight the importance of monitoring Vibrio species in different aquatic environments.


Tumor-agnostic plasma assay for circulating tumor DNA detects minimal residual disease and predicts outcome in locally advanced squamous cell carcinoma of the head and neck.
Forty to fifty percent of patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) relapse despite multimodal treatment. Circulating tumor DNA (ctDNA) has the potential to detect minimal residual disease (MRD) after curative-intent therapy and to identify earlier which patients will progress. We developed a tumor-agnostic plasma ctDNA assay to detect MRD in unselected LA SCCHN with the aim of predicting progression-free survival (PFS) and overall survival without the need for tumor sequencing. A 26-gene next-generation sequencing panel was constructed that included the most frequently mutated genes in SCCHN and two HPV-16 genes. MRD was assessed in each patient through an in-house informatic workflow informed by somatic mutations identified in the corresponding pre-treatment plasma sample. The presence of MRD was defined as the detection of ctDNA in one plasma sample collected within 1-12 weeks of the end of curative treatment. The primary endpoint was the PFS rate at 2 years. At least 32 patients were planned for inclusion with the hypothesis that PFS at 2 years was >80% in MRD-negative patients and <30% in MRD-positive patients (α = 0.05, β = 0.9). We sequenced DNA from 116 plasma samples derived from 53 LA SCCHN patients who underwent curative-intent treatment. ctDNA was detected in 41/53 (77%) patients in the pre-treatment samples. Out of these 41 patients, 17 (41%) were MRD positive after treatment. The 2-year PFS rate was 23.53% (9.9% to 55.4%) and 86.6% (73.4% to 100%) in MRD-positive and MRD-negative patients, respectively (P < 0.05). Median survival was 28.37 months (14.30 months-not estimable) for MRD-positive patients and was not reached for the MRD-negative cohort (P = 0.011). Our ctDNA assay detects MRD in LA SCCHN and predicts disease progression and survival without the need for tumor sequencing, making this approach easily applicable in daily practice.


Design of high-transmission metallic meander stacks with different grating periodicities for subwavelength-imaging applications.
When replacing a bulk negative index material (NIM) with two resonant surfaces that allow for surface plasmon polariton (SPP) propagation it is possible to recreate the same near-field imaging effects as with Pendry's perfect lens. We show that a metallic meander structure is perfectly suited as such a resonant surface due to the tunability of the short (SRSPP) and long range surface plasmon (LRSPP) frequencies by means of geometrical variation. Furthermore, the Fano-type pass band between the SRSPP and LRSPP frequencies of a single meander sheet retains its dominant role when being stacked. Hence, the pass band frequency position, which is determined by the meander geometry, controls also the pass band of a meander stack. When building up stacks with different periodicities the pass band shifts in frequency for each sheet in a different way. We rigorously calculate the spectra of various meander designs and show that this shift can be compensated by changing the remaining geometrical parameters of each single sheet. We also present a basic idea how high- transmission stacks with different periodicities can be created to enable energy transfer at low loss over practically arbitrary distances inside such a stack. The possibility to stack meander sheets of varying periodicity might be the key to far field superlenses since a controlled transformation of evanescent modes to traveling wave modes of higher diffraction order could be enabled.


Process evaluation of the Getting it Right study and acceptability and feasibility of screening for depression with the aPHQ-9.
The Getting it Right study determined the validity, sensitivity, specificity and acceptability of the culturally adapted 9-item Patient Health Questionnaire (aPHQ-9) as a screening tool for depression in Aboriginal and Torres Strait Islander (hereafter referred to as Indigenous) people. In this process evaluation we aimed to explore staff perceptions about whether Getting it Right was conducted per protocol, and if the aPHQ-9 was considered an acceptable and feasible screening tool for depression in primary healthcare. This process evaluation will provide information for clinicians and policy makers about the experiences of staff and patients with Getting it Right and what they thought about using the aPHQ-9. Process evaluation using grounded theory approaches. Semi-structured interviews with primary healthcare staff from services participating in Getting it Right were triangulated with feedback (free-text and elicited) from participants collected during the validation study and field notes. Data were thematically analysed according to the Getting it Right study protocol to identify the acceptability and feasibility of the aPHQ-9. Primary healthcare staff (n = 36) and community members (n = 4) from nine of the ten participating Getting it Right services and Indigenous participants (n = 500) from the ten services that took part. Most staff reported that the research was conducted according to the study protocol. Staff from two services reported sometimes recruiting opportunistically (rather than recruiting consecutive patients attending the service as outlined in the main study protocol), when they spoke to patients who they knew from previous interactions, because they perceived their previous relationship may increase the likelihood of patients participating. All Getting it Right participants responded to at least six of the seven feedback questions and 20% provided free-text feedback. Most staff said they would use the aPHQ-9 and most participants said that the questions were easy to understand (87%), the response categories made sense (89%) and that they felt comfortable answering the questions (91%). Getting it Right was predominantly conducted according to the study protocol. The aPHQ-9, the first culturally adapted, nationally validated, freely available depression screening tool for use by Indigenous people, appears to be acceptable and feasible to use. Australian New Zealand Clinical Trial Registry ANZCTR12614000705684 , 03/07/2014.


[Italian cardiovascular mortality charts of the CUORE Project: are they comparable with the SCORE charts?].
The CUORE Project, an Italian longitudinal study, and the SCORE Project use similar methodology in data collection of cardiovascular risk factors and events. The aim of this study was to build the CUORE Project risk charts for the assessment of cardiovascular mortality and to compare them with the SCORE charts. Random population samples enrolled between 1980 and 1990 in Italy were included in the analysis: 7520 men aged 35-69 years without previous cardiovascular events with a mean follow-up period of 10 years for cardiovascular disease. ICD-9 codes of death certificates similar to those of the SCORE Project were considered in the analysis when they appear as first cause of death. Gender stratified Cox proportional hazard models were used to assess cardiovascular mortality, including age, systolic blood pressure, total cholesterol (or total-to-HDL cholesterol ratio) and smoking habit as risk factors. Results from gender stratified analysis considering total cholesterol showed that all risk factors included in the cardiovascular mortality Cox model of the CUORE Project were statistically significant. The correspondent area under the ROC curve was 0.822 (95% confidence interval 0.800-0.844) for men. The CUORE Project charts were quite similar to the correspondent charts of the SCORE Project: Lin's concordance coefficient was 0.964. Risk range of non-smoker men was 0-17% for the CUORE cardiovascular mortality risk chart (0-14% for the SCORE chart); risk range of smokers was 0-25% for the CUORE cardiovascular mortality risk chart (0-26% for the SCORE chart). Similar results were observed for the chart with total-to-HDL cholesterol ratio. The comparison between the CUORE and SCORE mortality risk charts demonstrates that the SCORE charts reflect quite well Italian cardiovascular mortality and, correspondingly, Italian cohorts of the CUORE Project are quite representative of European countries with a low risk of cardiovascular mortality.


