Photodynamic anti-inflammatory activity of meso-aryl substituted porphyrin derivative on mammalian macrophages.
Our group focused on a meso-aryl substituted porphyrin molecule for its photodynamic anti-inflammatory activities on the mammalian macrophages. The porphyrine derivative previously synthesized in this study was synthesized and characterized by 1H NMR. We then examined their immunomodulatory activities based on the changes in the pro-inflammatory cytokine production levels after LPS stimulation in dark and light activated conditions. Our results suggest that porphyrin derivative had anti-inflammatory photodynamic activity in vitro at subtoxic concentrations. Our study aims to pave a way for anti-inflammatory photodynamic therapy application in the inflammatory and autoimmune disorders. Most of the studies either focus on photodynamic cytotoxicity of the porphyrin derivatives to suppress the inflammation or porphyrin derivatives' anti-inflammatory activity without the photodynamic activation. Our future studies will focus on the generation and in vitro as well as in vivo characterization of the porphyrin derivatives with anti-inflammatory photodynamic therapy applications. In this way, novel drug candidates that would have lower side effects can be generated for the patients.


Patient Satisfaction with HIV and AIDS Services in Mizan-Tepi University Teaching Hospital, Southwest Ethiopia.
The World Health Organization and UNAIDS estimated that 36.9 million people were living with HIV in 2017 globally. In the same year, 1.8 million people became newly infected with HIV and 940,000 people died of AIDS-related illnesses. This study aimed to assess patient satisfaction with HIV and AIDS services in Mizan-Tepi University Teaching Hospital (MTUTH), Southwest Ethiopia. A cross-sectional study was conducted from December 01/2018 to January 31/2019 among 348 people living with HIV who were on highly active antiretroviral therapy (HAART). A systematic random sampling technique was applied to select the study participants. Face to face interview was employed using structured questionnaires. The questionnaire consisted of socio-demographic factors, clinical factors, and patient satisfaction indicators for HIV and AIDS services. Level of satisfaction was assessed based on 24 Likert-scale items. Logistic regression analysis was carried out to identify the independent predictors of patient satisfaction with the services given. A total of 348 respondents completed the interview, of which 213 (61.20%) were male. The mean age of the respondents was 35.67 (SD=8.40). The overall level of clients' satisfaction with HIV and AIDS services was 55.2%. Educational status of secondary school and above [AOR 2.41, 95% CI: 1.24-4.69], duration of advice above 10 min [AOR 1.74, 95% CI: 1.09-2.79], CD4 count >500 [AOR 2.20, 95% CI: 1.37-3.54], and duration of treatment of 2 years and above [AOR 1.93, 95% CI: 1.07-3.49] were identified as factors significantly associated with client satisfaction. Overall, 55.20% of patients were satisfied with HIV and AIDS services given at the ART clinic of MTUTH. Educational status, CD4 count, duration of advice, and duration of treatment were found to be independent predictors of patient satisfaction with ART services. Increasing client satisfaction is important through patient counseling and care.


Experimental demonstration of coherence effects and linearity in microdensitometry.
Microdensitometer measurements of photographic film transmittance made at high spatial frequencies demonstrate that the basic instrument is nonlinear in that its response is a function of the spatial frequency and the mode of illumination. A method developed for measuring the spatial coherence, making use of a Wollaston prism shearing interferometer, has been applied to typical microdensitometers, documenting the existence of the partial coherence. The trace of a phase edge was found to be a graphical means of demonstrating one of the consequences of the partial coherence. Since partial coherence is present in all image-forming instruments, a linear instrument that avoids the imaging step and collects all the transmitted light has been developed. This linear instrument is limited in spatial frequency only by the size of the scanning spot. The system transfer function is the Fourier transform of the scanning spot irradiance. A linear microdensitometer was assembled on an optical bench using a cw laser source and standard microscope objectives, and it was used to trace a series of samples to test its response at high spatial frequencies. The linearity is demonstrated with both edge width measurements and flat response to a phase edge.


Response Surface Methodology As a New Approach for Finding Optimal MALDI Matrix Spraying Parameters for Mass Spectrometry Imaging.
Automated spraying devices have become ubiquitous in laboratories employing matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), in part because they permit control of a number of matrix application parameters that can easily be reproduced for intra- and interlaboratory studies. Determining the optimal parameters for MALDI matrix application, such as temperature, flow rate, spraying velocity, number of spraying cycles, and solvent composition for matrix application, is critical for obtaining high-quality MALDI-MSI data. However, there are no established approaches for optimizing these multiple parameters simultaneously. Instead optimization is performed iteratively (i.e., one parameter at a time), which is time-consuming and can lead to overall nonoptimal settings. In this report, we demonstrate the use a novel experimental design and the response surface methodology to optimize five parameters of MALDI matrix application using a robotic sprayer. Thirty-two combinations of MALDI matrix spraying conditions were tested, which allowed us to elucidate relationships between each of the application parameters as determined by MALDI-MS (specifically, using a 15 T Fourier transform ion cyclotron resonance mass spectrometer). As such, we were able to determine the optimal automated spraying parameters that minimized signal delocalization and enabled high MALDI sensitivity. We envision this optimization strategy can be utilized for other matrix application approaches and MALDI-MSI analyses of other molecular classes and tissue types.


AESOPS: a randomised controlled trial of the clinical effectiveness and cost-effectiveness of opportunistic screening and stepped care interventions for older hazardous alcohol users in primary care.
There is clear evidence of the detrimental impact of hazardous alcohol consumption on the physical and mental health of the population. Estimates suggest that hazardous alcohol consumption annually accounts for 150,000 hospital admissions and between 15,000 and 22,000 deaths in the UK. In the older population, hazardous alcohol consumption is associated with a wide range of physical, psychological and social problems. There is evidence of an association between increased alcohol consumption and increased risk of coronary heart disease, hypertension and haemorrhagic and ischaemic stroke, increased rates of alcohol-related liver disease and increased risk of a range of cancers. Alcohol is identified as one of the three main risk factors for falls. Excessive alcohol consumption in older age can also contribute to the onset of dementia and other age-related cognitive deficits and is implicated in one-third of all suicides in the older population. To compare the clinical effectiveness and cost-effectiveness of a stepped care intervention against a minimal intervention in the treatment of older hazardous alcohol users in primary care. A multicentre, pragmatic, two-armed randomised controlled trial with an economic evaluation. General practices in primary care in England and Scotland between April 2008 and October 2010. Adults aged ≥ 55 years scoring ≥ 8 on the Alcohol Use Disorders Identification Test (10-item) (AUDIT) were eligible. In total, 529 patients were randomised in the study. The minimal intervention group received a 5-minute brief advice intervention with the practice or research nurse involving feedback of the screening results and discussion regarding the health consequences of continued hazardous alcohol consumption. Those in the stepped care arm initially received a 20-minute session of behavioural change counselling, with referral to step 2 (motivational enhancement therapy) and step 3 (local specialist alcohol services) if indicated. Sessions were recorded and rated to ensure treatment fidelity. The primary outcome was average drinks per day (ADD) derived from extended AUDIT--Consumption (3-item) (AUDIT-C) at 12 months. Secondary outcomes were AUDIT-C score at 6 and 12 months; alcohol-related problems assessed using the Drinking Problems Index (DPI) at 6 and 12 months; health-related quality of life assessed using the Short Form Questionnaire-12 items (SF-12) at 6 and 12 months; ADD at 6 months; quality-adjusted life-years (QALYs) (for cost-utility analysis derived from European Quality of Life-5 Dimensions); and health and social care resource use associated with the two groups. Both groups reduced alcohol consumption between baseline and 12 months. The difference between groups in log-transformed ADD at 12 months was very small, at 0.025 [95% confidence interval (CI)--0.060 to 0.119], and not statistically significant. At month 6 the stepped care group had a lower ADD, but again the difference was not statistically significant. At months 6 and 12, the stepped care group had a lower DPI score, but this difference was not statistically significant at the 5% level. The stepped care group had a lower SF-12 mental component score and lower physical component score at month 6 and month 12, but these differences were not statistically significant at the 5% level. The overall average cost per patient, taking into account health and social care resource use, was £488 [standard deviation (SD) £826] in the stepped care group and £482 (SD £826) in the minimal intervention group at month 6. The mean QALY gains were slightly greater in the stepped care group than in the minimal intervention group, with a mean difference of 0.0058 (95% CI -0.0018 to 0.0133), generating an incremental cost-effectiveness ratio (ICER) of £1100 per QALY gained. At month 12, participants in the stepped care group incurred fewer costs, with a mean difference of -£194 (95% CI -£585 to £198), and had gained 0.0117 more QALYs (95% CI -0.0084 to 0.0318) than the control group. Therefore, from an economic perspective the minimal intervention was dominated by stepped care but, as would be expected given the effectiveness results, the difference was small and not statistically significant. Stepped care does not confer an advantage over minimal intervention in terms of reduction in alcohol consumption at 12 months post intervention when compared with a 5-minute brief (minimal) intervention. This trial is registered as ISRCTN52557360. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 25. See the HTA programme website for further project information.


Validation of pediatric diabetes case identification approaches for diagnosed cases by using information in the electronic health records of a large integrated managed health care organization.
We explored the utility of different algorithms for diabetes case identification by using electronic health records. Inpatient and outpatient diagnosis codes, as well as data on laboratory results and dispensing of antidiabetic medications were extracted from electronic health records of Kaiser Permanente Southern California members who were less than 20 years of age in 2009. Diabetes cases were ascertained by using the SEARCH for Diabetes in Youth Study protocol and comprised the "gold standard." Sensitivity, specificity, positive and negative predictive values, accuracy, and the area under the receiver operating characteristic curve (AUC) were compared in 1,000 bootstrapped samples. Based on data from 792,992 youth, of whom 1,568 had diabetes (77.2%, type 1 diabetes; 22.2%, type 2 diabetes; 0.6%, other), case identification accuracy was highest in 75% of bootstrapped samples for those who had 1 or more outpatient diabetes diagnoses or 1 or more insulin prescriptions (sensitivity, 95.9%; positive predictive value, 95.5%; AUC, 97.9%) and in 25% of samples for those who had 2 or more outpatient diabetes diagnoses and 1 or more antidiabetic medications (sensitivity, 92.4%; positive predictive value, 98.4%; AUC, 96.2%). Having 1 or more outpatient type 1 diabetes diagnoses (International Classification of Diseases, Ninth Revision, Clinical Modification, code 250.x1 or 250.x3) had the highest accuracy (94.4%) and AUC (94.1%) for type 1 diabetes; the absence of type 1 diabetes diagnosis had the highest accuracy (93.8%) and AUC (93.6%) for identifying type 2 diabetes. Information in the electronic health records from managed health care organizations provides an efficient and cost-effective source of data for childhood diabetes surveillance.


