Medical aromatherapy revisited-Basic mechanisms, critique, and a new development.
According to a series of recent meta-analyses and systematic reviews, aromatherapy has shown to be effective in treating patients with different medical conditions. However, many of the clinical studies are of rather low methodological quality. Moreover, there is much conceptual ambiguity with regard to what aromatherapy actually constitutes. In this paper, we discuss the conditions under which aromatherapy is most likely to be of medical value by outlining the workings of the olfactory system and the necessary requirements of odors to be therapeutic. We then introduce an aromatherapeutic inhaler that was tested in a series of studies involving 465 participants. This inhaler (AromaStick®) produced large to very large effects across a variety of physiological target systems (e.g., cardiovascular, endocrine, blood oxygenation, and pain), both short term and long term. Inhalation of volatile compounds from essential oils yields almost immediate, large, and clinically relevant effects as long as the scents are delivered highly concentrated from an appropriate device. The changes caused in the body seem side effect-free and can be sustained when inhalation is repeated.


Respiratory muscle force and ventilatory function in adolescents.
In 94 girls and 90 boys, aged 12.5-20.3 yr, the relationship of respiratory pressures or forces with lung volumes and ventilatory flows was studied. There was great variability in respiratory muscle performance, which helps to explain differences in lung volumes between individuals. Respiratory muscle force increases almost proportionally with thoracic dimensions, so that inspiratory and expiratory pressures generated at the level of residual volume (RV), functional residual capacity (FRC) and total lung capacity (TLC) are approximately constant with age. In the oldest boys there is evidence that the continued increase in lung volumes when they stop growing is due to a 'muscularity effect'. Boys generate larger pressures than girls at all lung volumes. Thus boys attain a larger TLC, and in spite of narrower airways, the same peak expiratory flow and a larger FIV1/FVC ratio than girls. Effort independent flows (FEV1 and MMEF), however, are larger in girls.


Chemotherapy-related polyneuropathy may deteriorate quality of life in patients with B-cell lymphoma.
This prospective study was performed to evaluate the effect of chemotherapy-related neurotoxicity on quality of life (QOL) of patients with lymphoma. Thirty-two patients with diffuse large B-cell or follicular lymphoma without prior evidence of neuropathy were enrolled. Patients underwent the evaluations based on neuropathy symptom and disability score, nerve conduction studies, and SF-36 questionnaire for QOL assessment. They received six cycles of chemotherapy every three weeks, and all evaluations were repeated during and after the completion of 6th cycle. Sensory neuropathy-associated symptoms were observed in 27 patients (84.4%), and polyneuropathy was confirmed by nerve conduction study in 14 patients (43.8%). These patients with polyneuropathy showed worse QOL in domains mainly associated with physical health status including "physical function" compared to patients without polyneuropathy. There was a significant association of neuropathy symptom and disability scores with "bodily pain" and "vitality" of QOL domains. The serial evaluations of patients with neuropathy showed a worsening of QOL and neuropathy symptom scores during chemotherapy, then improvement of these values after chemotherapy. Thus, the final nerve conduction study confirmed the decrease in polyneuropathy compared to the 2nd evaluation (P = 0.032). Chemotherapy-related polyneuropathy may deteriorate QOL of patients with lymphoma, mainly physical health-associated QOL.


A revision of the Old World Black Nightshades (Morelloid clade of Solanum L., Solanaceae).
The Morelloid clade, also known as the black nightshades or "Maurella" (Morella), is one of the 10 major clades within Solanum L. The pantropical clade consists of 75 currently recognised non-spiny herbaceous and suffrutescent species with simple or branched hairs with or without glandular tips, with a centre of distribution in the tropical Andes. A secondary centre of diversity is found in Africa, where a set of mainly polyploid taxa occur. A yet smaller set of species is found in Australasia and Europe, including Solanum nigrum L., the type of the genus Solanum. Due to the large number of published synonyms, combined with complex morphological variation, our understanding of species limits and diversity in the Morelloid clade has remained poor despite detailed morphological studies carried out in conjunction with breeding experiments. Here we provide the first taxonomic overview since the 19th century of the entire group in the Old World, including Africa, Asia, Australia, Europe and islands of the Pacific. Complete synonymy, morphological descriptions, distribution maps and common names and uses are provided for all 19 species occurring outside the Americas (i.e. Africa, Asia, Australia, Europe and islands of the Pacific). We treat 12 species native to the Old World, as well as 7 taxa that are putatively introduced and/or invasive in the region. The current knowledge of the origin of the polyploid species is summarised. A key to all of the species occurring in the Old World is provided, together with line drawings and colour figures to aid identification both in herbaria and in the field. Preliminary conservation assessments are provided for all species.


Subclinical thyroid dysfunction and the risk for fractures: a systematic review and meta-analysis.
Data on the association between subclinical thyroid dysfunction and fractures conflict. To assess the risk for hip and nonspine fractures associated with subclinical thyroid dysfunction among prospective cohorts. Search of MEDLINE and EMBASE (1946 to 16 March 2014) and reference lists of retrieved articles without language restriction. Two physicians screened and identified prospective cohorts that measured thyroid function and followed participants to assess fracture outcomes. One reviewer extracted data using a standardized protocol, and another verified data. Both reviewers independently assessed methodological quality of the studies. The 7 population-based cohorts of heterogeneous quality included 50,245 participants with 1966 hip and 3281 nonspine fractures. In random-effects models that included the 5 higher-quality studies, the pooled adjusted hazard ratios (HRs) of participants with subclinical hyperthyroidism versus euthyrodism were 1.38 (95% CI, 0.92 to 2.07) for hip fractures and 1.20 (CI, 0.83 to 1.72) for nonspine fractures without statistical heterogeneity (P = 0.82 and 0.52, respectively; I2= 0%). Pooled estimates for the 7 cohorts were 1.26 (CI, 0.96 to 1.65) for hip fractures and 1.16 (CI, 0.95 to 1.42) for nonspine fractures. When thyroxine recipients were excluded, the HRs for participants with subclinical hyperthyroidism were 2.16 (CI, 0.87 to 5.37) for hip fractures and 1.43 (CI, 0.73 to 2.78) for nonspine fractures. For participants with subclinical hypothyroidism, HRs from higher-quality studies were 1.12 (CI, 0.83 to 1.51) for hip fractures and 1.04 (CI, 0.76 to 1.42) for nonspine fractures (P for heterogeneity = 0.69 and 0.88, respectively; I2 = 0%). Selective reporting cannot be excluded. Adjustment for potential common confounders varied and was not adequately done across all studies. Subclinical hyperthyroidism might be associated with an increased risk for hip and nonspine fractures, but additional large, high-quality studies are needed. Swiss National Science Foundation.


Expression of the AMPA Receptor Subunits GluR1 and GluR2 is Associated with Granule Cell Maturation in the Dentate Gyrus.
The dentate gyrus produces new granule neurons throughout adulthood in mammals from rodents to humans. During granule cell maturation, defined markers are expressed in a highly regulated sequential process, which is necessary for directed neuronal differentiation. In the present study, we show that α-amino-3-hydroxy-5-methy-4-isoxazole propionate (AMPA) receptor subunits GluR1 and GluR2 are expressed in differentiated granule cells, but not in stem cells, in neonatal, and adult dentate gyrus. Using markers for neural progenitors, immature and mature granule cells, we found that GluR1 and GluR2 were expressed mainly in mature cells and in some immature cells. A time-course analysis of 5-bromo-2'-deoxyuridine staining revealed that granule cells express GluR1 around 3 weeks after being generated. In mice heterozygous for the alpha-isoform of calcium/calmodulin-dependent protein kinase II, a putative animal model of schizophrenia and bipolar disorder in which dentate gyrus granule cells fail to mature normally, GluR1 and GluR2 immunoreactivities were substantially downregulated in the dentate gyrus granule cells. In the granule cells of mutant mice, the expression of both presynaptic and postsynaptic markers was decreased, suggesting that GluR1 and GluR2 are also associated with synaptic maturation. Moreover, GluR1 and GluR2 were also expressed in mature granule cells of the neonatal dentate gyrus. Taken together, these findings indicate that GluR1 and GluR2 expression closely correlates with the neuronal maturation state, and that GluR1 and GluR2 are useful markers for mature granule cells in the dentate gyrus.


Risk factors for Giardia intestinalis infection in agricultural villages practicing wastewater irrigation in Mexico.
This study assessed the risk factors for Giardia intestinalis infection in an agricultural population in Mexico. Exposure groups included 2,257 individuals from households exposed to untreated wastewater, 2,147 from a group using the effluent from a series of reservoirs, and 2,344 from rain-fed agricultural villages. Stool samples were collected from 6,748 individuals. Wastewater samples were tested for fecal coliforms/100 ml and Giardia sp. cysts/L. Untreated wastewater samples contained 10(8) fecal coliforms/100 ml and up to 300 Giardia sp. cysts/L. Hydraulic retention (3-7 months) in the reservoirs, however, provided an improved effluent quality (10(1)-10(4) fecal coloforms/100 ml and < or = 5 Giardia sp. cysts/L). Children 1-14 years of age had the highest prevalence of infection (20%). Data showed marginal associations between storing drinking water in unprotected containers and lack of facilities for feces disposal and the risk of infection (odds ratios [ORs] = 1.76 and 1.19, 95% confidence intervals [CIs] = 0.95-3.23, and 0.97-1.45, respectively). Individuals purchasing vegetables at the city market had higher rates of infection than those buying at the village shop (OR = 2.49, 95% CI = 1.00-6.17). No excess risk was found in individuals exposed to untreated wastewater compared with controls (OR = 1.07, 95% CI = 0.84-1.36); the group using reservoir water was not different from the controls (OR = 1.22, 95% CI = 0.94-1.58). No risk from agricultural activities was detected (OR = 0.83). This pattern of infection may be addressed by primary health care and wastewater treatment.


A controlled study of services to enhance productive participation among people with HIV/AIDS.
This study assessed the effectiveness of a model program designed to increase productive participation among people living with HIV/AIDS within supportive-living facilities. Using a nonrandomized, two-group design, 65 study participants were assigned to either the model program or standard care. Data on productive participation were collected at 3, 6, and 9 months after completion of the model or standard program. Outcomes were compared at each time point. Forty-six participants completed the study. Participants in the two programs did not differ significantly on baseline demographic variables. Model program participants showed significantly higher levels of productive participation at all three time points (p < .05). Odds ratios were all > 3, reflecting that participants attending the model program were at least twice as likely to be productively engaged at all three time points. Results support the effectiveness of the model program in achieving sustained productive participation in persons living with HIV/AIDS.


