Methodological development of fuzzy-logic controllers from multivariable linear control.
It is the function of the design of a fuzzy-logic controller to determine the universes of discourse of the antecedents and the consequents, number of membership labels, distribution and shape of membership functions, rule formulation, etc. Much of the information is usually extracted from expert knowledge, operator experience, or heuristic thinking. It is hence difficult to mechanize the first-stage design of fuzzy-logic controllers using linguistic labels whose performance is no worse than that of conventional multivariable linear controllers such as state-feedback controllers, PID controllers, etc. In this paper, an original systematic seven-step linear-to-fuzzy (LIN2FUZ) algorithm is proposed for generating the labels, universes of discourse of the antecedents and the consequents, and fuzzy rules of ;basically linear' fuzzy-logic controllers, given the reference design of available conventional multivariable linear controllers. The functionally equivalent fuzzy-logic controllers can thus provide the sound basis for the further development to achieve performance beyond the capability or the conventional controllers. The validity and effectiveness of the proposed LIN2FUZ algorithm are demonstrated by a four-input one-output inverted pendulum system.


Delineation of the safe zone in surgery of sylvian insular triangle: morphometric analysis and magnetic resonance imaging study.
Surgery within the insula carries significant risk of morbidity, particularly hemiparesis, because of the difficulty in detecting the internal capsule boundaries. We analyzed the anatomy of the insula and identified landmarks anticipated to facilitate surgery for intrinsic insular lesions. Insular region anatomy was studied in 11 cadaveric brains harvested within 72 hours postmortem. MRI of the specimens was acquired using 3.0 T with T2-weighting and 25 directions of diffusion tensor imaging. Landmarks easily recognizable during surgery were identified on the surface of the insula. The interrelationships between surface landmarks and critical structures were analyzed. The posterior inferior insular point (PIIP) and the upper central insular point (UCIP) were newly established as landmarks on the insula. The PIIP corresponded to the obvious bend in the posterior long insular gyrus. The UCIP is the meeting point between the central insular sulcus and superior peri-insular sulcus. The corticospinal tract was identified as a high-intensity area in the posterior limb of the internal capsule on T2-weighted imaging and its course confirmed with diffusion tensor imaging tractography. The corticospinal tract took a course deep to the posterosuperior insula on T2-weighted imaging, 4.8 mm from the UCIP and 6.2 mm from the PIIP. The posterosuperior part of the insula forms the region at greatest risk to corticospinal tract injury. The PIIP and UCIP are crucial to understanding the relationship of the insula with the posterior limb of the internal capsule including the corticospinal tract.


Can baroreflex sensitivity and heart rate variability predict late neurological outcome in patients with traumatic brain injury?
Previous studies have suggested that depressed heart rate variability (HRV) and baroreflex sensitivity (BRS) are associated with early mortality and morbidity in patients with acute brain injuries of various etiologies. The aim of the present study was to assess changes in HRV and BRS in isolated traumatic brain injury (TBI), with the hypothesis that measurement of autonomic nervous system dysfunction can provide prognostic information on late neurological outcome. Nineteen patients with TBI, requiring mechanical ventilation, sedation and analgesia, and with arterial and intracranial pressure monitoring for at least 1 week, were included. Physiological and treatment variables were collected and power spectral analyses of HRV and BRS analyses in time domain were performed daily. HRV in the high-frequency (HF) and low-frequency (LF) domains, as well as LF/HF ratio and total power, were investigated. The power of these variables to predict poor (Glasgow Outcome Scale Extended [GOSE] score <5), late (1 y) neurological outcome was assessed. Total power, LF, HF, and BRS were all significantly depressed in patients with GOSE score <5. This difference could not be explained by a more severe brain injury at admission or more extensive use of sedative or analgesic drugs. The autonomic variables predicted the late neurological outcome with areas under the receiver-operating curves between 0.78 and 0.83 (sensitivity: 0.63 to 0.88 and specificity: 0.73 to 0.82). HRV and BRS measures in TBI patients during intensive care treatment, including sedative, analgesic, and vasoactive drugs, may identify patients with poor late neurological outcome.


Development and validation of a microRNA based diagnostic assay for primary tumor site classification of liver core biopsies.
Identification of the primary tumor site in patients with metastatic cancer is clinically important, but remains a challenge. Hence, efforts have been made towards establishing new diagnostic tools. Molecular profiling is a promising diagnostic approach, but tissue heterogeneity and inadequacy may negatively affect the accuracy and usability of molecular classifiers. We have developed and validated a microRNA-based classifier, which predicts the primary tumor site of liver biopsies, containing a limited number of tumor cells. Concurrently we explored the influence of surrounding normal tissue on classification. MicroRNA profiling was performed using quantitative Real-Time PCR on formalin-fixed paraffin-embedded samples. 278 primary tumors and liver metastases, representing nine primary tumor classes, as well as normal liver samples were used as a training set. A statistical model was applied to adjust for normal liver tissue contamination. Performance was estimated by cross-validation, followed by independent validation on 55 liver core biopsies with a tumor content as low as 10%. A microRNA classifier developed, using the statistical contamination model, showed an overall classification accuracy of 74.5% upon independent validation. Two-thirds of the samples were classified with high-confidence, with an accuracy of 92% on high-confidence predictions. A classifier trained without adjusting for liver tissue contamination, showed a classification accuracy of 38.2%. Our results indicate that surrounding normal tissue from the biopsy site may critically influence molecular classification. A significant improvement in classification accuracy was obtained when the influence of normal tissue was limited by application of a statistical contamination model.


Different Training Loads Partially Influence Physiological Responses to the Preparation Period in Basketball.
Ferioli, D, Bosio, A, La Torre, A, Carlomagno, D, Connolly, DR, and Rampinini, E. Different training loads partially influence physiological responses to preparation period in basketball. J Strength Cond Res 32(3): 790-797, 2018-The aim of this study was to compare the session rating of perceived exertion training load (sRPE-TL), training volume (TV), and the changes in physical fitness between professional (n = 14) and semiprofessional (n = 18) basketball players during the preparation period. Furthermore, relationships between sRPE-TL and TV with changes in physical fitness level were investigated. The players performed the Yo-Yo intermittent recovery test-level 1 (Yo-Yo IR1) before and after the preparation period. In addition, physiological responses to a standardized 6-minute continuous running test (Mognoni's test) and to a standardized 5-minute high-intensity intermittent running test (HIT) were measured. Session rating of perceived exertion-TL and TV were greater for professional (5,241 ± 1787 AU; 914 ± 122 minutes) compared with semiprofessional players (2,408 ± 487 AU; 583 ± 65 minutes). Despite these differences, Yo-Yo IR1 performance improvements (∼30%) and physiological adaptations to the Mognoni's test were similar between the 2 groups. Furthermore, physiological adaptations to HIT were slightly greater for professional compared with semiprofessional players; however, the magnitude of these effects was only small/moderate. No clear relationships were found between sRPE-TL and changes in Yo-Yo IR1 performance and Mognoni's test (rs ± 90% confidence interval [CI]: Yo-Yo IR1, 0.18 ± 0.30; Mognoni's test, -0.14 ± 0.29). Only moderate relationships were found between sRPE-TL and changes in HIT (rs ± 90% CI: [La], -0.48 ± 0.23; [H], -0.42 ± 0.25). These results raise doubts on the effectiveness of using high sRPE-TL and TV during the preparation period to improve the physical fitness level of players. The Yo-Yo IR1 seems to be sensitive to monitor changes induced by the preparation period; however, its use is not recommended to discriminate between adult basketball players of different competitive level.


Acting like a Tough Guy: Violent-Sexist Video Games, Identification with Game Characters, Masculine Beliefs, & Empathy for Female Violence Victims.
Empathy--putting oneself in another's shoes--has been described as the "social glue" that holds society together. This study investigates how exposure to sexist video games can decrease empathy for female violence victims. We hypothesized that playing violent-sexist video games would increase endorsement of masculine beliefs, especially among participants who highly identify with dominant and aggressive male game characters. We also hypothesized that the endorsement of masculine beliefs would reduce empathy toward female violence victims. Participants (N = 154) were randomly assigned to play a violent-sexist game, a violent-only game, or a non-violent game. After gameplay, measures of identification with the game character, traditional masculine beliefs, and empathy for female violence victims were assessed. We found that participants' gender and their identification with the violent male video game character moderated the effects of the exposure to sexist-violent video games on masculine beliefs. Our results supported the prediction that playing violent-sexist video games increases masculine beliefs, which occurred for male (but not female) participants who were highly identified with the game character. Masculine beliefs, in turn, negatively predicted empathic feelings for female violence victims. Overall, our study shows who is most affected by the exposure to sexist-violent video games, and why the effects occur. (200 words).


Systematic inference of copy-number genotypes from personal genome sequencing data reveals extensive olfactory receptor gene content diversity.
Copy-number variations (CNVs) are widespread in the human genome, but comprehensive assignments of integer locus copy-numbers (i.e., copy-number genotypes) that, for example, enable discrimination of homozygous from heterozygous CNVs, have remained challenging. Here we present CopySeq, a novel computational approach with an underlying statistical framework that analyzes the depth-of-coverage of high-throughput DNA sequencing reads, and can incorporate paired-end and breakpoint junction analysis based CNV-analysis approaches, to infer locus copy-number genotypes. We benchmarked CopySeq by genotyping 500 chromosome 1 CNV regions in 150 personal genomes sequenced at low-coverage. The assessed copy-number genotypes were highly concordant with our performed qPCR experiments (Pearson correlation coefficient 0.94), and with the published results of two microarray platforms (95-99% concordance). We further demonstrated the utility of CopySeq for analyzing gene regions enriched for segmental duplications by comprehensively inferring copy-number genotypes in the CNV-enriched >800 olfactory receptor (OR) human gene and pseudogene loci. CopySeq revealed that OR loci display an extensive range of locus copy-numbers across individuals, with zero to two copies in some OR loci, and two to nine copies in others. Among genetic variants affecting OR loci we identified deleterious variants including CNVs and SNPs affecting ~15% and ~20% of the human OR gene repertoire, respectively, implying that genetic variants with a possible impact on smell perception are widespread. Finally, we found that for several OR loci the reference genome appears to represent a minor-frequency variant, implying a necessary revision of the OR repertoire for future functional studies. CopySeq can ascertain genomic structural variation in specific gene families as well as at a genome-wide scale, where it may enable the quantitative evaluation of CNVs in genome-wide association studies involving high-throughput sequencing.