Transfusion requirements are correlated with the degree of proteolysis of von Willebrand factor during orthotopic liver transplantation.
During orthotopic liver transplantation (OLT) excessive bleeding is the main cause of death and graft failure. The acute bleeding tendency that accompanies OLT, particularly during the anhepatic period and after reperfusion of the graft, is due to the depletion or functional abnormalities of several hemostasis components caused by the enhanced activity of enzymes such as plasmin, trypsin and leukocyte proteases. We surmised that enhanced proteolysis might also cause abnormalities of von Willebrand factor (vWF), and that these abnormalities are implicated in the bleeding tendency that develops during OLT. Therefore, the pattern of vWF proteolysis was studied with 16 patients with chronic liver disease, in serial blood samples obtained before OLT, during the anhepatic stage, after graft reperfusion and at the end of the surgical procedure. vWF became markedly degraded during the anhepatic and reperfusion stages, as shown by the partial loss of high molecular weight multimers, the relative decrease of the intact 225 kD subunit and the increase of the native proteolytic fragments of 176 and 140 kD. Novel proteolytic fragments also became detectable. Using monoclonal antibody epitope mapping, it could be demonstrated that some of the proteolytic fragments corresponded in apparent molecular mass to those produced in vitro by incubating purified vWF with plasmin or elastase, but other fragments could not be attributed to these proteases. During the anhepatic and reperfusion stages there was a significant correlation between the degree of vWF degradation and the total amount of blood components transfused to replace blood losses. To evaluate whether or not vWF degradation could be controlled by the administration of a broad-spectrum protease inhibitor such as aprotinin, 5 patients were given a bolus dose of 500,000 U before surgery followed by 100,000 U/h during surgery, 5 were given a 2,000,000 U bolus followed by 500,000 U/h, and no aprotinin was given to the remaining 6 patients. There were no differences in the patterns or degrees of vWF degradation between patients treated with aprotinin or not. In conclusion, there is a marked degradation of a key hemostasis protein during OLT. These alterations may be of clinical significance, because they are correlated with the transfusion requirements.


Altered sodium channel behaviour causes myotonia in dominantly inherited myotonia congenita.
The cause of increased excitability in autosomal dominant myotonia congenita (MyC) was studied in resealed greater than 3-cm long segments of muscle fibres from eight patients. Three hours after biopsy only about 50% of the fibre segments had regained a normal resting potential. This differs from our experiences with normal muscle or other disorders of myotonia (e.g. recessive generalized myotonia) where nearly all cut fibres reseal and repolarize during this time. When the depolarized MyC fibre segments were placed in a solution containing 1 microM tetrodotoxin (TTX) they repolarized to -80 to -90 mV. In fibre segments with normal resting potential, in the absence of TTX, spontaneous myotonic runs were recorded intracellularly, occasionally with double spikes. For only one of the eight patients, the Cl- conductance was reduced (50% of the total membrane conductance vs the usual 75%), for the rest of the patients the steady-state current-voltage relationship was normal. Sodium currents through single membrane channels were recorded with a patch clamp. For every patient re-openings of the Na+ channels were observed throughout 10-ms depolarizing pulses. These are very uncommon in normal muscle. At potentials positive to the resting potential, the duration of the re-openings increased, but the current amplitude was the same. It is concluded that in myotonia congenita re-openings of Na+ channels are the major cause of hyperexcitability and that Cl- conductance is normal. If it is reduced in rare cases, it may potentiate the myotonia.


Financial implications of pharmacist-led Medicare annual wellness visits.
To determine if pharmacist-led Medicare Annual Wellness Visits (AWVs) are a feasible mechanism to financially support a pharmacist position in physicians' offices. Large, teaching, ambulatory clinic in North Carolina. The Mountain Area Health Education Family Health Center is a family medicine practice that houses a large medical residency program. The Department of Pharmacotherapy comprises five pharmacists and two pharmacy residents providing direct patient care. In April 2012, pharmacists began conducting Medicare AWVs for patients referred by their primary care physicians within the practice. Visit reimbursement, annual revenue, number of patients who must be seen to cover the cost of a pharmacist's salary. A small practice requires all eligible Medicare patients to complete an AWV to generate enough revenue to support a new pharmacist position. A medium-sized practice requires a 54% utilization rate, and a large practice requires an 18% utilization rate. Two additional AWVs per half-day of clinic are needed to support an existing pharmacotherapy clinic. A total of 1,070 AWVs per year are required to support a pharmacist's salary, regardless of practice size. AWV reimbursement may significantly contribute to supporting the cost of a pharmacist, particularly in medium- to large-sized practices. In larger practices, enough revenue can be generated to support the cost of multiple pharmacists.


Continuing animal tests on cosmetic ingredients for REACH in the EU
EU cosmetic ingredients are governed by two regulations that conflict. Regulation EC 1223/2009, the Cosmetic Regulation, bans in vivo (animal) testing for cosmetic product safety assessments, including both final products and ingredients. At the same time, the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) regulation can impose in vivo testing of those same ingredients under its chemical testing requirements. Here, we examined REACH dossiers for chemicals for which the only reported use is cosmetics to determine the extent of new in vivo testing caused by REACH. We found the REACH database has 3,206 chemical dossiers with cosmetics as a reported use. Of these, 419 report cosmetics as the only use, and 63 of these have in vivo tests completed after the Cosmetic Regulation ban on in vivo testing. Registrants largely used alternative, non-animal methods to evaluate ingredients for REACH, but some still conducted new in vivo tests to comply with REACH requirements for toxicity data and worker safety assessments. In some cases, ECHA, the agency that evaluates REACH dossiers, rejected registrants' alternative methods as insufficient and required new in vivo tests. As ECHA continues to evaluate dossiers, more requests for in vivo tests are likely. REACH tests on cosmetic ingredients appear only as "industrial chemicals legislation" tests in EU reports. Given the importance to consumers and the cosmetic industry of having cosmetics free of animal testing, the public should be made aware of REACH testing until the conflict between the regulations is resolved.