Physical Unclonable Function based on a Multi-Mode Optical Waveguide.
Physical unclonable functions are the physical equivalent of one-way mathematical transformations that, upon external excitation, can generate irreversible responses. Exceeding their mathematical counterparts, their inherent physical complexity renders them resilient to cloning and reverse engineering. When these features are combined with their time-invariant and deterministic operation, the necessity to store the responses (keys) in non-volatile means can be alleviated. This pivotal feature, makes them critical components for a wide range of cryptographic-authentication applications, where sensitive data storage is restricted. In this work, a physical unclonable function based on a single optical waveguide is experimentally and numerically validated. The system's responses consist of speckle-like images that stem from mode-mixing and scattering events of multiple guided transverse modes. The proposed configuration enables the system's response to be simultaneously governed by multiple physical scrambling mechanisms, thus offering a radical performance enhancement in terms of physical unclonability compared to conventional optical implementations. Additional features like physical re-configurability, render our scheme suitable for demanding authentication applications.


Adult skeletal muscle stem cells.
Skeletal muscles in vertebrates have a phenomenal regenerative capacity. A muscle that has been crushed can regenerate fully both structurally and functionally within a month. Remarkably, efficient regeneration continues to occur following repeated injuries. Thousands of muscle precursor cells are needed to accomplish regeneration following acute injury. The differentiated muscle cells, the multinucleated contractile myofibers, are terminally withdrawn from mitosis. The source of the regenerative precursors is the skeletal muscle stem cells-the mononucleated cells closely associated with myofibers, which are known as satellite cells. Satellite cells are mitotically quiescent or slow-cycling, committed to myogenesis, but undifferentiated. Disruption of the niche after muscle damage results in their exit from quiescence and progression towards commitment. They eventually arrest proliferation, differentiate, and fuse to damaged myofibers or make de novo myofibers. Satellite cells are one of the well-studied adult tissue-specific stem cells and have served as an excellent model for investigating adult stem cells. They have also emerged as an important standard in the field of ageing and stem cells. Several recent reviews have highlighted the importance of these cells as a model to understand stem cell biology. This chapter begins with the discovery of satellite cells as skeletal muscle stem cells and their developmental origin. We discuss transcription factors and signalling cues governing stem cell function of satellite cells and heterogeneity in the satellite cell pool. Apart from satellite cells, a number of other stem cells have been shown to make muscle and are being considered as candidate stem cells for amelioration of muscle degenerative diseases. We discuss these "offbeat" muscle stem cells and their status as adult skeletal muscle stem cells vis-a-vis satellite cells. The ageing context is highlighted in the concluding section.


Evaluating differences between measured personal exposures to volatile organic compounds and concentrations in outdoor and indoor air.
Accurate estimation of human exposures to volatile organic compounds (VOCs) is a key element of strategies designed to protect public health from the adverse effects of hazardous air pollutants. The focus here is on examining the capability of three different exposure metrics (outdoor community concentrations, indoor residential concentrations, and a simple time-weighted model) to estimate observed personal exposures to 14 VOCs. The analysis is based on 2-day average concentrations of individual VOCs measured concurrently in outdoor (O) air in three urban neighborhoods, indoor (I) air in participant's residences, and personal (P) air near the breathing zone of 71 healthy, nonsmoking adults. A median of four matched P-I-O samples was collected for each study participant in Minneapolis/St. Paul over three seasons (spring, summer, and fall) in 1999 using charcoal-based passive air samplers (3M model 3500 organic vapor monitors). Results show a clear pattern for the 14 VOCs, with P > I > O concentrations. Intra-individual variability typically spanned at least an order of magnitude, and inter-individual variability spanned 2 or more orders of magnitude for each of the 14 VOCs. Although both O and I concentrations generally underestimated personal exposures, I concentrations provided a substantially better estimate of measured P concentrations. Mean squared error (MSE) as well as correlation measures were used to assess estimator performance at the subject-specific level, and hierarchical, mixed effects models were used to estimate the bias and variance components of MSE by tertile of personal exposure. Bias and variance both tended to increase in the upper third of the P exposure distribution for O versus P and I versus P. A simple time-weighted model incorporating measured concentrations in both outdoor community air and indoor residential air provided no improvement over I concentration alone for the estimation of P exposure.


Argos inhibits epidermal growth factor receptor signalling by ligand sequestration.
The epidermal growth factor receptor (EGFR) has critical functions in development and in many human cancers. During development, the spatial extent of EGFR signalling is regulated by feedback loops comprising both well-understood activators and less well-characterized inhibitors. In Drosophila melanogaster the secreted protein Argos functions as the only known extracellular inhibitor of EGFR, with clearly identified roles in multiple stages of development. Argos is only expressed when the Drosophila EGFR (DER) is activated at high levels, and downregulates further DER signalling. Although there is ample genetic evidence that Argos inhibits DER activation, the biochemical mechanism has not been established. Here we show that Argos inhibits DER signalling without interacting directly with the receptor, but instead by sequestering the DER-activating ligand Spitz. Argos binds tightly to the EGF motif of Spitz and forms a 1:1 (Spitz:Argos) complex that does not bind DER in vitro or at the cell surface. Our results provide an insight into the mechanism of Argos function, and suggest new strategies for EGFR inhibitor design.


Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis.
Magnetic resonance imaging has linked chronic voltage-gated potassium channel (VGKC) complex antibody-mediated limbic encephalitis with generalized hippocampal atrophy. However, autoantibodies bind to specific rodent hippocampal subfields. Here, human hippocampal subfield (subiculum, cornu ammonis 1-3, and dentate gyrus) targets of immunomodulation-treated LGI1 VGKC-complex antibody-mediated limbic encephalitis were investigated using in vivo ultra-high resolution (0.39 × 0.39 × 1.0 mm3) 7.0 T magnetic resonance imaging [n = 18 patients, 17 patients (94%) positive for LGI1 antibody and one patient negative for LGI1/CASPR2 but positive for VGKC-complex antibodies, mean age: 64.0 ± 2.55 years, median 4 years post-limbic encephalitis onset; n = 18 controls]. First, hippocampal subfield quantitative morphometry indicated significant volume loss confined to bilateral CA3 [F(1,34) = 16.87, P < 0.0001], despite hyperintense signal evident in 5 of 18 patients on presentation. Second, early and later intervention (<3 versus >3 months from symptom onset) were associated with CA3 atrophy. Third, whole-brain voxel-by-voxel morphometry revealed no significant grey matter loss. Fourth, CA3 subfield atrophy was associated with severe episodic but not semantic amnesia for postmorbid autobiographical events that was predicted by variability in CA3 volume. The results raise important questions about the links with histopathology, the impact of the observed focal atrophy on other CA3-mediated reconstructive and episodic mechanisms, and the role of potential antibody-mediated pathogenicity as part of the pathophysiology cascade in humans.


Multi-PDZ domain protein 1 (MUPP1) is concentrated at tight junctions through its possible interaction with claudin-1 and junctional adhesion molecule.
Claudins, most of which end in valine at their COOH termini, constitute tight junction (TJ) strands, suggesting that TJ strands strongly attract PDZ-containing proteins. Indeed, ZO-1, -2, and -3, each of which contains three PDZ domains, were shown to directly bind to claudins. Using the yeast two-hybrid system, we identified ZO-1 and MUPP1 (multi-PDZ domain protein 1) as binding partners for the COOH terminus of claudin-1. MUPP1 has been identified as a protein that contains 13 PDZ domains, but it has not been well characterized. In vitro binding assays with recombinant MUPP1 confirmed the interaction between MUPP1 and claudin-1 and identified PDZ10 as the responsible domain for this interaction. A polyclonal antibody specific for MUPP1 was then generated. Immunofluorescence confocal microscopy as well as immunoelectron microscopy with this antibody revealed that in polarized epithelial cells MUPP1 was exclusively concentrated at TJs. Furthermore, in vitro binding and transfection experiments showed that junctional adhesion molecule, another TJ adhesion molecule, also bound to the PDZ9 domain of MUPP1. These findings suggested that MUPP1 is concentrated at TJs in epithelial cells through its binding to claudin and junctional adhesion molecule and that it may function as a multivalent scaffold protein that recruits various proteins to TJs.


Efficient synthesis of riboflavin-imprinted magnetic nanoparticles by boronate affinity-based surface imprinting for the selective recognition of riboflavin.
Riboflavin (vitamin B2), a cis-diol-containing compound, is an essential vitamin for maintaining human health mainly in energy metabolism and is a critical component of enzyme cofactors and flavoproteins. Thus, the determination of riboflavin in food products is essential in riboflavin-fortified foods. However, analysis of riboflavin at natural levels in foods or biological samples is difficult because of its very low concentration level and the presence of undesirable matrix effects which could interfere with the measuring system. Thus, it is essential to develop efficient and selective enrichment approaches for riboflavin. Molecularly imprinted polymers can be well used for riboflavin extraction and pre-concentration from food samples. In this study, we present riboflavin-imprinted magnetic nanoparticles as an ideal sorbent for the selective enrichment of riboflavin followed by direct fluorometric determination. The riboflavin-imprinted magnetic nanoparticles were prepared according to a newly reported strategy, called boronate affinity-based surface initiated imprinting. Magnetic nanoparticles and vinylphenylboronic acid were used as supporting materials and a functional monomer, respectively. The prepared riboflavin-imprinted magnetic nanoparticles exhibited several significant advantages, such as excellent selectivity, high binding affinity and low binding pH toward riboflavin, which made the molecularly imprinted material become an ideal sorbent for the selective enrichment of riboflavin. The prepared riboflavin-imprinted magnetic nanoparticles were successfully applied to the analysis of riboflavin in milk.