Evidence for separate ND10-binding and homo-oligomerization domains of Sp100.
Nuclear domains called ND10 or PML nuclear bodies consist of an aggregation of several proteins, most notably PML and Sp100. PML is essential in the nucleation and formation of ND10 as well as in the recruitment of other ND10-associated proteins such as Daxx, pRb, BLM and Sp100. In cells induced to overexpress Sp100, ND10 binding of Sp100 was saturable and excess Sp100 formed new aggregation sites devoid of other ND10-associated proteins, suggesting that homo-oligomerization is the basis for aggregation. To determine whether Sp100 binds to ND10 through hetero- or oligomerization, Sp100 deletion variants fused with GFP were transfected into cells with and without endogenous Sp100, and the localization of the GFP-labeled fragments was determined relative to ND10. Amino acids 29-152 were sufficient for deposition of the GFP-labeled fragments at ND10 in the absence of endogenous Sp100 (heterologous binding) and for self-aggregation (formation of new Sp100 deposits). None of the shorter fragments was deposited at ND10 or self-aggregated. The 29-152 amino acid fragment and some larger fragments, but not the full-size Sp100, induced elongation of ND10, which at their ends contain only Sp100, probably due to self-aggregation. By fusing a peptide consisting of the p53-binding domain from hMDM2 to the Sp100(29-152) fragment, this self-aggregation could be blocked while retaining the limited ND10 binding capacity, indicating that the Sp100 self-aggregation domain and the ND10 binding domain are separate entities. This fusion peptide was used to demonstrate the potential of ND10 to recruit p53 as a protein not usually present at this site. Such deposited p53 was protected from turnover. The capacity of ND10 to recruit Sp100 may serve primarily to reduce its availability.


Genetic diversity of the North African population revealed by the typing of SNPs in the DRD2/ANKK1 genomic region.
The dopamine - related genes, like dopamine D2 receptor (DRD2) gene and ankyrin repeat and kinase domain containing 1 (ANKK1) gene are implicated in neurological functions. Some polymorphisms of the DRD2/ANKK1 locus (TaqIA, TaqIB, TaqID) have been used to study genetic diversity and the evolution of human populations. The present investigation aims to assess the genetic diversity in seven North African populations in order to explore their genetic structure and to compare them to others worldwide populations studied for the same locus. Nine single nucleotide polymorphisms (SNPs) from the DRD2/ANKK1 locus (rs1800497 TaqIA, rs2242592, rs1124492, rs6277, rs6275, rs1079727, rs2002453, rs2234690 and rs1079597 TaqIB) were typed in 366 individuals from seven North African populations: six from Tunisia (Sousse, Smar, Kesra, Kairouan, Mehdia and Kerkennah) and one from Libya. The allelic frequencies of rs2002453 and rs2234690 were higher in the Smar population than in the other North African populations. More, the Smar population showed the lowest average heterozygosity (0.313). The principal component analysis (PCA) showed that the Smar population was clearly separated from others. Furthermore, linkage disequilibrium analysis shown a high linkage disequilibrium in the North African population and essentially in Smar population. Comparison with other world populations has shown that the heterozygosity of North African population was very close to that of the African and European populations. The PCA and the haplotypic analysis suggested the presence of an important Eurasian genetic component for the North African population. These results suggested that the Smar population was isolated from the others North Africans ones by its peculiar genetic structure because of isolation, endogamy and genetic drift. On the other hand, the North African population is characterized by a multi ancestral gene pool from Eurasia and sub-Saharan Africa due to human migration since prehistoric times.


The parental antagonism theory of language evolution: preliminary evidence for the proposal.
Language--as with most communication systems--likely evolved by means of natural selection. Accounts for the genetical selection of language can usually be divided into two scenarios, either of which used in isolation of the other appear insufficient to explain the phenomena: (1) there are group benefits from communicating, and (2) there are individual benefits from being a better communicator. In contrast, it is hypothesized that language phenotypes emerged during a coevolutionary struggle between parental genomes via genomic imprinting, which is differential gene expression depending on parental origin of the genetic element. It is hypothesized that relatedness asymmetries differentially selected for patrigene-caused language phenotypes to extract resources from mother (early in development) and matrigene-caused language phenotypes to influence degree of cooperativeness among asymmetric kin (later in development). This paper reports that imprinted genes have a high frequency of involvement in language phenotypes (~36%), considering their presumed rarity in the human genome (~2%). For example, two well-studied genes associated with language impairments (FOXP2 and UBE3A) exhibit parent-of- origin effects. Specifically, FOXP2 is putatively paternally expressed, whereas UBE3A is a maternally expressed imprinted gene. It is also hypothesized that the more unique and cooperative aspects of human language emerged to the benefit of matrilineal inclusive fitness. Consistent with this perspective, it is reported here that the X-chromosome has higher involvement in loci that have associations with language than would be expected by chance. It is also reported, for the first time, that human and chimpanzee maternally expressed overlapping imprinted genes exhibit greater evolutionary divergence (in terms of the degree of overlapping transcripts) than paternally expressed overlapping imprinted genes. Finally, an analysis of global language patterns reveals that paternally but not maternally silenced Alu elements are positively correlated with language diversity. Furthermore, there is a much higher than expected frequency of Alu elements inserted into the protein-coding machinery of imprinted and X-chromosomal language loci compared with nonimprinted language loci. Taken together these findings provide some support for parental antagonism theory. Unlike previous theories for language evolution, parental antagonism theory generates testable predictions at the proximate (e.g., neurocognitive areas important for social transmission and language capacities), ontogenetic (e.g., the function of language at different points of development), ultimate (e.g., inclusive fitness), and phylogenetic levels (e.g., the spread of maternally derived brain components in mammals, particularly in the hominin lineage), thus making human capacities for culture more tractable than previously thought.


A neuromuscular intervention for exercise-related medial leg pain.
Exercise-related medial leg pain (ERMLP) is a common complaint among athletes, and efforts toward rehabilitation are often unsuccessful. To evaluate the efficacy of a therapeutic intervention in ERMLP localized to soft tissue. A quasi-experimental, nonequivalent control-group study. Athletic training facility. 20 volunteer male and female athletes (18-22 y old) with ERMLP. Complete data were available for 13 participants. Treatment group (TRE, n = 7) received therapeutic intervention focused on relieving muscle hypertonicity in the deep compartment of the lower leg and restoring balance of the toe flexors and extensors. Control group (CON, n = 6) received no intervention. Self-reported pain intensity, pain threshold, and extensor hallucis longus to extensor digitorum brevis (EHL:EDB) electromyography ratio. There were no significant differences in age, duration of symptoms, or pain measures between the 2 groups at baseline. CON demonstrated no significant changes in any of the outcome measures in posttreatment testing, but significant between-groups differences were identified for pain during activity (CON mean = 6.5, 95% CI 5.05, 7.95; TRE mean = 3.5, 95% CI 1.67, 5.33; P = .01), change scores for pain during activity (CON mean = 0.33, 95% CI -1.25, 1.91; TRE mean = -3.43, 95% CI:-4.6, -2.25; P < .001), change scores in pressure threshold (CON mean = -0.25, 95% CI -0.74, 0.23; TRE mean = 0.72, 95% CI 0.22, 1.37; P = .006), and change in EHL:EDB ratios (CON mean = 0.05, 95% CI -0.22, 0.33; TRE mean = 1.07, 95% CI 0.75, 2.07; P < .046). Therapeutic interventions focused on restoring muscle balance appear to be effective in resolving ERMLP.


Molecular epidemiology and evolution of human respiratory syncytial virus and human metapneumovirus.
Human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV) are ubiquitous respiratory pathogens of the Pneumovirinae subfamily of the Paramyxoviridae. Two major surface antigens are expressed by both viruses; the highly conserved fusion (F) protein, and the extremely diverse attachment (G) glycoprotein. Both viruses comprise two genetic groups, A and B. Circulation frequencies of the two genetic groups fluctuate for both viruses, giving rise to frequently observed switching of the predominantly circulating group. Nucleotide sequence data for the F and G gene regions of HRSV and HMPV variants from the UK, The Netherlands, Bangkok and data available from Genbank were used to identify clades of both viruses. Several contemporary circulating clades of HRSV and HMPV were identified by phylogenetic reconstructions. The molecular epidemiology and evolutionary dynamics of clades were modelled in parallel. Times of origin were determined and positively selected sites were identified. Sustained circulation of contemporary clades of both viruses for decades and their global dissemination demonstrated that switching of the predominant genetic group did not arise through the emergence of novel lineages each respiratory season, but through the fluctuating circulation frequencies of pre-existing lineages which undergo proliferative and eclipse phases. An abundance of sites were identified as positively selected within the G protein but not the F protein of both viruses. For HRSV, these were discordant with previously identified residues under selection, suggesting the virus can evade immune responses by generating diversity at multiple sites within linear epitopes. For both viruses, different sites were identified as positively selected between genetic groups.


Multiple microtektite horizons in upper eocene marine sediments: no evidence for mass extinctions.
Microtektites have been recovered from three horizons in eight middle Eocene to middle Oligocene marine sediment sequences. Five of these occurrences are coeval and of latest Eocene age (37.5 to 38.0 million years ago); three are coeval and of early late Eocene age (38.5 to 39.5 million years ago); and three are of middle Oligocene age (31 to 32 million years ago). In addition, rare probable microtektites have been found in sediments with ages of about 36.0 to 36.5 million years. The microtektite horizon at 37.5 to 38.0 million years can be correlated with the North American tektite-strewn field, which has a fission track age (minimum) of 34 to 35 million years and a paleomagnetic age of 37.5 to 38.0 million years. There is no evidence for mass faunal extinctions at any of the microtektite horizons. Many of the distinct faunal changes that occurred in the middle Eocene to middle Oligocene can be related to the formation of the Antarctic ice sheet and the associated cooling phenomena and intensification of bottom currents that led to large-scale dissolution of calcium carbonate and erosion, which created areally extensive hiatuses in the deep-sea sediment records. The occurrence of microtektite horizons of several ages and the lack of evidence for faunal extinctions suggest that the effects of extraterrestrial bolide impacts may be unimportant in the biologic realm during middle Eocene to middle Oligocene time.