Cognitive status, stroke symptom reports, and modifiable risk factors among individuals with no diagnosis of stroke or transient ischemic attack in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study.
Vascular disorders that increase risk for stroke may be accompanied by decrements in cognitive functioning and by stroke symptoms in the absence of diagnosed stroke or transient ischemic attack. This study evaluates relationships among cognitive status, stroke symptom reports, and cardiovascular and behavioral factors. REasons for Geographic and Racial Differences in Stroke (REGARDS), a prospective population study of stroke incidence, assesses stroke risk with telephone interviews and in-home physicals. Excluding subjects with a history of stroke or transient ischemic attack, this analysis includes 14,566 black and white men and women > or =45 years of age. Incremental logistic models examine baseline relationships among cognitive status (Six-item Screener scores), stroke symptom reports, demographics, health behaviors, cardiovascular indices, and depressive symptoms. A history of stroke symptoms was related to impaired cognitive status after adjusting for age, gender, race, and education but not after adjusting for poor health behaviors, vascular risk factors, and depressive symptoms. Odds of experiencing a stroke symptom increased 35% with each of five modifiable factors (hypertension, diabetes, smoking, lack of exercise, depressive symptoms), and odds of cognitive impairment increased an additional 12% with each modifiable factor. Lifelong abstinence from alcohol, lack of exercise, and depressive symptoms were independently related to impaired cognitive status. The increased likelihood of cognitive impairment among subjects reporting stroke symptoms in the absence of a diagnosed stroke or transient ischemic attack suggests that such symptoms are not benign and may warrant clinical evaluation that includes a cognitive assessment. Future studies that include brain imaging may clarify the etiology of these symptoms.


Development of a sheep hind-limb muscle preparation for metabolic studies.
A sheep hind-limb preparation used for the study of muscle metabolism by arteriovenous (AV) difference procedures was validated by identifying the muscles which contribute to venous drainage at different positions along the lateral saphenous vein. Dissection of the hind limbs of six mature sheep (three wethers and three ewes) showed that venous blood from the plantar group (M. gastrocnemius, M. soleus, M. plantaris, M. flexo digitorum profundus), and from M. semitendinosus, M. biceps femoris, M. gracilis, M. pectineus and M. adductor muscles entered the lateral saphenous vein but the position of the tip of the blood sampling catheter was found to be critical. In order to sample venous blood from all of the muscles listed above, and to minimize the contribution of blood from non-muscular tissues, blood samples must be taken 25-26 cm from the junction of the cranial and caudal branches of the lateral saphenous vein (for average size sheep of body length about 108 cm and height at withers about 73 cm). The estimation of sheep hind-limb muscle mass is a necessary concomitant of AV difference studies, and a combined tritiated water and dye-dilution procedure has been used to measure both muscle mass and blood flow. The muscle mass estimated in vivo by this technique was closely similar to the true muscle mass obtained by dissection, the range of values of the difference between true and calculated muscle mass expressed as percentage of the true mass being 0.5-16%. It is concluded that these techniques are sufficiently accurate for use in the quantitation of exchange of metabolites across the hind-limb muscle preparation. Patterns of amino acid uptake and release by muscle need to be related to the amino acid profile of the tissue, and the amino acid content of a representative muscle, M. biceps femoris, was determined, and the results compared with published data.


Functional magnetic resonance imaging of the normal and abnormal visual system in early life.
Functional magnetic resonance imaging (fMRI) in young children may provide information about the development of the visual cortex, and may have predictive value for later visual performance. The purpose of this study was to evaluate the usefulness of fMRI for examining cerebral processing of vision in very young infants and in infants with brain damage. We examined 15 preterm infants, 12 children suspected of having a cerebral visual impairment and 10 children with a normal visual system, all of whom were either spontaneously asleep or sedated with chloral hydrate. Cortical response to stroboscopic light stimulation could be demonstrated in all technically acceptable data sets from children with a post-menstrual age (PMA) of > 41 weeks, but not in younger infants. Children < 60 weeks PMA showed either a blood oxygenation level-dependent (BOLD) signal increase or decrease, while all older children showed a signal decrease. The activated cortical volumes showed a linear relation to age for healthy children younger than 90 weeks PMA, but were small in children with visual impairment. In two children with unilateral damage to the optic radiations, activation was strongly asymmetrical with greatest activation on the healthy side. In future prospective studies, results from the period from birth to six months of age should be interpreted with caution, as inter-individual variation of cortical development may be confused with functional deficit.


Genetic Variation for Mitochondrial Function in the New Zealand Freshwater Snail Potamopyrgus antipodarum.
The proteins responsible for mitochondrial function are encoded by 2 different genomes with distinct inheritance regimes, rendering rigorous inference of genotype-phenotype connections intractable for all but a few model systems. Asexual organisms provide a powerful means to address these challenges because offspring produced without recombination inherit both nuclear and mitochondrial genomes from a single parent. As such, these offspring inherit mitonuclear genotypes that are identical to the mitonuclear genotypes of their parents and siblings but different from those of other asexual lineages. Here, we compared mitochondrial function across distinct asexual lineages of Potamopyrgus antipodarum, a New Zealand freshwater snail model for understanding the evolutionary consequences of asexuality. Our analyses revealed substantial phenotypic variation across asexual lineages at 3 levels of biological organization: mitogenomic, organellar, and organismal. These data demonstrate that different asexual lineages have different mitochondrial function phenotypes, likely reflecting heritable variation (i.e., the raw material for evolution) for mitochondrial function in P. antipodarum. The discovery of this variation combined with the methods developed here sets the stage to use P. antipodarum to study central evolutionary questions involving mitochondrial function, including whether mitochondrial mutation accumulation influences the maintenance of sexual reproduction in natural populations.


Trigger factor binding to ribosomes with nascent peptide chains of varying lengths and sequences.
Trigger factor (TF) is the first protein-folding chaperone to interact with a nascent peptide chain as it emerges from the ribosome. Here, we have used a spin down assay to estimate the affinities for the binding of TF to ribosome nascent chain complexes (RNCs) with peptides of varying lengths and sequences. An in vitro system for protein synthesis assembled from purified Escherichia coli components was used to produce RNCs stalled on truncated mRNAs. The affinity of TF to RNCs exposing RNA polymerase sequences increased with the length of the nascent peptides. TF bound to RNA polymerase RNCs with significantly higher affinity than to inner membrane protein leader peptidase and bacterioopsin RNCs. The latter two RNCs are substrates for signal recognition particle, suggesting complementary affinities of TF and signal recognition particle to nascent peptides targeted for cytoplasm and membrane.


Cis-Regulatory Evolution of Forkhead Box O1 (FOXO1), a Terminal Selector Gene for Decidual Stromal Cell Identity.
Studies in human and mouse have shown that decidual stromal cells (DSC), which develop in the innermost lining of uterus, mediate placentation by regulating maternal immune response against the fetus and the extent of fetal invasion. Investigating when and how DSC evolved is thus a key step to reconstructing the evolutionary history of mammalian pregnancy. We present molecular evidence placing the origin of DSC in the stem lineage of eutherians (extant placental mammals). The transcription factor forkhead box O1 (FOXO1) is a part of the core regulatory transcription factor complex (CoRC) that establishes the cell type identity of DSC. Decidualization, the process through which DSC differentiate from endometrial stromal fibroblasts, requires transcriptional upregulation of FOXO1 Contrary to other examples in mammals where gene recruitment is caused by the origin of an alternative promoter, FOXO1 is transcribed from the same promoter in DSC as in endometrial stromal fibroblasts. Comparing the activities of FOXO1 promoters from human, mouse, manatee (Afrotheria), and opossum (marsupial) revealed that FOXO1 promoter evolved responsiveness to decidualization signals in the stem lineage of eutherians. This eutherian vs. marsupial pattern of promoter activity was not observed in some other cell types expressing FOXO1, suggesting that this cis-regulatory evolution occurred specifically in the context of the origin of DSC. Sequence comparison revealed eutherian-specifically conserved nucleotides that contribute to the eutherian promoter activity. We conclude that the cis-regulatory activity of a terminal selector gene for decidual stromal cell identity evolved in the stem lineage of eutherians supporting a model where decidual cells are a eutherian innovation.


Burkholderia kururiensis sp. nov., a trichloroethylene (TCE)-degrading bacterium isolated from an aquifer polluted with TCE.
A trichloroethylene (TCE)-degrading bacterium was isolated from an aquifer sample collected at a TCE-polluted site in Japan by enriching with phenol as sole carbon source. The isolate, designated strain KP23T, was a Gram-negative, oval-shaped micro-organism. A phylogenetic study based on 16S rRNA gene sequences indicated that strain KP23T should be placed in the genus Burkholderia. Cellular fatty acids of the strain were mainly composed of C16:0, cyclopropanic acid C17:0 and cyclopropanic acid C19:0. Strain KP23T also contained notable amounts of C13:1 and C17:1. The G + C content of total DNA was 64.8 mol%. Strain KP23T oxidized various sugars and sugar alcohols as sole carbon source such as galactose, glucose, mannose, maltose, glycerol, inositol and mannitol. Comparisons of its phenotypic and genotypic characteristics with other known species belonging to the genus Burkholderia suggested that strain KP23T represents a new species in the genus. The name Burkholderia kururiensis is proposed for this species, with strain KP23T as the type strain (= JCM 10599T).


