Driver Take-Over Behaviour Study Based on Gaze Focalization and Vehicle Data in CARLA Simulator.
Autonomous vehicles are the near future of the automobile industry. However, until they reach Level 5, humans and cars will share this intermediate future. Therefore, studying the transition between autonomous and manual modes is a fascinating topic. Automated vehicles may still need to occasionally hand the control to drivers due to technology limitations and legal requirements. This paper presents a study of driver behaviour in the transition between autonomous and manual modes using a CARLA simulator. To our knowledge, this is the first take-over study with transitions conducted on this simulator. For this purpose, we obtain driver gaze focalization and fuse it with the road's semantic segmentation to track to where and when the user is paying attention, besides the actuators' reaction-time measurements provided in the literature. To track gaze focalization in a non-intrusive and inexpensive way, we use a method based on a camera developed in previous works. We devised it with the OpenFace 2.0 toolkit and a NARMAX calibration method. It transforms the face parameters extracted by the toolkit into the point where the user is looking on the simulator scene. The study was carried out by different users using our simulator, which is composed of three screens, a steering wheel and pedals. We distributed this proposal in two different computer systems due to the computational cost of the simulator based on the CARLA simulator. The robot operating system (ROS) framework is in charge of the communication of both systems to provide portability and flexibility to the proposal. Results of the transition analysis are provided using state-of-the-art metrics and a novel driver situation-awareness metric for 20 users in two different scenarios.


PHF8 targets histone methylation and RNA polymerase II to activate transcription.
Mutations in PHF8 are associated with X-linked mental retardation and cleft lip/cleft palate. PHF8 contains a plant homeodomain (PHD) in its N terminus and is a member of a family of JmjC domain-containing proteins. While PHDs can act as methyl lysine recognition motifs, JmjC domains can catalyze lysine demethylation. Here, we show that PHF8 is a histone demethylase that removes repressive histone H3 dimethyl lysine 9 marks. Our biochemical analysis revealed specific association of the PHF8 PHD with histone H3 trimethylated at lysine 4 (H3K4me3). Chromatin immunoprecipitation followed by high-throughput sequencing indicated that PHF8 is enriched at the transcription start sites of many active or poised genes, mirroring the presence of RNA polymerase II (RNAPII) and of H3K4me3-bearing nucleosomes. We show that PHF8 can act as a transcriptional coactivator and that its activation function largely depends on binding of the PHD to H3K4me3. Furthermore, we present evidence for direct interaction of PHF8 with the C-terminal domain of RNAPII. Importantly, a PHF8 disease mutant was defective in demethylation and in coactivation. This is the first demonstration of a chromatin-modifying enzyme that is globally recruited to promoters through its association with H3K4me3 and RNAPII.


Significant Escherichia coli attenuation by vegetative buffers on annual grasslands.
A study was conducted to estimate the retention efficiency of vegetative buffers for Escherichia coli deposited on grasslands in cattle fecal deposits and subject to natural rainfall-runoff conditions. The study was conducted on annual grasslands in California's northern Sierra Nevada foothills, a region with a distinct wet-dry season Mediterranean climate. We used 48, 2.0- by 3.0-m runoff plots to examine the efficacy of 0.1-, 1.1-, and 2.1-m buffers at three land slopes (5, 20, and 35%) and four dry vegetation matter levels (225, 560, 900, and 4500 kg/ha) across 27 rainfall-runoff events during two rainfall seasons. Buffer width treatments were implemented by placement of cattle fecal material containing known loads of E. coli 0.1, 1.1, or 2.1 m upslope of the plot runoff collector. Mean total runoff to total rainfall ratio per plot ranged from 0.014:1 to 0.019:1 and reflected the high infiltration capacity of these soils. Approximately 94.8 to 99.995% of total E. coli load applied to each plot appears to be either retained in the fecal pat and/or attenuated within 0.1 m downslope of the fecal pat, irrespective of the presence of a wider vegetated buffer. Relative to a 0.1-m buffer, we found 0.3 to 3.1 log10 reduction in E. coli discharge per additional meter of vegetative buffer across the range of residual dry vegetation matter levels, land slope, and rainfall and runoff conditions experienced during this project. Buffer efficiency was significantly reduced as runoff increased. These results support the assertion that grassland buffers are an effective method for reducing animal agricultural inputs of waterborne E. coli into surface waters.


Functional and pseudogenes are similarly organized and may equally contribute to the extensive antibody diversity of the IgVHII family.
Eleven germ-line immunoglobulin VH genes have been isolated from a BALB/c genomic library, using a cDNA probe specific for the GAT/NPa variable region. Restriction fragments of all genes were sequenced: two over 800 bp, covering signals of the 5'- and 3'-non-coding regions, three encompassing the complete coding region and part of the 5', the remaining sequences covering most of the V coding region. All sequences pertained to the VHII family, and were compared with the other 13 homologous genes already published. Characteristic features defining the family are clearly visible all along the sequences analyzed, including the 5'-non-coding region, the leader fragment and the intron organization. About half of the compared genes have pseudogene characteristics, defined either by a stop codon in the coding region or the lack of an initiator codon in the leader segment. Analysis of the replacement mutations, as compared with silent ones, indicate that they are highly clustered in complementarity determining regions, for both the functional and the pseudogenes, suggesting that all genes have been submitted to similar selective pressure, and that the pseudogene repertoire may be actively used, by recombination and/or conversion process. Signals that regulate transcription are highly conserved through the family barriers. The VHII group is the largest Ig V genes family, with extreme sequence divergences reaching 22% nucleotide differences. As no two genes were found identical out of the 24 members compared, and as two genes were found to differ by as little as three nucleotides, it seems that the previous estimate of 60 members might be much too low.


Expression of the forkhead transcription factor FOXP1 is associated with that of estrogen receptor-beta in primary invasive breast carcinomas.
We previously identified a correlation between estrogen receptor alpha (ERalpha) and the candidate tumour suppressor gene Forkhead Box P1 (FOXP1), whose nuclear protein expression in breast tumours was associated with improved patient survival. However, the expression pattern of FOXP1 in normal breast tissue is more reminiscent of the second receptor, ERbeta, which has an emerging role as a tumour suppressor in breast cancer and critically may underlie the ability of some ERalpha-negative tumours to respond to tamoxifen. In a series of 283 breast cancers, in which ERalpha-positive tumours were treated with tamoxifen, the nuclear expression of ERbeta correlated significantly with ERalpha (p = 0.004), low-tumour grade (p = 0.008) and nuclear FOXP1 (p = 0.01). High-grade tumours exhibited significantly more cytoplasmic ERbeta than the low-grade tumours (p = 0.006). Regression analysis demonstrated that FOXP1 expression was most closely related to nuclear ERbeta (p = 0.021). Neither, nuclear or cytoplasmic ERbeta expression demonstrated prognostic significance. FOXP1 is not estrogen regulated and silencing FOXP1 expression, using siRNA, did not affect ERalpha, ERbeta or progesterone receptor expression, suggesting ER and FOXP1 co-expression may reflect a common regulatory mechanism.


Efficient bone formation in a swine socket lift model using Escherichia coli-derived recombinant human bone morphogenetic protein-2 adsorbed in β-tricalcium phosphate.
Several preclinical studies have shown that Escherichia coli-derived bone morphogenetic protein-2 (E-BMP-2) is as effective as mammalian cell-derived bone morphogenetic protein-2 (C-BMP-2) in the treatment of bone defects. However, further investigation of the effectiveness and determination of the optimal dosage of E-BMP-2 in large animals are still necessary before its full application in humans. This study investigated the efficiency of different concentrations of E-BMP-2 adsorbed in β-TCP for bone augmentation and osseointegration of immediate dental implants in a swine socket lift model. Following exposure of the maxillary sinus lateral wall, a 3.4-mm (diameter) cavity was drilled and filled with 0.1 g of β-TCP containing different doses of E-BMP-2 (0, 10, 30, or 100 μg/site) to lift the Schneiderian membrane. A dental implant was then immediately inserted. Bone-to-implant contact (BIC) and bone density (BD) examined via histological analysis were used as parameters to assess E-BMP-2 efficiency in bone formation. The implant stability quotient (ISQ) was measured using Osstell to determine the effect of E-BMP-2/β-TCP on implant stability. After 8 weeks, the groups that received 30 and 100 μg of E-BMP-2 showed substantial new bone formation in the elevated space, while no bone formation was observed with β-TCP alone. Accordingly, BIC and BD presented a dose-dependent response to increasing doses of E-BMP-2. However, there was no increase in implant stability with E-BMP-2 treatment. In conclusion, the E-BMP-2/β-TCP combination was efficient in bone formation and osseointegration of dental implants in a socket lift model in mini-pigs.


Tedizolid: A New Oxazolidinone Antibiotic for Skin and Soft Tissue Infections.
To review the chemistry, pharmacology, microbiology, pharmacodynamics, pharmacokinetics, clinical efficacy, tolerability, drug interactions, dosing, and administration of tedizolid phosphate (TDZ). A search of PubMed using the terms "tedizolid," "torezolid," "TR-701," "TR-700," "DA-7157," and "DA-7218" was performed. The manufacturer's Web site was also reviewed to further identify relevant information. All English-language articles from 2006 to November 2014 appearing in these searches were reviewed for relevance to this paper. In addition, their bibliographies were reviewed to identify any articles not uncovered in the searches. TDZ is the second oxazolidinone antibiotic with a spectrum of activity targeted against gram-positive organisms including methicillin-resistant Staphylococcus aureus . It is administered via intravenous infusion or orally without regard to food. The primary route of elimination is fecal excretion. Advanced age, hepatic dysfunction, or renal impairment does not alter its disposition. Phase III clinical trials have demonstrated that TDZ 200 mg daily for 6 days is noninferior to linezolid 600 mg twice daily for 10 days in the treatment of adults with skin and soft tissue infections caused or suspected to be caused by gram-positive organisms. TDZ has a side effect profile similar to that of linezolid and a lower potential for drug interactions. TDZ has been shown to be safe and effective for the treatment of adults with skin and soft tissue infections. Further research is needed to refine its role, particularly for the treatment of patients requiring a longer duration of therapy and in those receiving concomitant serotonergic agents.