Electrodeposition of hyaluronic acid and hyaluronic acid-bovine serum albumin films from aqueous solutions.
Hyaluronic acid (HYH) films were prepared from aqueous sodium hyaluronate (HYNa) solutions by anodic electrodeposition. The film thickness was varied in the range of 0-20 microm by the variation of the deposition time and HYNa concentration. The deposition rate was low at HYNa concentration below 1 g L(-1) and increased significantly in the range of 3-5 g L(-1). The addition of bovine serum albumin (BSA) to the HYNa solutions resulted in increased deposition yield, which was attributed to the formation of composite HYH-BSA films. The thickness of the HYH-BSA films deposited by anodic electrodeposition was varied in the range of 0-80 microm. The HYH and composite HYH-BSA films were studied by scanning electron microscopy, thermogravimetric analysis, differential thermal analysis, Fourier transform infrared spectroscopy and circular dichroism spectroscopy. The deposition mechanism and kinetics of deposition are discussed.


Persistent high MR signal of the posterior pituitary gland in central diabetes insipidus.
We describe three cases of central diabetes insipidus, each with a different pathogenesis, in which unexpected hyperintensity of the posterior pituitary gland was seen on T1-weighted MR images obtained at the time of presentation. In the first case (idiopathic), the posterior pituitary signal persisted more than 10 years; in the second case (Langerhans cell histiocytosis), the signal disappeared within 3 months, despite early specific chemotherapy with etoposide; and in the third case (transient), the posterior signal disappeared within 1 year, but it was documented at the time of spontaneous reversal of polyuria and polydipsia.


Low plasma vitamin B-12 in Kenyan school children is highly prevalent and improved by supplemental animal source foods.
The high prevalence of vitamin B-12 deficiency in many regions of the world is becoming recognized as a widespread public health problem, but it is not known to what extent this deficiency results from a low intake of the vitamin or from its malabsorption from food. In rural Kenya, where a previous study identified a high prevalence of inadequate vitamin B-12 intakes, this study examined whether plasma vitamin B-12 concentrations were associated with dietary sources of the vitamin at baseline and could be increased by supplementation with animal source foods (ASF). The 4 experimental groups in 503 school children were: 1) control (no food provided); 2) githeri (a maize and bean staple with added oil); 3) githeri + meat (githeri + minced beef); or 4) githeri + milk (githeri + milk). Feedings were isocaloric. Dietary data were collected at baseline, and biochemical data at baseline and after 1 and 2 y of feeding. Baseline plasma vitamin B-12 concentration was 193.6 +/- 105.3 pmol/L and correlated with % energy from ASF (r = 0.308, P < 0.001). The odds ratio for low plasma vitamin B-12 (<148 pmol/L), which occurred in 40% of children, was 6.28 [95% CI: 3.07-12.82] for the lowest vs. highest ASF intake tertile (P < 0.001). Feeding ASF (meat or milk) greatly reduced the prevalence of low plasma vitamin B-12 (P < 0.001). The high prevalence of low plasma vitamin B-12 concentrations in these children is predicted by a low intake of ASF, and supplemental ASF improves vitamin B-12 status.


A novel set of Austrian reference unit costs for comprehensive societal perspectives consistent with latest European costing methods for economic evaluations.
Decision making in public health often happens against the background of scarce resources. The systematic use of economic evaluations can be a main enabler in the alignment of public health goals with budgetary constraints. However, the lack of standardized methodology in terms of costing method and perspective are a critical barrier to the implementation of economic evaluations and the international comparability of results. We present a novel set of 22 reference unit costs (RUCs) optimized for cross-sectoral economic evaluations in Austria suitable for international comparability calculated using the standardized PECUNIA RUC Template. The common framework for costing and reporting, as well as the easy availability of the RUCs will reduce the burden on researchers and policy makers in future economic evaluations. The higher quality, accuracy, transparency and availability of economic evidence for policy design will help to improve the efficiency of public health-relevant healthcare decisions and make it easier for policy makers to bring funding arrangements and decision making across multiple sectors in line with Health-in-All-Policies goals.


Physical activity level and future risk of mild cognitive impairment or dementia: a critically appraised topic.
The relationships between physical activity, cognition, and development of neurodegenerative diseases represent an area of intense research interest. Meta-analyses and prospective cohort studies show that greater levels of physical activity are associated with lower dementia risk. Most studies, however, depend on self-report data that are subject to recall and other biases. Obtaining objective and quantitative physical activity data could strengthen observational study validity. To examine the association between objectively measured daytime activity and mild cognitive impairment (MCI) or Alzheimer disease (AD). The objective was addressed through the development of a structured, critically appraised topic. We incorporated a clinical scenario, background information, a structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, clinical epidemiologists, a medical librarian, and behavioral neurology and neuropsychiatry content experts. We selected a prospective, single-center cohort study of 716 cognitively normal elderly participants followed for 3.5 years. Greater levels of physical activity, as measured using wrist actigraphy, were associated with a lower risk of incident MCI or AD (hazard ratio, 0.477; 95% confidence interval, 0.273-0.832). Objective measurement confirms that greater levels of physical activity are associated with decreased risk of a future diagnosis of MCI or AD. Further studies are needed to confirm the temporal association of exercise and future cognitive health and understand the relevant underlying biological mechanisms.