A preliminary report on the English phonology of typically developing English-Mandarin bilingual preschool Singaporean children.
There are no published data on typical phonological development for Singaporean children. There is therefore the risk that children's speech in Singapore may be misdiagnosed or that clinicians may set goals erroneously. This paper reports a preliminary study on the English phonology of typically developing 4;0-4;5-year-old Chinese Singaporean children who speak English and Mandarin. Seventy children were recruited throughout Singapore, and speech samples were collected in English using the Phonology Assessment of the Diagnostic Evaluation of Articulation and Phonology (DEAP). The participants were divided equally into two groups: English-dominant and Mandarin-dominant. Their speech samples were compared with British English targets (BT) and Singapore English targets (ST) in terms of phonological accuracy and types of phonological processes used. The results showed that Singaporean children's phonological accuracy scores increased significantly when scored against ST instead of BT. When scored against ST, English-dominant children were found to perform similarly to their DEAP counterparts. However, Mandarin-dominant children had significantly less accurate consonant production in English and exhibited more interference effects from Mandarin phonology than English-dominant children. In this preliminary study, the results highlight the importance of speech and language therapists using local dialect pronunciations to be the target of speech assessments so as to provide appropriate assessment and intervention. It is also essential to account for the language background and language dominance of the children. More local normative data are needed for the typical acquisition of Singapore English in children, especially for children whose dominant language is not English.


Glucocorticoids but not vasopressin or oxytocin inhibit luteinizing hormone secretion in patients with psychogenic amenorrhea.
Activation of the hypothalamus-pituitary-adrenal (HPA) axis is suggested to play a role in the stress-related inhibition of LH secretion. The aim of our study was to investigate the effects of vasopressin and oxytocin, which are increased in pituitary portal plasma in response to stress, and of glucocorticoids, the final product of HPA activation during stress, on basal plasma LH levels and on pituitary LH response to the GnRH test in amenorrheic (n = 33) and fertile (n = 13) women. Plasma LH levels were evaluated by radioimmunoassay in 2 different experimental conditions: 1. Basal secretion; 2. The GnRH test (10 micrograms + 10 micrograms after a 120-minute interval). These 2 evaluations were done in the presence of both placebo and a pharmacological dose of desmopressin (an analogue of vasopressin) (16.6 ngr/minute), oxytocin (0.2 ngr/minute) or hydrocortisone (4.1 mg/minute). None of these drugs modified basal plasma LH levels either in amenorrheic patients or in controls. Hydrocortisone inhibited the GnRH-induced LH increase in amenorrheic women. These data suggest that the glucocorticoids might play a role in LH secretion and indicate a possible participation of the HPA axis in the impairment of the hypothalamus-pituitary-gonadal axis in women with psychogenic amenorrhea.


CTLA-4 +49A/G and CT60 gene polymorphisms in primary Sjögren syndrome.
CTLA-4 encodes cytotoxic T lymphocyte-associated antigen-4, a cell-surface molecule providing a negative signal for T-cell activation. CTLA-4 gene polymorphisms have been widely studied in connection with genetic susceptibility to various autoimmune diseases, but studies have led to contradictory results in different populations. This case-control study sought to investigate whether CTLA-4 CT60 and/or +49A/G polymorphisms were involved in the genetic predisposition to primary Sjögren syndrome (pSS). We analysed CTLA-4 CT60 and +49A/G polymorphisms in a first cohort of 142 patients with pSS (cohort 1) and 241 controls, all of Caucasian origin. A replication study was performed on a second cohort of 139 patients with pSS (cohort 2). In cohort 1, the CTLA-4 +49A/G*A allele was found on 73% of chromosomes in patients with pSS, compared with 66% in controls (p = 0.036; odds ratio (OR) 1.41, 95% confidence interval (CI) 1.02 to 1.95). No difference in CTLA-4 CT60 allelic or genotypic distribution was observed between patients (n = 142) and controls (n = 241). In the replication cohort, the CTLA-4 +49A/G*A allele was found on 62% of chromosomes in patients with pSS, compared with 66% in controls (p = 0.30; OR 0.85, 95% CI 0.63 to 1.16). Thus, the CTLA-4 +49A/G*A allele excess among patients from cohort 1 was counterbalanced by its under-representation in cohort 2. When the results from the patients in both cohorts were pooled (n = 281), there was no difference in CTLA-4 +49A/G allelic or genotypic distribution in comparison with controls. Our results demonstrate a lack of association between CTLA-4 CT60 or +49A/G polymorphisms and pSS. Premature conclusions might have been made if a replication study had not been performed. These results illustrate the importance of case-control studies performed on a large number of patients. In fact, sampling bias may account for some contradictory results previously reported for CTLA-4 association studies in autoimmune diseases.


Advertised foods on children's television.
To assess the quantity and nutritional value of foods advertised on children's television following new regulations and an expanded number of networks. Children's television hours were surveyed (with use of a method modeled on previously published studies, for purposes of comparison). Seven local network affiliates; all but one are broadcast nationally. Children viewed an average of 21.3 commercials per hour, each lasting an average of 28.6 seconds. Food advertisements accounted for 47.8% of these commercials. Ninety-one percent of advertised foods are high in fat, sugar, and/or salt. Compared with data collected before new regulations and networks, children now watch more numerous but shorter commercials. Cereals and sweet snacks are advertised proportionately less. Processed foods, canned and prepared foods, and dairy products are more frequently advertised. The proportion of foods high in fat, salt, and sugar has not changed. Commercials advertising unhealthy foods account for a large portion of children's televised viewing time. Current regulations and the incursion of cable networks into the children's television market have not meaningfully impacted the nature or number of food advertisements.


Asymmetric bias in perception of facial affect among Roman and Arabic script readers.
The asymmetric chimeric faces test is used frequently as an indicator of right hemisphere involvement in the perception of facial affect, as the test is considered free of linguistic elements. Much of the original research with the asymmetric chimeric faces test was conducted with subjects reading left-to-right Roman script, i.e., English. As readers of right-to-left scripts, such as Arabic, demonstrated a mixed or weak rightward bias in judgements of facial affect, the influence of habitual scanning direction was thought to intersect with laterality. We administered the asymmetric chimeric faces test to 1239 adults who represented a range of script experience, i.e., Roman script readers (English and French), Arabic readers, bidirectional readers of Roman and Arabic scripts, and illiterates. Our findings supported the hypothesis that the bias in facial affect judgement is rooted in laterality, but can be influenced by script direction. Specifically, right-handed readers of Roman script demonstrated the greatest mean leftward score, and mixed-handed Arabic script readers demonstrated the greatest mean rightward score. Biliterates showed a gradual shift in asymmetric perception, as their scores fell between those of Roman and Arabic script readers, basically distributed in the order expected by their handedness and most often used script. Illiterates, whose only directional influence was laterality, showed a slight leftward bias.


Specific considerations for research on the effectiveness of multisectoral collaboration: methods and lessons from 12 country case studies.
The success of the Sustainable Development Goals (SDGs) is predicated on multisectoral collaboration (MSC), and the COVID-19 pandemic makes it more urgent to learn how this can be done better. Complex challenges facing countries, such as COVID-19, cut across health, education, environment, financial and other sectors. Addressing these challenges requires the range of responsible sectors and intersecting services - across health, education, social and financial protection, economic development, law enforcement, among others - transform the way they work together towards shared goals. While the necessity of MSC is recognized, research is needed to understand how sectors collaborate, inform how to do so more efficiently, effectively and equitably, and ascertain similarities and differences across contexts. To answer these questions and inform practice, research to strengthen the evidence-base on MSC is critical. This paper draws on a 12-country study series on MSC for health and sustainable development, in the context of the health and rights of women, children and adolescents. It is written by core members of the research coordination and country teams. Issues were analyzed during the study period through 'real-time' discussions and structured reporting, as well as through literature reviews and retrospective feedback and analysis at the end of the study. We identify four considerations that are unique to MSC research which will be of interest to other researchers, in the context of COVID-19 and beyond: 1) use theoretical frameworks to frame research questions as relevant to all sectors and to facilitate theoretical generalizability and evolution; 2) specifically incorporate sectoral analysis into MSC research methods; 3) develop a core set of research questions, using mixed methods and contextual adaptations as needed, with agreement on criteria for research rigor; and 4) identify shared indicators of success and failure across sectors to assess MSCs. In responding to COVID-19 it is evident that effective MSC is an urgent priority. It enables partners from diverse sectors to effectively convene to do more together than alone. Our findings have practical relevance for achieving this objective and contribute to the growing literature on partnerships and collaboration. We must seize the opportunity here to identify remaining knowledge gaps on how diverse sectors can work together efficiently and effectively in different settings to accelerate progress towards achieving shared goals.


A clinical and radiological study of biodegradable subacromial spacer in the treatment of massive irreparable rotator cuff tears.
The aim of this retrospective study was to report the clinical and radiographic results of the biodegradable subacromial spacer (InSpace Balloon®) implantation in patients with massive irreparable rotator cuff tears. From February 2014 to October 2015, 30 patients affected by massive irreparable rotator cuff tears were treated with the implantation of InSpace Balloon®. Clinical evaluation (Constant Score and VAS), X-rays and MR imaging were performed preoperatively in all patients and 3, 6, 12 and 24 months after surgery, dividing patients in different groups according to the time elapsed from surgery. Constant Score increased from 39.89 to 62.33 points (p 0.0002) in the 6 months group and from 41.66 to 65.38 points (p< 0.0001) in the 12 months group. ROM (Range of Movement) and ADL (Activity of Daily Living) significantly improved with the contemporary reduction of VAS and pain at 12 months and, furthermore, an increase of functional performance with reduction of pain was registered at 24 months. Our results supported the surgical procedure of the arthroscopic implantation of biodegradable subacromial InSpace Balloon® for irreparable massive cuff tears in worker patients and with recreational activities' demands in order to recover the shoulder function with a reduction of the pain.


Seven weeks of Western diet in apolipoprotein-E-deficient mice induce metabolic syndrome and non-alcoholic steatohepatitis with liver fibrosis.
Non-alcoholic steatohepatitis (NASH) is characterised by hepatic steatosis, inflammation and fibrosis, which might progress to cirrhosis. Human NASH is associated with metabolic syndrome (MS). Currently, rodent NASH models either lack significant fibrosis or MS. ApoE(-/-) mice are a MS model used in cardiovascular research. The aim of this work was to establish and characterise a novel mouse NASH model with significant fibrosis and MS. ApoE(-/-) and wild-type mice (wt) were fed either a western-diet (WD), methionine-choline-deficient-diet (MCD) or normal chow. Liver histology, RT-PCR, hepatic hydroxyproline content, triglycerides and cholesterol levels, and fasting glucose levels assessed hepatic steatosis, inflammation and fibrosis. Further, portal pressure was measured invasively, and kidney pathology was assessed by histology. ApoE(-/-) mice receiving WD showed abnormal glucose tolerance, hepatomegaly, weight gain and full spectrum of NASH including hepatic steatosis, fibrosis and inflammation, with no sign of renal damage. MCD-animals showed less severe liver fibrosis, but detectable renal pathological changes, besides weight loss and unchanged glucose tolerance. This study describes a murine NASH model with distinct hepatic steatosis, inflammation and fibrosis, without renal pathology. ApoE(-/-) mice receiving WD represent a novel and fast model with all characteristic features of NASH and MS well suitable for NASH research.


