Influence of UVB, UVA and UVA1 irradiation on histamine release from human basophils and mast cells in vitro in the presence and absence of antioxidants.
UV irradiation is widely used for the treatment of atopic eczema. In recent years, UVA1 phototherapy has gained increasing attention. This study analyzed the influence of different UV wavelengths--especially UVA1--on histamine release from human basophils and mast cells. The modulation of this parameter might be responsible for some of the therapeutic effects of UV irradiation. Enriched human basophils and human mast cells (HMC1 cell line) were irradiated with increasing doses of UVB, UVA and UVA1 in vitro. After irradiation, different stimulants were added to induce histamine release. In additional experiments, basophils were preincubated with superoxide dismutase, ascorbate or trolox to study the role of antioxidants in the modulation of histamine release after UV irradiation. UVA and UVA1 significantly inhibited histamine release from basophils and mast cells. UVB only had an inhibitory effect on mast cells. Preincubation with superoxide dismutase and ascorbate did not influence the inhibitory effect of UVA1 on basophil histamine release, whereas trolox decreased significantly the histamine release from nonirradiated basophils.


Quantifying Chaos by Various Computational Methods. Part 1: Simple Systems.
The aim of the paper was to analyze the given nonlinear problem by different methods of computation of the Lyapunov exponents (Wolf method, Rosenstein method, Kantz method, the method based on the modification of a neural network, and the synchronization method) for the classical problems governed by difference and differential equations (Hénon map, hyperchaotic Hénon map, logistic map, Rössler attractor, Lorenz attractor) and with the use of both Fourier spectra and Gauss wavelets. It has been shown that a modification of the neural network method makes it possible to compute a spectrum of Lyapunov exponents, and then to detect a transition of the system regular dynamics into chaos, hyperchaos, and others. The aim of the comparison was to evaluate the considered algorithms, study their convergence, and also identify the most suitable algorithms for specific system types and objectives. Moreover, an algorithm of calculation of the spectrum of Lyapunov exponents based on a trained neural network has been proposed. It has been proven that the developed method yields good results for different types of systems and does not require a priori knowledge of the system equations.


Developmental Methylmercury Exposure Affects Swimming Behavior and Foraging Efficiency of Yellow Perch (Perca flavescens) Larvae.
Methylmercury (MeHg) is a pervasive and ubiquitous environmental neurotoxicant within aquatic ecosystems, known to alter behavior in fish and other vertebrates. This study sought to assess the behavioral effects of developmental MeHg exposure on larval yellow perch (Perca flavescens)-a nonmodel fish species native to the Great Lakes. Embryos were exposed to MeHg (0, 30, 100, 300, and 1000 nM) for 20 h and then reared to 25 days post fertilization (dpf) for analyses of spontaneous swimming, visual motor response (VMR), and foraging efficiency. MeHg exposures rendered total mercury (THg) body burdens of 0.02, 0.21, 0.95, 3.14, and 14.93 μg/g (wet weight). Organisms exposed to 1000 nM exhibited high mortality; thus, they were excluded from downstream behavioral analyses. All MeHg exposures tested were associated with a reduction in spontaneous swimming at 17 and 25 dpf. Exposure to 30 and 100 nM MeHg caused altered locomotor output during the VMR assay at 21 dpf, whereas exposure to 100 nM MeHg was associated with decreased foraging efficiency at 25 dpf. For the sake of comparison, the second-lowest exposure tested here rendered a THg burden that represents the permissible level of consumable fish in the United States. Moreover, this dose is reported in roughly two-thirds of consumable fish species monitored in the United States, according to the Food and Drug Administration. Although the THg body burdens reported here were higher than expected in the environment, our study is the first to analyze the effects of MeHg exposure on fundamental survival behaviors of yellow perch larvae and advances in the exploration of the ecological relevance of behavioral end points.


HIV incidence among high-risk Puerto Rican drug users: a comparison of East Harlem, New York, and Bayamón, Puerto Rico.
Significant differences in HIV-related risk behaviors have been found between Puerto Rican drug users in New York City (NY) and Puerto Rico (PR). An examination of HIV incidence rates and characteristics of seroconverters in each location was undertaken. Baseline and follow-up interviewing and HIV testing were conducted in 1998 to 2002 with seronegative Puerto Rican injection drug users (IDUs) and crack smokers from East Harlem, NY (n = 455) and Bayamón, PR (n = 268). There were a total of 32 seroconverters, 9 in NY and 23 in PR, for seroconversion rates of 0.88/100 person-years at risk (pyr; 95% CI, 0.31-1.45) in NY and 3.37/100 pyr (95% CI, 2.02-4.72) in PR (P < 0.001). In PR, variables significantly related to seroconversion were younger age and using shooting galleries. Being in methadone treatment was protective against seroconversion. In NY, crack use was significantly related to seroconversion. The higher seroconversion rate found in PR indicates a need to enhance HIV prevention efforts, including increasing methadone treatment and access to sterile syringes. The need to address sexual risk behaviors in both locations was also indicated. Resources focusing on reducing HIV transmission in the Caribbean should include efforts to target the drug use-HIV epidemic in PR.


Benefits from antidepressants: synthesis of 6-week patient-level outcomes from double-blind placebo-controlled randomized trials of fluoxetine and venlafaxine.
Some meta-analyses suggest that efficacy of antidepressants for major depression is overstated and limited to severe depression. To determine the short-term efficacy of antidepressants for treating major depressive disorder in youth, adult, and geriatric populations. Reanalysis of all intent-to-treat person-level longitudinal data during the first 6 weeks of treatment of major depressive disorder from 12 adult, 4 geriatric, and 4 youth randomized controlled trials of fluoxetine hydrochloride and 21 adult trials of venlafaxine hydrochloride. All sponsor-conducted randomized controlled trials of fluoxetine and venlafaxine. Children's Depression Rating Scale-Revised scores (youth population), Hamilton Depression Rating Scale scores (adult and geriatric populations), and estimated response and remission rates at 6 weeks were analyzed for 2635 adults, 960 geriatric patients, and 708 youths receiving fluoxetine and for 2421 adults receiving immediate-release venlafaxine and 2461 adults receiving extended-release venlafaxine. Patients in all age and drug groups had significantly greater improvement relative to control patients receiving placebo. The differential rate of improvement was largest for adults receiving fluoxetine (34.6% greater than those receiving placebo). Youths had the largest treated vs control difference in response rates (24.1%) and remission rates (30.1%), with adult differences generally in the 15.6% (remission) to 21.4% (response) range. Geriatric patients had the smallest drug-placebo differences, an 18.5% greater rate of improvement, 9.9% for response and 6.5% for remission. Immediate-release venlafaxine produced larger effects than extended-release venlafaxine. Baseline severity could not be shown to affect symptom reduction. To our knowledge, this is the first research synthesis in this area to use complete longitudinal person-level data from a large set of published and unpublished studies. The results do not support previous findings that antidepressants show little benefit except for severe depression. The antidepressants fluoxetine and venlafaxine are efficacious for major depressive disorder in all age groups, although more so in youths and adults compared with geriatric patients. Baseline severity was not significantly related to degree of treatment advantage over placebo.


Treatment of deeply located acute intravascular thrombi with therapeutic ultrasound guided by diagnostic ultrasound and intravenous microbubbles.
We sought to determine the added value of simultaneous imaging of intravenously infused microbubbles that are being used to dissolve an intravascular thrombus with therapeutic ultrasound (TUS). In a chronic canine arteriovenous graft occluded by a thrombus, TUS (1 MHz) was applied through a 6-cm-thick tissue-mimicking phantom (measured mean +/- SD peak negative pressure through the phantom, 958 +/- 104 kPa) during an intravenous infusion of either saline (n = 6 occlusions) or lipid-encapsulated microbubbles (ImaRx Therapeutics, Inc, Tucson, AZ). Therapeutic ultrasound was intermittently applied during the microbubble infusion either at set time intervals (n = 6 occlusions) or when simultaneous diagnostic ultrasound (DUS) indicated a sustained presence of microbubbles (n = 12 occlusions). Success was defined as return of rapid flow within the graft (grade 3 flow). Diagnostic ultrasound showed microbubbles moving through small channels within the thrombus before angiographic evidence of flow in the graft. This guided the timing of TUS application better than using set time intervals. Angiographic clearance of the thrombus and restoration of grade 3 flow at 45 minutes of treatment were seen in 33% of deeply located thrombosed grafts treated with TUS at set time intervals and 92% of grafts treated with TUS guided by DUS (P < .001 compared with set time intervals). The use of TUS with intravenous microbubbles has a high success rate in recanalizing deeply located thrombosed arteriovenous grafts when performed with DUS guidance.


Cerebellar vermal volumes and behavioral correlates in children with autism spectrum disorder.
Cerebellar histopathological abnormalities have been well documented in autism, although findings of structural differences, as determined by magnetic resonance imaging, have been less consistent. This report explores specific cerebellar vermal structures and their relation with severity of symptoms and cognitive functioning in young children with autism spectrum disorder (ASD). Children with ASD aged 3 to 4 years were compared with typically developing children (TD) matched to the ASD children on chronological age, and children with developmental delay (DD) matched to the ASD children on both chronological and mental age. Volumes of the cerebellum and midsagittal vermal areas were measured from 3-D T1-weighted magnetic resonance images. Children with ASD had reduced total vermis volumes compared with children with TD after controlling for age, sex, and overall cerebral volume or cerebellum volume. In particular, the vermis lobe VI-VII area was reduced in children ASD compared with TD children. Children with DD had smaller total vermis areas compared with children with ASD and TD. Within the ASD group, cerebellar measurements were not correlated with symptom severity, or verbal, non-verbal or full scale IQ. Within the DD group, larger cerebellar measurements were correlated with fewer impairments. The specific relation between altered cerebellar structure and symptom expression in autism remains unclear.


Revisiting the nucleolus: from marker to dynamic integrator of cancer signaling.
Key signaling pathways (such as phosphoinositide 3-kinase, Myc, and RAS) act as sensors of energy, stress, and nutrient availability and integrate these inputs to directly control ribosome production and gene expression at the translational level. This activity is normally directly coupled to cell growth, division, and survival. However, it remains poorly understood the extent to which changes in ribosome number and nucleolar integrity downstream of these key signaling pathways contribute to their oncogenic activity. Emerging studies provide interesting insight into how deregulations in RNA polymerase I activity may lead to tumorigenesis and suggest that new drugs targeting ribosomal DNA transcription may hold great promise for the treatment of cancer.


