Crosstalk Between Dysfunctional Mitochondria and Inflammation in Glaucomatous Neurodegeneration.
Mitochondrial dysfunction and excessive inflammatory responses are both sufficient to induce pathology in age-dependent neurodegenerations. However, emerging evidence indicates crosstalk between damaged mitochondrial and inflammatory signaling can exacerbate issues in chronic neurodegenerations. This review discusses evidence for the interaction between mitochondrial damage and inflammation, with a focus on glaucomatous neurodegeneration, and proposes that positive feedback resulting from this crosstalk drives pathology. Mitochondrial dysfunction exacerbates inflammatory signaling in multiple ways. Damaged mitochondrial DNA is a damage-associated molecular pattern, which activates the NLRP3 inflammasome; priming and activation of the NLRP3 inflammasome, and the resulting liberation of IL-1β and IL-18 via the gasdermin D pore, is a major pathway to enhance inflammatory responses. The rise in reactive oxygen species induced by mitochondrial damage also activates inflammatory pathways, while blockage of Complex enzymes is sufficient to increase inflammatory signaling. Impaired mitophagy contributes to inflammation as the inability to turnover mitochondria in a timely manner increases levels of ROS and damaged mtDNA, with the latter likely to stimulate the cGAS-STING pathway to increase interferon signaling. Mitochondrial associated ER membrane contacts and the mitochondria-associated adaptor molecule MAVS can activate NLRP3 inflammasome signaling. In addition to dysfunctional mitochondria increasing inflammation, the corollary also occurs, with inflammation reducing mitochondrial function and ATP production; the resulting downward spiral accelerates degeneration. Evidence from several preclinical models including the DBA/2J mouse, microbead injection and transient elevation of IOP, in addition to patient data, implicates both mitochondrial damage and inflammation in glaucomatous neurodegeneration. The pressure-dependent hypoxia and the resulting metabolic vulnerability is associated with mitochondrial damage and IL-1β release. Links between mitochondrial dysfunction and inflammation can occur in retinal ganglion cells, microglia cells and astrocytes. In summary, crosstalk between damaged mitochondria and increased inflammatory signaling enhances pathology in glaucomatous neurodegeneration, with implications for other complex age-dependent neurodegenerations like Alzheimer's and Parkinson's disease.


Factors Affecting Process Temperature and Biogas Production in Small-scale Rural Biogas Digesters in Winter in Northern Vietnam.
This study investigated the main factors influencing digester temperature and methods to reduce heat losses during the cold season in the subtropics. Four composite digesters (two insulated and two uninsulated) were buried underground to measure their internal temperature (°C) at a depth of 140 cm and 180 cm, biogas production and methane (CH4) concentration in biogas from August to February. In parallel the temperature of the air (100 cm above ground), in the slurry mixing tank and in the soil (10, 100, 140, and 180 cm depth) was measured by thermocouple. The influent amount was measured daily and the influent chemical composition was measured monthly during the whole experimental period. Seasonal variations in air temperature significantly affected the temperature in the soil, mixing tank and digester. Consequently, biogas production, which is temperature dependent, was influenced by the season. The main factors determining the internal temperature in the digesters were insulation with Styrofoam, air temperature and temperature of slurry in the mixing tank. Biogas production is low due to the cold climate conditions in winter in Northern Vietnam, but the study proved that storing slurry in the mixing tank until its temperature peak at around 14:00 h will increase the temperature in the digester and thus increase potential biogas production. Algorithms are provided linking digester temperature to the temperature of slurry in the mixing tank.


Gene expression in the rat brain: high similarity but unique differences between frontomedial-, temporal- and occipital cortex.
The six-layered neocortex of the mammalian brain may appear largely homologous, but is in reality a modular structure of anatomically and functionally distinct areas. However, global gene expression seems to be almost identical across the cerebral cortex and only a few genes have so far been reported to show regional enrichment in specific cortical areas. In the present study on adult rat brain, we have corroborated the strikingly similar gene expression among cortical areas. However, differential expression analysis has allowed for the identification of 30, 24 and 11 genes enriched in frontomedial -, temporal- or occipital cortex, respectively. A large proportion of these 65 genes appear to be involved in signal transduction, including the ion channel Fxyd6, the neuropeptide Grp and the nuclear receptor Rorb. We also find that the majority of these genes display increased expression levels around birth and show distinct preferences for certain cortical layers and cell types in rodents. Since specific patterns of expression often are linked to equally specialised biological functions, we propose that these cortex sub-region enriched genes are important for proper functioning of the cortical regions in question.


Treatment of premenstrual dysphoria with alprazolam. A controlled study.
Thirty women who met DSM-III-R criteria for late luteal phase dysphoric disorder completed a double-blind, randomly assigned crossover treatment study comparing alprazolam with placebo. Alprazolam was found to be superior to placebo. The outcome measures included physicians' global ratings as well as patients' prospective (daily) ratings and retrospective assessments. Improved study design, which addressed methodologic flaws of most previous studies of treatment outcome of "premenstrual syndrome" may account, in part, for our ability to demonstrate significant drug/placebo differences. This includes extensive screening to eliminate women who had premenstrual exacerbations of a more persistent mental illness rather than a discrete premenstrual disorder, use of prospective ratings to confirm retrospective reports of symptom patterns, placebo washout before randomization, and use of patients as their own controls.


Purple membrane: color, crystallinity, and the effect of dimethyl sulfoxide.
In an effort to understand the nature of chromophore-protein interactions in bacteriorhodopsin (bR), we have reinvestigated dimethyl sulfoxide (DMSO)-induced changes in bR [Oesterhelt et al. (1973) Eur. J. Biochem. 40, 453-463]. We observe that dark-adapted bR (bR560) in aqueous DMSO undergoes reversible transformation to a species absorbing maximally at 480 nm (bR480). Beginning at 40% DMSO, this change results in complete conversion to bR480 at 60% DMSO. The kinetics of the reaction reveal that this transformation takes place predominantly through the all-trans isomeric form of the pigment. Thermal isomerization of the 13-cis chromophore to the all-trans form is, therefore, the rate-limiting step in the formation of bR480 from the dark-adapted bR. As in native bR, the chromophore in bR480 is linked to the protein via a protonated Schiff base, and its isomeric composition is predominantly all-trans. The formation of bR480 is associated with minor changes in the protein secondary structure, and the membrane retains crystallinity. These changes in the protein structure result in a diminished chromophore-protein interaction near the Schiff base region in bR480. Thus, we attribute the observed spectroscopic changes in bR in DMSO to structural alteration of the protein. The 13-cis chromophoric pigment appears to be resistant to this solvent-induced change. The changes in the protein structure need not be very large; displacement of the protein counterion(s) to the Schiff base, resulting from minor changes in the protein structure, can produce the observed spectral shift.


Examining participant engagement in an information technology-based physical activity and nutrition intervention for men: the manup randomized controlled trial.
Males experience a shorter life expectancy and higher rates of chronic diseases compared to their female counterparts. To improve health outcomes among males, interventions specifically developed for males that target their health behaviors are needed. Information technology (IT)-based interventions may be a promising intervention approach in this population group, however, little is known about how to maximize engagement and retention in Web-based programs. The current study sought to explore attributes hypothesized to influence user engagement among a subsample of participants from the ManUp study, a randomized controlled trial testing the efficacy of an interactive Web-based intervention for promoting physical activity and nutrition among middle-aged males. Semistructured interviews were conducted and audiotaped with 20 of the ManUp participants. Interview questions were based on a conceptual model of engagement and centered on why participants took part in the study, what they liked and did not like about the intervention they received, and how they think the intervention could be improved. Interview recordings were transcribed and coded into themes. There were five themes that were identified in the study. These themes were: (1) users' motives, (2) users' desired outcomes, (3) users' positive experiences, (4) users' negative emotions, and (5) attributes desired by user. There is little research in the field that has explored user experiences in human-computer interactions and how such experiences may relate to engagement, especially among males. Although not conclusive, the current study provides some insight into what personal attributes of middle-aged males (such as their key motives and goals for participating) and attributes of the intervention materials (such as usability, control, and interactivity) may impact on user engagement in this group. These findings will be helpful for informing the design and implementation of future health behavior interventions for males. Australian New Zealand Clinical Trials Registry: ACTRN12611000081910; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12611000081910 (Archived by WebCite at http://www.webcitation.org/6M4lBlvCA).


Effects of gamete source and culture conditions on the competence of in vitro-produced embryos for post-transfer survival in cattle.
One limitation to the use of in vitro-produced embryos in cattle production systems is the fact that pregnancy rates after transfer to recipients are typically lower than when embryos produced in vivo are transferred. Conceptually, the oocyte and spermatozoon from which the embryo is derived could affect competence for post-transfer survival. There are sire differences in embryonic survival after transfer, but there is little evidence that an embryo's ability to establish pregnancy is determined by sex sorting of spermatozoa by flow cytometry. The role of the source of the oocyte as a determinant of embryonic survival after transfer has not been examined carefully. Conditions for embryo culture after fertilisation can have an impact on the ability of the embryo to establish pregnancy following transfer. Among the specific molecules produced in the reproductive tract of the cow that have been shown to improve competence of in vitro-produced embryos for post-transfer survival are colony-stimulating factor 2, insulin-like growth factor-1 (for recipients exposed to heat stress) and hyaluronan (for less-advanced embryos). There is also a report that embryo competence for post-transfer survival can be improved by inclusion of a carbon-activated air filtration system in the incubator used to culture embryos. Progress in developing culture systems to improve embryonic competence for survival after transfer would be hastened by the development of in vitro assays that accurately predict the potential of an embryo to establish pregnancy after transfer. A group of 52 genes has been identified that are differentially expressed in embryos that developed to term v. embryos that did not establish pregnancy. Perhaps a gene microarray consisting of these genes, alone or in combination with other genes, could be used to screen embryos for competence to establish pregnancy.