Local interactions drive the formation of nonnative structure in the denatured state of human alpha-lactalbumin: a high resolution structural characterization of a peptide model in aqueous solution.
There are a small number of peptides derived from proteins that have a propensity to adopt structure in aqueous solution which is similar to the structure they possess in the parent protein. There are far fewer examples of protein fragments which adopt stable nonnative structures in isolation. Understanding how nonnative interactions are involved in protein folding is crucial to our understanding of the topic. Here we show that a small, 11 amino acid peptide corresponding to residues 101-111 of the protein alpha-lactalbumin is remarkably structured in isolation in aqueous solution. The peptide has been characterized by 1H NMR, and 170 ROE-derived constraints were used to calculate a structure. The calculations yielded a single, high-resolution structure for residues 101-107 that is nonnative in both the backbone and side-chain conformations. In the pH 6.5 crystal structure, residues 101-105 are in an irregular turn-like conformation and residues 106-111 form an alpha-helix. In the pH 4.2 crystal structure, residues 101-105 form an alpha-helix, and residues 106-111 form a loopike structure. Both of these structures are significantly different from the conformation adopted by our peptide. The structure in the peptide model is primarily the result of local side-chain interactions that force the backbone to adopt a nonnative 310/turn-like structure in residues 103-106. The structure in aqueous solution was compared to the structure in 30% trifluoroethanol (TFE), and clear differences were observed. In particular, one of the side-chain interactions, a hydrophobic cluster involving residues 101-105, is different in the two solvents and residues 107-111 are considerably more ordered in 30% TFE. The implications of the nonnative structure for the folding of alpha-lactalbumin is discussed.


Troubling "environments": postgenomics, Bajan wheezing, and Lévi-Strauss.
Postgenomics is intended to move beyond the search for genes to explore disease as a result of genes interacting with their environment, revealing how they have relevance for health. This addition of environment confers genomic research with new cultural life, making it relevant to public health discourse, government interventions, and health disparities. Drawing on ethnographic research following an American genetics of asthma study conducted in Barbados, I explore the ways environment gets construed by the multiple communities involved-U.S. researchers, Bajan officials, medical practitioners, and patient participants. I draw on Lévi-Strauss to argue that plural competing environments give mana to the American postgenomic project as intervention on racial injustice, household practices, pollution, and other aspects of asthma.


Testing the unitary theory of language lateralization using functional transcranial Doppler sonography in adults.
Hemispheric dominance for language can vary from task to task, but it is unclear if this reflects error of measurement or independent lateralization of different language systems. We used functional transcranial Doppler sonography to assess language lateralization within the middle cerebral artery territory in 37 adults (seven left-handers) on six tasks, each given on two occasions. Tasks taxed different aspects of language function. A pre-registered structural equation analysis was used to compare models of means and covariances. For most people, a single lateralized factor explained most of the covariance between tasks. A minority, however, showed dissociation of asymmetry, giving a second factor. This was mostly derived from a receptive task, which was highly reliable but not lateralized. The results suggest that variation in the strength of language lateralization reflects true individual differences and not just error of measurement. The inclusion of several tasks in a laterality battery makes it easier to detect cases of atypical asymmetry.


Toxicity and hazard of vanadium to mallard ducks (Anas platyrhynchos) and Canada geese (Branta canadensis).
A recent Canada goose (Branta canadensis) die-off at a petroleum refinery fly ash pond in Delaware was attributed to vanadium (V) toxicity. Because of the paucity of V toxicity data for wild birds, a series of studies was undertaken using the forms of V believed to have resulted in this incident. In 7-d single oral dose trials with mallard drakes (Anas platyrhynchos), the estimated median lethal dose (LD50) for vanadium pentoxide was 113 mg/kg body weight, while the LD50 for sodium metavanadate was 75.5 mg/kg. Sodium metavanadate was found to be even more potent (LD50 = 37.2 mg/kg) in male Canada geese. The most distinctive histopathological lesion of both forms of V was lympho-granulocytic enteritis with hemorrhage into the intestinal lumen. Vanadium accumulation in liver and kidney was proportional to the administered dose, and predictive analyses based on these data suggest that V concentrations of 10 microg/g dry weight (dw) in liver and 25 microg/g dw in kidney are associated with mortality (>90% confidence that exposure is >LD50) in mallards acutely exposed to sodium metavanadate. Chronic exposure to increasing dietary concentrations of sodium metavanadate (38.5 to 2651 ppm) over 67 d resulted in V accumulation in liver and kidney (25.2 and 13.6 microg/g dw, respectively), mild intestinal hemorrhage, blood chemistry changes, and evidence of hepatic oxidative stress in mallards, although some of these responses may have been confounded by food avoidance and weight loss. Dietary exposure of mallards to 250 ppm sodium metavanadate for 4 wk resulted in modest accumulation of V in liver and kidney (<5 microg/g dw) and mild intestinal hemorrhage. Based on these data and other observations, it is unlikely that chronic low-level dietary exposure to V poses a direct lethal hazard to wildlife. However, point sources, such as the V-laden fly ash pond encountered by geese at the petroleum refinery in Delaware, may pose a significant hazard to water birds.


Relationship between urinary concentrations of di(2-ethylhexyl) phthalate (DEHP) metabolites and reproductive hormones in polyvinyl chloride production workers.
We investigated the relationship between urinary metabolites of di(2-ethylhexyl) phthalate (DEHP) and reproductive hormones in workers of polyvinyl chloride (PVC) production plants. After exposure, most of the DEHP is rapidly metabolised to mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), which may be associated with reproductive hormone interruption and testicular toxicity. Some studies report that urinary concentrations of phthalate metabolites for plastics workers are significantly higher than for the general population. However, little is known about the disruption of reproductive hormones for DEHP exposure workers. This cross-sectional study of 82 male workers measured the biomarkers for their reproductive hormones and their exposure to DEHP. Relationships between urinary concentrations of DEHP metabolites were estimated using multivariate linear regression and quartile analysis models. The geometric means of urinary creatinine-adjusted (μg/g-Cre) concentrations of MEHP, MEOHP and MEHHP during the post-shift period were 23.9, 66.9 and 84.6, respectively. In multiple regression models adjusted for potential confounders, there were significant positive associations between urinary concentrations of DEHP metabolites and estradiol (E2) (p<0.01), and in the ratio of E2 to testosterone (p<0.05). Moreover, quartile analysis showed significant positive relationships between the total urinary concentration of DEHP metabolites and E2 (ptrend=0.024), and in the ratio of E2 to testosterone (ptrend=0.031). Relationships between reproductive hormones and the total urinary concentration of DEHP metabolites in male PVC production workers were significantly positive. This indicated that aromatase activity had increased in male workers exposed to DEHP, which is consistent with animal studies.


Superoxide-mediated activation of uncoupling protein 2 causes pancreatic beta cell dysfunction.
Failure to secrete adequate amounts of insulin in response to increasing concentrations of glucose is an important feature of type 2 diabetes. The mechanism for loss of glucose responsiveness is unknown. Uncoupling protein 2 (UCP2), by virtue of its mitochondrial proton leak activity and consequent negative effect on ATP production, impairs glucose-stimulated insulin secretion. Of interest, it has recently been shown that superoxide, when added to isolated mitochondria, activates UCP2-mediated proton leak. Since obesity and chronic hyperglycemia increase mitochondrial superoxide production, as well as UCP2 expression in pancreatic beta cells, a superoxide-UCP2 pathway could contribute importantly to obesity- and hyperglycemia-induced beta cell dysfunction. This study demonstrates that endogenously produced mitochondrial superoxide activates UCP2-mediated proton leak, thus lowering ATP levels and impairing glucose-stimulated insulin secretion. Furthermore, hyperglycemia- and obesity-induced loss of glucose responsiveness is prevented by reduction of mitochondrial superoxide production or gene knockout of UCP2. Importantly, reduction of superoxide has no beneficial effect in the absence of UCP2, and superoxide levels are increased further in the absence of UCP2, demonstrating that the adverse effects of superoxide on beta cell glucose sensing are caused by activation of UCP2. Therefore, superoxide-mediated activation of UCP2 could play an important role in the pathogenesis of beta cell dysfunction and type 2 diabetes.


A genetic variant of the sperm-specific SLO3 K+ channel has altered pH and Ca2+ sensitivities.
To fertilize an oocyte, sperm must first undergo capacitation in which the sperm plasma membrane becomes hyperpolarized via activation of potassium (K+) channels and resultant K+ efflux. Sperm-specific SLO3 K+ channels are responsible for these membrane potential changes critical for fertilization in mouse sperm, and they are only sensitive to pH i However, in human sperm, the major K+ conductance is both Ca2+- and pH i -sensitive. It has been debated whether Ca2+-sensitive SLO1 channels substitute for human SLO3 (hSLO3) in human sperm or whether human SLO3 channels have acquired Ca2+ sensitivity. Here we show that hSLO3 is rapidly evolving and reveal a natural structural variant with enhanced apparent Ca2+ and pH sensitivities. This variant allele (C382R) alters an amino acid side chain at a principal interface between the intramembrane-gated pore and the cytoplasmic gating ring of the channel. Because the gating ring contains sensors to intracellular factors such as pH and Ca2+, the effectiveness of transduction between the gating ring and the pore domain appears to be enhanced. Our results suggest that sperm-specific genes can evolve rapidly and that natural genetic variation may have led to a SLO3 variant that differs from wild type in both pH and intracellular Ca2+ sensitivities. Whether this physiological variation confers differences in fertility among males remains to be established.