Pectobacterium parvum sp. nov., having a Salmonella SPI-1-like Type III secretion system and low virulence.
Pectobacterium strains isolated from potato stems in Finland, Poland and the Netherlands were subjected to polyphasic analyses to characterize their genomic and phenotypic features. Phylogenetic analysis based on 382 core proteins showed that the isolates clustered closest to Pectobacterium polaris but could be divided into two clades. Average nucleotide identity (ANI) analysis revealed that the isolates in one of the clades included the P. polaris type strain, whereas the second clade was at the border of the species P. polaris with a 96 % ANI value. In silico genome-to-genome comparisons between the isolates revealed values below 70%, patristic distances based on 1294 core proteins were at the level observed between closely related Pectobacterium species, and the two groups of bacteria differed in genome size, G+C content and results of amplified fragment length polymorphism and Biolog analyses. Comparisons between the genomes revealed that the isolates of the atypical group contained SPI-1-type Type III secretion island and genes coding for proteins known for toxic effects on nematodes or insects, and lacked many genes coding for previously characterized virulence determinants affecting rotting of plant tissue by soft rot bacteria. Furthermore, the atypical isolates could be differentiated from P. polaris by their low virulence, production of antibacterial metabolites and a citrate-negative phenotype. Based on the results of a polyphasic approach including genome-to-genome comparisons, biochemical and virulence assays, presented in this report, we propose delineation of the atypical isolates as a novel species Pectobacterium parvum, for which the isolate s0421T (CFBP 8630T=LMG 30828T) is suggested as a type strain.


How do parents' depression and anxiety, and infants' negative temperament relate to parent-infant face-to-face interactions?
The present study investigated the associations of mothers' and fathers' lifetime depression and anxiety symptoms, and of infants' negative temperament with parents' and infants' gaze, facial expressions of emotion, and synchrony. We observed infants' (age between 3.5 and 5.5 months, N = 101) and parents' gaze and facial expressions during 4-min naturalistic face-to-face interactions. Parents' lifetime symptoms of depression and anxiety were assessed with clinical interviews, and infants' negative temperament was measured with standardized observations. Parents with more depressive symptoms and their infants expressed less positive and more neutral affect. Parents' lifetime anxiety symptoms were not significantly related to parents' expressions of affect, while they were linked to longer durations of gaze to parent, and to more positive and negative affect in infants. Parents' lifetime depression or anxiety was not related to synchrony. Infants' temperament did not predict infants' or parents' interactive behavior. The study reveals that more depression symptoms in parents are linked to more neutral affect from parents and from infants during face-to-face interactions, while parents' anxiety symptoms are related to more attention to parent and less neutral affect from infants (but not from parents).


RTP801 regulates maneb- and mancozeb-induced cytotoxicity via NF-κB.
Environmental factors have been implicated in the pathogenesis of neurodegenerative diseases. Maneb (MB) and mancozeb (MZ) have been extensively used as pesticides. Exposure to MB lowers the threshold for dopaminergic damage triggered by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. MB and MZ potentiate 1-methyl-4-phenylpyridium (MPP(+))-induced cytotoxicity in rat pheochromocytoma (PC12) cells partially via nuclear factor kappa B (NF-κB) activation. RTP801 dramatically increased by oxidative stresses and DNA damage is the possible mechanism of neurotoxins-induced cell death in many studies. This study demonstrated that MB and MZ induced DNA damage as seen in comet assay. The expressions of RTP801 protein and mRNA were elevated after MB and MZ exposures. By knocking down RTP801 using shRNA, we demonstrated that NF-κB activation by MB and MZ was regulated by RTP801 and cell death triggered by MB and MZ was associated with RTP801 elevation. This revealed that the toxic mechanisms of dithiocarbamates are via the cross talk between RTP801 and NF-κB.


The Single Item Literacy Screener: evaluation of a brief instrument to identify limited reading ability.
Reading skills are important for accessing health information, using health care services, managing one's health and achieving desirable health outcomes. Our objective was to assess the diagnostic accuracy of the Single Item Literacy Screener (SILS) to identify limited reading ability, one component of health literacy, as measured by the S-TOFHLA. Cross-sectional interview with 999 adults with diabetes residing in Vermont and bordering states. Participants were randomly recruited from Primary Care practices in the Vermont Diabetes Information System June 2003-December 2004. The main outcome was limited reading ability. The primary predictor was the SILS. Of the 999 persons screened, 169 (17%) had limited reading ability. The sensitivity of the SILS in detecting limited reading ability was 54% [95% CI: 47%, 61%] and the specificity was 83% [95% CI: 81%, 86%] with an area under the Receiver Operating Characteristics Curve (ROC) of 0.73 [95% CI: 0.69, 0.78]. Seven hundred seventy (77%) screened negative on the SILS and 692 of these subjects had adequate reading skills (negative predictive value = 0.90 [95% CI: 0.88, 0.92]). Of the 229 who scored positive on the SILS, 92 had limited reading ability (positive predictive value = 0.4 [95% CI: 0.34, 0.47]). The SILS is a simple instrument designed to identify patients with limited reading ability who need help reading health-related materials. The SILS performs moderately well at ruling out limited reading ability in adults and allows providers to target additional assessment of health literacy skills to those most in need. Further study of the use of the SILS in clinical settings and with more diverse populations is warranted.


[A case report of Byler's syndrome].
The case report describes a progressive familial intrahepatic cholestasis II type Byler's syndrome with structural abnormality of the bile canalicular membrane. A child with a rare hereditary pathology,who is on the waiting list for liver transplantation, on the background of complex treatment, including diet therapy, drug therapy achieved a positive dynamics of clinical and laboratory parameters, acceleration of physical, psychomotor and intellectual development, that in general has improved the surgery prognosis and quality of life of the patient.


Synergistic targeting of AML stem/progenitor cells with IAP antagonist birinapant and demethylating agents.
Acute myeloid leukemia (AML) therapy has limited long-term efficacy because patients frequently develop disease relapse because of the inability of standard chemotherapeutic agents to target AML stem/progenitor cells. Here, we identify deregulated apoptotic components in AML stem/progenitor cells and investigate the individual and combinatorial effects of the novel inhibitor of apoptosis (IAP) protein antagonist and second mitochondrial-derived activator of caspases (SMAC) mimetic birinapant and demethylating epigenetic modulators. Protein expression was measured by reversed-phase protein array in AML patient (n = 511) and normal (n = 21) samples and by western blot in drug-treated cells. The antileukemic activity of birinapant and demethylating agents was assessed in vitro and in an in vivo AML mouse xenograft model (n = 10 mice per group). All statistical tests were two-sided. Compared with bulk AML cells, CD34(+)38(-) AML stem/progenitors expressed increased cIAP1 and caspase-8 levels and decreased SMAC levels (one-way analysis of variance followed by Tukey's multiple comparison test, P < .001). Birinapant induced death receptor-/caspase-8-mediated apoptosis in AML cells, including in AML stem/progenitor cells, but not in normal CD34(+) cells. Demethylating agents modulated extrinsic apoptosis pathway components and, when combined with birinapant, were highly synergistic in vitro (combination index < 1), and also more effective in vivo (P < .001, by Student t test, for the median survival of birinapant plus 5-azacytadine vs birinapant alone or vs controls). cIAP1, SMAC, and caspase-8 appear to play a role in AML stem cell survival, and synergistic targeting of these cells with birinapant and demethylating agents shows potential utility in leukemia therapy.