FP prostanoid receptor-mediated induction of the expression of early growth response factor-1 by activation of a Ras/Raf/mitogen-activated protein kinase signaling cascade.
FP prostanoid receptors are G-protein-coupled receptors whose physiological activator is prostaglandin-F(2alpha) (PGF(2alpha)). PGF(2alpha) has been implicated in wound healing and cardiac hypertrophy, which are both known to involve the induction of the immediate-early response gene, early growth response factor-1 (EGR-1). We hypothesized that activation of the human FP receptor by PGF(2alpha) could induce the expression of EGR-1 and found that 1 muM PGF(2alpha) produced a time-dependent induction of both mRNA and protein expression for EGR-1. This FP receptor-mediated induction of EGR-1 expression involved activation of the small GTPase Ras followed by activation of C-Raf and the mitogen-activated protein (MAP) kinase kinases 1 and 2 (MEK1/2). Thus, induction of EGR-1 expression by PGF(2alpha) was blocked using dominant-negative constructs of Ras and C-Raf and the Raf kinase inhibitor 4-(4-(3-(4-chloro-3-trifluoromethylphenyl)ureido)phenoxy)-pyridine-2-carboxyllic acid methyamide-4-methylbenzenesulfonate (BAY43-9006). Likewise, the MEK1/2 inhibitor 2'-amino-3'-methoxyflavone (PD98059) blocked the induction of EGR-1 expression by PGF(2alpha). FP receptor stimulation by PGF(2alpha) induced the phosphorylation of C-Raf, MEK1/2, and extracellular signal-regulated kinases 1 and 2, consistent with the activation of a MAP kinase signaling cascade. PGF(2alpha) was also found to induce the expression of EGR-1 in rat cardiomyocytes through the activation of endogenous FP receptors. This induction of EGR-1 expression in cardiomyocytes also involved the activation of Raf and MAP kinase signaling and was dependent on the activation of protein kinase C. This is the first report to show the regulation of EGR-1 expression after PGF(2alpha) activation of FP receptors and suggests that this could be an early event involved in wound healing and cardiac hypertrophy.


Assessment of the financial implications for laparoscopic liver surgery: a single-centre UK cost analysis for minor and major hepatectomy.
Laparoscopic hepatectomy is progressively gaining popularity. However, it is still unclear whether the laparoscopic approach offers cost advantages compared with the open approach, especially when major hepatectomies are required. Data providing useful insights into the costs of the laparoscopic approach for clinicians and hospitals are needed. The aim of this study is to assess the financial implications of the laparoscopic approach for two standardized minor and major hepatectomies: left lateral sectionectomy and right hepatectomy. A cost comparison analysis of patients undergoing laparoscopic right hepatectomy (LRH) and laparoscopic left lateral sectionectomy (LLLS) versus the open counterparts was performed. Data considered for the comparison analysis were operative costs (theatre cost, consumables and surgeon/anaesthetic labour cost), postoperative costs (hospital stay, complication management and readmissions) and overall costs. A total of 149 patients were included: 38 patients underwent LRH and 46 open right hepatectomy (ORH); 46 patients underwent LLLS and 19 open left lateral sectionectomy (OLLS). For LRH the mean operative, postoperative and overall costs were £10,181, £4,037 and £14,218; for ORH the mean operative, postoperative and overall costs were £6,483 (p < 0.0001), £10,304 (p < 0.0001) and £16,787 (p = 0.886). Regarding LLLS, the mean operative, postoperative and overall costs were £5,460, £2,599 and £8,059; for OLLS the mean operative, postoperative and overall costs were £5,841 (p = 0.874), £5,796 (p < 0.0001) and £11,637 (p = 0.0001). Our data support the cost advantage of the laparoscopic approach for left lateral sectionectomy and the cost neutrality for right hepatectomy.


Optoelectronic detection of millimetre-wave signals with travelling-wave uni-travelling carrier photodiodes.
Optically pumped mixing in travelling-wave uni-travelling carrier photodiodes is proposed as a novel technique for detecting millimetre-wave signals. An experimental demonstration was performed at a frequency of 100 GHz. From DC measurements, an increase in the responsivity was found at high levels of optical power. The mixing mechanism is attributed to the variation of the responsivity with the applied reverse bias and the optical input power. The maximum intermediate frequency power was found to be -35 dBm for a 4 dBm radio frequency power, while an average conversion loss of 40 dB was achieved. A wide dynamic range of more than 42 dB was measured, limited by the maximum available millimetre-wave power.


Molecular profile of ductal carcinoma in situ of the breast in BRCA1 and BRCA2 germline mutation carriers.
Ductal carcinoma in situ (DCIS) is an established late precursor of sporadic invasive breast cancer and to a large extent parallels its invasive counterpart with respect to molecular changes and immunophenotype. Invasive breast cancers in germline BRCA1 and BRCA2 mutation carriers have a distinct "basal" and "luminal" immunophenotype, respectively, but the immunophenotype of their precursor lesions has hardly been studied, and this was the aim of this study. DCIS lesions of 25 proven BRCA1 and 9 proven BRCA2 germline mutation carriers and their 22 and 6, respectively, accompanying invasive lesions were stained by immunohistochemistry for oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER)2/neu, cytokeratin (CK)5/6, CK14, epidermal growth factor receptor (EGFR) and Ki67. DCIS lesions in BRCA1 mutation carriers were mostly of the basal molecular type with low ER/PR/HER2 expression, while they frequently expressed CK5/6, CK14 and EGFR, and were mostly grade 3 and highly proliferative. DCIS lesions in BRCA2 mutation carriers were mostly of luminal molecular type with frequent expression of ER/PR, and infrequent expression of CK5/6, CK14 and EGFR, and they were mostly grade 3 and showed low proliferation. In BRCA1 and BRCA2 mutation carriers there was a high concordance between DCIS lesions and their concomitant invasive counterpart with regard to expression of individual markers as well as "molecular" subtype. Although the number of cases studied was low, DCIS lesions in BRCA1 and BRCA2 mutations carriers are usually of the basal and luminal molecular type, respectively, similar to their accompanying invasive cancers, thereby providing evidence that DCIS is a direct precursor lesion in these hereditary predisposed patients. This also suggests that crucial carcinogenetic events leading to these phenotypes in hereditary predisposed patients occur before the stage of invasion.


Formal homo-Nazarov and other cyclization reactions of activated cyclopropanes.
The Nazarov cyclization of divinyl ketones gives access to cyclopentenones. Replacing one of the vinyl groups by a cyclopropane leads to a formal homo-Nazarov process for the synthesis of cyclohexenones. In contrast to the Nazarov reaction, the cyclization of vinyl-cyclopropyl ketones is a stepwise process, often requiring harsh conditions. Herein, we describe two different approaches for further polarization of the three-membered ring of vinyl-cyclopropyl ketones to allow the formal homo-Nazarov reaction under mild catalytic conditions. In the first approach, the introduction of an ester group α to the carbonyl on the cyclopropane gave a more than tenfold increase in reaction rate, allowing us to extend the scope of the reaction to non-electron-rich aryl donor substituents in the β position to the carbonyl on the cyclopropane. In this case, a proof of principle for asymmetric induction could be achieved using chiral Lewis acid catalysts. In the second approach, heteroatoms, especially nitrogen, were introduced β to the carbonyl on the cyclopropane. In this case, the reaction was especially successful when the vinyl group was replaced by an indole heterocycle. With a free indole, the formal homo-Nazarov cyclization on the C3 position of indole was observed using a copper catalyst. In contrast, a new cyclization reaction on the N1 position was observed with Brønsted acid catalysts. Both reactions were applied to the synthesis of natural alkaloids. Preliminary investigations on the rationalization of the observed regioselectivity are also reported.


The expanded Global Registry of Acute Coronary Events: baseline characteristics, management practices, and hospital outcomes of patients with acute coronary syndromes.
The Global Registry of Acute Coronary Events (GRACE)-a prospective, multinational study of patients hospitalized with acute coronary syndromes (ACSs)-was designed to improve the quality of care for patients with an ACS. Expanded GRACE aims to test the feasibility of a simplified data collection tool and provision of quarterly feedback to index individual hospital management practices to an international reference cohort. We describe the objectives; study design; study and data management; and the characteristics, management, and hospital outcomes of patients > or =18 years old enrolled with a presumptive diagnosis of ACS. From 2001 to 2007, 31,982 patients were enrolled at 184 hospitals in 25 countries; 30% were diagnosed with ST-segment elevation myocardial infarction, 31% with non-ST-segment myocardial infarction, 26% with unstable angina, and 12% with another cardiac/noncardiac final diagnosis. The median age was 65 (interquartile range 55-75) years; 24% were >75 years old, and 33% were women. In general, increases were observed over time across the spectrum of ACS (1) in the use in the first 24 hours and at discharge of aspirin, clopidogrel, beta-blockers, and angiotensin-converting enzyme inhibitors/receptor blockers; (2) in the use at discharge of statins; (3) in the early use of glycoprotein IIb/IIIa inhibitors and low-molecular-weight heparin; and (4) in the use of cardiac catheterization and percutaneous coronary intervention. An increase in the use of primary percutaneous coronary intervention and a similar decrease in the use of fibrinolysis in ST-segment elevation myocardial infarction were also seen. Over the course of 7 years, general increases in the use of evidence-based therapies for ACS patients were observed in the expanded GRACE.


Role of low molecular weight organic acids on pyrite dissolution in aqueous systems: implications for catalytic chromium (VI) treatment.
A systematic study combining batch experiments with spectroscopic analyses was carried out to better understand the effects of various organic acids on pyrite dissolution and subsequent Cr(VI) removal in aqueous systems. Our results suggest that organic acids had no effect on total Fe dissolution from pyrite relative to systems containing no acid. However, while nearly 100% of total Fe dissolved from pyrite was in Fe(II) form in the absence of ligands, the addition of organic acids led to significant oxidation of Fe(II) species to Fe(III). The degree and extent of Fe(II) oxidation increased in the order: tartrate < salicylate < oxalate ≈ citrate < EDTA. Except for salicylate (an aromatic compound), this stimulatory effect observed in Fe(II) oxidation was well correlated with the strength of Fe-ligand complexes. In systems containing Cr(VI), the amount of Fe dissolved increased significantly relative to non-Cr(VI) containing system, and the ligands enhanced the dissolution of surface oxidation products from pyrite. Overall, it is clear that the dissolution of pyrite with organic acids had very little effect on solution phase Cr(VI) removal, but significantly stimulated surface phase Cr(VI) reduction by removing surface oxidation products, and thus creating new surface sites for extended Cr(VI) removal.


