Primary care strategies for promoting parent-child interactions and school readiness in at-risk families: the Bellevue Project for Early Language, Literacy, and Education Success.
To determine the effects of pediatric primary care interventions on parent-child interactions in families with low socioeconomic status. In this randomized controlled trial, participants were randomized to 1 of 2 interventions (Video Interaction Project [VIP] or Building Blocks [BB]) or the control group. Urban public hospital pediatric primary care clinic. Mother-newborn dyads enrolled post partum from November 1, 2005, through October 31, 2008. In the VIP group, mothers and newborns participated in 1-on-1 sessions with a child development specialist who facilitated interactions in play and shared reading by reviewing videos made of the parent and child on primary care visit days; learning materials and parenting pamphlets were also provided. In the BB group, parenting materials, including age-specific newsletters suggesting interactive activities, learning materials, and parent-completed developmental questionnaires, were mailed to the mothers. Parent-child interactions were assessed at 6 months with the StimQ-Infant and a 24-hour shared reading recall diary. A total of 410 families were assessed. The VIP group had a higher increased StimQ score (mean difference, 3.6 points; 95% confidence interval, 1.5 to 5.6 points; Cohen d, 0.51; 0.22 to 0.81) and more reading activities compared to the control group. The BB group also had an increased overall StimQ score compared with the control group (Cohen d, 0.31; 95% confidence interval, 0.03 to 0.60). The greatest effects for the VIP group were found for mothers with a ninth-grade or higher reading level (Cohen d, 0.68; 95% confidence interval, 0.33 to 1.03). The VIP and BB groups each led to increased parent-child interactions. Pediatric primary care represents a significant opportunity for enhancing developmental trajectories in at-risk children. clinicaltrials.gov Identifier: NCT00212576.


Understanding Preferences for Interventions To Reduce Microbiological Contamination in Dutch Vegetable Production.
Understanding growers' preferences regarding interventions to improve the microbiological safety of their produce could help to design more effective strategies for the adoption of such food safety measures by growers. The objective of this survey study was to obtain insights for the design of interventions that could stimulate growers to increase the frequency of irrigation water sampling and water testing to reduce possible microbiological contamination of their fresh produce. The results showed that price intervention, referring to making the intervention less costly by reducing the price via discounts, is the most effective strategy to change growers' intentions to increase their frequency of irrigation water testing. Moreover, a sense of urgency affects their intentions to increase the frequency of irrigation water testing. The findings of this survey support the hypothesis that, to date, safety is not perceived as a quality control issue under normal circumstances, but safety becomes an overriding attribute in a food crisis.


Twenty-two points to consider for clinical trials in systemic sclerosis, based on EULAR standards.
SSc is clinically and aetiopathogenically heterogeneous. Consensus standards for more uniform trial design and selection of outcome measures are needed. The objective of this study was to develop evidence-based points to consider (PTCs) for future clinical trials in SSc. Thirteen international SSc experts experienced in SSc clinical trial design were invited to participate. One researcher with experience in systematic literature review and three trainees were also included. A systematic review using PubMed and the Cochrane Central Register of Controlled Trials was conducted and PTCs when designing clinical trials in SSc were developed. As part of that development we conducted an Internet-based Delphi exercise regarding the main points to be made in the consensus statement. Consensus was defined as achieving a median score of ≥7 of 9. By consensus, the experts decided to develop PTCs for each individual organ system. The current document provides a unifying outline on PTCs regarding general trial design, inclusion/exclusion criteria and analysis. Consensus was achieved regarding all the main points of the PTCs. Using European League Against Rheumatism suggestions for PTCs, a general outline for PTCs for controlled clinical trials in SSc was developed. Specific outlines for individual organ systems are to be published separately. This general outline should lead to more uniform and higher-quality trials and clearly delineate areas where further research is needed.


'… in the project they really care for us': meaning and experiences of participating in a clinical study of first-line treatment for malaria and HIV in Tanzanian adults.
Critiques of biomedical research in low-resource settings typically centre on clinical trials and the 'dissymmetries of power' between the researched and those benefiting from the products of research. It is important to extend this critical lens to other forms of global health research. We conducted a qualitative study in Tanzania to explore meaning and experiences of participating in a clinical observational study evaluating the safety and efficacy of current practice for treating HIV and malaria co-infection. Focus group discussions and in-depth interviews were undertaken with 124 study participants, study staff and health workers. Participants' understanding of the study's research aims was limited, but the practice of participation - engaging with research staff and materials - appeared to facilitate interpretations of the study's value, conceptualised as a 'service'. For those peripheral to the study, however, interpretations of it reflected existing suspicions of experimental research. Our findings indicate the importance of considering the expectations, roles and responsibilities constructed through the practice of participation in different types of research, and how they relate to legacies of research. Understanding how networks of research practice intersect local social and historical contexts can extend discussions of collaboration and engagement with research in low-resource settings.


Pharmacokinetic Analysis and in Vivo Antitumor Efficacy of Taccalonolides AF and AJ.
The taccalonolides are microtubule stabilizers that covalently bind tubulin and circumvent clinically relevant forms of resistance to other drugs of this class. Efforts are under way to identify a taccalonolide with optimal properties for clinical development. The structurally similar taccalonolides AF and AJ have comparable microtubule-stabilizing activities in vitro, but taccalonolide AF has excellent in vivo antitumor efficacy when administered systemically, while taccalonolide AJ does not elicit this activity even at maximum tolerated dose. The hypothesis that pharmacokinetic differences underlie the differential efficacies of taccalonolides AF and AJ was tested. The effects of serum on their in vivo potency, metabolism by human liver microsomes and in vivo pharmacokinetic properties were evaluated. Taccalonolides AF and AJ were found to have elimination half-lives of 44 and 8.1 min, respectively. Furthermore, taccalonolide AJ was found to have excellent and highly persistent antitumor efficacy when administered directly to the tumor, suggesting that the lack of antitumor efficacy seen with systemic administration of AJ is likely due to its short half-life in vivo. These results help define why some, but not all, taccalonolides inhibit the growth of tumors at systemically tolerable doses and prompt studies to further improve their pharmacokinetic profile and antitumor efficacy.


The clinical use of structural MRI in Alzheimer disease.
Structural imaging based on magnetic resonance is an integral part of the clinical assessment of patients with suspected Alzheimer dementia. Prospective data on the natural history of change in structural markers from preclinical to overt stages of Alzheimer disease are radically changing how the disease is conceptualized, and will influence its future diagnosis and treatment. Atrophy of medial temporal structures is now considered to be a valid diagnostic marker at the mild cognitive impairment stage. Structural imaging is also included in diagnostic criteria for the most prevalent non-Alzheimer dementias, reflecting its value in differential diagnosis. In addition, rates of whole-brain and hippocampal atrophy are sensitive markers of neurodegeneration, and are increasingly used as outcome measures in trials of potentially disease-modifying therapies. Large multicenter studies are currently investigating the value of other imaging and nonimaging markers as adjuncts to clinical assessment in diagnosis and monitoring of progression. The utility of structural imaging and other markers will be increased by standardization of acquisition and analysis methods, and by development of robust algorithms for automated assessment.


Host races of the cotton aphid, Aphis gossypii, in asexual populations from wild plants of taro and brinjal.
Worldwide, several studies have shown that adaptation to different host plants in phytophagous insects can promote speciation. The cotton aphid, Aphis gossypii Glover (Homoptera: Aphididae: Aphidini), is a highly polyphagous species, but its populations increase by parthenogenetic reproduction alone in Indian subcontinent. This study showed that genotypes living in wild plants of taro, Colocasia esculenta var. esculenta (L.) Schott (Alismatales: Araceae), and brinjal, Solanum torvum Swartz (Solanales: Solanaceae), behave as distinct host races. Success rates of colonization after reciprocal host transfers were very poor. Clones of A. gossypii from wild taro partly survived in the first generation when transferred to wild brinjal, but nymph mortality was 100% in the second generation. In contrast, brinjal clones, when transferred to taro, could not survive even in the first generation. Significant differences between the clones from two host species were also recorded in development time, generation time, fecundity, intrinsic rate of increase, net reproductive rate, and mean relative growth rate. Morphologically, aphids of wild taro clones possessed longer proboscis and fore-femora than the aphids of the brinjal clones. The results showed that A. gossypii exists as distinct host races with different abilities of colonizing host plants, and its populations appear to have more potential of sympatic evolution than previously regarded.


In Vivo Killing Capacity of Cytotoxic T Cells Is Limited and Involves Dynamic Interactions and T Cell Cooperativity.
According to in vitro assays, T cells are thought to kill rapidly and efficiently, but the efficacy and dynamics of cytotoxic T lymphocyte (CTL)-mediated killing of virus-infected cells in vivo remains elusive. We used two-photon microscopy to quantify CTL-mediated killing in mice infected with herpesviruses or poxviruses. On average, one CTL killed 2-16 virus-infected cells per day as determined by real-time imaging and by mathematical modeling. In contrast, upon virus-induced MHC class I downmodulation, CTLs failed to destroy their targets. During killing, CTLs remained migratory and formed motile kinapses rather than static synapses with targets. Viruses encoding the calcium sensor GCaMP6s revealed strong heterogeneity in individual CTL functional capacity. Furthermore, the probability of death of infected cells increased for those contacted by more than two CTLs, indicative of CTL cooperation. Thus, direct visualization of CTLs during killing of virus-infected cells reveals crucial parameters of CD8(+) T cell immunity.


Two incision mini open carpal tunnel release- a minimally invasive alternative to endoscopic release.
Surgical techniques for carpal tunnel release are constantly evolving to reduce complications. This retrospective study was planned to identify the outcome and complications associated with a new operating technique for release of carpal tunnel using two incisions. It was conducted at the Aga Khan University Hospital, Karachi, and comprised patients undergoing surgical release of carpal tunnel syndrome (CTS) between January 2011 and December 2014. Of the 54 patients,38(70.4%) cases were of right-sided CTS. The mean operating time was 12.5±4.9 minutes. Complete relief from symptoms was observed in all the patients and the only complication noted was superficial infection in 2(3.7%) patients.The outcomes and complications associated with this technique were comparable with other standard techniques. No major complication (e.g. neurovascular injury) was reported, which showed that this technique was safe and had no additional risks. Therefore, it can be used as an alternative to endoscopic release which is expensive and requires special training and equipment.