Biomarkers of cartilage and surrounding joint tissue.
The identification and clinical demonstration of efficacy and safety of osteo- and chondro-protective drugs are met with certain difficulties. During the last few decades, the pharmaceutical industry has, in the field of rheumatology, experienced disappointments associated with the development of disease modification. Today, the vast amount of patients suffering from serious, chronic joint diseases can only be offered treatments aimed at improving symptoms, such as pain and acute inflammation, and are not aimed at protecting the joint tissue. This huge, unmet medical need has been the driver behind the development of improved analytical techniques allowing better and more efficient clinical trial design, implementation and analysis. With this review, we aim to provide a brief and general overview of biochemical markers of joint tissue, with special focus on neoepitopes. Furthermore, we highlight recent studies applying biochemical markers in joint degenerative diseases. These disorders, including osteoarthritis, rheumatoid arthritis and spondyloarthropathies, are the most predominant disorders in Europe and the USA, and have enormous socioeconomical impact.


On the use of different dielectric constants for computing individual and pairwise terms in poisson-boltzmann studies of protein ionization equilibrium.
Poisson-Boltzmann (PB) models are a fast and common tool for studying electrostatic processes in proteins, particularly their ionization equilibrium (protonation and/or reduction), often yielding quite good results when compared with more detailed models. Yet, they are conceptually very simple and necessarily approximate, their empirical character being most evident when it comes to the choice of the dielectric constant assigned to the protein region. The present study analyzes several factors affecting the ability of PB-based methods to model protein ionization equilibrium. We give particular attention to a suggestion made by Warshel and co-workers (e.g., Sham et al. J. Phys. Chem. B 1997, 101, 4458) of using different protein dielectric constants for computing the individual (site) and the pairwise (site-site) terms of the ionization free energies. Our prediction of pK(a) values for several proteins indicates that no advantage is obtained by such a procedure, even for sites that are buried and/or display large pK(a) shifts relative to the solution values. In particular, the present methodology gives the best predictions using a dielectric constant around 20, for shifted/buried and nonshifted/exposed sites alike. The similarities and differences between the PB model and Warshel's PDLD/S model are discussed, as well as the reasons behind their apparently discrepant results. The present PB model is shown to predict also good reduction potentials in redox proteins.


The role of regulated mRNA stability in establishing bicoid morphogen gradient in Drosophila embryonic development.
The Bicoid morphogen is amongst the earliest triggers of differential spatial pattern of gene expression and subsequent cell fate determination in the embryonic development of Drosophila. This maternally deposited morphogen is thought to diffuse in the embryo, establishing a concentration gradient which is sensed by downstream genes. In most model based analyses of this process, the translation of the bicoid mRNA is thought to take place at a fixed rate from the anterior pole of the embryo and a supply of the resulting protein at a constant rate is assumed. Is this process of morphogen generation a passive one as assumed in the modelling literature so far, or would available data support an alternate hypothesis that the stability of the mRNA is regulated by active processes? We introduce a model in which the stability of the maternal mRNA is regulated by being held constant for a length of time, followed by rapid degradation. With this more realistic model of the source, we have analysed three computational models of spatial morphogen propagation along the anterior-posterior axis: (a) passive diffusion modelled as a deterministic differential equation, (b) diffusion enhanced by a cytoplasmic flow term; and (c) diffusion modelled by stochastic simulation of the corresponding chemical reactions. Parameter estimation on these models by matching to publicly available data on spatio-temporal Bicoid profiles suggests strong support for regulated stability over either a constant supply rate or one where the maternal mRNA is permitted to degrade in a passive manner.


Buying 'legal' recreational drugs does not mean that you are not breaking the law.
Recreational drug use in the UK is common; sources of recreational drugs are changing, with increasing purchase of legal highs from the Internet. Previous studies have shown that there is not consistency of active ingredient(s) in legal highs purchased from the Internet. The aim of this study was to determine the impact of the 16 April 2010 change to the Misuse of Drugs Act (1971) on the content of 'legal highs' purchased over the Internet and supplied within the UK. Legal highs were purchased from a number of different Internet suppliers and the active ingredients determined by analysis undertaken within a Home Office approved and licensed laboratory set in a UK academic institution. The active ingredient(s) detected on screening were then compared to the UK legislation in force at the time of purchase to determine whether each individual 'legal' high was in fact legal or not. All 18 products purchased prior to the change in the UK legislation contained active ingredients that were legal under the Misuse of Drugs Act (1971) in force at that time. Six products were purchased and analysed after the changes to the UK Misuse of Drugs Act (1971) on the 16 April 2010. Five of the products contained information, either on the Internet site or the packaging, stating that the product contained legal substances; the final product did not specify the active ingredient and so purchasers would be unable to determine if this was truly a legal product. Five of the six products contained an active ingredient that is a Class B drug under the Misuse of Drugs Act (1971); the other product contained an unlicensed medicine not controlled under the Misuse of Drugs Act (1971). We have shown in this study that some drugs sold as 'legal' highs contain drugs that are controlled under the Misuse of Drugs Act (1971). Under current UK legislation, individuals purchasing legal highs that contained controlled drugs would be subject to the same penalties as if they had knowingly purchased a controlled drug. Dissemination of information on the harm associated with the use of legal highs should also inform individuals that they may be purchasing controlled substances and the potential legal consequences of this.


Response to glucose loading of the lean squirrel monkey in unrestrained conditions.
The response of blood glucose (BG), free fatty acids (FFA), and insulin (IRI) to both intravenous (IVGTT) and oral (OGTT) glucose tolerance tests was evaluated in unrestrained, permanently catheterized squirrel monkeys. The mean glucose assimilation rate (K value) for 25 IVGTT was 7.75 +/- 2.84. FFA maximally decayed 54 percent from a mean basal of 1,008 +/- 221 mueq/l associated with a onefold increment inIRI from basal (7.5 +/- 3.5 muU/ml) at 2-5 min. No significant changes were found during intravenous saline loading alone. OGTT (4g/kg) produced peak BG levels at 15-30 min with an immediate FFA decrease of 63 percent and a onefold IRI increment. Carcass composition analyses from 17 animals showed a total extractable lipid content of 6.2 percent. The K value, significantly higher than previously reported, appears to fit well with that expected for the species. The rapid decrease in FFA and BG concentrations demonstrate an apparent high efficiency of a low IRI increment. The association of the low IRI after loading with a low triglyceride depot is discussed.


Occupational asthma due to different spices.
We describe a 27-year-old subject who developed rhinitis and asthma symptoms 1 year after starting to prepare a certain kind of sausage. He was previously diagnosed as having allergy to coconut, banana, and kiwi and allergic rhinitis to horse, cat, dog, and cow. A positive immediate skin prick test (SPT) for paprika (dry powder of Capsicum annuum [Solanaceae]), coriander (Coriandrum sativum [umbelliferous]), and mace (shell of nutmeg, Myristica fragrans [Myristicaceae]) at a concentration of 10% (w/v) was obtained. SPT with other sausage ingredients, mites, pollens, and molds were negative. By ELISA, specific IgE antibodies to paprika, coriander, and mace were demonstrated. By ELISA-inhibition assays, a partial cross-reactivity was found among IgE-binding components from paprika and mace. The immunoblot analysis showed two IgE-reactive protein bands able to bind to IgE from mace of 20 and 40 kDa and two other bands from coriander extract of 50 and 56 kDa. No bands were detected from paprika extract. Specific bronchial inhalation challenges showed an immediate asthmatic reaction to extracts from paprika, coriander, and mace with a maximum fall in FEV1 of 26%, 40%, and 31%, respectively, with no late asthmatic reactions. In summary, we demonstrate that inhalation of dust from paprika, coriander, and mace can result in an IgE-mediated reaction to these spices. In this patient, occupational asthma was due to spices from botanically unrelated species.


Cardiovascular risk profile of patients included in stent trials; a pooled analysis of individual patient data from randomised clinical trials: insights from 33 prospective stent trials in Europe.
Few data document trends in cardiovascular (CV) risk-factors in patients with or without previous symptomatic CV disease. We assessed the prevalence and trends in (non) modifiable CV risk-factors, and the use of cardioprotective therapies in patients enrolled in coronary stent trials. This analysis included prospective data on 10,253 mainly European adults who were enrolled in 32 coronary stent studies between 1995 and 2006. Data was collected at the time of enrolment using a standardised patient clinical record form, and was analysed by considering three consecutive time periods: 1995-1997 (I), 1998-2002 (II) and 2003-2006 (III) rendering approximately equal numbers per period. Overall the proportion of active smokers remained constant (Period I to III: 28%, 27%, 21%, p=0.45), however the proportion increased in females below 50 years (about 2%/ year, R.RR: 1.20, P: 0.05 period III versus I). Prevalent diabetes increased (16%, 17%, 25%; p=0.029). The prevalence of a body-mass index (BMI) ≥25 kg/m² was high, but no trend was observed (69%, 68%, 70%; p=0.24). The proportion of patients with elevated blood pressure (i.e., ≥140/90 mmHg, in diabetes ≥130/80 mmHg) remained unchanged (55%, 50.%, 53%; p=0.22), despite an increase in the number of patients taking anti-hypertensive agents (84%, 89%, 90%; p=0.30). Conversely, the proportion of patients with elevated total cholesterol (i.e., ≥4.5 mmol/L) decreased (80%, 66%, 52%; p=0.002), which was consistent with the increase in patients taking lipid lowering drugs (32%, 62%, 69%; p=0.083). The portion of patients reaching therapeutic targets for blood lipids improved, but no improvement was seen in blood pressure control (p=0.29). There is an unmet clinical need in primary and secondary CV prevention in Europe. Patients requiring PCI are an important target population in whom lifestyle changes and aggressive secondary preventative measures should be aimed. Ultimately PCI should open the door towards optimising secondary prevention.


