Alcohol and substance abuse.
Alcoholic liver disease is an important cause of cirrhosis, liver-associated death, and need for liver transplant. Up to 50% of recipients use some alcohol, and perhaps 10% drink addictively. Careful evaluation by an addiction medicine specialist is the best predictive instrument before transplant surgery, whereas the 6-month rule lacks sensitivity and specificity. Addictive drinking, but not minor slips, is associated with increased mortality. There is no standard therapy for alcoholism in alcoholics waiting for a transplant or for those who have undergone a transplant. Stably abstinent, methadone-maintained opiate-dependent patients should continue methadone; are generally good candidates for liver transplant; and show low relapse rates. Pre- and post-transplant smoking rates are high and cause significant morbidity and mortality. Transplant teams should encourage smoking cessation treatments. Marijuana use in liver transplant recipients is common, although risks associated with this practice are unknown.


Understanding and enhancing motor recovery after stroke using transcranial magnetic stimulation.
Stroke is the leading cause of long-term disability. Understanding how people recover from stroke and other brain lesions remain one of the biggest conundrums in neuroscience. As a result, concerted efforts in recent years have focused on investigating the neurophysiological changes that occur in the brain after stroke, and in developing novel strategies to enhance motor recovery. In particular, transcranial magnetic stimulation (TMS) is a non-invasive tool that has been used to investigate the brain plasticity changes resulting from stroke and as a therapeutic modality to safely improve motor function. In this review, we discuss the contributions of TMS to understand how different motor areas, such as the ipsilesional hemisphere, secondary motor areas, and contralesional hemisphere are involved in motor recovery. We also consider recent studies using repetitive TMS (rTMS) in stroke patients to enhance upper extremity function. Although further studies are needed, these investigations provide an important starting point to understand the stimulation parameters and patient characteristics that may influence the optimal response to non-invasive brain stimulation. Future directions of rTMS are discussed in the context of post-stroke motor recovery.


An economic model: value of antimicrobial-coated sutures to society, hospitals, and third-party payers in preventing abdominal surgical site infections.
While the persistence of high surgical site infection (SSI) rates has prompted the advent of more expensive sutures that are coated with antimicrobial agents to prevent SSIs, the economic value of such sutures has yet to be determined. Using TreeAge Pro, we developed a decision analytic model to determine the cost-effectiveness of using antimicrobial sutures in abdominal incisions from the hospital, third-party payer, and societal perspectives. Sensitivity analyses systematically varied the risk of developing an SSI (range, 5%-20%), the cost of triclosan-coated sutures (range, $5-$25/inch), and triclosan-coated suture efficacy in preventing infection (range, 5%-50%) to highlight the range of costs associated with using such sutures. Triclosan-coated sutures saved $4,109-$13,975 (hospital perspective), $4,133-$14,297 (third-party payer perspective), and $40,127-$53,244 (societal perspective) per SSI prevented, when a surgery had a 15% SSI risk, depending on their efficacy. If the SSI risk was no more than 5% and the efficacy in preventing SSIs was no more than 10%, triclosan-coated sutures resulted in extra expenditure for hospitals and third-party payers (resulting in extra costs of $1,626 and $1,071 per SSI prevented for hospitals and third-party payers, respectively; SSI risk, 5%; efficacy, 10%). Our results suggest that switching to triclosan-coated sutures from the uncoated sutures can both prevent SSIs and save substantial costs for hospitals, third-party payers, and society, as long as efficacy in preventing SSIs is at least 10% and SSI risk is at least 10%.


Empowerment of people with a long-term work disability: development of the 'VrijBaan' questionnaire.
To develop an instrument that measures empowerment among people with a long-term work disability. A six-dimension empowerment model was chosen as a theoretical framework. These dimensions are as follows: competence, self-determination, meaning, impact, positive identity and group orientation. A literature search was conducted to find instruments that currently are being used to measure one or more of these constructs. Validated and applicable instruments from this search were used in a preliminary questionnaire. A pilot test was conducted consulting the target population and experts. On basis of changes from this pilot, a concept questionnaire was conducted. In a field test, this questionnaire was sent to 976 subjects who followed a vocational rehabilitation course in the years 2001-2003. Item-total correlations and factor analyses were performed on the collected data to reduce the number of items. Factor analysis was performed, and internal consistency was determined to get insight into the psychometric properties of the final questionnaire. From all subjects who were approached, 385 (39%) returned usable questionnaires that could be analysed. Item reduction by item-total correlations and factor analysis resulted in a final questionnaire consisting of 62 items divided over the six subscales. Internal consistency of the subscales was good: all subscales had Cronbach's alphas between 0.80 and 0.91. Some inter-correlation existed between the subscales competence, self-determination and impact. The 'VrijBaan' questionnaire was developed to measure empowerment among people with a long-term work disability. Although the results support the internal consistency of the subscales, further psychometric work is needed to improve the quality of this questionnaire.


Assessing drivers of benthic macroinvertebrate community structure in African highland streams: An exploration using multivariate analysis.
Understanding the drivers of community structure is fundamental for adequately managing ecosystems under global change. Here we used a large dataset of eighty-four headwater stream sites in three catchments in the Eastern Highlands of Zimbabwe, which represent a variety of abiotic conditions and levels of impairment, to examine the drivers of benthic macroinvertebrate community structure. We focused our assessment on macroinvertebrate family level community composition and functional feeding group classifications. Taxonomic richness was weakly positively correlated with ammonium, phosphates and pH, and weakly negatively correlated with detrital cover and dissolved oxygen. Measured abiotic variables, however, had limited influence on both macroinvertebrate diversity and functional feeding group structure, with the exception of ammonium, channel width and phosphates. This reflected the fact that many macroinvertebrate families and functional feeding guilds were well represented across a broad range of habitats. Predatory macroinvertebrates were relatively abundant, with collector-filterers having the lowest relative abundances. The findings of the study suggest that for certain ecological questions, a more detailed taxonomic resolution may be required to adequately understand the ecology of aquatic macroinvertebrates within river systems. We further recommend management and conservation initiatives on the Save River system, which showed significant impact from catchment developmental pressures, such as urbanisation, agriculture and illegal mining.


Juicy stories on female reproductive tissue development: coordinating the hormone flows.
In the past 20-30 years, developmental biologists have made tremendous progress in identifying genes required for the specification of individual cell types of an organ and in describing how they interact in genetic networks. In comparison, very little is known about the mechanisms that regulate tissue polarity and overall organ patterning. Gynoecia and fruits from members of the Brassicaceae family of flowering plants provide excellent model systems to study organ patterning and tissue specification because they become partitioned into distinct domains whose formation is determined by polarity establishment both at a cellular and whole tissue level. Interactions among key regulators of Arabidopsis gynoecium and fruit development have revealed a network of upstream transcription factor activities required for such tissue differentiation. Regulation of the plant hormone auxin is emerging as both an immediate downstream output and input of these activities, and here we aim to provide an overview of the current knowledge regarding the link between auxin and female reproductive development in plants. In this review, we will also demonstrate how available data can be exploited in a mathematical modeling approach to reveal and understand the feedback regulatory circuits that underpin the polarity establishment, necessary to guide auxin flows.


An integrodifference model for vegetation patterns in semi-arid environments with seasonality.
Vegetation patterns are a characteristic feature of semi-deserts occurring on all continents except Antarctica. In some semi-arid regions, the climate is characterised by seasonality, which yields a synchronisation of seed dispersal with the dry season or the beginning of the wet season. We reformulate the Klausmeier model, a reaction-advection-diffusion system that describes the plant-water dynamics in semi-arid environments, as an integrodifference model to account for the temporal separation of plant growth processes during the wet season and seed dispersal processes during the dry season. The model further accounts for nonlocal processes involved in the dispersal of seeds. Our analysis focusses on the onset of spatial patterns. The Klausmeier partial differential equations (PDE) model is linked to the integrodifference model in an appropriate limit, which yields a control parameter for the temporal separation of seed dispersal events. We find that the conditions for pattern onset in the integrodifference model are equivalent to those for the continuous PDE model and hence independent of the time between seed dispersal events. We thus conclude that in the context of seed dispersal, a PDE model provides a sufficiently accurate description, even if the environment is seasonal. This emphasises the validity of results that have previously been obtained for the PDE model. Further, we numerically investigate the effects of changes to seed dispersal behaviour on the onset of patterns. We find that long-range seed dispersal inhibits the formation of spatial patterns and that the seed dispersal kernel's decay at infinity is a significant regulator of patterning.


Engineered microenvironments for controlled stem cell differentiation.
In a developing organism, tissues emerge from coordinated sequences of cell renewal, differentiation, and assembly that are orchestrated by spatial and temporal gradients of multiple regulatory factors. The composition, architecture, signaling, and biomechanics of the cellular microenvironment act in concert to provide the necessary cues regulating cell function in the developing and adult organism. With recent major advances in stem cell biology, tissue engineering is becoming increasingly oriented toward biologically inspired in vitro cellular microenvironments designed to guide stem cell growth, differentiation, and functional assembly. The premise is that to unlock the full potential of stem cells, at least some aspects of the dynamic three-dimensional (3D) environments that are associated with their renewal, differentiation, and assembly in native tissues need to be reconstructed. In the general context of tissue engineering, we discuss the environments for guiding stem cell function by an interactive use of biomaterial scaffolds and bioreactors, and focus on the interplay between molecular and physical regulatory factors. We highlight some illustrative examples of controllable cell environments developed through the interaction of stem cell biology and tissue engineering at multiple levels.