Gene-Dairy Food Interactions and Health Outcomes: A Review of Nutrigenetic Studies.
Each person differs from the next by an average of over 3 million genetic variations in their DNA. This genetic diversity is responsible for many of the interindividual differences in food preferences, nutritional needs, and dietary responses between humans. The field of nutrigenetics aims to utilize this type of genetic information in order to personalize diets for optimal health. One of the most well-studied genetic variants affecting human dietary patterns and health is the lactase persistence mutation, which enables an individual to digest milk sugar into adulthood. Lactase persistence is one of the most influential Mendelian factors affecting human dietary patterns to occur since the beginning of the Neolithic Revolution. However, the lactase persistence mutation is only one of many mutations that can influence the relationship between dairy intake and disease risk. The purpose of this review is to summarize the available nutrigenetic literature investigating the relationships between genetics, dairy intake, and health outcomes. Nonetheless, the understanding of an individual's nutrigenetic responses is just one component of personalized nutrition. In addition to nutrigenetic responses, future studies should also take into account nutrigenomic responses (epigenomic, transcriptomic, proteomic, metabolomic), and phenotypic/characteristic traits (age, gender, activity level, disease status, etc.), as these factors all interact with diet to influence health.


A positional marker for the dorsal embryonic retina is homologous to the high-affinity laminin receptor.
In a search for determinants of positional information in the embryonic eye, we isolated two monoclonal antibodies that label strongly the dorsal part of the undifferentiated embryonic retina in mammals, bird and cold-blooded vertebrates. In the chick, the optic tectum is labeled in a corresponding fashion, the ventral tectum more heavily than the dorsal tectum. Through biochemical and molecular analysis both antibodies were found to recognize a protein that has been cloned repeatedly, first in a screen with antibodies to the '68K-laminin receptor' (Wewer et al. (1986) Cancer Res. 47, 5691-5698), a name that may not exhaustively describe its function. Western blots show the protein to be present in most or all tissues, and Western and Southern blots reveal a high degree of conservation in the detected signals up to invertebrates and bacteria. Despite the very strong and selective labeling of the dorsal retina in conventional immunohistochemical preparations, the protein and its mRNA are present in even amounts throughout the embryonic retina, as demonstrated by Western and Northern blots of bisected retinas, and immunohistochemically in retinas fixed with ethylene glycole bissuccinimide (EGS), an NH2-group crosslinker with very long spacer arm. This indicates that the dorsoventral asymmetry in the embryonic retina is not in the amount but in the configuration of this protein; whether this difference relates to laminin binding is not known.


Acute myocardial infarction and COPD attributed to ambient SO2 in Iran.
Acute myocardial infarction (MI) and chronic obstructive pulmonary disease (COPD) are important diseases worldwide. Inhalation is the major route of short-term exposure to air sulfur dioxide (SO2) that negatively affect human health. The objective of this study was to estimate the health effects of short-term exposure to SO2 in Khorramabad, Iran using the AirQ software developed by the World Health Organization (WHO). Daily mean SO2 concentrations were used as the estimates of human short-term exposure and allow calculation of the attributable excess relative risk of an acute MI and hospital admissions due to COPD (HACOPD). The annual mean SO2 concentration in Khorramabad was 51.33µg/m3. Based on the relative risk (RR) and baseline incidence (BI) approach of WHO, an increased risk of 2.7% (95% CI: 1.1-4.2%) of acute MI and 2.0% (95% CI: 0-4.6%) of HACOPD, respectively, were attributed to a 10µg/m3 SO2 increase. Since the geographic, demographic, and climatic characteristics are different from the areas in which the risk relationships were developed and not evaluated here, further investigations will be needed to fully quantify other health impacts of SO2. A decreased risk for MIs and COPD attributable to SO2 could be achieved if mitigation strategies and measures are implemented to reduce the exposure.


Effectiveness of subsidies in promoting healthy food purchases and consumption: a review of field experiments.
To systematically review evidence from field interventions on the effectiveness of monetary subsidies in promoting healthier food purchases and consumption. Keyword and reference searches were conducted in five electronic databases: Cochrane Library, EconLit, MEDLINE, PsycINFO and Web of Science. Studies were included based on the following criteria: (i) intervention: field experiments; (ii) population: adolescents 12–17 years old or adults 18 years and older; (iii) design: randomized controlled trials, cohort studies or pre–post studies; (iv) subsidy: price discounts or vouchers for healthier foods; (v) outcome: food purchases or consumption; (vi) period: 1990–2012; and (vii) language: English. Twenty-four articles on twenty distinct experiments were included with study quality assessed using predefined methodological criteria. Interventions were conducted in seven countries: the USA (n 14), Canada (n 1), France (n 1), Germany (n 1), Netherlands (n 1), South Africa (n 1) and the UK (n 1). Subsidies applied to different types of foods such as fruits, vegetables and low-fat snacks sold in supermarkets, cafeterias, vending machines, farmers' markets or restaurants. Interventions enrolled various population subgroups such as school/ university students, metropolitan transit workers and low-income women. All but one study found subsidies on healthier foods to significantly increase the purchase and consumption of promoted products. Study limitations include small and convenience samples, short intervention and follow-up duration, and lack of cost-effectiveness and overall diet assessment. Subsidizing healthier foods tends to be effective in modifying dietary behaviour. Future studies should examine its long-term effectiveness and cost-effectiveness at the population level and its impact on overall diet intake.


The construct and measurement equivalence of cocaine and opioid dependences: a National Drug Abuse Treatment Clinical Trials Network (CTN) study.
Although DSM-IV criteria are widely used in making diagnoses of substance use disorders, gaps exist regarding diagnosis classification, use of dependence criteria, and effects of measurement bias on diagnosis assessment. We examined the construct and measurement equivalence of diagnostic criteria for cocaine and opioid dependences, including whether each criterion maps onto the dependence construct, how well each criterion performs, how much information each contributes to a diagnosis, and whether symptom-endorsing is equivalent between demographic groups. Item response theory (IRT) and multiple indicators-multiple causes (MIMIC) modeling were performed on a sample of stimulant-using methadone maintenance patients enrolled in a multisite study of the National Drug Abuse Treatment Clinical Trials Network (CTN) (N=383). Participants were recruited from six community-based methadone maintenance treatment programs associated with the CTN and major U.S. providers. Cocaine and opioid dependences were assessed by DSM-IV Checklist. IRT modeling showed that symptoms of cocaine and opioid dependences, respectively, were arrayed along a continuum of severity. All symptoms had moderate to high discrimination in distinguishing drug users between severity levels. "Withdrawal" identified the most severe symptom of the cocaine dependence continuum. MIMIC modeling revealed some support for measurement equivalence. Study results suggest that self-reported symptoms of cocaine and opioid dependences and their underlying constructs can be measured appropriately among treatment-seeking polysubstance users.


Ontogenetic Development of Vestibulo-Ocular Reflexes in Amphibians.
Vestibulo-ocular reflexes (VOR) ensure gaze stability during locomotion and passively induced head/body movements. In precocial vertebrates such as amphibians, vestibular reflexes are required very early at the onset of locomotor activity. While the formation of inner ears and the assembly of sensory-motor pathways is largely completed soon after hatching, angular and translational/tilt VOR display differential functional onsets and mature with different time courses. Otolith-derived eye movements appear immediately after hatching, whereas the appearance and progressive amelioration of semicircular canal-evoked eye movements is delayed and dependent on the acquisition of sufficiently large semicircular canal diameters. Moreover, semicircular canal functionality is also required to tune the initially omnidirectional otolith-derived VOR. The tuning is due to a reinforcement of those vestibulo-ocular connections that are co-activated by semicircular canal and otolith inputs during natural head/body motion. This suggests that molecular mechanisms initially guide the basic ontogenetic wiring, whereas semicircular canal-dependent activity is required to establish the spatio-temporal specificity of the reflex. While a robust VOR is activated during passive head/body movements, locomotor efference copies provide the major source for compensatory eye movements during tail- and limb-based swimming of larval and adult frogs. The integration of active/passive motion-related signals for gaze stabilization occurs in central vestibular neurons that are arranged as segmentally iterated functional groups along rhombomere 1-8. However, at variance with the topographic maps of most other sensory systems, the sensory-motor transformation of motion-related signals occurs in segmentally specific neuronal groups defined by the extraocular motor output targets.


Two-dimensional microscale engineering of protein-based nanoparticles for cell guidance.
Cell responses, such as positioning, morphological changes, proliferation, and apoptosis, are the result of complex chemical, topographical, and biological stimuli. Here we show the macroscopic responses of cells when nanoscale profiles made with inclusion bodies (IBs) are used for the 2D engineering of biological interfaces at the microscale. A deep statistical data treatment of fibroblasts cultivated on supports patterned with green fluorescent protein and human basic fibroblast growth factor-derived IBs demonstrates that these cells preferentially adhere to the IB areas and align and elongate according to specific patterns. These findings prove the potential of surface patterning with functional IBs as protein-based nanomaterials for tissue engineering.


The art of using t-SNE for single-cell transcriptomics.
Single-cell transcriptomics yields ever growing data sets containing RNA expression levels for thousands of genes from up to millions of cells. Common data analysis pipelines include a dimensionality reduction step for visualising the data in two dimensions, most frequently performed using t-distributed stochastic neighbour embedding (t-SNE). It excels at revealing local structure in high-dimensional data, but naive applications often suffer from severe shortcomings, e.g. the global structure of the data is not represented accurately. Here we describe how to circumvent such pitfalls, and develop a protocol for creating more faithful t-SNE visualisations. It includes PCA initialisation, a high learning rate, and multi-scale similarity kernels; for very large data sets, we additionally use exaggeration and downsampling-based initialisation. We use published single-cell RNA-seq data sets to demonstrate that this protocol yields superior results compared to the naive application of t-SNE.


