The social determinants of health and health service access: an in depth study in four poor communities in Phnom Penh Cambodia.
Increasing urbanization and population density, and persisting inequities in health outcomes across socioeconomic groupings have raised concerns internationally regarding the health of the urban poor. These concerns are also evident in Cambodia, which prompted the design of a study to identify and describe the main barriers to access to health services by the poor in the capital city, Phnom Penh. SOURCES AND METHODS: Main sources of data were through a household survey, followed by in-depth qualitative interviews with mothers, local authorities and health centre workers in four very poor communities in Phnom Penh. Despite low incomes and education levels, the study communities have moderate levels of access to services for curative and preventive care. However, qualitative findings demonstrate that households contextualize poor health and health access in terms of their daily living conditions, particularly in relation to environmental conditions and social insecurity. The interactions of low education, poor living conditions and high food costs in the context of low and irregular incomes reinforce a pattern of "living from moment to moment" and results in a cycle of disadvantage and ill health in these communities. There were three main factors that put poor communities at a health disadvantage; these are the everyday living conditions of communities, social and economic inequality and the extent to which a society assesses and acts on inequities in their health care access. In order to improve access to health and health services for the urban poor, expansion of public health functions and capacities will be required, including building partnerships between health providers, municipal authorities and civil society.


A Call for Better Data on Prevalence and Health Surveillance of People With Intellectual and Developmental Disabilities.
The U.S. approach to the health of people with intellectual and developmental disabilities (IDD) is fraught with paradox. The health of this population has been of longstanding concern, yet we understand their health less well than many other groups. The U.S. spends much more per person on the well-being of people with IDD compared to the general population, yet the outcomes of those expenditures are disappointing and include significant preventable health disparities. Even as expectations for people with IDD have changed to include better health and greater participation in their communities, eligibility for services that support these outcomes is rooted in expectations of dependence and poverty. This article is a call for better data that considers a series of questions to provide context for understanding the need and directions for better health surveillance of people with IDD.


Adipose tissue omega-3 and omega-6 fatty acid content and breast cancer in the EURAMIC study. European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Breast Cancer.
The fatty acid content of adipose tissue in postmenopausal breast cancer cases and controls from five European countries in the European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Cancer (EURAMIC) breast cancer study (1991-1992) was used to explore the hypothesis that fatty acids of the omega-3 family inhibit breast cancer and that the degree of inhibition depends on background levels of omega-6 polyunsaturates. Considered in isolation, the level of omega-3 or omega-6 fat in adipose tissue displayed little consistent association with breast cancer across study centers. The ratio of long-chain omega-3 fatty acids to total omega-6 fat showed an inverse association with breast cancer in four of five centers. In Malaga, Spain, the odds ratio for the highest tertile relative to the lowest reached 0.32 (95% confidence interval 0.13-0.82). In this center, total omega-6 fatty acid was strongly associated with breast cancer. With all centers pooled, the odds ratio for long-chain omega-3 to total omega-6 reached 0.80 for the second tertile and 0.65 for the third tertile, a downward trend bordering on statistical significance (p for trend = 0.055). While not definitive, these results provide evidence for the hypothesis that the balance between omega-3 and omega-6 fat may play a role in breast cancer.


Patients' and health care professionals' perceptions of blood transfusion: a systematic review.
Blood transfusions are frequently prescribed for acute and chronic conditions; however, the extent to which patients' and health care professionals' (HCPs') perceptions of transfusion have been investigated is unclear. Patients' treatment perceptions influence how patients cope with illnesses or symptoms. HCPs' perceptions may influence treatment decision making. This was a systematic review of studies post-1984 reporting adult patients' and HCPs' perceptions of blood transfusion. Seven databases were searched using a three-domain search strategy capturing synonyms relating to: 1) blood transfusion, 2) perceptions, and 3) participant group (patients or HCPs). Study and sample characteristics were extracted and narratively summarized. Reported perceptions were extracted and synthesized using inductive qualitative methods to identify key themes. Thirty-two studies were included: 14 investigated patients' perceptions and 18 HCPs' perceptions. Surgical patients were the highest represented patient group. HCPs were from a wide range of professions. Transfusions were perceived by patients and HCPs as being of low-to-moderate risk. Risk and negative emotions were perceived to influence preference for alternatives. Five themes emerged from the synthesis, classified as Safety/risk, Negative emotions, Alternatives (e.g., autologous, monitoring), Health benefits, and Decision making. "Safety/risk" and "Negative emotions" were most frequently investigated over time, yet periods of research inactivity are apparent. The literature has identified themes on how transfusions are perceived by patients and HCPs, which overlap with recognized discussion points for transfusion specialists. These themes may help HCPs when educating patients about transfusion or consenting patients. Theory-based qualitative methods may add an important dimension to this work.


Golgi and vacuolar membrane proteins reach the vacuole in vps1 mutant yeast cells via the plasma membrane.
The Vps1 protein of Saccharomyces cerevisiae is an 80-kD GTPase associated with the Golgi apparatus. Vps1p appears to play a direct role in the retention of late Golgi membrane proteins, which are mislocalized to the vacuolar membrane in its absence. The pathway by which late Golgi and vacuolar membrane proteins reach the vacuole in vps1 delta mutants was investigated by analyzing transport of these proteins in vps1 delta cells that also contained temperature sensitive mutations in either the SEC4 or END4 genes, which are required for a late step in secretion and the internalization step of endocytosis, respectively. Not only was vacuolar transport of a Golgi membrane protein blocked in the vps1 delta sec4-ts and vps1 delta end4-ts double mutant cells at the non-permissive temperature but vacuolar delivery of the vacuolar membrane protein, alkaline phosphatase was also blocked in these cells. Moreover, both proteins expressed in the vps1 delta end4-ts cells at the elevated temperature could be detected on the plasma membrane by a protease digestion assay indicating that these proteins are transported to the vacuole via the plasma membrane in vps1 mutant cells. These data strongly suggest that a loss of Vps1p function causes all membrane traffic departing from the late Golgi normally destined for the prevacuolar compartment to instead be diverted to the plasma membrane. We propose a model in which Vps1p is required for formation of vesicles from the late Golgi apparatus that carry vacuolar and Golgi membrane proteins bound for the prevacuolar compartment.


Scientific writing: a randomized controlled trial comparing standard and on-line instruction.
Writing plays a central role in the communication of scientific ideas and is therefore a key aspect in researcher education, ultimately determining the success and long-term sustainability of their careers. Despite the growing popularity of e-learning, we are not aware of any existing study comparing on-line vs. traditional classroom-based methods for teaching scientific writing. Forty eight participants from a medical, nursing and physiotherapy background from US and Brazil were randomly assigned to two groups (n = 24 per group): An on-line writing workshop group (on-line group), in which participants used virtual communication, google docs and standard writing templates, and a standard writing guidance training (standard group) where participants received standard instruction without the aid of virtual communication and writing templates. Two outcomes, manuscript quality was assessed using the scores obtained in Six subgroup analysis scale as the primary outcome measure, and satisfaction scores with Likert scale were evaluated. To control for observer variability, inter-observer reliability was assessed using Fleiss's kappa. A post-hoc analysis comparing rates of communication between mentors and participants was performed. Nonparametric tests were used to assess intervention efficacy. Excellent inter-observer reliability among three reviewers was found, with an Intraclass Correlation Coefficient (ICC) agreement = 0.931882 and ICC consistency = 0.932485. On-line group had better overall manuscript quality (p = 0.0017, SSQSavg score 75.3 +/- 14.21, ranging from 37 to 94) compared to the standard group (47.27 +/- 14.64, ranging from 20 to 72). Participant satisfaction was higher in the on-line group (4.3 +/- 0.73) compared to the standard group (3.09 +/- 1.11) (p = 0.001). The standard group also had fewer communication events compared to the on-line group (0.91 +/- 0.81 vs. 2.05 +/- 1.23; p = 0.0219). Our protocol for on-line scientific writing instruction is better than standard face-to-face instruction in terms of writing quality and student satisfaction. Future studies should evaluate the protocol efficacy in larger longitudinal cohorts involving participants from different languages.


ACR Appropriateness Criteria Crohn Disease.
Crohn disease is a chronic inflammatory disorder involving the gastrointestinal tract, characterized by episodic flares and times of remission. Underlying structural damage occurs progressively, with recurrent bouts of inflammation. The diagnosis and management of this disease process is dependent on several clinical, laboratory, imaging, endoscopic, and histologic factors. In recent years, with the maturation of CT enterography, and MR enterography, imaging has played an increasingly important role in relation to Crohn Disease. In addition to these specialized examination modalities, ultrasound and routine CT have potential uses. Fluoroscopy, radiography, and nuclear medicine may be less beneficial depending on the clinical scenario. The imaging modality best suited to evaluating this disease may change, depending on the target population, severity of presentation, and specific clinical situation. This document presents seven clinical scenarios (variants) in both the adult and pediatric populations and rates the appropriateness of the available imaging options. They are summarized in a consolidated table, and the underlying rationale and supporting literature are presented in the accompanying narrative. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.


Group Size Predicts Social but Not Nonsocial Cognition in Lemurs.
The social intelligence hypothesis suggests that living in large social networks was the primary selective pressure for the evolution of complex cognition in primates. This hypothesis is supported by comparative studies demonstrating a positive relationship between social group size and relative brain size across primates. However, the relationship between brain size and cognition remains equivocal. Moreover, there have been no experimental studies directly testing the association between group size and cognition across primates. We tested the social intelligence hypothesis by comparing 6 primate species (total N = 96) characterized by different group sizes on two cognitive tasks. Here, we show that a species' typical social group size predicts performance on cognitive measures of social cognition, but not a nonsocial measure of inhibitory control. We also show that a species' mean brain size (in absolute or relative terms) does not predict performance on either task in these species. These data provide evidence for a relationship between group size and social cognition in primates, and reveal the potential for cognitive evolution without concomitant changes in brain size. Furthermore our results underscore the need for more empirical studies of animal cognition, which have the power to reveal species differences in cognition not detectable by proxy variables, such as brain size.