Narratives About Mental Illnesses in China: The Voices of Generation Y.
This study explores the cultured understanding of mental health and mental illnesses among members of Generation Y in China through a narrative approach. Five prominent narratives are identified through the analysis of stories about mental illnesses collected through semistructured interviews with college students. These five narratives feature the tragic genius, the psychotic criminal, the fragile victim, the antisocial recluse, and the homosexual. These narratives are gendered, in that women are the primary protagonists in the narrative about the fragile victim, while men are featured prominently in the narratives about the tragic genius, the psychotic criminal, and the antisocial recluse. Our study demonstrates that these narratives are based on, and will further reinforce, highly cultural-specific stereotypes and biases about mental illnesses in China. Theoretical and practical implications of this study are discussed.


A guide for use and interpretation of kinesiologic electromyographic data.
Physical therapists are among the most common users of electromyography as a method for understanding function and dysfunction of the neuromuscular system. However, there is no collection of references or a source that provides an overview or synthesis of information that serves to guide either the user or the consumer of electromyography and the data derived. Thus, the purpose of this article is to present a guide, accompanied by an inclusive reference list, for the use and interpretation of kinesiologic electromyographic data. The guide is divided into 4 major sections: collecting, managing, normalizing, and analyzing kinesiologic electromyographic data. In the first of these sections, the issues affecting data collection with both indwelling and surface electrodes are discussed. In the second section, data management through alternative forms of data processing is addressed. In the third section, various reasons and procedures for data normalization are discussed. The last section reviews qualitative descriptors once used as the only means of analyzing data, then focuses on more quantitative procedures that predominate today. The guide is intended as a tool for students, educators, clinicians, and beginning researchers who use and interpret kinesiologic electromyographic data. Modifications will likely be needed as alternative forms of collecting, managing, normalizing, and analyzing electromyographic data are proposed, used in various settings, and reported in the literature.


Sequence specific resonance assignment via Multicanonical Monte Carlo search using an ABACUS approach.
ABACUS [Grishaev et al. (2005) Proteins 61:36-43] is a novel protocol for automated protein structure determination via NMR. ABACUS starts from molecular fragments defined by unassigned J-coupled spin-systems and involves a Monte Carlo stochastic search in assignment space, probabilistic sequence selection, and assembly of fragments into structures that are used to guide the stochastic search. Here, we report further development of the two main algorithms that increase the flexibility and robustness of the method. Performance of the BACUS [Grishaev and Llinás (2004) J Biomol NMR 28:1-101] algorithm was significantly improved through use of sequential connectivities available from through-bond correlated 3D-NMR experiments, and a new set of likelihood probabilities derived from a database of 56 ultra high resolution X-ray structures. A Multicanonical Monte Carlo procedure, Fragment Monte Carlo (FMC), was developed for sequence-specific assignment of spin-systems. It relies on an enhanced assignment sampling and provides the uncertainty of assignments in a quantitative manner. The efficiency of the protocol was validated on data from four proteins of between 68-116 residues, yielding 100% accuracy in sequence specific assignment of backbone and side chain resonances.


Evaluation of Electronic Health Records on the Nursing Process and Patient Outcomes Regarding Fall and Pressure Injuries.
Digitalizing the nursing process has become a trend in medical care. The purpose of this study was to evaluate implementation of the Standardized Computerized Nursing Process Documentation System and patient outcomes. We analyzed hospitalized patients' electronic health record database with a total of 19 659 patients in 2015. The analysis focused on nurses' selection of nursing care plans for patients with a high risk of falls or pressure injuries through admission assessments. The effectiveness of implemented nursing care plans following falls or pressure injuries was explored. The results reveal that 55% of the hospitalized patients had a risk of falling, and 27.85% of patients were at risk of pressure injuries. Patients receiving nursing care plan who experienced falls or pressure injuries were significantly higher than those without a nursing care plan (P < .001). This study could not provide direct evidence for the effect of nursing care plans on reducing the incidence of falls and pressure injuries, which may be attributable to patient characteristics. Furthermore, an analysis on data from 2007 to 2017 using a run chart revealed that the mean incidence rate for pressure injuries decreased, whereas that for falls remained stable. The results indicate that the system did not increase the occurrence of such incidences.


A molecular approach to drought-induced reduction in leaf CO2 exchange in drought-resistant Quercus ilex.
Drought-induced reduction of leaf gas exchange entails a complex regulation of the plant leaf metabolism. We used a combined molecular and physiological approach to understand leaf photosynthetic and respiratory responses of 2-year-old Quercus ilex seedlings to drought. Mild drought stress resulted in glucose accumulation while net photosynthetic CO2 uptake (Pn ) remained unchanged, suggesting a role of glucose in stress signaling and/or osmoregulation. Simple sugars and sugar alcohols increased throughout moderate-to-very severe drought stress conditions, in parallel to a progressive decline in Pn and the quantum efficiency of photosystem II; by contrast, minor changes occurred in respiration rates until drought stress was very severe. At very severe drought stress, 2-oxoglutarate dehydrogenase complex gene expression significantly decreased, and the abundance of most amino acids dramatically increased, especially that of proline and γ-aminobutyric acid (GABA) suggesting enhanced protection against oxidative damage and a reorganization of the tricarboxylic cycle acid cycle via the GABA shunt. Altogether, our results point to Q. ilex drought tolerance being linked to signaling and osmoregulation by hexoses during early stages of drought stress, and enhanced protection against oxidative damage by polyols and amino acids under severe drought stress.