The Swedish joint action method against drink driving-a study of suspected drink drivers' own experiences.
In Sweden, a joint action method called SMADIT is in use, where the police quickly offer help from the social services or the dependency care and treatment service to suspected drink drivers. The objective of this article is to analyze the experiences of suspected drink drivers who accepted the offer of help and what it meant for them. The knowledge can be used to improve procedures and consultations. Furthermore, it can allow the basic premises of the method to be examined; for example, the importance of offering help quickly. To enable comparisons over time, in-depth interviews were conducted with 12 suspected drink drivers on 2 occasions with 1 year between. To varying degrees the informants knew about their alcohol problems but were unsure whether they would have sought help by themselves. Therefore, the original ideas of the method with an initial contact with the social services or the dependency care and treatment service within 24 h was found to be important. However, the results also showed that some of the informants needed some time before the first meeting because they were in shock from the drink driving incident or in need of sleep. Therefore, the drink driver's situation and individual wishes always have to be considered. The article also shows that an encouraging attitude among the police, the social services, and the dependency care and treatment service is important for the success of the SMADIT method. The informants are satisfied with the method and in retrospect the incident and the SMADIT offer of help are described as a turning point in their lives. One year after being offered help the informants were no longer focused solely on the personal consequences of drink driving, as they were shortly after the incident. Instead, they had gained insights into the harm they could have done to other road users when they drove while drunk. One conclusion from this article is that SMADIT, as an innovative method that can be deployed more rapidly than other alcohol-impaired driving countermeasures, should be considered as a good complement to conventional methods to deal with drink driving. Based on the results, we recommend a trial of the joint action method against drink driving in other jurisdictions.


Evaluating Auditory Neural Activities and Information Transfer Using Phase and Spike Train Correlation Algorithms.
The coherence of neural activities among different areas in the brain has received great attention because it is valuable in understanding the functional mechanism of brain structures. While many methodologies, such as time-frequency and entropy analysis, have been applied to evaluate relations between neural signals, these techniques haven't been effective in assessing neural communication in order to reach conclusions. Considering various measurements, the results analyzed by the above-mentioned algorithms may be influenced by the types of neural signals and their amplitudes, which affect their reliability and consistency. In this study, we introduced two new methods, phase-phase and spike train correlations, to analyze the neural signals communications among various areas of the brain, aiming to decipher neural information communications between different brain structures of normal rats and those with noise-induced tinnitus, a ringing condition in the ear or head. To test the proposed methodologies, a set of electrophysiological recordings of tinnitus-related spontaneous activities were conducted in the auditory cortex (AC), inferior colliculus (IC), and dorsal cochlear nucleus (DCN). The results using the two proposed algorithms were demonstrated and compared to those obtained by the transfer entropy (TE) method using the same experimental data set. Both algorithms yielded a result in a consistent scale of zero to one indicating the strength of correlation and showed a similar trend to results by TE. The experimental results on rats have shown information flow within and between most structures with a stronger correlation at lower frequencies.


Salivary Immunoglobulin A Secretion Rate Is Negatively Associated with Cancer Mortality: The West of Scotland Twenty-07 Study.
Immunoglobulins are essential for combating infectious disease although very high levels can indicate underlying pathology. The present study examined associations between secretory immunoglobulin A (sIgA) in saliva and mortality rates in the general population. Participants were 639 adults from the eldest cohort of the West of Scotland Twenty-07 Study aged 63 years at the time of saliva sampling in 1995. From unstimulated 2-minute saliva samples, saliva volume and S-IgA concentration were measured, and S-IgA secretion rate determined as their product. Mortality data were tracked for 19 years. Cox proportional hazard models were applied to compute hazard ratios (HR) for all-cause mortality from sIgA secretion rate. Associations were adjusted for gender, assay batch, household occupational group, smoking, medication usage, and self-reported health. There was a negative association between log sIgA secretion rate and all-cause mortality, HR = 0.81, 95%CI = 0.73-0.91, p < .001. Further analysis of specific causes of mortality revealed that the all-cause association was due to an underlying association with cancer mortality and in particular with cancers other than lung cancer. The HR for non-lung cancer was 0.68 (95%CI = 0.54 to 0.85) implying a 32% reduction in mortality risk per standard deviation rise in log sIgA secretion rate. Effects were stronger for men than women. For deaths from respiratory diseases, sIgA secretion had a non-linear relationship with mortality risk whereby only the very lowest levels of secretion were associated with elevated risk. SIgA concentration revealed a similar but weaker pattern of association. In the present study, higher secretion rates of sIgA were associated with a decreased risk of death from cancer, specifically non-lung cancer, as well as from respiratory disease. Thus, it appears that sIgA plays a protective role among older adults, and could serve as a marker of mortality risk, specifically cancer mortality.


Vascular expression of extracellular superoxide dismutase in atherosclerosis.
We characterized a novel form of extracellular superoxide dismutase (ecSOD) in atherosclerotic vessels. Specific activity and protein expression of ecSOD was increased two- to threefold in apo E-deficient compared with control aortas. RNase protection assays demonstrated that the expected ecSOD transcript was not increased in either apo E-deficient mice or cholesterol-fed LDL receptor-deficient mice, but that a second, lower molecular weight transcript was present and became predominant as atherosclerosis progressed. Sequence analysis revealed that this novel ecSOD has a 10-bp deletion in the 3' untranslated region and an asparagine to aspartic acid mutation at amino acid 21. Studies of isolated macrophages and immunohistochemistry suggested that the truncated ecSOD transcript was expressed by lipid-laden but not control macrophages. Recombinant wild-type and novel ecSODs expressed in Sf9 cells exhibited similar SOD activities. These experiments show that ecSOD expression is increased in atherosclerotic vessels and that this is characterized by an alteration in mRNA and protein structure. Further, the source of this altered ecSOD is likely the lipid-laden macrophage. The enzymatic properties of this novel ecSOD may have important implications for the function of the lipid-laden macrophage and the atherosclerotic process.


Modeling the complex genetic architectures of brain disease.
The genetic architecture of each individual comprises common and rare variants that, acting alone and in combination, confer risk of disease. The cell-type-specific and/or context-dependent functional consequences of the risk variants linked to brain disease must be resolved. Coupling human induced pluripotent stem cell (hiPSC)-based technology with CRISPR-based genome engineering facilitates precise isogenic comparisons of variants across genetic backgrounds. Although functional-validation studies are typically performed on one variant in isolation and in one cell type at a time, complex genetic diseases require multiplexed gene perturbations to interrogate combinations of genes and resolve physiologically relevant disease biology. Our aim is to discuss advances at the intersection of genomics, hiPSCs and CRISPR. A better understanding of the molecular mechanisms underlying disease risk will improve genetic diagnosis, drive phenotypic drug discovery and pave the way toward precision medicine.


5-Aminolevulinic acid-assisted resection of pediatric dysembryoplastic neuroepithelial tumor: illustrative case.
5-Aminolevulinic acid (5-ALA) is approved as an adjunct for the resection of high-grade gliomas and is associated with improved outcomes. Dysembryoplastic neuroepithelial tumors (DNETs) are benign glioneural tumors occurring primarily in pediatric patients and often manifesting with seizure disorder. The goal of the surgical intervention is to obtain gross-total resection, which is associated, in the majority of cases, with seizure freedom. The authors present the first case report of a pediatric patient who underwent gross-total resection of a 5-ALA-positive DNET with no evidence of recurrent seizures (Engel class I). Fluorescence-guided surgery using 5-ALA facilitated gross-total resection of the mass.


Surgical complications in neuromuscular scoliosis operated with posterior- only approach using pedicle screw fixation.
There are no reports describing complications with posterior spinal fusion (PSF) with segmental spinal instrumentation (SSI) using pedicle screw fixation in patients with neuromuscular scoliosis. Fifty neuromuscular patients (18 cerebral palsy, 18 Duchenne muscular dystrophy, 8 spinal muscular atrophy and 6 others) were divided in two groups according to severity of curves; group I (< 90 degrees ) and group II (> 90 degrees ). All underwent PSF and SSI with pedicle screw fixation. There were no anterior procedures. Perioperative (within three months of surgery) and postoperative (after three months of surgery) complications were retrospectively reviewed. There were fifty (37 perioperative, 13 postoperative) complications. Hemo/pneumothorax, pleural effusion, pulmonary edema requiring ICU care, complete spinal cord injury, deep wound infection and death were major complications; while atelectesis, pneumonia, mild pleural effusion, UTI, ileus, vomiting, gastritis, tingling sensation or radiating pain in lower limb, superficial infection and wound dehiscence were minor complications. Regarding perioperative complications, 34(68%) patients had at least one major or one minor complication. There were 16 patients with pulmonary, 14 with abdominal, 3 with wound related, 2 with neurological and 1 cardiovascular complications, respectively. There were two deaths, one due to cardiac arrest and other due to hypovolemic shock. Regarding postoperative complications 7 patients had coccygodynia, 3 had screw head prominence, 2 had bed sore and 1 had implant loosening, respectively. There was a significant relationship between age and increased intraoperative blood loss (p = 0.024). However it did not increased complications or need for ICU care. Similarly intraoperative blood loss > 3500 ml, severity of curve or need of pelvic fixation did not increase the complication rate or need for ICU. DMD patients had higher chances of coccygodynia postoperatively. Although posterior-only approach using pedicle screw fixation had good correction rate, complications were similar to previous reports. There were few unusual complications like coccygodynia.


Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy.
In this Timeline, we describe the characteristics of tumour antigens that are recognized by spontaneous T cell responses in cancer patients and the paths that led to their identification. We explain on what genetic basis most, but not all, of these antigens are tumour specific: that is, present on tumour cells but not on normal cells. We also discuss how strategies that target these tumour-specific antigens can lead either to tumour-specific or to crossreactive T cell responses, which is an issue that has important safety implications in immunotherapy. These safety issues are even more of a concern for strategies targeting antigens that are not known to induce spontaneous T cell responses in patients.


Comparison of Fatal or Irreversible Events With Extended-Duration Betrixaban Versus Standard Dose Enoxaparin in Acutely Ill Medical Patients: An APEX Trial Substudy.
Extended-duration betrixaban showed a significant reduction in venous thromboembolism in the APEX trial (Acute Medically Ill VTE Prevention With Extended Duration Betrixaban Study). Given the variable clinical impact of different efficacy and safety events, one approach to assess net clinical outcomes is to include only those events that are either fatal or cause irreversible harm. This was a post hoc analysis of the APEX trial-a multicenter, double-blind, randomized controlled trial comparing extended-duration betrixaban versus standard-of-care enoxaparin. A composite of all fatal or irreversible safety (fatal bleeding or intracranial hemorrhage) and efficacy events (cardiopulmonary death, myocardial infarction, pulmonary embolism, and ischemic stroke) was evaluated in a time-to-first event analysis. In patients with positive D-dimer results, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.80% versus 3.54%; hazard ratio, 0.73; absolute risk reduction, 1.26%; number needed to treat, 79 [P=0.033]) and at study end at 77 days (6.27% versus 4.36%; hazard ratio, 0.70; absolute risk reduction, 1.91%; number needed to treat, 52 [P=0.005]) versus enoxaparin. In all patients, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.08% versus 2.90%; hazard ratio, 0.71; absolute risk reduction, 1.18%; number needed to treat, 86 [P=0.006]) and 77 days (5.17% versus 3.64%; hazard ratio, 0.70; absolute risk reduction, 1.53%; number needed to treat, 65 [P=0.002]). Among hospitalized medically ill patients, extended-duration betrixaban demonstrated an ≈30% reduction in fatal or irreversible ischemic or bleeding events compared with standard-duration enoxaparin. A total of 65 patients would require treatment with betrixaban to prevent 1 fatal or irreversible event versus enoxaparin. URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01583218.


Dynamics of the immune reaction to pancreatic cancer from inception to invasion.
The dynamics of cancer immunosurveillance remain incompletely understood, hampering efforts to develop immunotherapy of cancer. We evaluated the evolving in vivo immune response to a spontaneous tumor in a genetically defined mouse model of pancreatic ductal adenocarcinoma from the inception of preinvasive disease to invasive cancer. We observed a prominent leukocytic infiltration even around the lowest grade preinvasive lesions, but immunosuppressive cells, including tumor-associated macrophages, myeloid-derived suppressor cells (MDSC), and regulatory T cells (Treg), dominated the early response and persisted through invasive cancer. Effector T cells, however, were scarce in preinvasive lesions, found in only a subset of advanced cancers, and showed no evidence of activation. The lack of tumor-infiltrating effector T cells strongly correlated with the presence of intratumoral MDSC with a near mutual exclusion. In vitro, we found that MDSC suppressed T-cell proliferation. Overall, our results show that suppressive cells of the host immune system appear early during pancreatic tumorigenesis, preceding and outweighing antitumor cellular immunity, and likely contribute to disease progression. Thus, in contrast to the hypothesis that an early "elimination phase" of cancer immunosurveillance is eventually overwhelmed by a growing invasive tumor, our findings suggest that productive tumor immunity may be undermined from the start. Efforts to test potent inhibitors of MDSC, tumor-associated macrophages, and Treg, particularly early in the disease represent important next steps for developing novel immunotherapy of cancer.


Comparative cost of illness analysis and assessment of health care burden of Duchenne and Becker muscular dystrophies in Germany.
Our study aimed to determine the burden of illness in dystrophinopathy type Duchenne (DMD) and Becker (BMD), both leading to progressive disability, reduced working capacity and high health care utilization. A micro-costing method was used to examine the direct, indirect and informal care costs measuring the economic burden of DMD in comparison to BMD on patients, relatives, payers and society in Germany and to determine the health care burden of these diseases. Standardized questionnaires were developed based on predefined structured interview guidelines to obtain data directly from patients and caregivers using the German dystrophinopathy patient registry. The health-related quality of life (HRQOL) was analyzed using PedsQL™ Measurement Model. In total, 363 patients with genetically confirmed dystrophinopathies were enrolled. Estimated annual disease burden including direct medical/non-medical, indirect and informal care costs of DMD added up to € 78,913 while total costs in BMD were € 39,060. Informal care costs, indirect costs caused by loss of productivity and absenteeism of patients and caregivers as well as medical costs of rehabilitation services and medical aids were identified as the most important cost drivers. Total costs notably increased with disease progression and were consistent with the clinical severity; however, patients' HRQOL declined with disease progression. In conclusion, early assessments of economic aspects and the disease burden are essential to gain extensive knowledge of a distinct disease and above all play an important role in funding drug development programs for rare diseases. Therefore, our results may help to accelerate payer negotiations such as the pricing and reimbursement of new therapies, and will hopefully contribute to facilitating the efficient translation of innovations from clinical research over marketing authorization to patient access to a causative treatment.


Incremental learning of tasks from user demonstrations, past experiences, and vocal comments.
Since many years the robotics community is envisioning robot assistants sharing the same environment with humans. It became obvious that they have to interact with humans and should adapt to individual user needs. Especially the high variety of tasks robot assistants will be facing requires a highly adaptive and user-friendly programming interface. One possible solution to this programming problem is the learning-by-demonstration paradigm, where the robot is supposed to observe the execution of a task, acquire task knowledge, and reproduce it. In this paper, a system to record, interpret, and reason over demonstrations of household tasks is presented. The focus is on the model-based representation of manipulation tasks, which serves as a basis for incremental reasoning over the acquired task knowledge. The aim of the reasoning is to condense and interconnect the data, resulting in more general task knowledge. A measure for the assessment of information content of task features is introduced. This measure for the relevance of certain features relies both on general background knowledge as well as task-specific knowledge gathered from the user demonstrations. Beside the autonomous information estimation of features, speech comments during the execution, pointing out the relevance of features are considered as well. The results of the incremental growth of the task knowledge when more task demonstrations become available and their fusion with relevance information gained from speech comments is demonstrated within the task of laying a table.


A mouse model of peripheral postischemic dysesthesia: involvement of reperfusion-induced oxidative stress and TRPA1 channel.
Peripheral postischemic dysesthesia was examined behaviorally in mice and we investigated the underlying molecular mechanism with a focus on oxidative stress. Hind-paw ischemia was induced by tight compression of the ankle with a rubber band, and reperfusion was achieved by cutting the rubber tourniquet. We found that reperfusion after ischemia markedly provoked licking of the reperfused hind paw, which was significantly inhibited by systemic administration of the antioxidant N-acetyl-l-cysteine and the transient receptor potential (TRP) A1 channel blocker HC-030031 [2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide]. Postischemic licking was also significantly inhibited by an intraplantar injection of another antioxidant, phenyl-N-tert-butylnitrone. The TRPV1 channel blocker BCTC [N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide] did not inhibit postischemic licking. An intraplantar injection of hydrogen peroxide elicited hind-paw licking, which was inhibited by N-acetyl-l-cysteine, phenyl-N-tert-butylnitrone, and HC-030031. Postischemic licking was not affected by chemical depletion of sensory C-fibers, but it was inhibited by morphine, which has been shown to inhibit the C- and Aδ-fiber-evoked responses of dorsal horn neurons. Interestingly, postischemic licking was not inhibited by gabapentin and pregabalin, which have been shown to inhibit the C-fiber- but not Aδ-fiber-evoked response. The present results suggest that ischemia-reperfusion induces oxidative stress, which activates TRPA1 channels to provoke postischemic licking. It has been suggested that this behavior is mediated by myelinated (probably Aδ-type) afferent fibers. Oxidative stress and TRPA1 channels may be potential targets to treat peripheral ischemia-associated dysesthesia.


The use of the isometric squat as a measure of strength and explosiveness.
The isometric squat has been used to detect changes in kinetic variables as a result of training; however, controversy exists in its application to dynamic multijoint tasks. Thus, the purpose of this study was to further examine the relationship between isometric squat kinetic variables and isoinertial strength measures. Subjects (17 men, 1-repetition maximum [1RM]: 148.2 ± 23.4 kg) performed squats 2 d · wk(-1) for 12 weeks and were tested on 1RM squat, 1RM partial squat, and isometric squat at 90° and 120° of knee flexion. Test-retest reliability was very good for all isometric measures (intraclass correlation coefficients > 0.90); however, rate of force development 250 milliseconds at 90° and 120° seemed to have a higher systematic error (relative technical error of measurement = 8.12%, 9.44%). Pearson product-moment correlations indicated strong relationships between isometric peak force at 90° (IPF 90°) and 1RM squat (r = 0.86), and IPF 120° and 1RM partial squat (r = 0.79). Impulse 250 milliseconds (IMP) at 90° and 120° exhibited moderate to strong correlations with 1RM squat (r = 0.70, 0.58) and partial squat (r = 0.73, 0.62), respectively. Rate of force development at 90° and 120° exhibited weak to moderate correlations with 1RM squat (r = 0.55, 0.43) and partial squat (r = 0.32, 0.42), respectively. These findings demonstrate a degree of joint angle specificity to dynamic tasks for rapid and peak isometric force production. In conclusion, an isometric squat performed at 90° and 120° is a reliable testing measure that can provide a strong indication of changes in strength and explosiveness during training.