Predictors and moderators of response to enhanced cognitive behaviour therapy and interpersonal psychotherapy for the treatment of eating disorders.
Consistent predictors, and more especially moderators, of response to psychological treatments for eating disorders have not been identified. The present exploratory study examined predictors and moderators of outcome in adult patients who took part in a randomised clinical trial comparing two leading treatments for these disorders, enhanced cognitive behavioural therapy (CBT-E) and interpersonal psychotherapy (IPT). Four potentially important findings emerged. Firstly, patients with a longer duration of disorder were less likely to benefit from either treatment. Second, across the two treatments the presence, at baseline, of higher levels of over-evaluation of the importance of shape predicted a less good treatment outcome. Third DSM-IV diagnosis did not predict treatment outcome. Fourth, with the exception of patients with baseline low self-esteem who achieved a better outcome with CBT-E, it was generally not possible to identify a subgroup of patients who would differentially benefit from one or other treatment.


Local and bulk (13)C hyperpolarization in nitrogen-vacancy-centred diamonds at variable fields and orientations.
Polarizing nuclear spins is of fundamental importance in biology, chemistry and physics. Methods for hyperpolarizing (13)C nuclei from free electrons in bulk usually demand operation at cryogenic temperatures. Room temperature approaches targeting diamonds with nitrogen-vacancy centres could alleviate this need; however, hitherto proposed strategies lack generality as they demand stringent conditions on the strength and/or alignment of the magnetic field. We report here an approach for achieving efficient electron-(13)C spin-alignment transfers, compatible with a broad range of magnetic field strengths and field orientations with respect to the diamond crystal. This versatility results from combining coherent microwave- and incoherent laser-induced transitions between selected energy states of the coupled electron-nuclear spin manifold. (13)C-detected nuclear magnetic resonance experiments demonstrate that this hyperpolarization can be transferred via first-shell or via distant (13)Cs throughout the nuclear bulk ensemble. This method opens new perspectives for applications of diamond nitrogen-vacancy centres in nuclear magnetic resonance, and in quantum information processing.


Phosphoproteomic strategies in cancer research: a minireview.
Understanding the cellular processes is central to comprehend disease conditions and is also true for cancer research. Proteomic studies provide significant insight into cancer mechanisms and aid in the diagnosis and prognosis of the disease. Phosphoproteome is one of the most studied complements of the whole proteome given its importance in the understanding of cellular processes such as signaling and regulations. Over the last decade, several new methods have been developed for phosphoproteome analysis. A significant amount of these efforts pertains to cancer research. The current use of powerful analytical instruments in phosphoproteomic approaches has paved the way for deeper and sensitive investigations. However, these methods and techniques need further improvements to deal with challenges posed by the complexity of samples and scarcity of phosphoproteins in the whole proteome, throughput and reproducibility. This review aims to provide a comprehensive summary of the variety of steps used in phosphoproteomic methods applied in cancer research including the enrichment and fractionation strategies. This will allow researchers to evaluate and choose a better combination of steps for their phosphoproteome studies.


Evaluation of factors that affect analytic variability of urine protein-to-creatinine ratio determination in dogs.
To determine whether preanalytic and analytic factors affect evaluation of the urinary protein-to-creatinine (UPC) ratio in dogs. 50 canine urine samples. The UPC ratio was measured to assess the intra-assay imprecision (20 measurements within a single session), the influence of predilution (1:10, 1:20, and 1:100) for urine creatinine concentration measurement, and the effect of storage at room temperature (approx 20°C), 4°C, and -20°C. The coefficient of variation at room temperature determined with the 1:20 predilution was < 10.0%, with the highest coefficients of variation found in samples with a low protein concentration or low urine specific gravity. This variability could result in misclassification of samples with UPC ratios close to the thresholds defined by the International Renal Interest Society to classify dogs as nonproteinuric (0.2), borderline proteinuric (0.21 to 0.50), or proteinuric (> 0.51). A proportional bias was found in samples prediluted 1:10, compared with samples prediluted 1:20 or 1:100. At room temperature, the UPC ratio did not significantly increase after 2 and 4 hours. After 12 hours at room temperature and at 4°C, the UPC ratio significantly increased. The UPC ratio did not significantly change during 3 months of storage at -20°C. The intra-assay precision of the UPC ratio was sufficiently low to avoid misclassification of samples, except for values close to 0.2 or 0.5. The optimal predilution ratio for urine creatinine concentration measurement was 1:20. A 1:100 predilution is recommended in samples with a urine specific gravity > 1.030. The UPC ratio must be measured as soon as samples are collected. Alternatively, samples should be immediately frozen to increase their stability and minimize the risk of misclassification of proteinuria.


Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype--ACOSOG Z1031.
Preoperative aromatase inhibitor (AI) treatment promotes breast-conserving surgery (BCS) for estrogen receptor (ER)-positive breast cancer. To study this treatment option, responses to three AIs were compared in a randomized phase II neoadjuvant trial designed to select agents for phase III investigations. Three hundred seventy-seven postmenopausal women with clinical stage II to III ER-positive (Allred score 6-8) breast cancer were randomly assigned to receive neoadjuvant exemestane, letrozole, or anastrozole. The primary end point was clinical response. Secondary end points included BCS, Ki67 proliferation marker changes, the Preoperative Endocrine Prognostic Index (PEPI), and PAM50-based intrinsic subtype analysis. On the basis of clinical response rates, letrozole and anastrozole were selected for further investigation; however, no other differences in surgical outcome, PEPI score, or Ki67 suppression were detected. The BCS rate for mastectomy-only patients at presentation was 51%. PAM50 analysis identified AI-unresponsive nonluminal subtypes (human epidermal growth factor receptor 2 enriched or basal-like) in 3.3% of patients. Clinical response and surgical outcomes were similar in luminal A (LumA) versus luminal B tumors; however, a PEPI of 0 (best prognostic group) was highest in the LumA subset (27.1% v 10.7%; P = .004). Neoadjuvant AI treatment markedly improved surgical outcomes. Ki67 and PEPI data demonstrated that the three agents tested are biologically equivalent and therefore likely to have similar adjuvant activities. LumA tumors were more likely to have favorable biomarker characteristics after treatment; however, occasional paradoxical increases in Ki67 (12% of tumors with > 5% increase after therapy) suggest treatment-resistant cells, present in some LumA tumors, can be detected by post-treatment profiling.


Distinguishing right from left colon by the pattern of gene expression.
Distinct epidemiological and clinicopathological characteristics of colorectal carcinomas (CRCs) based on their anatomical location suggest different risk factors and pathways of transformation associated with proximal and distal colon carcinogenesis. These differences may reflect distinct biological characteristics of proximal and distal colonic mucosa, acquired in embryonic or postnatal development, that determine a differential response to uniformly distributed environmental factors. Alternatively, the differences in the epidemiology of proximal and distal CRCs could result from the presence of different procarcinogenic factors in the ascending versus descending colon, acting on cells with either similar or distinct biological characteristics. We applied cDNA microarray technology to explore the possibility that mucosal epithelium from adult proximal and distal colon can be distinguished by their pattern of gene expression. In addition, gene expression was studied in fetal (17-24 weeks gestation) proximal and distal colon. More than 1000 genes were expressed differentially in adult ascending versus descending colon, with 165 genes showing >2-fold and 49 genes showing >3-fold differences in expression. With almost complete concordance, biopsies of adult colonic epithelium can be correctly classified as proximal or distal by gene expression profile. Only 87 genes were expressed differently in ascending and descending fetal colon, indicating that, although anatomically relevant differences are already established in embryonic colon, additional changes in gene expression occur in postnatal development.


Neurotoxic unc-8 mutants encode constitutively active DEG/ENaC channels that are blocked by divalent cations.
Ion channels of the DEG/ENaC family can induce neurodegeneration under conditions in which they become hyperactivated. The Caenorhabditis elegans DEG/ENaC channel MEC-4(d) encodes a mutant channel with a substitution in the pore domain that causes swelling and death of the six touch neurons in which it is expressed. Dominant mutations in the C. elegans DEG/ENaC channel subunit UNC-8 result in uncoordinated movement. Here we show that this unc-8 movement defect is correlated with the selective death of cholinergic motor neurons in the ventral nerve cord. Experiments in Xenopus laevis ooctyes confirm that these mutant proteins, UNC-8(G387E) and UNC-8(A586T), encode hyperactivated channels that are strongly inhibited by extracellular calcium and magnesium. Reduction of extracellular divalent cations exacerbates UNC-8(G387E) toxicity in oocytes. We suggest that inhibition by extracellular divalent cations limits UNC-8 toxicity and may contribute to the selective death of neurons that express UNC-8 in vivo.


A tree-based context model for object recognition.
There has been a growing interest in exploiting contextual information in addition to local features to detect and localize multiple object categories in an image. A context model can rule out some unlikely combinations or locations of objects and guide detectors to produce a semantically coherent interpretation of a scene. However, the performance benefit of context models has been limited because most of the previous methods were tested on data sets with only a few object categories, in which most images contain one or two object categories. In this paper, we introduce a new data set with images that contain many instances of different object categories, and propose an efficient model that captures the contextual information among more than a hundred object categories using a tree structure. Our model incorporates global image features, dependencies between object categories, and outputs of local detectors into one probabilistic framework. We demonstrate that our context model improves object recognition performance and provides a coherent interpretation of a scene, which enables a reliable image querying system by multiple object categories. In addition, our model can be applied to scene understanding tasks that local detectors alone cannot solve, such as detecting objects out of context or querying for the most typical and the least typical scenes in a data set.