Correlates of overweight and obesity among American Indian/Alaska Native and Non-Hispanic White children and adolescents: National Survey of Children's Health, 2007.
Risk factors for overweight and obesity may be different for American Indian and Alaska Native (AI/AN) children compared to children of other racial/ethnic backgrounds, as obesity prevalence among AI/AN children remains much higher. Using data from the 2007 National Survey of Children's Health, behavioral (child's sport team participation, vigorous physical activity, television viewing, and computer use), household (parental physical activity, frequency of family meals, rules limiting television viewing, and television in the child's bedroom), neighborhood (neighborhood support, perceived community and school safety, and presence of parks, sidewalks, and recreation centers in the neighborhood), and sociodemographic (child's age and sex, household structure, and poverty status) correlates of overweight/obesity (body mass index ≥85th percentile for age and sex) were assessed among 10-17 year-old non-Hispanic white (NHW) and AI/AN children residing in Alaska, Arizona, Montana, New Mexico, North Dakota, Oklahoma, and South Dakota (n = 5,372). Prevalence of overweight/obesity was 29.0 % among NHW children and 48.3 % among AI/AN children in this sample. Viewing more than 2 h of television per day (adjusted odds ratio [aOR] = 2.0; 95 % confidence interval [CI] = 1.5-2.8), a lack of neighborhood support (aOR = 1.9; 95 % CI = 1.1-3.5), and demographic characteristics were significantly associated with overweight/obesity in the pooled sample. Lack of sport team participation was significantly associated with overweight/obesity only among AI/AN children (aOR = 2.7; 95 % CI = 1.3-5.2). Culturally sensitive interventions targeting individual predictors, such as sports team participation and television viewing, in conjunction with neighborhood-level factors, may be effective in addressing childhood overweight/obesity among AI/AN children. Longitudinal studies are needed to confirm these findings.


Drug fatalities and treatment fatalism: Complicating the ageing cohort theory.
Deaths related to drug 'misuse' remain at an all-time high in the United Kingdom (UK). Older heroin consumers are particularly at risk, with the highest rates of deaths among people aged 40-49 and the steepest rises in the over-fifty age bracket. Accordingly, a popular theory for the UK's increase in drug-related deaths, made by the government, and propelled in the media, is that there is an ageing cohort of heroin users with age-related health complications predisposing them to an overdose. However, drawing on in-depth interviews with those people deemed to be most at risk, this article works to complicate this theory, with participants citing a shift in (a) experience and responsibility, (b) route of administration, (c) desired effects, (d) acceptance of their drug use and 'user' status and (e) valuing health. Disrupting age as a given risk factor, this article turns attention away from the individual and these 'natural' processes to what participants describe as a singular, punitive, and inflexible treatment system and its intersecting structures. Approaching life and death as a matter of sociomaterial 'mattering', this article rethinks a reductionist, causal link between age and drug-related death with a treatment despondency and fatalism that could prove fatal.


Thapsigargin decreases the Na(+)- Ca(2+) exchanger mediated Ca(2+) entry in pig coronary artery smooth muscle.
Na(+)- Ca(2+) exchanger (NCX) has been proposed to play a role in refilling the sarco/endoplasmic reticulum (SER) Ca(2+) pool along with the SER Ca(2+) pump (SERCA). Here, SERCA inhibitor thapsigargin was used to determine the effects of SER Ca(2+) depletion on NCX-SERCA interactions in smooth muscle cells cultured from pig coronary artery. The cells were Na(+)-loaded and then placed in either a Na(+)-containing or in a Na(+)-substituted solution. Subsequently, the difference in Ca(2+) entry between the two groups was examined and defined as the NCX mediated Ca(2+) entry. The NCX mediated Ca(2+) entry in the smooth muscle cells was monitored using two methods: Ca(2+)sensitive fluorescence dye Fluo-4 and radioactive Ca(2+). Ca(2+)-entry was greater in the Na(+)-substituted cells than in the Na(+)-containing cells when measured by either method. This difference was established to be NCX-mediated as it was sensitive to the NCX inhibitors. Thapsigargin diminished the NCX mediated Ca(2+) entry as determined by either method. Immunofluorescence confocal microscopy was used to determine the co-localization of NCX1 and subsarcolemmal SERCA2 in the cells incubated in the Na(+)-substituted solution with or without thapsigargin. SER Ca(2+) depletion with thapsigargin increased the co-localization between NCX1 and the subsarcolemmal SERCA2. Thus, inhibition of SERCA2 leads to blockade of constant Ca(2+) entry through NCX1 and also increases proximity between NCX1 and SERCA2. This blockade of Ca(2+) entry may protect the cells against Ca(2+)-overload during ischemia-reperfusion when SERCA2 is known to be damaged.


A pyramid-based approach to segmentation applied to region matching.
In this paper, we attempt to place segmentation schemes utilizing the pyramid architecture on a firm footing. We show that there are some images which cannot be segmented in principle. An efficient segmentation scheme is also developed using pyramid relinking. This scheme will normally have a time complexity which is a sublinear function of the image diameter, which compares favorably to other schemes. The efficacy of our approach to segmentation using pyramid schemes is demonstrated in the context of region matching. The global features we use are compared to those used in previous approaches and this comparison will indicate that our approach is more robust than the standard moment-based techniques.


Analysis of the avian coronavirus spike protein reveals heterogeneity in the glycans present.
Infectious bronchitis virus (IBV) is an economically important coronavirus, causing damaging losses to the poultry industry worldwide as the causative agent of infectious bronchitis. The coronavirus spike (S) glycoprotein is a large type I membrane protein protruding from the surface of the virion, which facilitates attachment and entry into host cells. The IBV S protein is cleaved into two subunits, S1 and S2, the latter of which has been identified as a determinant of cellular tropism. Recent studies expressing coronavirus S proteins in mammalian and insect cells have identified a high level of glycosylation on the protein's surface. Here we used IBV propagated in embryonated hens' eggs to explore the glycan profile of viruses derived from infection in cells of the natural host, chickens. We identified multiple glycan types on the surface of the protein and found a strain-specific dependence on complex glycans for recognition of the S2 subunit by a monoclonal antibody in vitro, with no effect on viral replication following the chemical inhibition of complex glycosylation. Virus neutralization by monoclonal or polyclonal antibodies was not affected. Following analysis of predicted glycosylation sites for the S protein of four IBV strains, we confirmed glycosylation at 18 sites by mass spectrometry for the pathogenic laboratory strain M41-CK. Further characterization revealed heterogeneity among the glycans present at six of these sites, indicating a difference in the glycan profile of individual S proteins on the IBV virion. These results demonstrate a non-specific role for complex glycans in IBV replication, with an indication of an involvement in antibody recognition but not neutralisation.


Single filament behavior of microtubules in the presence of added divalent counterions.
Microtubules (MTs) are hollow biopolymeric filaments that function to define the shape of eukaryotic cells, serve as a platform for intracellular vesicular transport, and separate chromosomes during mitosis. One means of physiological regulation of MT mechanics and dynamics, critical to their adaptability in such processes, is through electrostatics due to the strong polyelectrolyte nature of MTs. Here, we show that in the presence of physiologically relevant amounts of divalent salts, MTs experience a dramatic increase in persistence length or stiffness, which is counter to theoretical expectations and experimental observations in similar systems (e.g., DNA). Divalent salt-dependent effects on MT dynamics were also observed with respect to suppressing depolymerization as well as reducing dispersion in kinesin-driven molecular motor transport assays. These results establish a novel mechanism by which MT dynamics, mechanics, and interaction with molecular motors may be regulated by physiologically relevant concentrations of divalent salts.


Humic Substances Delay Aging of the Photosynthetic Apparatus of Chara hispida.
In freshwaters, dissolved humic substances (HSs) distinguish apparently HS-avoiding Charophytes from apparently HS-tolerant ones, but the underlying mechanisms so far remain obscure. In this contribution, we tested direct and indirect effects of HSs on Chara hispida (L.) Hartm. Using Rhodamine B, we showed that C. hispida is able to adsorb or even uptake and, subsequently, desorb and depurate organic compounds in the molecular mass range of the applied fulvic acids. To classify direct and indirect HS-mediated effects due to reduced light quantities, or to effects more strongly elicited by red relative to blue light, plants were exposed to HSs directly as well as through a neutral foil, or shaded by means of an external HS-containing reservoir (low-light variant). We showed that the apparently HS-tolerant C. hispida exhibited reduced lipid peroxidation and non photochemical quenching of chlorphyll fluorescence when exposed to HSs. Plants directly exposed to HSs were significantly different from control as well as to foil-shaded plants in terms of chl a+b, VAZ/chl, and β-Car/chl; yet, in low-light plants these variables did not differ from control and HS-exposed plants, suggesting that the shift in favor of red lights in the low-light variant led to a reduction in its cells' internal antioxidant content. However, the Fv/Fm ratio in HS-exposed plants decreased more slowly than in all other exposure variants, indicating that the photosynthetic apparatus aged more slowly, by a mechanism yet to be discovered. Our study indicates that both direct and indirect effects contribute to the HS tolerance of C. hispida.


Plasma insulin, leptin, adiponectin, resistin, ghrelin, and melatonin in nonalcoholic steatohepatitis patients treated with melatonin.
Insulin resistance, oxidative stress, and an abnormal production of adipokines and cytokines are implicated in the pathogenesis of nonalcoholic steatohepatitis (NASH). Recently, we reported a significant improvement in plasma liver enzymes among patients with NASH treated with melatonin. In this study, we investigated the effect of melatonin, administered at a dose of 10 mg/day for 28 days to 16 patients with histologically proven NASH on insulin resistance (HOMA-IR), on the plasma levels of adiponectin, leptin, ghrelin, and resistin. Additionally, plasma levels of aminotransferases and gamma glutamyltranspeptidase as well as plasma concentrations of melatonin were evaluated. Median baseline values of HOMA-IR, leptin (ng/mL), and resistin (pg/mL) in patients with NASH were significantly higher in comparison with controls: 4.90 versus 1.60, 10.70 versus 4.30, and 152 versus 91, respectively. Median adiponectin level (μg/mL) was decreased in patients compared to controls: 6.40 versus 16.25; no significant difference in ghrelin levels between patients and controls was found. After melatonin treatment, the median value of HOMA-IR was significantly reduced by 60% as compared to baseline values, whereas adiponectin, leptin, and ghrelin plasma levels rose significantly by 119%, 33%, and 20%, respectively; the difference between pre-/posttreatment in plasma resistin levels was not significant. These findings make melatonin a suitable candidate for testing in patients with NASH in the large controlled clinical trials.