Study of the cwaRS-ldcA Operon Coding a Two-Component System and a Putative L,D-Carboxypeptidase in Lactobacillus paracasei.
The cell surface is the primary recognition site between the bacterium and the host. An operon of three genes, LSEI_0219 (cwaR), LSEI_0220 (cwaS), and LSEI_0221 (ldcA), has been previously identified as required for the establishment of Lactobacillus paracasei in the gut. The genes cwaR and cwaS encode a predicted two-component system (TCS) and ldcA a predicted D-alanyl-D-alanine carboxypeptidase which is a peptidoglycan (PG) biosynthesis enzyme. We explored the functionality and the physiological role of these three genes, particularly their impact on the bacterial cell wall architecture and on the bacterial adaptation to environmental perturbations in the gut. The functionality of CwaS/R proteins as a TCS has been demonstrated by biochemical analysis. It is involved in the transcriptional regulation of several genes of the PG biosynthesis. Analysis of the muropeptides of PG in mutants allowed us to re-annotate LSEI_0221 as a putative L,D-carboxypeptidase (LdcA). The absence of this protein coincided with a decrease of two surface antigens: LSEI_0020, corresponding to p40 or msp2 whose implication in the host epithelial homeostasis has been recently studied, and LSEI_2029 which has never been functionally characterized. The inactivation of each of these three genes induces susceptibility to antimicrobial peptides (hBD1, hBD2, and CCL20), which could be the main cause of the gut establishment deficiency. Thus, this operon is necessary for the presence of two surface antigens and for a suitable cell wall architecture.


Increased hospitalizations among sarcoidosis patients from 1998 to 2008: a population-based cohort study.
Diagnostic and treatment approaches for sarcoidosis have changed dramatically over the past decade. Yet, the most recent reports of trends in hospitalizations of sarcoidosis patients are over ten years old. The objectives of this study were to determine the incidence of sarcoidosis among hospitalized patients and to analyze recent trends and seasonality of hospitalizations in sarcoidosis patients. We performed a retrospective cohort study of the Nationwide Inpatient Sample from 1998 through 2008. We identified all hospitalizations with a primary or secondary diagnosis of sarcoidosis (ICD-9-CM code 135). Incidence was modeled as a seasonal time series about a linear trend. Time series analysis of the monthly number of hospitalizations revealed a distinct positive linear trend. Over the study period, the number of hospitalized patients with sarcoidosis increased from 37,516 to 70,947 cases. Trends were most pronounced in patients older than 55 years (p < 0.0001), African Americans (p < 0.0001), females (p = 0.0289), and non-Medicaid populations (p < 0.0001). Hospitalizations are seasonal with highest incidence in January through March. Hospitalizations among sarcoidosis patients have almost doubled during the past decade, with disproportionate rate increases in African Americans, women, and older patients. The rate also increases among patients with insurance other than Medicaid. This study indicates the need for heightened surveillance of sarcoidosis patients given the unknown consequences of evolving treatment approaches. Our results point to a need for research investigating risk factors for hospitalization, including medications, co-morbidities, demographics, and socioeconomic status.


Sclerotherapy with use of doxycycline after percutaneous drainage of postoperative lymphoceles.
To assess the use of doxycycline as a sclerosing agent after percutaneous drainage of postoperative lymphoceles. Symptomatic postoperative lymphoceles (n = 21) in 18 patients were treated by percutaneous tube drainage for an average of 10.8 days. Sclerosis was performed when the patient became asymptomatic, drainage had slowed to less than 30 mL/d and follow-up imaging (CT or US) showed either near complete or total resolution of the lymphocele. Doxycycline (500 mg) combined with 1% lidocaine (5 mL) was instilled into the cavity with use of a syringe after any remaining lymphocele fluid was removed through the tube. When possible, patients were instructed to perform a series of maneuvers for the next hour to distribute the sclerosing agent evenly throughout the cavity. After 1 hour, the sclerosing agent was aspirated from the cavity and the drainage tube was removed. Three patients with four lymphoceles underwent sclerotherapy immediately after percutaneous insertion of a drainage tube and aspiration of the lymphocele. No patients underwent previous sclerosis with any agent. Successful treatment of postoperative lymphoceles was achieved in 17 of 18 patients. Primary success was achieved in 17 of 21 lymphoceles treated. There were four lymphocele recurrences in three patients. Three of the four recurrences were successfully treated by means of repeated drainage and sclerotherapy. One recurrent lymphocele persisted after re-treatment with 1 g of doxycycline. This patient underwent successful surgical repair. There were no complications related to doxycycline sclerosis. The mean duration of drainage for initial and recurrent lymphoceles was 10.8 days (range, 0-30 days). Sclerotherapy with use of doxycycline after percutaneous drainage is an easy, safe, inexpensive, and effective means of treating postoperative lymphoceles.


Pressure induced superconductivity in pristine 1T-TiSe2.
The interplay between superconductivity and the charge-density wave (CDW) state in pure 1T-TiSe(2) is examined through a high-pressure study extending up to pressures of 10 GPa between sub-Kelvin and room temperatures. At a critical pressure of 2 GPa a superconducting phase sets in and persists up to pressures of 4 GPa. The maximum superconducting transition temperature is 1.8 K. These findings complement the recent discovery of superconductivity in copper-intercalated 1T-TiSe(2). The comparisons of the normal state and superconducting properties of the two systems reveal the possibility that the emergent electronic state qualitatively depends on the manner in which the CDW state is destabilized, making this a unique example where two different superconducting domes are obtained by two different methods from the same parent compound.


Non-thermal inactivation of Listeria spp. in a typical dry-fermented sausage: "Bergamasco" salami.
Aim of the present study was the evaluation of the growth potential of Listeria spp. inoculated in the typical North Italian dry fermented sausage "Bergamasco" salami during its production. As it was necessary to carry out the challenge test in the production line of the industry, according to the guidelines of the European Reference Laboratory for Listeria monocytogenes, a non-pathogenic "surrogate" microorganism was used: for the inoculum, two strains of Listeria innocua (1 ATCC, 1 strain isolated from a similar substrate) were used. The inoculation of the samples occurred during grinding and mixing of the sausage mass, before the filling. To avoid cross-contamination, the control samples were produced before the contaminated ones. After the dripping, salamis were subjected to the normal production process (drying and maturation in five steps at specific temperatures and humidity rates). The inoculated products were subjected to the enumeration of Listeria spp. at T0 (day of inoculation) and at T4 (post-drying), and every 10 days during curing (T10, T20, T30, T40, T50, T60, T70, T80 and T90), as this salami is generally sold as whole piece with varying levels of curing (from T20 to T90). Since the product may be cut in half and vacuumpacked, at each of the times starting from T20, half salami was vacuum-packed and stored for 30 days at 12°C, at the end of the which Listeria spp. enumeration was performed again. At all times and for each type of samples of each of the three batches, the enumeration of the natural microflora (Total Viable Count, lactic acid bacteria, Pseudomonas spp., Enterobacteriaceae) and the determination of water activity and pH were performed on control samples. The product was characterized by a high concentration of microflora (8-8.5 Log UFC/g), consisting mainly of lactic acid bacteria, added to the mixture at the beginning of the production process. The pH showed a decrease over time, expected for this type of products, due to the development of lactic acid bacteria (final pH: 5.42-5.55). The water activity reached values able to inhibit the development of Listeria spp. (final aw: 0.826-0.863). Listeria counts in the tested batches of "Bergamasco" salami showed the absence of significant growth in the product with a reduction of loads if compared to T0, between -0.59 and -1.04 Log CFU/g. Even in the samples subjected to vacuum packaging and storage at 12°C, the absence of significant increase of lactic acid bacteria in the product was highlighted with further decrease of bacterial loads (-0.70/-0.79 Log CFU/g if compared to T20). Considering the worst case scenario (thus the batch with the highest growth potential), in the products stored in the curing room at 14-16°C, at humidity of 80% and in the samples stored at 12°C and vacuum packaged, the threshold indicated by the EURL Lm guidelines (+0.5 Log CFU/g) for the growth of Listeria spp. was not reached, allowing to classify "Bergamasco" salami in the category 1.3 of the EC Reg. 2073/2005 as "Ready-to-eat food unable to support the growth of Listeria monocytogenes".


Antarctic marine biodiversity--what do we know about the distribution of life in the Southern Ocean?
The remote and hostile Southern Ocean is home to a diverse and rich community of life that thrives in an environment dominated by glaciations and strong currents. Marine biological studies in the region date back to the nineteenth century, but despite this long history of research, relatively little is known about the complex interactions between the highly seasonal physical environment and the species that inhabit the Southern Ocean. Oceanographically, the Southern Ocean is a major driver of global ocean circulation and plays a vital role in interacting with the deep water circulation in each of the Pacific, Atlantic, and Indian oceans. The Census of Antarctic Marine Life and the Scientific Committee on Antarctic Research Marine Biodiversity Information Network (SCAR-MarBIN) have strived to coordinate and unify the available scientific expertise and biodiversity data to improve our understanding of Southern Ocean biodiversity. Taxonomic lists for all marine species have been compiled to form the Register of Antarctic Marine Species, which currently includes over 8,200 species. SCAR-MarBIN has brought together over 1 million distribution records for Southern Ocean species, forming a baseline against which future change can be judged. The sample locations and numbers of known species from different regions were mapped and the depth distributions of benthic samples plotted. Our knowledge of the biodiversity of the Southern Ocean is largely determined by the relative inaccessibility of the region. Benthic sampling is largely restricted to the shelf; little is known about the fauna of the deep sea. The location of scientific bases heavily influences the distribution pattern of sample and observation data, and the logistical supply routes are the focus of much of the at-sea and pelagic work. Taxa such as mollusks and echinoderms are well represented within existing datasets with high numbers of georeferenced records. Other taxa, including the species-rich nematodes, are represented by just a handful of digital records.