Addition of N-terminal pro-B-type natriuretic peptide levels to electrocardiography criteria for detection of left ventricular hypertrophy: the ARIRANG study.
The utility of electrocardiography (ECG) in screening for left ventricular hypertrophy (LVH) in general populations is limited mainly because its low sensitivity. B-type natriuretic peptide (BNP) is released due to the remodeling processes of LVH and could improve the diagnostic accuracy for the ECG criteria for LVH. We hypothesized that addition of BNP levels to ECG criteria could aid LVH detection compared with ECG alone in a general population. We enrolled consecutive 343 subjects from a community-based cohort. LVH was defined as LV mass index > 95 g/m(2) for females and > 115 g/m(2) for males according to echocardiography. The area under the receiver operator characteristic (ROC) curve to detect LVH was 0.55 (95% confidence interval [CI], 0.50-0.61) in Sokolow-Lyon criteria and 0.53 (0.47-0.59) in the Cornell voltage criteria. After addition of N-terminal-proBNP levels to the model, the corresponding areas under the ROC were 0.63 (0.58-0.69) and 0.64 (0.59-0.69), respectively. P values for the comparison in areas under the ROC for models with and without N-terminal-proBNP levels were < 0.001. These data suggest that addition of N-terminal-proBNP levels to ECG criteria could significantly improve the diagnostic accuracy of LVH in general populations.


Citrate-based fluorescent materials for low-cost chloride sensing in the diagnosis of Cystic Fibrosis.
Chloride is an essential electrolyte that maintains homeostasis within the body, where abnormal chloride levels in biological fluids may indicate various diseases such as Cystic Fibrosis. However, current analytical solutions for chloride detection fail to meet the clinical needs of both high performance and low material or labor costs, hindering translation into clinical settings. Here we present a new class of fluorescence chloride sensors derived from a facile citrate -based synthesis platform that utilize dynamic quenching mechanisms. Based on this low-cost platform, we demonstrate for the first time a selective sensing strategy that uses a single fluorophore to detect multiple halides simultaneously, promising both selectivity and automation to improve performance and reduce labor costs. We also demonstrate the clinical utility of citrate-based sensors as a new sweat chloride test method for the diagnosis of Cystic Fibrosis by performing analytical validation with sweat controls and clinical validation with sweat from individuals with or without Cystic Fibrosis. Lastly, molecular modeling studies reveal the structural mechanism behind chloride sensing, serving to expand this class of fluorescence sensors with improved chloride sensitivities. Thus citrate-based fluorescent materials may enable low-cost, automated multi-analysis systems for simpler, yet accurate, point-of-care diagnostics that can be readily translated into clinical settings. More broadly, a wide range of medical, industrial, and environmental applications can be achieved with such a facile synthesis platform, demonstrated in our citrate-based biodegradable polymers with intrinsic fluorescence sensing.


Curcumin Ingestion Inhibits Mastocytosis and Suppresses Intestinal Anaphylaxis in a Murine Model of Food Allergy.
IgE antibodies and mast cells play critical roles in the establishment of allergic responses to food antigens. Curcumin, the active ingredient of the curry spice turmeric, has anti-inflammatory properties, and thus may have the capacity to regulate Th2 cells and mucosal mast cell function during allergic responses. We assessed whether curcumin ingestion during oral allergen exposure can modulate the development of food allergy using a murine model of ovalbumin (OVA)-induced intestinal anaphylaxis. Herein, we demonstrate that frequent ingestion of curcumin during oral OVA exposure inhibits the development of mastocytosis and intestinal anaphylaxis in OVA-challenged allergic mice. Intragastric (i.g.) exposure to OVA in sensitized BALB/c mice induced a robust IgE-mediated response accompanied by enhanced OVA-IgE levels, intestinal mastocytosis, elevated serum mMCP-1, and acute diarrhea. In contrast, mice exposed to oral curcumin throughout the experimental regimen appeared to be normal and did not exhibit intense allergic diarrhea or a significant enhancement of OVA-IgE and intestinal mast cell expansion and activation. Furthermore, allergic diarrhea, mast cell activation and expansion, and Th2 responses were also suppressed in mice exposed to curcumin during the OVA-challenge phase alone, despite the presence of elevated levels of OVA-IgE, suggesting that curcumin may have a direct suppressive effect on intestinal mast cell activation and reverse food allergy symptoms in allergen-sensitized individuals. This was confirmed by observations that curcumin attenuated the expansion of both adoptively transferred bone marrow-derived mast cells (BMMCs), and inhibited their survival and activation during cell culture. Finally, the suppression of intestinal anaphylaxis by curcumin was directly linked with the inhibition of NF-κB activation in curcumin-treated allergic mice, and curcumin inhibited the phosphorylation of the p65 subunit of NF-κB in BMMCs. In summary, our data demonstrates a protective role for curcumin during allergic responses to food antigens, suggesting that frequent ingestion of this spice may modulate the outcome of disease in susceptible individuals.


"Meet me at the hill where we used to park": interpersonal processes associated with victim recantation.
Our study used live telephone conversations between domestic violence perpetrators and victims to answer novel questions about how and why victims arrive at their decision to recant and/or refuse prosecution efforts. From October 2008 to June 2011, we conducted a qualitative study involving 25 heterosexual couples, where the male perpetrator was being held in a Detention Facility (in the U.S.) for felony-level domestic violence and made telephone calls to his female victim during the pre-prosecution period. We used 30-192 min of conversational data for each couple to examine: 1) interpersonal processes associated with the victim's intention to recant; and 2) the couple's construction of the recantation plan once the victim intended to recant. We used constructivist grounded theory to guide data analysis, which allowed for the construction of a novel recantation framework, while acknowledging the underlying coercive interpersonal dynamic. Our results showed that consistently across couples, a victim's recantation intention was foremost influenced by the perpetrator's appeals to the victim's sympathy through descriptions of his suffering from mental and physical problems, intolerable jail conditions, and life without her. The intention was solidified by the perpetrator's minimization of the abuse, and the couple invoking images of life without each other. Once the victim arrived at her decision to recant, the couple constructed the recantation plan by redefining the abuse event to protect the perpetrator, blaming the State for the couple's separation, and exchanging specific instructions on what should be said or done. Our findings advance scientific knowledge through identifying, in the context of ongoing interactions, strategies perpetrators used--sympathy appeals and minimization--to successfully persuade their victim and strategies the couple used to preserve their relationship.Practitioners must double their efforts to hold perpetrators accountable for their actions, and efforts made to link victims to trusted advocates who can help them defend against perpetrators' sophisticated techniques.


The significance of nanomaterial post-exposure responses in Daphnia magna standard acute immobilisation assay: Example with testing TiO2 nanoparticles.
One of the most widely used aquatic standarized tests for the toxicity screening of chemicals is the acute toxicity test with the freshwater crustacean Daphnia magna, which has also been applied in the toxicity screening of manufactured nanoparticles (NPs). However, in the case of non-soluble NPs most of the results of this test have showed no effect. The aim of the work presented here was to modify the standardized test by the least possible extent to make it more sensitive for non-soluble particles. The standard acute immobilisation assay with daphnids was modified by prolonging the exposure period and by measuring additional endpoints. Daphnids were exposed to TiO2 NPs in a standard acute test (48h of exposure), a standard acute test (48h of exposure) followed by 24h recovery period in clean medium or a prolonged exposure in the NPs solutions totaling 72h. Together with immobility, the adsorption of NPs to body surfaces was also observed as an alternative measure of the NPs effects. Our results showed almost no effect of TiO2 NPs on D. magna after the 48h standard acute test, while immobility was increased when the exposure period to TiO2 NPs was prolonged from 48h to 72h. Even when daphnids were transferred to clean medium for additional 24h after 48h of exposure to TiO2 NPs the immobility increased. We conclude that by transferring the daphnids to clean medium at the end of the 48h exposure to TiO2 NPs, the delayed effects of the tested material can be seen. This methodological step could improve the sensitivity of D. magna test as a model in nanomaterial environmental risk assessment.


A mobile phone application for the assessment and management of youth mental health problems in primary care: a randomised controlled trial.
Over 75% of mental health problems begin in adolescence and primary care has been identified as the target setting for mental health intervention by the World Health Organisation. The mobiletype program is a mental health assessment and management mobile phone application which monitors mood, stress, coping strategies, activities, eating, sleeping, exercise patterns, and alcohol and cannabis use at least daily, and transmits this information to general practitioners (GPs) via a secure website in summary format for medical review. We conducted a randomised controlled trial in primary care to examine the mental health benefits of the mobiletype program. Patients aged 14 to 24 years were recruited from rural and metropolitan general practices. GPs identified and referred eligible participants (those with mild or more mental health concerns) who were randomly assigned to either the intervention group (where mood, stress, and daily activities were monitored) or the attention comparison group (where only daily activities were monitored). Both groups self-monitored for 2 to 4 weeks and reviewed the monitoring data with their GP. GPs, participants, and researchers were blind to group allocation at randomisation. Participants completed pre-, post-, and 6-week post-test measures of the Depression, Anxiety, Stress Scale and an Emotional Self Awareness (ESA) Scale. Of the 163 participants assessed for eligibility, 118 were randomised and 114 participants were included in analyses (intervention group n = 68, comparison group n = 46). Mixed model analyses revealed a significant group by time interaction on ESA with a medium size of effect suggesting that the mobiletype program significantly increases ESA compared to an attention comparison. There was no significant group by time interaction for depression, anxiety, or stress, but a medium to large significant main effect for time for each of these mental health measures. Post-hoc analyses suggested that participation in the RCT lead to enhanced GP mental health care at pre-test and improved mental health outcomes. Monitoring mental health symptoms appears to increase ESA and implementing a mental health program in primary care and providing frequent reminders, clinical resources, and support to GPs substantially improved mental health outcomes for the sample as a whole. ClinicalTrials.gov NCT00794222.