Use of Designated Nurse PICC Teams and CLABSI Prevention Practices Among U.S. Hospitals: A Survey-Based Study.
The use of peripherally inserted central catheters (PICCs) has increased substantially within hospitals during the past several years. Yet, the prevalence and practices of designated nurse PICC teams (i.e., specially trained nurses who are responsible for PICC insertions at a hospital) are unknown. We, therefore, identified the prevalence of and factors associated with having a designated nurse PICC team among U.S. acute care hospitals. We conducted a survey of infection preventionists at a random sample of U.S. hospitals in May 2013, which asked about personnel who insert PICCs and the use of practices to prevent device-associated infections, including central line-associated bloodstream infection. We compared practice use between hospitals that have a designated nurse PICC team versus those that do not. Survey response rate was 70% (403/575). According to the respondents, nurse PICC teams inserted PICCs in more than 60% of U.S. hospitals in 2013. Moreover, certain practices to prevent central line-associated bloodstream infection, including maximum sterile barrier precautions (93% versus 88%, P = 0.06), chlorhexidine gluconate for insertion site antisepsis (96% versus 87%, P = .003) and facility-wide insertion checklists (95% versus 87%, P = 0.02) were regularly used by a higher percentage of hospitals with nurse PICC teams compared with those without. These data suggest that nurse PICC teams play an integral role in PICC use at many hospitals and that use of such teams may promote key practices to prevent complications. Better understanding of the role, composition, and practice of such teams is an important area for future study.


Engineered Membranes for Residual Cell Trapping on Microfluidic Blood Plasma Separation Systems: A Comparison between Porous and Nanofibrous Membranes.
Blood-based clinical diagnostics require challenging limit-of-detection for low abundance, circulating molecules in plasma. Micro-scale blood plasma separation (BPS) has achieved remarkable results in terms of plasma yield or purity, but rarely achieving both at the same time. Here, we proposed the first use of electrospun polylactic-acid (PLA) membranes as filters to remove residual cell population from continuous hydrodynamic-BPS devices. The membranes hydrophilicity was improved by adopting a wet chemistry approach via surface aminolysis as demonstrated through Fourier Transform Infrared Spectroscopy and Water Contact Angle analysis. The usability of PLA-membranes was assessed through degradation measurements at extreme pH values. Plasma purity and hemolysis were evaluated on plasma samples with residual red blood cell content (1, 3, 5% hematocrit) corresponding to output from existing hydrodynamic BPS systems. Commercially available membranes for BPS were used as benchmark. Results highlighted that the electrospun membranes are suitable for downstream residual cell removal from blood, permitting the collection of up to 2 mL of pure and low-hemolyzed plasma. Fluorometric DNA quantification revealed that electrospun membranes did not significantly affect the concentration of circulating DNA. PLA-based electrospun membranes can be combined with hydrodynamic BPS in order to achieve high volume plasma separation at over 99% plasma purity.


Integration of a virus membrane protein into the lipid bilayer of target cells as a prerequisite for immune cytolysis. Specific cytolysis after virosome-target cell fusion.
Structural requirements for membrane antigens on target cells to mediate immune cytolysis were studied in a model system with purified membrane proteins from Semliki Forest virus (SFV). These SFV spike proteins were isolated in the form of detergent- and lipid-free protein micelles (29S complexes) or, after reconstitution into lipid vesicles, in the form of virosomes. Both the 29S complexes and the virosomes were found to bind well to murine tumor cells (P815 or Eb). When these cells, however, were used as target cells in complement-dependent lysis or in antibody-dependent cell- mediated cytotoxicity assays in the presence of anti-SFV serum, they were not lysed, although they effectively bound the antibody and consumed complement. The same tumor cells infected with SFV served as positive controls in both assays. Different results were obtained when inactivated Sendai virus was added as a fusion reagent to the cells coated with either virosomes or 29S complexes. Under these conditions the virosome-coated cells became susceptible to SFV- specific lysis, whereas the 29S complex-coated cells remained resistant. Evidence that the susceptibility to lysis ofvirosome-coated cells was dependent on active fusion and, therefore, integration of the viral antigens into the lipid bilayer of the target cells was derived from control experiments with enzyme-treated Sendai virus preparations. The 29S complexes and the virosomes partially and selectively blocked the target cell lysis by anti-H-2 sera but not by anti-non-H-2 sera confirming our previous finding that major histocompatibility antigens serve as receptors for SFV. The general significance of these findings for mechanisms of immune cytolysis is dicussed.


The effect of nesiritide on renal function and other clinical parameters in patients with decompensated heart failure and preserved ejection fraction.
The role of nesiritide in patients with decompensated heart failure with preserved ejection fraction (dHFpEF) has not been previously studied. In this investigation, the authors retrospectively analyzed the effect of nesiritide on renal function and clinical outcomes in patients admitted with dHFpEF. Of the 658 patients included, 328 were treated with nesiritide while 330 patients were treated with standard diuretic therapy. In both the nesiritide and no nesiritide groups, there was a significant change in mean glomerular filtration rate (GFR) and creatinine at 72 hours as well as at day of discharge (P<.001). This trend did not progress at 1 month in the nesiritide group, although it did in the no nesiritide group. At 1 month after therapy, however, there was a significant difference between the two groups in the mean change of GFR and creatinine (P<.001). There was no significant difference in >25% decrease of GFR anytime through day 30 (25% vs 29.69%, P=.236) between the two groups. On multivariate analysis, nesiritide was an important predictor of renal function at 1 month (P<.05). Thus, nesiritide can be administered safely without negatively impacting long-term renal function in patients admitted with dHFpEF.


Nonlinear distortion of optical pulses by self-produced free carriers in short or highly lossy silicon-based waveguides.
An explicit analytical solution for the asymmetric attenuation of optical pulses by self-produced free carriers in silicon waveguides is derived. It allows us to quantify the pulse distortion and to calculate explicitly the free-carrier density and the nonlinear phase shifts caused by the Kerr effect and by free-carrier refraction. We show that omitting two-photon absorption (TPA) as a cause of attenuation and accounting only for free-carrier absorption (FCA) as done in the derivation appropriately models the pulse propagation in short or highly lossy silicon-based waveguides such as plasmonic waveguides with particular use for high-energy input pulses. Moreover, this formulation is also aimed at serving as a tool in discussing the role of FCA in its competition with TPA when used for continuum generation or pulse compression in low-loss silicon waveguides. We show that sech-shaped intensity pulses maintain their shape independently of the intensity or pulse width and self-induced FCA may act as an ideal limiter on them. Pulse propagation under self-induced free-carrier absorption exhibits some features of superluminal propagation such as fast or even backward travelling. We find that input pulses need to have a sufficiently steep front slope to be compressible at all and illustrate this with the FCA-induced pulse broadening for Lorentzian-shaped input pulses.


Consumption and exposure assessment to toothpaste in French families.
The aim of the study was to assess the consumption and the exposure to toothpaste in French families leaving the consumers free to use their own product at home according to their habits. Consumption data were collected on 104 families. 206 adults (103 women and 103 men) and 195 children aged 2-17 participated in the study. Differences in toothpaste consumption depending on gender and on age were highlighted. As an example, frequency data were higher in adult women (2.0 day-1 on average) than in adult men (1.8 day-1 on average); amount per use data were higher in adult men (1.2 g on average) than in adult women (0.9 g on average). The frequency of use and the amount of toothpaste used per application increased with age. The exposure to toothpaste decreased with age. Children aged 2-6 were the most exposed to toothpaste with a P95 value equal to 8.2 mg/kg bw/day. Adult's P95 exposure value was equal to 2.8 mg/kg bw/day. Exposure values were in the same order of magnitude for both genders in children and in adults. These new data will be useful for safety assessors, especially children data which remain scarce.


Emergent Decompressive Craniectomy in Patients with Fixed DilatedPupils; A Single Center Experience.
This is a case series which report the clinical results of decompressive craniectomy in 4 patients with dilated pupils secondary to traumatic brain injury and postoperative edema. Between 2011 and 2012, four patients, 3 males and 1 female, aged between 35 and 64 with mean age of 50.1±8.9 years, underwent decompressive craniectomy due to brain traumatic edema. The follow up period ranged between 1 to 6 months. All patients had Glasgow coma score (GCS) of 3-4 at admission, and the duration of pupils being mydriatic was less than 20 minutes before the operation. All patients had moderate disability with GCS of 4 after the operation. Decompressive craniectomy can be a life-saving procedure which provides a better outcome in patients with dilated pupils secondary to brain trauma injury and postoperative edema with timing of less than 20 minutes. However, the small number of the patients in this study is the main limitation to the accuracy of the results, and more studies with larger number of patients are warranted to evaluate the efficiency of decompressive craniectomy in patients with dilated pupils.


On benzo[b][1,4]diazepinium-olates, -thiolates and -carboxylates as anti-Hückel mesomeric betaines.
2,3-Diaminophenol 4, 3,4-diaminophenol 5, 4-methoxy-1,2-diaminobenzene 6, 3,4-diaminobenzenethiol 7, 2,3-diaminobenzoic acid 8, and 3,4-diaminobenzoic acid 9 were reacted with 2,4-pentanedione to yield the corresponding benzo[b][1,4]diazepinium salts, respectively. The hydroxy-benzo[b][1,4]diazepinium salts 17 and 18 do not form mesomeric betaines (MB) on deprotonation. Instead, they are converted into the diimines 24 and 25. By contrast, the 7-mercaptobenzo[b][1,4]diazepinium salt 20 yields the corresponding thiolate on increasing the pH of the solution. This MB, which possesses 4n pi-electrons, does not fit into the classification system of heterocyclic mesomeric betaines accepted today. Deprotonation of the betaine results in the formation of an instable anionic thiolate 31 which oxidizes immediately to the disulfide 32. The carboxy derivatives 21 and 22 readily form cross-conjugated mesomeric betaines. Whereas the diimine 34 proved to be instable, the sodium salt of the diimine 36 was unambiguously characterized. An X-ray single crystal analysis of 22 as its picrate is presented in order to gain additional insights into these 4n pi-electron systems.