Pretreatment qEEG biomarkers for predicting pharmacological treatment outcome in major depressive disorder: Independent validation from the NeuroPharm study.
Several electroencephalogram (EEG) biomarkers for prediction of drug response in major depressive disorder (MDD) have been proposed, but validations in larger independent datasets are missing. In the current study, we investigated the prognostic value of previously suggested EEG biomarkers. We gathered data that matched prior studies in terms of EEG methodology, clinical criteria for MDD, and statistical approach as closely as possible. The NeuroPharm study is a non-randomized and open label prospective clinical trial. One hundred antidepressant free patients with MDD were enrolled in the study and 79 (57 female) were included in the per-protocol analysis. The biomarkers candidates for cross-validation were derived from prior studies such as iSPOT-D and EMBARC and include frontal and occipital alpha power and asymmetry and delta and theta activity at anterior cingulate cortex (ACC). The alpha asymmetry, reported in two out of six prior studies, could be partially validated. We found that in female patients, larger right than left frontal alpha power prior to drug treatment was associated with better clinical outcome 8 weeks later. Moreover, female non-responder had higher central left alpha power relative to the right. In contrast to prior reports, we found that lower theta activity at ACC was present in remitters and was associated with greater improvement at week 8. We provide evidence that in women with MDD, alpha asymmetry seems to be the most promising EEG biomarker for prediction of treatment response. Registration number: NCT02869035.


Acute myocardial infarction: contrast-enhanced multi-detector row CT in a porcine model.
To assess the role of contrast material-enhanced retrospectively electrocardiographically (ECG) gated multi-detector row computed tomography (CT) in the detection of acute myocardial infarction in a porcine model of total coronary occlusion. Seven Yorkshire farm pigs were studied with contrast-enhanced retrospectively ECG-gated multi-detector row CT 3 hours after total occlusion of the distal left anterior descending artery (n = 5) or the second diagonal branch (n = 2). Reformatted short-axis end-systolic and end-diastolic CT data sets were assessed for myocardial perfusion deficits, coronary occlusion, and abnormal myocardial wall motion. Perfusion deficits were compared with microsphere-determined blood flow and triphenyltetrazolium chloride (TTC)-stained tissue samples for infarct assessment by using Bland-Altman analysis and analysis of variance. Myocardial perfusion deficits, occlusion of the left anterior descending artery or second diagonal branch, and akinesis of the infarcted segment were identified in all five animals that completed the study. One animal died, and one data set had nondiagnostic image quality. The CT end-diastolic (mean, 16.1% +/- 4.8 [SD]; range, 8.6%-22.2%) and end-systolic (mean, 17.0% +/- 6.4; range, 8.7%-26.8%) volume of perfusion deficit was similar to that of infarcted tissue at TTC staining (mean, 13.6% +/- 6.0; range, 7.8%-30.9%). Infarcted myocardium at CT demonstrated a 76.1% reduction in microsphere-determined blood flow and a significant reduction of myocardial CT attenuation compared with normal myocardium (P <.01). Myocardial wall motion analysis demonstrated absence of systolic wall thickening in infarcted myocardium. Multi-detector row CT with retrospective ECG gating permits the detection and further characterization of acute myocardial infarction in a porcine model of complete coronary occlusion.


Low- and high-density lipoproteins modulate function, apoptosis, and proliferation of primary human and murine pancreatic beta-cells.
A low high-density lipoprotein (HDL) plasma concentration and the abundance of small dense low-density lipoproteins (LDL) are risk factors for developing type 2 diabetes. We therefore investigated whether HDL and LDL play a role in the regulation of pancreatic islet cell apoptosis, proliferation, and secretory function. Isolated mouse and human islets were exposed to plasma lipoproteins of healthy human donors. In murine and human beta-cells, LDL decreased both proliferation and maximal glucose-stimulated insulin secretion. The comparative analysis of beta-cells from wild-type and LDL receptor-deficient mice revealed that the inhibitory effect of LDL on insulin secretion but not proliferation requires the LDL receptor. HDL was found to modulate the survival of both human and murine islets by decreasing basal as well as IL-1beta and glucose-induced apoptosis. IL-1beta-induced beta-cell apoptosis was also inhibited in the presence of either the delipidated protein or the deproteinated lipid moieties of HDL, apolipoprotein A1 (the main protein component of HDL), or sphingosine-1-phosphate (a bioactive sphingolipid mostly carried by HDL). In murine beta-cells, the protective effect of HDL against IL-1beta-induced apoptosis was also observed in the absence of the HDL receptor scavenger receptor class B type 1. Our data show that both LDL and HDL affect function or survival of beta-cells and raise the question whether dyslipidemia contributes to beta-cell failure and hence the manifestation and progression of type 2 diabetes mellitus.


The dynamics of mammalian P body transport, assembly, and disassembly in vivo.
Exported mRNAs are targeted for translation or can undergo degradation by several decay mechanisms. The 5'-->3' degradation machinery localizes to cytoplasmic P bodies (PBs). We followed the dynamic properties of PBs in vivo and investigated the mechanism by which PBs scan the cytoplasm. Using proteins of the decapping machinery, we asked whether PBs actively scan the cytoplasm or whether a diffusion-based mechanism is sufficient. Live-cell imaging showed that PBs were anchored mainly to microtubules. Quantitative single-particle tracking demonstrated that most PBs exhibited spatially confined motion dependent on microtubule motion, whereas stationary PB pairs were identified at the centrosome. Some PBs translocated in long-range movements on microtubules. PB mobility was compared with mitochondria, endoplasmic reticulum, peroxisomes, SMN bodies, and stress granules, and diffusion coefficients were calculated. Disruption of the microtubule network caused a significant reduction in PB mobility together with an induction of PB assembly. However, FRAP measurements showed that the dynamic flux of assembled PB components was not affected by such treatments. FRAP analysis showed that the decapping enzyme Dcp2 is a nondynamic PB core protein, whereas Dcp1 proteins continuously exchanged with the cytoplasm. This study reveals the mechanism of PB transport, and it demonstrates how PB assembly and disassembly integrate with the presence of an intact cytoskeleton.


A secreted SPRY domain-containing protein (SPRYSEC) from the plant-parasitic nematode Globodera rostochiensis interacts with a CC-NB-LRR protein from a susceptible tomato.
Esophageal gland secretions from nematodes are believed to include effectors that play important roles in plant parasitism. We have identified a novel gene family encoding secreted proteins specifically expressed in the dorsal esophageal gland of Globodera rostochiensis early in the parasitic cycle, and which contain the B30.2/SPRY domain. The secondary structure of these proteins, named the secreted SPRY domain-containing proteins (SPRYSEC), includes highly conserved regions folding into beta-strands interspersed with loops varying in sequence and in length. Mapping sequence diversity onto a three-dimensional structure model of the SPRYSEC indicated that most of the variability is in the extended loops that shape the so-called surface A in the SPRY domains. Seven of nine amino acid sites subjected to diversifying selection in the SPRYSEC are also at this surface. In both yeast-two-hybrid screening using a library from a susceptible tomato and in an in vitro pull-down assay, one of the SPRYSEC interacted with the leucine-rich repeat (LRR) region of a novel coiled-coil nucleotide-binding LRR protein, which is highly similar to members of the SW5 resistance gene cluster. Given that the tomato cultivar used is susceptible to nematode infection, this SPRYSEC could be an evolutionary intermediate that binds to a classical immune receptor but does not yet, or no longer, triggers a resistance response. Alternatively, this SPRYSEC may bind to the immune receptor to downregulate its activity.


Does platelet-rich plasma accelerate recovery after rotator cuff repair? A prospective cohort study.
Platelet-rich plasma (PRP) has been recently used to enhance and accelerate the healing of musculoskeletal injuries and diseases, but evidence is still lacking, especially on its effects after rotator cuff repair. Platelet-rich plasma accelerates recovery after arthroscopic rotator cuff repair in pain relief, functional outcome, overall satisfaction, and enhanced structural integrity of repaired tendon. Cohort study; Level of evidence, 2. Forty-two patients with full-thickness rotator cuff tears were included. Patients were informed about the use of PRP before surgery and decided themselves whether to have PRP placed at the time of surgery. Nineteen patients underwent arthroscopic rotator cuff repair with PRP and 23 without. Platelet-rich plasma was prepared via plateletpheresis and applied in the form of a gel threaded to a suture and placed at the interface between tendon and bone. Outcomes were assessed preoperatively and at 3, 6, 12, and finally at a minimum of 16 months after surgery (at an average of 19.7 ± 1.9 months) with respect to pain, range of motion, strength, and overall satisfaction, and with respect to functional scores as determined using the following scoring systems: the American Shoulder and Elbow Surgeon (ASES) system, the Constant system, the University of California at Los Angeles (UCLA) system, the Disabilities of the Arm, Shoulder and Hand (DASH) system, the Simple Shoulder Test (SST) system, and the Shoulder Pain and Disability Index (SPADI) system. At a minimum of 9 months after surgery, repaired tendon structural integrities were assessed by magnetic resonance imaging. Platelet-rich plasma gel application to arthroscopic rotator cuff repairs did not accelerate recovery with respect to pain, range of motion, strength, functional scores, or overall satisfaction as compared with conventional repair at any time point. Whereas magnetic resonance imaging demonstrated a retear rate of 26.7% in the PRP group and 41.2% in the conventional group, there was no statistical significance between the groups (P = .388). The results suggest that PRP application during arthroscopic rotator cuff repair did not clearly demonstrate accelerated recovery clinically or anatomically except for an improvement in internal rotation. Nevertheless, as the study may have been underpowered to detect clinically important differences in the structural integrity, additional investigations, including the optimization of PRP preparation and a larger randomized study powered for healing rate, are necessary to further determine the effect of PRP.