Renal proximal tubular metabolism of protein-linked pentosidine, an advanced glycation end product.
Pentosidine, an advanced glycation end product, accumulates in plasma proteins of uremic patients. Its fate is, however, yet to be fully understood. Three cell lines, JTC-12 (proximal tubular cells), MDCK (distal tubular cells), and BALB3T3 (nonrenal cells), were cultured in a double chamber system and were exposed to uremic serum, and the contents of protein-linked pentosidine derived from uremic sera were determined in each medium by HPLC assay. The presence of pentosidine in the cytoplasm of these cells was assessed by immunoperoxidase staining. When the apical cell membrane was exposed to uremic serum (fortified in the upper chamber), the contents of protein-linked pentosidine in the upper medium decreased by up to 30% after 24- and 48-hour incubations of JTC-12 cells but not of other cells. On the other hand, the contents of protein-linked pentosidine in the lower medium did not change. By contrast, exposure of the basolateral cell membrane of the three cell lines to uremic serum (fortified in the lower chamber) did not change the contents of protein-linked pentosidine both in the upper and lower medium after a 24-hour incubation. Pentosidine was detected immunohistochemically in the cytoplasm of JTC-12 cells, but not of BALB3T3 and MDCK cells, the apical membranes of which were exposed to uremic sera for 8 h. The immunoreaction disappeared 48 h after exposure. Pentosidine was not detected in the cytoplasm of JTC-12 cells, the basolateral membranes of which were exposed to uremic sera. The relevance of the in vitro results to humans was demonstrated by immunohistochemical studies in normal human kidney tissues showing that pentosidine was identified in the proximal renal tubules. These results suggest that the proximal tubular cells play a role in the disposal of plasma pentosidine.


Altered renal FGF23-mediated activity involving MAPK and Wnt: effects of the Hyp mutation.
Fibroblast growth factor-23 (FGF23), a hormone central to renal phosphate handling, is elevated in multiple hypophosphatemic disorders. Initial FGF23-dependent Erk1/2 activity in the kidney localizes to the distal convoluted tubule (DCT) with the co-receptor α-Klotho (KL), distinct from Npt2a in proximal tubules (PT). The Hyp mouse model of X-linked hypophosphatemic rickets (XLH) is characterized by hypophosphatemia with increased Fgf23, and patients with XLH elevate FGF23 following combination therapy of phosphate and calcitriol. The molecular signaling underlying renal FGF23 activity, and whether these pathways are altered in hypophosphatemic disorders, is unknown. To examine Npt2a in vivo, mice were injected with FGF23. Initial p-Erk1/2 activity in the DCT occurred within 10 min; however, Npt2a protein was latently reduced in the PT at 30-60 min, and was independent of Npt2a mRNA changes. KL-null mice had no DCT p-Erk1/2 staining following FGF23 delivery. Under basal conditions in Hyp mice, c-Fos and Egr1, markers of renal Fgf23 activity, were increased; however, KL mRNA was reduced 60% (P<0.05). Despite the prevailing hypophosphatemia and elevated Fgf23, FGF23 injections into Hyp mice activated p-Erk1/2 in the DCT. FGF23 injection also resulted in phospho-β-catenin (p-β-cat) co-localization with KL in wild-type mice, and Hyp mice demonstrated strong p-β-cat staining under basal conditions, indicating potential crosstalk between mitogen-activated protein kinase and Wnt signaling. Collectively, these studies refine the mechanisms for FGF23 bioactivity, and demonstrate novel suppression of Wnt signaling in a KL-dependent DCT-PT axis, which is likely altered in XLH. Finally, the current treatment of phosphate and calcitriol for hypophosphatemic disorders may increase FGF23 activity.


Quantum Chemical Study of Supercritical Carbon Dioxide Effects on Combustion Kinetics.
In oxy-fuel combustion, the pure oxygen (O2), diluted with CO2 is used as oxidant instead air. Hence, the combustion products (CO2 and H2O) are free from pollution by nitrogen oxides. Moreover, high pressures result in the near-liquid density of CO2 at supercritical state (sCO2). Unfortunately, the effects of sCO2 on the combustion kinetics are far from being understood. To assist in this understanding, in this work we are using quantum chemistry methods. Here we investigate potential energy surfaces of important combustion reactions in the presence of the carbon dioxide molecule. All transition states and reactant and product complexes are reported for three reactions: H2CO + HO2 → HCO + H2O2 (R1), 2HO2 → H2O2 + O2 (R2), and CO + OH → CO2 + H (R3). In reaction R3, covalent binding of CO2 to the OH radical and then the CO molecule opens a new pathway, including hydrogen transfer from oxygen to carbon atoms followed by CH bond dissociation. Compared to the bimolecular OH + CO mechanism, this pathway reduces the activation barrier by 5 kcal/mol and is expected to accelerate the reaction. In the case of hydroperoxyl self-reaction 2HO2 → H2O2 + O2 the intermediates, containing covalent bonds to CO2 are found not to be competitive. However, the spectator CO2 molecule can stabilize the cyclic transition state and lower the barrier by 3 kcal/mol. Formation of covalent intermediates is also discovered in the H2CO + HO2 → HCO + H2O2 reaction, but these species lead to substantially higher activation barriers, which makes them unlikely to play a role in hydrogen transfer kinetics. The van der Waals complexation with carbon dioxide also stabilizes the transition state and reduces the reaction barrier. These results indicate that the CO2 environment is likely to have a catalytic effect on combustion reactions, which needs to be included in kinetic combustion mechanisms in supercritical CO2.


Work-related electrical fatalities in Australia, 1982-1984.
Work-related electrical fatalities were studied as part of a larger investigation into all work-related fatalities in Australia in the period 1982-1984. The 95 electrical fatalities (all men) represented an incidence of 0.49 per 100,000 persons (0.79/100,000 men) in the employed civilian labor force during the study period. Electricity was the fifth highest cause of work-related fatalities in Australia and resulted in 10% of all workplace deaths. Ninety-four percent of the workers were performing their usual tasks at the time of their death, and 38% of them were doing work of an electrical nature at the time. The greatest number of deaths occurred on farms and nonconstruction industrial sites, with overhead powerlines as the main source of current. Better placement of overhead powerlines, improved worker awareness of electrical hazards, and the use of residual current devices would probably have prevented most of the deaths.


Development of levofloxacin inhalation solution to treat Pseudomonas aeruginosa in patients with cystic fibrosis.
Inhaled therapies allow for the targeted delivery of antimicrobials directly into the lungs and have been widely used in the treatment of cystic fibrosis (CF) acute pulmonary exacerbations. Nebulized levofloxacin solution (MP-376) is a novel therapy that is currently being evaluated in phase I, II, and III clinical trials among patients with stable CF and recent isolation of Pseudomonas aeruginosa from sputum. Phase I studies have investigated the single and multiple-dose pharmacokinetics of MP-376 and shown that it is rapidly absorbed from the lungs and results in low systemic concentrations. A subsequent phase IB study found that MP-376 pharmacokinetics were comparable among adults and children 6-16 years of age. Further phase II studies reported that sputum P. aeruginosa density decreased in a dose-dependent manner among patients who were randomized to MP-376 when compared with patients who received placebo. Improvements in pulmonary function and a decrease in the need for other antipseudomonal antibiotics were also reported for patients who received inhaled levofloxacin. The most common adverse event was dysgeusia (abnormal taste sensation), which was reported by nearly half of the participants who received MP-376. No serious drug-related adverse events were reported. These findings are encouraging; however, data from the two ongoing phase III trials are needed to determine whether MP-376 demonstrates substantial evidence of safety and efficacy as a chronic CF maintenance therapy and therefore may be useful in routine clinical practice.


Biomass consumption by surface fires across Earth's most fire prone continent.
Landscape fire is a key but poorly understood component of the global carbon cycle. Predicting biomass consumption by fire at large spatial scales is essential to understanding carbon dynamics and hence how fire management can reduce greenhouse gas emissions and increase ecosystem carbon storage. An Australia-wide field-based survey (at 113 locations) across large-scale macroecological gradients (climate, productivity and fire regimes) enabled estimation of how biomass combustion by surface fire directly affects continental-scale carbon budgets. In terms of biomass consumption, we found clear trade-offs between the frequency and severity of surface fires. In temperate southern Australia, characterised by less frequent and more severe fires, biomass consumed per fire was typically very high. In contrast, surface fires in the tropical savannas of northern Australia were very frequent but less severe, with much lower consumption of biomass per fire (about a quarter of that in the far south). When biomass consumption was expressed on an annual basis, biomass consumed was far greater in the tropical savannas (>20 times that of the far south). This trade-off is also apparent in the ratio of annual carbon consumption to net primary production (NPP). Across Australia's naturally vegetated land area, annual carbon consumption by surface fire is equivalent to about 11% of NPP, with a sharp contrast between temperate southern Australia (6%) and tropical northern Australia (46%). Our results emphasise that fire management to reduce greenhouse gas emissions should focus on fire prone tropical savanna landscapes, where the vast bulk of biomass consumption occurs globally. In these landscapes, grass biomass is a key driver of frequency, intensity and combustion completeness of surface fires, and management actions that increase grass biomass are likely to lead to increases in greenhouse gas emissions from savanna fires.


Missing data: discussion points from the PSI missing data expert group.
The Points to Consider Document on Missing Data was adopted by the Committee of Health and Medicinal Products (CHMP) in December 2001. In September 2007 the CHMP issued a recommendation to review the document, with particular emphasis on summarizing and critically appraising the pattern of drop-outs, explaining the role and limitations of the 'last observation carried forward' method and describing the CHMP's cautionary stance on the use of mixed models. In preparation for the release of the updated guidance document, statisticians in the Pharmaceutical Industry held a one-day expert group meeting in September 2008. Topics that were debated included minimizing the extent of missing data and understanding the missing data mechanism, defining the principles for handling missing data and understanding the assumptions underlying different analysis methods. A clear message from the meeting was that at present, biostatisticians tend only to react to missing data. Limited pro-active planning is undertaken when designing clinical trials. Missing data mechanisms for a trial need to be considered during the planning phase and the impact on the objectives assessed. Another area for improvement is in the understanding of the pattern of missing data observed during a trial and thus the missing data mechanism via the plotting of data; for example, use of Kaplan-Meier curves looking at time to withdrawal.