Using the Theory of Planned Behavior to predict implementation of harm reduction strategies among MDMA/ecstasy users.
This prospective study was designed to test whether the variables proposed by the Theory of Planned Behavior (TPB) were associated with baseline intention to implement and subsequent use of 2 MDMA/ecstasy-specific harm reduction interventions: preloading/postloading and pill testing/pill checking. Using targeted Facebook advertisements, an international sample of 391 recreational ecstasy users were recruited to complete questionnaires assessing their ecstasy consumption history, and their attitudes, subjective norms, perceived behavioral control, habit strength (past strategy use), and intention to use these two strategies. Attitudes, subjective norms, and perceived behavioral control were significantly associated with baseline intention to preload/postload and pill test/pill check. Out of the 391 baseline participants, 100 completed the two-month follow-up assessment. Baseline habit strength and frequency of ecstasy consumption during the three months prior to baseline were the only significant predictors of how often participants used the preloading/postloading strategy during the follow-up. Baseline intention to pill test/pill check was the only significant predictor of how often participants used this strategy during the follow-up. These findings provide partial support for TPB variables as both correlates of baseline intention to implement and predictors of subsequent use of these two strategies. Future investigations could assess whether factors related to ecstasy consumption (e.g., subjective level of intoxication, craving, negative consequences following consumption), and environmental factors (e.g., accessibility and availability of harm reduction resources) improve the prediction of how often ecstasy users employ these and other harm reduction strategies. (PsycINFO Database Record


Farmyard point discharges and their influence on nutrient and labile carbon dynamics in a second order stream draining through a dairy unit.
Two small piped sources deriving from a single farmyard together with the receiving second order stream above and below the farmyard region were sampled over a two-year period. Although not measured directly, observations at the time of sampling suggested that maximum drain flow was about 2% of downstream base flow. Both point sources were flowing on each sampling occasion (~62) and usually had concentrations of phosphorus (P), nitrate (NO(3)-N) and biological oxygen demand (BOD) well above those from the upstream site. Individual sample concentrations ranged over more than two orders of magnitude for most determinants and a large proportion of the total P was present as soluble (inorganic and organic) and therefore labile forms. More than 70% of samples collected at the downstream site had concentrations that were >1.2 times those of the corresponding upstream site. On certain sampling occasions >80% of total dissolved phosphorus (TDP) and >90% of the BOD and NO(3) instantaneous load appeared to originate from the farmyard region with the composition of downstream samples being completely overwhelmed after the passage through the farmyard. Extrapolations using instantaneous loads suggest that the farmyard and adjacent areas contributed on average 25-30% of the total and dissolved annual downstream P load of 3 kg P ha(-1) and 1.7 kg P ha(-1), respectively. There was no clear relationship between the relative proportion of the contaminant loading originating from the farmyard region and hydrological events. This emphasises the potential localised significance that small, highly concentrated, continuous or semi-continuous farmyard sources can impact headwater streams during periods of low stream flow.


Large-scale excited-state calculation using dynamical polarizability evaluated by divide-and-conquer based coupled cluster linear response method.
This study attempted to propose an efficient scheme at the coupled cluster linear response (CCLR) level to perform large-scale excited-state calculations of not only local excitations but also nonlocal ones such as charge transfers and transitions between delocalized orbitals. Although standard applications of fragmentation techniques to the excited-state calculations brought about the limitations that could only deal with local excitations, this study solved the problem by evaluating the excited states as the poles of dynamical polarizability. Because such an approach previously succeeded at the time-dependent density functional theory level [H. Nakai and T. Yoshikawa, J. Chem. Phys. 146, 124123 (2017)], this study was considered as an extension to the CCLR level. To evaluate the dynamical polarizability at the CCLR level, we revisited three equivalent formulas, namely, coupled-perturbed self-consistent field (CPSCF), random phase approximation (RPA), and Green's function (GF). We further extended these formulas to the linear-scaling methods based on the divide-and-conquer (DC) technique. We implemented the CCLR with singles and doubles (CCSDLR) program for the six schemes, i.e., the standard and DC-type CPSCF, RPA, and GF. Illustrative applications of the present methods demonstrated the accuracy and efficiency. Although the standard three treatments could exactly reproduced the conventional frequency-domain CCSDLR results, their computational costs were commonly higher than that of the conventional ones due to large amount of computations for individual frequencies of the external electric field. The DC-type treatments, which approximately reproduced the conventional results, could achieve quasilinear scaling computational costs. Among them, DC-GF was found to exhibit the best performance.


A microfluidic platform for high-throughput multiplexed protein quantitation.
We present a high-throughput microfluidic platform capable of quantitating up to 384 biomarkers in 4 distinct samples by immunoassay. The microfluidic device contains 384 unit cells, which can be individually programmed with pairs of capture and detection antibody. Samples are quantitated in each unit cell by four independent MITOMI detection areas, allowing four samples to be analyzed in parallel for a total of 1,536 assays per device. We show that the device can be pre-assembled and stored for weeks at elevated temperature and we performed proof-of-concept experiments simultaneously quantitating IL-6, IL-1β, TNF-α, PSA, and GFP. Finally, we show that the platform can be used to identify functional antibody combinations by screening 64 antibody combinations requiring up to 384 unique assays per device.


Inherited Disorders of Neurotransmitters: Classification and Practical Approaches for Diagnosis and Treatment.
Neurotransmitter deficiencies are rare neurological disorders with clinical onset during childhood. The disorders are caused by genetic defects in the enzymes involved in synthesis, degradation, or transport of neurotransmitters or by defects in the cofactor biosynthesis such as tetrahydrobiopterin (BH4). With the newly described DNAJC12 deficiency, a chaperon-associated neurotransmitter disorder, the pathophysiological spectrum has been broadened. All deficiencies result in a lack of monoamine neurotransmitters, especially dopamine and its products, with a subset leading to decreased levels of serotonin. Symptoms can occur already in the neonatal period. Classical signs are hypotonia, movement disorders, autonomous dysregulations, and impaired development. Diagnosis depends on quantitative detection of neurotransmitters in cerebrospinal fluid, since peripheral markers in blood or urine are less reliable. Treatment is based on supplementation of the missing neurotransmitter precursors or restoring deficient cofactors for endogenous enzymatic synthesis. In recent years, knowledge about this orphan group of diseases increased substantially among clinicians. However, the difficult task of integrating clinical symptoms and laboratory values still leads to a critical delay in diagnosis and therapy for patients. This review aims at enhancing the understanding of neurotransmitter disorders and should help practicing clinicians to choose useful diagnostic steps on the way to a valid diagnosis.


Preclinical assessment of CNS drug action using eye movements in mice.
The drug development process for CNS indications is hampered by a paucity of preclinical tests that accurately predict drug efficacy in humans. Here, we show that a wide variety of CNS-active drugs induce characteristic alterations in visual stimulus-induced and/or spontaneous eye movements in mice. Active compounds included sedatives and antipsychotic, antidepressant, and antiseizure drugs as well as drugs of abuse, such as cocaine, morphine, and phencyclidine. The use of quantitative eye-movement analysis was demonstrated by comparing it with the commonly used rotarod test of motor coordination and by using eye movements to monitor pharmacokinetics, blood-brain barrier penetration, drug-receptor interactions, heavy metal toxicity, pharmacologic treatment in a model of schizophrenia, and degenerative CNS disease. We conclude that eye-movement analysis could complement existing animal tests to improve preclinical drug development.


Decision aid on radioactive iodine treatment for early stage papillary thyroid cancer--a randomized controlled trial.
Patients with early stage papillary thyroid carcinoma (PTC), are faced with the decision to either to accept or reject adjuvant radioactive iodine (RAI) treatment after thryroidectomy. This decision is often difficult because of conflicting reports of RAI treatment benefit and medical evidence uncertainty due to the lack of long-term randomized controlled trials. We report the protocol for a parallel, 2-arm, randomized trial comparing an intervention group exposed to a computerized decision aid (DA) relative to a control group receiving usual care. The DA explains the options of adjuvant radioactive iodine or no adjuvant radioactive iodine, as well as associated potential benefits, risks, and follow-up implications. Potentially eligible adult PTC patient participants will include: English-speaking individuals who have had recent thyroidectomy, and whose primary tumor was 1 to 4 cm in diameter, with no known metastases to lymph nodes or distant sites, with no other worrisome features, and who have not received RAI treatment for thyroid cancer. We will measure the effect of the DA on the following patient outcomes: a) knowledge about PTC and RAI treatment, b) decisional conflict, c) decisional regret, d) client satisfaction with information received about RAI treatment, and e) the final decision to accept or reject adjuvant RAI treatment and rationale. This trial will provide evidence of feasibility and efficacy of the use of a computerized DA in explaining complex issues relating to decision making about adjuvant RAI treatment in early stage PTC. Clinical Trials.gov Identifier: NCT01083550.