Hemoglobin Effects on Nitric Oxide Mediated Hypoxic Vasodilation.
The brain responds to hypoxia with an increase in cerebral blood flow (CBF). However, such an increase is generally believed to start only after the oxygen tension decreases to a certain threshold level. Although many mechanisms (different vasodilator and different generation and metabolism mechanisms of the vasodilator) have been proposed at the molecular level, none of them has gained universal acceptance. Nitric oxide (NO) has been proposed to play a central role in the regulation of oxygen supply since it is a vasodilator whose production and metabolism are both oxygen dependent. We have used a computational model that simulates blood flow and oxygen metabolism in the brain (BRAINSIGNALS) to test mechanism by which NO may elucidate hypoxic vasodilation. The first model proposed that NO was produced by the enzyme nitric oxide synthase (NOS) and metabolized by the mitochondrial enzyme cytochrome c oxidase (CCO). NO production declined with decreasing oxygen concentration given that oxygen is a substrate for nitric oxide synthase (NOS). However, this was balanced by NO metabolism by CCO, which also declined with decreasing oxygen concentration. However, the NOS effect was dominant; the resulting model profiles of hypoxic vasodilation only approximated the experimental curves when an unfeasibly low K m for oxygen for NOS was input into the model. We therefore modified the model such that NO generation was via the nitrite reductase activity of deoxyhemoglobin instead of NOS, whilst keeping the metabolism of NO by CCO the same. NO production increased with decreasing oxygen concentration, leading to an improved reproduction of the experimental CBF versus PaO2 curve. However, the threshold phenomenon was not perfectly reproduced. In this present work, we incorporated a wider variety of oxygen dependent and independent NO production and removal mechanisms. We found that the addition of NO removal via oxidation to nitrate mediated by oxyhemoglobin resulted in the optimum fit of the threshold phenomenon by the model. Our revised model suggests, but does not prove, that changes in NO concentration can be the primary cause of the relationship between pO2 and cerebral blood flow.


Who is the patient? Tensions between advance care planning and shared decision-making.
Shared decision-making takes many forms, involving different kinds of agents who share the requirement that they must have sufficient decision-making capacity for the decision in question. Advance care planning (ACP) is commonly viewed as a form of shared decision-making between carers and patients who anticipate losing decision-making capacity. What is unclear in this situation is the identity status of an individual who has become mentally incapacitated and how to evaluate their rights and interests. This is known as the identity problem of ACP. This paper suggests that the identity problem can be most convincingly addressed by understanding ACP based on narrative views of identity. These views, however, create a tension in our current medico-legal framework for attributing decision-making capacity. Current laws and guidelines favour maximum inclusiveness and hence mandate supported decision-making of those with reduced or only focally preserved decision-making capacity. Yet, an ACP framework based on narrative identity and the relevant capacities to construct such narratives results in more demanding capacity requirements than current medico-legal practice requires. The law thus espouses conflicting views as to who can be an appropriate decision-making authority for patient care. I therefore conclude that the law governing medical care needs to be clearer about how to resolve the identity problem and revisit its position on ACP or supported decision-making for those who have only focally preserved decision-making capacity.


Comparing insecticide-treated bed net use to Plasmodium falciparum infection among schoolchildren living near Lake Victoria, Kenya.
Under trial conditions insecticide-treated nets have been shown to provide significant clinical and mortality protection under a range of malaria transmission intensity conditions. There are, however, few operational impact data, notably in very intense transmission conditions. This study, reports on malaria infection among Kenyan schoolchildren living in areas of intense malaria transmission and their reported use of insecticide-treated bed nets. 5188 children in 54 schools were randomly sampled from seven counties surrounding Lake Victoria between May and June 2014. A questionnaire was administered to schoolchildren in classes 2-6 on the use of a long-lasting, insecticide-treated net (LLIN) the night before the survey and provided a single blood sample for a rapid diagnostic test for malaria infection. Analysis of the impact of insecticide-treated net use on malaria prevalence was undertaken using a multivariable, mixed effects, logistic regression at 95% confidence interval (CI), taking into account hierarchical nature of the data and results adjusted for school clusters. The overall prevalence of malaria infection was 48.7%, two-thirds (67.9%) of the children reported using LLIN, 91.3% of the children reported that their households own at least one LLIN and the household LLIN coverage was 2.5 persons per one LLIN. The prevalence of infection showed variation across the counties, with prevalence being highest in Busia (66.9%) and Homabay (51.8%) counties, and lowest in Migori County (29.6%). Generally, malaria parasite prevalence differed between age groups and gender with the highest prevalence occurring in children below 7 years (50.6%) and males (52.2%). Adjusting for county and school, there was a significant reduction in odds of malaria infection among the schoolchildren who reported LLIN use the previous night by 14 % (aOR 0.86, 95% CI 0.74-0.98, P < 0.027). Malaria transmission continues to be high around Lake Victoria. Despite evidence of increasing pyrethroid resistance and the likely overall efficacy of LLIN distributed several years prior to the survey, LLIN continue to provide protection against infection among school-aged children.


Absorption of solar radiation by clouds: observations versus models.
There has been a long history of unexplained anomalous absorption of solar radiation by clouds. Collocated satellite and surface measurements of solar radiation at five geographically diverse locations showed significant solar absorption by clouds, resulting in about 25 watts per square meter more global-mean absorption by the cloudy atmosphere than predicted by theoretical models. It has often been suggested that tropospheric aerosols could increase cloud absorption. But these aerosols are temporally and spatially heterogeneous, whereas the observed cloud absorption is remarkably invariant with respect to season and location. Although its physical cause is unknown, enhanced cloud absorption substantially alters our understanding of the atmosphere's energy budget.


What's in an Atom? A Comparison of Carbon and Silicon-Centred Amidinium⋅⋅⋅Carboxylate Frameworks*.
Despite their apparent similarity, framework materials based on tetraphenylmethane and tetraphenylsilane building blocks often have quite different structures and topologies. Herein, we describe a new silicon tetraamidinium compound and use it to prepare crystalline hydrogen bonded frameworks with carboxylate anions in water. The silicon-containing frameworks are compared with those prepared from the analogous carbon tetraamidinium: when biphenyldicarboxylate or tetrakis(4-carboxyphenyl)methane anions were used similar channel-containing networks are observed for both the silicon and carbon tetraamidinium. When terephthalate or bicarbonate anions were used, different products form. Insights into possible reasons for the different products are provided by a survey of the Cambridge Structural Database and quantum chemical calculations, both of which indicate that, contrary to expectations, tetraphenylsilane derivatives have less geometrical flexibility than tetraphenylmethane derivatives, that is, they are less able to distort away from ideal tetrahedral bond angles.


Naturally occurring vitreous chamber-based myopia in the Labrador retriever.
To investigate whether myopia is present in a breed of domestic dog, the Labrador retriever, and how the ocular components are related to refractive error in this breed. Cycloplegic refractive error was measured in 75 Labrador retrievers by retinoscopy. Corneal and crystalline lens radii of curvature were measured in the right eyes of 57 of these dogs using a video-based keratophakometer, with axial ocular dimensions measured using A-scan ultrasonography. Of the 75 dogs tested, 11 (14.7%) were myopic by at least -0.50 D in one eye, and 6 (8.0%) were myopic in both eyes (full range of refractive errors, +3.50 D to -5.00 D). Of the 57 dogs with ocular component measurements, seven (12.3%) were myopic by at least -0.50 D in the right eye. There was a significant negative correlation between refractive error and vitreous chamber depth (Spearman r = -0.42; P < 0.001). Myopic eyes had an elongated vitreous chamber depth (10.87+/-0.34 mm for myopic dogs, 10.02+/-0.40 mm for nonmyopic dogs; P < 0.0001, Kruskal-Wallis test). There was also a significant quadratic association between lens thickness and vitreous chamber depth (P < 0.005; R2 = 0. 11), indicating that thinner lenses occurred at both shorter and longer vitreous chamber depths. Myopia in the Labrador retriever is analogous to human myopia in that it is caused by an elongated vitreous chamber. Thinner crystalline lenses found at longer vitreous chamber depths may be analogous to lens thinning documented in human ocular development. The Labrador retriever warrants investigation as a potential model of myopia that is naturally occurring rather than experimentally induced.


Treatment of distal radius fractures.
The American Academy of Orthopaedic Surgeons has developed Appropriate Use Criteria (AUC) for treating distal radius fractures (DRF). Evidence-based information, in conjunction with the clinical expertise of physicians, was used to develop the criteria to improve patient care and obtain best outcomes while considering the subtleties and distinctions necessary in making clinical decisions. The DRF AUC clinical patient scenarios were derived from patient indications that generally accompany a DRF, as well as from current evidence-based clinical practice guidelines and supporting literature. The 216 indications and 10 treatments were developed by the Writing Panel, a group of clinicians who are specialists in this AUC topic. Next, the Review Panel, a separate group of volunteer physicians, independently reviewed these materials to ensure that they were representative of patient scenarios that clinicians are likely to encounter in daily practice. Finally, the multidisciplinary Voting Panel (made up of specialists and nonspecialists) rated the appropriateness of treatment of each patient scenario using a 9-point scale to designate a treatment as Appropriate (median rating, 7 to 9), May Be Appropriate (median rating, 4 to 6), or Rarely Appropriate (median rating, 1 to 3).


An immunodominant class I-restricted cytotoxic T lymphocyte determinant of human immunodeficiency virus type 1 induces CD4 class II-restricted help for itself.
We have observed that a peptide corresponding to an immunodominant epitope of the HIV-1 envelope protein recognized by class I MHC-restricted CD8+ CTL can also induce T cell help for itself. The help is necessary for restimulation of CTL precursors in vitro with peptide alone in the absence of exogenous lymphokines, can be removed by depletion of CD4+ T cells, and can be replaced by exogenous IL-2. Whereas the CTL in BALB/c or B10. D2 mice are restricted by the class I molecule Dd, the Th cells are restricted by the class II molecule Ad, and the help can be blocked by anti-Ad mAb. To examine the genetic regulation of the induction of help, we studied B10.A mice that share the class I Dd molecule, but have different class II molecules, Ak and Ek. Spleen cells of immune B10.A mice behave like CD4-depleted BALB/c spleen cells in that they cannot be restimulated in vitro by the peptide alone, but can with peptide plus IL-2. Therefore, in the absence of exogenous lymphokines, peptide-specific help is necessary for restimulation with this immunodominant CTL epitope peptide, and in H-2d mice, this peptide stimulates help for itself as well as CTL. We speculate on the implications of these findings for the immunodominance of this peptide in H-2d mice, and for the selective advantage of pairing certain class I and class II molecules in an MHC haplotype.