Alcohol craving in patients diagnosed with a severe mental illness and alcohol use disorder: bidirectional relationships between approach and avoidance inclinations and drinking.
The current study was undertaken to better understand the craving-drinking relationship among individuals dually diagnosed with a severe mental illness (SMI) and an alcohol use disorder (AUD). Using an ambivalence conceptualization of craving (Breiner, Stritzke, & Lang, 1999), we investigated the bidirectional relationships between desires and behavioral intentions to use (approach inclinations) and not use (avoidance inclinations) alcohol and drinking outcomes in patients diagnosed with an SMI-AUD. Patients (N = 278) seeking outpatient dual diagnosis treatment from a community mental health center were followed longitudinally over the course of 6 months. Assessments at baseline, 2-month, 4-month, and 6-month intervals included approach and avoidance inclinations, alcohol urges, readiness to change, and drinking outcomes. Time-lagged multilevel growth curve modeling found that avoidance inclinations moderated the effect of approach inclinations on subsequent drinking outcomes differentially over time. Specifically, avoidance inclinations attenuated the effect of approach on subsequent heavier drinking levels, and high avoidance/low approach demonstrated significant decreases on levels of drinking over time. Results also indicated that number of drinks consumed and heavy drinking days predicted subsequent approach inclinations differentially over time, such that lower levels of drinking predicted decreases in approach inclinations. Decreases in drinking also predicted higher subsequent avoidance inclinations, which were maintained over time. These findings highlight the complexity of subjective craving responses and the importance of measuring both approach and avoidance inclinations. Among those diagnosed with SMI-AUDs, treatment strategies that increase avoidance inclinations may increase abstinence rates in this difficult-to-treat population.


Endogenous cycles, activity patterns and energy expenditure of an intertidal fish is modified by artificial light pollution at night (ALAN).
The increase of global light emissions in recent years has highlighted the need for urgent evaluation of their impacts on the behaviour, ecology and physiology of organisms. Numerous species exhibit daily cycles or strong scototaxic behaviours that could potentially be influenced if natural lighting conditions or cycles are disrupted. Artificial Light Pollution at Night (ALAN) stands for situations where artificial light alters natural light-dark cycles, as well as light intensities and wavelengths. ALAN is increasingly recognized as a potential threat to biodiversity, mainly because a growing number of studies are demonstrating its influence on animal behaviour, migration, reproduction and biological interactions. Most of these studies have focused on terrestrial organisms and ecosystems with studies on the effects of ALAN on marine ecosystems being more occasional. However, with the increasing human use and development of the coastal zone, organisms that inhabit shallow coastal or intertidal systems could be at increasing risk from ALAN. In this study we measured the levels of artificial light intensity in the field and used these levels to conduct experimental trials to determine the impact of ALAN on an intertidal fish. Specifically, we measured ALAN effects on physiological performance (oxygen consumption) and behaviour (activity patterns) of "Baunco" the rockfish Girella laevifrons, one of the most abundant and ecologically important intertidal fish in the Southeastern Pacific littoral. Our results indicated that individuals exposed to ALAN exhibited increased oxygen consumption and activity when compared with control animals. Moreover, those fish exposed to ALAN stopped displaying the natural (circatidal and circadian) activity cycles that were observed in control fish throughout the experiment. These changes in physiological function and behaviour could have serious implications for the long-term sustainability of fish populations and indirect impacts on intertidal communities in areas affected by ALAN.


Production and processing studies on calpain-system gene markers for tenderness in Brahman cattle: 2. Objective meat quality.
Effects and interactions of calpain-system tenderness gene markers on objective meat quality traits of Brahman (Bos indicus) cattle were quantified within 2 concurrent experiments at different locations. Cattle were selected for study from commercial and research herds at weaning based on their genotype for calpastatin (CAST) and calpain 3 (CAPN3) gene markers for beef tenderness. Gene marker status for mu-calpain (CAPN1-4751 and CAPN1-316) was also determined for inclusion in statistical analyses. Eighty-two heifer and 82 castrated male cattle with 0 or 2 favorable alleles for CAST and CAPN3 were studied in New South Wales (NSW), and 143 castrated male cattle with 0, 1, or 2 favorable alleles for CAST and CAPN3 were studied in Western Australia (WA). The cattle were backgrounded for 6 to 8 mo and grain-fed for 117 d (NSW) or 80 d (WA) before slaughter. One-half the cattle in each experiment were implanted with a hormonal growth promotant during feedlotting. One side of each carcass was suspended from the Achilles tendon (AT) and the other from the pelvis (tenderstretch). The M. longissimus lumborum from both sides and the M. semitendinosus from the AT side were collected; then samples of each were aged at 1 degrees C for 1 or 7 d. Favorable alleles for one or more markers reduced shear force, with little effect on other meat quality traits. The size of effects of individual markers varied with site, muscle, method of carcass suspension, and aging period. Individual marker effects were additive as evident in cattle with 4 favorable alleles for CAST and CAPN3 markers, which had shear force reductions of 12.2 N (P < 0.001, NSW) and 9.3 N (P = 0.002, WA) in AT 7 d aged M. longissimus lumborum compared with those with no favorable alleles. There was no evidence (all P > 0.05) of interactions between the gene markers, or between the hormonal growth promotant and gene markers for any meat quality traits. This study provides further evidence that selection based on the CAST or CAPN3 gene markers improves meat tenderness in Brahman cattle, with little if any detrimental effects on other meat quality traits. The CAPN1-4751 gene marker also improved beef tenderness without affecting other objective meat quality traits in heterozygous cattle compared with homozygotes for the unfavorable allele.


Anion dependent redox changes in iron bis-terdentate nitroxide {NNO} chelates.
The reaction of [Fe(II)(BF(4))(2)]·6H(2)O with the nitroxide radical, 4,4-dimethyl-2,2-di(2-pyridyl) oxazolidine-N-oxide (L(•)), produces the mononuclear transition metal complex [Fe(II)(L(•))(2)](BF(4))(2) (1) which has been investigated using temperature dependent susceptibility, Mössbauer spectroscopy, electrochemistry, density functional theory (DFT) calculations, and X-ray structure analysis. Single crystal X-ray diffraction analysis and Mössbauer measurements reveal an octahedral low spin Fe(2+) environment where the pyridyl donors from L(•) coordinate equatorially while the oxygen containing the radical from L(•) coordinates axially forming a linear O(•)··Fe(II)··O(•) arrangement. Magnetic susceptibility measurements show a strong radical-radical intramolecular antiferromagnetic interaction mediated by the diamagnetic Fe(2+) center. This is supported by DFT calculations which show a mutual spatial overlap of 0.24 and a spin density population analysis which highlights the antiparallel spin alignment between the two ligands. Similarly the monocationic complex [Fe(III)(L(-))(2)](BPh(4))·0.5H(2)O (2) has been fully characterized with Fe-ligand and N-O bond length changes in the X-ray structure analysis, magnetic measurements revealing a Curie-like S = 1/2 ground state, electron paramagnetic resonance (EPR) spectra, DFT calculations, and electrochemistry measurements all consistent with assignment of Fe in the (III) state and both ligands in the L(-) form. 2 is formed by a rare, reductively induced oxidation of the Fe center, and all physical data are self-consistent. The electrochemical studies were undertaken for both 1 and 2, thus allowing common Fe-ligand redox intermediates to be identified and the results interpreted in terms of square reaction schemes.


Hierarchical structural control of visual properties in self-assembled photonic-plasmonic pigments.
We present a simple one-pot co-assembly method for the synthesis of hierarchically structured pigment particles consisting of silica inverse-opal bricks that are doped with plasmonic absorbers. We study the interplay between the plasmonic and photonic resonances and their effect on the visual appearance of macroscopic collections of photonic bricks that are distributed in randomized orientations. Manipulating the pore geometry tunes the wavelength- and angle-dependence of the scattering profile, which can be engineered to produce angle-dependent Bragg resonances that can either enhance or contrast with the color produced by the plasmonic absorber. By controlling the overall dimensions of the photonic bricks and their aspect ratios, their preferential alignment can either be encouraged or suppressed. This causes the Bragg resonance to appear either as uniform color travel in the former case or as sparse iridescent sparkle in the latter case. By manipulating the surface chemistry of these photonic bricks, which introduces a fourth length-scale (molecular) of independent tuning into our design, we can further engineer interactions between liquids and the pores. This allows the structural color to be maintained in oil-based formulations, and enables the creation of dynamic liquid-responsive images from the pigment.


Model-assisted analysis of spatial and temporal variations in fruit temperature and transpiration highlighting the role of fruit development.
Fruit physiology is strongly affected by both fruit temperature and water losses through transpiration. Fruit temperature and its transpiration vary with environmental factors and fruit characteristics. In line with previous studies, measurements of physical and thermal fruit properties were found to significantly vary between fruit tissues and maturity stages. To study the impact of these variations on fruit temperature and transpiration, a modelling approach was used. A physical model was developed to predict the spatial and temporal variations of fruit temperature and transpiration according to the spatial and temporal variations of environmental factors and thermal and physical fruit properties. Model predictions compared well to temperature measurements on mango fruits, making it possible to accurately simulate the daily temperature variations of the sunny and shaded sides of fruits. Model simulations indicated that fruit development induced an increase in both the temperature gradient within the fruit and fruit water losses, mainly due to fruit expansion. However, the evolution of fruit characteristics has only a very slight impact on the average temperature and the transpiration per surface unit. The importance of temperature and transpiration gradients highlighted in this study made it necessary to take spatial and temporal variations of environmental factors and fruit characteristics into account to model fruit physiology.


Good and bad fever.
Fever is considered a key actor of innate immunity aimed to fight infection. A new investigation reports an association of the use of antipyretic drugs with poorer outcome among patients with sepsis. In contrast, high temperature in non-infectious intensive care patients is associated with higher mortality.