Regional lumbar motion and patient-rated outcomes: a secondary analysis of data from a randomized clinical trial.
The purpose of this study was to examine the relationship in change scores between regional lumbar motion and patient-rated pain of the previous week and back-related function in chronic low back pain patients enrolled in a randomized clinical trial and treated with either exercise therapy or spinal manipulation using 6 different motion parameters. Regional lumbar motions were sampled using a 6 degrees of freedom instrumented spatial linkage system in 199 participants at baseline and 12-week follow-up. The regional lumbar motion data were analyzed as a total cohort as well as relative to subgroup stratifications; back pain only vs back and leg pain, and treatment modality. For identifying clinically meaningful improvements in the measurements of back pain and back-related function, we used a 30% threshold. The relationship between change scores in patient-rated outcomes and objective measures of regional lumbar motion was found to be weak. In contrast, distribution of pain and treatment received affected associations between motion parameters and patient-rated outcomes. Thus, stronger correlation coefficients and significant differences between clinically relevant improved vs no clinical relevant change were found in some motion parameters in the subgroup with back pain only and the treatment group receiving spinal manipulation. Overall, changes in regional lumbar motion were poorly associated with patient-rated outcomes measured by back-related function and back pain intensity scores. However, associations between regional lumbar motion vs patient-rated pain and back-related function were different in relative subgroups (back pain only vs back and leg pain and treatment).


Nitric oxide mediates the increase in local cerebral blood flow during focal seizures.
The role of nitric oxide (NO) in the increase in local cerebral blood flow (LCBF) elicited by focal cortical epileptic seizures was investigated in anesthetized adult rats. Seizures were induced by topical bicuculline methiodide applied through two cranial windows drilled over homotopic sites of the frontal cortex, and LCBF was measured by quantitative autoradiography by using 4-iodo[N-methyl-14C]antipyrine. Superfusion of an inhibitor of NO synthase, N omega-nitro-L-arginine (NA; 1 mM), for 45 min abolished the increase of LCBF induced by topical bicuculline methiodide (10 mM) [164 +/- 18 ml/100 g per min in the artificial cerebrospinal fluid (aCSF)-superfused side and 104 +/- 12 ml/100 g per ml in the NA-superfused side; P < 0.005]. This effect was reversed by coapplication of an excess of L-arginine substrate (10 mM) (218 +/- 22 ml/100 g per min in the aCSF-superfused side and 183 +/- 31 ml/100 g per min in the NA + L-Arg-superfused side) but not by 10 mM D-arginine, a stereoisomer with poor affinity for NO synthase (193 +/- 17 ml/100 g per min in the aCSF-superfused side and 139 +/- 21 ml/100 g per min in the NA + D-Arg-superfused side; P < 0.005). Superfusion of the guanylyl cyclase inhibitor methylene blue attenuated the LCBF increase elicited by topical bicuculline methiodide by 25% +/- 16% (P < 0.05). The present findings suggest that NO is the mediator of the vasodilation in response to focal epileptic seizures.


Crawling to collapse: ecologically unsound ornamental invertebrate fisheries.
Fishery management has historically been an inexact and reactionary discipline, often taking action only after a critical stock suffers overfishing or collapse. The invertebrate ornamental fishery in the State of Florida, with increasing catches over a more diverse array of species, is poised for collapse. Current management is static and the lack of an adaptive strategy will not allow for adequate responses associated with managing this multi-species fishery. The last decade has seen aquarium hobbyists shift their display preference from fish-only tanks to miniature reef ecosystems that include many invertebrate species, creating increased demand without proper oversight. The once small ornamental fishery has become an invertebrate-dominated major industry supplying five continents. Here, we analyzed the Florida Marine Life Fishery (FLML) landing data from 1994 to 2007 for all invertebrate species. The data were organized to reflect both ecosystem purpose (in the wild) and ecosystem services (commodities) for each reported species to address the following question: Are ornamental invertebrates being exploited for their fundamental ecosystem services and economic value at the expense of reef resilience? We found that 9 million individuals were collected in 2007, 6 million of which were grazers. The number of grazers now exceeds, by two-fold, the number of specimens collected for curio and ornamental purposes altogether, representing a major categorical shift. In general, landings have increased 10-fold since 1994, though the number of licenses has been dramatically reduced. Thus, despite current management strategies, the FLML Fishery appears to be crawling to collapse.


Inner-city health care. American College of Physicians.
The fundamental problems that beset the U.S. health care system--cost, quality, and access--differ in scope and intensity in inner cities. Current trends in health care are system-wide but are more difficult to accommodate in inner cities because of scarce resources and stresses to the health care system. In this position paper, the American College of Physicians seeks to highlight directions and innovations in public policy for inner-city health care with renewed determination that health care problems in the United States must be solved, especially in cities, where they are most extreme. Many persons in inner cities experience an urban health penalty because of the concentration of economic decline, job loss, and major health problems. Because the problems originate in a complex interaction of socioeconomic factors, behavior, environment, and disease that is related to race and ethnicity, multifaceted approaches that extend beyond the medical model are needed to improve health status. The College argues for tackling health problems of the inner city in the context of a comprehensive urban policy that addresses the root causes of poverty. In addition, this position paper contains more specific recommendations to improve health care delivery to inner cities. The College calls for a comprehensive urban partnership initiative to address all aspects of the urban penalty--social, economic, and health-related--and recommends solutions through public and private collaborations that can be adapted to the circumstances of each community. In addition, policy recommendations address health care coverage, providers, public health initiatives, community involvement, and short-term improvements to such existing programs as Medicaid.


Identification of tissue contamination by polymorphic deletion probe fluorescence in situ hybridization.
Potential sources of error in surgical pathology include specimen misidentification, unidentified tissue, and tissue contamination of paraffin blocks and slides. Current molecular approaches to characterize unidentified or misidentified tissue include fluorescence in situ hybridization identification of sex chromosomes (XY FISH) and microsatellite analysis. Polymorphic deletion probe (PDP) FISH, a novel FISH assay based on copy number variants, can distinguish between cells and tissues from 2 individuals in situ, independent of gender. Using a panel of 3 PDPs, we compared the genotypes of potential tissue contaminants (n=19) and unidentified tissues (n=6) with patient tissues to determine the utility of PDP FISH in resolving specimen identity. XY FISH was added to increase the informative potential of the assay, and microsatellite analysis was used as a gold standard to confirm PDP FISH results. PDP FISH distinguished between putative contaminants and patient tissues in 13 of 14 cases and indicated a high likelihood of 2 tissues originating from the same source in 11 of 11 cases. The assay has a sensitivity and specificity of 86% [6/7, exact 95% confidence interval (CI): 42%, 97%] and 100% (9/9, exact 1-sided 97.5% CI: 68%, 100%), respectively, and a positive predictive value and negative predictive value of 100% (6/6, exact 1-sided 97.5% CI: 54%, 100%) and 90% (9/10, exact 95% CI: 55%, 98%), respectively. PDP FISH is an accurate and practical molecular assay for the genetic characterization of potential tissue contaminants and unidentified tissues, especially in the setting of small sample size, and permits concomitant assessment of morphology.


Pore formation in fluctuating membranes.
We study the nucleation of a single pore in a fluctuating lipid membrane, specifically taking into account the membrane fluctuations, as well as the shape fluctuations of the pore. For large enough pores, the nucleation free energy is well-described by shifts in the effective membrane surface tension and the pore line tension. Using our framework, we derive the stability criteria for the various pore formation regimes. In addition to the well-known large-tension regime from the classical nucleation theory of pores, we also find a low-tension regime in which the effective line and surface tensions can change sign from their bare values. The latter scenario takes place at sufficiently high temperatures, where the opening of a stable pore of finite size is entropically favorable.


Neurocomputational account of how the human brain decides when to have a break.
No pain, no gain: cost-benefit trade-off has been formalized in classical decision theory to account for how we choose whether to engage effort. However, how the brain decides when to have breaks in the course of effort production remains poorly understood. We propose that decisions to cease and resume work are triggered by a cost evidence accumulation signal reaching upper and lower bounds, respectively. We developed a task in which participants are free to exert a physical effort knowing that their payoff would be proportional to their effort duration. Functional MRI and magnetoencephalography recordings conjointly revealed that the theoretical cost evidence accumulation signal was expressed in proprioceptive regions (bilateral posterior insula). Furthermore, the slopes and bounds of the accumulation process were adapted to the difficulty of the task and the money at stake. Cost evidence accumulation might therefore provide a dynamical mechanistic account of how the human brain maximizes benefits while preventing exhaustion.


Probiotic supplements and debridement of peri-implant mucositis: a randomized controlled trial.
The aim of this double-blind randomized placebo-controlled trial was to evaluate the effects of probiotic supplements in adjunct to conventional management of peri-implant mucositis. Forty-nine adult patients with peri-implant mucositis were consecutively recruited after informed consent. After initial mechanical debridement and oral hygiene instructions, the patients received a topical oil application (active or placebo) followed by twice-daily intake of lozenges (active or placebo) for 3 months. The active products contained a mix of two strains of Lactobacillus reuteri. Patients were clinically monitored and sampled at baseline and after 1, 2, 4, 12 and 26 weeks. The clinical end-points were pocket-probing depth (PPD), plaque index (PI) and bleeding on probing (BOP). In addition, the subgingival microbiota was processed with checkerboard DNA-DNA hybridization and samples of gingival crevicular fluid (GCF) were analyzed for selected cytokines with the aid of multiplex immunoassays. After 4 and 12 weeks, all clinical parameters were improved in both the test and the placebo group. PPD and BOP were significantly reduced compared with baseline (p < 0.05), but no significant differences were displayed between the groups. The clinical improvements persisted 3 months after the intervention. No major alterations of the subgingival microflora were disclosed and the levels of inflammatory mediators in GCF did not differ between the groups. Mechanical debridement and oral hygiene reinforcement resulted in clinical improvement of peri-implant mucositis and a reduction in cytokine levels. Probiotic supplements did not provide added benefit to placebo.