Dietary shortcomings in children on a gluten-free diet.
Coeliac disease (CD), or permanent gluten intolerance, is one of the most common chronic food-related diseases among children in Europe and the USA. The treatment is lifelong gluten-free diet (GFD) (i.e. the exclusion of wheat, rye and barley from the diet, which are important sources particularly of iron, dietary fibre and vitamin B). The present study aimed to evaluate dietary intakes of energy and nutrients in children and adolescents on GFD and compare these with intake of comparable age groups on a normal diet as well as current recommendations. Thirty children, 4-17 years of age with confirmed CD and on GFD were agreed to participate in this study at the Department of Pediatrics, Umeå University Hospital. Weight and height were used to calculate individual energy requirement according to Nordic Nutrition Recommendations 2004 (NNR-04). Dietary intake was assessed using 5-day food records and household measures were used for quantities. Twenty-five children completed their dietary record. Thirteen of the 25 children did not meet the recommended energy intake and the dietary intakes were inadequate regarding quality of macronutrients and quantity of minerals and vitamins. The mean intakes of sucrose and saturated fatty acids were above and the intakes of dietary fibre, vitamin D, magnesium and selenium below the NNR-04. High intakes of sucrose and saturated fat and a low intake of dietary fibre were also noted in a previous national survey on healthy children on a normal diet. The nutrient density of vitamin D, riboflavin, niacin, thiamine, magnesium and selenium were lower among CD children than healthy children but, for iron and calcium, it was higher in CD children. Children on GFD appear to follow the same trends as healthy children on a normal diet, with high intakes of saturated fat and sucrose and low intakes of dietary fibre, vitamin D and magnesium compared to recommendations.


Bone morphogenetic protein-2 functions as a negative regulator in the differentiation of myoblasts, but not as an inducer for the formations of cartilage and bone in mouse embryonic tongue.
In vitro studies using the myogenic cell line C2C12 demonstrate that bone morphogenetic protein-2 (BMP-2) converts the developmental pathway of C2C12 from a myogenic cell lineage to an osteoblastic cell lineage. Further, in vivo studies using null mutation mice demonstrate that BMPs inhibit the specification of the developmental fate of myogenic progenitor cells. However, the roles of BMPs in the phases of differentiation and maturation in skeletal muscles have yet to be determined. The present study attempts to define the function of BMP-2 in the final stage of differentiation of mouse tongue myoblast. Recombinant BMP-2 inhibited the expressions of markers for the differentiation of skeletal muscle cells, such as myogenin, muscle creatine kinase (MCK), and fast myosin heavy chain (fMyHC), whereas BMP-2 siRNA stimulated such markers. Neither the recombinant BMP-2 nor BMP-2 siRNA altered the expressions of markers for the formation of cartilage and bone, such as osteocalcin, alkaline phosphatase (ALP), collagen II, and collagen X. Further, no formation of cartilage and bone was observed in the recombinant BMP-2-treated tongues based on Alizarin red and Alcian blue stainings. Neither recombinant BMP-2 nor BMP-2 siRNA affected the expression of inhibitor of DNA binding/differentiation 1 (Id1). The ratios of chondrogenic and osteogenic markers relative to glyceraldehyde-3-phosphate dehydrogenase (GAPDH, a house keeping gene) were approximately 1000-fold lower than those of myogenic markers in the cultured tongue. BMP-2 functions as a negative regulator for the final differentiation of tongue myoblasts, but not as an inducer for the formation of cartilage and bone in cultured tongue, probably because the genes related to myogenesis are in an activation mode, while the genes related to chondrogenesis and osteogenesis are in a silencing mode.


Enabling location privacy and medical data encryption in patient telemonitoring systems.
Patient telemonitoring systems (PTS) deal with the acquisition, processing, and secure transmission of a patient's physiological and physical parameters to a remote location, where expert medical knowledge is available. In emergency situations, when the patient's life is threatened, the trend in modern PTS is to transmit the current location of the patient. Although research in communications security has led to mechanisms that sufficiently protect medical data, research related to location privacy area is still in its early stages. This paper proposes an architecture that enhances PTS through location privacy and data encryption. We study the most popular PTS technologies in conjunction with location privacy architectures and propose an innovative scheme that exploits a point-to-point protocol called Mist. We describe a prototype implementation, developed for validating the proposed framework along with the corresponding evaluation results.


The N-Terminal of Aquareovirus NS80 Is Required for Interacting with Viral Proteins and Viral Replication.
Reovirus replication and assembly occurs within viral inclusion bodies that formed in specific intracellular compartments of cytoplasm in infected cells. Previous study indicated that aquareovirus NS80 is able to form inclusion bodies, and also can retain viral proteins within its inclusions. To better understand how NS80 performed in viral replication and assembly, the functional regions of NS80 associated with other viral proteins in aquareovirus replication were investigated in this study. Deletion mutational analysis and rotavirus NSP5-based protein association platform were used to detect association regions. Immunofluorescence images indicated that different N-terminal regions of NS80 could associate with viral proteins VP1, VP4, VP6 and NS38. Further co-immunoprecipitation analysis confirmed the interaction between VP1, VP4, VP6 or NS38 with different regions covering the N-terminal amino acid (aa, 1-471) of NS80, respectively. Moreover, removal of NS80 N-terminal sequences required for interaction with proteins VP1, VP4, VP6 or NS38 not only prevented the capacity of NS80 to support viral replication in NS80 shRNA-based replication complementation assays, but also inhibited the expression of aquareovirus proteins, suggesting that N-terminal regions of NS80 are necessary for viral replication. These results provided a foundational basis for further understanding the role of NS80 in viral replication and assembly during aquareovirus infection.


A comparison of worldwide phonemic and genetic variation in human populations.
Worldwide patterns of genetic variation are driven by human demographic history. Here, we test whether this demographic history has left similar signatures on phonemes-sound units that distinguish meaning between words in languages-to those it has left on genes. We analyze, jointly and in parallel, phoneme inventories from 2,082 worldwide languages and microsatellite polymorphisms from 246 worldwide populations. On a global scale, both genetic distance and phonemic distance between populations are significantly correlated with geographic distance. Geographically close language pairs share significantly more phonemes than distant language pairs, whether or not the languages are closely related. The regional geographic axes of greatest phonemic differentiation correspond to axes of genetic differentiation, suggesting that there is a relationship between human dispersal and linguistic variation. However, the geographic distribution of phoneme inventory sizes does not follow the predictions of a serial founder effect during human expansion out of Africa. Furthermore, although geographically isolated populations lose genetic diversity via genetic drift, phonemes are not subject to drift in the same way: within a given geographic radius, languages that are relatively isolated exhibit more variance in number of phonemes than languages with many neighbors. This finding suggests that relatively isolated languages are more susceptible to phonemic change than languages with many neighbors. Within a language family, phoneme evolution along genetic, geographic, or cognate-based linguistic trees predicts similar ancestral phoneme states to those predicted from ancient sources. More genetic sampling could further elucidate the relative roles of vertical and horizontal transmission in phoneme evolution.


ORGANIC CHEMISTRY. Catalytic asymmetric hydroamination of unactivated internal olefins to aliphatic amines.
Catalytic assembly of enantiopure aliphatic amines from abundant and readily available precursors has long been recognized as a paramount challenge in synthetic chemistry. Here, we describe a mild and general copper-catalyzed hydroamination that effectively converts unactivated internal olefins—an important yet unexploited class of abundant feedstock chemicals—into highly enantioenriched α-branched amines (≥96% enantiomeric excess) featuring two minimally differentiated aliphatic substituents. This method provides a powerful means to access a broad range of advanced, highly functionalized enantioenriched amines of interest in pharmaceutical research and other areas.


Advanced endoscopic imaging: European Society of Gastrointestinal Endoscopy (ESGE) Technology Review.
Background and aim: This technical review is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the utilization of advanced endoscopic imaging in gastrointestinal (GI) endoscopy. Methods: This technical review is based on a systematic literature search to evaluate the evidence supporting the use of advanced endoscopic imaging throughout the GI tract. Technologies considered include narrowed-spectrum endoscopy (narrow band imaging [NBI]; flexible spectral imaging color enhancement [FICE]; i-Scan digital contrast [I-SCAN]), autofluorescence imaging (AFI), and confocal laser endomicroscopy (CLE). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendation and the quality of evidence. Main recommendations:1. We suggest advanced endoscopic imaging technologies improve mucosal visualization and enhance fine structural and microvascular detail. Expert endoscopic diagnosis may be improved by advanced imaging, but as yet in community-based practice no technology has been shown consistently to be diagnostically superior to current practice with high definition white light. (Low quality evidence.) 2. We recommend the use of validated classification systems to support the use of optical diagnosis with advanced endoscopic imaging in the upper and lower GI tracts (strong recommendation, moderate quality evidence). 3. We suggest that training improves performance in the use of advanced endoscopic imaging techniques and that it is a prerequisite for use in clinical practice. A learning curve exists and training alone does not guarantee sustained high performances in clinical practice. (Weak recommendation, low quality evidence.) Conclusion: Advanced endoscopic imaging can improve mucosal visualization and endoscopic diagnosis; however it requires training and the use of validated classification systems.


Krüppel-Like Factor 10 participates in cervical cancer immunoediting through transcriptional regulation of Pregnancy-Specific Beta-1 Glycoproteins.
Cervical cancer (CC) is associated with alterations in immune system balance, which is primarily due to a shift from Th1 to Th2 and the unbalance of Th17/Treg cells. Using in silico DNA copy number analysis, we have demonstrated that ~20% of CC samples exhibit gain of 8q22.3 and 19q13.31; the regions of the genome that encodes the KLF10 and PSG genes, respectively. Gene expression studies demonstrated that there were no alterations in KLF10 mRNA expression, whilst the PSG2 and -5 genes were up-regulated by 1.76 and 3.97-fold respectively in CC compared to normal tissue controls. siRNA and ChIP experiments in SiHa cells have demonstrated that KLF10 participates in immune response through regulation of IL6, IL25 and PSG2 and PSG5 genes. Using cervical tissues from KLF10-/- mice, we have identified down-regulation of PSG17, -21 and -23 and IL11. These results suggest that KLF10 may regulate immune system response genes in cervical cancer among other functions. KLF10 and PSG copy number variations and alterations in mRNA expression levels could represent novel molecular markers in CC.