Dietary inflammatory index and risk of epithelial ovarian cancer in African American women.
Chronic inflammation has been implicated in the development of epithelial ovarian cancer (EOC); yet the contribution of inflammatory foods and nutrients to EOC risk has been understudied. We investigated the association between the dietary inflammatory index (DII), a novel literature-derived tool to assess the inflammatory potential of one's diet, and EOC risk in African American (AA) women in the African American Cancer Epidemiology Study, the largest population-based case-control study of EOC in AA women to date. The energy-adjusted DII (E-DII) was computed per 1,000 kilocalories from dietary intake data collected through a food frequency questionnaire, which measured usual dietary intake in the year prior to diagnosis for cases or interview for controls. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression for the association between the E-DII and EOC risk. 493 cases and 662 controls were included in the analyses. We observed a 10% increase in EOC risk per a one-unit change in the E-DII (OR = 1.10, 95% CI = 1.03-1.17). Similarly, women consuming the most pro-inflammatory diet had a statistically significant increased EOC risk in comparison to the most anti-inflammatory diet (ORQuartile4/Quartile1 = 1.72; 95% CI = 1.18-2.51). We also observed effect modification by age (p < 0.05), where a strong, significant association between the E-DII and EOC risk was observed among women older than 60 years, but no association was observed in women aged 60 years or younger. Our findings suggest that a more pro-inflammatory diet was associated with an increased EOC risk, especially among women older than 60 years.


Adjuvant therapy of mucosal melanoma.
Mucosal melanoma is a rare subtype of melanoma and associated with extremely poor prognosis. However, standard adjuvant therapy for mucosal melanoma has not been established. Some approaches have been studied to reduce the risk of recurrence in patients. These include adjuvant chemotherapy, immunotherapy, targeted therapy, and radiotherapy (RT). In this review we aim to summarize and evaluate the therapies in development.


Using practice guidelines to allocate medical technologies. An ethics framework.
Clinical practice guidelines are expanding their scope of authority from clinical decision making to collective policy making, and promise to gain ground as resource allocation tools in coming years. A close examination of how guidelines approach patient selection criteria offers insight into their ethical implications when used as resource allocation or rationing instruments. The purposes of this paper are: a) to examine the structure of allocative reasoning found in clinical guidelines; b) to identify the ethical principles implied and compare how guidelines enact these principles with how explicit systems-level rationing exercises and health policy analyses have approached them; and c) to offer some preliminary suggestions for how these ethical issues might be addressed in the process of guideline development. The resulting framework can be used by guideline developers and users to understand and address some of the ethical issues raised by guidelines for the use of scarce technologies.


The mechanism of agonist induced Ca2+ signalling in intact endothelial cells studied confocally in in situ arteries.
In endothelial cells there remain uncertainties in the details of how Ca(2+) signals are generated and maintained, especially in intact preparations. In particular the role of the sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA), in contributing to the components of agonist-induced signals is unclear. The aim of this work was to increase understanding of the detailed mechanism of Ca(2+) signalling in endothelial cells using real time confocal imaging of Fluo-4 loaded intact rat tail arteries in response to muscarinic stimulation. In particular we have focused on the role of SERCA, and its interplay with capacitative Ca(2+) entry (CCE) and ER Ca(2+) release and uptake. We have determined its contribution to the Ca(2+) signal and how it varies with different physiological stimuli, including single and repeated carbachol applications and brief and prolonged exposures. In agreement with previous work, carbachol stimulated a rise in intracellular Ca(2+) in the endothelial cells, consisting of a rapid initial phase, then a plateau upon which oscillations of Ca(2+) were superimposed, followed by a decline to basal Ca(2+) levels upon carbachol removal. Our data support the following conclusions: (i) the size (amplitude and duration) of the Ca(2+) spike and early oscillations are limited by SERCA activity, thus both are increased if SERCA is inhibited. (ii) SERCA activity is such that brief applications of carbachol do not trigger CCE, presumably because the fall in luminal Ca(2+) is not sufficient to trigger it. However, longer applications sufficient to deplete the ER or even partial SERCA inhibition stimulate CCE. (iii) Ca(2+) entry occurs via STIM-mediated CCE and SERCA contributes to the cessation of CCE. In conclusion our data show how SERCA function is crucial to shaping endothelial cell Ca signals and its dynamic interplay with both CCE and ER Ca releases.


Behavioral demonstration of a somatosensory neuroprosthesis.
Tactile sensation is critical for effective object manipulation, but current prosthetic upper limbs make no provision for delivering somesthetic feedback to the user. For individuals who require use of prosthetic limbs, this lack of feedback transforms a mundane task into one that requires extreme concentration and effort. Although vibrotactile motors and sensory substitution devices can be used to convey gross sensations, a direct neural interface is required to provide detailed and intuitive sensory feedback. In light of this, we describe the implementation of a somatosensory prosthesis with which we elicit, through intracortical microstimulation (ICMS), percepts whose magnitude is graded according to the force exerted on the prosthetic finger. Specifically, the prosthesis consists of a sensorized finger, the force output of which is converted into a regime of ICMS delivered to primary somatosensory cortex through chronically implanted multi-electrode arrays. We show that the performance of animals (Rhesus macaques) on a tactile task is equivalent whether stimuli are delivered to the native finger or to the prosthetic finger.


A Biomimetic Nanodecoy Traps Zika Virus To Prevent Viral Infection and Fetal Microcephaly Development.
Zika virus (ZIKV) has emerged as a global health threat due to its unexpected causal link to devastating neurological disorders such as fetal microcephaly; however, to date, no approved vaccine or specific treatment is available for ZIKV infection. Here we develop a biomimetic nanodecoy (ND) that can trap ZIKV, divert ZIKV away from its intended targets, and inhibit ZIKV infection. The ND, which is composed of a gelatin nanoparticle core camouflaged by mosquito medium host cell membranes, effectively adsorbs ZIKV and inhibits ZIKV replication in ZIKV-susceptible cells. Using a mouse model, we demonstrate that NDs significantly attenuate the ZIKV-induced inflammatory responses and degenerative changes and thus improve the survival rate of ZIKV-challenged mice. Moreover, by trapping ZIKV, NDs successfully prevent ZIKV from passing through physiologic barriers into the fetal brain and thereby mitigate ZIKV-induced fetal microcephaly in pregnant mice. We anticipate that this study will provide new insights into the development of safe and effective protection against ZIKV and various other viruses that threaten public health.


The Spa2-related protein, Sph1p, is important for polarized growth in yeast.
The Saccharomyces cerevisiae protein Sph1p is both structurally and functionally related to the polarity protein, Spa2p. Sph1p and Spa2p are predicted to share three 100-amino acid domains each exceeding 30% sequence identity, and the amino-terminal domain of each protein contains a direct repeat common to Homo sapiens and Caenorhabditis elegans protein sequences. sph1- and spa2-deleted cells possess defects in mating projection morphology and pseudohyphal growth. sph1(Delta) spa2(Delta) double mutants also exhibit a strong haploid invasive growth defect and an exacerbated mating projection defect relative to either sph1(Delta) or spa2(Delta) single mutants. Consistent with a role in polarized growth, Sph1p localizes to growth sites in a cell cycle-dependent manner: Sph1p concentrates as a cortical patch at the presumptive bud site in unbudded cells, at the tip of small, medium and large buds, and at the bud neck prior to cytokinesis. In pheromone-treated cells, Sph1p localizes to the tip of the mating projection. Proper localization of Sph1p to sites of active growth during budding and mating requires Spa2p. Sph1p interacts in the two-hybrid system with three mitogen-activated protein (MAP) kinase kinases (MAPKKs): Mkk1p and Mkk2p, which function in the cell wall integrity/cell polarization MAP kinase pathway, and Ste7p, which operates in the pheromone and pseudohyphal signaling response pathways. Sph1p also interacts weakly with STE11, the MAPKKK known to activate STE7. Moreover, two-hybrid interactions between SPH1 and STE7 and STE11 occur independently of STE5, a proposed scaffolding protein which interacts with several members of this MAP kinase module. We speculate that Spa2p and Sph1p may function during pseudohyphal and haploid invasive growth to help tether this MAP kinase module to sites of polarized growth. Our results indicate that Spa2p and Sph1p comprise two related proteins important for the control of cell morphogenesis in yeast.


A Case Report and Literature Review of Eculizumab Withdrawal in Atypical Hemolytic-Uremic Syndrome.
BACKGROUND Recent advances in the treatment of atypical hemolytic-uremic syndrome (aHUS) have resulted to better long-term survival rates for patients with this life-threatening disease. However, many questions remain such as whether or not long-term treatment is necessary in some patients and what are the risks of prolonged therapy. CASE REPORT Here, we discuss the case of a 37-year-old woman with CFH and CD46 genetic abnormalities who developed aHUS with severe renal failure. She was successfully treated with three doses of rituximab and a three month treatment with eculizumab. After eculizumab withdrawal, symptoms of thrombotic micro-angiopathy (TMA) recurred, therefore eculizumab treatment was restarted. The patient exhibited normal renal function and no symptoms of aHUS at one-year follow-up with further eculizumab treatment. CONCLUSIONS This case highlights the clinical challenges of the diagnosis and management of patient with aHUS with complement-mediated TMA involvement. Attention was paid to the consequences of the treatment withdrawal. Exact information regarding genetic abnormalities and renal function associated with aHUS, as well as estimations of the relapse risk and monitoring of complement tests may provide insights into the efficacy of aHUS treatment, which will enable the prediction of therapeutic responses and testing of new treatment options. Improvements in our understanding of aHUS and its causes may facilitate the identification of patients in whom anti-complement therapies can be withdrawn without risk.