Correlates of Use and Perceived Effectiveness of Non-pharmacologic Strategies for Chronic Pain Among Patients Prescribed Long-term Opioid Therapy.
Non-pharmacologic treatments (NPTs) are recommended for chronic pain. Information is limited on patient use or perceptions of NPTs. We examined the frequency and correlates of use and self-rated helpfulness of NPTs for chronic pain among patients who are prescribed long-term opioid therapy (LTOT). Participants (n = 517) with musculoskeletal pain who were prescribed LTOT were recruited from two integrated health systems. They rated the frequency and utility of six clinician-directed and five self-directed NPTs for chronic pain. We categorized NPT use at four levels based on number of interventions used and frequency of use (none, low, moderate, high). Analyses examined clinical and demographic factors that differed among groups for both clinician-directed and self-directed NPTs. Seventy-one percent of participants reported use of any NPT for pain within the prior 6 months. NPTs were rated as being helpful by more than 50% of users for all treatments assessed (range 51-79%). High users of clinician-directed NPTs were younger than non-users or low-frequency users and had the most depressive symptoms. In both clinician-directed and self-directed categories, high NPT users had significantly higher pain disability compared to non-NPT users. No significant group differences were detected on other demographic or clinical variables. In multivariable analyses, clinician-directed NPT use was modestly associated with younger age (OR = 0.97, 95% CI = 0.96-0.98) and higher pain disability (OR = 1.01, 95% CI = 1.00-1.02). Variables associated with greater self-directed NPT use were some college education (OR = 1.80, 95% CI = 1.13-2.84), college graduate or more (OR = 2.02, 95% CI = 1.20-3.40), and higher pain disability (OR = 1.01, 95% CI = 1.01-1.02). NPT use was associated with higher pain disability and younger age for both clinician-directed and self-directed NPTs and higher education for self-directed NPTs. These strategies were rated as helpful by those that used them. These results can inform intervention implementation and be used to increase engagement in NPTs for chronic pain.


Imatinib for progressive and recurrent aggressive fibromatosis (desmoid tumors): an FNCLCC/French Sarcoma Group phase II trial with a long-term follow-up.
Imatinib evaluated as a new treatment option in patients with recurrent or established progressive aggressive fibromatosis/desmoid tumor (AF/DT). Forty patients with unresectable and progressive symptomatic AF/DT were treated with imatinib (400 mg/day for 1 year) in a Simon's optimal two-stage phase II study (P(0) = 10%, P(1) = 30%, α = 5%, β = 10%). The primary end point was non-progressive at 3 months (RECIST). The study population consisted of 28 women and 12 men, with a mean age of 41 (range 20-72 years). Most of the primary sites were extra-abdominal (24, 54.5%). Familial adenomatous polyposis was observed in six (15%) cases. The median follow-up was 34 months. Imatinib toxicity was similar to that previously reported in literature. Tumor assessment was validated by a central independent radiology committee for 35 patients At 3 months, one (3%) complete and three (9%) partial confirmed responses were observed. The non-progression rates at 3, 6 and 12 months were, respectively, 91%, 80% and 67%. The 2-year progression-free and overall survival rates were 55% and 95%, respectively. Two patients with mesenteric AF/DT died from progressive disease. Imatinib is active in the treatment of recurrent and progressive AF/DT, providing objective response and long-term stable disease in a large proportion of patients.


Effects of Viewing Conditions and Rotation Methods in a Collaborative Tabletop AR Environment.
We investigate the effects of viewing conditions and rotation methods on different types of collaborative tasks in a two-user colocated tabletop augmented reality (AR) environment. The viewing condition means how the manipulation of a tabletop world by one user is shown in the other users' views and the rotation method means what type of input devices is used to rotate the tabletop world for alternative orientations. Our experiment considered two viewing conditions (consistent view and inconsistent view), two rotation methods (direct turn and indirect turn), and two task types (synchronous and referring-strong type, and asynchronous and orientation-strong type). A 3D display environment called "Stereoscopic Collaboration in Augmented and Projective Environments (SCAPE)" was utilized as a test environment. According to the results, the viewing conditions had significant effects on several objective and subjective measurements. On task completion time, their effect for the synchronous and referring-strong type of task was opposite to that for the asynchronous and orientation-strong type of task. On the other hand, the rotation methods had significant effects only on the accumulated turn angle (for both task types) and the number of negotiation phrases (only in the inconsistent viewing condition for the asynchronous and orientation-strong type of task).


Breast-feeding history and overweight in 11 to 13-year-old children in Iran.
The relationship between breast-feeding history and risk of overweight in pre-adolescent children was investigated. Children's breast-feeding history and demographics were obtained in interviewer-administered questionnaires of a multistage cluster sample survey of 800 parents of children aged 11-13 years living in Yazd, Iran. Height and weight were measured in the children. Overweight was defined as body mass index >/=90th age- and sex-specific percentile of the 2000 Centers for Disease Control reference values. One hundred and four (13.0%) of 800 children were overweight. A total of 783 (97.9%) of the children had been breast fed. There was a markedly lower overweight prevalence among breast-fed than non breast-fed children. Controlling for age and sex, children breast fed for at least 24 months were substantially less likely to be overweight than children breast fed for less than 12 months (OR 0.56, 95% CI 0.31-0.9). A longer overall duration and duration of exclusive breast-feeding were associated significantly with the decreasing prevalence of overweight. This sample of Iranian children shows high rates of overweight at young ages but also high rates of breast-feeding. The duration of breast-feeding is inversely related with the prevalence of overweight in pre-adolescent children.


Development of novel ibuprofen-loaded solid dispersion with improved bioavailability using aqueous solution.
To develop a novel ibuprofen-loaded solid dispersion with enhanced bioavailability, various ibuprofen-loaded solid dispersions were prepared with water, HPMC and poloxamer. The effect of HPMC and poloxamer on aqueous solubility of ibuprofen was investigated. The dissolution and bioavailability of solid dispersion in rats were then evaluated compared to ibuprofen powder. When the amount of carrier increased with a decreased in HPMC/poloxamer ratio, the aqueous solubility of ibuprofen was elevated. The solid dispersion composed of ibuprofen/HPMC/poloxamer at the weight ratio of 10:3:2 improved the drug solubility approximately 4 fold. It gave significantly higher initial plasma concentration, AUC and Cmax of drug than did ibuprofen powder in rats. The solid dispersion improved the bioavailability of drug about 4-fold compared to ibuprofen powder. Thus, this ibuprofen-loaded solid dispersion with water, HPMC and poloxamer was a more effective oral dosage form for improving the bioavailability of poor water-soluble ibuprofen.


Phase I and pharmacokinetic study of BMS-188797, a new taxane analog, administered on a weekly schedule in patients with advanced malignancies.
The purpose of this study was to establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and preliminary activity of BMS-188797 administered weekly. Patients with advanced malignancies were treated with escalating doses of BMS-188797 on a weekly schedule as a 1-h i.v. infusion. Plasma sampling was performed to characterize the pharmacokinetics of BMS-188797. Eighteen patients with advanced malignancies were enrolled at three dose levels ranging from 35 to 65 mg/m(2). The number of patients evaluated at each dose level was as follows: 35 mg/m(2) (n = 3); 50 mg/m(2) (n = 9); and 65 mg/m(2) (n = 6). At 65 mg/m(2), three of six patients had a DLT (one had grade 4 neutropenia lasting >7 days, and two had grade 3 diarrhea). Expansion of the 50-mg/m(2) dose cohort to nine patients established this dose as the MTD, with one patient experiencing a DLT (grade 4 neutropenia with fever). Two partial responses were observed (lung cancer, 7+ months; ovarian cancer, 6+ months durations), as well as two minor responses (esophageal cancer, 5 months; ovarian cancer, 5 months). Both patients with partial responses had been clinically resistant to paclitaxel. Plasma pharmacokinetic mean values of maximum concentration (C(max)) and area under the curve (AUC(0-48)) increased in a dose-dependent manner within the range of doses used in this study, and in three of four patients, the DLTs correlated with AUC. The MTD and the recommended Phase II dose of weekly BMS-188797 is 50 mg/m(2). The drug demonstrates antitumor activity in taxane-refractory solid tumors and is now being evaluated in combination with carboplatin.


Intraspecific variation of a dominant grass and local adaptation in reciprocal garden communities along a US Great Plains' precipitation gradient: implications for grassland restoration with climate change.
Identifying suitable genetic stock for restoration often employs a 'best guess' approach. Without adaptive variation studies, restoration may be misguided. We test the extent to which climate in central US grasslands exerts selection pressure on a foundation grass big bluestem (Andropogon gerardii), widely used in restorations, and resulting in local adaptation. We seeded three regional ecotypes of A. gerardii in reciprocal transplant garden communities across 1150 km precipitation gradient. We measured ecological responses over several timescales (instantaneous gas exchange, medium-term chlorophyll absorbance, and long-term responses of establishment and cover) in response to climate and biotic factors and tested if ecotypes could expand range. The ecotype from the driest region exhibited greatest cover under low rainfall, suggesting local adaptation under abiotic stress. Unexpectedly, no evidence for cover differences between ecotypes exists at mesic sites where establishment and cover of all ecotypes were low, perhaps due to strong biotic pressures. Expression of adaptive differences is strongly environment specific. Given observed adaptive variation, the most conservative restoration strategy would be to plant the local ecotype, especially in drier locations. With superior performance of the most xeric ecotype under dry conditions and predicted drought, this ecotype may migrate eastward, naturally or with assistance in restorations.


