Live attenuated HIV vaccines: predicting the tradeoff between efficacy and safety.
The utility of live attenuated vaccines for controlling HIV epidemics is being debated. Live attenuated HIV vaccines (LAHVs) could be extremely effective in protecting against infection with wild-type strains, but may not be completely safe as the attenuated strain could cause AIDS in some vaccinated individuals. We present a theoretical framework for evaluating the consequences of the tradeoff between vaccine efficacy (in terms of preventing new infections with wild-type strains) and safety (in terms of vaccine-induced AIDS deaths). We use our framework to predict, for Zimbabwe and Thailand, the epidemiological impact of 1,000 different (specified by efficacy and safety characteristics) LAHVs. We predict that paradoxically: (i) in Zimbabwe (where transmission is high) LAHVs would significantly decrease the AIDS death rate, but (ii) in Thailand (where transmission is low) exactly the same vaccines (in terms of efficacy and safety characteristics) would increase the AIDS death rate. Our results imply that a threshold transmission rate exists that determines whether any given LAHV has a beneficial or a detrimental impact. We also determine the vaccine perversity point, which is defined in terms of the fraction of vaccinated individuals who progress to AIDS as a result of the vaccine strain. Vaccination with any LAHV that causes more than 5% of vaccinated individuals to progress to AIDS in 25 years would, even 50 years later, lead to perversity (i.e., increase the annual AIDS death rate) in Thailand; these same vaccines would lead to decreases in the annual AIDS death rate in Zimbabwe.


Utilization of endogenous and dietary urea in the large intestine of the mature horse.
The dynamics of N metabolism in mature horses were investigated when they were fed on a low-N diet or the same diet supplemented with sufficient urea or soybean meal to meet their theoretical N requirements. There were no differences in DM, organic matter or neutral-detergent-fibre digestibilities for the three diets. N digestibilities and digestible-N intakes were similar for the urea- and soyabean-supplemented diets and very low for the low-N diet. For all three diets plasma urea was degraded in the digestive tract to NH3 which was utilized by the bacterial population as a N source. NH3 was absorbed from the large intestine into the blood and converted to urea. NH3 was also incorporated into plasma proteins. The horses fed on the low-N diet degraded a greater proportion of endogenous urea in the digestive tract than did horses fed on the urea-or soyabean-supplemented diets. However, the horses fed on the urea diet had the highest degradation rate of urea. The quantity of urea degraded in the digestive tract of horses fed on the urea-supplemented and the low-N diets could not compensate for a lack of dietary crude protein in these diets. The horses were in a negative N balance when fed on the low-N and urea-supplemented diets and a positive N balance when fed on the soyabean-supplemented diet. Dietary urea supplementation did not benefit the horses.


Artificial Outdoor Nighttime Lights Associate with Altered Sleep Behavior in the American General Population.
Our study aims to explore the associations between outdoor nighttime lights (ONL) and sleep patterns in the human population. Cross-sectional telephone study of a representative sample of the general US population age 18 y or older. 19,136 noninstitutionalized individuals (participation rate: 83.2%) were interviewed by telephone. The Sleep-EVAL expert system administered questions on life and sleeping habits; health; sleep, mental and organic disorders (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; International Classification of Sleep Disorders, Second Edition; International Classification of Diseases, 10(th) Edition). Individuals were geolocated by longitude and latitude. Outdoor nighttime light measurements were obtained from the Defense Meteorological Satellite Program's Operational Linescan System (DMSP/OLS), with nighttime passes taking place between 19:30 and 22:30 local time. Light data were correlated precisely to the geolocation of each participant of the general population sample. Living in areas with greater ONL was associated with delayed bedtime (P < 0.0001) and wake up time (P < 0.0001), shorter sleep duration (P < 0.01), and increased daytime sleepiness (P < 0.0001). Living in areas with greater ONL also increased the dissatisfaction with sleep quantity and quality (P < 0.0001) and the likelihood of having a diagnostic profile congruent with a circadian rhythm disorder (P < 0.0001). Although they improve the overall safety of people and traffic, nighttime lights in our streets and cities are clearly linked with modifications in human sleep behaviors and also impinge on the daytime functioning of individuals living in areas with greater ONL.


Dietary intake, nutritional status and rehabilitation outcomes of stroke patients in hospital.
Nutrition affects rehabilitation through its influence on physical and mental functioning, although little attention has been paid to effects on rehabilitation outcomes. The present study aimed to describe nutritional status and food consumption in stroke patients within 2 weeks of hospital admission and before discharge, as well as to investigate the effects of nutritional and dietary factors on rehabilitation outcomes. One hundred patients from a consecutive cohort admitted to a metropolitan hospital with acute stroke were recruited and assessed by a single researcher, with 38 reassessed at discharge. Nutritional status was assessed using Mini-Nutritional Assessment and anthropometric indices and dietary intake was assessed by 1-day weighed dietary records. Rehabilitation outcomes were changes in Barthel index scores and the rehabilitation efficiency index. Few (n = 9; 10%) consumed ≥100% of the estimated average requirement (EAR) for energy within 2 weeks of admission and 13 (33%) had energy intakes <50% of EAR before discharge. A small but increasing proportion (7% at admission, 13% at discharge) were identified as being malnourished across the inpatient stay. Younger age, lower Barthel index and a higher energy intake in the early stages of admission predicted the extent and rate of restoration of functional abilities by discharge (F = 7.503, P = 0.001; F = 14.558, P < 0.001). Given a general finding of nutritional deterioration identified for these patients, as well as the identification of energy intake as a modifiable influence on the extent and rate of recovery, there is clearly scope for the multidisciplinary development of nutritional support for stroke patients to improve rehabilitation outcomes.


Do we have a new standard in suboptimal debulked disease?
Treatment options for patients with high-risk advanced-stage ovarian cancer continue to evolve, including consideration of neoadjuvant chemotherapy (NACT), timing of cytoreductive surgery, utilization of intraperitoneal (IP) chemotherapy, adoption of dose-dense weekly paclitaxel (Taxol), addition of maintenance chemotherapy, and incorporation of bevacizumab. Overall, the proportion of patients with suboptimal residual disease has declined, partly as a result of more aggressive primary surgery, and partly through selection of patients for delayed surgery following NACT. However, the risk of recurrence in this population remains high, and treatment decisions need to be individualized, with consideration of clinical goals, avoidance of treatment-related toxicity, control of disease-related symptoms, and minimization of any negative impact on the quality of life. Innovative trials are needed to evaluate early predictors of primary platinum resistance and facilitate the development of non-platinum alternative treatment regimens.


[Characteristics of antibiotic therapy in neonates with polyorgan insufficiency].
Polyorgan insufficiency (POI) is the main cause of death in ISU patients. The highest rates of morbidity and mortality due to POI are recorded among newborns. Antibbacterial therapy of probable infections processes is widely used in neonatology, however long-term antibacterial therapy is not favouable for newborn infants. The aim of the present study was to investigate the peculiarities of antibacterial therapy in newborn with POI. The trial enrolled 453 infants antibacterial therapy was used in all of them (100%). The most frequent drugs used in the treatment were the III and IV generation cephalosporines and aminoglycosides. The POI antibacterial therapy in severe cases was more intensive and prolonged. The most long-term therapy was applied to newborns weighting 1500 g. Recovery of the organ function served as a criterion for discontinuation of the antibacterial therapy. Antibacterial of neonate infants with POI requires optimization.


Evaluating the effectiveness of labor market interventions on reducing the impacts of the COVID-19 pandemic.
This paper evaluates whether different labor market policy interventions taken in response to the COVID-19 pandemic have been effective in reducing its adverse impacts. We construct a database covering 165 countries and 39 labor market interventions grouped into four pillars: stimulating the economy and jobs (pillar 1); supporting enterprises, employment, and incomes (pillar 2); protecting workers (pillar 3); and social dialogue (pillar 4). The results revealed that measures taken under pillars 1, 2, and 3 have reduced the impacts of the pandemic on economic growth; measures under pillar 4 were significantly associated with reducing its impacts on employment and those under pillar 2 with reducing its impacts on working hours.


[Preventive and interceptive orthodontics in the primary health care network of the Brazilian Unified Health System: the viewpoint of the dental surgeons of Florianopolis City Hall].
The scope of this exploratory study was to understand the viewpoint of the dental surgeons of the Primary Health Care (PHC) network in Florianópolis regarding the need, feasibility and interest in broadening preventive orthodontic services and in the implementation of interceptive orthodontics. A structured questionnaire was used to establish the viewpoint of all the primary care dental surgeons who perform clinical care in the network. The results indicate that: the majority are in favor provided that there is an appropriate structure to attend the needs of the population; the professionals consider themselves unqualified to perform the requisite procedures, so training would be necessary; there would be no need to deploy other orthodontic procedures in primary care than those analyzed; and the main difficulties that might be encountered were related to excess demand and the lack of human resources. Despite these obstacles, the majority of the professionals consider it positive and feasible to introduce this service, which could increase the comprehensiveness of health care and bolster primary care, thereby improving the health of the population.


ViralMSA: massively scalable reference-guided multiple sequence alignment of viral genomes.
In molecular epidemiology, the identification of clusters of transmissions typically requires the alignment of viral genomic sequence data. However, existing methods of multiple sequence alignment (MSA) scale poorly with respect to the number of sequences. ViralMSA is a user-friendly reference-guided MSA tool that leverages the algorithmic techniques of read mappers to enable the MSA of ultra-large viral genome datasets. It scales linearly with the number of sequences, and it is able to align tens of thousands of full viral genomes in seconds. However, alignments produced by ViralMSA omit insertions with respect to the reference genome. ViralMSA is freely available at https://github.com/niemasd/ViralMSA as an open-source software project. Supplementary data are available at Bioinformatics online.


Estrogens in rheumatoid arthritis; the immune system and bone.
Rheumatoid arthritis (RA) is an autoimmune disease that is more common in women than in men. The peak incidence in females coincides with menopause when the ovarian production of sex hormones drops markedly. RA is characterized by skeletal manifestations where production of pro-inflammatory mediators, connected to the inflammation in the joint, leads to bone loss. Animal studies have revealed distinct beneficial effects of estrogens on arthritis, and a positive effect of hormone replacement therapy has been reported in women with postmenopausal RA. This review will focus on the influence of female sex hormones in the pathogenesis and progression of RA.