Impact of visual impairment on use of community support services by elderly persons: the Blue Mountains Eye Study.
To estimate the impact of visual impairment in older Australians on the use of community support services. In the Blue Mountains Eye Study, 3654 people aged 49 or older were examined- 82.4% of eligible residents in an area west of Sydney, Australia. Presenting and best-corrected visual acuities were measured using a LogMAR chart. Subjects were categorized as having visual impairment if their better eye read 40 or fewer letters (20/40 or worse). Interview data included marital and other socioeconomic status measures, living status (alone or with spouse or other person), use of community support services, reliance on regular help from nonspouse family members or friends, and perceived ability to go out alone. After adjusting for age, gender, education, living status, walking disability, and health-related factors, for each one-line (five-letter) decrease in best-corrected visual acuity, there was a corresponding increase in reliance on community support services (odds ratio [OR], 1.17; 95% confidence interval, [CI] 1.07-1.28) or combined community and family support (OR 1.22; 95% CI, 1.12-1.32). Visually impaired persons were three times as likely to use regular support services provided by the municipality (OR 3.1; 95% CI, 1.8-5.1). A similar increased reliance on regular help from community, nonspouse family members, or friends was found. Visually impaired persons were also much more likely to state that they thought they were unable to go out alone (OR 6.2; 95% CI, 2.6-14.3). The findings were similar when presenting visual acuity was used to define visual impairment or after subjects with walking disabilities were excluded. Visual impairment seemed to have a greater effect on use of community support services in women than in men. After adjustment was made for confounding factors, visual impairment was found to affect significantly and negatively the independence of elderly people, particularly older women. Presenting visual acuity closely approximated best-corrected visual acuity in its impact on the use of community support services.


Concordant and discordant DNA methylation signatures of aging in human blood and brain.
DNA methylation is an epigenetic mark that balances plasticity with stability. While DNA methylation exhibits tissue specificity, it can also vary with age and potentially environmental exposures. In studies of DNA methylation, samples from specific tissues, especially brain, are frequently limited and so surrogate tissues are often used. As yet, we do not fully understand how DNA methylation profiles of these surrogate tissues relate to the profiles of the central tissue of interest. We have adapted principal component analysis to analyze data from the Illumina 450K Human Methylation array using a set of 17 individuals with 3 brain regions and whole blood. All of the top five principal components in our analysis were associated with a variable of interest: principal component 1 (PC1) differentiated brain from blood, PCs 2 and 3 were representative of tissue composition within brain and blood, respectively, and PCs 4 and 5 were associated with age of the individual (PC4 in brain and PC5 in both brain and blood). We validated our age-related PCs in four independent sample sets, including additional brain and blood samples and liver and buccal cells. Gene ontology analysis of all five PCs showed enrichment for processes that inform on the functions of each PC. Principal component analysis (PCA) allows simultaneous and independent analysis of tissue composition and other phenotypes of interest. We discovered an epigenetic signature of age that is not associated with cell type composition and required no correction for cellular heterogeneity.


Oregon hospice chaplains' experiences with patients requesting physician-assisted suicide.
Oregon's Death with Dignity Act (ODDA), which legalized physician-assisted suicide (PAS) for terminally ill individuals, was enacted in 1997. Eighty-six percent of the 171 patients who have died by PAS were enrolled in hospice. To survey hospice chaplains regarding their views on the ODDA and experiences working with patients who request PAS. Single, anonymous, mailed survey. All chaplains affiliated with one of Oregon's 50 hospices. Fifty of 77 hospice chaplains whom we identified (65%) returned the survey. Forty-two percent of respondents opposed the ODDA and 40% supported it. Over half of respondents had, in the previous 3 years, worked with a patient who had made an explicit request for assisted suicide. Conversation with patients around PAS focused on the role of faith and spirituality in this decision, reasons for wanting hastened death, and family concerns or reactions to PAS. Chaplains did not feel that they had a strong influence on the patient's decisions about PAS (mean score of 4 on a 0-10 scale), though three chaplains reported a patient who withdrew their request for PAS because of the chaplain's involvement. Chaplains reported provision of a nonjudgmental presence helped the relationship with the patient. Oregon hospice chaplains are divided in their views on legalized PAS, but primarily see their role to deliver support to patients no matter what the patient's final decision regarding PAS.


Block allograft technique versus standard guided bone regeneration: a randomized clinical trial.
The aim of this randomized clinical trial was to compare the potential of deproteinized bovine bone added to autologous bone or corticocancellous allograft block with or without the addition of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) to regenerate mandibular atrophic ridges. parallel, allocation ratio of 1:1 using a split-mouth model. Eligibility criteria for patients: adult patients; bilateral atrophic edentulous areas in the posterior area of the mandible; a preoperatory cone beam computed tomography scan; and absence of systemic diseases affecting the bone metabolism. Bone graft intervention for control group consisted of bone chips collected with a scraper mixed with deproteinized bovine bone covered with a resorbable membrane. Bone graft intervention for test group consisted of a corticocancellous allograft block, shaped before surgery, and protected with a collagen membrane. In addition, both groups received rhPDGF-BB or a saline solution as control. As primary outcome quantity, bone variation after a 1-year healing period was considered. A p-value of.05 was considered statistically significant. Sixteen patients were enrolled in this trial. A total of 50 implants and 32 bone grafts were placed. All patients concluded the study (no dropouts). Change at 1 year in bone volume was not significantly different between the two groups (p-value = .25). Effect of treatment in terms of change in bone volume at 1 year was not significant (p-value = .89) when saline solution was used while was at limit of significance when rhPDGF-BB was used (p-value = .052). After 1 year, all the implants were successfully integrated. The block allograft and the standard regenerative procedure showed similar results in terms of regenerated bone volume after 1 year of functional loading. The rhPDGF-BB positively influenced soft-tissue healing.


Efficacy of hyaluronic acid on intervertebral disc inflammation: An in vitro study using notochordal cell lines and human disc cells.
Hyaluronic acid (HA) is widely recognized as a therapeutic target and currently used in medicine. However, HA metabolism during intervertebral disc degeneration (IVDD) has not been completely elucidated. This study aimed to evaluate the efficacy of HA on intervertebral disc (IVD) inflammation and identify the main molecules modulating HA degradation in IVDs. To assess HA function in IVD cells in vitro, we treated human disc cells and U-CH1-N cells, a notochordal nucleus pulposus cell line, with HA or hyaluronidase. Real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis showed that tumor necrosis factor alpha (TNF-α)-mediated induction of the expression of TNF-α and cyclooxygenase-2 (COX2) was clearly neutralized by HA treatment, and the expression of TNF-α and COX2 was significantly induced by hyaluronidase treatment in both cell types. Additionally, Western blot analysis showed that hyaluronidase-induced phosphorylation of p38 and Erk1/2, and that TNF-α-mediated phosphorylation of p38 and Erk1/2 was clearly reduced by HA addition. In degenerating human IVD samples, immunohistochemistry for hyaluronidase showed that the expression of hyaluronidases including HYAL1, HYAL2, and cell migration-inducing protein (CEMIP) tended to increase in accordance with IVDD. In particular, HYAL1 showed statistically significant differences. In vitro study also confirmed a similar phenomenon that TNF-α treatment increased both messenger RNA and protein expression in both cell types. Our results demonstrated that HA could potentially suppress IVDD by regulating p38 and Erk1/2 pathways, and that the expression of HYAL1 was correlated with IVDD progression. These findings indicated that HYAL1 would be a potential molecular target for suppressing IVDD by controlling HA metabolism.


Malaria and mosquito net utilisation among schoolchildren in villages with or without healthcare facilities at different altitudes in Iringa District, Tanzania.
The endemicity of malaria in Tanzania is heterogenous, mainly associated with physical factors such as topography, climate and socio-economic status. The contributions of these factors in many regions of Tanzania have not been studied in detail. This study was carried out to determine the prevalence and transmission of malaria and mosquito nets coverage among schoolchildren in relation to altitude in villages with or without healthcare facilities in Iringa District,Tanzania. A cross-sectional survey of schoolchildren was carried out in six villages in three altitude transects (965-2075 m). In each transect a village with and without a healthcare facility were selected. The villages included Idodi (965m), Makifu (985m), Tosamaganga (1561m) Mangalali (1520m) Lulanzi (1917) and Kilolo (2075m). For the purpose of this study, the villages were categorised as lowlands (Idodi and Makifu), intermediate (Tosamaganga and Mangalali) and highlands (Lulanzi and Kilolo. Healthcare facilities were available at Idodi,Tosamaganga and Kilolo. Each child was asked whether or not slept under a mosquito net during the previous night. Mosquitoes were collected using pyrethrum spray catch technique in ten houses in each study village. Blood smears from a total of 1643 schoolchildren (mean age = 5.9-12.3 years) were examined for malaria infection. Plasmodium falciparum accounted for 93.1% of the malaria parasites. The prevalence of P. falciparum among children in Idodi, Makifu, Mangalali,Tosamaganga, was 51.51%, 73.66%, 22.79%, and 14.83%, respectively. Malaria parasites were not found among children in the highland villages of Lulanzi and Kilolo). The prevalence of malaria parasitaemia, packed cell volume, geometric mean parasite density and spleen rates were higher in children living in villages without healthcare facilities (P<0.001). Of the children, 16.1% (264/1643) slept under a mosquito net during the previous night. About three quarters (253/344) of the schoolchildren who had malaria parasites were not using mosquito nets. Mosquito net coverage was higher in lowland villages, accounting for 61.7% (163/264) of the total net use in the district. The majority (75.5%) of the mosquito net users were from village with health facilities (P<0.001). A total of 228 mosquitoes were collected, with Anopheles gambiae s.l. accounting for the majority (53.5%). Overall, 8.7% of the An. gambiae s.l. were infected with malaria sporozoites. Higher sporozoite rates were observed in mosquitoes collected in the lowlands. Communities living in areas without health facilities form the largest proportion of malaria-infected populations in Iringa district. Availability of healthcare service has an influence on mosquito net coverage. The results provide more evidence of the existence of a relationship between altitude variability or accessibility to healthcare services, and the burden of malaria in rural communities of Tanzania.


Quantifying the strength of the associations of prototype perceptions with behaviour, behavioural willingness and intentions: a meta-analysis.
Prototypes (i.e., social images representing perceptions of typical persons engaging in or refraining from certain behaviour) have been shown to explain health-related behaviours. The present meta-analysis quantified the strength of the associations of prototype perceptions with health motivation and behaviour. Specifically, the analysis addressed (i) the relationship of prototype favourability (i.e., degree of likability) and similarity (i.e., perceived resemblance to the self) with behaviour, willingness and intentions; (ii) the effect of the interaction between favourability and similarity; and (iii) the extent to which health-risk and health-protective prototypes differed in their association with these outcomes. A total of 80 independent studies were identified based on 69 articles. The results indicated that prototype favourability and similarity were related to behaviour, intentions and willingness with small-to-medium effect sizes (r+ = 0.12-0.43). Direct measures of prototype perceptions generally produced larger effects than indirect measures. The interaction between favourability and similarity produced small-to-large effect sizes (r+ = .22-.54). The results suggest that both health-risk and health-protective prototypes might be useful targets for interventions (r+ = .22-.54). In order to increase health-protective behaviours, intentions and behaviour could be targeted by increasing similarity to health-protective prototypes. Health-risk behaviour might be decreased by targeting willingness by modifying health-risk prototype favourability and similarity.