Effects of reduced-volume of sprint interval training and the time course of physiological and performance adaptations.
This study sought to determine the time course of training adaptations to two different sprint interval training programmes with the same sprint: rest ratio (1:8) but different sprint duration. Nine participants (M: 7; F: 2) were assigned to 15-second training group (15TG) consisting of 4-6 × 15-second sprints interspersed with 2-minute recovery, whereas eight participants (M: 5; F: 3) were assigned to 30-second training group (30TG) consisting of 4-6 × 30 second sprints interspersed with 4-minute recovery. Both groups performed their respective training twice per week over 9 weeks and changes in peak oxygen uptake (V˙O2peak) and time to exhaustion (TTE) were assessed every 3 weeks. Additional eight healthy active adults (M: 6; F: 2) completed the performance assessments 9 weeks apart without performing training (control group, CON). Following 9 weeks of training, both groups improved V˙O2peak (15TG: 12.1%; 30TG: 12.8%, P<.05) and TTE (15TG: 16.2%; 30TG: 12.8%, P<.01) to a similar extent. However, while both groups showed the greatest gains in V˙O2peak at 3 weeks (15TG: 16.6%; 30TG: 17.0%, P<.001), those in TTE were greatest at 9 weeks. CON did not change any of performance variables following 9 weeks. This study demonstrated that while the changes in cardiorespiratory function plateau within several weeks with sprint interval training, endurance capacity (TTE) is more sensitive to such training over a longer time frame in moderately-trained individuals. Furthermore, a 50% reduction in sprint duration does not diminish overall training adaptations over 9 weeks.


Noninvasive Diagnosis of Nonalcoholic Fatty Liver Disease and Quantification of Liver Fat Using a New Quantitative Ultrasound Technique.
Liver biopsy analysis is the standard method used to diagnose nonalcoholic fatty liver disease (NAFLD). Advanced magnetic resonance imaging is a noninvasive procedure that can accurately diagnose and quantify steatosis, but is expensive. Conventional ultrasound is more accessible but identifies steatosis with low levels of sensitivity, specificity, and quantitative accuracy, and results vary among technicians. A new quantitative ultrasound (QUS) technique can identify steatosis in animal models. We assessed the accuracy of QUS in the diagnosis and quantification of hepatic steatosis, comparing findings with those from magnetic resonance imaging proton density fat fraction (MRI-PDFF) analysis as a reference. We performed a prospective, cross-sectional analysis of a cohort of adults (N = 204) with NAFLD (MRI-PDFF, ≥5%) and without NAFLD (controls). Subjects underwent MRI-PDFF and QUS analyses of the liver on the same day at the University of California, San Diego, from February 2012 through March 2014. QUS parameters and backscatter coefficient (BSC) values were calculated. Patients were assigned randomly to training (n = 102; mean age, 51 ± 17 y; mean body mass index, 31 ± 7 kg/m(2)) and validation (n = 102; mean age, 49 ± 17 y; body mass index, 30 ± 6 kg/m(2)) groups; 69% of patients in each group had NAFLD. BSC (range, 0.00005-0.25 1/cm-sr) correlated with MRI-PDFF (Spearman ρ = 0.80; P < .0001). In the training group, the BSC analysis identified patients with NAFLD with an area under the curve value of 0.98 (95% confidence interval, 0.95-1.00; P < .0001). The optimal BSC cut-off value identified patients with NAFLD in the training and validation groups with 93% and 87% sensitivity, 97% and 91% specificity, 86% and 76% negative predictive values, and 99% and 95% positive predictive values, respectively. QUS measurements of BSC can accurately diagnose and quantify hepatic steatosis, based on a cross-sectional analysis that used MRI-PDFF as the reference. With further validation, QUS could be an inexpensive, widely available method to screen the general or at-risk population for NAFLD.


A user-generated data based approach to enhancing location prediction of financial services in sub-Saharan Africa.
The recent increase in user-generated content and social media adoption in developing countries offers an unprecedented opportunity to better understand the accessibility and spatial distribution of financial services in sub-Saharan Africa. Financial inclusion has been identified as a priority by multiple agencies in the region and on-the-ground efforts are currently underway to identify previously unknown financial access points in numerous developing African countries. Existing techniques for estimating the location of these access points rely on spatial analysis of often outdated or unsuitable publicly available datasets such as population density, road networks, etc., as well as expensive and time consuming surveys of locals in the region. In this work we propose an approach to augment existing spatial data analysis techniques through the inclusion of user-generated geo-content and geo-social media data. Through a comparison of standard regression models and machine learning techniques, this work proposes the use of alternative data sources to build prediction models for identifying financial access locations in countries where current estimation models are insufficient. With a better understanding of geospatial distribution patterns this work aims at reducing data acquisition costs and providing decision makers with critical data more quickly and efficiently. Finally, we present a mobile application built on the outcomes of this analysis that is currently being used to better inform on-the-ground data collection efforts.


Choledochal cysts: differences between pediatric and adult patients.
Choledochal cysts in children and adults are believed to be different, but direct comparison between them is lacking in the literature. This study was aimed to identify the clinicopathological differences between 42 children and 59 adults with choledochal cyst treated by same surgeons at the Cathay General Hospital. The mean follow-up period was 8.9 years. The result showed that the female-to-male ratios were 1.5:1 in pediatric patients and 4.9:1 in adult patients. Compared with adults with choledochal cyst, the pediatric patients presented more abdominal mass (52.4% vs 21.2%, P = 0.002) and less abdominal pain (76.2% vs. 98.0%, P = 0.002), are more frequently associated with anomalous pancreaticobiliary ductal union (85.7% vs. 59.6%, P = 0.005) and sudden severe stenosis of terminal choledochus (76.2% vs. 42.3%, P = 0.001), are less commonly associated with choledocholithiasis, are not associated with malignant transformation (0% vs 21.2%), and have fewer perioperative and long-term complications. Nevertheless, patients who received total excision had fewer surgical complications in both groups. This result shows that choledochal cysts in pediatric and adult patients are different in clinicopathological manifestations, prognosis, and the underlying abnormalities of the pancreaticobiliary system, suggesting that patients with choledochal cyst should be managed according to these differences.


Antiplatelet effects of Rhus verniciflua stokes heartwood and its active constituents--fisetin, butein, and sulfuretin--in rats.
Rhus verniciflua stokes (RVS) is known to promote blood circulation by preventing blood stasis, although the active ingredients and the underlying mechanism are unclear. Platelets are the primary cells that regulate circulation and contribute to the development of diverse cardiovascular diseases by aggregation and thrombosis. The study assessed the antiplatelet activity of RVS and sought to identify the active constituents. Pretreatment of washed platelets with RVS heartwood extract blunted the aggregatory response of platelets to collagen. In the subfractions, fisetin, butein, and sulfuretin were identified as effective inhibitors of platelet aggregation by collagen, thrombin, and adenosine-5'-diphosphate. Antiplatelet activities of all three compounds were concentration dependent, and fisetin had longer in vitro duration of action compared with butein or sulfuretin. Extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase activation by collagen was prevented by fisetin, whereas butein and sulfuretin failed to inhibit ERK and p38 activation was not affected by any of the compounds. Rats orally administered 100 mg/(kg·day(-1)) fisetin for 7 days were resistant to arterial thrombosis, although total extract of RVS heartwood exhibited little effect at a dose of 1000 mg/(kg·day(-1)). RVS heartwood may have cardiovascular protective activity by inhibiting platelet aggregation. The active constituents are fisetin, butein, and sulfuretin, and fisetin is orally effective against thrombosis.


Gut Feelings About α-Synuclein in Gastrointestinal Biopsies: Biomarker in the Making?
In recent years, several studies have investigated the potential of immunohistochemical detection of α-synuclein in the gastrointestinal tract to diagnose Parkinson's disease (PD). Although methodological heterogeneity has hindered comparability between studies, it has become increasingly apparent that the high sensitivity and specificity reported in preliminary studies has not been sustained in subsequent large-scale studies. What constitutes pathological α-synuclein in the alimentary canal that could distinguish between PD patients and controls and how this can be reliably detected represent key outstanding questions in the field. In this review, we will comment on and compare the variable technical aspects from previous studies, and by highlighting some advantages and shortcomings we hope to delineate a standardized approach to facilitate the consensus criteria urgently needed in the field. Furthermore, we will describe alternative detection techniques to conventional immunohistochemistry that have recently emerged and may facilitate ease of interpretation and reliability of gastrointestinal α-synuclein detection. Such techniques have the potential to detect the presence of pathological α-synuclein and include the paraffin-embedded tissue blot, the proximity ligation assay, the protein misfolding cyclic amplification technique, and the real-time quaking-induced conversion assay. Finally, we will review 2 nonsynonymous theories that have driven enteric α-synuclein research, namely, (1) that α-synuclein propagates in a prion-like fashion from the peripheral nervous system to the brain via vagal connections and (2) that gastrointestinal α-synuclein deposition may be used as a clinically useful biomarker in PD.


Primary malignant pericardial mesothelioma presenting as acute pericarditis.
We report on a 21-year-old man with fever, dyspnea, and pleuritic chest pain. An electrocardiography showed ST elevation in multiple lead and thoracic echocardiography revealed moderate pericardial effusion. He was initially diagnosed with acute pericarditis, and treated with nonsteroidal anti-inflammatory drugs and colchicines with clinical and laboratory improvement. After 1 month of medication, his symptoms recurred. An echocardiography showed constrictive physiology and the patient was treated with steroid on the top of current medication. The patient had been well for 7 months until dyspnea and edema developed, when an echocardiography showed marked increased pericardial thickness and constriction. Pericardial biopsy was performed and primary malignant pericardial mesothelioma was diagnosed. Malignancy should be considered in the differential diagnosis of recurrent pericarditis.