Analysis of the HLA class I associated peptide repertoire in a hepatocellular carcinoma cell line reveals tumor-specific peptides as putative targets for immunotherapy.
HLA class I molecules present peptides on the cell surface to CD8(+) T cells. The repertoire of peptides that associate to class I molecules represents the cellular proteome. Therefore, cells expressing different proteomes could generate different class I-associated peptide repertoires. A large number of peptides have been sequenced from HLA class I alleles, mostly from lymphoid cells. On the other hand, T cell immunotherapy is a goal in the fight against cancer, but the identification of T cell epitopes is a laborious task. Proteomic techniques allow the definition of putative T cell epitopes by the identification of HLA natural ligands in tumor cells. In this study, we have compared the HLA class I-associated peptide repertoire from the hepatocellular carcinoma (HCC) cell line SK-Hep-1 with that previously described from lymphoid cells. The analysis of the peptide pool confirmed that, as expected, the peptides from SK-Hep-1 derive from proteins localized in the same compartments as in lymphoid cells. Within this pool, we have identified 12 HLA class I peptides derived from HCC-related proteins. This confirms that tumor cell lines could be a good source of tumor associated antigens to be used, together with MS, to define putative epitopes for cytotoxic T cells from cancer patients.


Hemodynamic-induced changes in aortic valve area: implications for Doppler cardiac output determinations.
Monitoring cardiac output (CO) by transesophageal echocardiography involves measurements of ascending aortic flow and an initial measurement of aortic valve area (AVA). Hemodynamic-induced changes in AVA are a potential source of error for this simplified method. Our goal was to quantify these changes in AVA and their effects on CO calculations. In 17 anesthetized patients, a dobutamine infusion was titrated to achieve a 50% increase in ascending aortic flow velocity (V(max)). Hemodynamic and echocardiographic variables, including V(max) and planimetry of AVA, were determined at baseline and at maximal dobutamine dose. Dobutamine produced a 3.0 +/- 1.4 L/min increase in CO, a 54.5% +/- 19.6% increase in V(max), and a 50.6% +/- 34.2% increase in systolic blood pressure. AVA increased by 4.3% +/- 2.6% during dobutamine infusion (P < 0.001). The simplified CO method, which does not account for increases in AVA, produced a 0.32 +/- 0.24 L/min underestimation of CO. This investigation demonstrates hemodynamic-induced changes in AVA. The use of a single AVA measurement for all subsequent CO calculations introduces a clinically acceptable degree of error, supporting a simplified CO protocol requiring less probe manipulation and reduced procedural time. An intraoperative dobutamine infusion was used to increase aortic blood flow and demonstrate hemodynamic-induced changes in aortic valve area. These valve-area changes affect the accuracy of Doppler cardiac output determinations.


Evaluating the Contribution of Executive Functions to Language Tasks in Cognitively Demanding Contexts.
Purpose The purpose of this study was to determine the degree to which the executive functions of attention switching and inhibition predicted performance on language subtests from the Temple Assessment of Language and (Verbal) Short-Term Memory in Aphasia (TALSA; N. Martin, Minkina, Kohen, &Kalinyak-Fliszar, 2018) across 3 interval conditions (no delay, 5-s delay, and 5-s filled delay), which was designed to add a memory and executive load to language tasks. Method This study was a post hoc experimental design. Participants included 27 people with aphasia who were administered 5 subtests from the TALSA (Naming, Word Repetition, Nonword Repetition, Category Judgment, and Rhyming Judgment), which were selected to evaluate input and output levels of processing in the 3 interval conditions listed above. Three executive tasks were administered to evaluate inhibition (Simon and Flanker tasks) and attention switching (number-letter shifting). Results Independent variables were proportion correct on each TALSA task in 3 separate time conditions, and predictor variables were efficiency on the Simon task and number-letter shifting task. Linear regression modeling was completed, which revealed that inhibition was a significant predictor of proportion correct for Word Repetition and Category Judgment in the 5-s filled interval condition. Conclusions Our findings indicate that inhibition plays a role in completing tasks that require lexical and/or semantic processing in cognitively demanding conditions. Attention switching was not a significant predictor for any task. These results are an important step toward creating methods to evaluate executive skills in the context of language production. Supplemental Material https://doi.org/10.23641/asha.9765107.


Ca2+ transport in pancreatic beta-cells during glucose stimulation of insulin secretion.
The role of Ca2+ in the regulation of insulin secretion was evaluated using beta-cell-rich pancreatic islets isolated from ob/ob-mice. The glucose stimulation of the secretory activity is supposed to result from accumulation of Ca2+ in the submembrane cytoplasmic space. It is likely that this process reflects the balance between increased entry of Ca2+ into the beta-cells and an enhanced sequestration of Ca2+ in the organelle sinks. The proposed model can explain the cAMP potentiation of glucose-stimulated insulin release with suppression of the mitochondrial Ca2+ uptake. Furthermore, differences in the Ca2+ buffering capacity of the secretory granules may account for other characteristic features of glucose-stimulated insulin release, in particular its biphasic nature and sensitivity to suppression on withdrawal of nutrients.


Transcriptomic Signatures of Human Immunodeficiency Virus Post-Treatment Control.
Posttreatment controllers (PTCs) are rare HIV-infected individuals who can limit viral rebound after antiretroviral therapy interruption (ATI), but the mechanisms of this remain unclear. To investigate these mechanisms, we quantified various HIV RNA transcripts (via reverse transcription droplet digital PCR [RT-ddPCR]) and cellular transcriptomes (via RNA-seq) in blood cells from PTCs and noncontrollers (NCs) before and two time points after ATI. HIV transcription initiation did not significantly increase after ATI in PTCs or in NCs, whereas completed HIV transcripts increased at early ATI in both groups and multiply-spliced HIV transcripts increased only in NCs. Compared to NCs, PTCs showed lower levels of HIV DNA, more cell-associated HIV transcripts per total RNA at all times, no increase in multiply-spliced HIV RNA at early or late ATI, and a reduction in the ratio of completed/elongated HIV RNA after early ATI. NCs expressed higher levels of the IL-7 pathway before ATI and expressed higher levels of multiple cytokine, inflammation, HIV transcription, and cell death pathways after ATI. Compared to the baseline, the NCs upregulated interferon and cytokine (especially TNF) pathways during early and late ATI, whereas PTCs upregulated interferon and p53 pathways only at early ATI and downregulated gene translation during early and late ATI. In NCs, viral rebound after ATI is associated with increases in HIV transcriptional completion and splicing, rather than initiation. Differences in HIV and cellular transcription may contribute to posttreatment control, including an early limitation of spliced HIV RNA, a delayed reduction in completed HIV transcripts, and the differential expression of the IL-7, p53, and TNF pathways. IMPORTANCE The findings presented here provide new insights into how HIV and cellular gene expression change after stopping ART in both noncontrollers and posttreatment controllers. Posttreatment control is associated with an early ability to limit increases in multiply-spliced HIV RNA, a delayed (and presumably immune-mediated) ability to reverse an initial rise in processive/completed HIV transcripts, and multiple differences in cellular gene expression pathways. These differences may represent correlates or mechanisms of posttreatment control and may provide insight into the development and/or monitoring of therapeutic strategies that are aimed at a functional HIV cure.


Molecular analysis of Bacillus subtilis ada mutants deficient in the adaptive response to simple alkylating agents.
Previously, we isolated and characterized six Bacillus subtilis ada mutants that were hypersensitive to methylnitroso compounds and deficient in the adaptive response to alkylation. Cloning of the DNA complementing the defects revealed the presence of an ada operon consisting of two tandem and partially overlapping genes, adaA and adaB. The two genes encoded proteins with methylphosphotriester-DNA methyltransferase and O6-methylguanine-DNA methyltransferase activities, respectively. To locate the six mutations, the ada operon was divided into five overlapping regions of about 350 bp. The fragments of each region were amplified by polymerase chain reaction and analyzed by gel electrophoresis to detect single-strand conformation polymorphism. Nucleotide sequences of the fragments exhibiting mobility shifts were determined. Three of the mutants carried sequence alterations in the adaA gene: the adaA1 and adaA2 mutants had a one-base deletion and insertion, respectively, and the adaA5 mutant had a substitution of two consecutive bases causing changes of two amino acid residues next to the presumptive alkyl-accepting Cys-85 residue. Three mutants carried sequence alterations in the adaB gene: the adaB3 mutant contained a rearrangement, the adaB6 mutant contained a base substitution causing a change of the presumptive alkyl-accepting Cys-141 to Tyr, and the adaB4 mutant contained a base substitution changing Leu-167 to Pro. The adaB mutants produced ada transcripts upon treatment with low doses of alkylating agents, whereas the adaA mutant did not. We conclude that the AdaA protein functions as the transcriptional activator of this operon, while the AdaB protein specializes in repair of alkylated residues in DNA.


Improving the Conservation of Mediterranean Chondrichthyans: The ELASMOMED DNA Barcode Reference Library.
Cartilaginous fish are particularly vulnerable to anthropogenic stressors and environmental change because of their K-selected reproductive strategy. Accurate data from scientific surveys and landings are essential to assess conservation status and to develop robust protection and management plans. Currently available data are often incomplete or incorrect as a result of inaccurate species identifications, due to a high level of morphological stasis, especially among closely related taxa. Moreover, several diagnostic characters clearly visible in adult specimens are less evident in juveniles. Here we present results generated by the ELASMOMED Consortium, a regional network aiming to sample and DNA-barcode the Mediterranean Chondrichthyans with the ultimate goal to provide a comprehensive DNA barcode reference library. This library will support and improve the molecular taxonomy of this group and the effectiveness of management and conservation measures. We successfully barcoded 882 individuals belonging to 42 species (17 sharks, 24 batoids and one chimaera), including four endemic and several threatened ones. Morphological misidentifications were found across most orders, further confirming the need for a comprehensive DNA barcoding library as a valuable tool for the reliable identification of specimens in support of taxonomist who are reviewing current identification keys. Despite low intraspecific variation among their barcode sequences and reduced samples size, five species showed preliminary evidence of phylogeographic structure. Overall, the ELASMOMED initiative further emphasizes the key role accurate DNA barcoding libraries play in establishing reliable diagnostic species specific features in otherwise taxonomically problematic groups for biodiversity management and conservation actions.