Nonstarch polysaccharide hydrolysis products of soybean and canola meal protect against enterotoxigenic Escherichia coli in piglets.
Infectious diarrhea is a major problem in both children and piglets. Enterotoxigenic Escherichia coli (ETEC) infection results in fluid and electrolyte losses in the small intestine. We investigated the effect of nonstarch polysaccharide (NSP) hydrolysis products of soybean meal (SBM) and canola meal (CM) on net absorption of fluid and solutes during ETEC infection. Products were generated by incubating SBM and CM with a blend of carbohydrase enzymes. Following incubation, slurries were centrifuged and the supernatants mixed with absolute ethanol to produce 2 product types: 80% ethanol-soluble (ES) and 80% ethanol-insoluble (EI). Products from SBM and CM were studied in 2 independent experiments in which 2 factors were investigated: product type (EI vs. ES) and time of ETEC infection (before vs. after perfusion). Pairs of small intestine segments, one noninfected and the other ETEC infected, were perfused simultaneously with different products for 7.5 h. Net absorption of fluid and solutes were determined. In both experiments, ETEC-infected segments perfused with saline control had lower (P < or = 0.05) net fluid and solute absorption compared with SBM and CM products. The interaction (P < or = 0.05) between product type and time of infection on fluid absorption was only evident for SBM, in which case perfusing ES products before infection resulted in higher fluid absorption (735 +/- 22 microL/cm2) compared with ETEC infection before perfusion (428 +/- 34 microL/cm2). In conclusion, NSP hydrolysis products of SBM and CM, particularly ES from SBM, were beneficial in maintaining fluid balance during ETEC infection, suggesting potential for controlling ETEC-induced diarrhea in piglets.


An overview of the socio-cultural and psychiatric aspects of women's reproductive health in West Africa.
The challenges associated with women reproductive health in West African sub region have over the years become a source of concern to relevant world bodies such as WHO, UNFPA, World Bank etc. Some of these challenges include Infertility, Family Planning and Female Genital Mutilation (FGM). However, of greater concern is the scourge of Sexually Transmitted Diseases (STDs) most especially HIV/ AIDS and the unacceptably high maternal mortality in the sub region where Nigeria alone accounts for the highest percentage (10%) of the global 60,000 maternal deaths annually. Significant psychiatric complications such as anxiety and depression are associated with menstruation and menopause. However, the postpartum period is the most vulnerable with significant proportion of women developing such psychopathologies as Puerperal (maternity) blues, Postpartum Depression (PPD) and Acute Organic Brain Syndrome. Sociocultural factors, the dearth of psychiatrists in West Africa coupled with the poor or non-recognition of the psychiatric complications by the obstetric staff have not allowed enough clinical attention to be paid to these problems. It is thus advocated that improvement in the maternal and child health care component of the primary health care (PHC) services will go a long way to attenuate the psychiatric complications associated with childbirth.


Time trends of non-alcoholic beverage consumption among adults in Germany, 1990-2011.
In Germany, information on trends in non-alcoholic beverage intake over the last decades is sparse. The aim of this analysis is to examine trends in non-alcoholic beverage consumption among adults living in Germany between 1990 and 2011 with special focus on gender, age and education level. We used self-reported food frequency questionnaire information from 25 to 69 year old participants of three German National Health Interview and Examination Surveys conducted in 1990-1992 (n = 7466), 1997-1999 (n = 5825) and 2008-2011 (n = 5375) and focused on consumption frequency of fruit juice, soft drinks, water, tea and coffee. Positive answers in the categories "almost daily", "daily" and "daily and more" were categorized as frequent beverage intake. Proportion estimates and 95%-CI were weighted to better reflect the German population using SAS 9.4 survey procedures for complex sample designs. Between 1990-1992 and 2008-2011, the proportion of men and women who reported to frequently drink juice, soft drinks, water or tea has increased from 21.9% (95%-CI: 20.8-23.0%) to 27.2% (25.6-29.0%), 10.0% (9.0-11.1%) to 18.7% (17.3-20.3%), 59.1% (56.8-61.4%) to 87.6% (86.2-88.9%), and 32.2% (30.3-34.2%) to 39.2% (36.9-41.5%), respectively. Frequent consumption of coffee decreased from 80.6% (79.1-82.0%) in 1990-1992 to 74.9% (73.3-76.5%) in 1997-1999 and increased to 81.2% (79.8-82.6%) in 2008-2011. Frequent consumption of juice increased over time among men with middle and high education (17.7% (15.7-19.8%) to 26.4% (23.4-29.6%) and 22.9% (20.2-25.8%) to 32.7% (29.4-36.2%), respectively), whereas a similar increase was only seen among women with low education (19.8% (17.1-22.9%) to 28.4% (22.9-34.7%). Frequent soft drink consumption increased among men in all age and education groups but among women only in the 25 to 34 year age group and in the low education group. Frequent water consumption increased about 20% or more among men and women, in all age and education groups. The results show changes in non-alcoholic beverage consumption over the past two decades in Germany. Exploring non-alcoholic beverage intake over time is important for the evaluation of consumption patterns with regard to guidelines and to design appropriate prevention measures.


Practice of venom immunotherapy in the United Kingdom: a national audit and review of literature.
Venom immunotherapy (VIT) is the only effective treatment for prevention of serious allergic reactions to bee and wasp stings in sensitized individuals. However, controversies exist relating to diagnosis, indications for treatment and treatment schedules. We audited current practice of VIT in the United Kingdom to evaluate adherence to international guidelines. An online questionnaire was sent to all clinicians practising immunotherapy identified on the British Society of Allergy and Clinical Immunology website. Eighty-six questionnaires were sent and 53 responses (61.6%) were received. Of these, 48 (85%) carried out VIT at their centre. Skin prick tests (SPT) and serum venom-specific IgE (SSIgE) were equally preferred as first-line investigation. Fifty percent of the respondents perform intradermal tests if both SPT and SSIgE are negative. While 8% of respondents commence VIT in patients with negative SSIgE and a history of severe reaction, 57% prefer to repeat the tests in 6-12 months if serum tryptase is elevated. If the insect responsible is uncertain and SSIgE is detected against bee and wasp venoms, 22% of the respondents will desensitize to both while 32% initiate treatment against the venom with the higher SSIgE. A protocol of weekly up-dosing for 12 weeks is preferred for induction and only 25% of respondents have ever used rush or ultra-rush protocols. Three years is thought to be optimum duration of VIT by most (56%). Eleven percent perform sting challenges at the end of treatment. Although 47% measure SSIgE at the end of treatment, only 3% use these results as a basis for discontinuing VIT. Currently there is considerable variation in the diagnosis and management of hymenoptera venom allergy in the United Kingdom. This audit has demonstrated that the current international guidelines for the diagnosis and management of hymenoptera venom allergy are not being followed by UK allergy practitioners.


Pain after barium enema: effect of CO2 and air on double-contrast study.
One hundred fifty-one consecutive patients scheduled for double-contrast barium enema studies were assigned randomly to insufflation with either air or carbon dioxide (CO2) in a double-blind, prospective trial. Within 24 hours after the enema study, the patients were contacted by telephone by an interviewer, who completed a standard questionnaire. Radiographs from the enema studies were assessed for quality by two radiologists. Pain experienced after the procedure was graded from 0 (none) to 4 (severe). Clinically relevant (grades 2-4) pain was experienced by 30% of patients after insufflation with room air, compared with 11% of patients in whom CO2 was used for insufflation (P = .005). The mean pain score for CO2 was 0.4, and for room air, 1.2 (P less than .005). Although five patients experienced grade 4 pain after insufflation with air, no patient reported severe pain after CO2 insufflation. Post-evacuation films confirmed there was significantly less residual gas in the CO2 group. The quality of radiographs was equal in the two groups. CO2 has advantages for use in the double-contrast barium enema examination.


Diffusing an Innovation: Clinician Perceptions of Continuous Predictive Analytics Monitoring in Intensive Care.
The purpose of this article is to describe neonatal intensive care unit clinician perceptions of a continuous predictive analytics technology and how those perceptions influenced clinician adoption. Adopting and integrating new technology into care is notoriously slow and difficult; realizing expected gains remain a challenge. Semistructured interviews from a cross-section of neonatal physicians (n = 14) and nurses (n = 8) from a single U.S. medical center were collected 18 months following the conclusion of the predictive monitoring technology randomized control trial. Following qualitative descriptive analysis, innovation attributes from Diffusion of Innovation Theory-guided thematic development. Results suggest that the combination of physical location as well as lack of integration into work flow or methods of using data in care decisionmaking may have delayed clinicians from routinely paying attention to the data. Once data were routinely collected, documented, and reported during patient rounds and patient handoffs, clinicians came to view data as another vital sign. Through clinicians' observation of senior physicians and nurses, and ongoing dialogue about data trends and patient status, clinicians learned how to integrate these data in care decision making (e.g., differential diagnosis) and came to value the technology as beneficial to care delivery. The use of newly created predictive technologies that provide early warning of illness may require implementation strategies that acknowledge the risk-benefit of treatment clinicians must balance and take advantage of existing clinician training methods.


Accurate prediction of black rot epidemics in vineyards using a weather-driven disease model.
Grapevine black rot caused by Guignardia bidwellii is a serious threat in vineyards, especially in areas with cool and humid springs. A mechanistic, weather-driven model was recently developed for the detailed prediction of black rot epidemics. The aim of this work was to evaluate the model by comparison with observed disease development in leaves and clusters in a vineyard in north Italy from 2013 to 2015. The model accurately predicted disease onset. The probability of predicting new infections that did not occur (i.e. unjustified alarms) was ≤0.180, while the probability of missing actual infections was 0.175 for leaves and 0.263 for clusters. In 78% of these false negative predictions, the difference between expected and actual disease onset was ±2 days; therefore, only one infection period was actually missed by the model. The model slightly overestimated disease severity (mainly on leaves) when the observed disease severity was >0.6. The model was highly accurate and robust in predicting the infection periods and dynamics of black rot epidemics. The model can be used for scheduling fungicide sprays in vineyards. © 2016 Society of Chemical Industry.


One-step approach for the synthesis of CoFe2O4@rGO core-shell nanocomposites as efficient adsorbent for removal of organic pollutants.
CoFe2O4-reduced graphene oxide nanocomposites (CFG) have been successfully synthesized via one-step solvothermal method. The prepared CFG are characterized by X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, field emission scanning electron microscopy (FESEM), vibrating sample magnetometer and so on. The FESEM results show that CFG have uniform core-shell structure with an average diameter of about 75 nm and the thickness of the outer graphene shell is about 15-20 nm. The mass ratio of CoFe2O4 to graphene oxide is a key factor affecting the formation of core-shell hybrids. CFG display much higher adsorption capacity for anionic dyes than cationic dyes owing to the favorable electrostatic interaction. The adsorption capacity for methyl orange is observed as high as 263 mg g-1 at 298 K, and the adsorption isotherms follow the Langmuir model. Furthermore, the specific saturation magnetization (Ms) of CFG is 32.8 emu g-1, and the as-synthesized nanocomposites can be easily separated by external magnetic field after adsorption. The results suggest that CFG have great potential for the practical industrial wastewater treatment.