Epinastine (WAL 801CL) modulates the noncholinergic contraction in guinea-pig airways in vitro by a prejunctional 5-HT1-like receptor.
Electrical field stimulation (EFS) of guinea-pig airways, in vitro, evokes an excitatory nonadrenergic noncholinergic (eNANC) contraction mediated by release of tachykinins from sensory nerve endings. Epinastine (WAL 801CL) is an antihistaminic drug with binding affinity at certain other receptors, including alpha-adrenergic receptors and various serotonin (5-HT) receptor subtypes. It is used in asthma treatment; however, its mechanism of action remains to be fully defined. We have investigated whether epinastine could modulate the eNANC contraction in guinea-pig airways in vitro, and have tried to elucidate its receptor mechanism. Epinastine (0.1-100 microM) produced a concentration-dependent inhibition of the noncholinergic contraction, with a maximum inhibition of 91 +/- 7% at 100 microM. Pretreatment of the tissues with combined 5-HT1/5-HT2 antagonists, methysergide (1 microM) or methiothepin (0.1 microM), significantly attenuated the inhibitory effect of epinastine on the noncholinergic contraction. Pretreatment with tropisetron (1 microM), a 5-HT3 antagonist, ketanserin (10 microM), a 5-HT2 antagonist, thioperamide (10 microM), a histamine H3 antagonist, or phentolamine (10 microM), an alpha-adrenergic antagonist, however, had no effect. Chlorpheniramine (10 microM), another histamine H1 receptor antagonist without significant 5-HT receptor binding affinity, did not produce any inhibition of the eNANC contraction. Epinastine (100 microM) did not displace the dose-response curve to exogenously applied substance P (0.01-10 microM). These results suggest that epinastine, although identified as a 5-HT antagonist, acts as a 5-HT1 agonist and that it inhibits the noncholinergic contraction in guinea-pig airways through stimulation of a prejunctional 5-HT1-like receptor, located to sensory nerves.


Impact of GP gatekeeping on quality of care, and health outcomes, use, and expenditure: a systematic review.
GPs often act as gatekeepers, authorising patients' access to specialty care. Gatekeeping is frequently perceived as lowering health service use and health expenditure. However, there is little evidence suggesting that gatekeeping is more beneficial than direct access in terms of patient- and health-related outcomes. To establish the impact of GP gatekeeping on quality of care, health use and expenditure, and health outcomes and patient satisfaction. A systematic review. The databases MEDLINE, PreMEDLINE, Embase, and the Cochrane Library were searched for relevant articles using a search strategy. Two authors independently screened search results and assessed the quality of studies. Electronic searches identified 4899 studies (after removing duplicates), of which 25 met the inclusion criteria. Gatekeeping was associated with better quality of care and appropriate referral for further hospital visits and investigation. However, one study reported unfavourable outcomes for patients with cancer under gatekeeping, and some concerns were raised about the accuracy of diagnoses made by gatekeepers. Gatekeeping resulted in fewer hospitalisations and use of specialist care, but inevitably was associated with more primary care visits. Patients were less satisfied with gatekeeping than direct-access systems. Gatekeeping was associated with lower healthcare use and expenditure, and better quality of care, but with lower patient satisfaction. Survival rate of patients with cancer in gatekeeping schemes was significantly lower than those in direct access, although primary care gatekeeping was not otherwise associated with delayed patient referral. The long-term outcomes of gatekeeping arrangements should be carefully studied before devising new gatekeeping policies.


Cytochrome c: Using Biological Insight toward Engineering an Optimized Anticancer Biodrug.
The heme protein cytochrome c (Cyt c) plays pivotal roles in cellular life and death processes. In the respiratory chain of mitochondria, it serves as an electron transfer protein, contributing to the proliferation of healthy cells. In the cell cytoplasm, it activates intrinsic apoptosis to terminate damaged cells. Insight into these mechanisms and the associated physicochemical properties and biomolecular interactions of Cyt c informs on the anticancer therapeutic potential of the protein, especially in its ability to subvert the current limitations of small molecule-based chemotherapy. In this review, we explore the development of Cyt c as an anticancer drug by identifying cancer types that would be receptive to the cytotoxicity of the protein and factors that can be finetuned to enhance its apoptotic potency. To this end, some information is obtained by characterizing known drugs that operate, in part, by triggering Cyt c induced apoptosis. The application of different smart drug delivery systems is surveyed to highlight important features for maintaining Cyt c stability and activity and improving its specificity for cancer cells and high drug payload release while recognizing the continuing limitations. This work serves to elucidate on the optimization of the strategies to translate Cyt c to the clinical market.


Foxl2 up-regulates aromatase gene transcription in a female-specific manner by binding to the promoter as well as interacting with ad4 binding protein/steroidogenic factor 1.
Increasing evidence suggests the crucial role of estrogen in ovarian differentiation of nonmammalian vertebrates including fish. The present study has investigated the plausible role of Foxl2 in ovarian differentiation through transcriptional regulation of aromatase gene, using monosex fry of tilapia. Foxl2 expression is sexually dimorphic, like Cyp19a1, colocalizing with Cyp19a1 and Ad4BP/SF-1 in the stromal cells and interstitial cells in gonads of normal XX and sex-reversed XY fish, before the occurrence of morphological sex differentiation. Under in vitro conditions, Foxl2 binds to the sequence ACAAATA in the promoter region of the Cyp19a1 gene directly through its forkhead domain and activates the transcription of Cyp19a1 with its C terminus. Foxl2 can also interact through the forkhead domain with the ligand-binding domain of Ad4BP/SF-1 to form a heterodimer and enhance the Ad4BP/SF-1 mediated Cyp19a1 transcription. Disruption of endogenous Foxl2 in XX tilapia by overexpression of its dominant negative mutant (M3) induces varying degrees of testicular development with occasional sex reversal from ovary to testis. Such fish display reduced expression of Cyp19a1 as well as a drop in the serum levels of 17beta-estradiol and 11-ketotestosterone. Although the XY fish with wild-type tilapia Foxl2 (tFoxl2) overexpression never exhibited a complete sex reversal, there were significant structural changes, such as tissue degeneration, somatic cell proliferation, and induction of aromatase, with increased serum levels of 17beta-estradiol and 11-ketotestosterone. Altogether, these results suggest that Foxl2 plays a decisive role in the ovarian differentiation of the Nile tilapia by regulating aromatase expression and possibly the entire steroidogenic pathway.


National outcomes of penetrating keratoplasty. Risks of endophthalmitis and retinal detachment.
We studied rehospitalization for endophthalmitis or retinal detachment (RD) in 40,351 Medicare beneficiaries who were admitted to US hospitals for penetrating keratoplasty (PK) between 1984 and 1987. This cohort represents 56.5% of all PKs performed during this period for recipients of age to receive Medicare benefits. Penetrating keratoplasty was combined with intracapsular cataract extraction in 1188 patients (2.9%) and with extracapsular cataract extraction in 7038 patients (17.4%). Anterior vitrectomy was performed in 8428 patients (20.9%). The risk of rehospitalization for endophthalmitis within 6 months of PK was 0.77%. Concurrent anterior vitrectomy increased this risk to 1.03% (P = .004). The risk of rehospitalization for RD within 2 years of PK was 1.85%. Concurrent anterior vitrectomy increased this risk to 2.49% (P = .0001). Combined PK and intracapsular cataract extraction demonstrated a 3.9-fold increased rate of RD compared with PK and extracapsular cataract extraction (P = .0001). Anterior vitrectomy with PK and extracapsular cataract extraction increased the risk of RD 4.3-fold compared with PK and extracapsular cataract extraction alone (P = .007). Men were at a 68% higher risk of RD than women (P = .0001). The risk of rehospitalization for endophthalmitis following PK is five times higher and the risk of RD two times higher than that reported following cataract surgery. Anterior vitrectomy, however, results in similar risk increases following either surgery.


Prevalence of Gnathostoma spinigerum infection in wild and cultured swamp eels in Vietnam.
Human infections with Gnathostoma spinigerum frequently occur in southern Vietnam. Previous investigations have implicated infected swamp eels (Monopterus albus) as an important source of infection to humans. Because aquaculture of M. alba is an important farming activity in Vietnam, a 2-yr study was carried out to assess the relative importance of farmed and wild eels as potential sources of gnathostome infections in humans. Eels sold for public consumption in markets in southern provinces were examined between November 2005 and August 2007. Although no infections were detected in 1,020 cultured eels and 1,021 wild-caught eels collected from November 2005 to September 2006, larval G. spinigerum (AL3) infections were first detected in September 2006 in 28 of 230 wild-caught eels (12.2%) obtained from markets in Long An province and the Hoc Mon district of Ho Chi Minh City. Subsequently, monthly surveillance of wild-caught eels from these markets was carried out through August 2007. Prevalence of AL3 varied monthly, ranging from 0.8 to 19.6%. Both prevalence and infection intensity were higher during the latter part of the rainy season (August- October). These results demonstrate that potentially zoonotic G. spinigerum larvae are common in wild eels in southern Vietnam and present a risk to consumers of raw fish dishes, especially during the annual rainy season. This information could help target public health education efforts in the region. The basis for the seasonal variation on eel infections is not known, but may be related to climate effects (flooding, higher temperatures) on intermediate host species ecology.


Diverse Reagent Scaffolds Provide Differential Selectivity of 2'-OH Acylation in RNA.
RNA 2'-OH acylation is widely used both for mapping structure and for conjugating RNA, generally relying on selective reactions with unpaired nucleotides over paired ones. Common reagents for this acylation have been chiefly restricted to two similar aryl scaffolds, leaving open the question of how more broadly varied reagent structure might affect selectivity. Here, we prepared a set of 10 structurally diverse acylimidazole reagents and employed deep sequencing to profile their reactivity and selectivity in an RNA library of systematically varied structure. We show that structure-directed reactivity profiles vary significantly with the reagent scaffold, and we document new acylating agents that have altered selectivity profiles, including reagents that show elevated selectivity within loops, as well as compounds with reduced off-target reactivity in loop closing base pairs. Interestingly, we also show that the simplest reagent (acetylimidazole) is cell permeable and is small enough to map RNA structure in the presence of protein contacts that block other reagents. Finally, we describe reagents that show elevated selectivity within small loops, with applications in site-selective labeling. The results provide new tools for improved conjugation and mapping of RNA.