Antibody-Independent Quantification of Cytomegalovirus Virion Protein Incorporation Using HiBiT.
Human cytomegalovirus (HCMV) is a large double-stranded DNA virus and member of the β-herpesvirus family. HCMV is ubiquitous in the human population and causes lifelong infections. HCMV infection is associated with high morbidity and mortality in immunocompromised individuals and the virus is a major cause of virus-mediated congenital disease. There have been a number of HCMV entry receptors identified that use one of two viral receptor binding complexes, including the gH/gL/gO complex and the pentamer made up of gH/gL/UL128/UL130/UL131a. Cytomegaloviruses (CMVs) are typically host-restricted requiring the use of species-specific modeling and culture conditions. We use rat CMV (RCMV) to study CMV-accelerated vascular disease and chronic allograft rejection. RCMV encodes homologous versions of the entry complex proteins but their incorporation and copy number per virion are still unknown. In this methods article, we describe a novel approach of HiBiT tagging viral proteins in order to detect and quantify protein incorporation into particles. This method is independent of protein-specific antibodies and can be standardized using a commercially available HiBiT protein standard. Using bacterial artificial chromosome (BAC) recombineering, we have constructed two individual viruses containing a HiBiT tag fused to the C'-terminus of either the UL128 homolog (R129) or the UL130 homolog (R131). Viruses containing these mutations were rescued, purified and analyzed. Our data demonstrate that R129 and R131 are both incorporated into RCMV virions at equimolar ratios relative to genome copy number, supporting this antibody-free approach for quantifying viral protein incorporation and its application toward the identification of domains required for incorporation.


Cognitive Restraint and History of Dieting Are Negatively Associated with Organic Food Consumption in a Large Population-Based Sample of Organic Food Consumers.
Organic food consumption has risen in many countries during the past decades, but individual motives leading to these choices remain unclear. This study aimed to evaluate the associations between cognitive restraint (CR), history of dieting and organic food intake. This cross-sectional analysis included 20,085 organic food consumers from the NutriNet-Santé cohort. CR (range score 1-4) was evaluated by the Three-Factor-Eating-Questionnaire and practice of dieting (never vs. past/current) was assessed by an ad hoc questionnaire. Frequencies of organic food intake overall and in 16 food groups were assessed by the Organic Food Frequency Questionnaire. Linear regression and analysis of covariance (ANCOVA) were performed to investigate the association between CR score, history of dieting and contribution of organic food intake to the total food intake. A lower overall contribution of organic options in the diet was observed in women with higher levels of CR (β = -3.61%, 95% CI: -4.32; -2.91 for 1 point of CR, p < 0.001) and with a history of dieting (31.1 ± 0.4% in past/current vs. 32.6 ± 0.3% in never dieters; p = 0.001). Consistent associations were observed in men with a history of dieting (26.4 ± 0.8% in past/current vs. 28.7 ± 0.4% in never dieters; p = 0.012). Overall, individuals-in particular women-with higher CR scores or with a history of dieting selected fewer organic food options. Our findings illustrate the complexity of potentially concurrent motives to food choices, in a context of increasing interest in organic food consumption.


Improved activity estimation with MC-JOSEM versus TEW-JOSEM in 111In SPECT.
We have previously developed a fast Monte Carlo (MC)-based joint ordered-subset expectation maximization (JOSEM) iterative reconstruction algorithm, MC-JOSEM. A phantom study was performed to compare quantitative imaging performance of MC-JOSEM with that of a triple-energy-window approach (TEW) in which estimated scatter was also included additively within JOSEM, TEW-JOSEM. We acquired high-count projections of a 5.5 cm3 sphere of 111In at different locations in the water-filled torso phantom; high-count projections were then obtained with 111In only in the liver or only in the soft-tissue background compartment, so that we could generate synthetic projections for spheres surrounded by various activity distributions. MC scatter estimates used by MC-JOSEM were computed once after five iterations of TEW-JOSEM. Images of different combinations of liver/background and sphere/background activity concentration ratios were reconstructed by both TEW-JOSEM and MC-JOSEM for 40 iterations. For activity estimation in the sphere, MC-JOSEM always produced better relative bias and relative standard deviation than TEW-JOSEM for each sphere location, iteration number, and activity combination. The average relative bias of activity estimates in the sphere for MC-JOSEM after 40 iterations was -6.9%, versus -15.8% for TEW-JOSEM, while the average relative standard deviation of the sphere activity estimates was 16.1% for MC-JOSEM, versus 27.4% for TEW-JOSEM. Additionally, the average relative bias of activity concentration estimates in the liver and the background for MC-JOSEM after 40 iterations was -3.9%, versus -12.2% for TEW-JOSEM, while the average relative standard deviation of these estimates was 2.5% for MC-JOSEM, versus 3.4% for TEW-JOSEM. MC-JOSEM is a promising approach for quantitative activity estimation in 111In SPECT.


Analyzing Global Components in Developmental Dyscalculia and Dyslexia.
The study examined whether developmental deficits in reading and numerical skills could be expressed in terms of global factors by reference to the rate and amount (RAM) and difference engine (DEM) models. From a sample of 325 fifth grade children, we identified 5 children with dyslexia, 16 with dyscalculia, 7 with a "mixed pattern," and 49 control children. Children were asked to read aloud words presented individually that varied for frequency and length and to respond (either vocally or manually) to a series of simple number tasks (addition, subtraction, number reading, and number comparisons). Reaction times were measured. Results indicated that the deficit of children with dyscalculia and children with a mixed pattern on numerical tasks could be explained by a single global factor, similarly to the reading deficit shown by children with dyslexia. As predicted by the DEM, increases in task difficulty were accompanied by a corresponding increase in inter-individual variability for both the reading and numerical tasks. These relationships were constant across the four groups of children but differed in terms of slope and intercept on the x-axis, indicating that two different general rules underlie performance in reading and numerical skills. The study shows for the first time that, as previously shown for reading, also numerical performance can be explained with reference to a global factor. The advantage of this approach is that it takes into account the over-additivity effect, i.e., the presence of larger group differences in the case of more difficult conditions over and above the characteristics of the experimental conditions. It is concluded that reference to models such as the RAM and DEM can be useful in delineating the characteristics of the dyscalculic deficit as well as in the description of co-morbid disturbances, as in the case of dyslexia and dyscalculia.