Randomized Trial of Liposomal Amikacin for Inhalation in Nontuberculous Mycobacterial Lung Disease.
Lengthy, multidrug, toxic, and low-efficacy regimens limit management of pulmonary nontuberculous mycobacterial disease. In this phase II study, we investigated the efficacy and safety of liposomal amikacin for inhalation (LAI) in treatment-refractory pulmonary nontuberculous mycobacterial (Mycobacterium avium complex [MAC] or Mycobacterium abscessus) disease. During the double-blind phase, patients were randomly assigned to LAI (590 mg) or placebo once daily added to their multidrug regimen for 84 days. Both groups could receive open-label LAI for 84 additional days. The primary endpoint was change from baseline to Day 84 on a semiquantitative mycobacterial growth scale. Other endpoints included sputum conversion, 6-minute-walk distance, and adverse events. The modified intention-to-treat population included 89 (LAI = 44; placebo = 45) patients. The average age of the sample was 59 years; 88% were female; 92% were white; and 80 and 59 patients completed study drug dosing during the double-blind and open-label phases, respectively. The primary endpoint was not achieved (P = 0.072); however, a greater proportion of the LAI group demonstrated at least one negative sputum culture (14 [32%] of 44 vs. 4 [9%] of 45; P = 0.006) and improvement in 6-minute-walk test (+20.6 m vs. -25.0 m; P = 0.017) at Day 84. A treatment effect was seen predominantly in patients without cystic fibrosis with MAC and was sustained 1 year after LAI. Most adverse events were respiratory, and in some patients it led to drug discontinuation. Although the primary endpoint was not reached, LAI added to a multidrug regimen produced improvements in sputum conversion and 6-minute-walk distance versus placebo with limited systemic toxicity in patients with refractory MAC lung disease. Further research in this area is needed. Clinical trial registered with www.clinicaltrials.gov (NCT01315236).


Applying the impairment, activity limitation, and participation restriction constructs of the ICF model to osteoarthritis and low back pain trials: a reanalysis.
To test the hypothesis that interventions targeting the relief of pain and disability in musculoskeletal diseases may have differential effects on activity limitation and participation restriction as defined in the International Classification of Functioning, Disability and Health (ICF). Full data were obtained for 3 randomized controlled trials that used the Western Ontario and McMaster Universities Osteoarthritis Measure (WOMAC), the Medical Outcomes Study Short-form 36 (SF-36), or the Oswestry Disability Questionnaire as their primary outcome measures. The trial outcomes were reanalyzed using items previously designated as assessing pure activity limitation (A) or participation restriction (P), or a mixture of the 2 (A/P) only, and the results compared with the outcomes found using the full scales, which assess a mixture of outcome domains. The results did not refute the hypothesis. An exercise-based intervention and injection therapies both appeared to have more effect on participation restriction (P) than on activity limitation (A), while a drug-based intervention had more effect on A than on P. Different interventions used to treat musculoskeletal disorders may have differential effects on impairment, activity limitation, and restricted participation. The use of outcome measures that do not differentiate these 3 domains may obscure the true value of an intervention.


Variation of angle parameters in asians: an anterior segment optical coherence tomography study in a population of singapore malays.
To assess variations in angle parameters using anterior segment optical coherence tomography (AS-OCT) and to investigate demographic, ocular and systemic associations of angle width. This was a substudy of a population based, cross-sectional survey of 3280 (78.7% response rate) Malay people aged 40 to 80 years in Singapore. All participants underwent a standardized interview and ocular and systemic examination. AS-OCT was performed on 291 consecutive patients in standardized dark conditions. Angle opening distance (AOD-500) and trabecular-iris space area (TISA-500) 500 microm from the scleral spur were determined for the nasal and temporal angles. Anterior chamber depth (ACD) was also measured. AS-OCT measurements were analyzed in 239 (82.1%) right eyes. Mean AOD 500 was smaller in women than in men, both nasally (0.255 vs. 0.293 mm, P = 0.026) and temporally (0.245 vs. 0.286 mm, P = 0.023). Mean TISA-500 was smaller in women in the nasal quadrant only (0.104 vs. 0.117 mm, P = 0.035). Mean ACD was smaller in women than in men (2.71 vs. 2.87 mm, P = 0.001). Multiple linear regression showed that axial length and ACD were significantly associated with AOD-500 and TISA-500 both nasally (adjusted R(2) = 0.34 for AOD-500 and 0.20 for TISA-500) and temporally (adjusted R(2) = 0.35 for AOD-500 and 0.24 for TISA-500). Body mass index, HbA(1c), systolic blood pressure, intraocular pressure, cup-to-disc ratio, and central corneal thickness were not significantly associated with AOD-500, TISA-500, or ACD. In this Malay population, angle width measured by AS-OCT was smaller in women than in men, and in eyes with shorter axial length and shallower ACD.


Exposure to particulate matters (PM2.5) and airborne nicotine in computer game rooms after implementation of smoke-free legislation in South Korea.
In South Korea, computer game rooms are subject to regulations mandating a designated nonsmoking area pursuant to Article 7 of the Enforcement Rules of the National Health Promotion Act; nonsmoking areas must be enclosed on all sides by solid and impermeable partitions. Using PM(2.5) monitors (SidePak AM510) and airborne nicotine monitors, we measured concentrations in smoking and nonsmoking areas to examine whether separation of the nonsmoking areas as currently practiced is a viable way to protect the nonsmoking area from secondhand smoke exposure. Convenient samplings were conducted at 28 computer game rooms randomly selected from 14 districts in Seoul, South Korea between August and September 2009. The medians (interquartile range) of PM(2.5) concentrations in smoking and nonsmoking areas were 69.3 μg/m(3) (34.5-116.5 μg/m(3)) and 34 μg/m(3) (15.0-57.0 μg/m(3)), while those of airborne nicotine were 0.41 μg/m(3) (0.25-0.69 μg/m(3)) and 0.12 μg/m(3) (0.06-0.16 μg/m(3)), respectively. Concentrations of airborne nicotine and PM(2.5) in nonsmoking areas were substantially positively associated with those in smoking areas. The Spearman correlation coefficients for them were 0.68 (p = .02) and 0.1 (p = 0.7), respectively. According to our modeling result, unit increase of airborne nicotine concentration in a smoking area contributed to 7 (95% CI = 2.5-19.8) times increase of the concentration in the adjacent nonsmoking area after controlling for the degree of partition left closed and the indoor space volume. Our study thus provides evidence for the introduction of more rigorous policy initiatives aimed at encouraging a complete smoking ban in such venues.


Evidence for transcriptional and post-translational regulation of sucrose synthase in pea nodules by the cellular redox state.
Nitrogen fixation (NF) in legume nodules is very sensitive to environmental constraints. Nodule sucrose synthase (SS; EC 184.108.40.206) has been suggested to play a crucial role in those circumstances because its downregulation leads to an impaired glycolytic carbon flux and, therefore, a depletion of carbon substrates for bacteroids. In the present study, the likelihood of SS being regulated by oxidative signaling has been addressed by the in vivo supply of paraquat (PQ) to nodulated pea plants and the in vitro effects of oxidizing and reducing agents on nodule SS. PQ produced cellular redox imbalance leading to an inhibition of NF. This was preceded by the downregulation of SS gene expression, protein content, and activity. In vitro, oxidizing agents were able to inhibit SS activity and this inhibition was completely reversed by the addition of dithiothreitol. The overall results are consistent with a regulation model of nodule SS exerted by the cellular redox state at both the transcriptional and post-translational levels. The importance of such mechanisms for the regulation of NF in response to environmental stresses are discussed.


Tarsal navicular stress fractures.
Stress fractures of the tarsal navicular bone are being recognized with increasing frequency in physically active persons. Diagnosis is commonly delayed, and outcome often suffers because physicians lack familiarity with the condition. Navicular stress fractures typically present in a running athlete who has gradually increasing pain in the dorsal mid-foot with occasional radiation of pain down the medial arch. Because initial plain films are often normal, the next diagnostic test of choice is triple-phase bone scan, which is positive early in the process and localizes the lesion well. After a positive bone scan, a computed tomographic scan should be obtained to provide anatomic detail and guide therapy. Nondisplaced, noncomminuted fractures respond well to six weeks of non-weight-bearing cast immobilization. Displacement, comminution, and delayed or nonunion fractures are indications for surgical open reduction internal fixation.


Characteristics and management of mirror syndrome: a systematic review (1956-2016).
To describe the clinical features of mirror syndrome and to correlate the effects of different treatments with the fetal outcomes. Online search up to May 2016 was conducted in the PubMed, Embase (Ovid platform) and clinicalTrials.gov without restrictions of language, date or journal. Only papers providing both fetal and maternal presentations and outcomes were included. The study included 74 papers (n=111), with an additional two patients diagnosed at our center (n=113). The mean gestational age at diagnosis was 27 weeks±30 days (16-39 weeks). Whether early or late gestational age at diagnosis, and whether mother and fetus show symptoms simultaneously or on different dates, has insignificant impact on fetal outcome (P=0.06 and P=0.46, respectively). Edema (84%) followed by hypertension (60.1%) were the leading maternal findings. Fetal hydrops (94.7%) and placental edema (62.8%) were the commonest sonographic features. Procedures correcting fetal hydrops/anemia in utero as well as labor induction were the only treatment options correlated with improved fetal survival (χ2 analysis, P=0.01 and Fisher's exact test, P=0.02; respectively). The overall rate of fetal/neonatal mortality was 67.26%. The gestational age at diagnosis and sequence of presentation have insignificant impact on fetal outcome. Improved fetal survival was associated with procedural interventions that correct fetal hydrops as well as labor induction.


Do morphology and stage explain the inferior lung cancer survival in Denmark?
Danish lung cancer patients diagnosed during 1983-1987 experienced 5-yr relative survival rates 2-7% inferior to patients in the other Nordic countries, despite the similarity of cancer registration and healthcare systems in the Nordic countries. Is the inferior relative survival in Denmark due to differences in morphology or stage of lung cancers? The present study compared in detail the survival of 92,719 patients diagnosed with lung cancer during 1978-1992 in Denmark, Finland, and Norway. In particular, differences in morphology and extent of disease were studied. A poor survival rate for small cell anaplastic lung carcinoma compared with all other morphologies was confirmed. However, this could not explain the relative survival differences observed between countries. Extent of disease was the most important predictor of survival. Part of the observed survival differences could be explained by a less favourable stage distribution in Denmark, combined with a slightly lower relative survival rate for those with metastatic disease. Differences in treatment are unlikely to explain the findings, although delays in diagnosing and treating patients in Denmark compared with neighbouring countries could partially explain the lower patient survival in Denmark. In conclusion, the main factor in the lower survival rate in Denmark is unfavourable stage distribution.