Screening for potential susceptibility to rubella in an antenatal population: A multivariate analysis.
Rubella causes disease in the fetus. Immunity to rubella is therefore, routinely screened in pregnant women. In this retrospective observational study, we assessed the levels of potential susceptibility to rubella in the population of a north London antenatal clinic. Risk factors for potential susceptibility to rubella and changes in potential susceptibility to rubella over time were studied. Almost all women were screened for potential susceptibility to rubella (99.8%). The majority were predicted to be immune (96.8%). Women booking in later years within the study period showed higher levels of potential susceptibility to rubella. Booking during each subsequent year in the study gave women an odds ratio of 0.91 (CI:0.84, 0.98, P = 0.009) of being predicted to have immunity against rubella. Age was associated with predicted immunity to rubella, with a 5.1% (CI:3.3%, 6.9%, P < 0.001) increased likelihood for every year older. Previous pregnancy was predictive of immunity against rubella with an odds ratio of 1.41 (CI 1.21, 1.61, P = 0.001). Those from a non-white ethnicity were less likely to have antibodies predictive of immunity (OR: 0.730, CI: 0.581, 0.879 P < 0.001). Country of birth was associated with differences in potential susceptibility, with those being born outside of the British Isles having an odds ratio for predicted immunity of 0.63 (CI:0.35,0.91, P = 0.001). Being born in a high-risk country for rubella non-immunity was also a risk factor, giving an odds ratio of predicted immunity to rubella of 0.55 (CI:0.32, 0.77, P < 0.001).


XBMPRII, a novel Xenopus type II receptor mediating BMP signaling in embryonic tissues.
Bone Morphogenetic Proteins (BMPs) are potent regulators of embryonic cell fate that are presumed to initiate signal transduction in recipient cells through multimeric, transmembrane, serine/threonine kinase complexes made up of type I and type II receptors. BMPRII was identified previously in mammals as the only type II receptor that binds BMPs, but not activin or TGFbeta, in vitro. We report the cloning and functional analysis in vivo of its Xenopus homolog, XBMPRII. XBMPRII is expressed maternally and zygotically in an initially unrestricted manner. Strikingly, XBMPRII transcripts then become restricted to the mesodermal precursors during gastrulation. Expression is lower in the dorsal organizer region, potentially providing a mechanism to suppress the actions of BMP4 on dorsally fated tissues. Similar to the results seen for a truncated type I BMP receptor (tBR), a dominant-negative form of XBMPRII (tBRII) can dorsalize ventral mesoderm, induce extensive secondary body axes, block mesoderm induction by BMP4 and directly neuralize ectoderm, strongly suggesting that XBMPRII mediates BMP signals in vivo. However, although both tBRII and tBR can induce partial secondary axes, marker analysis shows that tBRII-induced axes are more anteriorly extended. Additionally, coinjection of tBRII and tBR synergistically increases the incidence of secondary axis formation. A truncated activin type II receptor (deltaXAR1) is known to block both activin and BMP signaling in vivo. Here we show that such crossreactivity does not occur for tBRII, in that it does not affect activin signaling. Furthermore, our studies indicate that the full-length activin type II receptor (XAR1) overcomes a block in BMP4 signaling imposed by tBRII, implicating XAR1 as a common component of BMP and activin signaling pathways in vivo. These data implicate XBMPRII as a type II receptor with high selectivity for BMP signaling, and therefore as a critical mediator of the effects of BMPs as mesodermal patterning agents and suppressors of neural fate during embryogenesis.


Tai chi for rheumatoid arthritis: systematic review.
The objective of this systematic review is to evaluate data from controlled clinical trials testing the effectiveness of tai chi for treating rheumatoid arthritis (RA). Systematic searches were conducted on Medline, Pubmed, AMED, British Nursing Index, CINAHL, EMBASE, PsycInfo, The Cochrane Library 2007, Issue 1, the UK National Research Register and ClinicalTrials.gov, Korean medical databases, Qigong and Energy Medicine Database and Chinese databases up to January 2007. Hand-searches included conference proceedings and our own files. There were no restrictions regarding the language of publication. All controlled trials of tai chi for patients with RA were considered for inclusion. Methodological quality was assessed using the Jadad score. The searches identified 45 potentially relevant studies. Two randomized clinical trials (RCTs) and three non-randomized controlled clinical trials (CCTs) met all inclusion criteria. The included RCTs reported some positive findings for tai chi on disability index, quality of life, depression and mood for RA patients. Two RCTs assessed pain outcomes and did not demonstrate effectiveness on pain reduction compared with education plus stretching exercise and usual activity control. The extent of heterogeneity in these RCTs prevented a meaningful meta-analysis. Currently there are few trials testing the effectiveness of tai chi in the management of RA. The studies that are available are of low methodological quality. Collectively this evidence is not convincing enough to suggest that tai chi is an effective treatment for RA. The value of tai chi for this indication therefore remains unproven.


[Late conversions following endoprosthetic repair of abdominal aortic aneurysms].
Presented herein is a review of the literature concerning late open conversions after endoprosthetic repair of abdominal aortic aneurysms, followed by analyzing the data on frequency and terms of performing late conversions, indications, options of surgical technique, lethality, and remote results.


Diagnostic value of glypican-3 in alpha fetoprotein negative hepatocellular carcinoma patients.
The prognosis of patients with hepatocellular carcinoma(HCC) is generally very poor with a 5-year survival rate of less than 15% since most of them are diagnosed clinically at their late stage. However, the differential diagnosis between alpha fetoprotein(AFP) negative HCC and cirrhotic nodules is still difficult. To evaluate the diagnostic value of glypican-3(GPC3) in patients with AFP negative hepatitis B related HCC. The liver tissue GPC3 (GPC3L) expression was tested from 426 for surgery and 179 of needle biopsies of hepatitis B related HCC patients using immunohistochemistry staining. Serum GPC3 (GPC3S) and AFP were also measured. Among surgical HCC samples, 80.0% of GPC3L expression was positive, however, in paracarcinomatous and cirrhotic nodules were negative. In needle biopsy tissues, GPC3L positively expression was in 74.9%. The sensitivity of AFP>400 µg/L was 25.4%. The GPC3S >3.5 µg/L was determined as a positive. The area of ROC curve of GPC3S was 0.68(95% CI 0.56-0.79,P<0.05) in all HCC patients,0.81 (95% CI 0.62 -0. 98, P<0.05) in AFP greater or equal to 400 µg/L and 0.64 (95% CI 0.51-0.77, P=0.051) in AFP negative patients. The GPC3S was positive in 48.8% of patients with AFP negative. No difference was observed between GPC3L/GPC3S and serum AFP. GPC3 may be helpful in improving diagnosis of HCC and in differentiating diagnosis between AFP negative HCC and cirrhotic nodules.


Surgical vs. transcatheter pulmonary vein isolation as first invasive treatment in patients with atrial fibrillation: a matched group comparison.
Pulmonary vein isolation (PVI) can be considered for treatment of symptomatic atrial fibrillation (AF). Nowadays, in addition to transcatheter ablation, thoracoscopic surgical PVI is available. The aim of this study is to compare clinical outcome of surgical with transcatheter PVI as first invasive treatment strategy of AF. From June 2009 to November 2011, 33 patients underwent minimally invasive surgical PVI, and were matched (1:2 fashion) retrospectively according to age, sex, and AF type, with 66 patients who underwent transcatheter PVI. Success was defined as freedom from atrial arrhythmias on 24 h Holter monitoring without use of anti-arrhythmic drugs (AADs) at 1 year. Mean age was 52 ± 10 years, 82% were male. Paroxysmal AF was present in 76 patients (77%), persistent AF in 23 (23%) patients. None underwent prior ablations, and failed on 1.2 ± 0.6 AADs. At 12 months, complete freedom from atrial arrhythmias without AADs in the surgical PVI group was 88% compared with 41% in the transcatheter PVI group (P < 0.001). Freedom from atrial arrhythmias with AADs was 91 vs. 62%, in the surgical vs. transcatheter PVI group, respectively (P = 0.002). Complications occurred in seven (21%) surgical PVI patients, and three (5%) transcatheter PVI patients (P = 0.015). In present matched study comparing a surgical with transcatheter PVI treatment strategy in symptomatic AF patients failed on AADs, but without prior ablations, a surgical PVI strategy was more effective to prevent recurrence of atrial arrhythmias, than a transcatheter PVI treatment strategy. However, complications were more frequent with surgical PVI.


Rate-induced tipping from periodic attractors: Partial tipping and connecting orbits.
We consider how breakdown of the quasistatic approximation for attractors can lead to rate-induced tipping, where a qualitative change in tracking/tipping behaviour of trajectories can be characterised in terms of a critical rate. Associated with rate-induced tipping (where tracking of a branch of quasistatic attractors breaks down), we find a new phenomenon for attractors that are not simply equilibria: partial tipping of the pullback attractor where certain phases of the periodic attractor tip and others track the quasistatic attractor. For a specific model system with a parameter shift between two asymptotically autonomous systems with periodic attractors, we characterise thresholds of rate-induced tipping to partial and total tipping. We show these thresholds can be found in terms of certain periodic-to-periodic and periodic-to-equilibrium connections that we determine using Lin's method for an augmented system.


HHCDB: a database of human heterochromatin regions.
Heterochromatin plays essential roles in eukaryotic genomes, such as regulating genes, maintaining genome integrity and silencing repetitive DNA elements. Identifying genome-wide heterochromatin regions is crucial for studying transcriptional regulation. We propose the Human Heterochromatin Chromatin Database (HHCDB) for archiving heterochromatin regions defined by specific or combined histone modifications (H3K27me3, H3K9me2, H3K9me3) according to a unified pipeline. 42 839 743 heterochromatin regions were identified from 578 samples derived from 241 cell-types/cell lines and 92 tissue types. Genomic information is provided in HHCDB, including chromatin location, gene structure, transcripts, distance from transcription start site, neighboring genes, CpG islands, transposable elements, 3D genomic structure and functional annotations. Furthermore, transcriptome data from 73 single cells were analyzed and integrated to explore cell type-specific heterochromatin-related genes. HHCDB affords rich visualization through the UCSC Genome Browser and our self-developed tools. We have also developed a specialized online analysis platform to mine differential heterochromatin regions in cancers. We performed several analyses to explore the function of cancer-specific heterochromatin-related genes, including clinical feature analysis, immune cell infiltration analysis and the construction of drug-target networks. HHCDB is a valuable resource for studying epigenetic regulation, 3D genomics and heterochromatin regulation in development and disease. HHCDB is freely accessible at http://hhcdb.edbc.org/.