Entropic organization of interphase chromosomes.
Chromosomes are not distributed randomly in nuclei. Appropriate positioning can activate (or repress) genes by bringing them closer to active (or inactive) compartments like euchromatin (or heterochromatin), and this is usually assumed to be driven by specific local forces (e.g., involving H bonds between nucleosomes or between nucleosomes and the lamina). Using Monte Carlo simulations, we demonstrate that nonspecific (entropic) forces acting alone are sufficient to position and shape self-avoiding polymers within a confining sphere in the ways seen in nuclei. We suggest that they can drive long flexible polymers (representing gene-rich chromosomes) to the interior, compact/thick ones (and heterochromatin) to the periphery, looped (but not linear) ones into appropriately shaped (ellipsoidal) territories, and polymers with large terminal beads (representing centromeric heterochromatin) into peripheral chromocenters. Flexible polymers tend to intermingle less than others, which is in accord with observations that gene-dense (and so flexible) chromosomes make poor translocation partners. Thus, entropic forces probably participate in the self-organization of chromosomes within nuclei.


The structural complexity of old field vegetation and the recruitment of bird-dispersed plant species.
The input of bird-disseminated seeds into four old fields of different structural complexity was examined. Seed input was greatest along the edges of fields. Significantly more seeds were found in a 13 year old field that had structurally complex vegetation, than in a 3-year-old field with a single layer of vegetation. The lower input into the latter field was a function of both low fruit availability and low structural complexity of the field. Similarly, more seeds were found in a 2-year-old field which had artificial structures, simulating saplings, placed in it than in an adjacent control field of the same age. The shape of the structures was not a significant factor in the input of seeds. Timing of seed deposition was correlated with fruit ripening times, relative nutritional value of the fruit and the movements of frugivorous birds. The input of bird-disseminated seeds into fields appears to be directly related to the structural complexity of the vegetation. Woody plants increase the structural complexity of the old fields and serve as recruitment foci for bird-disseminated seeds. Thus, seed deposition by birds influences vegetation pattern, and conversely, the presence of recruitment foci in the vegetation may influence bird dispersal patterns of bird-disseminated seeds.


Coronary lumen volume to myocardial mass ratio in primary microvascular angina.
Microvascular angina (MVA) is an incompletely understood clinical entity. Computational analysis of coronary Computed Tomography Angiography (CTA) has shown an association between low coronary lumen volume to myocardial mass (V/M) ratio and lower Fractional Flow Reserve values, independent of plaque measures. We hypothesized that low V/M ratio may be present in patients with MVA. A retrospective case-control analysis was performed using patients fulfilling guideline criteria for MVA with controls matched for age, gender, coronary risk factors and atherosclerotic plaque burden. V/M was extracted off site (Heartflow Inc; Redwood City, CA) employing allometric scaling laws that allow the definition of the coronary circulation beyond the epicardium. FFRCT values were calculated in the major epicardial coronary arteries for each group. A total of 30 patients with MVA and 32 matched controls were included in the study. Mean total coronary lumen volume (2302 mm3 ± 109 vs 2978 mm3 ± 134, p < 0.001) and mean myocardial mass (90.4 g ± 13.7 vs 100.4 g ± 20.1, p = 0.029) were lower in MVA patients compared to controls. Mean V/M ratio was significantly lower in MVA compared to controls (25.6 mm3/g ± 5.9 vs 30.0 mm3/g ± 6.5, p = 0.007; c-statistic 0.69). V/M ratio did not differ significantly between subclasses of angina severity (p = 0.747). No difference in mean nadir FFRCT values was found between MVA and control groups in the LAD (0.86 ± 0.07 vs 0.83 ± 0.07, p = 0.154), LCX (0.90 ± 0.05 vs 0.90 ± 0.06, p = 0.240) and RCA (0.90 ± 0.04 vs 0.90 ± 0.03, p = 0.773) vessels. Patients with microvascular angina demonstrate a significantly lower coronary CTA-derived coronary volume/myocardial mass ratio than asymptomatic controls.


Small glutamine-rich tetratricopeptide repeat-containing protein alpha (SGTA), a candidate gene for polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) is a heterogenic, complex common genetic disease. Multiple pathways are involved in its pathogenesis, including the androgen signaling pathway and insulin signaling pathway. Small glutamine-rich tetratricopeptide repeat-containing protein alpha (SGTA) is a putative member of the androgen receptor-chaperone-co-chaperone complex, and may play a role in androgen signaling as a co-chaperone. Polymorphisms in the SGTA gene have not been evaluated for a role in PCOS. Women with and without PCOS (287 cases, 187 controls) were genotyped for three single nucleotide polymorphisms (SNPs) in SGTA. SNPs and haplotypes were determined and tested for association with PCOS and component traits of PCOS. For SNP rs1640262, homozygotes for the minor allele were protected against PCOS (P = 0.009). Haplotype 1 (G-A-T) was associated with increased risk of PCOS (P = 0.015). In women with PCOS, haplotype 2 (A-G-C) was associated with increased insulin resistance (P = 0.013), consequently resulting in increased insulin secretion (P = 0.014). This study presents genetic evidence suggesting a potential role of SGTA in the pathogenesis of PCOS. SGTA may provide a connection between multiple pathways in PCOS.


Pilot performance and preference for short cycles of automation in adaptive function allocation.
The present experiment examined pilot response to the rapid cycling of automation. The experiment was conducted using a multi-task simulation environment consisting of tracking, fuel management, and system monitoring sub-tasks. Monitoring and fuel management sub-tasks were performed manually in all conditions. The tracking sub-task cycled between manual and automated control at fixed intervals of either 15, 30 or 60 sec. These cycle times were completely crossed with three levels of tracking difficulty giving nine within-subject conditions which lasted 5 min each. Performance was measured on each of the sub-tasks, as was pilot fatigue level and subjective workload for the respective conditions. Results indicated that both difficulty and cycle duration significantly affected tracking performance which was degraded with task difficulty and longer cycle times. Fuel management and system monitoring performance were unaffected by tracking difficulty and automation duration. However, a subsequent analysis was conducted using the 15 sec period immediately following each automation episode as a 'window' of performance. A different pattern of results was observed. Tracking performance was similarly affected by difficulty, but was no longer affected by cycle duration. Furthermore, fuel management error indicated a trend toward better performance in low difficulty conditions. Results illustrate micro trade-offs within sub-tasks and macro trade-offs between sub-tasks. Overall, the results support the contention that excessively short cycles of automation prove disruptive to performance in multi-task conditions.


Subjective symptoms among motorcycling traffic policemen.
This study investigated the prevalence of subjective symptoms among current and former motorcycling policemen. The subjects of this study consisted of 46 current and 72 former motorcycling traffic policemen from a certain city located in the central part of Japan. They were requested to reply to questions on a self-administered questionnaire regarding age, work history, and subjective symptoms (16 items) during the month preceding the completion of the questionnaire. Shoulder stiffness and low-back pain were frequently encountered. On the whole, the prevalence of subjective symptoms was higher among the current motorcycling policemen, even though they were younger. Assessing the prevalence of subjective symptoms by the median value of experience of motorcycle riding revealed that the high-exposure subgroup in the group that currently ride motorcycles had higher prevalence rates for all the symptoms. The prevalence of subjective symptoms among currently motorcycling traffic policemen seems to be transient, and it declines after the cessation of motorcycle riding or the reallocation to other worktasks, such as office work.


Nitrogen-doped graphene: beyond single substitution and enhanced molecular sensing.
Graphene is a two-dimensional network in which sp(2)-hybridized carbon atoms are arranged in two different triangular sub-lattices (A and B). By incorporating nitrogen atoms into graphene, its physico-chemical properties could be significantly altered depending on the doping configuration within the sub-lattices. Here, we describe the synthesis of large-area, highly-crystalline monolayer N-doped graphene (NG) sheets via atmospheric-pressure chemical vapor deposition, yielding a unique N-doping site composed of two quasi-adjacent substitutional nitrogen atoms within the same graphene sub-lattice (N(2)(AA)). Scanning tunneling microscopy and spectroscopy (STM and STS) of NG revealed the presence of localized states in the conduction band induced by N(2)(AA)-doping, which was confirmed by ab initio calculations. Furthermore, we demonstrated for the first time that NG could be used to efficiently probe organic molecules via a highly improved graphene enhanced Raman scattering.


Volume Measures Using a Digital Image Analysis System are Reliable in Diabetic Foot Ulcers.
Reliable measures of wound size are critical to wound healing research and clinical management. Measurement of full-thickness wounds is increasingly being done using digital images and photogrammetric software, such as VeVMD (Vista Medical, Winnipeg, Manitoba, Canada), to estimate wound volume. The reliability of VeVMD in determining wound volume is unknown. The present study sought to examine the reliability of wound volume measurements obtained using VeVMD. A cross-sectional study of adults with full-thickness, neuropathic, diabetic foot ulcers (DFU) at 2 sites in the US Midwest was undertaken. Ulcer images were obtained, stored, and used to obtain measures of wound volume using VeVMD. Four raters independently completed wound measures, and then repeated these measures 2 weeks after the first measurement. Raters were blinded to the comparison measurements. Inter- and intra-rater correlations were computed. Thirty-three enrolled subjects with 33 DFU were included in the analyses. Inter-rater reliability was 0.745 and intra-rater reliability was 0.868. Four ulcers showed noticeably less agreement between raters; these ulcers had small, but deeply recessed areas, resulting in differences in defining the wound margin. When these 4 ulcers were removed, inter- and intra-rater reliabilities were excellent (0.970 and 0.981, respectively). Reliabilities of volume measurements obtained with VeVMD were acceptable in DFU, even when raters had different definitions of the ulcer margin or changed their definition from time to time. However, conclusions cannot be drawn regarding the performance of VeVMD in other wound types.