Task-based evaluation of a 4D MAP-RBI-EM image reconstruction method for gated myocardial perfusion SPECT using a human observer study.
We evaluated the performance of a new 4D image reconstruction method for improved 4D gated myocardial perfusion (MP) SPECT using a task-based human observer study. We used a realistic 4D NURBS-based Cardiac-Torso (NCAT) phantom that models cardiac beating motion. Half of the population was normal; the other half had a regional hypokinetic wall motion abnormality. Noise-free and noisy projection data with 16 gates/cardiac cycle were generated using an analytical projector that included the effects of attenuation, collimator-detector response, and scatter (ADS), and were reconstructed using the 3D FBP without and 3D OS-EM with ADS corrections followed by different cut-off frequencies of a 4D linear post-filter. A 4D iterative maximum a posteriori rescaled-block (MAP-RBI)-EM image reconstruction method with ADS corrections was also used to reconstruct the projection data using various values of the weighting factor for its prior. The trade-offs between bias and noise were represented by the normalized mean squared error (NMSE) and averaged normalized standard deviation (NSDav), respectively. They were used to select reasonable ranges of the reconstructed images for use in a human observer study. The observers were trained with the simulated cine images and were instructed to rate their confidence on the absence or presence of a motion defect on a continuous scale. We then applied receiver operating characteristic (ROC) analysis and used the area under the ROC curve (AUC) index. The results showed that significant differences in detection performance among the different NMSE-NSDav combinations were found and the optimal trade-off from optimized reconstruction parameters corresponded to a maximum AUC value. The 4D MAP-RBI-EM with ADS correction, which had the best trade-off among the tested reconstruction methods, also had the highest AUC value, resulting in significantly better human observer detection performance when detecting regional myocardial wall motion abnormality. We concluded that the NMSE-NSDav trade-off was shown to agree with observer performance for the detection task of the regional motion abnormality, and the optimized 4D MAP-RBI-EM method with ADS corrections provides significant improvement compared to 3D FBP and 3D OS-EM with ADS corrections in detecting regional myocardial wall motion abnormali in 4D gated MP SPECT.


Influence of optic disc-fovea distance on macular thickness measurements with OCT in healthy myopic eyes.
Assessment of macular thickness is important in the evaluation of various eye diseases. This study aimed to determine the influence of the optic disc-fovea distance (DFD) on macular thickness in myopic eyes. We determined the DFD and the macular thickness in 138 eyes from 138 healthy myopic subjects using the Cirrus HD-OCT. Correlation analysis and multiple linear regression were performed to determine the influence of DFD, axial length, disc area, and β-PPA on macular thickness. To further remove the confounding effect of ocular magnification on the DFD and OCT scan area, a subgroup analysis was performed in eyes with a limited axial length range (24-25 mm). DFD was significantly correlated with both regional (central, inner, and outer ETDRS subfields) and overall average macular thickness at a Bonferroni corrected P value of 0.004 (r ranging from -0.27 to -0.47), except for the temporal outer (r = -0.15, P = 0.089) and inferior outer (r = -0.22, P = 0.011) macular thickness. In the multivariable analysis, DFD was significantly associated with the average inner and outer macular thickness, the central subfield thickness, and the overall macular thickness (all P < 0.001), independent of ocular magnification and other covariates. Our findings indicate that eyes with a greater DFD have a lower macular thickness.


Altered pattern of circulating miRNAs in HIV lipodystrophy perturbs key adipose differentiation and inflammation pathways.
We identified a microRNA (miRNA) profile characterizing HIV lipodystrophy and explored the downstream mechanistic implications with respect to adipocyte biology and the associated clinical phenotype. miRNA profiles were extracted from small extracellular vesicles (sEVs) of HIV-infected individuals with and without lipodystrophic changes and individuals without HIV, among whom we previously showed significant reductions in adipose Dicer expression related to HIV. miR-20a-3p was increased and miR-324-5p and miR-186 were reduced in sEVs from HIV lipodystrophic individuals. Changes in these miRNAs correlated with adipose Dicer expression and clinical markers of lipodystrophy, including fat redistribution, insulin resistance, and hypertriglyceridemia. Human preadipocytes transfected with mimic miR-20a-3p, anti-miR-324-5p, or anti-miR-186 induced consistent changes in latent transforming growth factor beta binding protein 2 (Ltbp2), Wisp2, and Nebl expression. Knockdown of Ltbp2 downregulated markers of adipocyte differentiation (Fabp4, Pparγ, C/ebpa, Fasn, adiponectin, Glut4, CD36), and Lamin C, and increased expression of genes involved in inflammation (IL1β, IL6, and Ccl20). Our studies suggest a likely unique sEV miRNA signature related to dysregulation of Dicer in adipose tissue in HIV. Enhanced miR-20a-3p or depletion of miR-186 and miR-324-5p may downregulate Ltbp2 in HIV, leading to dysregulation in adipose differentiation and inflammation, which could contribute to acquired HIV lipodystrophy and associated metabolic and inflammatory perturbations.


Diphtheria toxin-murine granulocyte-macrophage colony-stimulating factor-induced hepatotoxicity is mediated by Kupffer cells.
DT388GMCSF, a fusion toxin composed of the NH2-terminal region of diphtheria toxin (DT) fused to human granulocyte-macrophage colony-stimulating factor (GMCSF) has shown efficacy in the treatment of acute myeloid leukemia. However, the primary dose-limiting side effect is liver toxicity. We have reproduced liver toxicity in rats using the rodent cell-tropic DT-murine GMCSF (DT390mGMCSF). Serum aspartate aminotransferase and alanine aminotransferase were elevated 15- and 4-fold, respectively, in DT390mGMCSF-treated rats relative to controls. Histologic analysis revealed hepatocyte swelling; however, this did not lead to hepatic necrosis or overt histopathologic changes in the liver. Immunohistochemical staining showed apoptotic cells in the sinusoids, and depletion of cells expressing the monocyte/macrophage markers, ED1 and ED2, indicating that Kupffer cells (KC) are targets of DT390mGMCSF. In contrast, sinusoidal endothelial cells seemed intact. In vitro, DT390mGMCSF was directly cytotoxic to primary KC but not hepatocytes. Two related fusion toxins, DT388GMCSF, which targets the human GMCSF receptor, and DT390mIL-3, which targets the rodent IL-3 receptor, induced a less than 2-fold elevation in serum transaminases and did not deplete KC in vivo. In addition, DTU2mGMCSF, a modified form of DT390mGMCSF with enhanced tumor cell specificity, was not hepatotoxic and was significantly less toxic to KC in vivo and in vitro. These results show that DT390mGMCSF causes liver toxicity by targeting KC, and establish a model for studying how this leads to hepatocyte injury. Furthermore, alternative fusion toxins with potentially reduced hepatotoxicity are presented.


Further development of an instrument to assess psychological flexibility in people with chronic pain.
Recently, an expansion of traditional coping models for chronic pain has been offered. This model specifically includes acceptance of chronic pain, as well as the more general process of psychological flexibility. Psychological flexibility includes qualities of behavior such as acceptance and mindfulness, and the capacity to take committed and values-directed or goals-directed action, among other qualities. The present study was intended to refine and validate a measure of psychological flexibility, titled the Brief Pain Response Inventory (BPRI), and determine its relation with key indices of patient functioning. In total, 205 adults with chronic pain who were beginning a program of treatment completed a battery of self-report questionnaires. Exploratory factor analysis indicated the presence of two factors within the items of the BPRI: Flexible Action and Willing Engagement. Subscale and total scores were generally unrelated with patient background variables, although they were related to, and accounted for significant variance in, measures of emotional, physical, and psychosocial functioning. These analyses provide additional support for the relevance of psychological flexibility to the problem of chronic pain, as well as initial evidence for the BPRI as a measure of this process.


Fetal and neonatal alloimmune thrombocytopenia: harvesting the evidence to develop a clinical approach to management.
Neonatal alloimmune thrombocytopenia (NAIT) is the most common cause of severe thrombocytopenia in an otherwise healthy newborn. The most serious complication is intracranial hemorrhage, which can occur either in the fetus or the newborn. Despite the known serious sequelae, both antenatal management and neonatal treatment modalities are plagued by the lack of gold standard evidence to appropriately direct therapy. Maternal, risk-based therapeutic approaches range from invasive protocols to relatively benign noninvasive strategies to avoid serious procedural complications. Intravenous immunoglobulin (IVIG) with or without steroids and fetal blood sampling constitute the mainstay of antenatal management. Neonatal interventions principally focus on the use of antigen-negative compatible or random donor platelets and IVIG. While awaiting the results of controlled trials, each institution must develop a standardized, collaborative, multidisciplinary approach to the screening, diagnostic evaluation, and management of unexpected and anticipated NAIT based on experience, product availability, and emerging scientific data.


An on-demand coherent single-electron source.
We report on the electron analog of the single-photon gun. On-demand single-electron injection in a quantum conductor was obtained using a quantum dot connected to the conductor via a tunnel barrier. Electron emission was triggered by the application of a potential step that compensated for the dot-charging energy. Depending on the barrier transparency, the quantum emission time ranged from 0.1 to 10 nanoseconds. The single-electron source should prove useful for the use of quantum bits in ballistic conductors. Additionally, periodic sequences of single-electron emission and absorption generate a quantized alternating current.