The interparental relationship: Meta-analytic associations with children's maladjustment and responses to interparental conflict.
The aim of the current meta-analysis was to aggregate concurrent and longitudinal empirical research on associations between the interparental relationship and both children's maladjustment (i.e., externalizing and internalizing symptoms) and children's responses to interparental conflict (i.e., emotional, behavioral, cognitive, and physiological). Based on major theoretical frameworks, we distinguished between six dimensions of the interparental relationship: relationship quality, conflict frequency, hostile, disengaged, and unconstructive forms of conflict, and child-related conflict. A final selection of 169 studies for child maladjustment and 61 studies for child responses to conflict were included. The findings revealed by the expansive and fine-grained approach of this meta-analysis support and challenge theoretical hypotheses about the relative predictive value of dimensions of the interparental relationship for children's functioning. Although hostility was specifically more strongly associated with children's externalizing behavior and emotional responses to conflict, disengaged and unconstructive conflict behavior posed similar risks for the other domains of child functioning. In addition, relationship quality, conflict frequency, and child-related conflict warrant more attention in theoretical frameworks, as these dimensions posed similar risks to child functioning as the different forms of conflict. Moreover, most associations between the interparental relationship and child functioning endured over time. Also, developmental and gender differences appeared to depend on the specific forms of interparental conflict and the domain of child functioning. In sum, the results support the growing consensus that prevention and intervention programs aimed at children's mental health could benefit from an alternative or additional focus on the interparental relationship. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND).
Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.


Intramyocardial Injection of Mesenchymal Precursor Cells and Successful Temporary Weaning From Left Ventricular Assist Device Support in Patients With Advanced Heart Failure: A Randomized Clinical Trial.
Left ventricular assist device (LVAD) therapy improves myocardial function, but few patients recover sufficiently for explant, which has focused attention on stem cells to augment cardiac recovery. To assess efficacy and adverse effects of intramyocardial injections of mesenchymal precursor cells (MPCs) during LVAD implant. A randomized phase 2 clinical trial involving patients with advanced heart failure, undergoing LVAD implant, at 19 North American centers (July 2015-August 2017). The 1-year follow-up ended August 2018. Intramyocardial injections of 150 million allogeneic MPCs or cryoprotective medium as a sham treatment in a 2:1 ratio (n = 106 vs n = 53). The primary efficacy end point was the proportion of successful temporary weans (of 3 planned assessments) from LVAD support within 6 months of randomization. This end point was assessed using a Bayesian analysis with a predefined threshold of a posterior probability of 80% to indicate success. The 1-year primary safety end point was the incidence of intervention-related adverse events (myocarditis, myocardial rupture, neoplasm, hypersensitivity reactions, and immune sensitization). Secondary end points included readmissions and adverse events at 6 months and 1-year survival. Of 159 patients (mean age, 56 years; 11.3% women), 155 (97.5%) completed 1-year of follow-up. The posterior probability that MPCs increased the likelihood of successful weaning was 69%; below the predefined threshold for success. The mean proportion of successful temporary weaning from LVAD support over 6 months was 61% in the MPC group and 58% in the control group (rate ratio [RR], 1.08; 95% CI, 0.83-1.41; P = .55). No patient experienced a primary safety end point. Of 10 prespecified secondary end points reported, 9 did not reach statistical significance. One-year mortality was not significantly different between the MPC group and the control group (14.2% vs 15.1%; hazard ratio [HR], 0.89; 95%, CI, 0.38-2.11; P = .80). The rate of serious adverse events was not significantly different between groups (70.9 vs 78.7 per 100 patient-months; difference, -7.89; 95% CI, -39.95 to 24.17; P = .63) nor was the rate of readmissions (0.68 vs 0.75 per 100 patient-months; difference, -0.07; 95% CI, -0.41 to 0.27; P = .68). Among patients with advanced heart failure, intramyocardial injections of mesenchymal precursor cells, compared with injections of a cryoprotective medium as sham treatment, did not improve successful temporary weaning from left ventricular assist device support at 6 months. The findings do not support the use of intramyocardial mesenchymal stem cells to promote cardiac recovery as measured by temporary weaning from device support. clinicaltrials.gov Identifier: NCT02362646.


Open access, library and publisher competition, and the evolution of general commerce.
Discussions of the economics of scholarly communication are usually devoted to Open Access, rising journal prices, publisher profits, and boycotts. That ignores what seems a much more important development in this market. Publishers, through the oft-reviled Big Deal packages, are providing much greater and more egalitarian access to the journal literature, an approximation to true Open Access. In the process, they are also marginalizing libraries and obtaining a greater share of the resources going into scholarly communication. This is enabling a continuation of publisher profits as well as of what for decades has been called "unsustainable journal price escalation." It is also inhibiting the spread of Open Access and potentially leading to an oligopoly of publishers controlling distribution through large-scale licensing. The Big Deal practices are worth studying for several general reasons. The degree to which publishers succeed in diminishing the role of libraries may be an indicator of the degree and speed at which universities transform themselves. More importantly, these Big Deals appear to point the way to the future of the whole economy, where progress is characterized by declining privacy, increasing price discrimination, increasing opaqueness in pricing, increasing reliance on low-paid or unpaid work of others for profits, and business models that depend on customer inertia.


Type 1 and type 2 T-cell profiles in idiopathic thrombocytopenic purpura.
Adult idiopathic thrombocytopenic purpura (ITP) is a chronic acquired organ-specific autoimmune hemorrhagic disease characterized by the production of antibodies against antigens on the membranes of platelet, resulting in enhanced Fc-mediated destruction of the platelets by macrophages in the reticuloendothelial system. Dysfunctional cellular immunity is considered important in the pathophysiology of ITP. The aim of this study was to explore the profile of type1 and type2 T cells in chronic ITP patients. The balance of Th1/Th2 and Tc1/Tc2 was studied by simultaneous analysis of intracellular cytokines of peripheral blood mononuclear cells and splenocytes in short-term cultures activated with PMA/ionomycin as well as mRNA expression of T-bet and GATA-3 in peripheral blood mononuclear cells and splenocytes using real-time polymerase chain reaction. Patients with active disease but not patients in remission had significant higher Th1/Th2 (p<0.01) and Tc1/Tc2 (p<0.01) ratios in peripheral blood (PB) and significant higher Th1/Th2 ratio in splenocytes (p<0.01) than those in the control group. The Tc1/Tc2 ratio in splenocytes in ITP patients was higher than that in control, but did not reach significant difference (p=0.082). GATA-3 mRNA expression in ITP patients was significantly lower both in PB (p<0.01) and in splenocytes (p<0.01) than in corresponding samples from controls while there was no difference in T-bet expression. Our data indicate that ITP is a T1 cell (Th1 and Tc1) predominant disease although the precise mechanisms await further functional assay. The T-bet/GATA-3 ratio may provide a surrogate marker of T1/T2 cytokine balance. Shifting the cytokine patterns from T1 to T2 might be a potential immunotherapy for ITP.


Novel hepatic progenitor cell surface markers in the adult rat liver.
Hepatic progenitor/oval cells appear in injured livers when hepatocyte proliferation is impaired. These cells can differentiate into hepatocytes and cholangiocytes and could be useful for cell and gene therapy applications. In this work, we studied progenitor/oval cell surface markers in the liver of rats subjected to 2-acetylaminofluorene treatment followed by partial hepatectomy (2-AAF/PH) by using rat genome 230 2.0 Array chips and subsequent RT-PCR, immunofluorescent (IF), immunohistochemical (IHC) and in situ hybridization (ISH) analyses. We also studied expression of the identified novel cell surface markers in fetal rat liver progenitor cells and FAO-1 hepatoma cells. Novel cell surface markers in adult progenitor cells included tight junction proteins, integrins, cadherins, cell adhesion molecules, receptors, membrane channels and other transmembrane proteins. From the panel of 21 cell surface markers, 9 were overexpressed in fetal progenitor cells, 6 in FAO-1 cells and 6 are unique for the adult progenitors (CD133, claudin-7, cadherin 22, mucin-1, ros-1, Gabrp). The specificity of progenitor/oval cell surface markers was confirmed by ISH and double IF analyses. Moreover, study of progenitor cells purified with Ep-CAM antibodies from D-galactosamine injured rat liver, a noncarcinogenic model of progenitor cell activation, verified that progenitor cells expressed these markers. We identified novel cell surface markers specific for hepatic progenitor/oval cells, which offers powerful tool for their identification, isolation and studies of their physiology and pathophysiology. Our studies also reveal the mesenchymal/epithelial phenotype of these cells and the existence of species diversity in the hepatic progenitor cell identity.


The natural history of progressive fibrosing interstitial lung diseases.
We used data from the INBUILD and INPULSIS trials to investigate the natural history of progressive fibrosing interstitial lung diseases (ILDs).Subjects in the two INPULSIS trials had a clinical diagnosis of idiopathic pulmonary fibrosis (IPF) while subjects in the INBUILD trial had a progressive fibrosing ILD other than IPF and met protocol-defined criteria for ILD progression despite management. Using data from the placebo groups, we compared the rate of decline in forced vital capacity (FVC) (mL·year-1) and mortality over 52 weeks in the INBUILD trial with pooled data from the INPULSIS trials.The adjusted mean annual rate of decline in FVC in the INBUILD trial (n=331) was similar to that observed in the INPULSIS trials (n=423) (-192.9 mL·year-1 and -221.0 mL·year-1, respectively; nominal p-value=0.19). The proportion of subjects who had a relative decline in FVC >10% predicted at Week 52 was 48.9% in the INBUILD trial and 48.7% in the INPULSIS trials, and the proportion who died over 52 weeks was 5.1% in the INBUILD trial and 7.8% in the INPULSIS trials. A relative decline in FVC >10% predicted was associated with an increased risk of death in the INBUILD trial (hazard ratio 3.64) and the INPULSIS trials (hazard ratio 3.95).These findings indicate that patients with fibrosing ILDs other than IPF, who are progressing despite management, have a subsequent clinical course similar to patients with untreated IPF, with a high risk of further ILD progression and early mortality.