Structure of bone morphogenetic protein 9 procomplex.
Bone morphogenetic proteins (BMPs) belong to the TGF-β family, whose 33 members regulate multiple aspects of morphogenesis. TGF-β family members are secreted as procomplexes containing a small growth factor dimer associated with two larger prodomains. As isolated procomplexes, some members are latent, whereas most are active; what determines these differences is unknown. Here, studies on pro-BMP structures and binding to receptors lead to insights into mechanisms that regulate latency in the TGF-β family and into the functions of their highly divergent prodomains. The observed open-armed, nonlatent conformation of pro-BMP9 and pro-BMP7 contrasts with the cross-armed, latent conformation of pro-TGF-β1. Despite markedly different arm orientations in pro-BMP and pro-TGF-β, the arm domain of the prodomain can similarly associate with the growth factor, whereas prodomain elements N- and C-terminal to the arm associate differently with the growth factor and may compete with one another to regulate latency and stepwise displacement by type I and II receptors. Sequence conservation suggests that pro-BMP9 can adopt both cross-armed and open-armed conformations. We propose that interactors in the matrix stabilize a cross-armed pro-BMP conformation and regulate transition between cross-armed, latent and open-armed, nonlatent pro-BMP conformations.


Derivatives of light scattering properties of a nonspherical particle computed with the T-matrix method.
Based on the T-matrix formalism, we analytically calculate derivatives of light scattering quantities by a nonspherical particle with respect to its microphysical parameters. Illustrative computations are performed for a spheroid, and the results agree with those obtained by finite differencing. The proposed formalism also predicts correctly derivatives for a sphere obtained by linearized Lorenz-Mie theory.


Binders alternative to Portland cement and waste management for sustainable construction - Part 2.
The paper represents the "state of the art" on sustainability in construction materials. In Part 1 of the paper, issues related to production, microstructures, chemical nature, engineering properties, and durability of mixtures based on binders alternative to Portland cement were presented. This second part of the paper concerns the use of traditional and innovative Portland-free lime-based mortars in the conservation of cultural heritage, and the recycling and management of wastes to reduce consumption of natural resources in the production of construction materials. The latter is one of the main concerns in terms of sustainability since nowadays more than 75% of wastes are disposed of in landfills.


Does prospective payment really contain nursing home costs?
To examine whether nursing homes would behave more efficiently, without compromising their quality of care, under prospective payment. Four data sets for 1994: the Skilled Nursing Facility Minimum Data Set, the Online Survey Certification and Reporting System file, the Area Resource File, and the Hospital Wage Indices File. A national sample of 4,635 nursing homes is included in the analysis. Using a modified hybrid functional form to estimate nursing home costs, we distinguish our study from previous research by controlling for quality differences (related to both care and life) and addressing the issues of output and quality endogeneity, as well as using more recent national data. Factor analysis was used to operationalize quality variables. To address the endogeneity problems, instrumental measures were created for nursing home output and quality variables. Nursing homes in states using prospective payment systems do not have lower costs than their counterpart facilities under retrospective cost-based payment systems, after quality differences among facilities are controlled for and the endogeneity problem of quality variables is addressed. The effects of prospective payment on nursing home cost reduction may be through quality cuts, rather than cost efficiency. If nursing home payments under prospective payment systems are not adjusted for quality, nursing homes may respond by cutting their quality levels, rather than controlling costs. Future outcomes research may provide useful insights into the adjustment of quality in the design of prospective payment for nursing home care.


Optimizing HIV prevention for women: a review of evidence from microbicide studies and considerations for gender-sensitive microbicide introduction.
Microbicides were conceptualized as a product that could give women increased agency over HIV prevention. However, gender-related norms and inequalities that place women and girls at risk of acquiring HIV are also likely to affect their ability to use microbicides. Understanding how gendered norms and inequalities may pose obstacles to women's microbicide use is important to inform product design, microbicide trial implementation and eventually microbicide and other antiretroviral-based prevention programmes. We reviewed published vaginal microbicide studies to identify gender-related factors that are likely to affect microbicide acceptability, access and adherence. We make recommendations on product design, trial implementation, positioning, marketing and delivery of microbicides in a way that takes into account the gender-related norms and inequalities identified in the review. We conducted PubMed searches for microbicide studies published in journals between 2000 and 2013. Search terms included trial names (e.g. "MDP301"), microbicide product names (e.g. "BufferGel"), researchers' names (e.g. "van der Straten") and other relevant terms (e.g. "microbicide"). We included microbicide clinical trials; surrogate studies in which a vaginal gel, ring or diaphragm was used without an active ingredient; and hypothetical studies in which no product was used. Social and behavioural studies implemented in conjunction with clinical trials and surrogate studies were also included. Although we recognize the importance of rectal microbicides to women, we did not include studies of rectal microbicides, as most of them focused on men who have sex with men. Using a standardized review template, three reviewers read the articles and looked for gender-related findings in key domains (e.g. product acceptability, sexual pleasure, partner communication, microbicide access and adherence). The gendered norms, roles and relations that will likely affect women's ability to access and use microbicides are related to two broad categories: norms regulating women's and men's sexuality and power dynamics within intimate relationships. Though norms about women's and men's sexuality vary among cultural contexts, women's sexual behaviour and pleasure are typically less socially acceptable and more restricted than men's. These norms drive the need for woman-initiated HIV prevention, but also have implications for microbicide acceptability and how they are likely to be used by women of different ages and relationship types. Women's limited power to negotiate the circumstances of their intimate relationships and sex lives will impact their ability to access and use microbicides. Men's role in women's effective microbicide use can range from opposition to non-interference to active support. Identifying an effective microbicide that women can use consistently is vital to the future of HIV prevention for women. Once such a microbicide is identified and licensed, positioning, marketing and delivering microbicides in a way that takes into account the gendered norms and inequalities we have identified would help maximize access and adherence. It also has the potential to improve communication about sexuality, strengthen relationships between women and men and increase women's agency over their bodies and their health.


Neighbourhood deprivation and smoking and quit behaviour among smokers in Mexico: findings from the ITC Mexico Survey.
In high-income countries (HICs), higher neighbourhood socioeconomic deprivation is associated with higher levels of smoking. Few studies in low-income and middle-income countries (LMICs) have investigated the role of the neighbourhood environment on smoking behaviour. To determine whether neighbourhood socioeconomic deprivation is related to smoking intensity, quit attempts, quit success and smoking relapse among a cohort of smokers in Mexico from 2010 to 2012. Data were analysed from adult smokers and recent ex-smokers who participated in waves 4-6 of the International Tobacco Control (ITC) Mexico Survey. Data were linked to the Mexican government's composite index of neighbourhood socioeconomic deprivation, which is based on 2010 Mexican Census data. We used generalised estimating equations to determine associations between neighbourhood deprivation and individual smoking behaviours. Contrary to past findings in HICs, higher neighbourhood socioeconomic deprivation was associated with lower smoking intensity. Quit attempts showed a U-shaped pattern whereby smokers living in high/very high deprivation neighbourhoods and smokers living in very low deprivation neighbourhoods were more likely to make a quit attempt than smokers living in other neighbourhoods. We did not find significant differences in neighbourhood deprivation on relapse or successful quitting, with the possible exception of people living in medium-deprivation neighbourhoods having a higher likelihood of successful quitting than people living in very low deprivation neighbourhoods (p=0.06). Neighbourhood socioeconomic environments in Mexico appear to operate in an opposing manner to those in HICs. Further research should investigate whether rapid implementation of strong tobacco control policies in LMICs, as occurred in Mexico during the follow-up period, avoids the concentration of tobacco-related disparities among socioeconomically disadvantaged groups.


The Organizational Account of Function is an Etiological Account of Function.
The debate on the notion of function has been historically dominated by dispositional and etiological accounts, but recently a third contender has gained prominence: the organizational account. This original theory of function is intended to offer an alternative account based on the notion of self-maintaining system. However, there is a set of cases where organizational accounts seem to generate counterintuitive results. These cases involve cross-generational traits, that is, traits that do not contribute in any relevant way to the self-maintenance of the organism carrying them, but instead have very important effects on organisms that belong to the next generation. We argue that any plausible solution to the problem of cross-generational traits shows that the organizational account just is a version of the etiological theory and, furthermore, that it does not provide any substantive advantage over standard etiological theories of function.


High resolution LT-STM imaging of PTCDA molecules assembled on an InSb(001) c(8 × 2) surface.
The self-assembling of 3,4,9,10-perylene-tetracarboxylic-dianhydride (PTCDA) molecules deposited on an InSb(001) c(8 × 2) surface at sub-monolayer quantities has been investigated at low temperature (77 K) using scanning tunnelling microscopy. Sub-molecular resolution was obtained on PTCDA molecules. The results reveal that individual PTCDA molecules are arranged on the substrate in chains parallel to the [110] crystallographic direction, correlated with characteristic features of the low temperature InSb(001) c(8 × 2) surface electronic structure. A structural model for PTCDA molecules adsorbed on InSb is proposed.


Localization of immunogenic regions on the flagellin proteins of Campylobacter jejuni 81116.
The purpose of this study was to localize antigenic regions on the flagellin protein of Campylobacter jejuni 81116. This strain has two flagellin genes, flaA and flaB, which are 95% identical; only flaA seems to be expressed in motile C. jejuni 81116 cells. Fragments of flaA and flaB were cloned in the bacterial expression vector pEX, and the expression products were incubated with flagellin-specific antibodies. Monoclonal antibodies to broadly cross-reactive epitopes recognized fragments that are located in the termini (CF16 and CF17) and in the center (CF15) of both flagellin A and B proteins. Most of the serotype-specific monoclonal antibodies (CF1, CF2, CD3, CF4, and CF13) reacted with only the center of flagellin A in an area where flagellin A and B differ in 6 amino acid residues. The epitopes in this area were further characterized by competitive binding experiments. The charge and molecular weight microheterogeneity of flagellin, as determined by two-dimensional gel electrophoresis, were unrelated to the expression of both flagellin genes or parts thereof.