Diclofenac protects cultured human corneal epithelial cells against hyperosmolarity and ameliorates corneal surface damage in a rat model of dry eye.
Dry eye syndrome (DES) is characterized by an increase in tear osmolarity and induction of the expression and nuclear localization of an osmoprotective transcription factor (nuclear factor of activated T-cells 5 [NFAT5]) that plays an important role in providing protection against hyperosmotic tears. In this study, we screened medicines already in clinical use with a view of finding compounds that protect cultured human corneal epithelial cells against hyperosmolarity-induced cell damage. Viable cell number was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and cellular NFAT5 level was measured by immunoblotting. The rat model for DES was developed by removal of the lacrimal glands, with an assessment of corneal surface damage based on levels of fluorescein staining and epithelial apoptosis. Some nonsteroidal anti-inflammatory drugs (NSAIDs), including diclofenac sodium (diclofenac), were identified during the screening procedure. These NSAIDs were able to suppress hyperosmolarity-induced apoptosis and cell growth arrest. In contrast, other NSAIDs, including bromfenac sodium (bromfenac), did not exert such a protective action. Treatment of cells with diclofenac, but not bromfenac, stimulated both the nuclear localization and expression of NFAT5 under hyperosmotic conditions. In the rat model for DES, topical administration of diclofenac (but not bromfenac) to eyes reduced corneal surface damage without affecting the volume of tear fluid. Diclofenac appears to protect cells against hyperosmolarity-induced cell damage and NFAT5 would play an important role in this protective action. The findings reported here may also indicate that the topical administration of diclofenac to eyes may be therapeutically beneficial for DES patients.


Personal, Social and Environmental Risk Factors of Problematic Gambling Among High School Adolescents in Addis Ababa, Ethiopia.
Understanding risk factors of problematic gambling is prerequisite to effective intervention design to alleviate the negative consequences of gambling. This study explored the personal, social and environmental risk factors of problematic gambling in four high schools in Addis Ababa, Ethiopia, among students (N = 422) ranging from 12 to 21 years of age. Results from the cross-sectional survey showed that personal feelings (e.g., self-esteem, false perceptions about winning, drug abuse), social factors (e.g., peer influence, parental gambling), and environmental factors (e.g., accessibility of gambling venues, advertisements) were significant correlates of problematic gambling. The study also revealed that men were more at risk for severe problematic gambling than females. Among the identified types of gambling activities, the most prevalent ones were playing cards followed by flipping coin and pool gambling while internet gambling was among the least reported gambling activities. By identifying personal, social and environmental correlates of risky gambling activities this study provides evidence-based information for the systematic design and evaluation of educational interventions to prevent problematic gambling in young people.


Teaching medical error disclosure to residents using patient-centered simulation training.
To determine whether a standardized patient encounter and self-guided tutorial would improve first-year residents' self-efficacy for disclosing medical errors. In 2011, 55 first-year residents participated in a simulation in which they disclosed an error to a standardized patient playing the part of a family member. Residents completed the simulation twice, four weeks apart, and completed presession knowledge and self-efficacy (based on the Accreditation Council for Graduate Medical Education [ACGME] core competencies) assessments and repeated the self-efficacy assessment after the sessions. Residents reviewed the videos of their encounters either alone (self-debrief) or with a faculty observer (faculty debrief). Between sessions, they completed a self-paced learning tutorial. Two external faculty also rated the residents' performances using videos of the encounters. Residents' self-efficacy significantly increased from a Session 1 pretest mean (standard deviation) score of 119.6 (26.6) to a Session 2 posttest score of 150.3 (24.9) for all ACGME competencies (P < .001, Cohen's d = 1.19). The external reviewers' ratings provided additional, objective support for residents' improvement on questions assessing ACGME competencies (P = .001). Comparisons of the self-efficacy of residents in the self-debrief versus faculty debrief groups yielded no significant differences on any ACGME competencies. Timely, explicit, and empathetic disclosure of medical errors to patients and family is essential to maintaining trust and is an important part of patient-centered medical care. This intervention easily could be replicated in other settings and is applicable to many members of the health care team, not just to residents.


Management of hyperlipidaemia: guidelines of the British Hyperlipidaemia Association.
There is considerable evidence to suggest that the identification and treatment of dyslipidaemia will reduce the risk of premature CHD, i.e. before the age of 65. Diagnosis of the cause of raised plasma lipid levels will enable appropriate decisions to be taken with regard to management. The cornerstone of treatment is nutritional counselling and attention to other major risk factors for CHD, particularly smoking and hypertension. For a small percentage of patients with severe hyperlipidaemia drug therapy is indicated. Appropriate drug choices need to be made based on the particular lipid abnormality to be treated. In general those patients with clinical vascular disease are treated more aggressively than those where the aim is primary prevention. More research is needed to determine individual risk more precisely and to allow proper targeting of therapy. Genetic factors, qualitative changes in lipoproteins, lipoprotein (a), fibrinogen, and other coagulation and thrombotic factors are likely to be important in individual risk assessment. There is no doubt that more information is needed from prospective studies of lipid-lowering therapy in terms of risk benefit for affected individuals. Hopefully the major studies currently underway will fill some of the gaps in our knowledge. Until then aggressive therapy with drugs should be reserved for those at highest risk where the benefit is likely to be greatest.


Relationships between the endangered Pustertaler-Sprinzen and three related European cattle breeds as analysed with 20 microsatellite loci.
We estimated the genetic relationships between the endangered German Pustertaler-Sprinzen cattle breed and the Pinzgauer, Vosges and Simmental breeds--decided upon after consultation of the available historical literature. Within-breed diversity of the four breeds was also assessed. Twenty microsatellite markers were amplified in 27-50 unrelated individuals from populations of each breed. Within-breed variation was estimated from average heterozygosity values and mean number of alleles. Breed relationships were evaluated by genetic distance and a neighbour-joining tree was calculated from these estimates. Bootstrap resampling of loci tested the robustness of the tree topology obtained. A tree was also constructed from distance matrices using individual animals as operational taxonomic units. From both the average heterozygosity values and mean number of alleles calculated, the Pustertaler breed appears to be no more genetically impoverished than the other breeds analysed. The breed tree showed an 85% support for the Pustertaler-Pinzgauer grouping, and this result is echoed in the genetic distance values and allele-sharing individual tree.


Adult-born hippocampal neurons promote cognitive flexibility in mice.
The hippocampus is involved in segregating memories, an ability that utilizes the neural process of pattern separation and allows for cognitive flexibility. We evaluated a proposed role for adult hippocampal neurogenesis in cognitive flexibility using variants of the active place avoidance task and two independent methods of ablating adult-born neurons, focal X-irradiation of the hippocampus, and genetic ablation of glial fibrillary acidic protein positive neural progenitor cells, in mice. We found that ablation of adult neurogenesis did not impair the ability to learn the initial location of a shock zone. However, when conflict was introduced by switching the location of the shock zone to the opposite side of the room, irradiated and transgenic mice entered the new shock zone location significantly more than their respective controls. This impairment was associated with increased upregulation of the immediate early gene Arc in the dorsal dentate gyrus, suggesting a role for adult neurogenesis in modulating network excitability and/or synaptic plasticity. Additional experiments revealed that irradiated mice were also impaired in learning to avoid a rotating shock zone when it was added to an initially learned stationary shock zone, but were unimpaired in learning the identical simultaneous task variant if it was their initial experience with place avoidance. Impaired avoidance could not be attributed to a deficit in extinction or an inability to learn a new shock zone location in a different environment. Together these results demonstrate that adult neurogenesis contributes to cognitive flexibility when it requires changing a learned response to a stimulus-evoked memory.


Endoscopic and stroboscopic presentation of the larynx in male-to-female transsexual persons.
Male-to-female transsexual (MFT) persons often attempt to produce a female-sounding voice as part of the transition process. Endoscopic and stroboscopic data about how they accomplish this with an anatomically male larynx are lacking. To describe vocal fold activity in MFT persons producing their feminine voice and identify signs of vocal misuse or hyperfunction in MFT speakers, if any. Prospective, nonrandomized, descriptive study of a convenience sample of MFT persons. All MFT persons had endoscopic and stroboscopic procedures completed. Images were rated on a range of parameters by two experienced voice therapists to derive the descriptions. MFT participant self-report of voice use/symptoms and listener identifications of speaker gender from a perceptual task were also obtained. Incomplete glottal closure was common with a posterior glottal gap predominating. Phase closure ratios also were skewed toward more "open" time for nearly half of the group. Supraglottic constriction was seen to varying degrees in all, and voice complaints were reported by 67% of the group. MFT speakers who reported a "passing" feminine voice had glottal gap configurations more similar to anatomic females than males and tended toward more open phase closure ratios, perhaps consistent with breathy or soft voice production. Indications of vocal hyperfunction were present for all participants either by self-report or on the laryngeal examination.


Spatial components of bird diversity in the Andes of Colombia: implications for designing a regional reserve system.
Beta diversity, or the turnover in species composition among sampling sites in a region, is an important criterion for obtaining adequate representation of regional biodiversity in systems of protected areas. Recently, the additive model for partitioning regional (gamma) diversity (in opposition to the multiplicative model) has been proposed because it allows a direct measure of the contribution of beta diversity to gamma diversity. We determined avian beta diversity along latitudinal (among neighboring river drainages) and elevational axes in a 1347-km2 region on the western slope of the Central Cordillera of the Colombian Andes, where a regional system of protected areas is being designed. We then compared avian beta diversity between sites based on rapid versus long-term (>1 year) inventories and between fragmented sites versus continuous forest. Overall, beta diversity represented 63.1% of gamma diversity among 16 sites. Elevational differences in species composition accounted for 43.3% of regional diversity, whereas differences among drainages accounted for 19.8%. A complementary cluster analysis showed that sites grouped by elevational zones. Rapid inventories overestimated beta diversity because of sampling effects, but the effect was biologically small. Estimators of species richness derived from species accumulation curves provided a useful alternative to compensate for undersampling in short-term surveys. Forest fragmentation increased beta diversity because of differential local extinction of populations. Nevertheless, in our region, forest fragments contributed to gamma diversity because they contained complementary sets of species. More importantly, they contained populations of special-interest species. Although the region is relatively small, our analyses indicate that spatial differentiation of the biota is an important factor for deciding number and location of protected areas in the Andean region.