Melatonin modulates aromatase activity in MCF-7 human breast cancer cells.
Most of the current knowledge about the mechanisms by which melatonin inhibits the growth of breast cancer cells point to an interaction of melatonin with estrogen-responsive pathways, thus behaving as an antiestrogenic hormone. However, a possible effect of melatonin on the local synthesis of estrogens had not been examined. The objective of this work was to study whether melatonin may modify the aromatase activity in MCF-7 breast cancer cells thus modulating the local estrogen biosynthesis. In MCF-7 cells cultured with testosterone in estradiol-free media, melatonin (1 nM) counteracts the testosterone-induced cell proliferation dependent on the local biosynthesis of estrogens from testosterone by the aromatase activity of the cells. We found that melatonin reduces the aromatase activity (measured by the tritiated water release assay) of MCF-7 cells both at basal conditions and when aromatase activity was stimulated by cAMP or cortisol. The greatest inhibition of the aromatase activity was obtained with 1 nm melatonin, the same concentration that gives the highest antiproliferative and anti-invasive effects of MCF-7 cells. Finally, by RT-PCR, we found that melatonin downregulates aromatase expression at the transcriptional level in the MCF-7 cells. We conclude that melatonin, at physiological concentrations, decreases aromatase activity and expression in MCF-7 cells. This aromatase inhibitory effect of melatonin, together with its already known antiestrogenic properties interacting with the estrogen-receptor, makes this indoleamine an interesting tool to be considered in the prevention and treatment of hormone-dependent mammary neoplasias.


Current advances of targeting HGF/c-Met pathway in gastric cancer.
Despite the advances in systemic chemotherapy, gastric adenocarcinoma (GC) remains the third most common cause of cancer-related deaths with poor prognosis. The heterogeneity of GC indicates that novel biomarkers should be established in order to further classify tumors and develop individual targeted therapies. High-quality preclinical and clinical research has demonstrated that growth factor (HGF)-hepatocyte growth factor receptor (c-Met) pathway plays a pivotal role on the growth, survival and invasiveness of GC. In particular, aberrant activation of HGF/c-Met signaling pathway has been associated with poor clinical outcomes, suggesting the therapeutic potential of c-Met. This has stimulated the development and evaluation of a number of c-Met targeted agents in an advance disease setting. In this review, we summarize the current state of the art in the advances on the inhibition of c-Met pathway, with particular emphasis on the clinical testing of c-Met targeted therapeutic agents. Furthermore, we discuss the challenges facing the incorporation of c-Met targeted agents in randomized trials, with the idea that the definition of the appropriate genetic and molecular context for the use of these agents remains the priority.


Anxiogenic effects of neurosteroid exposure: sex differences and altered GABAA receptor pharmacology in adult rats.
Acute exposure to progesterone or its neurosteroid derivative allopregnanolone (3alpha,5alpha-THP) is anxiolytic, consistent with the GABA modulatory effects of 3alpha,5alpha-THP at the GABA(A) receptor. However, continuous exposure to progesterone increases anxiety in association with increased expression of the benzodiazepine-insensitive GABA(A) receptor alpha4 subunit. Furthermore, negative mood symptoms and altered GABA(A) receptor pharmacology in patients with premenstrual dysphoric disorder occur in the early luteal phase in association with peak circulating levels of progesterone and 3alpha,5alpha-THP. Because sex differences have been reported in steroid-regulated anxiety responses, the present study investigated the role of sex and development in the regulation of anxiety after short-term exposure to 3alpha,5alpha-THP. To this end, we compared the effects of hormone administration in adult male, adult female, and juvenile female rats. Increased anxiety in the elevated plus maze was evident in all groups after 48-h exposure to either 3alpha,5alpha-THP or progesterone. At this time point, alterations in the anxiolytic profile of benzodiazepine agonists and antagonists were also observed in both adult males and females in the elevated plus maze. However, sex differences in the acoustic startle response were observed after short-term hormone treatment such that only female rats displayed an increased response indicative of higher anxiety levels. These results suggest that although neurosteroid exposure may influence both the pharmacological properties of the GABA(A) receptor and the manifestation of anxiety in both sexes, the effects of neurosteroids may be modulated in a sex- and task-specific manner.


The Developmental Leadership Questionnaire (DLQ): some psychometric properties.
The development leadership model (Larsson et al., 2003), designed to introduce refinements to the transformational leadership model, has been adopted for use in the Swedish Armed Forces. The Developmental Leadership Questionnaire (DLQ) was constructed to measure important parts of the model. The main aim of the study was to evaluate some psychometric properties of the DLQ. Most analyses are based on two subsets of individuals from a sample mostly consisting of male Swedish, military officers, each of whom has rated a given leader (n = 450 and 449 respectively). A second sample consisted of Swedish military cadets (n = 141). The dimensionality was assessed with a confirmatory factor analysis. Most DLQ scales were reasonably well reproduced and showed high or acceptable internal consistency. When related to perceived results of leadership (self-rated by leaders and rated by subordinates), results from multiple regression analyses supported what could be predicted by the theoretical model. It was concluded that the DLQ has acceptable psychometric properties and that the theoretical refinements introduced to the developmental leadership model were empirically supported.


An interlaboratory comparison of nanosilver characterisation and hazard identification: Harmonising techniques for high quality data.
Within the FP7 EU project NanoValid a consortium of six partners jointly investigated the hazard of silver nanoparticles (AgNPs) paying special attention to methodical aspects that are important for providing high-quality ecotoxicity data. Laboratories were supplied with the same original stock dispersion of AgNPs. All partners applied a harmonised procedure for storage and preparation of toxicity test suspensions. Altogether ten different toxicity assays with a range of environmentally relevant test species from different trophic levels were conducted in parallel to AgNP characterisation in the respective test media. The paper presents a comprehensive dataset of toxicity values and AgNP characteristics like hydrodynamic sizes of AgNP agglomerates and the share (%) of Ag(+)-species (the concentration of Ag(+)-species in relation to the total measured concentration of Ag). The studied AgNP preparation (20.4±6.8 nm primary size, mean total Ag concentration 41.14 mg/L, 46-68% of soluble Ag(+)-species in stock, 123.8±12.2 nm mean z-average value in dH2O) showed extreme toxicity to crustaceans Daphnia magna, algae Pseudokirchneriella subcapitata and zebrafish Danio rerio embryos (EC50<0.01 mg total Ag/L), was very toxic in the in vitro assay with rainbow trout Oncorhynchus mykiss gut cells (EC50: 0.01-1 mg total Ag/L); toxic to bacteria Vibrio fischeri, protozoa Tetrahymena thermophila (EC50: 1-10 mg total Ag/L) and harmful to marine crustaceans Artemia franciscana (EC50: 10-100 mg total Ag/L). Along with AgNPs, also the toxicity of AgNO3 was analyzed. The toxicity data revealed the same hazard ranking for AgNPs and AgNO3 (i.e. the EC50 values were in the same order of magnitude) proving the importance of soluble Ag(+)-species analysis for predicting the hazard of AgNPs. The study clearly points to the need for harmonised procedures for the characterisation of NMs. Harmonised procedures should consider: (i) measuring the AgNP properties like hydrodynamic size and metal ions species in each toxicity test medium at a range of concentrations, and (ii) including soluble metal salt control both in toxicity testing as well as in Ag(+)-species measurements. The present study is among the first nanomaterial interlaboratory comparison studies with the aim to improve the hazard identification testing protocols.


Social innovation for the promotion of health equity.
The role of social innovations in transforming the lives of individuals and communities has been a source of popular attention in recent years. This article systematically reviews the available evidence of the relationship between social innovation and its promotion of health equity. Guided by Fair Foundations: The VicHealth framework for health equity and examining four types of social innovation--social movements, service-related social innovations, social enterprise and digital social innovations--we find a growing literature on social innovation activities, but inconsistent evaluative evidence of their impacts on health equities, particularly at the socio-economic, political and cultural level of the framework. Distinctive characteristics of social innovations related to the promotion of health equity include the mobilization of latent or unrealised value through new combinations of (social, cultural and material) resources; growing bridging social capital and purposeful approaches to linking individual knowledge and experience to institutional change. These have implications for health promotion practice and for research about social innovation and health equity.


Social conditions as fundamental causes of health inequalities: theory, evidence, and policy implications.
Link and Phelan (1995) developed the theory of fundamental causes to explain why the association between socioeconomic status (SES) and mortality has persisted despite radical changes in the diseases and risk factors that are presumed to explain it. They proposed that the enduring association results because SES embodies an array of resources, such as money, knowledge, prestige, power, and beneficial social connections that protect health no matter what mechanisms are relevant at any given time. In this article, we explicate the theory, review key findings, discuss refinements and limits to the theory, and discuss implications for health policies that might reduce health inequalities. We advocate policies that encourage medical and other health-promoting advances while at the same time breaking or weakening the link between these advances and socioeconomic resources. This can be accomplished either by reducing disparities in socioeconomic resources themselves or by developing interventions that, by their nature, are more equally distributed across SES groups.


Oscillatory magnetic anisotropy originating from quantum well states in Fe films.
The magnetic anisotropy of Fe film grown on vicinal Ag(1,1,10) surfaces was studied with the in situ magneto-optic Kerr effect. Below 200 K, strong oscillations of the uniaxial magnetic anisotropy as a function of Fe thickness with a period of 5.7 monolayers are found, which can even cause the easy magnetization axis to oscillate between perpendicular and parallel to the steps. Such novel oscillation of the anisotropy is attributed to the quantum well states of d-band electrons at the Fermi level in the Fe film. This is unlike the previously observed oscillatory behaviors of ferromagnetic films caused by the quantum well states in nonmagnetic interfacing layers.