Resistance of common carp (Cyprinus carpio L.) to oxidative stress after chloramine-T treatment is increased by microalgae carotenoid-rich diet.
In fish aquaculture, disinfectants are used against bacterial and protozoal infections. These compounds cause oxidative stress that may stimulate the generation of reactive oxygen species, and subsequently the alteration in antioxidant systems of exposed organisms. Antioxidants like carotenoids present in microalgae increase carp resistance to oxidative stress after chemical treatment. The aim of these experiments was to prove increased resistance of common carp (Cyprinus carpio L.) juveniles fed on experimental diets with microalgae biomass supplement (Algadiets) to oxidative stress caused by a disinfectant chloramine-T. In indoor experiments fish were fed on laboratory-prepared extruded diets containing supplement of Chlorella spp. (cf. C. vulgaris Beijerinck) biomass which contains antioxidants (carotenoids) like lutein. The young-of-the-year-old fish were acclimatized and fed on basal diet (control group) and the on diets containing 1, 2, 5 and 10% (w/w) of spray-dried Chlorella biomass (Algadiet 1, 2, 5 and 10) for 14 days followed by 6 weeks. Consequently, fish were treated daily with chloramine-T (Chl-T) at concentration of 10 mg x l(-1) for 1 h in three consecutive days. After this treatment, the indices of oxidative stress and antioxidant enzyme activity were assayed in fish gill, muscle and hepatopancreas. The fish fed on different Algadiets had increased antioxidant enzyme activities of glutathione peroxidase, glutathione reductase and catalase in flesh after the exposure to Chl-T. Higher activities of superoxide dismutase, glutathione peroxidase and glutathione reductase were also observed in the hepatopancreas in all tested concentrations compared to the control group fed on the basal diet. The increased production and activity of antioxidant enzymes confirmed improved protection ability of fish tissues against oxidative damage when microalgae biomass was supplemented to the fish diet which was more pronounced by higher microalgae supplement in Algadiet 5 and 10 where the content of carotenoids was 105 mg and 214 mg per kilogram of fed, respectively. The results show the positive effect of carotenoids from microalgae biomass to maintain the antioxidant capacity which increases resistance of fish to oxidative stress.


Complementary and conventional providers in cancer care: experience of communication with patients and steps to improve communication with other providers.
Effective interdisciplinary communication is important to achieve better quality in health care. The aims of this study were to compare conventional and complementary providers' experience of communication about complementary therapies and conventional medicine with their cancer patients, and to investigate how they experience interdisciplinary communication and cooperation. This study analyzed data from a self-administrated questionnaire. A total of 606 different health care providers, from four counties in Norway, completed the questionnaire. The survey was developed to describe aspects of the communication pattern among oncology doctors, nurses, family physicians and complementary therapists (acupuncturists, massage therapists and reflexologists/zone-therapists). Between-group differences were analyzed using chi-square, ANOVA and Fisher's exact tests. Significance level was defined as p < 0.05 without adjustment for multiple comparisons. Conventional providers and complementary therapists had different patterns of communication with their cancer patients regarding complementary therapies. While complementary therapists advised their patients to apply both complementary and conventional modalities, medical doctors were less supportive of their patients' use of complementary therapies. Of conventional providers, nurses expressed more positive attitudes toward complementary therapies. Opportunities to improve communication between conventional and complementary providers were most strongly supported by complementary providers and nurses; medical doctors were less supportive of such attempts. A number of doctors showed lack of respect for complementary therapists, but asked for more research, guidelines for complementary modalities and training in conventional medicine for complementary therapists. For better quality of care, greater communication about complementary therapy use is needed between cancer patients and their conventional and complementary providers. In addition, more communication between conventional and complementary providers is needed. Nurses may have a crucial role in facilitating communication, as they are positive toward complementary therapies and they have more direct communication with patients about their treatment preferences.


Focus issue introduction: nonlinear optics 2013.
Nonlinear Optics has continued to develop over the last few years at an extremely fast pace, with significant advances being reported in nonlinear optical metamaterials, optical signal processing, quantum optics, nonlinear optics at subwavelength scale, and biophotonics. These exciting new developments have generated significant potential for a broad spectrum of technological applications in which nonlinear-optical processes play a central role.


Predictors of clinical outcome after stent placement in atherosclerotic renal artery stenosis: a systematic review and meta-analysis of prospective studies.
To determine clinical predictors for blood pressure and/or renal function improvement after renal artery stent placement in atherosclerotic renal artery stenosis (ARAS). We searched PubMed, EMBASE and Cochrane databases for prospective studies investigating clinical predictive variables for renal function and/or blood pressure improvement after stent placement in ARAS. Eleven studies (1552 participants) were selected for our systematic review and meta-analysis. Meta-regression analysis was performed to investigate heterogeneity and to determine independent predictors for the outcome variables. Bias was evaluated by use of the Cochrane risk of bias tool. Multivariate meta-regression analysis showed no predictors for renal function improvement. High baseline diastolic blood pressure (DBP) and pulse pressure were significantly associated with the decrease in blood pressure after intervention. These results were consistent with the predictors reported by the individual studies. Meta-analysis showed a nonsignificant decline in serum creatinine of 4.7 μmol/l [95% confidence interval (Cl) -13.8 to 4.5]. Overall, systolic blood pressure (SBP) fell by 19.2 mmHg (95% Cl -22.7 to -15.7) and DBP decreased 8.9 mmHg (95% Cl -10.8 to -7.0). Risk of bias was present in the majority of the studies. The present review did not find a clinical characteristic that reliably predicts renal function outcome. High baseline pulse pressure predicted a smaller decrease in SBP after intervention and the best clinical predictor for a larger DBP reduction was a high pretreatment DBP.


Neutralizing antibodies associated with viremia control in a subset of individuals after treatment of acute human immunodeficiency virus type 1 infection.
Immediate treatment of acute human immunodeficiency virus type 1 (HIV-1) infection has been associated with subsequent control of viremia in a subset of patients after therapy cessation, but the immune responses contributing to control have not been fully defined. Here we examined neutralizing antibodies as a correlate of viremia control following treatment interruption in HIV-1-infected individuals in whom highly active antiretriviral therapy (HAART) was initiated during early seroconversion and who remained on therapy for 1 to 3 years. Immediately following treatment interruption, neutralizing antibodies were undetectable with T-cell-line adapted strains and the autologous primary HIV-1 isolate in seven of nine subjects. Env- and Gag-specific antibodies as measured by enzyme-linked immunosorbent assay were also low or undetectable at this time. Despite this apparent poor maturation of the virus-specific B-cell response during HAART, autologous neutralizing antibodies emerged rapidly and correlated with a spontaneous downregulation in rebound viremia following treatment interruption in three subjects. Control of rebound viremia was seen in other subjects in the absence of detectable neutralizing antibodies. The results indicate that virus-specific B-cell priming occurs despite the early institution of HAART, allowing rapid secondary neutralizing-antibody production following treatment interruption in a subset of individuals. Since early HAART limits viral diversification, we hypothesize that potent neutralizing-antibody responses to autologous virus are able to mature and that in some persons these responses contribute to the control of plasma viremia after treatment cessation.


Clinical Presentation, Cardiac Magnetic Resonance Findings, and Prognosis of Patients with Arrhythmogenic Right Ventricular Cardiomyopathy - An Experience from Pakistan.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart-muscle disease, characterized by fibro-fatty replacement and ventricular arrhythmias, that primarily affects the right ventricle (RV). We aimed to look at the clinical presentation, cardiac magnetic resonance (CMR) imaging findings and prognosis of patients with ARVC in Pakistan. It is a retrospective observational study, 17 consecutive patients with CMR and other findings consistent with ARVC, were enrolled from 2010 to 2019 at a single center. Out of 17 patients, 12 (70.6%) were male with a mean age of 33.5 ± 17.5 years. Family history of sudden cardiac death was present in 3 (17.7%) patients while one (5.9%) patient had family history of ARVC. Syncope was the first presenting symptom in eight (47.1%) patients. On 12 leads ECG, T wave inversion in precordial leads was found in 6 (35.4%) patients, and epsilon wave was present in only 3 (17.7%) patients. On echocardiogram, 13 (76.5%) patients had dilated RV with reduced systolic function. On CMR, majority of patients (n = 14, 82.4%) were found to have RV dilatation with regional dyskinesia and fatty infiltration, 9 (52.9%) of them had left ventricular involvement also. Follow-up was available for 14 patients (82.4%) with a mean follow-up period of 35.5 ± 19.7 months. Three (21.4%) of them died and 10 (71.4%) got admissions for heart failure during follow-up period. Arrhythmia related events are the main presenting symptoms of ARVC in this region, and left ventricular involvement in ARVC is not rare in this population. The mortality is relatively high, probably due to advanced disease at the time of presentation and less medical facilities available.


Reflections on the early invasive clinical cardiac electrophysiology era through fifty manuscripts: 1967-1992.
In 1967, researchers in The Netherlands and France independently reported a new technique, later called programmed electrical stimulation. The ability to reproducibly initiate and terminate arrhythmias heralded the beginning of invasive clinical cardiac electrophysiology as a medical discipline. Over the next fifty years, insights into the pathophysiologic basis of arrhythmias would transform the field into an interventional specialty with a tremendous armamentarium of procedures. In 2015, the variety and complexity of these procedures were major reasons that led to the recommendation for an increase in the training period from one year to two years. The purpose of this manuscript is to present fifty manuscripts from the early invasive clinical cardiac electrophysiology era, between 1967 and 1992, to serve as an educational resource for current and future electrophysiologists. It is our hope that reflection on the transition from a predominantly noninvasive discipline to one where procedures are commonly utilized will lead to more thoughtful patient care today and to inspiration for innovation tomorrow. In the words of the late Dr. Mark E. Josephson, "It is only by getting back to the basics that the field of electrophysiology will continue to grow instead of stagnate."