Prognostic value of human papillomavirus in the survival of cervical cancer patients: an overview of the evidence.
Some studies have suggested that the presence in tumors of nucleic acids from human papillomavirus (HPV) constitutes a prognostic marker of disease severity in cervical cancer. There are two conflicting lines of evidence in this regard. First, the presence of HPV 18 is equated to rapid progression through early disease stages, possibly resulting in a more aggressive clinical course. Although fragmentary, in terms of the clinical and epidemiological basis, this line of evidence has some experimental support. Second, the absence of HPV from the tumor would confer a worse prognosis than if any viral types were present. Unlike the former, the latter line of evidence is not bolstered by experimental data but emerged from persuasive clinical studies, which had adequate sample sizes, used survival end points, and controlled for confounders. The absence of HPV in some tumors could indicate that they originated through different oncogenic mechanisms, perhaps resulting in different cell proliferation rates and, consequently, distinct clinical behavior. On the other hand, HPV detectability could simply be a correlate of other genuine prognostic characteristics, which would explain its association with survival. Both the nature and the mechanism of the prognostic role for HPV in cervical cancer remain to be elucidated. The paucity of studies can be attributed to the labor-intensive nature of assays for HPV. It is hoped that the advent of the polymerase chain reaction method will facilitate the conduct of retrospective studies of archival histopathology specimens and survival information.(ABSTRACT TRUNCATED AT 250 WORDS)


Design of a Precision Medication Dispenser: Preventing Overdose by Increasing Accuracy and Precision of Dosage.
Liquid medication overdose in pediatric patients results in over 70000 visits to the emergency room yearly in the USA. Various studies have demonstrated that the root cause of this high incidence is due to user and device error in dose measurement. The standard measuring cup and syringe suffer from the challenge of accurately measuring and dispensing viscous liquids, which comprise the majority of children's medication formulations. Here, we describe the development of a precision medication dispenser that overcomes challenges associated with viscous fluid flow at low volumes and flow rates, while incorporating various ergonomic and user-friendly features. The device performs with >95% accuracy and 94% precision across the 1-5-mL range of volume, a significant improvement when compared to current commercially available dispensers.


Energy Cost of Standing in a Multi-Ethnic Cohort: Are Energy-Savers a Minority or the Majority?
The disease risks associated with sedentary behavior are now firmly established, and consequently there is much interest in methods of increasing low-intensity physical activity. In this context, it is a widely held belief that altering posture allocation can modify energy expenditure (EE) to impact upon body weight regulation and health. However, we recently showed the existence of two distinct phenotypes pertaining to the energy cost of standing-with the majority of a Caucasian cohort showing no sustained increase in EE during standing relative to sitting. Here we investigated whether this phenomenon is also observed across a multi-ethnic male cohort. To determine the magnitude and time-course of changes in EE and respiratory quotient (RQ) during steady-state standing versus sitting, and to explore inter-individual variability in these responses across 4 ethnic groups (European, Indian, Chinese, African). Min-by-min monitoring using posture-adapted ventilated-hood indirect calorimetry was conducted in 35 healthy, men (20-43 years) during 10 min of steady-state standing versus sitting comfortably. 69% of subjects showed little or no increase (<5%) in EE during standing compared to sitting (energy savers). Furthermore, the proportion of energy savers did not significantly differ between ethnic groups, despite ethnic differences in anthropometry; with body weight as the primary predictor of the energy cost of standing maintenance (r2 = 0.30, p = 0.001). Our results indicate that the majority of individuals in a multi-ethnic cohort display a postural energy-saver phenotype. The mechanisms by which the large majority of individuals appear to maintain sitting and standing postures at the same energetic cost remains to be elucidated but is of considerable importance to our understanding of the spontaneous physical activity compartment of EE and its potential as a target for weight regulation.


Oscillometry and pulmonary MRI measurements of ventilation heterogeneity in obstructive lung disease: relationship to quality of life and disease control.
Ventilation heterogeneity is a hallmark finding in obstructive lung disease and may be evaluated using a variety of methods, including multiple-breath gas washout and pulmonary imaging. Such methods provide an opportunity to better understand the relationships between structural and functional abnormalities in the lungs, and their relationships with important clinical outcomes. We measured ventilation heterogeneity and respiratory impedance in 100 subjects [50 patients with asthma, 22 ex-smokers, and 28 patients with chronic obstructive pulmonary disease (COPD)] using oscillometry and hyperpolarized 3He magnetic resonance imaging (MRI) and determined their relationships with quality of life scores and disease control/exacerbations. We also coregistered MRI ventilation maps to a computational airway tree model to generate patient-specific respiratory impedance predictions for comparison with experimental measurements. In COPD and asthma patients, respectively, forced oscillation technique (FOT)-derived peripheral resistance (5-19 Hz) and MRI ventilation defect percentage (VDP) were significantly related to quality of life (FOT: COPD ρ = 0.4, P = 0.004; asthma ρ = -0.3, P = 0.04; VDP: COPD ρ = 0.6, P = 0.003; asthma ρ = -0.3, P = 0.04). Patients with poorly controlled asthma (Asthmatic Control Questionnaire >2) had significantly increased resistance (5 Hz: P = 0.01; 5-19 Hz: P = 0.006) and reactance (5 Hz: P = 0.03). FOT-derived peripheral resistance (5-19 Hz) was significantly related to VDP in patients with asthma and COPD patients (asthma: ρ = 0.5, P < 0.001; COPD: ρ = 0.5, P = 0.01), whereas total respiratory impedance was related to VDP only in patients with asthma (resistance 5 Hz: ρ = 0.3, P = 0.02; reactance 5 Hz: ρ = -0.5, P < 0.001). Model-predicted and FOT-measured reactance (5 Hz) were correlated in patients with asthma (ρ = 0.5, P = 0.001), whereas in COPD patients, model-predicted and FOT-measured resistance (5-19 Hz) were correlated (ρ = 0.5, P = 0.004). In summary, in patients with asthma and COPD patients, we observed significant, independent relationships for FOT-measured impedance and MRI ventilation heterogeneity measurements with one another and with quality of life scores. NEW & NOTEWORTHY In 100 patients, including patients with asthma and ex-smokers, 3He MRI ventilation heterogeneity and respiratory system impedance were correlated and both were independently related to quality of life scores and asthma control. These findings demonstrated the critical relationships between respiratory system impedance and ventilation heterogeneity and their role in determining quality of life and disease control. These observations underscore the dominant role that abnormalities in the lung periphery play in ventilation heterogeneity that results in patients' symptoms.


Cerulein hyperstimulation decreases AMP-activated protein kinase levels at the site of maximal zymogen activation.
The premature activation of digestive enzyme zymogens in the pancreatic acinar cell is an important initiating event in acute pancreatitis. We have previously demonstrated that vacuolar ATPase (vATPase) activity is required for zymogen activation. Adenosine monophosphate-activated protein kinase (AMPK) regulates vATPase function in kidney and epididymal clear cells. To determine whether AMPK could affect pancreatitis responses, its effects were first examined in a cellular model of pancreatitis, cerulein-hyperstimulated (100 nM) pancreatic acini. This treatment caused a prominent increase in trypsin and chymotrypsin activities. Pretreatment with AICAR or metformin (AMPK activators) or compound C (an AMPK inhibitor) reduced or increased cerulein-induced zymogen activation, respectively. The association of the vATPase E subunit with membranes, a marker of its activation, tended to be inversely related to AMPK activity (assessed by AICAR and compound C treatments). Cerulein treatment did not change AMPK (α and β) levels but did lead to an increase in its activation (phosphorylation of Thr172) and induced the time-dependent translocation of the enzyme to a Triton-insoluble compartment. Basal in vivo studies showed that AMPK was widely distributed between membrane and soluble fractions generated by differential centrifugation. After cerulein hyperstimulation, AMPK levels selectively decreased in fractions containing the highest levels of active zymogens. These studies suggest that AMPK activity has a protective role in the pancreatic acinar cell that inhibits zymogen activation in the basal state, and this AMPK effect is reduced during pancreatitis. Therapies that prevent the selective reduction of AMPK in compartments that support zymogen activation could reduce injury during pancreatitis.


Sleep disturbances in adults with eczema are associated with impaired overall health: a US population-based study.
Sleep disturbances are associated with poor health outcomes in adults. However, little is known about the sleep disturbances that occur in adult eczema. We studied the association between adult eczema and sleep disturbance and their impact on overall health and health care utilization. We used the 2012 National Health Interview Survey, a cross-sectional questionnaire of 34,613 adults. Eczema was associated with higher odds of fatigue (odds ratio (95% confidence interval): 2.97 (2.65-3.34)), regular daytime sleepiness (2.66 (2.34-3.01)), and regular insomnia (2.36 (2.11-2.64)), even after controlling for sleep duration, history of allergic disease, sociodemographics, and body mass index. There were significant interactions between eczema and fatigue, sleepiness, and insomnia as predictors of poorer overall health status, number of sick days, and doctor visits, such that eczema and each of the sleep symptoms were associated with higher odds of poorer outcomes than either eczema or sleep symptoms alone. Latent class analysis was used and identified five classes of fatigue, sleep disturbances, and allergic disorders. Two classes had high probabilities of eczema: one with high probabilities of asthma, hay fever, food allergy, and multiple sleep symptoms and the other with intermediate probability of insomnia alone. Future studies are warranted to better characterize sleep loss in eczema and develop strategies for treatment and prevention.


Can post-hoc video review of robotic pancreaticoduodenectomy predict portal/superior mesenteric vein margin status in pancreatic adenocarcinoma?
Achieving margin negative resection is a significant determinant of outcome in pancreatic adenocarcinoma (PDA). However, because of the fibrotic nature of PDA, it can be difficult to discriminate fibrosis from active disease intra-operatively. We sought to determine if post-hoc video review of robotic pancreatico-duodenectomy (RPD) could predict the portal/superior mesenteric vein (PV/SMV) margin status on final pathology. Experienced pancreatic surgeons, blinded to patient and operative variables, reviewed the PV/SMV margin for available RPD videos of consecutive PDA patients from 9/2012 through 6/2017. 107 RPD videos were reviewed. Of 76 patients (71%) predicted to have a negative vein margin on video review, 20 patients (26%) had a pathologic positive margin. 25 of 31 patients (81%) predicted to have positive margin on video review were positive on pathology. The specificity of video prediction was 90.3% with a sensitivity of 55.6% and an accuracy of 75.7%. Post-hoc video review prediction is unable to reliably predict a positive (R1) margin at the portal vein/SMV, suggesting that intra-operative clinical assessment may be suboptimal in determining the need for more extensive resections.