Single small enhancing CT lesions in Indian patients with epilepsy: clinical, radiological and pathological considerations.
Thirty consecutive Indian patients with focal or generalised seizures and single, small (less than 10 mm), enhancing lesions on CT scans (SSECTL) were studied. Five patients (Group A) were treated with anticonvulsants alone and did not have a biopsy. In ten patients (Group B) a CT guided stereotaxic biopsy of the lesion was carried out and in the remainder (15-Group C) and excision biopsy of the lesion was carried out following CT guided stereotaxic localisation. In all patients in Group B the lesion were reported as "chronic nonspecific inflammation". In seven of 15 patients in Group C the lesions showed a cysticercus with a granuloma and in a further five the pathology was that of a "parasitic granuloma" but the parasite could not be identified. Biopsy did not reveal a tuberculoma or neoplasm in any of the patients. The lesions studied are the same as "disappearing" CT lesions reported in Indian patients, as in 12 of 15 patients in Groups A and B, who could be followed up for more than three months, the lesions had spontaneously disappeared or left calcific residues. It is concluded that in Indian epileptic patients with SSECTL cysticercosis is the commonest aetiology. A treatment protocol for these patients is suggested on the basis of the findings.


Unveiling Glycerolipid Fragmentation by Cryogenic Infrared Spectroscopy.
Mass spectrometry is routinely employed for structure elucidation of molecules. Structural information can be retrieved from intact molecular ions by fragmentation; however, the interpretation of fragment spectra is often hampered by poor understanding of the underlying dissociation mechanisms. For example, neutral headgroup loss from protonated glycerolipids has been postulated to proceed via an intramolecular ring closure but the mechanism and resulting ring size have never been experimentally confirmed. Here we use cryogenic gas-phase infrared (IR) spectroscopy in combination with computational chemistry to unravel the structures of fragment ions and thereby shed light on elusive dissociation mechanisms. Using the example of glycerolipid fragmentation, we study the formation of protonated five-membered dioxolane and six-membered dioxane rings and show that dioxolane rings are predominant throughout different glycerolipid classes and fragmentation channels. For comparison, pure dioxolane and dioxane ions were generated from tailor-made dehydroxyl derivatives inspired by natural 1,2- and 1,3-diacylglycerols and subsequently interrogated using IR spectroscopy. Furthermore, the cyclic structure of an intermediate fragment occurring in the phosphatidylcholine fragmentation pathway was spectroscopically confirmed. Overall, the results contribute substantially to the understanding of glycerolipid fragmentation and showcase the value of vibrational ion spectroscopy to mechanistically elucidate crucial fragmentation pathways in lipidomics.


AAC technologies to enhance participation and access to meaningful societal roles for adolescents and adults with developmental disabilities who require AAC.
In this paper we review published research describing the use of augmentative and alternative communication (AAC) to support societal participation by adolescents and adults with developmental disabilities who require AAC. We focus on three major participation domains: post-secondary education and training, the workplace, and community living and social interaction opportunities. Based on the findings of the review, we highlight five needed areas of research and development related to AAC technology: face to face communication; distance communication and interconnectivity; training and support for system use; adapted applications and cognitive tools; and supports for independent operation, development, and maintenance.


Biocatalytic behaviour of immobilized Rhizopus oryzae lipase in the 1,3-selective ethanolysis of sunflower oil to obtain a biofuel similar to biodiesel.
A new biofuel similar to biodiesel was obtained in the 1,3-selective transesterification reaction of sunflower oil with ethanol using as biocatalyst a Rhizopus oryzae lipase (ROL) immobilized on Sepiolite, an inorganic support. The studied lipase was a low cost powdered enzyme preparation, Biolipase-R, from Biocon-Spain, a multipurpose additive used in food industry. In this respect, it is developed a study to optimize the immobilization procedure of these lipases on Sepiolite. Covalent immobilization was achieved by the development of an inorganic-organic hybrid linker formed by a functionalized hydrocarbon chain with a pendant benzaldehyde, bonded to the AlPO4 support surface. Thus, the covalent immobilization of lipases on amorphous AlPO4/sepiolite (20/80 wt %) support was evaluated by using two different linkers (p-hydroxybenzaldehyde and benzylamine-terephthalic aldehyde, respectively). Besides, the catalytic behavior of lipases after physical adsorption on the demineralized sepiolite was also evaluated. Obtained results indicated that covalent immobilization with the p-hydroxybenzaldehyde linker gave the best biocatalytic behavior. Thus, this covalently immobilized lipase showed a remarkable stability as well as an excellent capacity of reutilization (more than five successive reuses) without a significant loss of its initial catalytic activity. This could allow a more efficient fabrication of biodiesel minimizing the glycerol waste production.


Localization of the N-terminal and C-terminal ends of triadin with respect to the sarcoplasmic reticulum membrane of rabbit skeletal muscle.
Antibodies were raised against synthetic peptides corresponding to the N-terminal (residues 2-17) and C-terminal (residues 691-706) ends of rabbit skeletal muscle triadin, a 95 kDa protein located in the sarcoplasmic reticulum membrane at the triad junction. The specificity of the antibodies generated was tested by ELISA and Western blot analysis. These tests demonstrated the ability of the antibodies to react specifically with the proteins. The anti-N-terminus antibodies bound to sarcoplasmic reticulum vesicles, indicating that the N-terminal end of the membrane-embedded triadin is exposed on the cytoplasmic side of the vesicles. In contrast, the anti-C-terminus antibodies were able to react with sarcoplasmic reticulum vesicles only after permeabilization of the vesicles with a detergent, indicating that the C-terminal end is exposed on the luminal side of the vesicles. These immunological data were complemented by proteolysis experiments using carboxypeptidases and endoproteinase Arg C. A mixture of carboxypeptidases A, B and Y was used to induce degradation of the C-terminal end of triadin in sarcoplasmic reticulum vesicles. This degradation, and a concomitant loss of reactivity of the anti-C-terminus antibodies in Western blots, was observed only when the vesicles were permeabilized, providing further evidence for the luminal localization of the C-terminal end of triadin. Treatment of sarcoplasmic reticulum vesicles with endoproteinase Arg C resulted in the removal of the N-terminal end of triadin, probably due to cleavage after Arg-34. This is a further indication of the cytoplasmic localization of the N-terminal end of triadin (and of its first 34 amino acids). When the proteolysis with endoproteinase Arg C was carried out with permeabilized vesicles, the cleavage occurred after Arg-141 or Arg-157, indicating that at least one of these residues is luminal.


[Higher physical activity levels are associated with lower prevalence of cardiovascular risk factors in Chile].
Little is known about the relationship between physical activity (PA) and cardiovascular risk factors in the Chilean population. To investigate the association between different levels and intensities of PA and the prevalence of cardiovascular (CV) risk factors in Chilean adults. Data from the National Health Survey 2009-10 including 5157 participants, provided by the Epidemiology Department of the Ministry of Health, was analyzed in this study. The prevalence of type 2 diabetes mellitus, hypertension, metabolic syndrome and dyslipidemia were determined using international criteria. PA levels were determined using the Global Physical Activity Questionnaire (GPAQ v2) and different levels of PA were derived from it (transport-related, moderate and vigorous PA). Quartiles of PA were determined to investigate the association between PA and cardiovascular risk factors. Twenty three percent of women and 17.1% of men did not meet the PA recommendation (≥ 600 METs.min.week-1). When prevalence of CV risk factors were compared between inactive individuals (< 600 METs.min.week-1) and active individuals (≥ 9500 METs.min.week-1) a significantly lower prevalence of diabetes mellitus (6.2% and 10%), hypertension (18.0% and 12.4%) and metabolic syndrome (8.9% and 12.1%) for women and men, respectively, was found in the active participants. Similar results were found for high versus low transport-related PA. Increasing levels of PA are associated with a significantly lower frequency of cardiovascular risk factors in Chilean adults.


Costs of regulating ammonia emissions from livestock farms near Natura 2000 areas - analyses of case farms from Germany, Netherlands and Denmark.
Natura 2000 areas are designated according to the EU's Birds and Habitats Directives in order to protect particular habitats and species. A variety of these habitats and species are particularly sensitive to deposition of nitrogen caused by ammonia emissions. Livestock farming is the primary source of this pollution. The purpose of this paper is to compare the costs of reaching the ammonia emission targets for different livestock farms near Natura 2000 sites in the Netherlands, Germany (Schleswig-Holstein), and Denmark. These countries have some of the highest NH3 deposition rates in Europe, and Germany in particular will have to implement new measures to reach the NEC requirements for 2030. This will also benefit nature sites in Denmark as a large share of the ammonia emissions is dispersed over long distances. The general regulation includes implementation of BAT technologies and emission ceilings. The analysis looks at regulatory aspects, the emission requirements and the cost of implementing the technologies to reduce emissions further. The selected case farms are a finisher farm and a dairy farm, and the distance to a Natura 2000 site is 400 and 2000 m. In all three countries, relatively few livestock farms are situated near or inside Natura 2000 areas. The regulatory approach is very different in the three countries and key issues are: additional deposition from projects, neighbouring livestock farms (cumulation), the inclusion of background deposition and the use of the critical loads concept. The Dutch PAS system is interesting as projected reductions in emissions are distributed as additional "room for development" today. The costs for the case farm with finishers in Schleswig-Holstein are the highest as the Filter Decree requires the use of air scrubbers. The findings suggest that farms 400 m from a Natura 2000 site in the Netherlands face lower and less costly constraints than in the other countries, whereas the opposite is the case for farms 2000 m from Natura 2000 sites. The requirements near Natura 2000, where strict requirements apply, are so high that farms will expand at a different site instead.