Estimates of genetic parameters for fatty acids in brisket adipose tissue of Canadian commercial crossbred beef steers.
Heritability and genetic and phenotypic correlations between 15 individuals and 10 groups of fatty acids with a concentration greater than 0.5% in the brisket adipose tissue of 223 Angus and Charolais based crossbred commercial steers were estimated using univariate and bivariate animal models. Individual saturated fatty acids were low to moderately heritable, with heritability estimates ranging from 0.05 (C16:0) to 0.31 (C15:0). Individual monounsaturated fatty acids were low to moderately highly heritable ranging from 0.04 (9c C17:1 and 11c C18:1) to 0.51 (9c C14:1). Polyunsaturated fatty acid C18:2n-6 was moderately heritable (0.17). Among groups of fatty acids, heritability estimates ranged from 0.03 for branched chain fatty acid (BCFA) and n-6/n-3 to 0.16 for n-6 and Health Index. A range of low (0.00) to high (1.00) phenotypic and genetic correlations was observed among the 25 fatty acids considered in this study. In general, fatty acids such as conjugated linoleic acid (CLA) and 11t C18:1, with potential health benefits, showed significant antagonistic correlations with unhealthy fatty acids such as C14:0 and C16:0. The results from this study provide insight into the direct genetic control of host genes on fatty acid composition of beef tissues and will facilitate designs of genetic selection and/or genetic based diet management to improve fatty acid composition in beef cattle.


Abdominal wall hernias after open abdominal aortic aneurysm repair: prospective radiographic detection and clinical implications.
The purpose of this study was to evaluate the prevalence of radiographically detected abdominal wall defects (AWD) after open abdominal aortic aneurysm (AAA) repair and to correlate it with prospectively gathered clinical information. Fine collimation, high-resolution, serial follow-up computed tomography (CT) scans for 99 patients in the control group of the Guidant Ancure device trial were reviewed. CT scans were obtained at 12, 24, 36, 48, and 60 months. AWDs, defined as discontinuity of the fascial layer with protrusion of abdominal contents, were identified. Clinical information regarding AWDs was retrieved from the study registry. The prevalence of AWD exceeds 20% and plateaus at 24 months. Eight patients (8%) had clinical evidence of ventral incisional hernias. One patient underwent repair, but no other patient developed hernia incarceration or intestinal obstruction or required additional procedures related to the AWD. AWDs are radiographic findings occurring frequently after open AAA repair. Radiographic evaluation is more sensitive than clinical observation for detection of ventral hernias. Clinical events and reinterventions related to these radiographic abnormalities are rare.


Evaluation of the Neuropathic Component of Chronic Low Back Pain.
Assessment of neuropathic pain in chronic low back syndromes is important. However, there is currently no gold standard for its diagnosis. The aim of this observational cross-sectional study was to assess the neuropathic component of pain in various chronic low back pain syndromes using a range of diagnostic tests. Included in this study were 63 patients with chronic axial low back pain (ALBP), 48 patients with chronic radicular syndromes (CRS) comprising 23 with discogenic compression (CDRS) and 25 with lumbar spinal stenosis (LSS), and 74 controls. PainDETECT questionnaire (PDQ), quantitative sensory testing (QST), and skin biopsy with evaluation of intraepidermal nerve fiber density (IENFD) were used to assess the neuropathic pain component. Positive PDQ (≥19) was obtained more frequently in patients with CDRS and LSS (26.1% and 12.0%, respectively) compared with patients with ALBP (1.6%, P<0.001). The proportion of patients with sensory loss confirmed by QST was lowest in the ALBP subgroup (23.8%) compared with CDRS (47.8%), and LSS (68.0%) subgroups (P<0.001). A reduction in IENFD was disclosed in a proportion of up to 52.0% of affected roots in patients with CRS. Neuropathic pain is quite frequent in CRS, and QST reveals sensory loss as a frequent abnormality in patients with CRS. Using a cut-off value of 19, PDQ identified a neuropathic component in a relatively low proportion of patients with CRS. CRS may be associated with a reduction in IENFD.


Race disparities in pubertal timing: Implications for cardiovascular disease risk among African American women.
Compared to white girls, sexual maturation is accelerated in African American girls as measured by indicators of pubertal development, including age at first menses. Increasing epidemiological evidence suggests that the timing of pubertal development may have strong implications for cardio-metabolic health in adolescence and adulthood. In fact, younger menarcheal age has been related prospectively to poorer cardiovascular risk factor profiles, a worsening of these profiles over time, and an increase in risk for cardiovascular events, including non-fatal incident cardiovascular disease and cardiovascular-specific and all-cause mortality. Yet, because this literature has been limited almost exclusively to white girls/women, whether this same association is present among African American girls/women has not been clarified. In the current narrative review, the well-established vulnerability of African American girls to experience earlier pubertal onset is discussed as are findings from literatures examining the health outcomes of earlier pubertal timing and its antecedents, including early life adversity exposures often experienced disproportionately in African American girls. Gaps in these literatures are highlighted especially with respect to the paucity of research among minority girls/women, and a conceptual framework is posited suggesting disparities in pubertal timing between African American and white girls may partially contribute to well-established disparities in adulthood risk for cardio-metabolic disease between African American and white women. Future research in these areas may point to novel areas for intervention in preventing or lessening the heightened cardio-metabolic risk among African American women, an important public health objective.


Pediatric Lyme Arthritis of the Hip: The Great Imitator?
Lyme arthritis (LA) of the hip can present similarly to septic arthritis (SA) and transient synovitis (TS). The primary purpose of this study was to determine clinical and laboratory parameters differentiating LA of the hip from SA or TS among children who had undergone hip aspiration during the evaluation of hip pain. This was a retrospective review of all patients who underwent hip aspiration for the evaluation of hip pain at a tertiary care children's hospital in a Lyme endemic area. Clinical and laboratory data were reviewed and comparative analyses were performed between those diagnosed with LA, SA, and TS. Independent samples t test, ANOVA, and χ test were used to compare clinical and laboratory variables as appropriate. Multivariable logistic regression was used to elucidate independent predictors of LA. Statistical significance was set at P<0.05. Ninety-three hip aspirations (93 patients) were included in the final analysis. Seventeen patients were diagnosed with LA, 40 with SA, and 36 with TS. Multivariable logistic regression revealed febrile history (OR=16.3; 95% CI, 2.35-113.0) and increased peripheral white blood cell (WBC) count (OR=1.26; 95% CI, 1.01-1.58) to be significantly associated with increased odds of being diagnosed with SA versus LA. Increased erythrocyte sedimentation rate (ESR) was significantly associated with increased odds of being diagnosed with LA versus TS (OR=1.06; 95% CI, 1.02-1.10), whereas febrile history (OR=0.06; 95% CI, 0.01-0.49) and increased peripheral WBC count (OR=0.8; 95% CI, 0.65-0.98) were associated with decreased odds of LA. Children presenting in a Lyme endemic area with an isolated hip effusion are more likely to have LA versus SA if they have no history of fever and a decreased peripheral WBC count. Compared with TS, patients with LA are more likely to have an elevated ESR. This study adds to existing knowledge because there are few investigations examining isolated LA of the hip. Level III-retrospective case-control study.


TSSAR: TSS annotation regime for dRNA-seq data.
Differential RNA sequencing (dRNA-seq) is a high-throughput screening technique designed to examine the architecture of bacterial operons in general and the precise position of transcription start sites (TSS) in particular. Hitherto, dRNA-seq data were analyzed by visualizing the sequencing reads mapped to the reference genome and manually annotating reliable positions. This is very labor intensive and, due to the subjectivity, biased. Here, we present TSSAR, a tool for automated de novo TSS annotation from dRNA-seq data that respects the statistics of dRNA-seq libraries. TSSAR uses the premise that the number of sequencing reads starting at a certain genomic position within a transcriptional active region follows a Poisson distribution with a parameter that depends on the local strength of expression. The differences of two dRNA-seq library counts thus follow a Skellam distribution. This provides a statistical basis to identify significantly enriched primary transcripts.We assessed the performance by analyzing a publicly available dRNA-seq data set using TSSAR and two simple approaches that utilize user-defined score cutoffs. We evaluated the power of reproducing the manual TSS annotation. Furthermore, the same data set was used to reproduce 74 experimentally validated TSS in H. pylori from reliable techniques such as RACE or primer extension. Both analyses showed that TSSAR outperforms the static cutoff-dependent approaches. Having an automated and efficient tool for analyzing dRNA-seq data facilitates the use of the dRNA-seq technique and promotes its application to more sophisticated analysis. For instance, monitoring the plasticity and dynamics of the transcriptomal architecture triggered by different stimuli and growth conditions becomes possible.The main asset of a novel tool for dRNA-seq analysis that reaches out to a broad user community is usability. As such, we provide TSSAR both as intuitive RESTful Web service ( http://rna.tbi.univie.ac.at/TSSAR) together with a set of post-processing and analysis tools, as well as a stand-alone version for use in high-throughput dRNA-seq data analysis pipelines.


A Rapid and Low-Cost PCR Thermal Cycler for Infectious Disease Diagnostics.
The ability to make rapid diagnosis of infectious diseases broadly available in a portable, low-cost format would mark a great step forward in global health. Many molecular diagnostic assays are developed based on using thermal cyclers to carry out polymerase chain reaction (PCR) and reverse-transcription PCR for DNA and RNA amplification and detection, respectively. Unfortunately, most commercial thermal cyclers are expensive and need continuous electrical power supply, so they are not suitable for uses in low-resource settings. We have previously reported a low-cost and simple approach to amplify DNA using vacuum insulated stainless steel thermoses food cans, which we have named it thermos thermal cycler or TTC. Here, we describe the use of an improved set up to enable the detection of viral RNA targets by reverse-transcription PCR (RT-PCR), thus expanding the TTC's ability to identify highly infectious, RNA virus-based diseases in low resource settings. The TTC was successful in demonstrating high-speed and sensitive detection of DNA or RNA targets of sexually transmitted diseases, HIV/AIDS, Ebola hemorrhagic fever, and dengue fever. Our innovative TTC costs less than $200 to build and has a capacity of at least eight tubes. In terms of speed, the TTC's performance exceeded that of commercial thermal cyclers tested. When coupled with low-cost endpoint detection technologies such as nucleic acid lateral-flow assay or a cell-phone-based fluorescence detector, the TTC will increase the availability of on-site molecular diagnostics in low-resource settings.