Comparison of Healthcare Utilization Between Informal Caregivers and Non-Caregivers: An Analysis of the Health Information National Trends Survey.
Objective: The demands of providing unpaid care for someone with a disabling health condition (i.e., informal caregiving) can limit attention to one's own health needs. Using a nationally representative survey, this study examines whether caregivers report different healthcare utilization relative to non-caregivers. Method: Participants in the Health Information National Trends Survey 5, Cycle 1 reported whether they provided unpaid care and healthcare utilization outcomes. Logistic regressions and chi-square tests with jackknife variance estimation were used. Results: Caregivers (N = 391) did not differ from non-caregivers (N = 2,894) in time since routine checkup or number of healthcare appointments in the past year (p values > .25). Among caregivers, number of healthcare appointments differed according to caregivers' relationship to the care recipient (p = .04). Discussion: Findings suggest that informal caregivers access routine healthcare at a frequency similar to non-caregivers. Further research should determine whether this utilization is optimal, or whether increased utilization during caregiving might help attenuate caregivers' longer term morbidity.


Novobiocin-induced elimination of F'lac and mini-F plasmids from Escherichia coli.
Novobiocin eliminated (cured) F'lac and three low-copy-number mini-F plasmids (pML31, pMF21, and pMF45) from Escherichia coli to different extents. F'lac was cured 0 to 3%. pML31, whose replication region is contained on the 9-kilobase f5 EcoRI restriction enzyme fragment of F, was eliminated 10 to 92%. pMF21, deleted of the origin of mini-F replication at 42.6 kilobases on the F map and known to initiate from an origin at 45.1 kilobases, and its closely related derivative pMF45 were cured to the greatest extent (greater than 97%). pMF45 was eliminated from a wild-type bacterial strain but not from an isogenic novobiocin-resistant gyrB mutant strain, indicating involvement of the B subunit of DNA gyrase in the curing phenomenon. The number of bacteria containing pMF45 halved with each generation of growth in the presence of novobiocin, as is predicted for complete inhibition of plasmid DNA replication.


Trophic predator-prey relationships promote transport of microplastics compared with the single Hypoaspis aculeifer and Folsomia candida.
Although the roles of earthworms and soil collembolans in the transport of microplastics have been studied previously, the effects of the soil biota at different trophic levels and interspecific relationships remain poorly understood. Here, we examine three soil microarthropod species to explore their effects on the transport of microplastics. The selected Folsomia candida and Hypoaspis aculeifer are extensively used model organisms, and Damaeus exspinosus is a common and abundant indigenous species in China. A model food chain (prey-collembolan and predator-mite) was structured to test the role of the predator-prey relationship in the transport of microplastics. Commercial Polyvinyl chloride (PVC) particles (Diameter: 80-250 μm) were selected as the test microplastics, because large amounts of PVC have persisted and accumulated in the environment. Synchronized soil microarthropods were held in plates for seven days to determine the movement of microplastics. The 5000 microplastic particles were carefully placed in the center of each plate prior to the introduction of the animals. Our results clearly show that all three microarthropod species moved and dispersed the microplastics in the plates. The 0.54%, 1.8% and 4.6% of the added microplastic particles were moved by collembolan, predatory mite and oribatid mite, respectively. Soil microarthropods (<0.2 cm) transported microplastic particles up to 9 cm. The avoidance behavior was observed in the collembolans in respect of the microplastics. The predatory -prey relationship did promote the transport of microplastics in the plates, increasing transport by 40% compared with the effects of adding single species (P < .05). Soil microarthropods commonly occur in surface soils (0-5 cm) and, due to their small body size, they can enter soil pores. Our results therefore suggest that the movement of microplastics by soil microarthropods may influence the exposure of other soil biota to microplastics and change the physical properties of soils.


Decreased expression of cell adhesion genes in cancer stem-like cells isolated from primary oral squamous cell carcinomas.
The goal of this study was to isolate cancer stem-like cells marked by high expression of CD44, a putative cancer stem cell marker, from primary oral squamous cell carcinomas and identify distinctive gene expression patterns in these cells. From 1 October 2013 to 4 September 2015, 76 stage III-IV primary oral squamous cell carcinoma of the gingivobuccal sulcus were resected. In all, 13 tumours were analysed by immunohistochemistry to visualise CD44-expressing cells. Expression of CD44 within The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma RNA-sequencing data was also assessed. Seventy resected tumours were dissociated into single cells and stained with antibodies to CD44 as well as CD45 and CD31 (together referred as Lineage/Lin). From 45 of these, CD44+Lin- and CD44-Lin- subpopulations were successfully isolated using fluorescence-activated cell sorting, and good-quality RNA was obtained from 14 such sorted pairs. Libraries from five pairs were sequenced and the results analysed using bioinformatics tools. Reverse transcription quantitative polymerase chain reaction was performed to experimentally validate the differential expression of selected candidate genes identified from the transcriptome sequencing in the same 5 and an additional 9 tumours. CD44 was expressed on the surface of poorly differentiated tumour cells, and within the The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma samples, its messenger RNA levels were higher in tumours compared to normal. Transcriptomics revealed that 102 genes were upregulated and 85 genes were downregulated in CD44+Lin- compared to CD44-Lin- cells in at least 3 of the 5 tumours sequenced. The upregulated genes included those involved in immune regulation, while the downregulated genes were enriched for genes involved in cell adhesion. Decreased expression of PCDH18, MGP, SPARCL1 and KRTDAP was confirmed by reverse transcription quantitative polymerase chain reaction. Lower expression of the cell-cell adhesion molecule PCDH18 correlated with poorer overall survival in the The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma data highlighting it as a potential negative prognostic factor in this cancer.


Reservoir and reservoir-less pressure effects on arterial waves in the canine aorta.
A time-domain approach to couple the Windkessel effect and wave propagation has been recently introduced. The technique assumes that the measured pressure in the aorta (P) is the sum of a reservoir pressure (Pr), due to the storage of blood, and an excess pressure (Pe), due to the waves. Since the subtraction of Pr from P results in a smaller component of Pe, we hypothesized that using the reservoir-wave approach would produce smaller values of wave speed and intensities. Therefore, the aim of this study is to quantify the differences in wave speed and intensity using P, wave-only, and Pe, reservoir-wave techniques. Pressure and flow were measured in the canine aorta in the control condition and during total occlusion at four sites. Wave speed was determined using the PU-loop (c) and PeU-loop (ce) methods, and wave intensity analysis was performed using P and separately using Pe; the magnitude and time of the main waves and the reflection index were calculated. Both analyses produced similar wave intensity analysis curves, and no significant differences in the timing of the waves, except onset of the forward expansion wave, indicated that distal occlusions have little effect on haemodynamics in the ascending aorta. We consistently found lower values of wave speed and intensities when the reservoir-wave model was applied. In particular, the magnitude of the backward waves was markedly smaller, even during proximal occlusions. In the absence of other independent techniques or evidence, it is not currently possible to decide which of the two models is more correct.


IL-2/anti-IL-2 antibody complexes show strong biological activity by avoiding interaction with IL-2 receptor alpha subunit CD25.
IL-2 is crucial to T cell homeostasis, especially of CD4(+) T regulatory cells and memory CD8(+) cells, as evidenced by vigorous proliferation of these cells in vivo following injections of superagonist IL-2/anti-IL-2 antibody complexes. The mechanism of IL-2/anti-IL-2 antibody complexes is unknown owing to a lack of understanding of IL-2 homeostasis. We show that IL-2 receptor alpha (CD25) plays a crucial role in IL-2 homeostasis. Thus, prolongation of IL-2 half-life and blocking of CD25 using antibodies or CD25-deficient mice led in combination, but not alone, to vigorous IL-2-mediated T cell proliferation, similar to IL-2/anti-IL-2 antibody complexes. These data suggest an unpredicted role for CD25 in IL-2 homeostasis.


Plague and other human infections caused by Yersinia species.
With an estimated 100 million victims, pandemically and epidemically occurring plague has been looked upon as a classical scourge of mankind during the last two millenia. Without treatment at least 50% of the affected individuals die from infection with Yersinia pestis, a bacterium belonging to the family of Enterobacteriaceae. The disease takes a fulminant course. After an incubation period of 2-6 days, bubonic plague primarily attacks one group of lymph nodes. The onset of pulmonic plague, transmitted by droplet infection, takes place within several hours and causes bronchopneumonia. Early recognition facilitates a promising antibiotic therapy with tetracycline, streptomycin or chloramphenicol. Human beings acquire the bacteria through bites of fleas from domestic rats in densely populated cities of countries with low hygienic standards, or sporadically in the open country from infected wild rodents. Laboratory procedure includes microscopy supplemented by immunofluorescence and cultivation of the bacterium from clinical material. Direct serology and PCR result in a fast detection of specific antigens or nucleotide sequences. Determination of serum antibodies is principally used for epidemiological investigation. Today, physicians in the civilized western world lack experience for the recognition of plague, and analytical techniques for diagnosis are only available in some specialized laboratories. Yersiniosis becomes primarily manifest as gastroenteritis caused by Yersinia enterocolitica or as pseudoappendicitis caused by Yersinia pseudotuberculosis and requires antibiotics only in severe septic cases. Different extraintestinal symptoms may be observed in dependence on the patient's HLA type and gender. The ubiquitous germ is mainly transmitted by the fecal-oral route via infected domestic or farm animals and contaminated food. The relevant virulence factors are encoded on a 70 kB plasmid common to all Yersinia species and strains that are human pathogens. The most important tools for laboratory diagnosis are culture from suitable body fluids and serological detection of specific antibodies. The infection rate among healthy individuals in Europe in terms of percentage of elevated IgA or IgG titers has been quoted to be 3-40% in different investigations but does not significantly correlate to direct bacteriological detection.


Let me take the wheel: Illusory control and sense of agency.
Illusory control refers to an effect in games of chance where features associated with skilful situations increase expectancies of success. Past work has operationalized illusory control in terms of subjective ratings or behaviour, with limited consideration of the relationship between these definitions, or the broader construct of agency. This study used a novel card-guessing task in 78 participants to investigate the relationship between subjective and behavioural illusory control. We compared trials in which participants (a) had no opportunity to exercise illusory control, (b) could exercise illusory control for free, or (c) could pay to exercise illusory control. Contingency Judgment and Intentional Binding tasks assessed explicit and implicit sense of agency, respectively. On the card-guessing task, confidence was higher when participants exerted control than in the baseline condition. In a complementary model, participants were more likely to exercise control when their confidence was high, and this effect was accentuated in the pay condition relative to the free condition. Decisions to pay were positively correlated with control ratings on the Contingency Judgment task, but were not significantly related to Intentional Binding. These results establish an association between subjective and behavioural illusory control and locate the construct within the cognitive literature on agency.