Temperament moderates developmental changes in vigilance to emotional faces in infants: Evidence from an eye-tracking study.
Affect-biased attention reflects the prioritization of attention to stimuli that individuals deem to be motivationally and/or affectively salient. Normative affect-biased attention is early-emerging, providing an experience-expectant function for socioemotional development. Evidence is limited regarding how reactive and regulatory aspects of temperament may shape maturational changes in affect-biased attention that operate at the earliest stages of information processing. This study implemented a novel eye-tracking paradigm designed to capture attention vigilance in infants. We assessed temperamental negative affect (NA) and attention control (AC) using laboratory observations and parent-reports, respectively. Among infants (N = 161 in the final analysis) aged 4 to 24 months (Mean = 12.05, SD = 5.46; 86 males), there was a significant age effect on fixation latency to emotional versus neutral faces only in infants characterized with high NA and high AC. Specifically, in infants with these temperament traits, older infants showed shorter latency (i.e., greater vigilance) toward neutral faces, which are potentially novel and unfamiliar to infants. The age effect on vigilance toward emotional faces was not significant. The findings support the argument that the development of affect-biased attention is associated with multiple temperament processes that potentially interact over time.


Understanding facilitators of and barriers to health promotion practice.
The health promotion best practices literature is imbued with hope for knowledge mobilization, enhanced practice, and improved population health. Given constrained medical care systems, health promotion is key to reducing the significant burden of chronic disease. However, we have seen little evidence of change. This article investigates facilitators of, and barriers to, three stages of health promotion practice in public health organizations, interagency coalitions, and volunteer committees. The article focuses not on what works but why it does or does not, drawing on five case studies within the Canadian Heart Health Initiative. Results indicate that the presence or absence of appropriately committed and/or skilled people, funds and/or resources, and priority and/or interest are the most common factors affecting all stages of health promotion practice. The article extends the literature on internal and external factors affecting health promotion and highlights strategic influences to consider in support of effective health promotion practice.


[The medical social characteristic of patients of private stomatological clinics].
The article deals with results of anonymous questionnaire survey of patient in private dental clinics "LiderDent" (241 respondents of able-bodied age) and "GelioDent" (419 respondents of able-bodied age). The purpose of the study was to investigate peculiarities of medical and social characteristics. The questionnaire included questions concerning social status of respondents, their financial condition, self-assessment of dental health and its maintenance at the proper level for a number of parameters, as well as evaluation of work of private dental organizations. The assessment of dental health of elderly patients established that 58.1% of respondents rated their dental health as good, 27.8% as satisfactory; and 4.1% of respondents estimated their dental health as bad. The analysis included also evaluation of negative health habits of respondents resulting in dental diseases and afflict damage to teeth and oral cavity. It was found that more than half of respondents had higher education. They consider themselves as financially secure, they did not smoke and had good condition of oral cavity. They choose dentists according recommendation of friends and seek dental care only in case of obvious signs of disease. The analysis of possible reasons for seeking dental professional revealed that 75.5% of respondents seek dental care when there are "obvious signs of disease and deterioration of health", 21.2% "when first signs of disease occurred" and 3.3% "only in critical situation". It is concluded that dental professional of private medical centers should be more widely carried out sanitary and educational work with population in order to increase the medical activity of patient, as well as to increase their awareness of ways and means of maintaining the dental health.


MC3: a steady-state model and constraint consistency checker for biochemical networks.
Stoichiometric models provide a structural framework for analyzing steady-state cellular behavior. Models are developed either through augmentations of existing models or more recently through automatic reconstruction tools. There is currently no standardized practice or method for validating the properties of a model before placing it in the public domain. Considerable effort is often required to understand a model's inconsistencies before its reuse within new research efforts. We present a review of common issues in stoichiometric models typically uncovered during pathway analysis and constraint-based optimization, and we detail succinct and efficient ways to find them. We present MC3, Model and Constraint Consistency Checker, a computational tool that can be used for two purposes: (a) identifying potential connectivity and topological issues for a given stoichiometric matrix, S, and (b) flagging issues that arise during constraint-based optimization. The MC3 tool includes three distinct checking components. The first examines the results of computing the basis for the null space for Sv = 0; the second uses connectivity analysis; and the third utilizes Flux Variability Analysis. MC3 takes as input a stoichiometric matrix and flux constraints, and generates a report summarizing issues. We report the results of applying MC3 to published models for several systems including Escherichia coli, an adipocyte cell, a Chinese Hamster Ovary cell, and Leishmania major. Several issues with no prior documentation are identified. MC3 provides a standalone MATLAB-based comprehensive tool for model validation, a task currently performed either ad hoc or implemented in part within other computational tools.


Spatiotemporal dynamics across visual cortical laminae support a predictive coding framework for interpreting mismatch responses.
Context modulates neocortical processing of sensory data. Unexpected visual stimuli elicit large responses in primary visual cortex (V1)-a phenomenon known as deviance detection (DD) at the neural level, or "mismatch negativity" (MMN) when measured with EEG. It remains unclear how visual DD/MMN signals emerge across cortical layers, in temporal relation to the onset of deviant stimuli, and with respect to brain oscillations. Here we employed a visual "oddball" sequence-a classic paradigm for studying aberrant DD/MMN in neuropsychiatric populations-and recorded local field potentials in V1 of awake mice with 16-channel multielectrode arrays. Multiunit activity and current source density profiles showed that although basic adaptation to redundant stimuli was present early (50 ms) in layer 4 responses, DD emerged later (150-230 ms) in supragranular layers (L2/3). This DD signal coincided with increased delta/theta (2-7 Hz) and high-gamma (70-80 Hz) oscillations in L2/3 and decreased beta oscillations (26-36 Hz) in L1. These results clarify the neocortical dynamics elicited during an oddball paradigm at a microcircuit level. They are consistent with a predictive coding framework, which posits that predictive suppression is present in cortical feed-back circuits, which synapse in L1, whereas "prediction errors" engage cortical feed-forward processing streams, which emanate from L2/3.


Evaluation of serodiagnostic tests for T.b. gambiense human African trypanosomiasis in southern Sudan.
A survey was conducted in a low-endemic and in a non-endemic area of Sudan to evaluate the specificity and efficiency of different serological antibody detection techniques for Trypanosoma brucei gambiense. Comparisons were made of the card agglutination test for trypanosomiasis (CATT) on diluted blood, on diluted plasma and on eluates from blood dried on filter paper, the LATEX test on diluted plasma and an ELISA on diluted plasma and filter paper. The specificities of all the serological tests were not significantly different from CATT on diluted blood (99.5%). The specificity of CATT on diluted blood was similar (99.3%). The highest sensitivities (100%) were observed with CATT on diluted blood and with CATT and LATEX on diluted plasma. CATT on diluted blood was more cost-efficient than the classic test, CATT on whole blood.


Regulation of cGMP-dependent current in On bipolar cells by calcium/calmodulin-dependent kinase.
The metabotropic receptor mGluR6 is localized to the dendrites of On bipolar cells and mediates synaptic input from photoreceptors. The binding of glutamate to the receptor activates a phosphodiesterase (PDE), which then hydrolyzes cGMP. A nonselective cationic conductance, believed to be gated directly by cGMP, is turned off as a result of the fall in cGMP levels, and the cell hyperpolarizes. Here we present evidence for regulation of the conductance by an additional mechanism that it is independent of cGMP. Whole-cell recordings were obtained from On bipolar cells in slices of tiger salamander retina. Dialysis of cells with 1 microM KN-62 or 10 microM KN-93, two inhibitors of type II calmodulin-dependent protein kinase (CaMKII), depressed cGMP-dependent currents. This depression persisted when hydrolysis of cGMP was prevented with IBMX, a broad-spectrum PDE inhibitor, suggesting that CaMKII acts downstream from the PDE in the cascade. The depression of cGMP-dependent currents was probably not due to a direct interaction of the inhibitors with the channels as neither 1 microM KN-62 or 10 microM KN-93 was found to have any effect on cyclic nucleotide-gated channels when applied directly to excised patches of rod outer segments. We propose that phosphorylation by CaMKII may be an important mechanism for regulating the cGMP-dependent conductance of On bipolar cells.


Biogenesis of a bacterial organelle: the carboxysome assembly pathway.
The carboxysome is a protein-based organelle for carbon fixation in cyanobacteria, keystone organisms in the global carbon cycle. It is composed of thousands of subunits including hexameric and pentameric proteins that form a shell to encapsulate the enzymes ribulose 1,5-bisphosphate carboxylase/oxygenase and carbonic anhydrase. Here, we describe the stages of carboxysome assembly and the requisite gene products necessary for progression through each. Our results demonstrate that, unlike membrane-bound organelles of eukaryotes, in carboxysomes the interior of the compartment forms first, at a distinct site within the cell. Subsequently, shell proteins encapsulate this procarboxysome, inducing budding and distribution of functional organelles within the cell. We propose that the principles of carboxysome assembly that we have uncovered extend to diverse bacterial microcompartments.


Cannabis Smoking-induced Diffuse Alveolar Hemorrhage.
Cannabis smoking is common among adolescents and young adults. Diffuse alveolar hemorrhage (DAH) is a rare and life-threatening complication of cannabis abuse. DAH is characterized by bleeding into alveoli secondary to the disruption of the alveolar-capillary basement membrane as a result of an injury at the level of alveolar microcirculation. The differential diagnosis of DAH includes systemic vasculitis, bland pulmonary hemorrhage, and alveolar damage. The impact of cannabis on the respiratory function includes mucus hypersecretion, inflammatory edema, and increased alveolar permeability. Moreover, in vitro coagulation studies on rats showed that two major cannabinoids, cannabinol and THC, have antithrombotic activity. We present two cases of cannabis use resulting in acute lung injury and diffuse alveolar hemorrhage.