Solubilization of the alternative oxidase of cuckoo-pint (Arum maculatum) mitochondria. Stimulation by high concentrations of ions and effects of specific inhibitors.
Selective solubilization of cyanide- and antimycin-insensitive duroquinol oxidase activity from cuckoo-pint (Arum maculatum) mitochondria was achieved using taurocholate. Inhibitor-sensitivities and water-forming DQH2 (tetramethyl-p-hydroquinone, reduced form): O2 stoichiometry were the same for the alternative oxidase of intact Arum mitochondria. Cyanide-insensitive oxidation of DQH2 by intact and solubilized mitochondria was stimulated by up to four-fold by high concentrations of anions high in the Hofmeister series, such as phosphate, sulphate or citrate. Optimal (0.7 M) sodium citrate increased Vmax. for DQH2 oxidation by the solubilized preparation from 450 to 2400 nmol of O2 X min-1 X mg of protein-1 and decreased the apparent Km for DQH2 from 0.53 to 0.38 mM. Inhibition of solubilized DQH2 oxidase activity by CLAM (m-chlorobenzhydroxamic acid) and SHAM (salicylhydroxamic acid) was mixed competitive/non-competitive, with apparent inhibition constants for CLAM of 25 microM (Ki) and 81 microM (KI) and for SHAM of 53 microM (Ki) and 490 microM (KI). Propyl gallate and UHDBT were non-competitive inhibitors with respect to DQH2 (apparent Ki = 0.3 microM and 12 nM respectively). Low concentrations of C18 fatty acids selectively inhibited cyanide-insensitive oxidation by intact and solubilized mitochondria, and inhibition was reversed by 1% (w/v) bovine serum albumin. Inhibition was competitive with DQH2, suggesting that fatty acids interfere reversably with the binding of DQH2 to the oxidase. These results tend to support the view that quinol oxidation by the alternative pathway of Arum maculatum mitochondria is catalysed by a quinol oxidase protein, rather than by a non-enzymic mechanism involving fatty acid peroxidative reaction. [Rustin, Dupont & Lance (1983) Trends Biochem. Sci. 8, 155-157; (1983) Arch. Biochem. Biophys. 225, 630-639].


Giant lung cavity due to three different pathogens in a patient receiving inhaled salmeterol plus fluticasone propionate for asthma.
High-dose and long-term use of inhaled corticosteroids may cause systemic and local side effects such as opportunistic infections. Here we report a patient with asthma who developed a giant cavity in the lung while using inhaled salmeterol plus fluticasone propionate. A 57-year-old female patient presented with a three-week history of cough, hemoptysis, and dyspnea. She had a diagnosis of asthma for 4 years and was using an inhaled salmeterol plus fluticasone treatment intermitently for 2 years. A giant cavity was detected in the patient's chest X-ray. As a result of further investigations, three different microorganisms were isolated from the samples of sputum, bronchial lavage and lung biopsy. Staphylococcus aureus was the first microorganism that was isolated from the sputum and the bronchial lavage. Afterwards, Candida albicans was detected in both the bronchial lavage fluid and the histologic examination of the tissue samples obtained by percutaneous lung biopsy. Appropriate antibiotics and antifungals were prescribed. Moderate clinical and radiological response to the treatment was obtained. During the outpatient follow-up, Mycobacterium tuberculosis growth which was sensitive to all of the major anti-tuberculosis drugs was reported in the mycobacterial culture, and the patient was started on anti-tuberculosis treatment. Tuberculosis and other opportunistic infections are a potential consequence of inhaled corticosteroid use. Clinicians overseeing such patients need to be vigilant about the need for timely investigations about tuberculosis before and during prescribing medications containing inhaled corticosteroids.


Reclassification of Graphium tectonae as Parascedosporium tectonae gen. nov., comb. nov., Pseudallescheria africana as Petriellopsis africana gen. nov., comb. nov. and Pseudallescheria fimeti as Lophotrichus fimeti comb. nov.
During a biodiversity survey of Argentinian soil fungi, we recovered a rare Scedosporium-like fungus which was proven to be genetically and morphologically different from known species of Scedosporium (anamorph of Pseudallescheria) and relatives and is proposed here as representing a new genus. This genus is mainly characterized by producing sympodial conidia from denticulate conidiogenous cells. This isolate was morphologically identical to Graphium tectonae and thus the new combination Parascedosporium tectonae gen. nov., comb. nov. is proposed. Sequence analysis of four regions of three genes, i.e. beta-tubulin (two loci), calmodulin and the internal transcribed spacer region of the 5.8S rRNA, confirmed our proposal. Both the phylogenetic analysis and morphological studies excluded Pseudallescheria africana and Pseudallescheria fimeti from the genus Pseudallescheria. The former is proposed as a member of the new genus Petriellopsis, and the latter has been accommodated in Lophotrichus. The type strains of Parascedosporium tectonae gen. nov., comb. nov., Petriellopsis africana gen. nov., comb. nov. and Lophotrichus fimeti comb. nov. are respectively CBS 127.84(T), CBS 311.72(T) and CBS 129.78(T).


Optimizing community linkage to care and antiretroviral therapy Initiation: Lessons from the Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS) and their adaptation in Nigeria ART Surge.
Ineffective linkage to care (LTC) is a known challenge for community HIV testing. To overcome this challenge, a robust linkage to care strategy was adopted by the 2018 Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS). The NAIIS linkage to care strategy was further adapted to improve Nigeria's programmatic efforts to achieve the 1st 90 as part of the Nigeria Antiretroviral Therapy (ART) Surge initiative, which also included targeted community testing. In this paper we provide an overview of the NAIIS LTC strategy and describe the impact of this strategy on both the NAIIS and the Surge initiatives. The NAIIS collaborated with community-based organizations (CBOs) and deployed mobile health (mHealth) technology with real-time dashboards to manage and optimize community LTC for people living with HIV (PLHIV) diagnosed during the survey. In NAIIS, CBOs' role was to facilitate linkage of identified PLHIV in community to facility of their choice. For the ART Surge, we modified the NAIIS LTC strategy by empowering both CBOs and mobile community teams as responsible for not only active LTC but also for community testing, ART initiation, and retention in care. Of the 2,739 PLHIV 15 years and above identified in NAIIS, 1,975 (72.1%) were either unaware of their HIV-positive status (N = 1890) or were aware of their HIV-positive status but not receiving treatment (N = 85). Of these, 1,342 (67.9%) were linked to care, of which 952 (70.9%) were initiated on ART. Among 1,890 newly diagnosed PLHIV, 1,278 (67.6%) were linked to care, 33.7% self-linked and 66.3% were linked by CBOs. Among 85 known PLHIV not on treatment, 64 (75.3%) were linked; 32.8% self-linked and 67.2% were linked by a CBO. In the ART Surge, LTC and treatment initiation rates were 98% and 100%, respectively. Three-month retention for monthly treatment initiation cohorts improved from 76% to 90% over 6 months. Active LTC strategies by local CBOs and mobile community teams improved LTC and ART initiation in the ART Surge initiative. The use of mHealth technology resulted in timely and accurate documentation of results in NAIIS. By deploying mHealth in addition to active LTC, CBOs and mobile community teams could effectively scale up ART with real-time documentation of client-level outcomes.