Calibration methodology of low-cost sensors for high-quality monitoring of fine particulate matter.
Low concentrations of pollutants may already be associated with significant health effects. An accurate assessment of individual exposure to pollutants therefore requires measuring pollutant concentrations at the finest possible spatial and temporal scales. Low-cost sensors (LCS) of particulate matter (PM) meet this need so well that their use is constantly growing worldwide. However, everyone agrees that LCS must be calibrated before use. Several calibration studies have already been published, but there is not yet a standardized and well-established methodology for PM sensors. In this work, we develop a method combining an adaptation of an approach developed for gas-phase pollutants with a dust event preprocessing to calibrate PM LCS (PMS7003) commonly used in urban environments. From the selection of outliers to model tuning and error estimation, the developed protocol allows to analyze, process and calibrate LCS data using multilinear (MLR) and random forest (RFR) regressions for comparison with a reference instrument. We demonstrate that the calibration performance was very good for PM1 and PM2.5 but turns out less good for PM10 (R2 = 0.94, RMSE = 0.55 μg/m3, NRMSE = 12 % for PM1 with MLR, R2 = 0.92, RMSE = 0.70 μg/m3, NRMSE = 12 % for PM2.5 with RFR and R2 = 0.54, RMSE = 2.98 μg/m3, NRMSE = 27 % for PM10 with RFR). Dust events removal significantly improved LCS accuracy for PM2.5 (11 % increase of R2 and 49 % decrease of RMSE) but no significant changes for PM1. Best calibration models included internal relative humidity and temperature for PM2.5 and only internal relative humidity for PM1. It turns out that PM10 cannot be properly measured and calibrated because of technical limitations of the PMS7003 sensor. This work therefore provides guidelines for PM LCS calibration. This represents a first step toward standardizing calibration protocols and facilitating collaborative research.


Potential for use of retinoic acid as an oral vaccine adjuvant.
Despite the heavy burden of diarrhoeal disease across much of the tropical world, only two diarrhoea-causing pathogens, cholera and rotavirus, are the target of commercially available vaccines. Oral vaccines are generally less immunogenic than the best parenteral vaccines, but the reasons for this are still debated. Over the past decade, several lines of evidence from work in experimental animals have suggested that all-trans retinoic acid (ATRA), a form of vitamin A which is highly transcriptionally active, can alter the homing receptor expression of T lymphocytes. Increased expression of α4β7 integrin and the chemokine receptor CCR9 following exposure to ATRA can be used to redirect T cells to the gut. Early work in human volunteers suggests that oral ATRA administration 1 h prior to dosing with oral typhoid vaccine can augment secretion of specific IgA against vaccine-derived lipopolysaccharide into gut secretions. In this review, we set out the rationale for using ATRA in this way and assess its likely applicability to vaccination programmes for protection of children in low-income countries from the considerable mortality caused by diarrhoeal disease. Comparison of recent work in experimental animals, non-human primates and men suggests that a more detailed understanding of ATRA dosage and kinetics will be important to taking forward translational work into human vaccinology.


Erythropoietin does not affect TNF and IL-6 production directly.
The tissue-protective action of erythropoietin (EPO) in animal models is often associated with reduced inflammation. However, there are many contrasting reports of the effect of EPO on the production of inflammatory cytokines induced by lipopolysaccharide (LPS) in vitro, with different papers reporting an inhibition, an upregulation, or a lack of effect. Negative results are likely underestimated by a publication bias. As EPO has anti-inflammatory actions in models associated with tissue injury, we hypothesized that EPO could specifically inhibit the induction of inflammatory cytokines by danger signals associated with cell death, and investigated its effect on the induction of IL-6 or TNF by high-mobility group-box 1 protein (HMGB1) or by necrotic cells. We did not observe any significant effect of EPO in these models; neither EPO affected the response induced by TLR agonists different from LPS, or by extracellular ATP-mediated activation of the inflammasome. We conclude that the inhibition of inflammation by EPO is likely to be an indirect effect, secondary to its tissue-protective activity, or that it requires a prior priming induced by the injury.


Feasibility of eliminating ocular Chlamydia trachomatis with repeat mass antibiotic treatments.
Mass antibiotic administrations for ocular chlamydial infection play a key role in the World Health Organization's trachoma control program. Mathematical models suggest that it is possible to eliminate trachoma locally with repeat mass treatment, depending on the coverage level of the population, frequency of mass treatments, and rate that infection returns into a community after each mass treatment. Precise estimates of this latter parameter have never been reported. To determine the rate at which chlamydial infection returns to a population after mass treatment and to estimate the treatment frequency required for elimination of ocular chlamydia from a community. Longitudinal cohort study of 24 randomly selected villages from the Gurage Zone in Ethiopia conducted February 2003 to October 2003. A total of 1332 children aged 1 to 5 years were monitored for prevalence of ocular chlamydial infection pretreatment and 2 and 6 months posttreatment. All individuals older than 1 year were eligible for single-dose oral azithromycin treatment. Pregnant women were offered tetracycline eye ointment. Prevalence of ocular chlamydial infection, measured by polymerase chain reaction, in children aged 1 to 5 years, in each of 24 villages at each time point was used to estimate the rate of return of infection and the treatment frequency necessary for elimination. The prevalence of infection was 56.3% pretreatment (95% confidence interval [CI], 47.5%-65.1%), 6.7% 2 months posttreatment (95% CI, 4.2%-9.2%), and 11.0% 6 months posttreatment (95% CI, 7.3%-14.7%). Infection returned after treatment at an exponential rate of 12.3% per month (95% CI, 4.6%-19.9% per month). The minimum treatment frequency necessary for elimination was calculated to be once every 11.6 months (95% CI, 7.2-30.9 months), given a coverage level of 80%. Thus, biannual treatment, already being performed in some areas, was estimated to be more than frequent enough to eventually eliminate infection. The rate at which ocular chlamydial infection returns to a community after mass treatment suggests that elimination of infection in a hyperendemic area is feasible with biannual mass antibiotic administrations and attainable coverage levels.


Lanatoside C, a cardiac glycoside, acts through protein kinase Cδ to cause apoptosis of human hepatocellular carcinoma cells.
Recent studies have revealed that cardiac glycosides, such as digitalis and digoxin, have anticancer activity and may serve as lead compounds for the development of cancer treatments. The poor prognosis of hepatocellular carcinoma (HCC) patients reflects the development of resistance to current chemotherapeutic agents, highlighting the need for discovering new small-molecule therapeutics. Here, we found that lanatoside C, an anti-arrhythmic agent extracted from Digitalis lanata, inhibited the growth of HCC cells and dramatically decreased tumor volume as well as delayed tumor growth without obvious body weight loss. Moreover, lanatoside C triggered mitochondrial membrane potential (MMP) loss, activation of caspases and translocation of apoptosis-inducing factor (AIF) into the nucleus, which suggests that lanatoside C induced apoptosis through both caspase-dependent and -independent pathways. Furthermore, we discovered that lanatoside C activated protein kinase delta (PKCδ) via Thr505 phosphorylation and subsequent membrane translocation. Inhibition of PKCδ reversed lanatoside C-induced MMP loss and apoptosis, confirming that lanatoside C caused apoptosis through PKCδ activation. We also found that the AKT/mTOR pathway was negatively regulated by lanatoside C through PKCδ activation. In conclusion, we provide the first demonstration that the anticancer effects of lanatoside C are mainly attributable to PKCδ activation.


What should men living with haemophilia need to know? The perspectives of Canadian men with haemophilia.
Haemophilia is an inherited bleeding disorder affecting approximately 3000 Canadian men (Walker 2012). To manage their disease effectively individuals must be knowledgeable about the disease, bleed prevention strategies, treatment approaches, and complications. Data on individuals' knowledge levels are scarce. The availability of such data could lead to better educational strategies for disease management. The aim of this study was to determine current knowledge levels, needs and gaps among Canadian individuals with haemophilia to facilitate optimal disease management. A survey was disseminated to adult males with haemophilia at three Haemophilia Treatment Centres (HTCs) in Canada. Self-reported current knowledge levels and knowledge seeking were measured. Survey respondents reported highest levels of knowledge in the following areas: identifying and treating a bleed, haemophilia and physical activity, travel, career issues and genetics. Lower levels of knowledge were reported in the areas of sexual activity, product safety, information about factor, haemophilia and ageing, advocacy, timing of prophylactic infusions, and new or alternative therapies. Treating a bleed was the most commonly sought information, followed by information about factor, product safety, identifying a bleed and other health care issues. There was a positive correlation between knowledge seeking and severity of disease. HTC attendance was associated with knowledge seeking, and HTCs were the most frequented knowledge source, followed by the Canadian Haemophilia Society website. Canadian men were well informed; the HTC's role in knowledge sharing was recognized. Timing of infusions, sexual activity and ageing are areas which should be targeted in knowledge sharing.


CNVassoc: Association analysis of CNV data using R.
Copy number variants (CNV) are a potentially important component of the genetic contribution to risk of common complex diseases. Analysis of the association between CNVs and disease requires that uncertainty in CNV copy-number calls, which can be substantial, be taken into account; failure to consider this uncertainty can lead to biased results. Therefore, there is a need to develop and use appropriate statistical tools. To address this issue, we have developed CNVassoc, an R package for carrying out association analysis of common copy number variants in population-based studies. This package includes functions for testing for association with different classes of response variables (e.g. class status, censored data, counts) under a series of study designs (case-control, cohort, etc) and inheritance models, adjusting for covariates. The package includes functions for inferring copy number (CNV genotype calling), but can also accept copy number data generated by other algorithms (e.g. CANARY, CGHcall, IMPUTE). Here we present a new R package, CNVassoc, that can deal with different types of CNV arising from different platforms such as MLPA o aCGH. Through a real data example we illustrate that our method is able to incorporate uncertainty in the association process. We also show how our package can also be useful when analyzing imputed data when analyzing imputed SNPs. Through a simulation study we show that CNVassoc outperforms CNVtools in terms of computing time as well as in convergence failure rate. We provide a package that outperforms the existing ones in terms of modelling flexibility, power, convergence rate, ease of covariate adjustment, and requirements for sample size and signal quality. Therefore, we offer CNVassoc as a method for routine use in CNV association studies.