Spontaneous pustular dermatitis in a newborn piglet associated with a poxvirus.
Poxvirus was recovered from pustular skin lesions in a newborn piglet. The lesions were present at birth, suggesting transplacental infection had occurred. The lesions were circular, 1 cm in diameter, and were found over the entire skin surface, bulbs of the heels, coronets, tongue and buccal mucosa. Histologically, cells in the stratum intermedium were undergoing ballooning degeneration and necrosis, coalescing to form vesicles. The lumen of vesicles was filled with fluid and inflammatory cells. Degenerating epithelial cell nuclei were often vacuolated and eosinophilic intracytoplasmic inclusions were in many ballooned cells. The size and morphology of the virions recovered from vesicular fluid, place them in the poxvirus group.


A syndrome of acne vulgaris and subclinical dermographic urticaria.
Patients with acne vulgaris and subclinical dermographism constitute a distinct, common, and hitherto unrecognized group. One hundred and thirty such clinical patients were observed in a private dermatology practice. These patients relate that their acne produces the symptoms of itching, burning, soreness, and/or tenderness. The lesions are characterized clinically by one or a combination of the following signs: erythema, violaceous discoloration, ecchymoses, and a scarlet to livid halo about the pustule or inflamed closed comedone. I tested for the dermographic phenomena in patients with acne both entering and already being treated in a private dermatology practice over a two-year period. Patient's age, sex, whether or not dermographism predated or postdated onset of acne, symptoms of lesions, premenstrual flare, and history of atopy were recorded. Most patients were between the ages of twenty and forty years, and the majority were women. All had symptomatic lesions, and a significant minority noted no prior dermographic capability. The vast majority of women had premenstrual flares. A greater number of these patients were atopic than had been anticipated. The nonsedating antihistamine terfenadine mitigated both the signs and symptoms of the process. The syndrome of acne vulgaris with dermographism presenting as a unique visual and symptomatic variant of common acne is frequently seen, easily recognized, and highly treatable.


Bioceramic root repair material (BCRRM) for root-end obturation in apical surgery. An analysis of 174 teeth after 1 year.
The objective of this paper was the analysis of the 1-year outcome of teeth treated with apical surgery and a recently introduced bioceramic root repair material (BCRRM) for root-end filling. Patients were consecutively enrolled from 2015 to 2017. Apical surgery included the modern technique, i.e. the use of a surgical microscope, ultrasonic preparation of a root-end cavity, and retrofilling with BCRRM. The cohort comprised 150 patients with 174 treated teeth. Patients were recalled one year after surgery for a clinical and radiographic re-examination. Three experienced observers evaluated the periapical radiographs with regard to periapical healing utilizing the healing criteria established by Rud et al. (1972) and Molven et al. (1987). Based on the clinical findings and the radiographic assessment, healing was judged as successful, uncertain, or failed. Study parameters included gender, age, type of treated tooth, and type of BCRRM (regular vs. fast set putty). At the 1-year follow-up, 170 teeth could be reexamined (drop-out rate 2.3%). Healing outcome was categorized as successful in 94.1%, uncertain in 4.1%, and failed in 1.8%. No significant differences were observed when comparing the success rates among the different subcategories of study parameters. The lowest success rate was noted in mandibular premolars (86.7%) but without reaching statistical significance. In conclusion, BCRRM appears to be a biocompatible root-end filling material showing excellent 1-year results. The success rate was similar to recently reported success rates for BCRRM in apical surgery.


The neural mechanisms underlying the acute effect of cigarette smoking on chronic smokers.
Although previous research had related structural changes and impaired cognition to chronic cigarette smoking, recent neuroimaging studies have associated nicotine, which is a main chemical substance in cigarettes, with improvements in cognitive functions (e.g. improved attention performance). However, information about the alterations of whole-brain functional connectivity after acute cigarette smoking is limited. In this study, 22 smokers underwent resting-state functional magnetic resonance imaging (rs-fMRI) after abstaining from smoking for 12 hours (state of abstinence, SOA). Subsequently, the smokers were allowed to smoke two cigarettes (state of satisfaction, SOS) before they underwent a second rs-fMRI. Twenty non-smokers were also recruited to undergo rs-fMRI. In addition, high-resolution 3D T1-weighted images were acquired using the same magnetic resonance imaging(fMRI)scanner for all participants. The results showed that smokers had structural changes in insula, thalamus, medial frontal cortex and several regions of the default mode network (DMN) compared with non-smokers. Voxel-wise group comparisons of newly developed global brain connectivity (GBC) showed that smokers in the SOA condition had higher GBC in the insula and superior frontal gyrus compared with non-smokers. However, smokers in the SOS condition demonstrated significantly lower GBC in several regions of the DMN, as compared with smokers in the SOA condition. These results suggest that structural integrity combined with dysfunction of the DMN might be involved in relapses after a short period of time among smokers.


A root-expressed magnesium transporter of the MRS2/MGT gene family in Arabidopsis thaliana allows for growth in low-Mg2+ environments.
The MRS2/MGT gene family in Arabidopsis thaliana belongs to the superfamily of CorA-MRS2-ALR-type membrane proteins. Proteins of this type are characterized by a GMN tripeptide motif (Gly-Met-Asn) at the end of the first of two C-terminal transmembrane domains and have been characterized as magnesium transporters. Using the recently established mag-fura-2 system allowing direct measurement of Mg(2+) uptake into mitochondria of Saccharomyces cerevisiae, we find that all members of the Arabidopsis family complement the corresponding yeast mrs2 mutant. Highly different patterns of tissue-specific expression were observed for the MRS2/MGT family members in planta. Six of them are expressed in root tissues, indicating a possible involvement in plant magnesium supply and distribution after uptake from the soil substrate. Homozygous T-DNA insertion knockout lines were obtained for four members of the MRS2/MGT gene family. A strong, magnesium-dependent phenotype of growth retardation was found for mrs2-7 when Mg(2+) concentrations were lowered to 50 microM in hydroponic cultures. Ectopic overexpression of MRS2-7 from the cauliflower mosaic virus 35S promoter results in complementation and increased biomass accumulation. Green fluorescent protein reporter gene fusions indicate a location of MRS2-7 in the endomembrane system. Hence, contrary to what is frequently found in analyses of plant gene families, a single gene family member knockout results in a strong, environmentally dependent phenotype.


Diagnosis and initial management in psoriatic arthritis: a qualitative study with patients.
PsA is an inflammatory condition that can cause pain, fatigue, swelling and joint stiffness. The consequences include impaired physical function, a high psychosocial burden, reduced quality of life and work disability. The presenting symptoms can be non-specific and varied, leading to delays in diagnosis or referral to specialist teams. The aim of this study was to explore patients' experiences of being diagnosed and the initial management of PsA. The study used a qualitative design, with data collected in one-to-one, face-to-face semi-structured interviews. Fifteen newly diagnosed patients (<24 months) from three hospital sites in the southwest of England participated. Interviews were transcribed, anonymized and analysed using inductive thematic analysis. The following two main themes with sub-themes represent the data: symptom onset to specialist care: 'it was the blind leading the blind' (making sense of symptoms; mis-diagnosis and missed opportunities; and fast and easy access to expertise); and diagnosis as a turning point: 'having somebody say you've got something wrong with you, I was euphoric' (validation and reassurance; weighing up treatment options; taking on self-management; and acknowledging loss and change). Participants were already dealing with functional limitations and were highly distressed and anxious by the time they received their diagnosis. Physical and mental outcomes could be improved by the implementation of existing psoriasis management guidelines and strategies for earlier referral from primary care to rheumatology and by the development of guidelines on educational, self-management and psychological support provision soon after diagnosis.


Three methods of information assessment for optical data processing.
The determination of the specific information in a message has proved of interest in coding (for instance in a hologram) as well as in data processing itself. Also, simple considerations about the definition of optical information have grown into several groups of processing methods. At first the concept of characteristic spatial frequency bands, which describe essential features of any object, leads to compression of its Fourier terms in order to increase the transfer density of a transmitting system and the storage capacity of the recording media. With the emphasis being put on the informative value of the reference in holography, geometrical compression is applied in particular to the coding of printed texts. The second and third groups of methods apparently deal with opposite approaches. Assuming a given message, one may select some parts of its spectrum for further processing or carry out average signals from the collections it contains. Both cases-sampling and averaging-permit the extraction of a group of data belonging to a set of discrete signals. The following developments are presented: image replicating at a determined energy level, step-by-step phase sampling grids, study of the displacement law for moving objects by random sampling of disturbed wavefronts and recording of incoherent holograms, on the one hand, and construction of average letters for comparison between manuscripts, average Fourier holograms, and power spectra, on the other hand. A last illustration is provided in connection with the appraisal of psychological tests.


Results of two consecutive trials of dose-intensive chemotherapy with doxorubicin and ifosfamide in patients with sarcomas.
The authors evaluate the efficacy and feasibility of dose-intensive doxorubicin and ifosfamide combination chemotherapy in patients with sarcomas. From January 1995 to April 1996, 33 evaluable patients with either metastatic sarcoma or primary sarcomas with a high-risk for metastases (all except one was previously untreated with chemotherapy) were treated on two consecutive protocols. The median age was 45 years (range, 15-68 years). The first protocol included doxorubicin at 75 mg/m2 given as a 72-hour infusion on days 1 to 3 along with ifosfamide at 2 g/m2/d over 2 hours x 5, days 1 to 5 (protocol AI 75/10). Granulocyte colony-stimulating factor (G-CSF) was used only if indicated according to American Society of Clinical Oncology guidelines. The second protocol included doxorubicin at 90 mg/m2 as a 72-hour continuous infusion and ifosfamide at 2.5 g/m2/d for 4 days (protocol AI 90/10) with prophylactic G-CSF. A median of four cycles were administered (range, 1-6). Three patients achieved a pathologic complete response (CR) and 18 patients achieved a partial response (PR) for a response rate (RR) of 64% (95% confidence interval (CI), 45-80%). Response rate for the subset of patients with soft-tissue sarcomas was 66% (95% CI, 46-82%). Only three patients progressed on therapy. Febrile neutropenia was noted in 31% of cycles at AI 75/10 and in 56% of cycles at AI 90/10. One patient developed reversible grade 3 central nervous system (CNS) toxicity. There was one treatment-related death on AI 90/10 secondary to doxorubicin cardiac toxicity at a cumulative dose of 435 mg/m2. Dose-intensive doxorubicin plus ifosfamide is feasible in appropriately selected patients and appears to be a very active regimen in patients with sarcomas. The authors are currently testing this regimen with G-CSF and thrombopoietin.