Modulation of network excitability by persistent activity: how working memory affects the response to incoming stimuli.
Persistent activity and match effects are widely regarded as neuronal correlates of short-term storage and manipulation of information, with the first serving active maintenance and the latter supporting the comparison between memory contents and incoming sensory information. The mechanistic and functional relationship between these two basic neurophysiological signatures of working memory remains elusive. We propose that match signals are generated as a result of transient changes in local network excitability brought about by persistent activity. Neurons more active will be more excitable, and thus more responsive to external inputs. Accordingly, network responses are jointly determined by the incoming stimulus and the ongoing pattern of persistent activity. Using a spiking model network, we show that this mechanism is able to reproduce most of the experimental phenomenology of match effects as exposed by single-cell recordings during delayed-response tasks. The model provides a unified, parsimonious mechanistic account of the main neuronal correlates of working memory, makes several experimentally testable predictions, and demonstrates a new functional role for persistent activity.


Residential and school greenspace and academic performance: Evidence from the GINIplus and LISA longitudinal studies of German adolescents.
Few studies have reported the association between greenspace and academic performance at school level. We examined associations between both residential and school greenspace and individual school grades in German adolescents. German and maths grades from the latest school certificate, residential and school greenspace, and covariates were available for 1351 10 and 15 years old Munich children and 1078 Wesel children from two German birth cohorts - GINIplus and LISA. Residential and school greenspace was assessed by the Normalized Difference Vegetation Index (NDVI), tree cover, and (in Munich only) proportion of agricultural land, forest, and urban green space in 500-m and 1000-m circular buffers. Longitudinal associations between each exposure-outcome pair were assessed by logistic mixed effects models with person and school as random intercepts and adjusted for potential confounders. No associations were observed between any of the greenspace variables and grades in Wesel children. Several statistically significant associations were observed with German and maths grades in Munich children, however associations were inconsistent across sensitivity analyses. There is no evidence of an association of higher greenspace at residence, school or combined with improved academic performance in German adolescents from the GINIplus and LISA longitudinal studies.


The unique paired retinal vascular pattern in marsupials: structural, functional and evolutionary perspectives based on observations in a range of species.
In the few marsupial species studied to date that possess a retinal vasculature, the arterial and venous segments, down to the smallest calibre capillaries, have been shown to occur in pairs. It is a pattern seen in the marsupial central nervous system (CNS) but not in other tissues in this group or in any tissues in eutherian mammals. The aim of the present study was to investigate the presence of retinal vessels in a range of non-eutherian mammalian species (marsupials and monotremes) and to determine if the pattern of paired vessels was a widespread phenomenon within this animal group. Species studied included a monotreme, the short-billed echidna (Tachyglossus aculeatus) and a range of Australian marsupials, the honey possum (Tarispedidae rostratus), fat-tailed dunnart (Sminthopsis crassicaudata), grey-bellied dunnart (Sminthopsis griseoventer), numbat (Myrmecobius fasciatus), broad-footed marsupial mouse (Antechinus godmani) and the North American opossum (Didelphis virginiana). Eyes were fixed in glutaraldehyde or paraformaldehyde and retinas were embedded in resin for light and electron microscopic analysis. Examination revealed that in those species with retinal vessels (fat-tailed dunnart, grey-bellied dunnart, numbat, marsupial mouse, North American opossum) the pattern of vessels differs from the conventional plexus-like arrangement of mammalian retinal vasculature (that is, anastomotic networks of capillaries between arterioles and venules). In marsupials retinal vessels always occur in closely related pairs, with the arteriolar limb usually situated on the vitread aspect. Vessels penetrate the retina and branch to form layers of paired capillaries as far as the outer nuclear layer in some species. The capillaries form blind-ended hairpin loops and display classical morphological features of CNS capillaries The phylogenetic relations of this vascular pattern in the marsupial CNS and retina, and in the CNS of a few other classes of non-mammalian vertebrates, suggest that retinal vascularisation may have evolved independently in marsupial and eutherian mammals and that the former may have evolved from a common primitive mammal-like reptilian ancestor which possessed paired vasculature in the CNS. Eutherian mammals may have evolved from an ancestor with anastomotic networks in the CNS or this pattern may have evolved later in eutherian mammal evolutionary radiation. The possible functional and physiological significance of the paired vessels is discussed.


A Patient Safety Educational Tool for Patients With Chronic Kidney Disease: Development and Usability Study.
Chronic kidney disease (CKD) is a health condition that threatens patient safety; however, few interventions provide patient-centered education about kidney-specific safety hazards. We sought to develop and test the usability of a mobile tablet-based educational tool designed to promote patient awareness of relevant safety topics in CKD. We used plain language principles to develop content for the educational tool, targeting four patient-actionable safety objectives that are relevant for individuals with CKD. These four objectives included avoidance of nonsteroidal anti-inflammatory drugs (NSAIDs); hypoglycemia awareness (among individuals with diabetes); temporary cessation of certain medications during acute volume depletion to prevent acute kidney injury (ie, "sick day protocol"); and contrast dye risk awareness. Our teaching strategies optimized human-computer interaction and content retention using audio, animation, and clinical vignettes to reinforce themes. For example, using a vignette of a patient with CKD with pain and pictures of common NSAIDs, participants were asked "Which of the following pain medicines are safe for Mr. Smith to take for his belly pain?" Assessment methods consisted of preknowledge and postknowledge surveys, with provision of correct responses and explanations. Usability testing of the tablet-based tool was performed among 12 patients with any stage of CKD, and program tasks were rated upon completion as no error, noncritical error (self-corrected), or critical error (needing assistance). The 12 participants in this usability study were predominantly 65 years of age or older (n=7, 58%) and female (n=7, 58%); all participants owned a mobile device and used it daily. Among the 725 total tasks that the participants completed, there were 31 noncritical errors (4.3%) and 15 critical errors (2.1%); 1 participant accounted for 30 of the total errors. Of the 12 participants, 10 (83%) easily completed 90% or more of their tasks. Most participants rated the use of the tablet as very easy (n=7, 58%), the activity length as "just right" (rather than too long or too short) (n=10, 83%), and the use of clinical vignettes as helpful (n=10, 83%); all participants stated that they would recommend this activity to others. The median rating of the activity was 8 on a scale of 1 to 10 (where 10 is best). We incorporated all participant recommendations into the final version of the educational tool. A tablet-based patient safety educational tool is acceptable and usable by individuals with CKD. Future studies leveraging iterations of this educational tool will explore its impact on health outcomes in this high-risk population.


Effect of immersion in CO2-enriched water on free radical release and total antioxidant status in peripheral arterial occlusive disease.
The aim of this paper was to investigate the release of oxygen free radicals in patients with peripheral occlusive arterial disease and the effects of immersion of the legs and feet in carbon dioxide (CO(2))-enriched water. Twenty-five patients with peripheral occlusive arterial disease (Fontaine stage II) and 15 healthy controls were treated by immersing the lower legs in either CO(2)-enriched or normal spa water. Blood samples were collected in heparinized tubes and total antioxidant status (TAS) and reactive oxygen metabolites (ROMs) were measured after five treatments a week for two weeks. d-ROM plasma levels decreased in patients with peripheral occlusive disease after immersion in CO(2)-enriched water (P<0.001), and in healthy controls (P<0.01), in line with a significant increase in TAS (P<0.001). CO(2)-enriched water immersion had a positive effect, reducing free radical plasma levels and raising the levels of antioxidants, suggesting an improvement in the microcirculation.


An automated quantitative analysis of cell, nucleus and focal adhesion morphology.
Adherent cells sense the physical properties of their environment via focal adhesions. Improved understanding of how cells sense and response to their physical surroundings is aided by quantitative evaluation of focal adhesion size, number, orientation, and distribution in conjunction with the morphology of single cells and the corresponding nuclei. We developed a fast, user-friendly and automated image analysis algorithm capable of capturing and characterizing these individual components with a high level of accuracy. We demonstrate the robustness and applicability of the algorithm by quantifying morphological changes in response to a variety of environmental changes as well as manipulations of cellular components of mechanotransductions. Finally, as a proof-of-concept we use our algorithm to quantify the effect of Rho-associated kinase inhibitor Y-27632 on focal adhesion maturation. We show that a decrease in cell contractility leads to a decrease in focal adhesion size and aspect ratio.


Robustness of surrogates of biodiversity in marine benthic communities.
The usefulness of surrogates to estimate complex variables describing community structure, such as the various components of biodiversity, is long established. Most attention has been given to surrogates of species richness and species diversity and has focused on identifying a subset of taxa as a surrogate of total community richness or diversity. In adopting a surrogate measure, it is assumed that the relationship between the surrogate(s) and total richness or diversity is consistent in both space and time. These assumptions are rarely examined explicitly. We examined the robustness of potential surrogates of familial richness and multivariate community structure for macrofauna communities inhabiting artificial kelp holdfasts by comparing among communities of dissimilar ages and among communities established at different times of the year. This is important because most benthic "landscapes" will be a mosaic of patches reflecting different intensities, frequencies, and timing of disturbances. The total abundance of organisms and familial richness of crustaceans or polychaetes were all good predictors of total familial richness (R2 > 0.68). In contrast, while the familial richness of other groups, such as mollusks and echinoderms, were well correlated with total familial richness for communities at an early stage of development, the strength of these relationships declined with community age. For multivariate community structure, carefully selected subsets of approximately 10% of the total taxa yielded similar patterns to the total suite of taxa, irrespective of the age of the community. Thus, useful surrogates of both familial richness and multivariate community structure can be identified for this type of community. However, the choice of technique for selecting surrogate taxa largely depends on the nature of the pilot data available, and careful selection is required to ensure that surrogates perform consistently across different-aged communities. While the specific taxa selected as surrogates will vary among different communities, and possibly even among similar communities at different sites, the techniques and the concepts we address are applicable to any community type.


Active control of residual tool marks for freeform optics functionalization by novel biaxial servo assisted fly cutting.
The inherent residual tool marks (RTM) with particular patterns highly affect optical functions of the generated freeform optics in fast tool servo or slow tool servo (FTS/STS) diamond turning. In the present study, a novel biaxial servo assisted fly cutting (BSFC) method is developed for flexible control of the RTM to be a functional micro/nanotexture in freeform optics generation, which is generally hard to achieve in FTS/STS diamond turning. In the BSFC system, biaxial servo motions along the z-axis and side-feeding directions are mainly adopted for primary surface generation and RTM control, respectively. Active control of the RTM from the two aspects, namely, undesired effect elimination or effective functionalization, are experimentally demonstrated by fabricating a typical F-theta freeform surface with scattering homogenization and two functional microstructures with imposition of secondary phase gratings integrating both reflective and diffractive functions.