Lommel pulses: an analytic form for localized waves of the focus wave mode type with bandlimited spectrum.
A criticism of the focus wave mode (FWM) solution for localized pulses is that it contains backward propagating components that are difficult to generate in many practical situations. We describe a form of FWM where the strength of the backward propagating components is identically zero and derive special cases where the field can be written in an analytic form. In particular, a free-space version of "backward light" pulse is considered, which moves in the opposite direction with respect to all its spectral constituents.


Enhanced Recovery After Colorectal Surgery (ERAS) in Elderly Patients Is Feasible and Achieves Similar Results as in Younger Patients.
Aim: Enhanced recovery after surgery (ERAS) is a multimodal approach that aims to optimize perioperative treatment. Whether elderly patients receiving colorectal surgery can adhere to and benefit from an ERAS approach is uncertain. The aim of this study was to compare patients in different age groups participating in an ERAS program. Method: In this substudy of a randomized controlled trial, we analyzed the interventional ERAS arm of adult patients eligible for laparoscopic or open colorectal resection with regard to the importance of age. Patients were divided into three groups based on age: ≤65 years (n = 79), 66-79 years (n = 56), and ≥80 years (n = 19). The primary end point was total postoperative hospital stay (THS). Secondary end points were postoperative hospital stay, postoperative complications, postoperative C-reactive protein levels, readmission rate, mortality, and patient adherence to the different ERAS elements. All parameters and measuring the adherence to the ERAS protocol were recorded before surgery, on the day of the operation, and daily until discharge. Results: There were no significant differences in length of THS between age groups (≤65 years, median 5 [range 2-47] days; 66-79 years, median 5.5 [range 2-36] days; ≥80 years, median 7 [range 3-50] days; p = .53). All secondary outcomes were similar between age groups. Patient adherence to the ERAS protocol was as good in the elderly as it was in the younger patients. Conclusion: Elderly patients adhered to and benefited from an ERAS program, similar to their younger counterparts.


A telepsychiatry model to support psychiatric outreach in the public sector in South Africa.
The access of rural Mental Health Care Users in South Africa to specialist psychiatrists and quality mental health care is currently sub-optimal. Health professionals and planners working in psychiatry lack a well-defined and feasible outreach model to facilitate the delivery of services to remote and rural areas. In response to this challenge, a three-year action research telepsychiatry study was undertaken by the Departments of Psychiatry and TeleHealth at the University of KwaZulu-Natal, to develop a telepsychiatry outreach model based on local research and international evidence. The Model draws on needs and infrastructure assessments of the designated psychiatric hospitals in the province, a review of the published international evidence on telepsychiatry and videoconference-based education, and an evaluation of local clinical and educational telepsychiatry implementations in KwaZulu-Natal. The Model proposed is "virtual", i.e. not bound to provincial or district referral patterns, aims not to add to the burden on the current workforce and is intended to be integrated into psychiatry outreach services and policy. The Model should be subjected to in situ testing for validation and implementation. It is hoped that an implementation of this Model will improve the access of Mental Health Care Users to specialist psychiatry care.


Upregulation of endogenous ICAM-1 reduces ovarian cancer cell growth in the absence of immune cells.
Ovarian cancer is a difficult-to-treat cancer with a 5-year survival rate of only ∼45%, due to late diagnosis and therapy resistance. In need of new therapeutic approaches, induction of intercellular adhesion molecule (ICAM)-1 expression might be of interest, since the expression of ICAM-1 is lower in ovarian cancer cells compared with healthy ovarian cells and correlated with decreased tumorigenicity. Whereas ICAM-1 expression on tumor cells is of importance for attracting immune cells, ICAM-1 might also induce tumorigenicity and chemoresistance. In ovarian cancer, such a role of ICAM-1 is unclear. Here, we investigated whether ICAM-1 has a cell-biological role by bidirectional modulation of ICAM-1 expression using ICAM-targeting artificial transcription factors. For a panel of ovarian cancer cells, tumor growth and cisplatin sensitivity were evaluated. Induction of ICAM-1 expression (ranging from 3- to 228-fold on mRNA level and 1.7- to 108-fold on protein level) resulted in indications of decreased ovarian cancer cell growth and reduced cisplatin sensitivity. Repression ranged from 48 to 94% on mRNA level and 47 to 91% on protein level. This study shows that, next to its established immunogenic role, ICAM-1 affects cell biological behavior of ovarian cancer cells and, importantly, that reexpression by artificial transcription factors represents a powerful approach for functional validation of genes epigenetically silenced in cancer, such as ICAM-1.


Driven to distraction: dual-Task studies of simulated driving and conversing on a cellular telephone.
Dual-task studies assessed the effects of cellular-phone conversations on performance of a simulated driving task. Performance was not disrupted by listening to radio broadcasts or listening to a book on tape. Nor was it disrupted by a continuous shadowing task using a handheld phone, ruling out, in this case, dual-task interpretations associated with holding the phone, listening, or speaking, However significant interference was observed in a word-generation variant of the shadowing task, and this deficit increased with the difficulty of driving. Moreover unconstrained conversations using either a handheld or a hands-free cell phone resulted in a twofold increase in the failure to detect simulated traffic signals and slower reactions to those signals that were detected. We suggest that cellular-phone use disrupts performance by diverting attention to an engaging cognitive context other than the one immediately associated with driving.


Private health investments under competing risks: Evidence from malaria control in Senegal.
This study exploits the introduction of high subsidies for anti-malaria products in Senegal in 2009 to investigate whether malaria prevents parents from investing in child health. A simple model of health investments under competing mortality risks predicts that private expenses to fight malaria and other diseases should increase in response to anti-malaria public interventions. We test and validate this prediction using original panel data from a household expenditure survey combined with geographical information on malaria prevalence. We find that health expenditures in malarious regions catch up with non-malarious regions. The same result holds for parental health-seeking behavior against other diseases like diarrhea. These patterns cannot be explained by differential trends between regions. Our results suggest that behavioral responses to anti-malaria campaigns magnify their impact on all-cause mortality for children.


Familial aspects of coeliac disease.
The incidence of coeliac disease amongst first-degree relatives of 115 patients with coeliac disease aged between nine and 75 years has been studied. Of 689 relatives 526 were living of whom 324 were willing to be investigated. One hundred and eighty-two relatives underwent jujunal biopsy. Forty-one were considered to have coeliac disease, 22 per cent of those biopsied, or 11-2 per cent of the available relatives. One-third of the relatives discovered to have coeliac disease were asymptomatic but all had at least one abnormal result amongst the laboratory indices used. Twenty-two per cent of the relatives with haemoglobin less than 13-0 g, 43 per cent with serum folate less than 3-0 pg/ml, 24 per cent with serum albumin less than 4-0 g/100 ml, with serum iron less than 60 mug/100 ml or with serum alkaline phosphatase above 13 K.A. units had coeliac disease. Less than 5 per cent of relatives with H.L.A. antigens other than H.L.A. 8 had coeliac disease compared with one in four of those with H.L.A. 8. The high percentage of relatives with H.L.A. 8 antigens or with anticonnective tissue antibodies, amongst those with non-specific biopsy appearances suggests that these groups also contain a number of relatives with varying degrees of gluten intolerance.


Interleukin-6 does not mediate endotoxin-induced uveitis in mice: studies in gene deletion animals.
Interleukin-6 (IL-6) has been strongly implicated in anterior uveitis based on its presence in aqueous humor from infected eyes and its inflammatory effects when injected intravitreally into rats. We used IL-6-deficient mice to test further the hypothesis that IL-6 contributes to the development of endotoxin-induced uveitis. Uveitis was scored by histologic analysis of C3H/HeN mice 24 hours after intravitreal injections of up to 200 ng of recombinant murine IL-6. Uveitis was similarly measured in IL-6-deficient mice and congenic controls 24 hours after intravitreal injection of 250 ng of Escherichia coli endotoxin. Reverse transcription-polymerase chain reaction was used to detect mRNAs for several cytokines at 3 hours postinjection. The IL-6 concentration in aqueous humor samples was determined with a bioassay using the murine B9 plasmacytoma cell line. Direct injection of IL-6 did not induce uveitis. Mice genetically deficient in IL-6 developed endotoxin-induced uveitis that was comparable or more severe than congenic control mice. Compensatory changes in the expression of mRNA for other cytokines were not detected in irises from the IL-6-deficient mice. In IL-6-competent mice that received bilateral endotoxin injections, no correlation was found between the number of infiltrating cells in one eye and the IL-6 concentration in the aqueous humor of the contralateral eye. In marked contrast to previous conclusions with rats, IL-6 was not sufficient for inducing uveitis in mice. Additionally, IL-6 was not necessary for the development of uveitis subsequent to intravitreal injection of endotoxin in mice.


Microcanonical and thermal instanton rate theory for chemical reactions at all temperatures.
Semiclassical instanton theory is used to study the quantum effects of tunnelling and delocalization in molecular systems. An analysis of the approximations involved in the method is presented based on a recent first-principles derivation of instanton rate theory [J. Chem. Phys., 2016, 144, 114106]. It is known that the standard instanton method is unable to accurately compute thermal rates near the crossover temperature. The causes of this problem are identified and an improved method is proposed, whereby an instanton approximation to the microcanonical rate is defined and integrated numerically to obtain a thermal rate at any temperature. No new computational algorithms are required, but only data analysis of a number of standard instanton calculations.