Links between temporal acuity and multisensory integration across life span.
The temporal relationship between individual pieces of information from the different sensory modalities is one of the stronger cues to integrate such information into a unified perceptual gestalt, conveying numerous perceptual and behavioral advantages. Temporal acuity, however, varies greatly over the life span. It has previously been hypothesized that changes in temporal acuity in both development and healthy aging may thus play a key role in integrative abilities. This study tested the temporal acuity of 138 individuals ranging in age from 5 to 80. Temporal acuity and multisensory integration abilities were tested both within and across modalities (audition and vision) with simultaneity judgment and temporal order judgment tasks. We observed that temporal acuity, both within and across modalities, improved throughout development into adulthood and subsequently declined with healthy aging, as did the ability to integrate multisensory speech information. Of importance, throughout development, temporal acuity of simple stimuli (i.e., flashes and beeps) predicted individuals' abilities to integrate more complex speech information. However, in the aging population, although temporal acuity declined with healthy aging and was accompanied by declines in integrative abilities, temporal acuity was not able to predict integration at the individual level. Together, these results suggest that the impact of temporal acuity on multisensory integration varies throughout the life span. Although the maturation of temporal acuity drives the rise of multisensory integrative abilities during development, it is unable to account for changes in integrative abilities in healthy aging. The differential relationships between age, temporal acuity, and multisensory integration suggest an important role for experience in these processes. (PsycINFO Database Record


Histological changes in cervical lymph nodes following clinical irradiation.
Clinical radiation in man is shown to have similar effects to single dose irradiation in animals. While it is not possible by examining individual nodes to estimate the dose of radiation they have received, progressive changes with increasing doses can be seen leading to loss of lymphoid tissue and replacement by fibrous tissue. Functional changes probably occur, leading to loss of the filtering power of the nodes and their by-pass by anatomotic lymph channels. The purpose of this paper is in no way an appeal to discard radiation as a form of treatment for cancer. The destructive effects of radiation have been known form some time, but the significance of the regional nodes in the immune response to tumour has only recently been considered. A reappraisal is required of the way radiation therapy is given, so that as much as possbile of the immune mechanism may be left undamaged.


Clinical features and imaging examination assessment of cervical lymph nodes for thyroid carcinoma.
The purpose of this study is to investigate the relationship between clinical characteristics and cervical lymph node metastasis (LNM) in patients with thyroid carcinoma, as well as estimate the preoperative diagnosis values of ultrasound (US) and contrast enhanced computed tomography (CECT) examinations on the neck for detection of cervical LNM in thyroid carcinoma. A retrospective analysis of 3 026 patients with surgically proven thyroid carcinoma was conducted. Patients' clinical characteristics, including gender, age, tumor size, bilateral lesions, multifocality, adenomatous nodules, Hashimoto's thyroiditis (HT), and extrathyroidal extension, were collected to explore their association with cervical LNM in thyroid carcinoma. Preoperative assessments for central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM) were conducted through US and CECT. The diagnostic value of US, CECT and US combined with CECT for detection of LNM located in various cervical compartments was estimated based on the pathological results. The risk of cervical LNM was higher in thyroid cancer patients who were male, age < 55 years old, tumor size > 10 mm, bilateral lesions, and extrathyroidal extension, while multifocality, adenomatous nodules and HT had no significant effect on LNM. US, CECT and US combined with CECT all had a higher sensitivity to LLNM (93.1%, 57.8%, 95.4%) than to CLNM (32.3%, 29.0%, 43.4%). US and CECT had a high specificity to both CLNM and LLNM (94.3-97.8%). Preoperative clinical characteristics and imaging examinations on patients with thyroid carcinoma are crucial to the evaluation of cervical lymph nodes and conducive to individualizing surgical treatments by clinicians. US combined with CECT are superior to single US or CECT alone in detection of CLNM and LLNM.


HaCaT human keratinocytes express IGF-II, IGFBP-6, and an acid-activated protease with activity against IGFBP-6.
The insulin-like growth factor (IGF) system plays an important role in skin. HaCaT human keratinocytes proliferate in response to IGFs and synthesize IGF-binding protein-3 (IGFBP-3). Recently, IGFBP-6 was also identified by NH2-terminal sequencing, but it has not been identified by Western ligand blotting. In the present study, IGFBP-6 was detected in HaCaT-conditioned medium by use of immunoblotting and Western ligand blotting with 125I-labeled IGF-II. Proteolytic activity against IGFBPs, an important mechanism for regulation of their activity, was then studied. An acid-activated, cathepsin D-like protease that cleaved both IGFBP-6 and IGFBP-3 was detected. Although proteolysis did not substantially reduce the size of immunoreactive IGFBP-6, it greatly reduced the ability of IGFBP-6 to bind 125I-IGF-II as determined by Western ligand blotting and solution assay. HaCaT keratinocytes do not express IGF-I mRNA, but IGF-II mRNA and protein expression was detected. These observations suggest the possibility of an autocrine IGF-II loop that is regulated by the relative expression of IGF-II, IGFBP-3, and IGFBP-6, and IGFBP proteases in these keratinocytes, although demonstration of this loop requires further study.


Denosumab for bone health in prostate and breast cancer patients receiving endocrine therapy? A systematic review and a meta-analysis of randomized trials.
Hormonal therapies for receptor positive-breast and prostate cancer patients have shown clinical efficacy but also several side effects including osteoporosis, loss of bone mass and increased fracture risk. Denosumab represents an anti RANKL (receptor activator of nuclear factor-kB ligand) monoclonal anti-body acting as inhibitor of osteoclasts formation, function, and survival, then increasing bone mass. Herein, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the role of Denosumab in saving bone health in prostate and breast cancer patients receiving respectively androgen deprivation therapy and adjuvant endocrine therapy. Moreover, selected patients have to be treated with Denosumab at the dose of 60 mg every six month or placebo. Outcomes studied included the bone mass density (BMD) increase at 24 and 36 months, BMD loss, reduction of fractures risk (in particular vertebral) at 24 and 36 months and safety (overall, serious adverse events - SAEs and discontinuation rate). Our results showed a reduction of the BMD loss up to 36 months both at the lumbar and femoral level and a BMD increase both at 24 and 36 months. It was also found a reduction in the number of new vertebral and femoral fractures at 24 and 36 months. Finally, our pooled analysis showed that Denosumab did not affect both the SAEs and therapy discontinuation risk. In conclusion, Denosumab administration can be considered effective and safe in the prevention and management of the above mentioned adverse events related to hormonal therapies designed for breast and prostate tumors.


[Extracts of regenerating Planarians regulate proliferation of vertebrate cells].
The effects of extracts from intact and regenerating planarians on cell behaviour in culture were studied. The extracts were added to the culture of Chinese hamster fibroblasts and to the primary culture of human lymphocytes. Some extracts contained active agents which influenced the proliferation of fibroblasts increasing or decreasing the mitotic index. The extracts exerted no effect on the mitotic index of lymphocytes. When the extracts were added to the lymphocyte culture together with phytohemagglutinin, which induces the proliferation, the mitotic index somewhat increased. The extracts of regenerating planarians contain factors which activate and inhibit cell proliferation in culture. The active factors stimulated, rather than induced proliferation.


Molecular insight into cotton leaf curl geminivirus disease resistance in cultivated cotton (Gossypium hirsutum).
Cultivated cotton (Gossypium hirsutum) is the most important fibre crop in the world. Cotton leaf curl disease (CLCuD) is the major limiting factor and a threat to textile industry in India and Pakistan. All the local cotton cultivars exhibit moderate to no resistance against CLCuD. In this study, we evaluated an exotic cotton accession Mac7 as a resistance source to CLCuD by challenging it with viruliferous whiteflies and performing qPCR to evaluate the presence/absence and relative titre of CLCuD-associated geminiviruses/betasatellites. The results indicated that replication of pathogenicity determinant betasatellite is significantly attenuated in Mac7 and probably responsible for resistance phenotype. Afterwards, to decipher the genetic basis of CLCuD resistance in Mac7, we performed RNA sequencing on CLCuD-infested Mac7 and validated RNA-Seq data with qPCR on 24 independent genes. We performed co-expression network and pathway analysis for regulation of geminivirus/betasatellite-interacting genes. We identified nine novel modules with 52 hubs of highly connected genes in network topology within the co-expression network. Analysis of these hubs indicated the differential regulation of auxin stimulus and cellular localization pathways in response to CLCuD. We also analysed the differential regulation of geminivirus/betasatellite-interacting genes in Mac7. We further performed the functional validation of selected candidate genes via virus-induced gene silencing (VIGS). Finally, we evaluated the genomic context of resistance responsive genes and found that these genes are not specific to A or D sub-genomes of G. hirsutum. These results have important implications in understanding CLCuD resistance mechanism and developing a durable resistance in cultivated cotton.


Influence of femoral head size on impingement, dislocation and stress distribution in total hip replacement.
Dislocation remains a serious complication of total hip replacement. An insufficient range of motion can lead to impingement of the prosthetic neck on the acetabular cup. Together with the initiation of subluxation and dislocation, recurrent impingement can cause material failure in the liner. The objective of this study was to generate a validated finite element (FE) model capable of predicting the dislocation stability of different femoral head sizes with regard to impingement in different implant positions as well as the corresponding stress distribution in the liner. In order to cover posterior and anterior dislocation, two total hip dislocation associated manoeuvres were simulated using a three-dimensional nonlinear finite element model. The dislocation stability of two head sizes was determined numerically and experimentally. After validation, the FE model was used to analyse the dislocation stability of four different head sizes in variable implant positions. Range of motion (ROM) until impingement, the resisting moment that was developed and ROM until dislocation were evaluated. Additionally, stress distribution within the polyethylene liner during impingement and subluxation was determined. For both dislocation modes, a cup position of 45 degrees lateral abduction and 15 degrees up to 30 degrees anteversion resulted in appropriate ROM and dislocation stability. In general, larger head diameters revealed an increase in ROM and higher resisting moments. Stress analysis showed decreased contact pressures at the egress site of the liners with the larger inner diameters during subluxation. The analysis shows that an optimal implant position and a larger head diameter can reduce the risk of dislocation induced by impingement. The finite element model that was developed enables simplification of design variations compared to experimental studies since prototyping and assembling are replaced by prompt numerical simulation.