Activation of the RpoN-RpoS regulatory pathway during the enzootic life cycle of Borrelia burgdorferi.
The maintenance of Borrelia burgdorferi in its complex tick-mammalian enzootic life cycle is dependent on the organism's adaptation to its diverse niches. To this end, the RpoN-RpoS regulatory pathway in B. burgdorferi plays a central role in microbial survival and Lyme disease pathogenesis by up- or down-regulating the expression of a number of virulence-associated outer membrane lipoproteins in response to key environmental stimuli. Whereas a number of studies have reported on the expression of RpoS and its target genes, a more comprehensive understanding of when activation of the RpoN-RpoS pathway occurs, and when induction of the pathway is most relevant to specific stage(s) in the life cycle of B. burgdorferi, has been lacking. Herein, we examined the expression of rpoS and key lipoprotein genes regulated by RpoS, including ospC, ospA, and dbpA, throughout the entire tick-mammal infectious cycle of B. burgdorferi. Our data revealed that transcription of rpoS, ospC, and dbpA is highly induced in nymphal ticks when taking a blood meal. The RpoN-RpoS pathway remains active during the mammalian infection phase, as indicated by the sustained transcription of rpoS and dbpA in B. burgdorferi within mouse tissues following borrelial dissemination. However, dbpA transcription levels in fed larvae and intermolt larvae suggested that an additional layer of control likely is involved in the expression of the dbpBA operon. Our results also provide further evidence for the downregulation of ospA expression during mammalian infection, and the repression of ospC at later phases of mammalian infection by B. burgdorferi. Our study demonstrates that the RpoN-RpoS regulatory pathway is initially activated during the tick transmission of B. burgdorferi to its mammalian host, and is sustained during mammalian infection.


Phase 2 study of idarubicin in pediatric brain tumors: Pediatric Oncology Group study POG 9237.
Idarubicin (IDA), the 4-demethoxy analog of daunomycin, has had significant cytotoxicity in many malignancies. In previous reports, the alcohol metabolite of IDA, 4-demethoxydaunorubicinol (idarubicinol, or IDOL), had cytotoxic activity and the ability to penetrate the blood-brain barrier. For this reason, the Pediatric Oncology Group conducted a Phase 2 trial of IDA for children with recurrent or progressive brain tumors. Ninety-one eligible children were entered on this study, with ages ranging from 3 months to 19 years. Patients were stratified by tumor types into 6 categories: stratum 1, low-grade astrocytoma; stratum 2, malignant glioma (glioblastoma multiforme and anaplastic astrocytoma); stratum 3, medulloblastoma; stratum 4, brainstem glioma; stratum 5, ependymoma; and stratum 6, miscellaneous malignant tumors not included in the previous diagnoses. IDA(18 mg/m2) was infused over 4 h and followed by granulocyte colony-stimulating factor (G-CSF) beginning day 5 after infusion of IDA. G-CSF was continued until blood cell count recovery. Cycles were repeated at approximately 21-day intervals until patients developed progressive disease or had completed 6 cycles with stable or improved disease. Pharmacokinetic plasma and cerebrospinal fluid (CSF) samples were collected from a subset of these patients. Response was poor in all strata. Most patients developed progressive disease; however, in 21 patients with medulloblastoma there was 1 partial response, and 6 patients had stable disease (SD) that in 4 patients lasted more than 20 weeks. Grades 3/4 hematopoietic toxicities were the most common toxic events, and 14 infection-related events resulted in hospitalization of patients. Only 1 patient developed reduced cardiac function. The systemic clearance data for IDA and IDOL were nearly identical to those published on patients with leukemia, and the plasma elimination of the IDOL metabolite was substantially longer than that of the parent drug IDA. The peak CSF:plasma ratios of IDA and IDOL were very low. The overall response rates to IDA were disappointing despite periods of prolonged SD in nearly a fourth of the patients. We conclude from this data and from that in nonhuman primates that it is unlikely that IDA, daunomycin, or other related anthracyclines will be useful for treating primary CNS tumors.


An early warning system for Crimean-Congo haemorrhagic fever seasonality in Turkey based on remote sensing technology.
In the last few years, Crimean-Congo haemorrhagic fever (CCHF) has been reported as an emerging tickborne disease in Turkey. This paper deals with the preparation of an early warning system, aimed to predict the beginning of the CCHF season in Turkey based on a clear, simple and repeatable remotely-sensed signal. Decadal (mean of 10 days) values of the normalized difference vegetation index (NDVI) at 1 km resolution were used on a set of 952 confirmed, accurately geo-referenced, clinical cases between 2003 and 2006. A prerequisite is that the signal should be observable between 2 and 3 decadals before a given moment of the season to be of value as early warning. Decadals marking the 10th percentile or the 25th quartile in the frequency distribution of case reporting were selected as markers for the beginning of season of risk. Neither raw nor accumulated decadal NDVI signals were able to predict the onset of this season. However, when we defined the NDVI anomaly (NDVIa) as the positive difference between decadal NDVI values and the average for the previous year, this standardized measure gave a homogeneous overview of the changes in the NDVI signal producing a NDVIa slope for the decadals 10 to 13 that was always greater than 0. We conclude that observing this slope over time can be used as an early-warning system as it would predict the build-up of the number of cases 20 days in advance with an accuracy of 82% (10th percentile) or 98% (25th quartile).


The Rooibos Benefit Sharing Agreement-Breaking New Ground with Respect, Honesty, Fairness, and Care.
The 1992 Convention on Biological Diversity (CBD) and its 2010 Nagoya Protocol brought about a breakthrough in global policy making. They combined a concern for the environment with a commitment to resolving longstanding human injustices regarding access to, and use of biological resources. In particular, the traditional knowledge of indigenous communities was no longer going to be exploited without fair benefit sharing. Yet, for 25 years after the adoption of the CBD, there were no major benefit sharing agreements that led to significant funding streams for indigenous communities. This changed with the signing of the Rooibos Benefit Sharing Agreement in South Africa, described in this paper. As the authors report, the Rooibos Agreement is a superlative in two respects. It is the biggest benefit sharing agreement between industry and indigenous peoples to date. It is also the first industry-wide agreement to be formed in accordance with biodiversity legislation. This article is a co-production between traditional knowledge holders, the lawyer who represented their interests, the Co-Chair of the Nagoya Protocol negotiations, and an ethicist who analyzed the major challenges of this historic agreement. With no precedent in the benefit sharing world, the agreement stands as a concrete example of the 'art of the possible.' Although the rooibos case is unique in a number of aspects, the experience offers many transferable insights, including: patience; incrementalism; honesty; trust; genuine dialogue; strong legal support; a shared recognition that a fair, win-win deal is possible; government leadership; and unity amongst indigenous peoples. Such ingredients of success can apply well beyond southern Africa.


Effects of meditation experience on functional connectivity of distributed brain networks.
This study sought to examine the effect of meditation experience on brain networks underlying cognitive actions employed during contemplative practice. In a previous study, we proposed a basic model of naturalistic cognitive fluctuations that occur during the practice of focused attention meditation. This model specifies four intervals in a cognitive cycle: mind wandering (MW), awareness of MW, shifting of attention, and sustained attention. Using subjective input from experienced practitioners during meditation, we identified activity in salience network regions during awareness of MW and executive network regions during shifting and sustained attention. Brain regions associated with the default mode were active during MW. In the present study, we reasoned that repeated activation of attentional brain networks over years of practice may induce lasting functional connectivity changes within relevant circuits. To investigate this possibility, we created seeds representing the networks that were active during the four phases of the earlier study, and examined functional connectivity during the resting state in the same participants. Connectivity maps were then contrasted between participants with high vs. low meditation experience. Participants with more meditation experience exhibited increased connectivity within attentional networks, as well as between attentional regions and medial frontal regions. These neural relationships may be involved in the development of cognitive skills, such as maintaining attention and disengaging from distraction, that are often reported with meditation practice. Furthermore, because altered connectivity of brain regions in experienced meditators was observed in a non-meditative (resting) state, this may represent a transference of cognitive abilities "off the cushion" into daily life.


Incidence and risk factors for dysphagia after anterior cervical fusion.
Retrospective database analysis. To determine the national incidence, mortality, and risk factors for dysphagia associated with anterior cervical spinal fusion surgery in the United States. Dysphagia is a known complication associated with anterior cervical fusion (ACF). A population-based database was analyzed to characterize the incidence of dysphagia in terms of demographics, mortality, and risk factors associated with ACF. Data from the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project were obtained from 2002 to 2009. Patients undergoing ACF for cervical myelopathy and/or radiculopathy were identified and separated into cohorts (1- to 2-level and 3+-level fusions), and incidences of dysphagia were identified. Demographics, length of stay, costs, mortality, and use of bone morphogenetic proteins (BMPs) were assessed. Statistical data were analyzed in SPSS (version 20), using the Student t test for discrete variables and the χ test for categorical data. Binomial logistic regression was used to identify independent predictors of dysphagia. A P value of less than 0.001 was used to denote significance. A total of 159,590 ACF cases were identified of which 139,434 were 1- to 2-level ACF and 20,156 were 3+-level ACF. The incidence of dysphagia in the 3+-level ACF group was double that of the 1- to 2-level ACF group (44.8 vs. 22.4 per 1000; P < 0.001). Patients with dysphagia were significantly older than patients without dysphagia (P < 0.001). Dysphagia was more common in males undergoing 1- to 2-level ACF (P < 0.001). BMP was used more frequently for patients with dysphagia in the 1- to 2-level ACF group (9.4% vs. 7.2% of cases; P < 0.001). Logistic regression analysis demonstrated that independent predictors for dysphagia included age (≥65 yr), male sex, 3+-level fusion, BMP use, and preoperative patient comorbidities. Dysphagia occurs twice as often after 3+-level ACF compared with 1- to 2-level ACF. Utilization of BMP was also linked to an increased incidence of dysphagia in the 1- to 2-level ACF group. Regardless of the number of levels fused, patients experiencing dysphagia had increased age, comorbid risk factors, hospitalizations, and costs. 3.