Conflicts of interest and spin in reviews of psychological therapies: a systematic review.
To explore conflicts of interest (COI) and their reporting in systematic reviews of psychological therapies, and to evaluate spin in the conclusions of the reviews. MEDLINE and PsycINFO databases were searched for systematic reviews published between 2010 and 2013 that assessed effects of psychological therapies for anxiety, depressive or personality disorders, and included at least one randomised controlled trial. Required COI disclosure by journal, disclosed COI by review authors, and the inclusion of own primary studies by review authors were extracted. Researcher allegiance, that is, that researchers concluded favourably about the interventions they have studied, as well as spin, that is, differences between results and conclusions of the reviews, were rated by 2 independent raters. 936 references were retrieved, 95 reviews fulfilled eligibility criteria. 59 compared psychological therapies with other forms of psychological therapies, and 36 psychological therapies with pharmacological interventions. Financial, non-financial, and personal COI were disclosed in 22, 4 and 1 review, respectively. 2 of 86 own primary studies of review authors included in 34 reviews were disclosed by review authors. In 15 of the reviews, authors showed an allegiance effect to the evaluated psychological therapy that was never disclosed. Spin in review conclusions was found in 27 of 95 reviews. Reviews with a conclusion in favour of psychological therapies (vs pharmacological interventions) were at high risk for a spin in conclusions (OR=8.31 (1.41 to 49.05)). Spin was related in trend to the inclusion of own primary studies in the systematic review (OR=2.08 (CI 0.83 to 5.18) p=0.11) and researcher allegiance (OR=2.63 (0.84 to 8.16) p=0.16). Non-financial COI, especially the inclusion of own primary studies into reviews and researcher allegiance, are frequently seen in systematic reviews of psychological therapies and need more transparency and better management.


Properties of cutaneous mechanoreceptors in the human hand related to touch sensation.
Recordings from single peripheral nerve fibres made it possible to analyse the functional properties of tactile afferent units supplying the glabrous skin of the human hand and to assess directly the relation between impulse discharge and perceptive experiences. The 17,000 tactile units in this skin area of the human hand are of four different types: two fast adapting types, FA I and FA II (formerly RA and PC), and two slowly adapting types, SA I and SA II. The receptive field characteristics and the densities in the skin of the type I units (FA I and SA I) indicate that these account for the detailed spatial resolution that is of paramount importance for the motor skill and the explorative role of the hand. The relationship between the stimulus amplitude and perceived intensity during sustained skin indentations did not match the corresponding stimulus response functions of SA units suggesting non-linear transformations within the central nervous system. These transformations, in turn, appear to vary between subjects. A single impulse in a single FA I unit may be felt when originating from the most important tactile regions of the hand, indicating that the psychophysical detection may be set by the threshold of the sense organs. Moreover, no significant noise seems to be superimposed in the respective central sensory pathways.


Limitations of noninvasive testing in assessing the "occluded" carotid artery.
Over a 3 year period eight cases of atherosclerotic pseudoocclusion were detected by carotid angiography. The diagnosis was based on the detection of a thin, delayed antegrade trickle of contrast medium distal to an area of extreme stenosis. In six of these cases both direct and indirect noninvasive tests were interpreted as showing total occlusion. In one case these tests were thought to demonstrate a normal bifurcation, and only once were they successful in suggesting the diagnosis of high-grade stenosis. Five of these eight patients subsequently underwent carotid endarterectomy. Patients who present with appropriate clinical indications for carotid endarterectomy should undergo angiography even when the noninvasive tests indicate a total occlusion of the internal carotid artery. In such circumstances the angiographic technique should be altered specifically to detect the possible presence of atheromatous pseudoocclusion.


Fast reconfiguration of high-frequency brain networks in response to surprising changes in auditory input.
How do human brain networks react to dynamic changes in the sensory environment? We measured rapid changes in brain network organization in response to brief, discrete, salient auditory stimuli. We estimated network topology and distance parameters in the immediate central response period, <1 s following auditory presentation of standard tones interspersed with occasional deviant tones in a mismatch-negativity (MMN) paradigm, using magnetoencephalography (MEG) to measure synchronization of high-frequency (gamma band; 33-64 Hz) oscillations in healthy volunteers. We found that global small-world parameters of the networks were conserved between the standard and deviant stimuli. However, surprising or unexpected auditory changes were associated with local changes in clustering of connections between temporal and frontal cortical areas and with increased interlobar, long-distance synchronization during the 120- to 250-ms epoch (coinciding with the MMN-evoked response). Network analysis of human MEG data can resolve fast local topological reconfiguration and more long-range synchronization of high-frequency networks as a systems-level representation of the brain's immediate response to salient stimuli in the dynamically changing sensory environment.


Analyzing Social Media Data to Understand Consumer Information Needs on Dietary Supplements.
Despite the high consumption of dietary supplements (DS), few reliable, relevant, and comprehensive online resources could satisfy information seekers. This research study aims to understand consumer information needs on DS using topic modeling, and to evaluate accuracy in correctly identifying topics from social media. We retrieved 16,095 unique questions posted on Yahoo! Answers relating to 438 unique DS ingredients mentioned in sub-section, "Alternative medicine" under the section, "Health" . We implemented an unsupervised topic modeling method, Correlation Explanation (CorEx) to unveil the various topics in which consumers are most interested. We manually reviewed the keywords of all the 200 topics generated by CorEx and assigned them to 38 health-related categories, corresponding to 12 higher-level groups. We found high accuracy (90-100%) in identifying questions that correctly align with the selected topics. The results could guide us to generate a more comprehensive and structured DS resource based on consumers' information needs.