(IN) FERTILITY AND THE MODERN FEMALE LIFE COURSE IN TWO SOUTHERN NIGERIAN COMMUNITIES.
Being "modern" is an aspiration for many in sub-Saharan Africa and entails certain widely held expectations regarding material living conditions and social status. Using ethnographic and survey data on female fertility from two communities of southern Nigeria, this article describes some of the ways women are becoming modern and analyzes the forces behind these changes. The discussion includes education, initiation rites, premarital pregnancy, marriage, and the influence of Pentecostal Christianity. In agreement with modernization theory, there is a trend toward women becoming more educated and autonomous. They also increasingly valorize monogamy, companionate marriage, smaller families, and inclusion in the formal economy. In contradiction to the expectations of modernization theory, there is no decline in supernatural beliefs. Contemporary Christian churches are important to women becoming modern by helping them develop networks through voluntary associations, responding to women's aspirations for material goods, alleviating kin obligations, and encouraging personal spiritual advancement. (Southern Nigeria women, fertility, modernity, Pentecostal Christianity).


A mosaic of functional kainate receptors in hippocampal interneurons.
Although some physiological functions of kainate receptors (KARs) still remain unclear, recent advances have highlighted a role in synaptic physiology. In hippocampal slices, kainate depresses GABA-mediated synaptic inhibition and increases the firing rate of interneurons. However, the sensitivity to agonists of these responses differs, suggesting that the presynaptic and somatic KARs have a distinct molecular composition. Hippocampal interneurons express several distinct KAR subunits that can assemble into heteromeric receptors with a variety of pharmacological properties and that, in principle, could fulfill different roles. To address which receptor types mediate each of the effects of kainate in interneurons, we used new compounds and mice deficient for specific KAR subunits. In a recombinant assay, 5-carboxyl-2,4-di-benzamido-benzoic acid (NS3763) acted exclusively on homomeric glutamate receptor subunit 5 (GluR5), whereas 3S,4aR,6S,8aR-6-((4-carboxyphenyl)methyl) 1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid (LY382884) antagonized homomeric GluR5 and any heteromeric combination containing GluR5 subunits. In hippocampal slices, LY382884, but not NS3763, was able to prevent kainate-induced depression of evoked IPSC. In contrast, neither prevented the concomitant increase in spontaneous IPSC frequency. The selectivity of these compounds was seen additionally in knock-out mice, such that they were inactive in GluR5-/- mice but completely effective in GluR6-/- mice. Our data indicate that in wild-type mice, CA1 interneurons express heteromeric GluR6 -KA2 receptors in their somatic compartments and GluR5-GluR6 or GluR5-KA2 at presynaptic terminals. However, functional compensation appears to take place in the null mutants, a new pharmacological profile emerging more compatible with the activity of homomeric receptors in both compartments: GluR5 in GluR6-/- mice and GluR6 in GluR5-/- mice.


Activity of pyronaridine and mepacrine against twelve strains of Plasmodium falciparum in vitro.
Pyronaridine, an acridine derivative, has been found effective in China for the treatment of drug-resistant falciparum malaria. The activities of pyronaridine and mepacrine were compared with those of standard antimalarial drugs in vitro against chloroquine-sensitive (CS) and chloroquine-resistant (CR) Plasmodium falciparum isolates to investigate cross resistance. The 50% inhibitory concentrations (IC(50)) against the resistant isolates were 2.8-fold higher than the sensitive isolates for pyronaridine (CS = 7.3 nM; CR = 20.5 nM) and 3.2-fold higher for mepacrine (CS = 13.3 nM; CR = 42.6 nM). These same isolates showed an 11-fold difference in sensitivity to chloroquine with mean IC(50) values of 21 nM for sensitive and 239 nM for resistant parasites. A significant correlation was observed between parasite sensitivity (IC(50)) to pyronaridine and the drugs, mepacrine, amodiaquine and chloroquine. However, the high level of activity seen with pyronaridine, even against the CR isolates, should encourage further field trials with this drug.


A PCR-based method to distinguish fungi of the rice sheath-blight complex, Rhizoctonia solani, R. oryzae and R. oryzae-sativae.
Identification of Rhizoctonia solani, R. oryzae and R. oryzae-sativae, components of the rice sheath disease complex, is extremely difficult and often inaccurate and as a result may hinder the success of extensive breeding programmes throughout Asia. In this study, primers designed from unique regions within the rDNA internal transcribed spacers have been used to develop a rapid PCR-based diagnostic test to provide an accurate identification of the species on rice. Tests on the specificity of the primers concerned showed that they provide the means for accurate identification of the Rhizoctonia species responsible for sheath diseases in rice.


Tonsils of the soft palate do not mediate the response of pigs to oral vaccination with heat-inactivated Mycobacterium bovis.
Mycobacterium bovis causes animal tuberculosis (TB) in cattle, humans, and other mammalian species, including pigs. The goal of this study was to experimentally assess the responses of pigs with and without a history of tonsillectomy to oral vaccination with heat-inactivated M. bovis and challenge with a virulent M. bovis field strain, to compare pig and wild boar responses using the same vaccination model as previously used in the Eurasian wild boar (Sus scrofa), to evaluate the use of several enzyme-linked immunosorbent assays (ELISAs) and lateral flow tests for in vivo TB diagnosis in pigs, and to verify if these tests are influenced by oral vaccination with inactivated M. bovis. At necropsy, the lesion and culture scores were 20% to 43% higher in the controls than those in the vaccinated pigs. Massive M. bovis growth from thoracic tissue samples was observed in 4 out of 9 controls but in none of the 10 vaccinated pigs. No effect of the presence or absence of tonsils was observed on these scores, suggesting that tonsils are not involved in the protective response to this vaccine in pigs. The serum antibody levels increased significantly only after challenge. At necropsy, the estimated sensitivities of the ELISAs and dual path platform (DPP) assays ranged from 89% to 94%. In the oral mucosa, no differences in gene expression were observed in the control group between the pigs with and without tonsils. In the vaccinated group, the mRNA levels for chemokine (C-C motif) receptor 7 (CCR7), interferon beta (IFN-β), and methylmalonyl coenzyme A mutase (MUT) were higher in pigs with tonsils. Complement component 3 mRNA levels in peripheral blood mononuclear cells (PBMC) increased with vaccination and decreased after M. bovis challenge. This information is relevant for pig production in regions that are endemic for M. bovis and for TB vaccine research.


Measuring rheumatoid factor in nonrheumatoid subjects: immunoturbidimetric assay, latex slide test, and enzyme-linked immunosorbent assay compared.
Previous studies of patients with rheumatoid arthritis (RA) have shown a good correlation between results from immunoturbidimetric assays of rheumatoid factor (RF) and latex fixation tests. To extend the research to non-RA subjects, we tested sera from 1000 pregnant women, half each in the first and third trimesters. By turbidimetry, 24 non-RA sera were regarded as positive for RF (greater than or equal to 20 int. units/mL) and 18 sera as borderline (15-19 int. units/mL). By the latex fixation test, 28 non-RA sera gave a clear reaction (positive) and 17 sera a weak reaction (borderline). The association between the tests was statistically highly significant (P less than 0.001). All sera with positive and borderline reactions were tested by enzyme-linked immunosorbent assay for RF isotypes, together with a random subsample of about one-sixth of the original serum samples. Positive RF results by immunoturbidimetry were predominantly due to the presence of IgM-RF. In contrast to some earlier findings, we saw no difference in the prevalence of positive RF reactions between sera from the first and third trimesters.


Self-reported history of Pap-smear in HIV-positive women in Northern Italy: a cross-sectional study.
The incidence of invasive cervical cancer in HIV-positive women is higher than in the general population. There is evidence that HIV-positive women do not participate sufficiently in cervical cancer screening in Italy, where cervical cancer is more than 10-fold higher in women with AIDS than in the general population. The aim of the present study was to evaluate the history of Pap-smear in HIV-positive women in Italy in recent years. We also examined the sociodemographic, clinical, and organizational factors associated with adherence to cervical cancer screening. A cross-sectional study was conducted between July 2006 and June 2007 in Emilia-Romagna region (Northern Italy). All HIV-positive women who received a follow-up visit in one of the 10 regional infectivology units were invited to participate. History of Pap-smear, including abnormal smears and subsequent treatment, was investigated through a self-administered anonymous questionnaire. The association between lack of Pap-smear in the year preceding the interview and selected characteristics was assessed by means of odds ratios (OR) and 95% confidence intervals adjusted for study centre and age. A total of 1,002 HIV-positive women were interviewed. Nine percent reported no history of Pap-smear, and 39% had no Pap-smear in the year prior to the date of questionnaire (last year). The lack of Pap-smear in the last year was significantly associated with age <35 years (OR = 1.4, compared to age > or =45 years), lower education level (OR = 1.3), first HIV-positive test in the last 2 years (OR = 1.4), and CD4 count <200 cells/microl (OR = 1.6). Conversely, when women were advised by a gynecologist rather than other health workers to undergo screening, it significantly increased adherence. Non-significantly higher proportions of lack of Pap-smear in the last year were found in women born in Central-Eastern Europe (OR = 1.8) and Africa (OR = 1.3). No difference in history of Pap-smear emerged by mode of HIV-acquisition or AIDS status.Three hundred five (34%) women reported a previous abnormal Pap-smear, and of the 178 (58%) referred for treatment, 97% complied. In recent years the self-reported history of Pap-smear in HIV-positive women, in some public clinics in Italy, is higher than previously reported, but further efforts are required to make sure cervical cancer screening is accessible to all HIV-positive women.