Predictors of Ominous Outcome in Infants who Undergo Cardiac Surgery and Cardiopulmonary By-Pass: S100B Protein.
S100B protein has been recently proposed as a consolidated marker of brain damage and death in adult, children and newborn patients. The present study evaluates whether the longitudinal measurement of S100B at different perioperative time-points may be a useful tool to identify the occurrence of perioperative early death in congenital heart disease (CHD) newborns. We conducted a case-control study in 88 CHD infants, without pre-existing neurological disorders or other co-morbidities, of whom 22 were complicated by perioperative death in the first week from surgery. Control group was composed by 66 uncomplicated CHD infants matched for age at surgical procedure. Blood samples were drawn at five predetermined timepoints before during and after surgery. In all CHD children, S100B levels showed a pattern characterized by a significant increase in protein's concentration from hospital admission up to 24-h after procedure reaching their maximum peak (P<0.01) during cardiopulmonary by-pass and at the end of the surgical procedure. Moreover, S100B concentrations in CHD death group were significantly higher (P<0.01) than controls at all monitoring time-points. The ROC curve analysis showed that S100B measured before surgical procedure was the best predictor of perioperative death, among a series of clinical and laboratory parameters, reaching at a cut-off of 0.1 µg/L a sensitivity of 100% and a specificity of 63.7%. The present data suggest that in CHD infants biochemical monitoring in the perioperative period is becoming possible and S100B can be included among a series of parameters for adverse outcome prediction.


Peritoneal adhesion: it can be life-threatening, and life-saving.
The inevitable post-inflammatory fibrosis and adhesion often compromises future treatment in peritoneal dialysis patients. Here, we describe a patient who experienced an unusual form of peritoneal adhesion that made her give up peritoneal dialysis. However, its unique pattern also saved her from infection caused by bowel perforation. The female patient discontinued peritoneal dialysis due to gradual dialysis inadequacy. Two months after shifting to hemodialysis with generally improved sense of well-being and no sign of abdominal illness, she was admitted to remove the Tenckhoff catheter. The procedure was smooth, but fever and abdominal pain not at the site of operation developed the next day. Abdominal ultrasound showed the presence of ascites and aspiration revealed slimy, green-yellowish pus that gave a negative result on bacterial culture. Abdominal computed tomography (CT) with oral contrast medium was performed, but failed to demonstrate the suspected bowel perforation. The examination, however, did show accumulation of pus inside the abdomen but outside the peritoneal cavity. We drained the pus with two 14-F Pig-tail catheters and the total amount of drainage approached 4000 ml. The second CT was performed with double dose of the contrast medium and found a leak of the contrast from the jejunum. She then received laparotomy and had the perforation site closed. In summary, this uremic patient suffered from pus accumulation inside her abdomen without obvious systemic toxic effect. The bowel perforation and pus formation might be caused by repeated peritonitis, but the peritoneal adhesion itself might also isolate her peritoneal cavity from the anticipated toxic injuries of bowel perforation.


Why don't we ask? A complementary method for assessing the status of great apes.
Species conservation is difficult. Threats to species are typically high and immediate. Effective solutions for counteracting these threats, however, require synthesis of high quality evidence, appropriately targeted activities, typically costly implementation, and rapid re-evaluation and adaptation. Conservation management can be ineffective if there is insufficient understanding of the complex ecological, political, socio-cultural, and economic factors that underlie conservation threats. When information about these factors is incomplete, conservation managers may be unaware of the most urgent threats or unable to envision all consequences of potential management strategies. Conservation research aims to address the gap between what is known and what knowledge is needed for effective conservation. Such research, however, generally addresses a subset of the factors that underlie conservation threats, producing a limited, simplistic, and often biased view of complex, real world situations. A combination of approaches is required to provide the complete picture necessary to engage in effective conservation. Orangutan conservation (Pongo spp.) offers an example: standard conservation assessments employ survey methods that focus on ecological variables, but do not usually address the socio-cultural factors that underlie threats. Here, we evaluate a complementary survey method based on interviews of nearly 7,000 people in 687 villages in Kalimantan, Indonesia. We address areas of potential methodological weakness in such surveys, including sampling and questionnaire design, respondent biases, statistical analyses, and sensitivity of resultant inferences. We show that interview-based surveys can provide cost-effective and statistically robust methods to better understand poorly known populations of species that are relatively easily identified by local people. Such surveys provide reasonably reliable estimates of relative presence and relative encounter rates of such species, as well as quantifying the main factors that threaten them. We recommend more extensive use of carefully designed and implemented interview surveys, in conjunction with more traditional field methods.


A NIR-light activated nanoplatform for sensitizing triple negative breast cancer against therapeutic resistance to enhance the treatment effect.
Current therapeutic strategies against triple negative breast cancer (TNBC) are limited by unconquered therapeutic resistance that shields TNBC cells from treatments such as chemotherapy and radiotherapy. Therefore, the construction of therapeutics capable of sensitizing TNBC cells towards conventional therapeutic strategies remains a formidable challenge in phymatology. Here, a NIR-light activated combination therapeutic nanoplatform is reported to cure TNBC by gene-silencing based sensitization of cancer cells toward treatment using mesoporous silica-coated gold nanorods (Au@MSNs) modified with DNAzyme, which can catalytically cleave survivin mRNA. The survivin DNAzyme is chemically modified on the surface of Au@MSNs using a thermally sensitive small molecule. Upon NIR light irradiation, the absorbed NIR light by gold nanorods is converted into heat to trigger bond breaking, releasing DNAzyme to silence survivin mRNA and sensitize TNBC. In vitro and in vivo results reveal the excellent therapeutic effects of this multifunctional nanocomposite against TNBC.


DREAM3: network inference using dynamic context likelihood of relatedness and the inferelator.
Many current works aiming to learn regulatory networks from systems biology data must balance model complexity with respect to data availability and quality. Methods that learn regulatory associations based on unit-less metrics, such as Mutual Information, are attractive in that they scale well and reduce the number of free parameters (model complexity) per interaction to a minimum. In contrast, methods for learning regulatory networks based on explicit dynamical models are more complex and scale less gracefully, but are attractive as they may allow direct prediction of transcriptional dynamics and resolve the directionality of many regulatory interactions. We aim to investigate whether scalable information based methods (like the Context Likelihood of Relatedness method) and more explicit dynamical models (like Inferelator 1.0) prove synergistic when combined. We test a pipeline where a novel modification of the Context Likelihood of Relatedness (mixed-CLR, modified to use time series data) is first used to define likely regulatory interactions and then Inferelator 1.0 is used for final model selection and to build an explicit dynamical model. Our method ranked 2nd out of 22 in the DREAM3 100-gene in silico networks challenge. Mixed-CLR and Inferelator 1.0 are complementary, demonstrating a large performance gain relative to any single tested method, with precision being especially high at low recall values. Partitioning the provided data set into four groups (knock-down, knock-out, time-series, and combined) revealed that using comprehensive knock-out data alone provides optimal performance. Inferelator 1.0 proved particularly powerful at resolving the directionality of regulatory interactions, i.e. "who regulates who" (approximately of identified true positives were correctly resolved). Performance drops for high in-degree genes, i.e. as the number of regulators per target gene increases, but not with out-degree, i.e. performance is not affected by the presence of regulatory hubs.


Persistent dysfunction of regenerated endothelium after balloon angioplasty of rabbit iliac artery.
This study investigated the vasodilator function of endothelium that regenerated after balloon angioplasty and the relation of this function to the extent of vascular injury and to subsequent intimal proliferation. Balloon angioplasty was performed in the left iliac artery of 47 New Zealand White rabbits. Vascular responses were examined in vitro 2 and 4 weeks after a "severe" injury (3.0-mm balloon) or a "moderate" injury (2.5-mm balloon). Both degrees of balloon injury caused complete endothelial denudation. Endothelial regrowth 2 weeks after either injury was confirmed histologically. Although the regenerated cells had irregular sizes and polygonal shapes and lacked the typical alignment in the direction of blood flow, immunocytochemical staining for factor VIII-related antigen identified these cells as endothelium. To study the vasodilator function of regenerated endothelium, rings of balloon-injured and control (contralateral) iliac arteries were suspended in organ chambers for recording of isometric force. Endothelium-dependent relaxation of balloon-injured vessels to acetylcholine and to the calcium ionophore A23187 were reduced at 2 and at 4 weeks after severe injury. After moderate injury, endothelium-dependent relaxations to these agents were reduced at 2 weeks but had normalized by 4 weeks. Endothelium-independent relaxation to sodium nitroprusside, however, was preserved in all study groups. Morphometric analysis revealed an inverse correlation between the degree of intimal thickening and maximal relaxation to acetylcholine (r = 0.45, p less than 0.01). Thus, there is a persistent attenuation of receptor- and nonreceptor-mediated endothelium-dependent relaxations after arterial injury. The regenerated cells have an altered morphological appearance, but staining for factor VIII-related antigen confirms their endothelial origin. The degree and duration of endothelial dysfunction depends on the severity of the initial injury and is related to the extent of intimal thickness.


Secondhand tobacco smoke in bars and restaurants in Santiago, Chile: evaluation of partial smoking ban legislation in public places.
To compare air nicotine concentrations according to the smoking policy selected by bars/restaurants in Santiago, Chile before and after the enactment of partial smoking ban legislation in 2007 (establishments could be smoke free, have segregated (mixed) smoking and non-smoking areas, or allow smoking in all areas). The study measured air nicotine concentrations over 7 days to characterise secondhand smoke exposure in 30 bars/restaurants in 2008. Owner/manager interviews and physical inspections were conducted. Median IQR air nicotine concentrations measured in all venues were 4.38 (0.61-13.62) μg/m(3). Air nicotine concentrations were higher in bars (median 7.22, IQR 2.48-15.64 μg/m(3)) compared to restaurants (1.12, 0.15-9.22 μg/m(3)). By smoking status, nicotine concentrations were higher in smoking venues (13.46, 5.31-16.87 μg/m(3)), followed by smoking areas in mixed venues (9.22, 5.09-14.90 μg/m(3)) and non-smoking areas in mixed venues (0.99, 0.19-1.27 μg/m(3)). Air nicotine concentrations were markedly lower in smoke-free venues (0.12, 0.11-0.46 μg/m(3)). After adjustment for differences in volume and ventilation, air nicotine concentrations were 3.2, 35.5 and 56.2 times higher in non-smoking areas in mixed venues, smoking areas in mixed venues and smoking venues, respectively, compared to smoke-free venues. Exposure to secondhand smoke remains high in bars and restaurants in Santiago, Chile. These findings demonstrate that the partial smoking ban legislation enacted in Chile in 2007 provides no protection to employees working in those venues. Enacting a comprehensive smoke-free legislation which protects all people from exposure to secondhand smoke in all public places and workplaces is urgently needed.