Genomic Comparison Among Global Isolates of L. interrogans Serovars Copenhageni and Icterohaemorrhagiae Identified Natural Genetic Variation Caused by an Indel.
Leptospirosis is a worldwide zoonosis, responsible for more than 1 million cases and 60,000 deaths every year. Among the 13 pathogenic species of the genus Leptospira, serovars belonging to L. interrogans serogroup Icterohaemorrhagiae are considered to be the most virulent strains, and responsible for majority of the reported severe cases. Serovars Copenhageni and Icterohaemorrhagiae are major representatives of this serogroup and despite their public health relevance, little is known regarding the genetic differences between these two serovars. In this study, we analyzed the genome sequences of 67 isolates belonging to L. interrogans serovars Copenhageni and Icterohaemorrhagiae to investigate the influence of spatial and temporal variations on DNA sequence diversity. Out of the 1072 SNPs identified, 276 were in non-coding regions and 796 in coding regions. Indel analyses identified 258 indels, out of which 191 were found in coding regions and 67 in non-coding regions. Our phylogenetic analyses based on SNP dataset revealed that both serovars are closely related but showed distinct spatial clustering. However, likelihood ratio test of the indel data statistically confirmed the presence of a frameshift mutation within a homopolymeric tract of lic12008 gene (related to LPS biosynthesis) in all the L. interrogans serovar Icterohaemorrhagiae strains but not in the Copenhageni strains. Therefore, this internal indel identified can genetically distinguish L. interrogans serovar Copenhageni from serovar Icterohaemorrhagiae with high discriminatory power. To our knowledge, this is the first study to identify global sequence variations (SNPs and Indels) in L. interrogans serovars Copenhageni and Icterohaemorrhagiae.


Understanding the decline of mean systolic blood pressure in Japan: an analysis of pooled data from the National Nutrition Survey, 1986-2002.
To assess the relationships between the observed drop in mean systolic blood pressure (SBP) in Japan in 1986-2002 and the use of antihypertensive treatment and lifestyle factors. A nationally representative sample of 90,554 men and 101,903 women aged 20 years and over was obtained from pooled data of annual cross-sectional surveys in Japan during 1986-2002. Using two-stage least squares with an instrumental variable, we examined the association between SBP and antihypertensive medication and lifestyle factors, including body mass index (BMI), physical activity, alcohol consumption, cigarette smoking and dietary salt intake. In the surveys, regular exercise was defined as exercise for more than 30 minutes at a time more than twice a week for over 1 year. Current smoking was defined as either daily or occasional cigarette use. Current drinking was defined as an intake of more than one standard cup of Japanese sake, one large bottle of regular beer, or one double measure of whisky at a time more than three times a week. Changes in mean predicted SBP in each sex and age group between 1986 and 2002 were decomposed into the respective contributions of these explanatory variables. Age-specific means of predicted SBP declined during this period by 1.8 (95% confidence interval, CI: 1.2-2.5) to 3.0 (95% CI: 2.4-3.6) mmHg in men and 3.7 (95% CI: 3.4-4.1) to 5.1 (95% CI: 4.5-5.7) mmHg in women. These reductions were partly explained by the increased use of medications across all sex and age groups and decreased mean BMI in women in their 30s and 40s. The contributions of treatment effects increased with age. Elevated mean BMI in men and elderly women offset part of the decline of their mean SBP. Declining mean SBP in Japan between 1986 and 2002 was partly attributable to the increased use of antihypertensive medications, especially in the older population, and lowered mean BMI in young women. However, a substantial part of the decline was left unexplained and needs to be investigated further. A still greater decline in SBP would be expected through improvements in body weight management, salt and alcohol intake, and treatment and control of hypertension.


Trans-activation of HIV-1 LTR-directed gene expression by tat requires protein kinase C.
Human immunodeficiency virus (HIV) spends a significant part of the viral life cycle as a latent provirus integrated into the host genome. Activation of latent HIV-1 requires mitogenic stimulation of the cell, which increases basal viral transcription, and the HIV-1 tat protein. As tat itself dramatically increases HIV-1 gene expression, it too is presumably regulated in the latent state, and may also be activated by mitogenic stimulation. We show here that depletion of protein kinase C (PKC), which is essential to the stimulation of T cells by several mitogens, dramatically reduces HIV-1 transactivation without affecting synthesis of tat protein. Transactivation in PKC-depleted cells can be restored by transfection with a PKC expression vector. The requirement for PKC in trans-activation does not involve the PMA-responsive enhancer elements responsible for the effect of mitogens on basal transcription. Our results indicate that PKC regulates the process of HIV-1 transactivation, suggesting a key role for the mitogenic induction of trans-activation in the transition of HIV from latency to productive growth.


Cold activity of Beauveria and Metarhizium, and thermotolerance of Beauveria.
Heat and cold are environmental abiotic factors that restrict the use of entomopathogenic fungi as agents for biological control of insects. The thermotolerance and cold activity of 60 entomopathogenic fungal isolates, including five species of Beauveria and one isolate of Engyodontium albus (=Beauveria alba) were examined as to tolerance of temperatures that might be encountered during field use. In addition, cold activity of eight Metarhizium spp. isolates was evaluated. The isolates were from various geographic regions, arthropod hosts or substrates. High variability in conidial thermotolerance was found among the Beauveria spp. isolates after exposure to 45 degrees C for 2 h, as evidenced by low (0-20%), medium (20-60%), or high germination (60-80%). The thermal death point (0% germination) for three rather thermotolerant B. bassiana isolates (CG 138, GHA and ARSEF 252) was 46 degrees C for 6 h. At low temperatures (5 degrees C), with few exceptions (e.g. CG 66, UFPE 479, CG 227, CG 02), most of the B. bassiana isolates germinated well (ca. 100%). On the other hand, only one isolate of Metarhizium sp. was cold-active (i.e. ARSEF 4343 from Macquarie Island, 54.4 degrees S, Australia). This probably is a M. frigidum isolate. The E. albus isolate (UFPE 3138) was the most susceptible isolate to both heat and cold stress. Isolates ARSEF 252 and GHA of B. bassiana, on the other hand, presented exceptionally high thermotolerance and cold activity. Some isolates with high cold activity, however, were thermosensitive (e.g. ARSEF 1682) and others with high thermotolerance had low cold activity (e.g. CG 227). An attempt to correlate the latitude of origin with thermotolerance or cold activity indicated that B. bassiana isolates from higher latitudes were more cold-active than isolates from nearer the equator, but there was not a similar correlation for heat.


Continental-scale variation in seaweed host-associated bacterial communities is a function of host condition, not geography.
Interactions between hosts and associated microbial communities can fundamentally shape the development and ecology of 'holobionts', from humans to marine habitat-forming organisms such as seaweeds. In marine systems, planktonic microbial community structure is mainly driven by geography and related environmental factors, but the large-scale drivers of host-associated microbial communities are largely unknown. Using 16S-rRNA gene sequencing, we characterized 260 seaweed-associated bacterial and archaeal communities on the kelp Ecklonia radiata from three biogeographical provinces spanning 10° of latitude and 35° of longitude across the Australian continent. These phylogenetically and taxonomically diverse communities were more strongly and consistently associated with host condition than geographical location or environmental variables, and a 'core' microbial community characteristic of healthy kelps appears to be lost when hosts become stressed. Microbial communities on stressed individuals were more similar to each other among locations than those on healthy hosts. In contrast to biogeographical patterns of planktonic marine microbial communities, host traits emerge as critical determinants of associated microbial community structure of these holobionts, even at a continental scale.


Ultraviolet irradiation of the eye and Fos-positive neurons induced in trigeminal brainstem after intravitreal or ocular surface transient receptor potential vanilloid 1 activation.
The interior structures of the eye are well supplied by the trigeminal nerve; however, the function of these afferent fibers is not well defined. The aim of this study was to use c-fos like immunohistochemistry (Fos-LI) to map the trigeminal brainstem complex after intravitreal microinjection or ocular surface application of capsaicin, a selective transient receptor potential vanilloid 1 (TRPV1) agonist in male rats under barbiturate anesthesia. The effect of ocular inflammation on Fos-LI was tested 2 or 7 days after UV irradiation of the eye. In non-inflamed controls, intravitreal capsaicin produced peaks of Fos-LI at the trigeminal subnucleus interpolaris/caudalis (Vi/Vcvl) transition and in superficial laminae at the caudalis/upper cervical cord (Vc/C1) junction regions. At the Vc/C1 junction intravitreal capsaicin induced Fos-LI in a dose-dependent manner, while at the Vi/Vcvl transition responses were similar after vehicle or capsaicin injections. Two days, but not 7 days, after UV irradiation intravitreal and ocular surface capsaicin-evoked Fos-LI at the Vc/C1 junction and nucleus tractus solitarius (NTS) were markedly enhanced, whereas the responses at the Vi/Vcvl transition were not different from non-inflamed controls. More than 80% of trigeminal ganglion neurons labeled after intravitreal microinjection of Fluorogold also expressed immunoreactivity for the TRPV1 receptor. These findings suggested that most intraocular trigeminal sensory nerves serve as nociceptors. The similar pattern and magnitude of Fos-LI after capsaicin suggested that TRPV1-responsive trigeminal nerves that supply intraocular and ocular surface tissues form a unified integrative circuit in the caudal brainstem. Intensity coding of capsaicin concentration and facilitation of Fos-LI expression after UV irradiation strongly supported the hypothesis that the Vc/C1 junction was critical for nociceptive processing related to ocular pain, whereas the Vi/Vcvl transition region likely served other functions in ocular homeostasis under naïve and inflamed conditions.


Efficacy of Topical Therapy with Newly Developed Terbinafine and Econazole Formulations in the Treatment of Dermatophytosis in Cats.
In the field of veterinary dermatology dermatophytosis is one of the most frequently occurring infectious diseases, therefore its treatment should be effective, convenient, safe and inexpensive. The aim of this study was to evaluate the efficacy of newly developed topical formulations in the treatment of cats with dermatophytosis. Evaluation of clinical efficacy and safety of terbinafine and econazole formulations administered topically twice a day was performed in 40 cats. Cats, suffering from the most widely spread Microsporum canis-induced dermatophytosis and treated with terbinafine hydrochloride 1% cream, recovered within 20.3±0.88 days; whereas when treated with econazole nitrate 1% cream, they recovered within 28.4±1.14 days. A positive therapeutic effect was yielded by combined treatment with local application of creams and whole coat spray with enilconazole 0.2% emulsion "Imaverol". Most cats treated with econazole cream revealed redness and irritation of the skin at the site of application. This study demonstrates that terbinafine tended to have superior clinical efficacy (p<0.001) in the treatment of dermatophytosis in cats compared to the azole tested.