Extending limits of resection for metastatic colorectal cancer: risk benefit ratio.
Improvements in treatment strategies and a better knowledge of tumor biology have contributed to an increase in the number of patients with colorectal liver metastases (CLM) who are candidate for surgery. These progresses are on going and the introduction of effective systemic therapy agents contributes further to the increase in the resectability of patients with advanced CLM.


Coronavirus Disease 2019 in Rheumatic Patients with Inflammatory Disorders: A Descriptive Study from a High Infection Incidence Region of Northern Spain.
Since the first confirmed case of severe acute respiratory syndrome coronavirus 2 in Spain in January 2020, the susceptibility of patients with rheumatic disease has remained unclear. In this report, we will describe the main features of coronavirus disease 2019 (COVID-19) that occurred in rheumatic patients with inflammatory disorders and try to identify features associated with severe disease. We included all rheumatic patients with immune-mediated diseases followed at 6 centers belonging to the public healthcare system in the Basque Country (Spain) and diagnosed with COVID-19 from March 1, 2020, to May 31, 2020. In total, 131 patients were included in this study. The most frequent rheumatic disease was rheumatoid arthritis (46.6%), and the main comorbidities were arterial hypertension (45%). Fortyseven percent were taking glucocorticoids (GC) (62 patients), 61.8% were under treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARD), and 25 patients (19.1%) were receiving targeted therapies (TT). Thirty-eight percent of patients required hospital admission, 2.3% required transfer to intensive care uni, and the rate of mortality was 9.2%. Associated factors in univariate analysis for a bad outcome were older age, use of GC, obesity, previous cardiovascular disease, and lymphopenia. Use of GC and lymphopenia remained within the multivariate model. The frequency of COVID-19 seems to be similar in rheumatic patients as in the general population. Advanced age, obesity, heart disease, glucocorticoids, and low levels of lymphocytes were more common among the patients with a bad outcome. Neither exposure to csDMARD nor TT was associated with severe cases.


Recent prescription status of oral analgesics in Japan in real-world clinical settings: retrospective study using a large-scale prescription database.
Background: Information on prescriptions of oral analgesics for the treatment of pain is beneficial. However, there have been few reports on the prescription status of oral analgesics from a nation-wide, large-scale prescription database in Japan. Research design and methods: The authors analyzed the prescription data of 2,042,302 patients prescribed oral analgesics in 2017. The numbers/proportions of patients prescribed oral analgesics, adherence with approved doses, co-prescription patterns, dose changes, drug adherence, and treatment-discontinuation rates were evaluated. Results: Loxoprofen was prescribed to 32.5% of the patients, followed by celecoxib, prescribed to 16.0% of patients. Acetaminophen and pregabalin were prescribed to 10.5% and 9.4% of patients, respectively. Many analgesics were prescribed at lower doses than the approved doses. The most frequently used concomitant medication was pregabalin. For duloxetine and pregabalin, high proportions of patients were prescribed these drugs for > 90 days. Conclusions: Loxoprofen was the most prescribed of the non-steroidal anti-inflammatory drugs in Japan. The information obtained provides an overview of prescribed oral analgesics in Japan and could be useful for potential research into prescribed oral analgesics in the future.


The Origin and Impact of Ideals in eHealth Research: Experiences From the U-CARE Research Environment.
The prevalence of information technology (IT) in society is a foundation for new modes of interaction between patients and health specialists. IT plays an important role in the renewal of care. Several countries have incorporated eHealth plans into their national health strategies. Part of the eHealth evolution concerns Internet psychological treatment and psychosocial care. These interventions are complex to design and evaluate due to legal, ethical, organizational, technical, and methodological challenges. The objective of our study was to seek to make explicit contributions to the understanding of ideals in eHealth research, and illuminate their implications for establishing an effective research environment. Our analysis draws from three years of experience in establishing an eHealth research environment, and the literature. We worked inductively to characterize challenging research ideals, and their origins, in our environment. Thereafter, we made a selective search of the literature to scrutinize and illuminate each ideal and it's implications. In this work, we propose a structured approach to address ideals in eHealth research. The scrutinized ideals are accountability, innovation, rigor, relevance, and sustainability. The approach supports researchers to systematically understand the ideals, their origin, and to manage their implications within an eHealth research environment. The complexity of eHealth research causes a need for sustainable, multi-disciplinary research environments. There is a need for a structured approach to organize eHealth research. The proposed approach helps to systematically scrutinize ideals, thus promoting high quality research.


Time-of-flight measurement techniques for airborne ultrasonic ranging.
Airborne ultrasonic ranging is used in a variety of different engineering applications for which other positional metrology techniques cannot be used, for example in closed-cell locations, when optical line of sight is limited, and when multipath effects preclude electromagnetic-based wireless systems. Although subject to fundamental physical limitations, e.g., because of the temperature dependence of acoustic velocity in air, these acoustic techniques often provide a cost-effective solution for applications in mobile robotics, structural inspection, and biomedical imaging. In this article, the different techniques and limitations of a range of airborne ultrasonic ranging approaches are reviewed, with an emphasis on the accuracy and repeatability of the measurements. Simple time-domain approaches are compared with their frequency-domain equivalents, and the use of hybrid models and biologically inspired approaches are discussed.


Protein tyrosine kinase is expressed and regulates ROMK1 location in the cortical collecting duct.
We previously demonstrated that dietary K intake regulates the expression of Src family PTK, which plays an important role in controlling the expression of ROMK1 in plasma membrane (Wei Y, Bloom P, Lin D-H, Gu RM, and Wang WH. Am J Physiol Renal Physiol 281: F206-F212, 2001). In the present study, we used the immunofluorescence staining technique to demonstrate the presence of c-Src, a member of Src family PTK, in the thick ascending limb (TAL) and collecting duct. Confocal microscopy shows that c-Src is highly expressed in the renal cortex and outer medulla. Moreover, c-Src and ROMK are coexpressed in the same nephron segment. Also, the positive staining of c-Src is visible in tubules stained with Tamm-Horsfall glycoprotein or aquaporin-2. This suggests that c-Src is present in the TAL, cortical collecting duct (CCD), and outer medullary collecting duct (OMCD). To study the role of PTK in the regulation of ROMK membrane expression in the TAL and CCD, we carried out immunocytochemical staining with ROMK antibody in the CCD or TAL from rats on either a high-K (HK) or K-deficient (KD) diet. A sharp membrane staining of ROMK can be observed in the TAL from rats on both HK and KD diets. However, a clear plasma membrane staining can be observed only in the CCD from rats on a HK diet but not from those on a KD diet. Treatment of the CCD from rats on a HK diet with phenylarsine oxide (PAO) decreases the positive staining in the plasma/subapical membrane and increases the ROMK staining in the intracellular compartment. However, PAO treatment did not significantly alter the staining pattern of ROMK in the TAL. Moreover, the biotinylation technique has also confirmed that neither herbimycin A nor PAO has significantly changed the biotin-labeled ROMK2 in HEK293 cells transfected with ROMK2 and c-Src. We conclude that c-Src is expressed in the TAL, CCD, and OMCD and that stimulation of PTK increases the ROMK channels in the intracellular compartment but decreases them in the apical/subapical membrane in the CCD.


Histoenzymological studies on the distribution of Ca++-activated adenosine triphosphatase amongst the constituents of the retinae of Varanus and Ptyas.
A comparative histoenzymological study of the distribution of Ca++-activated adenosine triphosphatase amongst the various constituents of the retinae of Varanus and Ptyas, hitherto not reported in the literature, has been made in great detail. The outer segment has shown an enzymatic activity of a very high degree both in Varanus and Ptyas. A detailed discussion is incorporated in analysing the possible role of the enzyme in the metabolic set-up of the area in relation to the resolution of the stimuli. Besides the outer segments, the areas possessing the lay-outs of nerve fibres and synaptic contacts have also shown ATPase activity of high degree in the retinae. The role of the ATPase in the nerve fibres and the synapses has been discussed in detail.


The Impact of Uremic Toxins on Vascular Smooth Muscle Cell Function.
Chronic kidney disease (CKD) is associated with profound vascular remodeling, which accelerates the progression of cardiovascular disease. This remodeling is characterized by intimal hyperplasia, accelerated atherosclerosis, excessive vascular calcification, and vascular stiffness. Vascular smooth muscle cell (VSMC) dysfunction has a key role in the remodeling process. Under uremic conditions, VSMCs can switch from a contractile phenotype to a synthetic phenotype, and undergo abnormal proliferation, migration, senescence, apoptosis, and calcification. A growing body of data from experiments in vitro and animal models suggests that uremic toxins (such as inorganic phosphate, indoxyl sulfate and advanced-glycation end products) may directly impact the VSMCs' physiological functions. Chronic, low-grade inflammation and oxidative stress-hallmarks of CKD-are also strong inducers of VSMC dysfunction. Here, we review current knowledge about the impact of uremic toxins on VSMC function in CKD, and the consequences for pathological vascular remodeling.


Individual growth of Heleobia piscium in natural populations (Gastropoda: Cochliopidae) from the multiple use natural Reserve Isla Martin Garcia, Buenos Aires, Argentina.
The present work analyses the individual growth of Heleobia piscium in natural conditions in coastal drainage channels of the Multiple Use Natural Reserve Isla Martín García, Buenos Aires, Argentina. Isla Martín García is located in the Upper Río de la Plata, to the south of the mouth of the Uruguay river (34 degrees 11' 25" S and 58 degrees 15' 38" W). Monthly collections were made from July 2005 to July 2006 in the eastern part of the island (Arena Beach). The population of H. piscium showed a complex and dynamic structure of sizes during a long period of the annual cycle. Two cohorts could be detected. The Bertalanffy growth equation was: Lt = 6 (1-e -1.85 (t+0.38)) and Lt = 3.9 (1-e -0.19 (t+4.84)) for cohorts 1 and 2, respectively. The pattern of population growth displayed a staggered model, where the greatest growth is observed during the summer. The reproductive period occurred during six months, from the beginning of summer to middle of fall. Based on only one reproductive effort, this pattern is not similar to that of other cogeneric species already studied.