HIV and housing assistance in four U.S. cities: variations in local experience.
This paper provides an account of how young, HIV-positive women manage their lives on limited budgets in four United States cities: New York City, New Orleans, Miami, and Chicago. The study findings elucidate city-to-city variability in housing assistance, and how this manifests in locality specific differences in the experience of HIV. Our research suggests that the receipt of housing assistance has ramifications for women's engagement in care, and for their health. Women not receiving aid often move frequently in and out of homelessness, or "double up" with others in complex household arrangements to share costs. Women with long-term housing assistance, while still struggling financially, possess a stable base from which to approach daily life and HIV care. This account suggests a need for empirical research assessing the impact of local variations in housing assistance on specific health outcomes for those with HIV. It also highlights the importance of understanding local contexts when designing housing interventions at both the individual and structural levels.


Risk factors of mortality and comparative in-vitro efficacy of anidulafungin, caspofungin, and micafungin for candidemia.
Although echinocandins have high in vitro antifungal efficacy according to prior reports, comparative studies on the clinical cure rates of anidulafungin, caspofungin, and micafungin in systemic candida infections have not yet been reported. Interpretation of clinical and microbiological responses to anidulafungin, caspofungin, and micafungin in 109 cases of candidemia was done according to the published criteria. The clinical cure rates between patients treated with echinocandins and patients treated with fluconazole were also compared. The minimal inhibitory concentrations (MICs) of anidulafungin, caspofungin, micafungin, and fluconazole for these 109 blood isolates of candida were determined with the Clinical and Laboratory Standards Institute M27-A reference microdilution method. Logistic regression with forward selection was used to determine the important factors of prognosis with variables such as age, underlying diseases, acute physiology and chronic health evaluation (APACHE) III score, persistent candidemia, and antimicrobial therapy. Among the 109 cases of candidemia, 70 were treated with echinocandins, azoles, or amphotericin B for ≥7 days. The clinical cure rate of cases treated with antifungal agents adequately (≥7 days) and inadequately (<7 days) were 44/70 (62.9%) and 4/39 (10.2%), respectively, with significant difference (p < 0.0001). Clinical cure rates of anidulafungin, caspofungin, micafungin, and fluconazole were 18/30 (60.0%), 8/9 (88.9%), 5/7 (71.4%), and 9/18 (50%), respectively. The difference in APACHE III score between treatment success and failure cases was significant. The MIC50/MIC90 of anidulafungin, caspofungin, and micafungin for all Candida spp. were 0.03/1 μg/mL, 0.06/0.5 μg/mL, and 0.008/1 μg/mL, respectively. Adequate antifungal therapy and APACHE III score are both independent factors affecting the clinical outcome. The clinical cure rate of the echinocandins group was higher than that of the fluconazole group without significant difference. Although caspofungin had the best clinical cure rate in this study, there was no significant difference between the clinical cure rates among these three echinocandins. All Candida spp. were susceptible in vitro to these three echinocandins.


Qilin is essential for cilia assembly and normal kidney development in zebrafish.
Defects in the cilium, a once thought vestigial organelle, have recently been implicated in many human diseases, including a number of cystic kidney diseases such as polycystic kidney disease (PKD), Bardet Bieldl Syndrome, and Meckel-Gruber Syndrome. In a forward genetic screen, qilin was identified as a novel gene important in the pathogenesis of kidney cysts in zebrafish. In this paper we characterized qilin(hi3959A) mutant's phenotypes in detail, investigated cilia formation in this mutant and performed structural and functional analysis of the Qilin protein. Results reveal Qilin's essential role in cilia assembly and maintenance in multiple organs, including the kidney, the lateral line organ, and the outer segment of the photoreceptor cell. In addition, rescue experiments suggest that defective pronephric cilia correlate with the formation of kidney cysts in qilin(hi3959A) mutants. Further, genetic analysis suggests that qilin interacts with multiple intraflagellar transport (IFT) complex B genes, which is supported by the striking phenotypic similarities between qilin(hi3959A) and IFT complex B mutants. Finally, through deletion analysis we provide evidence that the well-conserved N-terminus and the coiled-coil domain of Qilin are both essential and sufficient for its function. Taken all the observations together, we propose that Qilin acts in a similar role as IFT complex B proteins in cilia assembly, maintenance and kidney development in zebrafish.


Experimental verification of decoherence-free subspaces.
Using spontaneous parametric down-conversion, we produce polarization-entangled states of two photons and characterize them using two-photon tomography to measure the density matrix. A controllable decoherence is imposed on the states by passing the photons through thick, adjustable birefringent elements. When the system is subject to collective decoherence, one particular entangled state is seen to be decoherence-free, as predicted by theory. Such decoherence-free systems may have an important role for the future of quantum computation and information processing.


Close functional coupling between Ca2+ release-activated Ca2+ channels, arachidonic acid release, and leukotriene C4 secretion.
In non-excitable cells, one major route for Ca2+ influx is through store-operated Ca2+ channels in the plasma membrane. These channels are activated by the emptying of intracellular Ca2+ stores, and in some cell types, particularly of hemopoietic origin, store-operated influx occurs through Ca2+ release-activated Ca2+ (CRAC) channels. However, little is known about the downstream consequences of CRAC channel activation. Here, we report that Ca2+ entry through CRAC channels stimulates arachidonic acid production, whereas Ca2+ release from the stores is ineffective even though the latter evokes a robust intracellular Ca2+ signal. We find that arachidonic acid released by Ca2+ entering through CRAC channels is used to synthesize the potent paracrine proinflammatory signal leukotriene C4 (LTC4). Both pharmacological inhibitors of CRAC channels and mitochondrial depolarization, which impairs CRAC channel activity, suppress arachidonic acid release and LTC4 secretion. Thus, arachidonic acid release is preferentially stimulated by elevated subplasmalemmal Ca2+ levels due to open CRAC channels, suggesting that the enzyme is located close to the CRAC channels. Our results also identify a novel role for CRAC channels, namely the activation of a downstream signal transduction pathway resulting in the secretion of LTC4. Finally, mitochondria are key determinants of the generation of both intracellular (arachidonic acid) and paracrine (LTC4) signals through their effects on CRAC channel activity.


The use of memorised verbal scripts in the rehabilitation of action disorganisation syndrome.
We report data on the rehabilitation of action disorganisation syndrome (ADS). Although prior attempts to rehabilitate everyday actions in our patient, FK, had proved unsuccessful, we report positive results from using a verbalisation strategy. FK was taught a poem based on the steps involved in making a cup of tea. Following training, the everyday action was performed more successfully than prior to training, with the order of the actions in particular being improved when the poem was applied. In addition, there was evidence of error monitoring being carried out contingent on the verbalisation strategy. Across training sessions FK also became more likely to apply the poem and to perform the actions without prompting. However, there was relatively weak training effects across sessions, and the beneficial effects did not transfer to new tasks or to the same task with a different key object. The utility of the approach for severe cases of ADS is discussed.


Coronary artery disease in patients with dementia.
Our population is ageing. The prevalence of dementia is increasing as the population ages. Dementia is known to share many common risk factors with coronary artery disease including age, genetics, smoking, the components of the metabolic syndrome and inflammation. Despite the growing ageing population with dementia, there is underutilization of optimal care (pharmacotherapy and interventional procedures) in this cohort. Given common risk factors and potential benefit, patients with cognitive impairment and dementia should be offered contemporary care. However, further research evaluating optimal care in this patient cohort is warranted.


Auditory short-term memory capacity correlates with gray matter density in the left posterior STS in cognitively normal and dyslexic adults.
A central feature of auditory STM is its item-limited processing capacity. We investigated whether auditory STM capacity correlated with regional gray and white matter in the structural MRI images from 74 healthy adults, 40 of whom had a prior diagnosis of developmental dyslexia whereas 34 had no history of any cognitive impairment. Using whole-brain statistics, we identified a region in the left posterior STS where gray matter density was positively correlated with forward digit span, backward digit span, and performance on a "spoonerisms" task that required both auditory STM and phoneme manipulation. Across tasks and participant groups, the correlation was highly significant even when variance related to reading and auditory nonword repetition was factored out. Although the dyslexics had poorer phonological skills, the effect of auditory STM capacity in the left STS was the same as in the cognitively normal group. We also illustrate that the anatomical location of this effect is in proximity to a lesion site recently associated with reduced auditory STM capacity in patients with stroke damage. This result, therefore, indicates that gray matter density in the posterior STS predicts auditory STM capacity in the healthy and damaged brain. In conclusion, we suggest that our present findings are consistent with the view that there is an overlap between the mechanisms that support language processing and auditory STM.


Factors associated with early opioid dispensing compared with NSAID and muscle relaxant dispensing after a work-related low back injury.
The objective of this historical cohort study was to determine the claimant and prescriber factors associated with receiving opioids at first postinjury dispense compared with non-steroidal anti-inflammatory drugs (NSAIDs) and skeletal muscle relaxants (SMRs) in a sample of workers' compensation claimants with low back pain (LBP) claims between 1998 and 2009 in British Columbia, Canada. Administrative workers' compensation, prescription and healthcare data were linked. The association between claimant factors (sociodemographics, occupation, diagnosis, comorbidities, pre-injury prescriptions and healthcare) and prescriber factors (sex, birth year, specialty) with drug class(es) at first dispense (opioids vs NSAIDs/SMRs) was examined with multilevel multinomial logistic regression. Increasing days supplied with opioids in the previous year was associated with increased odds of receiving opioids only (1-14 days OR 1.62, 95% CI 1.51 to 1.75; ≥15 days OR 5.12, 95% CI 4.65 to 5.64) and opioids with NSAIDs/SMRs (1-14 days OR 1.49, 95% CI 1.39 to 1.60; ≥15 days OR 2.82, 95% CI 2.56 to 3.12). Other significant claimant factors included: pre-injury dispenses for NSAIDs, SMRs, antidepressants, anticonvulsants and sedative-hypnotics/anxiolytics; International Statistical Classification of Diseases and Related Health Problems, 9th Revision diagnosis; various pre-existing comorbidities; prior physician visits and hospitalisations; and year of injury, age, sex, health authority and occupation. Prescribers accounted for 25%-36% of the variability in the drug class(es) received, but prescriber sex, specialty and birth year did not explain observed between-prescriber variation. During this period in the opioid crisis, early postinjury dispensing was multifactorial, with several claimant factors associated with receiving opioids at first prescription. Prescriber variation in drug class choice appears particularly important, but was not explained by basic prescriber characteristics.