Development of a DNA microarray chip for the identification of sludge bacteria using an unsequenced random genomic DNA hybridization method.
A tool, based upon the DNA microarray chip, for the identification of specific bacteria from activated sludge, using the hybridization of genomic DNA with random probes, is described. This chip was developed using the genomic DNAs from Gordonia amarae, the natural filamentous actinomycete that causes sludge foaming and bulking, as well as a nonfilamentous floc forming bacterium (Zoogloea ramigera) and the skin pathogen Mycobacterium peregrinum without any sequence information. The sets of target probes on amine-coated glass were made from a genomic library, constructed with PCR products derived from randomly fragmented genomic DNAs extracted from pure cultures of the three strains. Initial hybridization results, when pure cultures were employed, showed the specificity of the probes as well as the resolution of the system, demonstrating the capabilities of this system to identify specific bacterial strains. The microarray was also tested for its ability to distinguish specific bacteria from among mixed bacterial communities, such as in sludge, soil, or spiked genomic DNA samples. The results showed that the probes are specific, with only mild cross-hybridization occurring in a small number of cases. Furthermore, the chip clearly discriminated the presence of all three strains when they were present alone or together within mixed samples. Moreover, using the spot intensity and DNA hybridization kinetics, the starting genomic DNA concentrations could be estimated relatively well, which would make it possible to predict the number of specific bacteria present within the test samples. Therefore, the random genomic hybridization approach, i.e., without any sequence information available for the probes, is a practical protocol for the identification of and screening for specific bacteria within any complex bacterial community from the environmental samples, such as in activated sludge, although the possibility of cross-hybridization may still exist.


Organizing an effective continuous medical education session.
Maintenance of professional competence remains an exercise of lifelong learning and an essential requirement for evidence -based medical practice. Physicians attend continuing medical education (CME) programs to update their knowledge. Often CME programs remain the main source of updating current information. CME organizers have considerable responsibility in determining appropriate curriculum for their meeting. Organizing an effective CME activity often requires understanding of the principles of adult education. Prior to deciding on the curriculum for a CME, course organizers should conduct needs assessment of physicians. CME planners need to be organize activities that would consistently improve physician competence. CME sessions that are interactive, using multiple methods of instructions for small groups of physicians from a single discipline are more likely to change physician knowledge and behavior. Effectiveness of a CME program should be evaluated at a level beyond measuring physician satisfaction. CME planners need to incorporate methods to determine the course attendees improvement of knowledge, skills and attitudes during the CME activities. Pre and post test of physicians using multiple choice questions form a useful method of assessment. Course organizers would need to ensure that the questions are appropriately constructed to assess the ability to use knowledge in real life situations.


Design and analysis of large-scale biological rhythm studies: a comparison of algorithms for detecting periodic signals in biological data.
To discover and study periodic processes in biological systems, we sought to identify periodic patterns in their gene expression data. We surveyed a large number of available methods for identifying periodicity in time series data and chose representatives of different mathematical perspectives that performed well on both synthetic data and biological data. Synthetic data were used to evaluate how each algorithm responds to different curve shapes, periods, phase shifts, noise levels and sampling rates. The biological datasets we tested represent a variety of periodic processes from different organisms, including the cell cycle and metabolic cycle in Saccharomyces cerevisiae, circadian rhythms in Mus musculus and the root clock in Arabidopsis thaliana. From these results, we discovered that each algorithm had different strengths. Based on our findings, we make recommendations for selecting and applying these methods depending on the nature of the data and the periodic patterns of interest. Additionally, these results can also be used to inform the design of large-scale biological rhythm experiments so that the resulting data can be used with these algorithms to detect periodic signals more effectively.


Risk factors for hepatocellular carcinoma in Hepatitis C patients with sustained virologic response to interferon therapy.
Although a variety of papers demonstrated inhibited hepatocarcinogenesis with interferon (IFN) therapy for chronic hepatitis C, a small number of hepatocellular carcinomas (HCCs) were still observed even in sustained virologic responders. To clarify factors affecting the development of HCC, we analyzed the frequency of HCC in sustained virologic responders over a long-term observation period. Seven hundred and ninety-two out of the 2623 IFN-treated hepatitis C patients who had undergone liver biopsy showed sustained virologic response. Screening for development of HCC was performed periodically during an average follow-up of 5.1 years. Fibrosis of the pretreatment liver biopsy sample was graded. Risk factors for HCC were analyzed by using Cox proportional hazards regression. Of 792 patients, 23 developed HCC. Univariate analysis showed that stage of hepatic fibrosis, age, and alcohol consumption were significantly associated with a risk of HCC (P<0.001). There was a significant difference in the cumulative incidence between patients stratified according to these variables (P<0.001). Pretreatment hepatic fibrosis score, age, and alcohol consumption may affect development of HCC even in sustained virologic responders. Thus, patients with these factors should be carefully followed even after eradication of the virus.


Status and Problems of Humanities Education with Respect to Pharmacy Education.
In 2006, a model core curriculum in pharmaceutical studies was developed prior to the outset of the 6-year pharmacy degree. In the 10 years that followed, medical care and life science technology has progressed, pharmaceutical laws have been revised, and the responsibilities of pharmacists have increased. In response to such social changes and needs, the Model Core Curriculum for Pharmacy Education was revised in December 2013. In order to play an active role as a pharmacist in any medical workplace, it is important for pharmacy students to develop their communication skills and attitudes in order to foster the trust of their patients and other medical professionals. In the new Model Core Curriculum, education in the humanities is clearly described as a foundation to pharmaceutical education, which pertains to the clinical role of a pharmacist; hence, each pharmacy school has outlined strategies for students to learn bioethics and medical ethics, and to develop communication skills. Today, although the importance of humanities education is rapidly increasing, it is difficult to immediately evaluate the outcome of learning humanities subjects and communication. Such an evaluation requires a longer-term perspective. This paper describes the status and problems of humanities education as a component of pharmacy education, and considers future directions of research in humanities education with respect to pharmacy education.


Visual saliency based on scale-space analysis in the frequency domain.
We address the issue of visual saliency from three perspectives. First, we consider saliency detection as a frequency domain analysis problem. Second, we achieve this by employing the concept of nonsaliency. Third, we simultaneously consider the detection of salient regions of different size. The paper proposes a new bottom-up paradigm for detecting visual saliency, characterized by a scale-space analysis of the amplitude spectrum of natural images. We show that the convolution of the image amplitude spectrum with a low-pass Gaussian kernel of an appropriate scale is equivalent to an image saliency detector. The saliency map is obtained by reconstructing the 2D signal using the original phase and the amplitude spectrum, filtered at a scale selected by minimizing saliency map entropy. A Hypercomplex Fourier Transform performs the analysis in the frequency domain. Using available databases, we demonstrate experimentally that the proposed model can predict human fixation data. We also introduce a new image database and use it to show that the saliency detector can highlight both small and large salient regions, as well as inhibit repeated distractors in cluttered images. In addition, we show that it is able to predict salient regions on which people focus their attention.


Two biosensors for phenolic compounds based on mushroom (Agaricus bisporus) homogenate: comparison in terms of some important parameters of the biosensors.
Interest in molecular imprinted polymer techniques has increased because they allows for the improvement of some stability characteristics of enzymes. The high stability of molecularly imprinted enzymes for a substrate can make them ideal alternatives as recognition elements for sensors. A bioimprinted mushroom tissue homogenate biosensor was constructed in a very simple way. For this purpose, sulfite was used. The enzyme, polyphenol oxidase, was first complexed by using a competitive inhibitor, sulfite, in aqueous medium and then the enzyme was immobilized on gelatin by crosslinking with glutaraldehyde on a glass electrode surface. Similarly, polyphenol oxidase uncomplexed with sulfite was also immobilized on a glass electrode in the same conditions. The aim of the study was to compare the two biosensors in terms of their repeatability and thermal, pH, and operational stability; also, the linear ranges of the two biosensors were compared with each other.


The impact of Th17 cells on transplant rejection and the induction of tolerance.
This review aims to provide an overview of the latest evidence for the involvement of Th17 cells in the rejection of solid organ allografts. It will also consider the implications of the relationship between the differentiation pathways of Th17 and regulatory T cells (Tregs), as well as their plasticity in the context of transplantation tolerance. In the absence of the Th1 lineage in vivo, Th17 cells are capable of rejecting cardiac allografts, showing the capacity of Th17 cells to cause allograft rejection, at least in experimental models. Th17 cells are relatively unsusceptible to suppression by Tregs, although this may be context dependent. Furthermore, addition of inflammatory signals to a Treg-inducing environment leads to Th17 development and established Tregs can be converted to Th17 cells under inflammatory conditions. The capacity of Th17 cells to cause allograft rejection is becoming increasingly clear. However, the role and contribution of Th17 cells in allograft rejection in the presence of the full orchestra of T helper cells remains elusive. The apparent resistance of Th17 to be suppressed by Tregs may pose a hurdle for effective immunosuppression and tolerance inducing protocols. Furthermore, the close developmental pathways of Th17 and Tregs and the ability of Tregs to convert into Th17 cells in the presence of inflammatory signals may impede the establishment of specific unresponsiveness to donor alloantigens in vivo.