The medial amygdaloid nucleus is involved in the cardiovascular pathway activated by noradrenaline into the lateral septal area of rats.
We have previously reported that noradrenaline (NA) microinjected into the lateral septal area (LSA) caused pressor and bradicardic responses that were mediated by vasopressin release into the circulation through the paraventricular nucleus of hypothalamus (PVN). Although PVN is the final structure involved in the cardiovascular responses caused by NA in the LSA, there is no evidence of direct connections between these areas, suggesting that some structures could be links in this pathway. In the present study, we verified the effect of reversible synaptic inactivation of the medial amygdaloid nucleus (MeA), bed nucleus of stria terminalis (BNST) or diagonal band of Broca (DBB) with Cobalt Chloride (CoCl(2) ) on the cardiovascular response to NA microinjection into the LSA of unanesthetized rats. Male Wistar rats had guide cannulae implanted into the LSA and the MeA, BNST or DBB for drug administration, and a femoral catheter for blood pressure and heart rate recordings. Local microinjection of CoCl(2) (1 mm in 100 nL) into the MeA significantly reduced the pressor and bradycardic responses caused by NA microinjection (21 nmol in 200 nL) into the LSA. In contrast, microinjection of CoCl(2) into the BNST or DBB did not change the cardiovascular responses to NA into the LSA. The results indicate that synapses within the MeA, but not in BNST or DBB, are involved in the cardiovascular pathway activated by NA microinjection into the LSA.


Disarming the virulence arsenal of Pseudomonas aeruginosa by blocking two-component system signaling.
Pseudomonas aeruginosa infections have reached a "critical" threat status making novel therapeutic approaches required. Inhibiting key signaling enzymes known as the histidine kinases (HKs), which are heavily involved with its pathogenicity, has been postulated to be an effective new strategy for treatment. Herein, we demonstrate the potential of this approach with benzothiazole-based HK inhibitors that perturb multiple virulence pathways in the burn wound P. aeruginosa isolate, PA14. Specifically, our compounds significantly reduce the level of toxic metabolites generated by this organism that are involved in quorum-sensing and redox-balancing mechanisms. They also decrease the ability of this organism to swarm and attach to surfaces, likely by influencing their motility appendages. Quantitative transcription analysis of inhibitor-treated cultures showed substantial perturbations to multiple pathways including expression of response regulator GacA, the cognate partner of the "super regulator" of virulence, HK GacS, as well as flagella and pili formation. These promising results establish that blocking of bacterial signaling in P. aeruginosa has dramatic consequences on virulence behaviours, especially in the context of surface-associated infections.


Reactivities of actin as a contractile protein.
The molecular basis for the mechanism of contraction in striated muscle, with primary emphasis on the interaction between the thick and thin filaments and the role of the thin (actin) filaments, is the theme presented. Recent information relating to actin-myosin interaction points up the fact that definitive statements cannot be made regarding the molecular interaction(s) that lead to contraction. Nevertheless, the properties of actin indicate that (a) actin in the monomeric state has properties differing markedly from actin in the polymer (filament) state; (b) these property differences may be significant in the contractile process, for they include changes in the reactivity of the bound nucleotide and actin-myosin complex formation; (c) the bound nucleotide seems to be required in the contraction process. For these, and other, reasons discussed, the tentative hypothesis is advanced that the contraction reaction involves local changes in the actin filament providing local monomer or monomer-like actin units in the reaction with myosin.


The role and remediation of animal allergens in allergic diseases.
Animal allergens are common causes of both acute and chronic allergic disease. The most important animal allergens are derived from mammals, principally cats, dogs, rats, mice, horses, and cows, which secrete or excrete allergens into the environment. Allergic sensitization may occur at home or in the workplace. Cat and dog allergens commonly cause allergies in the home and affect the general population. Laboratory animal handlers often have allergic reactions to rats and mice. Cow dander allergy is usually caused by occupational exposure and occurs in farmers and farm workers. Horse allergy occurs among people who regularly handle horses, either professionally or for recreational purposes. Over the past 20 years, the major animal allergens have been defined and characterized with regard to their molecular structure, immunogenicity, and environmental distribution. One remarkable finding has been the fact that most of the mammalian allergens that have thus far been cloned belong to a single family of proteins called the lipocalins. In addition to these molecular similarities, it has also been shown that most of the animal allergens are quite similar with regard to their aerodynamic properties. Although much is yet to be learned, progress is being made in our knowledge regarding the steps that may be necessary to control exposure to these allergens through environmental modifications in both homes and occupational settings. These measures include source control, air filtration devices, barrier devices, removal of carpeting and other reservoirs, and, in some cases, washing of the animal.


Drug infusion system manifold dead-volume impacts the delivery response time to changes in infused medication doses in vitro and also in vivo in anesthetized swine.
IV infusion systems can be configured with manifolds connecting multiple drug infusion lines to transcutaneous catheters. Prior in vitro studies suggest that there may be significant lag times for drug delivery to reflect changes in infusion rates set at the pump, especially with low drug and carrier flows and larger infusion system dead-volumes. Drug manifolds allow multiple infusions to connect to a single catheter port but add dead-volume. We hypothesized that the time course of physiological responses to drug infusion in vivo reflects the impact of dead-volume on drug delivery. The kinetic response to starting and stopping epinephrine infusion ([3 mL/h] with constant carrier flow [10 mL/h]) was compared for high- and low-dead-volume manifolds in vitro and in vivo. A manifold consisting of 4 sequential stopcocks with drug entering at the most upstream port was contrasted with a novel design comprising a tube with separate coaxial channels meeting at the downstream connector to the catheter, which virtually eliminates the manifold contribution to the dead-volume. The time to 50% (T50) and 90% (T90) increase or decrease in drug delivery in vitro or contractile response in a swine model in vivo were calculated for initiation and cessation of drug infusion. The time to steady state after initiation and cessation of drug infusion both in vitro and in vivo was much less with the coaxial low-dead-volume manifold than with the high-volume design. Drug delivery after initiation in vitro reached 50% and 90% of steady state in 1.4 ± 0.12 and 2.2 ± 0.42 minutes with the low-dead-volume manifold and in 7.1 ± 0.58 and 9.8 ± 1.6 minutes with the high-dead-volume manifold, respectively. The contractility in vivo reached 50% and 90% of the full response after drug initiation in 4.3 ± 1.3 and 9.9 ± 3.9 minutes with the low-dead-volume manifold and 11 ± 1.2 and 17 ± 2.6 minutes with the high-dead-volume manifold, respectively. Drug delivery in vitro decreased by 50% and 90% after drug cessation in 1.9 ± 0.17 and 3.5 ± 0.61 minutes with the low-dead-volume manifold and 10.0 ± 1.0 and 17.0 ± 2.8 minutes with the high-dead-volume manifold, respectively. The contractility in vivo decreased by 50% and 90% with drug cessation in 4.1 ± 1.1 and 14 ± 5.2 with the low-dead-volume manifold and 12 ± 2.7 and 23 ± 5.6 minutes with the high-dead-volume manifold, respectively. The architecture of the manifold impacts the in vivo biologic response, and the drug delivery rate, to changes in drug infusion rate set at the pump.


Partner-Level Factors Associated with Insertive and Receptive Condomless Anal Intercourse Among Transgender Women in Lima, Peru.
Condomless anal intercourse among transgender women (TW) in Peru has been shown to vary by the type of partner involved (e.g. primary vs. casual vs. transactional sex partner), but no previous studies have explored variations in partner-level patterns of condom use according to type of anal intercourse. We evaluated the relationship between partnership characteristics and condom use during insertive (IAI) versus receptive anal intercourse (RAI) among TW with recent, non-female partners. Condomless IAI was more common with transactional and casual sex partners and by TW who self-reported HIV-uninfected serostatus (p < 0.05), alcohol use disorders, or substance use before sex. Condomless RAI was more common with primary partners and by TW who described their HIV serostatus as unknown (p < 0.05). Examining partner-level differences between condomless IAI and RAI reveals distinct patterns of HIV/STI risk among TW, suggesting a need for HIV prevention strategies tailored to the specific contexts of partners, practices, and networks.


Controlled evaluation of pantethine, a natural hypolipidemic compound, in patients with different forms of hyperlipoproteinemia.
Pantethine (P), the stable disulphate form of pantetheine, major component and precursor of coenzyme A, was evaluated within a double-blind protocol (8 weeks for P or for a corresponding placebo) in 29 patients, 11 with type IIB hyperlipoproteinemia, 15 with type IV, and 3 with an isolated reduction of high density lipoprotein cholesterol (HDL-C) levels. In type IIB patients, P (300 mg t.i.d.) determined a highly significant lowering of plasma total and low density lipoprotein (LDL) associated cholesterol (-13.5% for both parameters). In the same patients, HDL-C levels increased about 10% at the end of treatment. Switching from P to placebo was associated with a rapid return to the baseline cholesterolemia. Both in type IIB and type IV patients, plasma triglyceride levels were reduced around 30%, when P was given as the first treatment; when it was preceded by placebo, reductions were less striking (respectively, -17.8% for type IIB and -13.0% for type IV, at the end of P treatment). HDL-C levels were not increased by P, either in type IV, and in the patients with low HDL cholesterolemia. In type IV, LDL cholesterol levels showed a variable response to P: they tended to increase when below 132 mg/dl, prior to treatment, and to be reduced when above this level. This study provides evidence for a significant hypocholesterolemic effect of P, a natural compound free of overt side effects. It also indicates that P may raise HDL-C levels in type IIB patients, while moderately reducing triglyceridemia.


Microbiological hazards related to xenotransplantation of porcine organs into man.
Pigs are emerging as the most likely providers of genetically engineered organs and cells for the purpose of clinical xenotransplantation. Introduction of clinical trials has been delayed primarily by uncertainties regarding the risk of swine pathogen transmission that could harm the recipient. The concern that xenotransplantation carries the potential for a new epidemic has been highlighted by recent experiences with both bovine spongiform encephalopathy and human immunodeficiency diseases. As clinical trials have been postponed and xenotransplantation teams are working actively to gather data for an estimation of the risk, this review provides the reader with a state-of-the-art estimation of the microbiological hazards related to xenotransplantation of porcine organs to man. Particular emphasis is put on viral and retroviral hazards. Both current diagnostic tools and those under development are described, along with breeding strategies to provide donor animals that would not put the recipient or the general population at risk.