A Probabilistic and Highly Efficient Topology Control Algorithm for Underwater Cooperating AUV Networks.
The aim of the Smart and Networking Underwater Robots in Cooperation Meshes (SWARMs) project is to make autonomous underwater vehicles (AUVs), remote operated vehicles (ROVs) and unmanned surface vehicles (USVs) more accessible and useful. To achieve cooperation and communication between different AUVs, these must be able to exchange messages, so an efficient and reliable communication network is necessary for SWARMs. In order to provide an efficient and reliable communication network for mission execution, one of the important and necessary issues is the topology control of the network of AUVs that are cooperating underwater. However, due to the specific properties of an underwater AUV cooperation network, such as the high mobility of AUVs, large transmission delays, low bandwidth, etc., the traditional topology control algorithms primarily designed for terrestrial wireless sensor networks cannot be used directly in the underwater environment. Moreover, these algorithms, in which the nodes adjust their transmission power once the current transmission power does not equal an optimal one, are costly in an underwater cooperating AUV network. Considering these facts, in this paper, we propose a Probabilistic Topology Control (PTC) algorithm for an underwater cooperating AUV network. In PTC, when the transmission power of an AUV is not equal to the optimal transmission power, then whether the transmission power needs to be adjusted or not will be determined based on the AUV's parameters. Each AUV determines their own transmission power adjustment probability based on the parameter deviations. The larger the deviation, the higher the transmission power adjustment probability is, and vice versa. For evaluating the performance of PTC, we combine the PTC algorithm with the Fuzzy logic Topology Control (FTC) algorithm and compare the performance of these two algorithms. The simulation results have demonstrated that the PTC is efficient at reducing the transmission power adjustment ratio while improving the network performance.


Grazing of the copepod Diaptomus connexus on purple sulphur bacteria in a meromictic salt lake.
A meromictic lake ecosystem (Mahoney Lake, BC, Canada) was investigated to elucidate the significance of chemocline bacteria in the total carbon cycle under natural conditions. In this lake, primary production by oxygenic phototrophs was insufficient to support the observed net secondary production of the calanoid copepod Diaptomus connexus and the rotifer Brachionus plicatilis, indicating the presence of additional food sources for consumers. Mahoney Lake harbours the densest population of phototrophic sulphur bacteria ever reported in a natural body of water. This layer is located at the interface between oxic and anoxic water layers and is dominated by the purple sulphur bacterium Amoebobacter purpureus. The transfer rates of A. purpureus carbon to D. connexus determined in stratified mesocosms were very low (0.71 ngC copepod(-1) day(-1)) and accounted for only 0.6% of the observed net biomass increase in the zooplankter. Stable stratification within the mesocosms prevented an upwelling of A. purpureus into the oxic part. However, measurements of carbon fluxes, infrared fluorescence microscopy and stable carbon analysis provided cumulative evidence that, under in situ conditions, the cell carbon of purple sulphur bacteria indeed enters the aerobic food chain via the grazing activity of D. connexus. Based on a two-source isotopic mixing model, A. purpureus represents at least 75-85% of the diet of D. connexus. Autumnal upwelling into oxic water layers and aggregation of A. purpureus cells appear to be the main factors determining the high carbon flux from purple sulphur bacteria to zooplankton under natural conditions, and most probably also play a key role in other aquatic ecosystems. Through this pathway, over 53% of the reduced organic matter of purple sulphur bacteria trapped in anoxic bottom waters is returned to the oxic realm.


[Proposed UNGASS indicators and the monitoring of the AIDS epidemic in Brazil].
The objective of this study was to analyze, on the national level, the process of monitoring the proposed UNGASS indicators through the use of the Brazilian National Program for STD/AIDS indicators. Two groups of proposed indicators were analyzed in 2002 and 2005 respectively, as part of the monitoring of the progress of the UNGASS Declaration of Commitment. The availability of information and limitations in calculating the proposed indicators in Brazil were analyzed and the appropriateness of the indicators for monitoring the epidemic in Brazil was discussed. Of the 13 quantitative indicators originally proposed by UNGASS, five were not included in the National Program. One was not included due to its qualitative nature. Two of the indicators were considered to be of little use and two were not included due to the lack of available data needed for their calculation. As the epidemic in Brazil is characterized as being concentrated, within the second group of proposed UNGASS indicators those that refer to the accompaniment of epidemic among high-risk population groups were prioritized. The study highlights that the National Program concentrates its efforts in the development, adaptation, and sharing of sampling methodologies for hard to reach populations. Such activities are geared towards estimating the size of vulnerable population groups, as well as obtaining more information regarding their knowledge, attitudes, and practices. The study concludes that by creating the possibility of international comparisons between advances achieved, the proposal of supranational indicators stimulates countries to discuss and make their construction viable. In a complementary way, the national monitoring systems should focus on program improvement by covering areas that permit the evaluation of specific control and intervention actions.


Multi-atlas image registration of clinical data with automated quality assessment using ventricle segmentation.
Registration is a core component of many imaging pipelines. In case of clinical scans, with lower resolution and sometimes substantial motion artifacts, registration can produce poor results. Visual assessment of registration quality in large clinical datasets is inefficient. In this work, we propose to automatically assess the quality of registration to an atlas in clinical FLAIR MRI scans of the brain. The method consists of automatically segmenting the ventricles of a given scan using a neural network, and comparing the segmentation to the atlas ventricles propagated to image space. We used the proposed method to improve clinical image registration to a general atlas by computing multiple registrations - one directly to the general atlas and others via different age-specific atlases - and then selecting the registration that yielded the highest ventricle overlap. Finally, as an example application of the complete pipeline, a voxelwise map of white matter hyperintensity burden was computed using only the scans with registration quality above a predefined threshold. Methods were evaluated in a single-site dataset of more than 1000 scans, as well as a multi-center dataset comprising 142 clinical scans from 12 sites. The automated ventricle segmentation reached a Dice coefficient with manual annotations of 0.89 in the single-site dataset, and 0.83 in the multi-center dataset. Registration via age-specific atlases could improve ventricle overlap compared to a direct registration to the general atlas (Dice similarity coefficient increase up to 0.15). Experiments also showed that selecting scans with the registration quality assessment method could improve the quality of average maps of white matter hyperintensity burden, instead of using all scans for the computation of the white matter hyperintensity map. In this work, we demonstrated the utility of an automated tool for assessing image registration quality in clinical scans. This image quality assessment step could ultimately assist in the translation of automated neuroimaging pipelines to the clinic.


The role of carbon dioxide therapy in the treatment of chronic wounds.
A wound is defined as chronic when it does not heal according to the normal repair times and mechanisms. This particular condition may be principally due to local hypoxia. Carbon dioxide (CO(2)) therapy refers to the transcutaneous or subcutaneous administration of CO(2) for therapeutical effects on both microcirculation and tissue oxygenation. In this study, we report the clinical and instrumental results of the application of CO(2) in the therapy of chronic wounds. The study included 70 patients affected by chronic ulcers. The patients were selected by aetiology and wound extension and equally divided into two homogeneous groups. In group A, CO(2) therapy was used in addition to the routine methods of treatment for such lesions (surgical and/or chemical debridement, advanced dressings according to the features of each lesion). In group B, patients were treated using routine methods alone. Both groups underwent to instrumental (laser doppler flow, measurement of TcPO(2)), clinical and photographic evaluation. In the group that underwent subcutaneous treatment with CO(2) therapy, the results highlighted a significant increase in tissue oxygenation values, which was confirmed by greater progress of the lesions in terms of both healing and reduction of the injured area. Considering the safety, efficacy and reliability of this method, even if further studies are necessary, we believe that it is useful to include subcutaneous carbon dioxide therapy in the treatment of wounds involving hypoxia-related damage.


The Andersen aerobic fitness test: reliability and validity in 10-year-old children.
High aerobic fitness is consistently associated with a favorable metabolic risk profile in children. Direct measurement of peak oxygen consumption (VO2peak) is often not feasible, thus indirect tests such as the Andersen test are required in many settings. The present study seeks to determine the reliability and validity of the Andersen test in 10-year-old children. A total of 118 10-year-old children (67 boys and 51 girls) were recruited from one school and performed four VO2peak tests over three weeks: three Andersen tests (indirect) and one continuous progressive treadmill test (direct). Of these, 104 children provided valid data on all Andersen tests and 103 children also provided valid data on the direct treadmill test. Reliability and validity were assessed using Bland Altman plots and linear regression analysis. Bias (mean change) and random error (limits of agreement) were 26.7±125.2 m for test 2 vs. test 1 (p<.001 for mean difference) and 3.9±88.8 m for test 3 vs. test 2 (p = .514 for mean difference). The equation to estimate VO2peak suggested by Andersen et al. (2008) showed a poor fit in the present sample; thus, we suggest a new equation: VO2peak = 23.262+0.050*Andersen distance -3.858*gender -0.376*body weight (R2 = 0.61, standard error of the estimate = 5.69, p<.001, boys = 0, girls = 1). The Andersen test provided reliable and valid data on a group level. However, a substantial degree of individual variability was found for estimates of VO2peak. Researchers should be aware of the amount of noise in indirect tests that estimate aerobic fitness.