High power room temperature 1014.8 nm Yb fiber amplifier and frequency quadrupling to 253.7 nm for laser cooling of mercury atoms.
An 8 W continuous wave linearly-polarized single-frequency 1014.8 nm fiber amplifier working at room temperature is developed with commercial double-clad single-mode Yb-doped silica fiber. Re-absorption at the laser wavelength and amplified spontaneous emission at longer wavelength are managed by optimizing the amplifier design. The laser has a linewidth of ~24 kHz without noticeable broadening after amplification. Using two resonant cavity frequency doublers, 1.03 W laser at 507.4 nm and 75 mW laser at 253.7 nm are generated with 4 W 1014.8 nm laser. Both absorption and saturated absorption spectra of the (1)S(0) - (3)P(1) transition of atomic mercury are measured with the 253.7 nm laser.


Equilibrium sampling approach to the interpretation of electron density maps.
The derivation of molecular models from spatial density data generated by X-ray crystallography or electron microscopy is an active field of research. Here, we introduce and evaluate an approach relying on the equilibrium sampling of energy landscapes describing restraints to experimental input data. Our procedure combines density restraints with replica exchange methodologies in the parameter space of the restraints, and we demonstrate its applicability to both flexible polymers and the assembly of protein complexes from rigid components. For the most difficult system studied, we highlight the importance of advanced data analysis techniques in mining poorly converged data further. Successful and unbiased interpretation of input density maps is a prerequisite for using this approach as an auxiliary restraint term in molecular simulations. Because these simulations will also utilize physical interaction potentials, we hope that they will contribute to deriving families of structural models for input data that are ambiguous per se.


High acceptability of HIV pre-exposure prophylaxis but challenges in adherence and use: qualitative insights from a phase I trial of intermittent and daily PrEP in at-risk populations in Kenya.
This paper used qualitative methods to explore experiences of men who have sex with men and female sex workers in Nairobi and Mtwapa, Kenya, who used oral pre-exposure prophylaxis (PrEP) for HIV prevention as part of a four-month trial of safety, acceptability and adherence. Fifty-one of 72 volunteers who took part in a randomized, placebo-controlled, blinded trial that compared daily and intermittent dosage of PrEP underwent qualitative assessments after completing the trial. Analyses identified three themes: (i) acceptability of PrEP was high, i.e. side effects were experienced early in the study but diminished over time, however characteristics of pills could improve comfort and use; (ii) social impacts such as stigma, rumors, and relationship difficulties due to being perceived as HIV positive were prevalent; (iii) adherence was challenged by complexities of daily life, in particular post-coital dosing adherence suffered from alcohol use around time of sex, mobile populations, and transactional sex work. These themes resonated across dosing regimens and gender, and while most participants favored the intermittent dosing schedule, those in the intermittent group noted particular challenges in adhering to the post-coital dose. Culturally appropriate and consistent counseling addressing these issues may be critical for PrEP effectiveness.


Association between suicide death and concordance with benzodiazepine treatment guidelines for anxiety and sleep disorders.
Guidelines for management of anxiety and sleep disorders emphasize antidepressant medications and/or psychotherapy as first/second-line and benzodiazepines as third-line treatments. We evaluated the association between suicide death and concordance with benzodiazepine guidelines. Retrospective case-control study of patients with anxiety and/or sleep disorders from health systems across 8 U.S. states within the Mental Health Research Network. Suicide death cases were matched to controls on year and health system. Appropriate benzodiazepine prescribing defined as: no monotherapy, no long duration, and/or age < 65 years. The association between guideline concordance and suicide death was evaluated, adjusting for diagnostic and treatment covariates. Sample included 6960 patients with anxiety disorders (2363 filled benzodiazepine) and 6215 with sleep disorders (1237 filled benzodiazepine). Benzodiazepine guideline concordance was associated with reduced odds for suicide in patients with anxiety disorders (OR = 0.611, 95% CI = 0.392-0.953, p = 0.03) and was driven by shorter duration of benzodiazepine use with concomitant psychotherapy or antidepressant medication. The association of benzodiazepine guideline concordance with suicide death did not meet statistical significance in the sleep disorder group (OR = 0.413, 95% CI = 0.154-1.11, p = 0.08). We found reduced odds for suicide in those with anxiety disorders who filled benzodiazepines in short-moderate duration with concomitant psychotherapy or antidepressant treatment.


Cyclic peptide production using a macrocyclase with enhanced substrate promiscuity and relaxed recognition determinants.
Macrocyclic peptides have promising therapeutic potential but the scaling up of their chemical synthesis is challenging. The cyanobactin macrocyclase PatGmac is an efficient tool for production but is limited to substrates containing 6-11 amino acids and at least one thiazoline or proline. Here we report a new cyanobactin macrocyclase that can cyclize longer peptide substrates and those not containing proline/thiazoline and thus allows exploring a wider chemical diversity.


Behaviour change techniques associated with smoking cessation in intervention and comparator groups of randomized controlled trials: a systematic review and meta-regression.
To estimate the strengths of associations between use of behaviour change techniques (BCTs) and clusters of BCTs in behavioural smoking cessation interventions and comparators with smoking cessation rates. Systematic review and meta-regression of biochemically verified smoking cessation rates on BCTs in interventions and comparators in randomized controlled trials, adjusting for a priori-defined potential confounding variables, together with moderation analyses. Studies were drawn from the Cochrane Tobacco Addiction Group Specialised Register. Data were extracted from published and unpublished (i.e. obtained from study authors) study materials by two independent coders. Adequately described intervention (k = 143) and comparator (k = 92) groups were included in the analyses (n = 43 992 participants). Using bivariate mixed-effects meta-regressions, while controlling for key a priori confounders, we regressed smoking cessation on (a) three BCT groupings consistent with dual-process theory (i.e. associative, reflective motivational and self-regulatory), (b) 17 expert-derived BCT groupings (i.e. BCT taxonomy version 1 clusters) and (c) individual BCTs from the BCT taxonomy version 1. Among person-delivered interventions, higher smoking cessation rates were predicted by BCTs targeting associative and self-regulatory processes (B = 0.034, 0.041, P < 0.05), and by three individual BCTs (prompting commitment, social reward, identity associated with changed behaviour). Among written interventions, BCTs targeting taxonomy cluster 10a (rewards) predicted higher smoking cessation (B = 0.394, P < 0.05). Moderation effects were observed for nicotine dependence, mental health status and mode of delivery. Among person-delivered behavioural smoking cessation interventions, specific behaviour change techniques and clusters of techniques are associated with higher success rates.


Risk-based zoning for urbanizing floodplains.
Urban floodplain development brings economic benefits and enhanced flood risks. Rapidly growing cities must often balance the economic benefits and increased risks of floodplain settlement. Planning can provide multiple flood mitigation and environmental benefits by combining traditional structural measures such as levees, increasingly popular landscape and design features (green infrastructure), and non-structural measures such as zoning. Flexibility in both structural and non-structural options, including zoning procedures, can reduce flood risks. This paper presents a linear programming formulation to assess cost-effective urban floodplain development decisions that consider benefits and costs of development along with expected flood damages. It uses a probabilistic approach to identify combinations of land-use allocations (residential and commercial development, flood channels, distributed runoff management) and zoning regulations (development zones in channel) to maximize benefits. The model is applied to a floodplain planning analysis for an urbanizing region in the Baja Sur peninsula of Mexico. The analysis demonstrates how (1) economic benefits drive floodplain development, (2) flexible zoning can improve economic returns, and (3) cities can use landscapes, enhanced by technology and design, to manage floods. The framework can incorporate additional green infrastructure benefits, and bridges typical disciplinary gaps for planning and engineering.


Mapping of signaling networks through synthetic genetic interaction analysis by RNAi.
The analysis of synthetic genetic interaction networks can reveal how biological systems achieve a high level of complexity with a limited repertoire of components. Studies in yeast and bacteria have taken advantage of collections of deletion strains to construct matrices of quantitative interaction profiles and infer gene function. Yet comparable approaches in higher organisms have been difficult to implement in a robust manner. Here we report a method to identify genetic interactions in tissue culture cells through RNAi. By performing more than 70,000 pairwise perturbations of signaling factors, we identified >600 interactions affecting different quantitative phenotypes of Drosophila melanogaster cells. Computational analysis of this interaction matrix allowed us to reconstruct signaling pathways and identify a conserved regulator of Ras-MAPK signaling. Large-scale genetic interaction mapping by RNAi is a versatile, scalable approach for revealing gene function and the connectivity of cellular networks.


Pelvic organ prolapse and stress urinary incontinence, do they share the same risk factors?
To determine whether there are differences in the etiologies of two of the most common pelvic floor disorders (PFD), pelvic organ prolapse (POP) and stress urinary incontinence (SUI). This cross-sectional descriptive study included 1042 women, referred to a pelvic floor unit in a tertiary Spanish hospital, between 2008 and 2012. Subjects at their fist visit were interviewed and examined generally and specifically (medical and urogynecological history). Collected parameters included: age, weight, height, medical and surgical background (including in-depth obstetrical and gynecological characteristics). The participants were classified into 3 different groups (POP, SUI, and mixed pathology). Descriptive analyses of each variable and multinomial logistic regression were performed to determine factors associated with POP and SUI. Patients with POP were older, thinner, with greater parity and their newborns tended to be heavier. Furthermore, forceps, vaginal tears and vaginal surgeries were more common in the POP group. In contrast, family history was an important factor for the development of SUI, with a 6.45-fold increase (95% CI: 3.69-11.24). Two protective factors were identified for POP, cesarean section reduces the risk by 3 fold (OR=0.33) (95% CI: 0.13-0.85) whereas pelvic floor rehabilitation produces a 2 fold reduction (OR=0.49) (95% CI: 0.31-0.76). Our data study demonstrates differences in potential triggers and risk factors for POP and SUI. Cesarean section and pelvic floor rehabilitation have a protective effect on preventing the development of POP. Bringing up that a personal medical care and a specific urogynecological follow-up should be developed for those who are more susceptible or at risk of PFD.