Disruption of the murine Ap2β1 gene causes nonsyndromic cleft palate.
Development of the secondary palate in mammals is a complex process that can be easily perturbed, leading to the common and distressing birth defect cleft palate. Animal models are particularly useful tools for dissecting underlying genetic components of cleft palate. We describe a new cleft palate model resulting from a transgene insertion mutation. Transgene insertional mutagenesis disrupts the genomic organization and expression of the Ap2β1 gene located on chromosome 11. This gene encodes the β2-adaptin subunit of the heterotetrameric adaptor protein 2 complex involved in clathrin-dependent endocytosis. Homozygous cleft palate mutant mice express no Ap2β1 messenger RNA or β2-adaptin protein and die during the perinatal period. Heterozygous mice are phenotypically normal despite expressing diminished β2-adaptin messenger RNA and protein compared with wildtype. Remarkably, the paralogous β1-adaptin subunit of the adaptor protein 1 complex partially substitutes for the missing β2-adaptin in embryonic fibroblasts from homozygous mutant mice, resulting in assembly of reduced levels of an adaptor protein 2 complex bearing β1-adaptin. This variant adaptor protein 2 complex is, therefore, apparently capable of maintaining viability of the homozygous mutant embryos until birth but insufficient to support palatogenesis. Nonsyndromic cleft palate in an animal model is associated with disruption of the Ap2β1 gene.


Household transmission of influenza A and B in a school-based study of non-pharmaceutical interventions.
The effect of school-based non-pharmaceutical interventions (NPIs) on influenza A and B transmission in children's households has not been estimated in published literature. We use data from a large school-based cluster randomized trial of improved hand and respiratory hygiene measures to explore the secondary transmission of influenza A and B in households of laboratory confirmed influenza cases. Data were taken from the Pittsburgh Influenza Prevention Project, a cluster-randomized trial of NPIs conducted in ten Pittsburgh, PA elementary schools during the 2007-2008 influenza season. We estimated two measures of influenza transmissibility in households; the susceptible infectious transmission probability, using variants of the Reed-Frost chain binomial model, and the secondary attack rate. We identified predictors of ILI using a logistic generalized estimating equation model. We estimate the secondary attack rates in intervention households to be 0.26 (95% confidence interval (CI) 0.19-0.34) compared to 0.30 (95% CI 0.23-0.38) in control households. Race and age were significant risk factors for secondary ILI acquisition in this study. We found no significant differences between the transmission probabilities for infectious individuals in intervention (0.19, 95% CI 0.14-0.25), and control households (0.22, 95% CI 0.16-0.29). Similarly, estimates for secondary attack rates and transmission probabilities for households with confirmed influenza A (0.31 and 0.22) were not significantly different from estimates from households with confirmed influenza B (0.25 and 0.20). While influenza A and B are thought to have different transmission characteristics, we find no significant differences in their transmissibility within households. Though our results suggest a potential effect, we found no statistically significant effect of school-based non-pharmaceutical interventions on transmission in symptomatic children's homes.


Periodic health examination, 1994 update: 1. Obesity in childhood. Canadian Task Force on the Periodic Health Examination.
To update the 1979 Canadian Task Force on the Periodic Health Examination recommendation on screening for childhood obesity by reviewing any new evidence concerning health risks in childhood and adulthood, and effective preventive or therapeutic interventions. Detection: routine measurement of height and weight, use of skinfold thickness measurements, calculation of body mass index (BMI). diet, exercise, behaviour modification and comprehensive family-based weight-reduction programs. Components of these interventions could be offered routinely or reserved for children and families who perceive obesity to be a present or potential problem. The task force reviewed the probability of obese children become obese adults as a risk factor for adult heart disease and overall related illness and death in adult life as well as obesity as a risk factor for physical and psychologic illness in childhood. A MEDLINE search for relevant articles published between January 1981 and February 1991 was undertaken. The task force's evidence-based rules for recommendations were used. If weight reduction in childhood were shown to prevent physical or psychologic illness in childhood, or illness and death in adult life, screening and treatment should be recommended. Screening for obesity may cause anxiety on the part of the child and family; malnutrition in children as a result of parents becoming overly anxious about the health risks of obesity has been reported. Most weight reduction programs have limited long-term effectiveness and can be costly. There is insufficient evidence of short-term or long-term benefits from screening for or treatment of childhood obesity to recommend such screening or recommend against it. There is fair evidence to recommend against very-low-kilojoule diets for preadolescents. There is insufficient evidence to recommend for or against exercise programs or intensive family-based programs for most obese children. These recommendations are similar to those of the American Academy of Pediatrics and the US Preventive Services Task Force. These guidelines were developed and endorsed by the Canadian task force, which is funded by Health Canada.


A biocompatible tissue scaffold produced by supercritical fluid processing for cartilage tissue engineering.
Supercritical fluids are used in various industrial fields, such as the food and medical industries, because they have beneficial physical and chemical properties and are also nonflammable and inexpensive. In particular, supercritical carbon dioxide (ScCO(2)) is attractive due to its mild critical temperature, pressure values, and nontoxicity. Poly(L-lactide-co-ɛ-caprolactone) (PLCL), which is a biocompatible, biodegradable, and very elastic polymer, has been used in cartilage tissue engineering. However, organic solvents, such as chloroform or dichloromethane, are usually used for the fabrication of a PLCL scaffold through conventional methods. This leads to a cytotoxic effect and long processing time for removing solvents. To alleviate these problems, supercritical fluid processing is introduced here. In this study, we fabricated a mechano-active PLCL scaffold by supercritical fluid processing for cartilage tissue engineering, and we compared it with a scaffold made by a conventional solvent-casting method in terms of physical and biological performance. Also, to examine the optimum condition for preparing scaffolds with ScCO(2), we investigated the effects of pressure, temperature, and the depressurization rate on PLCL foaming. The PLCL scaffolds produced by supercritical fluid processing had a homogeneously interconnected porous structure, and they exhibited a narrow pore size distribution. Also, there was no cytotoxicity of the scaffolds made with ScCO(2) compared to the scaffolds made by the solvent-pressing method. The scaffolds were seeded with chondrocytes, and they were subcutaneously implanted into nude mice for up to 4 weeks. In vivo accumulation of extracellular matrix of cell-scaffold constructs demonstrated that the PLCL scaffold made with ScCO(2) formed a mature and well-developed cartilaginous tissue compared to the PLCL scaffold formed by solvent pressing. Consequently, these results indicated that the PLCL scaffolds made by supercritical fluid processing offer well-interconnected and nontoxic substrates for cell growth, avoiding problems associated with a solvent residue. This suggests that these elastic PLCL scaffolds formed by supercritical fluid processing could be used for cartilage tissue engineering.


Uncertainty-Aware Multidimensional Ensemble Data Visualization and Exploration.
This paper presents an efficient visualization and exploration approach for modeling and characterizing the relationships and uncertainties in the context of a multidimensional ensemble dataset. Its core is a novel dissimilarity-preserving projection technique that characterizes not only the relationships among the mean values of the ensemble data objects but also the relationships among the distributions of ensemble members. This uncertainty-aware projection scheme leads to an improved understanding of the intrinsic structure in an ensemble dataset. The analysis of the ensemble dataset is further augmented by a suite of visual encoding and exploration tools. Experimental results on both artificial and real-world datasets demonstrate the effectiveness of our approach.


Conservation and divergence of meiotic DNA double strand break forming mechanisms in Arabidopsis thaliana.
In the current meiotic recombination initiation model, the SPO11 catalytic subunits associate with MTOPVIB to form a Topoisomerase VI-like complex that generates DNA double strand breaks (DSBs). Four additional proteins, PRD1/AtMEI1, PRD2/AtMEI4, PRD3/AtMER2 and the plant specific DFO are required for meiotic DSB formation. Here we show that (i) MTOPVIB and PRD1 provide the link between the catalytic sub-complex and the other DSB proteins, (ii) PRD3/AtMER2, while localized to the axis, does not assemble a canonical pre-DSB complex but establishes a direct link between the DSB-forming and resection machineries, (iii) DFO controls MTOPVIB foci formation and is part of a divergent RMM-like complex including PHS1/AtREC114 and PRD2/AtMEI4 but not PRD3/AtMER2, (iv) PHS1/AtREC114 is absolutely unnecessary for DSB formation despite having a conserved position within the DSB protein network and (v) MTOPVIB and PRD2/AtMEI4 interact directly with chromosome axis proteins to anchor the meiotic DSB machinery to the axis.


Screening for Higher Grain Yield and Biomass among Sixty Bread Wheat Genotypes Grown under Elevated CO2 and High-Temperature Conditions.
Global warming will inevitably affect crop development and productivity, increasing uncertainty regarding food production. The exploitation of genotypic variability can be a promising approach for selecting improved crop varieties that can counteract the adverse effects of future climate change. We investigated the natural variation in yield performance under combined elevated CO2 and high-temperature conditions in a set of 60 bread wheat genotypes (59 of the 8TH HTWSN CIMMYT collection and Gazul). Plant height, biomass production, yield components and phenological traits were assessed. Large variations in the selected traits were observed across genotypes. The CIMMYT genotypes showed higher biomass and grain yield when compared to Gazul, indicating that the former performed better than the latter under the studied environmental conditions. Principal component and hierarchical clustering analyses revealed that the 60 wheat genotypes employed different strategies to achieve final grain yield, highlighting that the genotypes that can preferentially increase grain and ear numbers per plant will display better yield responses under combined elevated levels of CO2 and temperature. This study demonstrates the success of the breeding programs under warmer temperatures and the plants' capacity to respond to the concurrence of certain environmental factors, opening new opportunities for the selection of widely adapted climate-resilient wheat genotypes.


Abdominal contents from two large early cretaceous compsognathids (Dinosauria: Theropoda) demonstrate feeding on confuciusornithids and dromaeosaurids.
Two skeletons of the large compsognathid Sinocalliopteryx gigas include intact abdominal contents. Both specimens come from the Jianshangou Beds of the lower Yixian Formation (Neocomian), Liaoning, China. The holotype of S. gigas preserves a partial dromaeosaurid leg in the abdominal cavity, here attributed to Sinornithosaurus. A second, newly-discovered specimen preserves the remains of at least two individuals of the primitive avialan, Confuciusornis sanctus, in addition to acid-etched bones from a possible ornithischian. Although it cannot be stated whether such prey items were scavenged or actively hunted, the presence of two Confuciusornis in a grossly similar state of digestion suggests they were consumed in rapid succession. Given the lack of clear arboreal adaptations in Sinocalliopteryx, we suggest it may have been an adept stealth hunter.