The long road to automation: neurocognitive development of letter-speech sound processing.
In transparent alphabetic languages, the expected standard for complete acquisition of letter-speech sound associations is within one year of reading instruction. The neural mechanisms underlying the acquisition of letter-speech sound associations have, however, hardly been investigated. The present article describes an ERP study with beginner and advanced readers in which the influence of letters on speech sound processing is investigated by comparing the MMN to speech sounds presented in isolation with the MMN to speech sounds accompanied by letters. Furthermore, SOA between letter and speech sound presentation was manipulated in order to investigate the development of the temporal window of integration for letter-speech sound processing. Beginner readers, despite one year of reading instruction, showed no early letter-speech sound integration, that is, no influence of the letter on the evocation of the MMN to the speech sound. Only later in the difference wave, at 650 msec, was an influence of the letter on speech sound processing revealed. Advanced readers, with 4 years of reading instruction, showed early and automatic letter-speech sound processing as revealed by an enhancement of the MMN amplitude, however, at a different temporal window of integration in comparison with experienced adult readers. The present results indicate a transition from mere association in beginner readers to more automatic, but still not "adult-like," integration in advanced readers. In contrast to general assumptions, the present study provides evidence for an extended development of letter-speech sound integration.


Antileukemic activity of Tillandsia recurvata and some of its cycloartanes.
Approximately 250,000 deaths were caused by leukemia globally in 2012 and about 40%-50% of all leukemia diagnoses end-up in death. Medicinal plants are a rich source for the discovery of new drugs against leukemia and other types of cancers. To this end, we subjected the Jamaican ball moss (Tillandsia recurvata) and its cycloartanes, as well as some analogs, to in vitro screening against a number of leukemia cell lines. The WST-1 anti-proliferation assay was used to determine the anticancer activity of ball moss and two cycloartanes isolated from ball moss and four of their analogs against four leukemia cell lines (HL-60, K562, MOLM-14, monoMac6). Ball moss crude methanolic extract showed activity with a 50% inhibition concentration (IC50) value of 3.028 μg/ml against the Molm-14 cell line but was ineffective against HL-60 cells. The six cycloartanes tested demonstrated varying activity against the four leukemia cancer cell lines with IC50 values ranging from 1.83 μM to 18.3 μM. Five out of the six cycloartanes demonstrated activity, while one was inactive against all four cell lines. The preliminary activity demonstrated by the Jamaican ball moss and its cycloartanes against selected leukemia cell lines continues to throw light on the broad anticancer activity of ball moss. Further studies to evaluate the efficacy of these molecules in other leukemia cell lines are required in order to validate the activity of these molecules, as well as to determine their mechanisms of action and ascertain the activity in vivo in order to establish efficacy and safety profiles.


Timing spatial conflict within the parietal cortex: a TMS study.
Orienting and motor attention are known to recruit different regions within right and left parietal lobes. However, the time course and the role played by these modules when visual information competes for different motor response are still unknown. To deal with this issue, single-pulse TMS was applied over the angular (AG) and the supramarginal (SMG) gyri of both hemispheres at several time intervals during the execution of a Simon task. Suppression of the conflict between stimulus and response positions (i.e., the Simon effect) was found when TMS pulse was applied 130 msec after stimulus onset over the right AG and after 160 msec when applied over the left AG and SMG. Interestingly, only stimulation of the left SMG suppressed the asymmetry in conflict magnitude between left- and right-hand responses, usually observed in the Simon task. The present data show that orienting attention and motor attention processes are temporally, functionally, and spatially separated in the posterior parietal cortex, and both contribute to prime motor response during spatial conflict.


Seroprevalence and incidence of hepatitis E virus among blood donors: A review.
Hepatitis E virus (HEV) is an RNA virus with 4 main genotypes. HEV-1 and HEV-2 infect solely humans, while HEV-3 and HEV-4 infect humans and various animals such as pigs, deer, and rabbits. HEV-5 and HEV-6 infect mainly wild boar. Recently, new genotypes, known as HEV-7 and HEV-8, were found to infect camels and humans. HEV is globally distributed into different epidemiological patterns based on socioeconomic factors and ecology. Although HEV is mainly transmitted through the fecal-oral route, it was also recognized as a transfusion-transmitted virus. Transmission through blood donation was documented worldwide with rising annual observations, accounting for more than 2.5% of all transmissions. HEV infection is usually asymptomatic or subclinical in immunocompetent individuals, so it remains questionable whether there is an urgent need to screen for HEV prior to blood transfusion. Moreover, recent studies conducted in the Middle East and North Africa (MENA) region indicate that HEV is highly endemic. Here, we provide a review on HEV epidemiology, transmission, and laboratory diagnosis, giving special emphasis to the newly discovered genotypes, HEV-7 and HEV-8. Furthermore, we underscore the findings of recent HEV seroprevalence and viremia studies among blood donors worldwide. We also shed light on similar studies performed among blood donors in the MENA region.


High resilience in the Yamal-Nenets social-ecological system, West Siberian Arctic, Russia.
Tundra ecosystems are vulnerable to hydrocarbon development, in part because small-scale, low-intensity disturbances can affect vegetation, permafrost soils, and wildlife out of proportion to their spatial extent. Scaling up to include human residents, tightly integrated arctic social-ecological systems (SESs) are believed similarly susceptible to industrial impacts and climate change. In contrast to northern Alaska and Canada, most terrestrial and aquatic components of West Siberian oil and gas fields are seasonally exploited by migratory herders, hunters, fishers, and domesticated reindeer (Rangifer tarandus L.). Despite anthropogenic fragmentation and transformation of a large proportion of the environment, recent socioeconomic upheaval, and pronounced climate warming, we find the Yamal-Nenets SES highly resilient according to a few key measures. We detail the remarkable extent to which the system has successfully reorganized in response to recent shocks and evaluate the limits of the system's capacity to respond. Our analytical approach combines quantitative methods with participant observation to understand the overall effects of rapid land use and climate change at the level of the entire Yamal system, detect thresholds crossed using surrogates, and identify potential traps. Institutional constraints and drivers were as important as the documented ecological changes. Particularly crucial to success is the unfettered movement of people and animals in space and time, which allows them to alternately avoid or exploit a wide range of natural and anthropogenic habitats. However, expansion of infrastructure, concomitant terrestrial and freshwater ecosystem degradation, climate change, and a massive influx of workers underway present a looming threat to future resilience.


Simple method for analyzing the birefringence of an elliptical-core fiber by an equivalent rectangular waveguide.
We present details of a simple method, incorporating first-order perturbation theory, to analyze the birefringence exhibited by elliptical-core fibers by using an equivalent rectangular-core waveguide. The results from this method are compared with those obtained from the finite-element and another approximate technique to demonstrate the accuracy of this simple method. The method may be extended to analyze waveguides of arbitrary geometry.


Effects of photobiomodulation therapy, pharmacological therapy, and physical exercise as single and/or combined treatment on the inflammatory response induced by experimental osteoarthritis.
Osteoarthritis (OA) triggers increased levels of inflammatory markers, including prostaglandin (PG) E2 and proinflammatory cytokines. The elevation of cytokine levels is closely associated with increased articular tissue degeneration. Thus, the use of combination therapies may presumably be able to enhance the effects on the modulation of inflammatory markers. The present study aimed to evaluate and compare the effects of photobiomodulation therapy (PBMT), physical exercise, and topical nonsteroidal anti-inflammatory drug (NSAID) use on the inflammatory process after they were applied either alone or in different combinations. OA was induced by intra-articular papain injection in the knee of rats. After 21 days, the animals began treatment with a topical NSAID and/or with physical exercise and/or PBMT. Treatments were performed three times a week for eight consecutive weeks, totaling 24 therapy sessions. Analysis of real-time polymerase chain reaction (RT-PCR) gene expression; interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) protein expression; and PGE2 levels by enzyme-linked immunosorbent assay (ELISA) was conducted. Our results showed that PBMT alone and Exerc + PBMT significantly reduced IL-1β gene expression (p < 0.05) while no treatment changed both IL-6 and TNF-α gene expression. Treatment with NSAID alone, PBMT alone, Exerc + PBMT, and NSAID + PBMT reduced IL-1β protein expression (p < 0.05). All therapies significantly reduced IL-6 and TNF-α protein expression (p < 0.05) compared with the OA group. Similarly, all therapies, except Exerc, reduced the levels of PGE2 (p < 0.05) compared with the OA group. The results from the present study indicate that treatment with PBMT is more effective in modulating the inflammatory process underlying OA when compared with the other therapies tested.


Using Drosophila pigmentation traits to study the mechanisms of cis-regulatory evolution.
One primary agenda of the developmental evolution field is to elucidate molecular mechanisms governing differences in animal form. While mounting evidence has established an important role for mutations in transcription controlling cis-regulatory elements (CREs), the underlying mechanisms that translate these alterations into differences in gene expression are poorly understood. Emerging studies focused on pigmentation differences among closely related Drosophila species have provided many examples of phenotypically relevant CRE changes, and have begun to illuminate how this process works at the level of regulatory sequence function and transcription factor binding. We review recent work in this field and highlight the conceptual and technical challenges that currently await experimental attention.