An expressed sequence tag (EST) library for Drosophila serrata, a model system for sexual selection and climatic adaptation studies.
The native Australian fly Drosophila serrata belongs to the highly speciose montium subgroup of the melanogaster species group. It has recently emerged as an excellent model system with which to address a number of important questions, including the evolution of traits under sexual selection and traits involved in climatic adaptation along latitudinal gradients. Understanding the molecular genetic basis of such traits has been limited by a lack of genomic resources for this species. Here, we present the first expressed sequence tag (EST) collection for D. serrata that will enable the identification of genes underlying sexually-selected phenotypes and physiological responses to environmental change and may help resolve controversial phylogenetic relationships within the montium subgroup. A normalized cDNA library was constructed from whole fly bodies at several developmental stages, including larvae and adults. Assembly of 11,616 clones sequenced from the 3' end allowed us to identify 6,607 unique contigs, of which at least 90% encoded peptides. Partial transcripts were discovered from a variety of genes of evolutionary interest by BLASTing contigs against the 12 Drosophila genomes currently sequenced. By incorporating into the cDNA library multiple individuals from populations spanning a large portion of the geographical range of D. serrata, we were able to identify 11,057 putative single nucleotide polymorphisms (SNPs), with 278 different contigs having at least one "double hit" SNP that is highly likely to be a real polymorphism. At least 394 EST-associated microsatellite markers, representing 355 different contigs, were also found, providing an additional set of genetic markers. The assembled EST library is available online at http://www.chenowethlab.org/serrata/index.cgi. We have provided the first gene collection and largest set of polymorphic genetic markers, to date, for the fly D. serrata. The EST collection will provide much needed genomic resources for this model species and facilitate comparative evolutionary studies within the montium subgroup of the D. melanogaster lineage.


Marek's disease virus infection in the eye: chronological study of the lesions, virus replication, and vaccine-induced protection.
Marek's disease virus (MDV) infection in the eye was studied chronologically after inoculating 1-day-old chickens with a very virulent MDV strain, Md5. The ocular lesions could be classified as early lesions (6-11 days postinoculation [dpi]) and late lesions (26 and 56 dpi), based upon the location and severity of the lesions. The early lesions involved iris, ciliary body, and choroid layer, and were characterized by endothelial cell hypertrophy, vasculitis, and infiltration of lymphocytes (mainly CD8+), plasma cells, macrophages, and heterophils. Expression of early MDV-antigen pp38 in the cells infiltrating choroid layer was detected as early as 11 dpi. Late lesions consisted of severe lymphohistiocytic uveitis, keratitis, pectenitis, vitreitis, retinitis, and segmental to diffuse retinal necrosis. Cell infiltration included macrophages, granulocytes, plasma cells, and both CD4+ and CD8+ cells of various sizes. Expression of early MDV-antigen pp38 was readily found within the retina, uveal tract, and corneal epithelium. No expression of late-antigen gB or oncoprotein meq was detected in any of the eyes examined. A second experiment was conducted to study the effect of vaccination on the development of ocular lesions. Both HVT and CVI988 were able to protect against the development of early ocular lesions in chickens infected with very virulent plus strain MDV 648A. However, only CVI988 conferred complete protection against the development of late ocular lesions. HVT conferred partial protection, as it reduced the frequency and severity of the late ocular lesions. These results enhance our understanding of the nature and pattern of MDV infection in the eye.


Genomic organization and promoter characterization of human CXCR4 gene.
CXCR4 is the receptor for the CXC chemokine SDF1 that has essential functions on embryo organogenesis, immunological functions and T lymphocyte trafficking. Recently, CXCR4 has drawn unexpected attention as it was recently identified as a co-factor required for entry of lymphotropic HIV isolates in CD4+ T lymphocytes. CXCR4 is the only SDF1 receptor identified so far. This suggests that CXCR4 expression is critical for the biological effects of SDF1. To investigate the mechanisms controlling both the constitutive and induced expression of CXCR4 receptors we have isolated and characterized the promoter region and determined the genomic structure of the human gene. The CXCR4 gene contains two exons separated by an intronic sequence. A 2.6 kb 5'-flanking region located upstream the CXCR4 open reading frame contains a TATA box and the transcription start site characteristic of a functional promoter. This region also contains putative consensus binding sequences for different transcription factors, some of them associated with the hemopoiesis and lymphocyte development.


Learning overcomplete representations.
In an overcomplete basis, the number of basis vectors is greater than the dimensionality of the input, and the representation of an input is not a unique combination of basis vectors. Overcomplete representations have been advocated because they have greater robustness in the presence of noise, can be sparser, and can have greater flexibility in matching structure in the data. Overcomplete codes have also been proposed as a model of some of the response properties of neurons in primary visual cortex. Previous work has focused on finding the best representation of a signal using a fixed overcomplete basis (or dictionary). We present an algorithm for learning an overcomplete basis by viewing it as probabilistic model of the observed data. We show that overcomplete bases can yield a better approximation of the underlying statistical distribution of the data and can thus lead to greater coding efficiency. This can be viewed as a generalization of the technique of independent component analysis and provides a method for Bayesian reconstruction of signals in the presence of noise and for blind source separation when there are more sources than mixtures.


Mindfulness for irritable bowel syndrome: protocol development for a controlled clinical trial.
Irritable bowel syndrome (IBS), a functional bowel disorder with symptoms of abdominal pain and disturbed defecation experienced by 10% of U.S. adults, results in significant disability, impaired quality of life, and health-care burden. Conventional medical care focusing on pharmacological approaches, diet, and lifestyle management has been partially effective in controlling symptoms. Behavioral treatments, such as cognitive-behavioral therapy and hypnosis, are promising. This paper describes an on-going feasibility study to assess the efficacy of mindfulness training, a behavioral treatment involving directing and sustaining attention to present-moment experience, for the treatment of IBS. The study design involves randomization of adult women with IBS according to Rome II criteria, to either an eight-week mindfulness training group (based on a Mindfulness-based Stress Reduction [MBSR] format) or a previously validated IBS social-support group as an attention-control condition. The primary hypothesis is that, compared to Support Group participants, those in the Mindfulness Program will demonstrate significant improvement in IBS symptoms as measured by the IBS Symptom Severity Scale [1]. 214 individuals have been screened for eligibility, of whom 148 were eligible for the study. Of those, 87 were enrolled, with 21 withdrawing after having given consent. 66 have completed or are in the process of completing the interventions. It is feasible to undertake a rigorous randomized clinical trial of mindfulness training for people with IBS, using a standardized MBSR protocol adapted for those experiencing IBS, compared to a control social-support group previously utilized in IBS studies. Clinical Trials.gov Identifier: NCT00680693.


Temporal event sequence simplification.
Electronic Health Records (EHRs) have emerged as a cost-effective data source for conducting medical research. The difficulty in using EHRs for research purposes, however, is that both patient selection and record analysis must be conducted across very large, and typically very noisy datasets. Our previous work introduced EventFlow, a visualization tool that transforms an entire dataset of temporal event records into an aggregated display, allowing researchers to analyze population-level patterns and trends. As datasets become larger and more varied, however, it becomes increasingly difficult to provide a succinct, summarizing display. This paper presents a series of user-driven data simplifications that allow researchers to pare event records down to their core elements. Furthermore, we present a novel metric for measuring visual complexity, and a language for codifying disjoint strategies into an overarching simplification framework. These simplifications were used by real-world researchers to gain new and valuable insights from initially overwhelming datasets.


Timeline of Psychological and Physiological Effects Occurring During Military Deployment on a Medical Team.
The negative effects of deployment on military mental health is a topic of major interest. Predeployment and postdeployment assessments are common, but to date there has been little to no intradeployment assessment of military members. This study attempts to determine the physiological and psychiatric effects on Servicemembers over the course of deployment, to provide a baseline data set and to allow for better prediction, prevention, and intervention on these negative effects. A retrospective analysis was performed on physiological and psychiatric data collected on a single deployed medical team between 16 January 2020 and 12 July 2020. Patient health screening questionnaires (PHQ-9) and physiological measurements were completed serially twice weekly on five active-duty military volunteers for the entirety of a scheduled 6-month deployment. Depression symptom development followed a linear trend (p = .0149) and severity followed a quadratic trend (p < .001) over a length of a deployment. Weight (p = .435) and pulse (p = .416) were not statistically altered. Mean arterial pressure (MAP) had a statistically significant reduction (p < .001). In this specific population, there was a linear relationship between time deployed and depression symptoms and severity. Depression symptom severity decreases toward the end of deployment but does not return to baseline before deployment's end.


Clear conscience grounded in relations: Expressions of Persian-speaking nurses in Sweden.
Conscience is an important concept in ethics, having various meanings in different cultures. Because a growing number of healthcare professionals are of immigrant background, particularly within the care of older people, demanding multiple ethical positions, it is important to explore the meaning of conscience among care providers within different cultural contexts. The study aimed to illuminate the meaning of conscience by enrolled nurses with an Iranian background working in residential care for Persian-speaking people with dementia. A phenomenological hermeneutical method guided the study. Participants and research context: A total of 10 enrolled nurses with Iranian background, aged 33-46 years, participated in the study. All worked full time in residential care settings for Persian-speaking people with dementia in a large city, in Sweden. Ethical considerations: The study was approved by the Regional Ethical Review Board for ethical vetting of research involving humans. Participants were given verbal and written study information and assured that their participation was voluntary and confidential. Three themes were constructed including perception of conscience, clear conscience grounded in relations and striving to keep a clear conscience. The conscience was perceived as an inner guide grounded in feelings, which is dynamic and subject to changes throughout life. Having a clear conscience meant being able to form a bond with others, to respect them and to get their confirmation that one does well. To have a clear conscience demanded listening to the voice of the conscience. The enrolled nurses strived to keep their conscience clear by being generous in helping others, accomplishing daily tasks well and behaving nicely in the hope of being treated the same way one day. Cultural frameworks and the context of practice needed to be considered in interpreting the meaning of conscience and clear conscience.


Optical digital comparison unit for equal-to, less-than, and greater-than determination.
A number of nonnumerical processing applications, including database management, full text search, and pattern recognition rely heavily on digital comparisons. The development of massive-capacity optical memories coupled with the high speed and parallelism of optics have led to the investigation of optical techniques for nonnumerical processing. This paper proposes a system design for an optical comparator capable of performing multiple equal-to, less-than, and greater-than comparisons between pairs of binary words. The comparator consists of three two-dimensional arrays of optical elements based on a new optical logic device called the light-amplifying optical switch. The first two stages contain inverters, NOR gates, and flip-flops, while the third stage is a custom-designed winner-takes-all network. With a compact design and with small high-speed devices a comparator with 2.5 × 10(4) pixels could theoretically attain a processing rate of approximately 4 × 10(10) 16-bit word comparisons/s.