Stone Age hut in Israel yields world's oldest evidence of bedding.
The earliest archaeological remains of dwelling huts built by Homo sapiens were found in various European Upper Paleolithic open-air camps. Although floors of huts were found in a small number of cases, modern organization of the home space that includes defined resting areas and bedding remains was not discovered. We report here the earliest in situ bedding exposed on a brush hut floor. It has recently been found at the previously submerged, excellently preserved 23,000-year-old fisher-hunter-gatherers' camp of Ohalo II, situated in Israel on the shore of the Sea of Galilee. The grass bedding consists of bunches of partially charred Puccinellia confer convoluta stems and leaves, covered by a thin compact layer of clay. It is arranged in a repeated pattern, on the floor, around a central hearth. This study describes the bedding in its original context on a well preserved intentionally constructed floor. It also reconstructs on the basis of direct evidence (combined with ethnographic analogies) the Upper Paleolithic hut as a house with three major components: a hearth, specific working locales, and a comfortable sleeping area near the walls.


Painful Temporomandibular Disorders, Bruxism and Oral Parafunctions before and during the COVID-19 Pandemic Era: A Sex Comparison among Dental Patients.
To evaluate the effect of the current coronavirus pandemic on the prevalence of bruxism, oral parafunctions and painful Temporo-Mandibular Disorders (TMDs) and to evaluate the influence of the pandemic on both sexes. This retrospective study included 288 dental patients who underwent complete anamnesis and examination according to the Diagnostic Criteria for TMD. The study evaluated two patient populations according to the date of examination: (a) pre-COVID-19 pandemic era (108 patients); (b) COVID 19 pandemic era, where 180 patients were examined during the pandemic. A significant increase in parafunction activity was found in both men and women (p < 0.001) during the COVID-19 pandemic. Awake bruxism (AB) and sleep bruxism (SB) was more prevalent during the COVID-19 pandemic solely in women (AB-p < 0.001; SB-p = 0.014). Men and women were affected by the ongoing stress due to the COVID-19 pandemic, yet women showed a higher influence as compared to men. The long-term exposure to elevated levels of anxiety and stress may aggravate or trigger stomatognathic detrimental conditions. Dentists should be aware and regularly monitor their patients regarding the possible existence and consequences of bruxism and TMD.


Mutant Huntingtin Disrupts the Nuclear Pore Complex.
Huntington's disease (HD) is caused by an expanded CAG repeat in the Huntingtin (HTT) gene. The mechanism(s) by which mutant HTT (mHTT) causes disease is unclear. Nucleocytoplasmic transport, the trafficking of macromolecules between the nucleus and cytoplasm, is tightly regulated by nuclear pore complexes (NPCs) made up of nucleoporins (NUPs). Previous studies offered clues that mHTT may disrupt nucleocytoplasmic transport and a mutation of an NUP can cause HD-like pathology. Therefore, we evaluated the NPC and nucleocytoplasmic transport in multiple models of HD, including mouse and fly models, neurons transfected with mHTT, HD iPSC-derived neurons, and human HD brain regions. These studies revealed severe mislocalization and aggregation of NUPs and defective nucleocytoplasmic transport. HD repeat-associated non-ATG (RAN) translation proteins also disrupted nucleocytoplasmic transport. Additionally, overexpression of NUPs and treatment with drugs that prevent aberrant NUP biology also mitigated this transport defect and neurotoxicity, providing future novel therapy targets.


Initial treatment response among HIV subtype F infected patients who started antiretroviral therapy based on integrase inhibitors.
: HIV-1 subtype B (54.4%) and subtype F (27.2%) are the most prevalent variants in patients who started antiretroviral therapy including an integrase inhibitor in the last 2 years in Northwest Spain. Virological response rates to antiretroviral therapy based on integrase inhibitor were significantly lower among F subtypes compared with B subtypes at weeks 12 (25.0% vs. 75.0%) and 24 (59.1% vs. 95.0%). Subtype F was independently associated with virological response at 24 weeks [odds ratio 11.8 (95% confidence interval 1.1-119.9); P = 0.037].


Anaerobic monodigestion of poultry manure: determination of operational parameters for CSTR.
In this work the anaerobic monodigestion for the treatment of turkey manure was evaluated, without its codigestion with another substrate. The effect of the organic loading rate (OLR) and the substrate concentration (high total solids (TS) concentration) or product concentration (high volatile fatty acids (VFA) and/or ammonia (NH(3)-N) concentrations) was studied. The results show that for a continuous stirred tank reactor (CSTR) operation, a maximum of 40 g/L of TS and 4.0 g/L of ammonium (NH(4)(+)) was required. In addition, the maximum organic loading rate (OLR) will not exceed 1.5 kg VS/m(3)d. Higher TS and NH(4)(+) concentrations and OLR lead to a reduction on the methane productivity and volatile solids (VS) removal. During the CSTR operation, a high alkalinity concentration (above 10 g/L CaCO(3)) was found; this situation allowed maintaining a constant and appropriate pH (close to 7.8), despite the VFA accumulation. In this sense, the alkalinity ratio (α) is a more appropriate control and monitoring parameter of the reactor operation compared to pH. Additionally, with this parameter a VS removal of 80% with a methane productivity of 0.50 m(3)(CH4)/m(3)(R)d is achieved.


Genome differences among varicella-zoster virus isolates.
The DNAs of 17 isolates of varicella-zoster virus (VZV) were analysed by restriction endonuclease cleavage and agarose gel electrophoresis. By comparing gel patterns of DNAs cleaved with only a few enzymes, all epidemiologically distinct isolates were shown to be unique. Two isolates recovered from members of a family infected in a common-source outbreak were identical to each other (4/4 enzymes) but distinct from the other strains. In addition, three isolates recovered at different times during the course of a single episode of zoster in another individual were identical by endonuclease analysis (4/4 enzymes) but once again were distinct from all other isolates. The differences that have been recognized in cleavage profiles of all VZV strains reported thus far map into four regions of the viral genome. Two of these variable regions lie within the long unique sequences while the other differences appear to map in each of the inverted repeat sequences.


Utilizing the Luminex Magnetic Bead-Based Suspension Array for Rapid Multiplexed Phosphoprotein Quantification.
The study of protein phosphorylation is critical for the advancement of our understanding of cellular responses to external and internal stimuli. Phosphorylation, the addition of phosphate groups, most often occurs on serine, threonine, or tyrosine residues due to the action of protein kinases. This structural change causes the protein to become activated (or deactivated) and enables it in turn to initiate the phosphorylation of other proteins in a cascade, eventually causing cell-wide changes such as apoptosis, cell differentiation, and growth (among others). Cellular phosphoprotein pathway dysregulation by mutation or chromosomal instability can often give the cell a selective advantage and lead to cancer. Obviously the understanding of these systems is of huge importance to the field of oncology.This chapter aims to provide a "how to" manual for one such technology, the 96-well plate-based xMAP® platform from Luminex. The system utilizes antibody-bound free-floating magnetic spheres which can easily be removed from suspension via magnetization. There are 100 unique bead sets (moving up to 500 bead sets for the most recent system) identified by the ratio of two dyes coating the microsphere. Each bead set is conjugated to a specific antibody which allows targeted protein extraction from low-concentration lysate solution. Biotinylated secondary antibodies/streptavidin-R-phycoerythrin (SAPE) complexes provide the quantification mechanism for the phosphoprotein of interest.


Methyl sulfone induces loss of metastatic properties and reemergence of normal phenotypes in a metastatic cloudman S-91 (M3) murine melanoma cell line.
The most deadly form of cancer is not lung or colon, breast or prostate; it is any cancer that has become metastatic. Mortality due to metastatic melanoma, one of the most aggressive and deadly cancers, has increased steadily over the last several decades. Unfortunately, the arsenal of chemotherapeutic agents available today is most often unsuccessful at extending and improving the life expectancy of afflicted individuals. We sought to identify an effective and nontoxic agent against metastatic melanoma. We chose to study Cloudman S-91 mouse melanoma cells (sub-clone M3, CCL53.1) because these cells are highly aggressive and metastatic, representing one of the deadliest types of cancer. Melanoma cells also had an experimental advantage because their morphology, which is easily monitored, relates to the physiology of metastatic cells and normal melanocytes. We chose to test methyl sulfone as a chemotherapeutic agent for two reasons. Because of its chemical structure, we speculated a potential anti-cancer activity by targeting microtubules. Equally important, methyl sulfone has a well-established safety profile in humans. Surprisingly, we found that malignant melanoma cells exposed to methyl sulfone demonstrated the loss of phenotypes characteristic of malignant cells, and the reemergence of phenotypes characteristic of healthy melanocytes. Briefly, over time methyl sulfone induced contact inhibition, loss of ability to migrate through an extracellular matrix, loss of anchorage-independent growth, proper wound healing followed by contact inhibition, irreversible senescence followed by arborization with melanosomes in arbors as seen in normal melanocytes. Methyl sulfone may have clinical potential as a non-toxic agent effective against metastatic melanoma. Additionally, methyl sulfone has promise as a tool to explore molecular mechanisms of metastatic transformation as well as fundamental processes such as cell migration, contact inhibition, wound healing and cellular senescence.


Influence of optimised treatment of people with hip fracture on time to operation, length of hospital stay, reoperations and mortality within 1 year.
Hip fractures are a major cause of hospital stay among the elderly, and result in increased disability and mortality. In this study from 1 April 2003 to 31 March 2004, the influence of optimised treatment of hip fracture on time to operation, length of hospital stay, reoperations and mortality within 1 year were investigated. Comparisons were made between the first 210 patients in the period and the last 210 patients, who followed the new clinical pathway introduced at the University Hospital in Lund, Sweden. Early surgery, within 24h, was not associated with reduced mortality, but was significantly associated with reduced length of stay (p<0.001). Significantly more cases of osteosynthesis for femoral neck fracture were reoperated compared with all other types of surgery (p<0.001) when reoperations with extraction of the hook pins in healed fractures were excluded. Mortality was significantly higher among men than women at 4 (p=0.025) and 12 (p=0.001) months after fracture and among medically fit patients with administrative delay to surgery compared with patients with no delay (p<0.001).