Randomized Controlled Study to Evaluate Microbial Ecological Effects of CPP-ACP and Cranberry on Dental Plaque.
Ecological approaches to dental caries prevention play a key role in attaining long-term control over the disease and maintaining a symbiotic oral microbiome. This study aimed to investigate the microbial ecological effects of 2 interventional dentifrices: a casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) dentifrice and the same dentifrice supplemented with a polyphenol-rich cranberry extract. The interventional toothpastes were compared with each other and with an active control fluoride dentifrice in a double-blinded randomized controlled trial. Real-time quantitative polymerase chain reaction (qPCR) analysis was used to determine changes in the bacterial loads of 14 key bacterial species (8 caries associated and 6 health associated) in the dental plaque of trial participants after they used the dentifrices for 5 to 6 wk. From the baseline to the recall visit, significant differences were observed between the treatment groups in the bacterial loads of 2 caries-associated bacterial species (Streptococcus mutans [P < 0.001] and Veillonella parvula [P < 0.001]) and 3 health-associated bacterial species (Corynebacterium durum [P = 0.008], Neisseria flavescens [P = 0.005], and Streptococcus sanguinis [P < 0.001]). Compared to the fluoride control dentifrice, the CPP-ACP dentifrice demonstrated significant differences for S. mutans (P = 0.032), C. durum (P = 0.007), and S. sanguinis (P < 0.001), while combination CPP-ACP-cranberry dentifrice showed significant differences for S. mutans (P < 0.001), V. parvula (P < 0.001), N. flavescens (P = 0.003), and S. sanguinis (P < 0.001). However, no significant differences were observed in the bacterial load comparisons between the CPP-ACP and combination dentifrices for any of the targeted bacterial species (P > 0.05). Overall, the results indicate that dentifrices containing CPP-ACP and polyphenol-rich cranberry extracts can influence a species-level shift in the ecology of the oral microbiome, resulting in a microbial community less associated with dental caries (Australian New Zealand Clinical Trial Registry ANZCTR 12618000095268). The results of this randomized controlled trial indicate that dentifrices containing casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and polyphenol-rich cranberry extracts were able to beneficially modulate the microbial ecology of dental plaque in a group of high caries-risk patients. This could contribute toward lowering the risk of developing new caries lesions, an important goal sought by patients, clinicians, and policy makers.


Quality-of-life and surgical treatments for rectal cancer--a longitudinal analysis using the California Cancer Registry.
Heterogeneous results for research investigating health-related quality of life (HRQL) in patients undergoing sphincter-ablating procedures for rectal cancer are likely due to single institution experiences and measurement of HRQL. To address this heterogeneity, we evaluated HRQL in patients with rectal cancer by type of surgery, location of tumor, and receipt of adjuvant therapy using an HRQL instrument that has not been used to address rectal cancer patients in a population-based sample over time. The Functional Assessment of Cancer Therapy-Colorectal instrument was administered at 9 and 19 months after diagnosis to a consecutive sample of 160 patients in Northern California identified by the California Cancer Registry. A broad multidimensional interpretation of HRQL was used to examine the impact of tumor location and treatment status, stage of disease, age, and gender. In general, men had lower social well-being scores, and younger patients had lower physical and emotional well-being scores and colorectal concerns scores. We found no differences in HRQL by either tumor location or type of surgery, at either 9 or 19 months after diagnosis. Lower physical well-being and greater adverse colorectal concerns were reported at 9 months among patients who received adjuvant therapy; however, only adverse colorectal concerns persisted over time. This study provides additional evidence that sphincter-ablating procedures do not necessarily reduce quality of life in patients with rectal cancer. Distinctive features of this study include a broad multidimensional interpretation of HRQL, the 19 months of longitudinal follow-up, and a prospective population-based study design.


Response inhibition impairment in high functioning autism and attention deficit hyperactivity disorder: evidence from near-infrared spectroscopy data.
Response inhibition, an important domain of executive function (EF), involves the ability to suppress irrelevant or interfering information and impulses. Previous studies have shown impairment of response inhibition in high functioning autism (HFA) and attention deficit hyperactivity disorder (ADHD), but more recent findings have been inconsistent. To date, almost no studies have been conducted using functional imaging techniques to directly compare inhibitory control between children with HFA and those with ADHD. Nineteen children with HFA, 16 age- and intelligence quotient (IQ)-matched children with ADHD, and 16 typically developing (TD) children were imaged using functional near-infrared spectroscopy (NIRS) while performing Go/No-go and Stroop tasks. Compared with the TD group, children in both the HFA and ADHD groups took more time to respond during the No-go blocks, with reaction time longest for HFA and shortest for TD. Children in the HFA and ADHD groups also made a greater number of reaction errors in the No-go blocks than those in the TD group. During the Stroop task, there were no significant differences between these three groups in reaction time and omission errors. Both the HFA and ADHD groups showed a higher level of inactivation in the right prefrontal cortex (PFC) during the No-go blocks, relative to the TD group. However, no significant differences were found between groups in the levels of oxyhemoglobin concentration in the PFC during the Stroop task. Functional brain imaging using NIRS showed reduced activation in the right PFC in children with HFA or ADHD during an inhibition task, indicating that inhibitory dysfunction is a shared feature of both HFA and ADHD.


Oxidative Stress-Induced Protein Damage Inhibits DNA Repair and Determines Mutation Risk and Therapeutic Efficacy.
The relationship between sun exposure and nonmelanoma skin cancer risk is well established. Solar UV (wavelength 280-400 nm) is firmly implicated in skin cancer development. Nucleotide excision repair (NER) protects against cancer by removing potentially mutagenic DNA lesions induced by UVB (280-320 nm). How the 20-fold more abundant UVA (320-400 nm) component of solar UV radiation increases skin cancer risk is not understood. Here it is demonstrated that the contribution of UVA to the effect of UV radiation on cultured human cells is largely independent of its ability to damage DNA. Instead, the effects of UVA reflect the induction of oxidative stress that causes extensive protein oxidation. Because NER proteins are among those damaged, UVA irradiation inhibits NER and increases the susceptibility of the cells to mutation by UVB. NER inhibition is a common consequence of oxidative stress. Exposure to chemical oxidants, treatment with drugs that deplete cellular antioxidants, and interventions that interfere with glucose metabolism to disrupt the supply of cellular reducing power all inhibit NER. Tumor cells are often in a condition of oxidative stress and one effect of the NER inhibition that results from stress-induced protein oxidation is an increased sensitivity to the anticancer drug cisplatin. As NER is both a defense against cancer and a significant determinant of cell survival after treatment with anticancer drugs, its attenuation by protein damage under conditions of oxidative stress has implications for both cancer risk and for the effectiveness of anticancer therapy. Mol Cancer Res; 14(7); 612-22. ©2016 AACR.


Discrete response patterns in the upper range of hypnotic suggestibility: A latent profile analysis.
High hypnotic suggestibility is a heterogeneous condition and there is accumulating evidence that highly suggestible individuals may be comprised of discrete subtypes with dissimilar cognitive and phenomenological profiles. This study applied latent profile analysis to response patterns on a diverse battery of difficult hypnotic suggestions in a sample of individuals in the upper range of hypnotic suggestibility. Comparisons among models indicated that a four-class model was optimal. One class was comprised of very highly suggestible (virtuoso) participants, two classes included highly suggestible participants who were alternately more responsive to inhibitory cognitive suggestions or posthypnotic amnesia suggestions, and the fourth class consisted primarily of medium suggestible participants. These results indicate that there are discrete response profiles in high hypnotic suggestibility. They further provide a number of insights regarding the optimization of hypnotic suggestibility measurement and have implications for the instrumental use of hypnosis for the modeling of different psychological conditions.


Obesity, Height, and Serum Androgen Metabolism among Postmenopausal Women in the Women's Health Initiative Observational Study.
Anthropometric measures, including obesity, are important risk factors for breast and endometrial cancers in postmenopausal women. It is unknown whether these risk factors are associated with androgen metabolism, another risk factor for these cancers. Using baseline data from 1,765 postmenopausal women in the Women's Health Initiative Observational Study, we conducted a cross-sectional analysis examining associations between anthropometric measures [current body mass index (BMI), waist-to-hip ratio (WHR), height, and recalled BMI at age 18) and serum androgen metabolites. Twelve androgens/androgen metabolites were quantified using LC-MS/MS. Geometric means of androgen/androgen metabolite concentrations were estimated using linear regression, adjusting for potential confounders and stratified by hormone therapy (HT) use. Regardless of HT use, higher current BMI (≥30 vs. <25 kg/m2) was associated with higher serum concentrations of dehydroepiandrosterone sulfate (DHEAS), 5α-reduced glucuronide metabolites [androsterone-glucuronide (ADT-G), 5α-androstane-3α,17β diol-3-glucuronide (3α-diol-3G), 3α-diol-17-glucuronide (3α-diol-17G)], and DHEAS:DHEA ratio (all P trend ≤ 0.02). BMI was also positively associated with unconjugated estrone:androstenedione and unconjugated estradiol:testosterone ratios among never/former HT users (all P trend < 0.001) but not among current users (P-int < 0.001). WHR was positively associated with adrenal androgens and 5α-reduced glucuronide metabolites in obese women only (BMI ≥ 30 kg/m2; all P-trend ≤ 0.01). BMI at age 18 was inversely associated with adrenal androgens (DHEA, DHEAS, androstenedione, testosterone) and 5α-reduced glucuronide metabolites in never/former HT users (all P trend < 0.06). Height was not associated with androgen metabolites. Current BMI is associated with androgen metabolism among postmenopausal women. This study contributes to our understanding of the link between obesity and cancer risk in postmenopausal women.


Phanerozoic trends in the global diversity of marine invertebrates.
It has previously been thought that there was a steep Cretaceous and Cenozoic radiation of marine invertebrates. This pattern can be replicated with a new data set of fossil occurrences representing 3.5 million specimens, but only when older analytical protocols are used. Moreover, analyses that employ sampling standardization and more robust counting methods show a modest rise in diversity with no clear trend after the mid-Cretaceous. Globally, locally, and at both high and low latitudes, diversity was less than twice as high in the Neogene as in the mid-Paleozoic. The ratio of global to local richness has changed little, and a latitudinal diversity gradient was present in the early Paleozoic.


T cell-independent antigens type 2.
In this review we have attempted to define the characteristics of TI-2 antigens that enable them to stimulate antibody production in the absence of T cell help. One of the most critical properties of this group of antigens is their ability to deliver prolonged and persistent signaling to the B cell. This by itself is not however sufficient to stimulate Ig synthesis, and they must therefore stimulate non-T cells to interact with the B cells either directly or indirectly via cytokine production. There is evidence implicating the NK cell and T cell as playing this important role in response to TI antigens. Furthermore, we discuss the importance of cytokines such as IL-3, GMCSF, and IFN-gamma, which significantly enhance antibody production by these antigens. Finally, we present evidence demonstrating that B cell activation via TI stimuli does not play merely a permissive role in allowing for cell cycle entry and enhanced responsiveness to other stimuli. Rather, the nature of the B cell activating signal is critical in determining the quantitative and qualitative profile of Ig isotype production.