Sterile inflammation in Drosophila.
The study of immune responses in Drosophila has already yielded significant results with impacts on our understanding of vertebrate immunity, such as the characterization of the Toll receptor. Several recent papers have focused on the humoral response to damage signals rather than pathogens, particularly damage signals from tumour-like tissues generated by loss of cell polarity or chromosomal instability. Both the triggers that generate this sterile inflammation and the systemic and local effects of it are only just beginning to be characterized in Drosophila. Here we review the molecular mechanisms that are known that give rise to the recruitment of Drosophila phagocytes, called hemocytes, as well as the signals, such as TNFα, that stimulated hemocytes emit at sites of perceived damage. The signalling consequences of inflammation, such as the activation of JNK, and the potential for modifying this response are also discussed.


[Stimulation of LH gene expression by GnRH. Role of protein kinases A and C].
Using anterior pituitary cells in culture, incubated in the presence of [35S] Met, we have previously demonstrated that GnRH stimulates the synthesis of LH polypeptide chains, an effect which was reproduced in a non additive manner by direct activation of protein kinases A and C (by cyclic AMP or diacylglycerol analogues, respectively), and abolished by actinomycin D. The respective roles of GnRH and protein kinases A and C in the stimulation of LH subunit gene expression was examined in the present study by evaluating the effects on the cellular levels of alpha and LH beta mRNAs of optimal concentrations of Buserelin (0.1 nM) an undegradable GnRH analogue, cholera toxin (6 nM) a cyclic AMP (AMPc) generator and 12-O-tetradecanoyl phorbol 13-acetate (TPA) a diacylglycerol analogue. The specific mRNAs were quantified by densitometry analysis of Northern blot hybridization using 32P-labeled single strand cDNAs. We observed TPA, like Buserelin, increased LH mRNA levels in a very similar manner, the alpha mRNA increasing 1.8 - 2.5 fold and the LH beta mRNA 1.4 - 1.7 fold after 5 h culture and 3.0 - 3.5 fold and 2.2 - 2.4 fold respectively, after 24 h. In the presence of cholera toxin, the changes were more rapid, the highest values being reached at 5 h (8.6 fold increase for alpha and 4.0 fold for LH beta mRNA). LH, radioimmunoassayed in parallel in the cell medium, increased 5.9 fold after 5 h and 7.1 fold after 24 h culture in the presence of Buserelin, and 2.9 fold and 5.4 fold, respectively, in the presence of TPA.(ABSTRACT TRUNCATED AT 250 WORDS)


Service use patterns and mental health symptoms among adolescents exposed to multiple types of trauma.
Few studies have explored how different trauma experiences influence service use. This study explores patterns of service use amongst 6483 adolescents aged between 13 and 18, and examines if such patterns are associated with trauma profiles, demographic variables, and mental health disorders. Data from the National Comorbidity Survey--Adolescent Supplement (NCS-A) were used. A latent class analysis identified four adolescent trauma sub-groups: 'high risk', 'sexual risk' 'non-sexual risk', and 'low risk'. Regression analysis was used to explore the relationship between service use, trauma classes, and mental health outcomes. Significant relationships were found between service use, trauma sub-groups, demographics and mental health outcomes. Despite the effectiveness of mental health services, only a minority of adolescents exposed to different traumas use such resources. However, this study may go some way towards providing an understanding of the trauma backgrounds, demographic predictors and mental health disorders associated with service use.


Divergent Evolution of Carbonaceous Aerosols during Dispersal of East Asian Haze.
Wintertime East Asia is plagued by severe haze episodes, characterized by large contributions of carbonaceous aerosols. However, the sources and atmospheric transformations of these major components are poorly constrained, hindering development of efficient mitigation strategies and detailed modelling of effects. Here we present dual carbon isotope (δ13C and Δ14C) signatures for black carbon (BC), organic carbon (OC) and water-soluble organic carbon (WSOC) aerosols collected in urban (Beijing and BC for Shanghai) and regional receptors (e.g., Korea Climate Observatory at Gosan) during January 2014. Fossil sources (>50%) dominate BC at all sites with most stemming from coal combustion, except for Shanghai, where liquid fossil source is largest. During source-to-receptor transport, the δ13C fingerprint becomes enriched for WSOC but depleted for water-insoluble OC (WIOC). This reveals that the atmospheric processing of these two major pools are fundamentally different. The photochemical aging (e.g., photodissociation, photooxidation) during formation and transport can release CO2/CO or short-chain VOCs with lighter carbon, whereas the remaining WSOC becomes increasingly enriched in δ13C. On the other hand, several processes, e.g., secondary formation, rearrangement reaction in the particle phase, and photooxidation can influence WIOC. Taken together, this study highlights high fossil contributions for all carbonaceous aerosol sub-compartments in East Asia, and suggests different transformation pathways for different classes of carbonaceous aerosols.


GlobalFiler(®) Express DNA amplification kit in South Africa: Extracting the past from the present.
In this study, the GlobalFiler(®) Express amplification kit was evaluated for forensic use in 541 South African individuals belonging to the Afrikaaner, amaXhosa,(1) amaZulu,(1) Asian Indian and Coloured population groups. Allelic frequencies, genetic diversity parameters and forensic informative metrics were calculated for each population. A total of 301 alleles were observed ranging between 5 and 44.2 repeat units, 43 were rarely observed partial repeats and seven were novel. The combined match probability (CMP) ranged from 2.21×10(-26) (Coloured) to 5.21×10(-25) (AmaZulu), and the combined power of exclusion (CPE) 0.9999999978 (Afrikaaner) to 0.99999999979 (AmaZulu) respectively. No significant departures from Hardy-Weinberg equilibrium (HWE) were observed after Bonferroni correction. Strong evidence of genetic structure was detected using the coancestry coefficient θ, Analysis of Molecular Variance (AMOVA) and an unsupervised Bayesian clustering method (STRUCTURE). The efficiency of assignment of individuals to population groups was evaluated by applying likelihood ratios with WHICHRUN, and the individual ancestral membership probabilities inferred by STRUCTURE. Likelihood ratios performed the best in the assignment of individuals to population groups. Signs of positive selection were detected for TH01 and D13S317 and purifying/balancing selection for locus SE33. These three loci also displayed the largest informativeness for assignment (In) values. The results of this study supports the use of the GlobalFiler(®) STR profiling kit for forensic applications in South Africa with the additional capability to predict ethnicity or continental origin of a random sample.


Spinal cord neuronal pathology in multiple sclerosis.
The objective of this study was to assess neuronal pathology in the spinal cord in multiple sclerosis (MS), both within myelinated and demyelinated tissue. Autopsy material was obtained from 38 MS cases and 21 controls. Transverse sections were taken from three spinal cord levels and stained using Luxol Fast Blue/Cresyl Violet and myelin protein immunohistochemistry. Measurements of neuronal number and size were made for all neurons within the anterior horns of the gray matter. Neurons were classified as motoneurons or interneurons according to size criteria. In comparison with controls, both motoneuron and interneuron number were reduced in MS cases at the upper cervical (interneuron P = 0.0549; motoneuron P = 0.0073) and upper thoracic (interneuron P = 0.0507; motoneuron P = 0.0144), but not the lumbar level. Interneuron cross-sectional area was reduced in MS cases at all levels (upper cervical, P = 0.0000; upper thoracic, P = 0.0002; lumbar, P = 0.0337). Neuronal loss appears to be predominantly related to local gray matter plaques, whereas interneuron atrophy occurs in both myelinated and demyelinated areas.


Efficacy of a foodlet-based multiple micronutrient supplement for preventing growth faltering, anemia, and micronutrient deficiency of infants: the four country IRIS trial pooled data analysis.
Diets of infants across the world are commonly deficient in multiple micronutrients during the period of growth faltering and dietary transition from milk to solid foods. A randomized placebo controlled trial was carried out in Indonesia, Peru, South Africa, and Vietnam, using a common protocol to investigate whether improving status for multiple micronutrients prevented growth faltering and anemia during infancy. The results of the pooled data analysis of the 4 countries for growth, anemia, and micronutrient status are reported. A total of 1134 infants were randomized to 4 treatment groups, with 283 receiving a daily placebo (P), 283 receiving a weekly multiple micronutrient supplement (WMM), 280 received a daily multiple micronutrient (DMM) supplement, and 288 received daily iron (DI) supplements. The DMM group had a significantly greater weight gain, growing at an average rate of 207 g/mo compared with 192 g/mo for the WMM group, and 186 g/mo for the DI and P groups. There were no differences in height gain. DMM was also the most effective treatment for controlling anemia and iron deficiency, besides improving zinc, retinol, tocopherol, and riboflavin status. DI supplementation alone increased zinc deficiency. The prevalence of multiple micronutrient deficiencies at baseline was high, with anemia affecting the majority, and was not fully controlled even after 6 mo of supplementation. These positive results indicate the need for larger effectiveness trials to examine how to deliver supplements at the program scale and to estimate cost benefits. Consideration should also be given to increasing the dosages of micronutrients being delivered in the foodlets.


2-((3,5-Dinitrobenzyl)thio)quinazolinones: Potent Antimycobacterial Agents Activated by Deazaflavin (F420)-Dependent Nitroreductase (Ddn).
Swapping the substituents in positions 2 and 4 of the previously synthesized but yet undisclosed 5-cyano-4-(methylthio)-2-arylpyrimidin-6-ones 4, ring closure, and further optimization led to the identification of the potent antitubercular 2-thio-substituted quinazolinone 26. Structure-activity relationship (SAR) studies indicated a crucial role for both meta-nitro substituents for antitubercular activity, while the introduction of polar substituents on the quinazolinone core allowed reduction of bovine serum albumin (BSA) binding (63c, 63d). While most of the tested quinazolinones exhibited no cytotoxicity against MRC-5, the most potent compound 26 was found to be mutagenic via the Ames test. This analogue exhibited moderate inhibitory potency against Mycobacterium tuberculosis thymidylate kinase, the target of the 3-cyanopyridones that lies at the basis of the current analogues, indicating that the whole-cell antimycobacterial activity of the present S-substituted thioquinazolinones is likely due to modulation of alternative or additional targets. Diminished antimycobacterial activity was observed against mutants affected in cofactor F420 biosynthesis (fbiC), cofactor reduction (fgd), or deazaflavin-dependent nitroreductase activity (rv3547), indicating that reductive activation of the 3,5-dinitrobenzyl analogues is key to antimycobacterial activity.