Isolation and analysis of primitive hemopoietic progenitor cells on the basis of differential expression of Qa-m7 antigen.
In the presence of the hemopoietic growth factor CSF-1, the later committed cells of the macrophage lineage can be detected by their ability to form small colonies in clonal agar culture (CFCCSF-1). Synergistic factors have been described that in combination with CSF-1 stimulate developmentally early hemopoietic progenitor cells of high proliferative potential (HPP-CFC). By using a monoclonal antibody to the Qa-m7 antigenic determinant, we investigated and compared the expression of Qa-m7 on CFCCSF-1 and on HPP-CFC of two types that grow in response to either 1) CSF-1 plus synergistic factor from human placenta-conditioned medium (HPP-CFCHplac+CSF-1) or 2) CSF-1 plus synergistic factor from conditioned medium of the WEHI-3 myelomonocytic cell line (HPP-CFCW+CSF-1). We have shown that HPP-CFC of both types express relatively more Qa-m7 antigen than CFCCSF-1 and can be separated and enriched on this basis by discontinuous buoyant density centrifugation and fluorescence-activated cell sorting of normal bone marrow. Significant enrichments of HPP-CFCHPlac+CSF-1 (43.5-fold) and HPP-CFCW+CSF-1 (28.8-fold) have been achieved with cloning efficiencies of HPP-CFC in the most enriched fractions reaching 4 to 5%. These results clearly illustrate the fact that there are populations of progenitor cells from normal, unperturbed bone marrow that strictly require a combination of two hemopoietic growth factors (CSF-1 plus synergistic factor) in order to be detected.


In silico functional profiling of human disease-associated and polymorphic amino acid substitutions.
An important challenge in translational bioinformatics is to understand how genetic variation gives rise to molecular changes at the protein level that can precipitate both monogenic and complex disease. To this end, we compiled datasets of human disease-associated amino acid substitutions (AAS) in the contexts of inherited monogenic disease, complex disease, functional polymorphisms with no known disease association, and somatic mutations in cancer, and compared them with respect to predicted functional sites in proteins. Using the sequence homology-based tool SIFT to estimate the proportion of deleterious AAS in each dataset, only complex disease AAS were found to be indistinguishable from neutral polymorphic AAS. Investigation of monogenic disease AAS predicted to be nondeleterious by SIFT were characterized by a significant enrichment for inherited AAS within solvent accessible residues, regions of intrinsic protein disorder, and an association with the loss or gain of various posttranslational modifications. Sites of structural and/or functional interest were therefore surmised to constitute useful additional features with which to identify the molecular disruptions caused by deleterious AAS. A range of bioinformatic tools, designed to predict structural and functional sites in protein sequences, were then employed to demonstrate that intrinsic biases exist in terms of the distribution of different types of human AAS with respect to specific structural, functional and pathological features. Our Web tool, designed to potentiate the functional profiling of novel AAS, has been made available at http://profile.mutdb.org/.


Ecological risk assessment of parent and halogenated polycyclic aromatic hydrocarbons in surface sediments from an urban river in south China.
In the present study, 16 priority polycyclic aromatic hydrocarbons (Σ(16) PAHs), including seven carcinogenic PAHs (Σ(7) PAHs) designated by the U.S. Environmental Protection Agency, in surface sediment from an urban river (Shenzhen, south China) were measured. The concentrations of Σ(16) PAHs and Σ(7) PAHs ranged from 27.92 to 7409 ng/g and 0.53 to 2326 ng/g, respectively. Source appointments indicated that the PAHs in surface sediments were mainly derived from coal combustion (36.6%), oil spills (22.2%), vehicle emission (19.5%), and waste incineration (12.1%). The ecological risks posed by PAHs and several halogenated PAHs in these sediment samples were assessed using two redefined guidelines incorporating the toxic equivalency quotients (TEQs) of individual PAH congeners: (1) TEQs effect range-low, and (2) TEQs effect range-median. The authors' results suggested that the PAHs they measured in most of the sediments in this urban river would not cause acute biological effects. On the contrary, the ecological risk posed by some halogenated PAHs was much higher than that of their corresponding parent PAHs. Finally, the relationships between PAH levels and catchment urbanization processes were examined. The results indicated that rapid urbanization has led to an obvious increase in PAH contamination in surface sediments.


Lipoprotein and apolipoprotein levels among Mexican-Americans in Starr County, Texas.
Mexican-Americans represent the single largest component of the US Hispanic population and have been shown to bear a disproportionate burden of chronic disease. A representative sample of 1,004 Mexican-Americans aged 15-74 years from Starr County, Tex., was recruited for this study. Each subject was provided a detailed physical evaluation that included measurement of fasting levels of cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol and its subfractions (HDL2 and HDL3) alpha- and beta-lipoprotein cholesterol, and low density lipoprotein cholesterol. Apolipoproteins A-I, A-II, B, C-II, C-III, and E were determined for approximately 550 of these individuals. Age- and sex-specific mean levels and percentile cut points are presented. The distributions of lipoproteins are quite similar to those of the general population except for consistently higher triglycerides in males and females and lower HDL cholesterol levels in females. These findings are consistent with the high frequency of obesity. Comparative age- and sex-specific data for the apolipoproteins are not widely available. Where such data exist, apolipoprotein levels observed in the Mexican-American population tend to be similar to or lower than the comparative data.


Welfare, maternal work, and on-time childhood vaccination rates.
To examine effects of Temporary Assistance for Needy Families welfare cash assistance and maternal work requirements on "on-time" childhood vaccination rates. A stratified random sample of Illinois children from low-income families affected by welfare reform was monitored from 1997 to 2004. Medical records from pediatricians' offices and Medicaid claims data were used to identify the timeliness of 18 recommended vaccinations. Random-intercept logistic models were used to estimate on-time vaccine administration as a function of welfare receipt and maternal work with adjustment for characteristics of the children and mothers and time-varying covariates pertaining to the administration window for each recommended vaccine dose. Of all recommended vaccinations, 55.9% were administered on time. On-time vaccination rates were higher when families were receiving welfare than not (57.4% vs 52.8%). Children in families that either were receiving welfare or had working mothers were 1.7 to 2.1 times more likely to receive vaccinations on time compared with children in families that were not receiving welfare and did not have working mothers. When vaccine doses were stratified according to welfare status, maternal work was associated with decreased on-time vaccination rates (odds ratio: 0.73 [95% confidence interval: 0.59-0.90]) when families received welfare but increased on-time vaccination rates (odds ratio: 1.68 [95% confidence interval: 1.27-2.22]) when they did not receive welfare. These results indicate that maternal work requirements of Temporary Assistance for Needy Families had negative effects on timely administration of childhood vaccinations, although receipt of welfare itself was associated with increased on-time rates.


Scattering and Gradient Forces from the Electromagnetic Stress Tensor Acting on a Dielectric Sphere.
The derivation of the scattering force and the gradient force on a spherical particle due to an electromagnetic wave often invokes the Clausius-Mossotti factor, based on an ad hoc physical model. In this article, we derive the expressions including the Clausius-Mossotti factor directly from the fundamental equations of classical electromagnetism. Starting from an analytic expression for the force on a spherical particle in a vacuum using the Maxwell stress tensor, as well as the Mie solution for the response of dielectric particles to an electromagnetic plane wave, we derive the scattering and gradient forces. In both cases, the Clausius-Mossotti factor arises rigorously from the derivation without any physical argumentation. The limits agree with expressions in the literature.


Healthcare needs and health service utilization by Syrian refugee women in Toronto.
Access to healthcare is an important part of the (re)settlement process for Syrian refugees in Canada. There is growing concern about the healthcare needs of the 54,560 Syrian refugees who were admitted to Canada by May 2018, 80% of whom are women and children. We explored the healthcare needs of newcomer Syrian women, their experiences in accessing and using health services, and the factors and conditions that shape whether and how they access and utilize health services in the Greater Toronto Area (GTA). This community-based qualitative descriptive interpretive study was informed by Yang & Hwang (2016) health service utilization framework. Focus group discussions were held with 58 Syrian newcomer women in the GTA. These discussions were conducted in Arabic, audio-recorded with participants' consent, translated into English and transcribed, and analyzed using thematic analysis. Participants' health concerns included chronic, long-term conditions as well as new and emerging issues. Initial health insurance and coverage were enabling factors to access to services, while language and social disconnection were barriers. Other factors, such as beliefs about naturopathic medicine, settlement in suburban areas with limited public transportation, and lack of linguistically, culturally, and gender-appropriate services negatively affected access to and use of healthcare services. Responding to the healthcare needs of Syrian newcomer women in a timely and comprehensive manner requires coordinated, multi-sector initiatives that can address the financial, social, and structural barriers to their access and use of services.


Antibacterial and antioxidant activity of essential oil terpenes against pathogenic and spoilage-forming bacteria and cell structure-activity relationships evaluated by SEM microscopy.
The antibacterial activity and antioxidant effect of the compounds α-terpineol, linalool, eucalyptol and α-pinene obtained from essential oils (EOs), against pathogenic and spoilage forming bacteria were determined. The antibacterial activities of these compounds were observed in vitro on four Gram-negative and three Gram-positive strains. S. putrefaciens was the most resistant bacteria to all tested components, with MIC values of 2% or higher, whereas E. coli O157:H7 was the most sensitive strain among the tested bacteria. Eucalyptol extended the lag phase of S. Typhimurium, E. coli O157:H7 and S. aureus at the concentrations of 0.7%, 0.6% and 1%, respectively. In vitro cell growth experiments showed the tested compounds had toxic effects on all bacterial species with different level of potency. Synergistic and additive effects were observed at least one dose pair of combination against S. Typhimurium, E. coli O157:H7 and S. aureus, however antagonistic effects were not found in these combinations. The results of this first study are encouraging for further investigations on mechanisms of antimicrobial activity of these EO components.