Buckling in armored droplets.
The buckling mechanism in droplets stabilized by solid particles (armored droplets) is tackled at a mesoscopic level using dissipative particle dynamics simulations. We consider one spherical water droplet in a decane solvent coated with nanoparticle monolayers of two different types: Janus (particles whose surface shows two regions with different wetting properties) and homogeneous. The chosen particles yield comparable initial three-phase contact angles, selected to maximize the adsorption energy at the interface. We study the interplay between the evolution of droplet shape, layering of the particles, and their distribution at the interface when the volume of the droplets is reduced. We show that Janus particles affect strongly the shape of the droplet with the formation of a crater-like depression. This evolution is actively controlled by a close-packed particle monolayer at the curved interface. In contrast, homogeneous particles follow passively the volume reduction of the droplet, whose shape does not deviate too much from spherical, even when a nanoparticle monolayer/bilayer transition is detected at the interface. We discuss how these buckled armored droplets might be of relevance in various applications including potential drug delivery systems and biomimetic design of functional surfaces.


Use of complementary and alternative medicine in patients with health complaints attributed to former dental amalgam fillings.
The dental filling material amalgam is generally well tolerated. However, a small proportion of dental patients experience health complaints which they attribute to amalgam. The symptom pattern is often similar to patients with medically unexplained physical symptoms (MUPS) and the health complaints may persist after amalgam removal. Among patients with MUPS, the use of complementary and alternative medicine (CAM) seems to be high. The aim of this survey was to describe the prevalence and range of CAM use among people with health complaints attributed to dental amalgam fillings in which the health problems persist after the removal of all amalgam fillings. Specific attention was paid to (1) self-reported effects of CAM, (2) differences in CAM use dependent on self-reported health, and (3) gender differences in self-reported CAM use. A survey was distributed to all members of The Norwegian dental patient association (NDPA) (n = 999), the response rate was 36.4%. The anonymous questionnaire asked for socio-demographic data, health complaints related to former amalgam fillings, subjectively perceived health status, symptoms, and experience with therapeutic interventions, mostly from the spectrum of CAM. Only participants who had all their fillings removed, which was the vast majority, were analysed. A total of 88.9% of included respondents had used at least one CAM modality, with a higher proportion of men (95.7%) compared to women (86.2%, p = 0.015). The most frequently used therapies were dietary supplements, vitamins and minerals recommended by a therapist (used by 66.7%) followed by self-prescribed dietary supplements, vitamins and minerals (59.0%), homeopathy (54.0%), acupuncture (48.8%) and special diets (47.5%). Use of CAM was similar for participants reporting normal to good health compared to participants reporting poor health. For all but two CAM modalities, the self-reported treatment effect was better in the group reporting normal to good health compared to the group reporting poor health. CAM was widely used by participants in our study, a finding similar to findings from studies of MUPS patients. To date, health problems associated with the use of dental amalgam is not an accepted diagnosis in the healthcare system. Consequently, people suffering from such complaints experience a lack of adequate treatment and support within conventional health care, which might have contributed to the high number of CAM users in this study.


Abundances of 30 elements in lunar rocks, soil, and core samples.
Abundances of 30 elements in seven lunar rocks and soil were determined by instrumental and radiochemical activation analysis. Seven major and minor elements in chips from 27 rocks were determined by instrumental activation analysis. Abundances of ten bulk elements overlap for the breccia rocks and soil samples. All lunar rare earth elements distribution patterns resemble those found in terrestrial abyssal subalkaline basalt, but with Eu depleted by about 60 percent in all lunar samples compared to the adjacent rare earth elements. Precipitation of plagioclase and hypersthene achondritic-like minerals from a melt could account for Eu depletion and the observed distribution of rare earth elements. Abundances of Ti, Al, Ca, Na, and Mn determined by instrumental activation analysis in five core-tube soil samples indicate uniformity for Al and Mn and apparent differences (10 to 20 percent) for Ti, Ca, and Na at 7.8 and 10.5 centimeters as compared to 0to5.2 centimeter depths.


Analysis of oligonucleotides by hydrophilic interaction liquid chromatography coupled to negative ion electrospray ionization mass spectrometry.
Hydrophilic interaction liquid chromatography (HILIC) is here successfully coupled to negative-ion electrospray ionization time-of-flight mass spectrometry (ESI-TOFMS) for the analysis of synthetic and chemically modified oligonucleotides. Separation was performed on a 2.1 mm × 100 mm PEEK ZIC HILIC column packed with hydrophilic stationary phase with a permanent zwitterionic functional group and a particle size of 3.5 μm with an average pore diameter of 200Å. A method was developed to separate homogeneous and heterogeneous oligonucleotides as well as methylated oligonucleotides using a quaternary pumping system containing ammonium acetate and water with an acetonitrile gradient. Analyses of oligonucleotides were performed by LC/MS with a detection limit of 2.5 picomole (20 mer) with signal to noise ratio (S/N) of 4.12. The influence of the eluent composition, type of buffer and its concentration, and organic modifier were also evaluated. The HILIC LC/MS method presented in this paper used common, 'MS friendly', mobile phases achieving sensitive and selective oligonucleotide analysis.


Factors influencing the cost of workers' compensation claims: The effects of settlement method, injury characteristics, and demographics.
This paper estimates an empirical model of the total costs of finalised workers' compensation claims. The sample was comprised of 8232 claims, made by workers in Western Australia, that were closed in 1990. It is reported that the variables representing the method of claim settlement is an important determinant of the cost of individual workers' compensation claims. In addition, it is also found that type of injury, gender, age, and occupational classification have significant effects on the model. Workers who, sustain musculoskeletal injuries, are male, and/or who are white collar workers incur significantly more costs. In addition to these effects, a positive linear relationship between age and costs was also observed. The empirical models, of the kind specified in this paper, may be capable of performing a useful prescriptive role in rehabilitation programs. Such models can enable "problematic" cases to be identified early in the claim process, so that they might be appropriately referred for intensive rehabilitation intervention.


Enumeration of Legionella pneumophila in cooling tower water systems.
Legionella pneumophila, the causative agent of Legionnaires' disease, is known to colonise and frequently grow in cooling tower waters. Disease is acquired by inhaling aerosol contaminated by legionellae. Determination of the count of Legionella pneumophila in cooling tower waters may, therefore, be useful for risk assessment. In our survey, 103 water samples from 50 cooling towers were examined over a five-year period to indicate the seasonal distribution and the ecology of L. pneumophila, as regards temperature and pH. L. pneumophila serogroup 1 was found in 44% of the isolated strains, which is primarily responsible for the majority of Legionnaires' disease. The large majority of examined towers had levels of L. pneumophila in the high-risk category. These cooling towers have been linked to many outbreaks of Legionnaires' disease.


High richness and dense seeding enhance grassland restoration establishment but have little effect on drought response.
Restorations commonly utilize seed addition to formerly arable lands where the development of native plant communities is severely dispersal limited. However, variation in seed addition practices may profoundly affect restoration outcomes. Theory and observations predict that species-rich seed mixtures and seeding at high densities should enhance native plant community establishment, minimize exotic species cover, and may promote resistance and resilience to, and recovery from, environmental perturbations. We studied the post-seeding establishment of native plant communities in large grassland restoration plots, which were sown at two densities crossed with two levels of species richness on formerly arable land in Nebraska, USA, and their responses to drought. To evaluate drought resistance, recovery, and resilience of restored plant communities, we erected rainfall manipulation structures and tracked the response of seeded species cover and total plant biomass during experimental drought relative to controls and in the post-drought growing season. High seed richness and high-density seeding treatments resulted in greater richness and cover of native, seeded species per 0.5 m2 compared to low-richness and low-density treatments. Cover differences in response to seed mixture richness were driven by native forbs. Richness and cover of exotic species were lowest in high-richness and high-density treatments. We found little evidence of differential drought resistance, recovery, and resilience among seeding treatments. Increases in exotic species across years were restricted to drought subplots, and were not affected by seeding treatments. Grassland restoration was generally enhanced and exotic cover reduced both by the use of high-richness seed mixtures and high-density seeding. Given the lack of restoration treatment effects on the resistance, recovery, or resilience of seeded species exposed to drought, and the increases in exotic species following drought, other forms of active management may be needed to produce restored plant communities that are robust to climate change.


The relationships between body composition and cardiovascular risk factors in young Australian men.
Cardiovascular (CV) disease is a leading cause of global mortality. Despite clear evidence of the coexistence of several risk factors in young people as children and an understanding of the importance of the health behaviors in controlling CV disease, there are limited data on the relationships between risk factors and CV disease in young people. Therefore further study is required. This study aimed to investigate associations among body composition, health behaviors and CV risk factors in young Australian men. Thirty five healthy men aged 18-25 years had their blood pressure (BP), blood lipids, body composition, resting metabolic rate (RMR), physical activity, dietary intake and cardiorespiratory fitness assessed. Participants were categorised according to the percentage of body fat into two groups: lean and overweight men. There were no between-group differences in the biochemical indicators except that overweight men had lower HDL-C compared to lean men. Both groups had similar mean energy, protein, fat, carbohydrate and alcohol intake, RMR, physical activity level (PAL) and energy expenditure (EE). Most of the participants (65.7%) had LDL≥2.5 mmol/L. Other common individual risk factors were body fat≥20% (42.9%), waist circumference≥88 cm (28.6%), PAL<1.8 (22.9%) and systolic BP≥130 mmHg (20%). The mean number of CV risk factors was lower among men having a high intake of monounsaturated fatty acids (MUFA, >12% of the energy intake) regardless of whether they were overweight or lean and did not seem to differ according to the source of MUFA consumed. It is a serious concern to observe such a high percentage of CV risk factors in a group of apparently healthy young men. The likelihood of multiple CV risk factors is greater among those with high body fatness and low MUFA intake. Intake of MUFA favorably affects CV risk factors regardless of the source.