Supporting metabolomics with adaptable software: design architectures for the end-user.
Large and disparate sets of LC-MS data are generated by modern metabolomics profiling initiatives, and while useful software tools are available to annotate and quantify compounds, the field requires continued software development in order to sustain methodological innovation. Advances in software development practices allow for a new paradigm in tool development for metabolomics, where increasingly the end-user can develop or redeploy utilities ranging from simple algorithms to complex workflows. Resources that provide an organized framework for development are described and illustrated with LC-MS processing packages that have leveraged their design tools. Full access to these resources depends in part on coding experience, but the emergence of workflow builders and pluggable frameworks strongly reduces the skill level required. Developers in the metabolomics community are encouraged to use these resources and design content for uptake and reuse.


Protein rib: a novel group B streptococcal cell surface protein that confers protective immunity and is expressed by most strains causing invasive infections.
The group B Streptococcus, an important cause of invasive infections in the neonate, is classified into four major serotypes (Ia, Ib, II, and III) based on the structure of the polysaccharide capsule. Since the capsule is a known virulence factor, it has been extensively studied, in particular in type III strains, which cause the majority of invasive infections. Two cell surface proteins, alpha and beta, have also been studied in detail since they confer protective immunity, but these proteins are usually not expressed by type III strains. We describe here a cell surface protein, designated protein Rib (resistance to proteases, immunity, group B), that confers protective immunity and is expressed by most strains of type III. Protein Rib was first identified as a distinct 95-kD protein in extracts of a type III strain, and was purified to homogeneity from that strain. Rabbit antiserum to protein Rib was used to demonstrate that it is expressed on the cell surface of 31 out of 33 type III strains, but only on 1 out of 25 strains representing the other three serotypes. Mouse protection tests showed that antiserum to protein Rib protects against lethal infection with three different strains expressing this antigen, including a strain representing a recently identified high virulence type III clone. Protein Rib is immunologically unrelated to the alpha and beta proteins, but shares several features with the alpha protein. Most importantly, the NH2-terminal amino acid sequences of the Rib and alpha proteins are identical at 6 out of 12 positions. In addition, both protein Rib and the alpha protein are relatively resistant to trypsin (and Rib is also resistant to pepsin) and both proteins vary greatly in size between different clinical isolates. Finally, both protein Rib and the alpha protein exhibit a regular ladderlike pattern in immunoblotting experiments, which may reflect a repetitive structure. Taken together, these data suggest that the Rib and alpha proteins are members of a family of proteins with related structure and function. Since protein Rib confers protective immunity, it may be valuable for the development of a protein vaccine against the group B Streptococcus, an encapsulated bacterium.


Combination of fludarabine and mitoxantrone in untreated stages III and IV low-grade lymphoma: S9501.
To determine the efficacy of combination fludarabine and mitoxantrone (FN) in untreated stages III and IV low-grade lymphoma. The major end point was to estimate progression-free survival (PFS) in all eligible patients. Seventy-eight eligible patients were registered. Chemotherapy courses were administered every 4 weeks with mitoxantrone 10 mg/m2 on day 1 and fludarabine 25 mg/m2 on days 1, 2, and 3 for a total of six to eight cycles. Pneumocystis carinii prophylaxis was required. Seventy-three patients (94%) attained an objective response. Complete remission was demonstrated in 34 patients (44%) and partial remission was demonstrated in 39 patients (50%). With a median follow-up time of 5.5 years, the median PFS was 32 months, with a 4-year PFS rate of 38%. Median survival has not been reached and 88% of all patients are alive at 4 years. The application of the International Prognostic Index and serologic staging showed significant differences in PFS in all risk groups, whereas overall survival was markedly worse for the highest-risk group in either prognostic model. Three prior Southwest Oncology Group trials using a regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone or a combination of prednisone, vincristine, methotrexate, cytarabine, cyclophosphamide, etoposide, nitrogen mustard, vincristine, procarbazine, and prednisone in similar patient populations demonstrated comparable clinical outcome, although the 4-year survival for FN was better. FN was well tolerated, but mild to severe reversible myelosuppression was noted. Other complications were rare. FN is an effective, safe chemotherapy combination for patients with advanced-stage, low-grade lymphoma. Clinical outcomes were comparable to prior published data using anthracycline-based regimens.


Ellagic acid protects against arsenic trioxide-induced cardiotoxicity in rat.
Arsenic trioxide (As2O3) is utilized for treating patients suffering from hematological malignancies particularly acute promyelocytic leukemia. Unfortunately, the extensive application of this chemotherapeutic agent has been limited due to its adverse effects such as cardiotoxicity. Ellagic acid, as a phenolic compound, has shown to exert antioxidant, anti-inflammatory, antifibrotic, and antiatherogenic properties. It is also capable of protecting against drug toxicity. In this study, we evaluated whether ellagic acid can protect against As2O3-induced heart injury in rats. Thirty-two male Wistar rats were randomly divided into four treatment groups, that is, control (0.2 mL of normal saline, intraperitoneally (ip)), As2O3 (5 mg/kg, ip), As2O3 plus ellagic acid, and ellagic acid (30 mg/kg, orally) groups. The drugs were administered daily for 10 days and pretreatment with ellagic acid was performed 1 h prior to As2O3 injection. Cardiotoxicity was characterized by electrocardiological, biochemical, and histopathological evaluations. Our results showed that ellagic acid pretreatment significantly ameliorated As2O3-induced increase in glutathione peroxidase activity and malondialdehyde concentration ( p < 0.05 and p < 0.001, respectively) and also diminished QTc prolongation ( p < 0.0001) and cardiac tissue damages. Pretreatment with ellagic acid also lowered the increased troponin I ( p < 0.0001) and creatine kinase isoenzyme MB ( p < 0.01) levels in response to As2O3. In conclusion, results of this study demonstrated that ellagic acid has beneficial cardioprotective effects against As2O3 toxicity. It is suggested that the protective effects were mediated by antioxidant properties of ellagic acid.


Clinical evaluation of 222 Iranian patients with halitosis.
The primary objectives of the study were to investigate the levels of volatile sulfur compounds (VSCs) in Iranian patients and to find the most prevalent class of halitosis among them. The secondary objective was to study the measures employed by the patients to reduce halitosis. 46.4% of the 222 patients were female (average 32.1 years) and 53.6% were male (average 32.1 years). Contrary to other reports, males were dominant in this study. All the subjects were evaluated through oral examination, gas chromatographic analysis, organoleptic assessment and mouth cleaning and rinsing test (MCART). Finally, each patient was classified according to current classification. The patients were also asked about the measures employed by them to reduce halitosis. The data were statistically analysed using SPSS software. Gas chromatographic analysis revealed that the median values for H(2)S, CH(3)SH and (CH(3))(2)S levels were 214 ppb, 64 ppb and 2 ppb, respectively. Average values of H(2)S, CH(3)SH and (CH(3))(2)S were 358.7 ppb, 143.0 ppb and 19.5 ppb, respectively. A correlation was demonstrated between organoleptic scores and the concentration of only H(2)S, CH(3)SH and the total of three gases. In 62.2% of the subjects, no oral pathologic condition was found, but tongue coating was observed. The patients were in only class I (genuine halitosis) and class II (pseudo-halitosis) halitosis. None of them was diagnosed as halitophobia. The percentages of classes I and II were 98.6% and 1.4%, respectively. The percentages of sub-classes of class I halitosis in total subjects were as follows: 60.8% physiologic halitosis, 37.8% oral pathologic halitosis and 0% extraoral pathologic halitosis. The mean value of organoleptic score for physiologic halitosis was 4.0 and those for oral pathologic halitosis and pseudo-halitosis were 4.3 and 1.6, respectively. MCART was a useful tool to distinguish oral halitosis from extraoral halitosis. Levels of VSCs were not as high as those measured in other countries. Although in most cases VSCs were a contributing factor to halitosis, VSCs levels were not useful diagnostic criteria for the minority of the patients. The most prevalent class and sub-class of halitosis in the patients were genuine halitosis and physiologic halitosis. Measures employed by the patients to reduce halitosis were mostly related to the oral cavity.


Trends in concentrations and use of agricultural herbicides for Corn Belt rivers, 1996-2006.
Trends in the concentrations and agricultural use of four herbicides (atrazine, acetochlor, metolachlor, and alachlor) were evaluated for major rivers of the Corn Belt for two partially overlapping time periods: 1996-2002 and 2000-2006. Trends were analyzed for 11 sites on the mainstems and selected tributaries in the Ohio, Upper Mississippi, and Missouri River Basins. Concentration trends were determined using a parametric regression model designed for analyzing seasonal variability, flow-related variability, and trends in pesticide concentrations (SEAWAVE-Q). The SEAWAVE-Q model accounts for the effect of changing flow conditions in order to separate changes caused by hydrologic conditions from changes caused by other factors, such as pesticide use. Most of the trends in atrazine and acetochlor concentrations for both time periods were relatively small and nonsignificant, but metolachlor and alachlor were dominated by varying magnitudes of concentration downtrends. Overall, with trends expressed as a percent change per year, trends in herbicide concentrations were consistent with trends in agricultural use; 84 of 88 comparisons for different sites, herbicides, and time periods showed no significant difference between concentration trends and agricultural use trends. Results indicate that decreasing use appears to have been the primary cause for the concentration downtrends during 1996-2006 and that, while there is some evidence that nonuse management factors may have reduced concentrations in some rivers, reliably evaluating the influence of these factors on pesticides in large streams and rivers will require improved, basin-specific information on both management practices and use over time.


In situ formation of nanoscale zero-value iron on fish-scale-based porous carbon for Cr(VI) adsorption.
Magnetic carbon materials that have nanoscale zero-valent iron (nZVI) supported on fish scale based hierarchical lamellar porous carbon (FHLC) is reported in this study. The nZVI on FHLC was in the form of body-centered-cubic iron (Fe) crystal. Although it was demonstrated that the specific surface area (SBET), total pore volume (Vt) and micropore volume (Vm) of the FHLC decreased with the increase of Fe contents, a certain amount of addition of iron nanoparticles on FHLC enhances the Cr(VI) adsorption properties. The as-prepared material shows faster adsorption rate and higher maximum adsorption capacity (357.14 mg/g) compared to bare FHLC (344.83 mg/g). In addition, this magnetic carbon material exhibits a high saturated magnetization (16.49 emu/g). It is indicated that the as-prepared carbon material not only can be used to remove Cr(VI) efficiently but also shows excellent magnetic separation performance from wastewater.