Protein resistance of dextran and dextran-poly(ethylene glycol) copolymer films.
The protein resistance of dextran and dextran-poly(ethylene glycol) (PEG) copolymer films was examined on an organosilica particle-based assay support. Comb-branched dextran-PEG copolymer films were synthesized in a two step process using the organosilica particle as a solid synthetic support. Particles modified with increasing amounts (0.1-1.2 mg m(-2)) of three molecular weights (10,000, 66,900, 400,000 g mol(-1)) of dextran were found to form relatively poor protein-resistant films compared to dextran-PEG copolymers and previously studied PEG films. The efficacy of the antifouling polymer films was found to be dependent on the grafted amount and its composition, with PEG layers being the most efficient, followed by dextran-PEG copolymers, and dextran alone being the least efficient. Immunoglobulin gamma (IgG) adsorption decreased from ∼5 to 0.5 mg m(-2) with increasing amounts of grafted dextran, but bovine serum albumin (BSA) adsorption increased above monolayer coverage (∼2 mg m(-2)) indicating ternary adsorption of the smaller protein within the dextran layer.


An autocrine insulin feedback loop maintains pancreatic beta-cell 3-phosphorylated inositol lipids.
Phosphatidylinositol 3-kinases (PI3Ks) have a central role in pancreatic beta-cell function. Downstream events include the regulation of K(ATP) channel activity, insulin secretion, gene transcription, and cell survival. Fewer data are available on the 3-phosphorylated inositol lipids (3-PIs) that are the primary products of these kinases. We characterized these PI3K products in insulin-secreting HIT T15 cells and were able to demonstrate, for the first time the presence of phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P(2)]. We then showed that glucose can significantly increase PtdIns(3,4,5)P(3), PtdIns(3,4)P(2), and notably PtdIns(3,5)P(2). We investigated the mechanism(s) whereby these molecules are generated under both basal and glucose-stimulated conditions. We postulated that insulin exocytosis could drive the rises in 3-PIs. In our experimental system, we could detect a rise in insulin secretion within 1 min of glucose stimulation, thus allowing the possibility that early rises in 3-PIs are regulated by secreted insulin. This was confirmed because blockade of the beta-cell insulin receptor completely abrogated the glucose-mediated increase of all three lipids, driving their concentrations below basal levels. Using primary pancreatic islets and either blockade of the insulin receptor or antibodies to insulin, we verified that basal insulin secretion is responsible for the maintenance of 3-PIs. Therefore, autocrine insulin signaling, a feature compromised in diabetes, is essential to up-regulate both basal and glucose-stimulated levels of a vital family of second messengers that preserve and drive pancreatic beta-cell function.


Directed force chain networks and stress response in static granular materials.
A theory of stress fields in two-dimensional granular materials based on directed force chain networks is presented. A general Boltzmann equation for the densities of force chains in different directions is proposed and a complete solution is obtained for a special case in which chains lie along a discrete set of directions. The analysis and results demonstrate the necessity of including nonlinear terms in the Boltzmann equation. A line of nontrivial fixed-point solutions is shown to govern the properties of large systems. In the vicinity of a generic fixed point, the response to a localized load shows a crossover from a single, centered peak at intermediate depths to two propagating peaks at large depths that broaden diffusively.


Defining the construct of Masters level clinical practice in healthcare based on the UK experience.
Growing emphasis on Masters level provision has been facilitated by the migration of education into Higher Education and the requirement for Continuing Professional Development. Paralleling this has been the development of specialisation in clinical practice. These factors have contributed to a proliferation of Masters courses aiming to develop specialist clinical practice. The aim of the study was to define the behaviours that are indicative of the construct of masters level clinical practice, using the UK experience as an example. A modified Delphi study employed a total population sample of course tutors of masters courses (nursing/midwifery, physiotherapy, radiography, interprofessional) in the UK assessing clinical practice (n = 48). Round 1 requested behaviours indicative of the construct of Masters level clinical practice. Data were analysed through descriptive coding identifying emerging themes to inform the behaviours included in round 2 that asked the participants to rank the importance of each behaviour on a 1-5 scale. Round 3 requested ranking the importance of the different behaviours to the construct. Descriptive analysis and the use of Kendall's coefficient of concordance and Spearman's rho enabled interpretation of consensus in rounds 2 and 3. The response rate for the Delphi study was very good. There was good consensus amongst the 28 behaviours identified for round 1. The second round enabled 21 behaviours agreed to be very important indicators of the construct to be taken into round 3. The ranking process in round 3 highlighted the importance of for example, a critical approach to practice and advanced clinical reasoning. The resulting 20 behaviours demonstrate good measurement validity and external validity. The components of the construct can therefore be used as the basis for further research.


Mammography segmentation with maximum likelihood active contours.
We present a computer-aided approach to segmenting suspicious lesions in digital mammograms, based on a novel maximum likelihood active contour model using level sets (MLACMLS). The algorithm estimates the segmentation contour that best separates the lesion from the background using the Gamma distribution to model the intensity of both regions (foreground and background). The Gamma distribution parameters are estimated by the algorithm. We evaluate the performance of MLACMLS on real mammographic images. Our results are compared to those of two leading related methods: The adaptive level set-based segmentation method (ALSSM) and the spiculation segmentation using level sets (SSLS) approach, and show higher segmentation accuracy (MLACMLS: 86.85% vs. ALSSM: 74.32% and SSLS: 57.11%). Moreover, our results are qualitatively compared with those of the Active Contour Without Edge (ACWOE) and show a better performance. Further, the suitability of using ML as the objective function as opposed to the KL divergence and to the energy functional of the ACWOE is also demonstrated. Our algorithm is also shown to be robust to the selection of a required single seed point.


Transcriptional analysis of adipose tissue during development reveals depot-specific responsiveness to maternal dietary supplementation.
Brown adipose tissue (BAT) undergoes pronounced changes after birth coincident with the loss of the BAT-specific uncoupling protein (UCP)1 and rapid fat growth. The extent to which this adaptation may vary between anatomical locations remains unknown, or whether the process is sensitive to maternal dietary supplementation. We, therefore, conducted a data mining based study on the major fat depots (i.e. epicardial, perirenal, sternal (which possess UCP1 at 7 days), subcutaneous and omental) (that do not possess UCP1) of young sheep during the first month of life. Initially we determined what effect adding 3% canola oil to the maternal diet has on mitochondrial protein abundance in those depots which possessed UCP1. This demonstrated that maternal dietary supplementation delayed the loss of mitochondrial proteins, with the amount of cytochrome C actually being increased. Using machine learning algorithms followed by weighted gene co-expression network analysis, we demonstrated that each depot could be segregated into a unique and concise set of modules containing co-expressed genes involved in adipose function. Finally using lipidomic analysis following the maternal dietary intervention, we confirmed the perirenal depot to be most responsive. These insights point at new research avenues for examining interventions to modulate fat development in early life.


Wind- and tidal driven ambient noise in seasonally ice-covered waters north of the Svalbard archipelago.
This paper presents analysis of a 1-year (2018-2019) recording of ambient noise (40-2000 Hz) at a seasonally ice-covered location on the continental slope between the Svalbard archipelago and the Nansen Basin, northeast Atlantic Arctic. Time series of ambient noise show highest correlations with ice concentration and wind speed. A log-wind speed regression model is fitted to spectral noise data for three categories of ice concentration. Wind-speed dependence decreases with increasing ice concentration and increases with frequency, except at high ice concentration. Periodicity in noise during the ice-covered season is related to the M2 and M4 tidal current constituents.


Interplay between FGF21 and insulin action in the liver regulates metabolism.
The hormone FGF21 regulates carbohydrate and lipid homeostasis as well as body weight, and increasing FGF21 improves metabolic abnormalities associated with obesity and diabetes. FGF21 is thought to act on its target tissues, including liver and adipose tissue, to improve insulin sensitivity and reduce adiposity. Here, we used mice with selective hepatic inactivation of the IR (LIRKO) to determine whether insulin sensitization in liver mediates FGF21 metabolic actions. Remarkably, hyperglycemia was completely normalized following FGF21 treatment in LIRKO mice, even though FGF21 did not reduce gluconeogenesis in these animals. Improvements in blood sugar were due in part to increased glucose uptake in brown fat, browning of white fat, and overall increased energy expenditure. These effects were preserved even after removal of the main interscapular brown fat pad. In contrast to its retained effects on reducing glucose levels, the effects of FGF21 on reducing circulating cholesterol and hepatic triglycerides and regulating the expression of key genes involved in cholesterol and lipid metabolism in liver were disrupted in LIRKO mice. Thus, FGF21 corrects hyperglycemia in diabetic mice independently of insulin action in the liver by increasing energy metabolism via activation of brown fat and browning of white fat, but intact liver insulin action is required for FGF21 to control hepatic lipid metabolism.


Sweet liking phenotype, alcohol craving and response to naltrexone treatment in alcohol dependence.
To investigate the relationship between the sweet liking/sweet disliking phenotype (a putative probe of brain opioid function), craving for alcohol and response to treatment with naltrexone in individuals with alcohol dependence. Forty individuals with alcohol dependence were enrolled in a 12-week open-label study of 50 mg of naltrexone with four sessions of motivational enhancement therapy. Prior to treatment, individuals completed a sweet preference test and the Penn Alcohol Craving Scale. Subjects were categorized as sweet liking (SL), n = 15, or sweet disliking (SDL), n = 25, via a standard sweet tasting paradigm. The sweet tasting results were blinded to the subjects and to treatment staff. SL status, pretreatment craving and their interaction were examined as predictors of frequency of abstinent days and heavy drinking days during treatment with naltrexone. SL and SDL subjects achieved similar reductions in percent heavy drinking days with treatment. During treatment, SDL subjects had 48% abstinent days compared to 30% for SL subjects (P = 0.034). Pretreatment craving did not predict % heavy drinking days or % abstinent days. An interaction effect was found between the SL/SDL phenotype and pretreatment craving such that SL subjects with high craving demonstrated higher rates of percent abstinent days whereas SDL subjects with high craving demonstrated lower rates of percent abstinent days, P < 0.001. These findings indicate that the SL/SDL phenotype may predict variation in response to naltrexone and/or counseling treatment. Furthermore, the SL/SDL phenotype may interact with craving to provide a more robust prediction of outcome with naltrexone or counseling.