A Bayesian nested patch occupancy model to estimate steelhead movement and abundance.
Anthropogenic impacts on riverine systems have, in part, led to management concerns regarding the population status of species using these systems. In an effort to assess the efficacy of restoration actions, and in order to improve monitoring of species of concern, managers have turned to PIT (passive integrated transponder) tag studies with in-stream detectors to monitor movements of tagged individuals throughout river networks. However, quantifying movements in a river network using PIT tag data with incomplete coverage and imperfect detections presents a challenge. We propose a flexible Bayesian analytic framework that models the imperfectly detected movements of tagged individuals in a nested PIT tag array river network. This model structure provides probabilistic estimates of up-stream migration routes for each tagged individual based on a set of underlying nested state variables. These movement estimates can be converted into abundance estimates when an estimate of abundance is available for a location within the river network. We apply the model framework to data from steelhead (Oncorhynchus mykiss) in the Upper Columbia River basin and evaluate model performance (precision/variance of simulated population sizes) as a function of population tagging rates and PIT tag array detection probability densities within the river system using a simulation framework. This simulation framework provides both model validation (precision) and the ability to evaluate expected performance improvements (variance) due to changes in tagging rates or PIT receiver array configuration. We also investigate the impact of different network configurations on model estimates. Results from such investigations can help inform decisions regarding future monitoring and management.


The oxidation of oxyhaemoglobin by glyceraldehyde and other simple monosaccharides.
Glyceraldehyde and other simple monosaccharides oxidize oxyhaemoglobin to methaemoglobin in phosphate buffer at pH 7.4 and 37 degrees C, with the concomitant production of H2O2 and an alpha-oxo aldehyde derivative of the monosaccharide. Simple monosaccharides also reduce methaemoglobin to ferrohaemichromes (non-intact haemoglobin) at pH 7.4 and 37 degrees C. Carbonmonoxyhaemoglobin is unreactive towards oxidation by autoxidizing glyceraldehyde. Free-radical production from autoxidizing monosaccharides with haemoglobins was observed by the e.s.r. technique of spin trapping with the spin trap 5,5-dimethyl-l-pyrroline N-oxide. Hydroxyl and l-hydroxyalkyl radical production observed from monosaccharide autoxidation was quenched in the presence of oxyhaemoglobin and methaemoglobin. The haemoglobins appear to quench the free radicals by reaction with the free radicals and/or the ene-diol precursor of the free radical.


Analysis of asymmetry in lipid and content mixing assays with reconstituted proteoliposomes containing the neuronal SNAREs.
Reconstitution assays with proteoliposomes provide a powerful tool to elucidate the mechanism of neurotransmitter release, but it is important to understand how these assays report on membrane fusion, and recent studies with yeast vacuolar SNAREs uncovered asymmetry in the results of lipid mixing assays. We have investigated whether such asymmetry also occurs in reconstitution assays with the neuronal SNAREs, using syntaxin-1-SNAP-25-containing liposomes and liposomes containing synaptobrevin (T and V liposomes, respectively), and fluorescent probes to monitor lipid and content mixing simultaneously. Switching the fluorescent probes placed on the T and V liposomes, we observed a striking asymmetry in both lipid and content mixing stimulated by a fragment spanning the two C2 domains of synaptotagmin-1, or by a peptide that spans the C-terminal half of the synaptobrevin SNARE motif. However, no such asymmetry was observed in assays performed in the presence of Munc18-1, Munc13-1, NSF and αSNAP, which coordinate the assembly-disassembly cycle of neuronal SNARE complexes. Our results show that switching fluorescent probes between the two types of liposomes provides a useful approach to better understand the reactions that occur between liposomes and detect heterogenous behavior in these reactions.


A syntax-preserving error resilience tool for JPEG 2000 based on error correcting arithmetic coding.
JPEG 2000 is the novel ISO standard for image and video coding. Besides its improved coding efficiency, it also provides a few error resilience tools in order to limit the effect of errors in the codestream, which can occur when the compressed image or video data are transmitted over an error-prone channel, as typically occurs in wireless communication scenarios. However, for very harsh channels, these tools often do not provide an adequate degree of error protection. In this paper, we propose a novel error-resilience tool for JPEG 2000, based on the concept of ternary arithmetic coders employing a forbidden symbol. Such coders introduce a controlled degree of redundancy during the encoding process, which can be exploited at the decoder side in order to detect and correct errors. We propose a maximum likelihood and a maximum a posteriori context-based decoder, specifically tailored to the JPEG 2000 arithmetic coder, which are able to carry out both hard and soft decoding of a corrupted code-stream. The proposed decoder extends the JPEG 2000 capabilities in error-prone scenarios, without violating the standard syntax. Extensive simulations on video sequences show that the proposed decoders largely outperform the standard in terms of PSNR and visual quality.


International Endometrial Tumor Analysis (IETA) terminology in women with postmenopausal bleeding and sonographic endometrial thickness ≥ 4.5 mm: agreement and reliability study.
To estimate intra- and interrater agreement and reliability with regard to describing ultrasound images of the endometrium using the International Endometrial Tumor Analysis (IETA) terminology. Four expert and four non-expert raters assessed videoclips of transvaginal ultrasound examinations of the endometrium obtained from 99 women with postmenopausal bleeding and sonographic endometrial thickness ≥ 4.5 mm but without fluid in the uterine cavity. The following features were rated: endometrial echogenicity, endometrial midline, bright edge, endometrial-myometrial junction, color score, vascular pattern, irregularly branching vessels and color splashes. The color content of the endometrial scan was estimated using a visual analog scale graded from 0 to 100. To estimate intrarater agreement and reliability, the same videoclips were assessed twice with a minimum of 2 months' interval. The raters were blinded to their own results and to those of the other raters. Interrater differences in the described prevalence of most IETA variables were substantial, and some variable categories were observed rarely. Specific agreement was poor for variables with many categories. For binary variables, specific agreement was better for absence than for presence of a category. For variables with more than two outcome categories, specific agreement for expert and non-expert raters was best for not-defined endometrial midline (93% and 96%), regular endometrial-myometrial junction (72% and 70%) and three-layer endometrial pattern (67% and 56%). The grayscale ultrasound variable with the best reliability was uniform vs non-uniform echogenicity (multirater kappa (κ), 0.55 for expert and 0.52 for non-expert raters), and the variables with the lowest reliability were appearance of the endometrial-myometrial junction (κ, 0.25 and 0.16) and the nine-category endometrial echogenicity variable (κ, 0.29 and 0.28). The most reliable color Doppler variable was color score (mean weighted κ, 0.77 and 0.69). Intra- and interrater agreement and reliability were similar for experts and non-experts. Inter- and intrarater agreement and reliability when using IETA terminology were limited. This may have implications when assessing the association between a particular ultrasound feature and a specific histological diagnosis, because lack of reproducibility reduces the reliability of the association between a feature and the outcome. Future studies should investigate whether using fewer categories of variable or offering practical training could improve agreement and reliability. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.


Evaluation of ocular surface in children with attention deficit hyperactivity disorder with respect to methylphenidate treatment.
This study aimed to screen the ocular surface of children with attention deficit hyperactivity disorder and identify the adverse effects of methylphenidate related to dry eye disease. This cross-sectional study included children with attention deficit hyperactivity disorder and healthy children (all aged 5-18 years). They were randomized into Group A (without methylphenidate treatment), Group B (with methylphenidate treatment), and Group C (healthy children). Tear film break-up time, Ocular Surface Disease Index questionnaire, tear meniscus height, tear meniscus area, and Schirmer test results were evaluated. Furthermore, symptom severity in attention deficit hyperactivity disorder was assessed by Turgay DSM-IV-based Child and Adolescent Behavioral Disorders Screening and Rating Scale and Conners Parent Rating Scale-48. Groups A, B, and C consisted of 34, 40, and 60 individuals (n=34, 40, and 60 eyes; age=11.44 ± 2.79, 11.70 ± 2.83, and 11.96 ± 3.63 years, median age=12, 12, and 11.5 years), respectively. Tear film break-up time, Ocular Surface Disease Index, tear meniscus height, tear meniscus area, and Schirmer test results were not significantly different between Groups A and C (p=0.964, 0.336, 0.445, 0.439, and 0.759, respectively). However, Group B showed a significant decrease in tear film break-up time (10.50 ± 3.39 vs. 12.52 ± 2.46 s; p=0.005), tear meniscus height (307.40 ± 5.53 vs. 310.82 ± 7.30 µm; p=0.025), tear meniscus area (0.024 ± 0.0037 vs. 0.026 ± 0.0046 mm2; p=0.010) and Schirmer test (12.75 ± 3.96 vs. 15.41 ± 3.75 mm; p=0.004) results compared with Group A. Compared with healthy children, children with attention deficit hyperactivity disorder showed ocular surface parameters suggestive of dry eye disease despite taking methylphenidate. Thus, they require close ophthalmologic follow-up to prevent sight-threatening dry eye complications.


Teaching quality improvement and patient safety to trainees: a systematic review.
To systematically review published quality improvement (QI) and patient safety (PS) curricula for medical students and/or residents to (1) determine educational content and teaching methods, (2) assess learning outcomes achieved, and (3) identify factors promoting or hindering curricular implementation. Data sources included Medline (to January 2009), EMBASE, HealthSTAR, and article bibliographies. Studies selected reported curricula outlining specific educational content and teaching format. For articles with an evaluative component, the authors abstracted methodological features, such as study design. For all articles, they conducted a thematic analysis to identify factors influencing successful implementation of the included curricula. Of 41 curricula that met the authors' criteria, 14 targeted medical students, 24 targeted residents, and 3 targeted both. Common educational content included continuous QI, root cause analysis, and systems thinking. Among 27 reports that included an evaluation, curricula were generally well accepted. Most curricula demonstrated improved knowledge. Thirteen studies (32%) successfully implemented local changes in care delivery, and seven (17%) significantly improved target processes of care. Factors that affected the successful curricular implementation included having sufficient numbers of faculty familiar with QI and PS content, addressing competing educational demands, and ensuring learners' buy-in and enthusiasm. Participants in some curricula also commented on discrepancies between curricular material and local institutional practice or culture. QI and PS curricula that target trainees usually improve learners' knowledge and frequently result in changes in clinical processes. However, successfully implementing such curricula requires attention to a number of learner, faculty, and organizational factors.