Chromium update: examining recent literature 1997-1998.
Trivalent chromium is an essential nutrient required for sugar and fat metabolism. The majority of people eating typical Western diets consume less than the upper limit of the estimated safe and adequate daily dietary intake, which is set at 50-200 micrograms per day. Insufficient chromium intake is associated with signs and symptoms similar to those seen in diabetes and cardiovascular diseases. The efficacy of chromium in the general population relates to its prevention of deficiency or a reduction in the risk of chronic diseases. It is possible that doses above the estimated safe and adequate daily dietary intake are necessary for the treatment of certain chronic disease states. In a study performed in China, the use of 1000 micrograms of chromium per day (five times above the upper limit of the estimated safe and adequate daily dietary intake) was highly effective in relieving many of the symptomatic manifestations of type 2 diabetes mellitus, including a return of the HbA1C levels into the normal range. Most recent evidence strongly supports the conclusion that there is little fear of toxic reactions from chromium consumption. In addition to type 2 diabetes mellitus, chromium supplementation may be useful to direct overall weight decrements specifically towards fat loss with the retention of lean body mass and to ameliorate many manifestations of aging.


Benchmarking time to initiation of end-of-life homecare nursing: a population-based cancer cohort study in regions across Canada.
Several studies have demonstrated the benefits of early initiation of end-of-life care, particularly homecare nursing services. However, there is little research on variations in the timing of when end-of-life homecare nursing is initiated and no established benchmarks. This is a retrospective cohort study of patients with a cancer-confirmed cause of death between 2004 and 2009, from three Canadian provinces (British Columbia, Nova Scotia, and Ontario). We linked multiple administrative health databases within each province to examine homecare use in the last 6 months of life. Our primary outcome was mean time (in days) to first end-of-life homecare nursing visit, starting from 6 months before death, by region. We developed an empiric benchmark for this outcome using a funnel plot, controlling for region size. Of the 28 regions, large variations in the outcome were observed, with the longest mean time (97 days) being two-fold longer than the shortest (55 days). On average, British Columbia and Nova Scotia had the first and second shortest mean times, respectively. The province of Ontario consistently had longer mean times. The empiric benchmark mean based on best-performing regions was 57 mean days. Significant variation exists for the time to initiation of end-of-life homecare nursing across regions. Understanding regional variation and developing an empiric benchmark for homecare nursing can support health system planners to set achievable targets for earlier initiation of end-of-life care.


Methodological considerations in using accelerometers to assess habitual physical activity in children aged 0-5 years.
This paper reviews the evidence behind the methodological decisions accelerometer users make when assessing habitual physical activity in children aged 0-5 years. The purpose of the review is to outline an evidence-guided protocol for using accelerometry in young children and to identify gaps in the evidence base where further investigation is required. Studies evaluating accelerometry methodologies in young children were reviewed in two age groups (0-2 years and 3-5 years) to examine: (i) which accelerometer should be used, (ii) where the accelerometer should be placed, (iii) which epoch should be used, (iv) how many days of monitoring are required, (v) how many minutes of monitoring per day are required, (vi) how data should be reduced, (vii) which cut-point definitions for identifying activity intensity should be used, and (viii) which physical activity outcomes should be reported and how. Critique of the available evidence provided a basis for the development of a recommended users protocol in 3-5-year olds, although several issues require further research. Because of the absence of methodological studies in children under 3 years, a protocol for the use of accelerometers in this age range could not be specified. Formative studies examining the utility, feasibility and validity of accelerometer-based physical activity assessments are required in children under 3 years of age. Recommendations for further research are outlined, based on the above findings, which, if undertaken, will enhance the accuracy of accelerometer-based assessments of habitual physical activity in young children.


Prehospital neurological deterioration in stroke.
Patients with stroke can experience neurological deterioration in the prehospital setting. We evaluated patients with stroke to determine factors associated with prehospital neurological deterioration (PND). Among the Greater Cincinnati/Northern Kentucky region (population ~1.3 million), we screened all 15 local hospitals' admissions from 2010 for acute stroke and included patients aged ≥20. The GCS was compared between emergency medical services (EMS) arrival and hospital arrival, with decrease ≥2 points considered PND. Data obtained retrospectively included demographics, medical history and medication use, stroke subtype (eg, ischaemic stroke (IS), intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH)) and IS subtype (eg, small vessel, large vessel, cardioembolic), seizure at onset, time intervals between symptom onset, EMS arrival and hospital arrival, EMS level of training, and blood pressure and serum glucose on EMS arrival. Of 2708 total patients who had a stroke, 1092 patients (median (IQR) age 74 (61-83) years; 56% women; 21% black) were analysed. PND occurred in 129 cases (12%), including 9% of IS, 24% of ICH and 16% of SAH. In multivariable analysis, black race, atrial fibrillation, haemorrhagic subtype and ALS level of transport were associated with PND. Haemorrhage and atrial fibrillation is associated with PND in stroke, and further investigation is needed to establish whether PND can be predicted. Further studies are also needed to assess whether preferential transport of patients with deterioration to hospitals equipped with higher levels of care is beneficial, identify why race is associated with deterioration and to test therapies targeting PND.


The prevalence of physical inactivity amongst Brazilian university students: its association with sociodemographic variables.
The prevalence of physical inactivity amongst adults has been increasing worldwide; however, few studies have been conducted on university freshmen. The present investigation was aimed at determining the prevalence of physical inactivity amongst Brazilian university freshmen and its association with sociodemographic variables. The database for the research project entitled, 'Evaluating health-related physical fitness of students from the Federal University of Santa Catarina, Brazil,' was used for this study. A total of 762 students (445 males) having 20.2 (4.7) mean age were studied. The participants' level of physical activity was measured by IPAQ; sociodemographic variables were self-reported and then recorded. The chi-square test and binary logistic regression were used for statistical analysis (significance level was set at p<0.05). The prevalence of physical inactivity was 13.8 % amongst the students studied. Female and night-course students presented a 1.69 (CI 95 %: 1.10-2.57) and 1.70 (CI95 %: 1.09-2.66) times greater chance of presenting physical inactivity than male students and those on day-courses, respectively. The main risk groups for physical inactivity were female and night-course students.


Risk of developing dementia in people with diabetes and mild cognitive impairment.
Diabetes mellitus is associated with cognitive dysfunction, but it is not clear whether the disorder increases the risk of conversion from mild cognitive impairment to dementia. To determine the association between diabetes mellitus and dementia conversion in people with mild cognitive impairment (Peterson's criteria) in a prospective community-based study. People over 65 years old were approached through primary care practices in south London, UK, and those with mild cognitive impairment (n = 103) were followed up for 4 years. Presence of diabetes was established from self-report and information from general practitioners. Nineteen participants progressed to dementia, with the predominant diagnosis being probable or possible Alzheimer's disease (in 84%). Only diabetes mellitus was associated with progression to dementia (hazard ratio 2.9, 95% CI 1.1-7.3) after adjustment for sociodemographic factors, APOE4, premorbid IQ and other health conditions. Diabetes mellitus increases not only the risks of dementia and mild cognitive impairment but also the risk of progression from such impairment to dementia.


The kinetics of folding of frataxin.
The role of the denatured state in protein folding represents a key issue for the proper evaluation of folding kinetics and mechanisms. The yeast ortholog of the human frataxin, a mitochondrial protein essential for iron homeostasis and responsible for Friedreich's ataxia, has been shown to undergo cold denaturation above 0 °C, in the absence of chemical denaturants. This interesting property provides the unique opportunity to explore experimentally the molecular mechanism of both the hot and cold denaturation. In this work, we present the characterization of the temperature and urea dependence of the folding kinetics of yeast frataxin, and show that while at neutral pH and in the absence of a denaturant a simple two-state model may satisfactorily describe the temperature dependence of the folding and unfolding rate constants, the results obtained in urea over a wide range of pH reveal an intriguing complexity, suggesting that folding of frataxin involves a broad smooth free energy barrier.


A high quality factor carbon nanotube mechanical resonator at 39 GHz.
We measure the mechanical resonances of an as-grown suspended carbon nanotube, detected via electrical mixing in the device. A sequence of modes extending to 39 GHz is observed with a quality factor of 35,000 in the highest mode. This unprecedentedly high combination corresponds to a thermal excited state probability below 10(-8) and a relaxation time of 140 ns with microsecond relaxation times for lower modes. The effect of electron tunneling on the mechanical resonance is found to depend on frequency as the tunneling time becomes comparable to the vibration period.


Likelihood approaches for proportional likelihood ratio model with right-censored data.
Regression methods for survival data with right censoring have been extensively studied under semiparametric transformation models such as the Cox regression model and the proportional odds model. However, their practical application could be limited because of possible violation of model assumption or lack of ready interpretation for the regression coefficients in some cases. As an alternative, in this paper, the proportional likelihood ratio model introduced by Luo and Tsai is extended to flexibly model the relationship between survival outcome and covariates. This model has a natural connection with many important semiparametric models such as generalized linear model and density ratio model and is closely related to biased sampling problems. Compared with the semiparametric transformation model, the proportional likelihood ratio model is appealing and practical in many ways because of its model flexibility and quite direct clinical interpretation. We present two likelihood approaches for the estimation and inference on the target regression parameters under independent and dependent censoring assumptions. Based on a conditional likelihood approach using uncensored failure times, a numerically simple estimation procedure is developed by maximizing a pairwise pseudo-likelihood. We also develop a full likelihood approach, and the most efficient maximum likelihood estimator is obtained by a profile likelihood. Simulation studies are conducted to assess the finite-sample properties of the proposed estimators and compare the efficiency of the two likelihood approaches. An application to survival data for bone marrow transplantation patients of acute leukemia is provided to illustrate the proposed method and other approaches for handling non-proportionality. The relative merits of these methods are discussed in concluding remarks.