Detection of sounds in the auditory stream: event-related fMRI evidence for differential activation to speech and nonspeech.
The detection of speech in an auditory stream is a requisite first step in processing spoken language. In this study, we used event-related fMRI to investigate the neural substrates mediating detection of speech compared with that of nonspeech auditory stimuli. Unlike previous studies addressing this issue, we contrasted speech with nonspeech analogues that were matched along key temporal and spectral dimensions. In an oddball detection task, listeners heard nonsense speech sounds, matched sine wave analogues (complex nonspeech), or single tones (simple nonspeech). Speech stimuli elicited significantly greater activation than both complex and simple nonspeech stimuli in classic receptive language areas, namely the middle temporal gyri bilaterally and in a locus lateralized to the left posterior superior temporal gyrus. In addition, speech activated a small cluster of the right inferior frontal gyrus. The activation of these areas in a simple detection task, which requires neither identification nor linguistic analysis, suggests they play a fundamental role in speech processing.


Adolescent Risk for Intimate Partner Violence Perpetration.
The prevention of intimate partner violence is a desirable individual and public health goal for society. The purpose of this study is to provide a comprehensive assessment of adolescent risk factors for partner violence in order to inform the development of evidence-based prevention strategies. We utilize data from the Rochester Youth Development Study, a two decade long prospective study of a representative community sample of 1000 participants that has extensive measures of adolescent characteristics, contexts, and behaviors that are potential precursors of partner violence. Using a developmental psychopathology framework, we assess self-reported partner violence perpetration in emerging adulthood (ages 20-22) and in adulthood (ages 29-30) utilizing the Conflict Tactics Scale. Our results indicate that risk factors for intimate partner violence span several developmental domains and are substantially similar for both genders. Internalizing and externalizing problem behaviors as well as early intimate relationships are especially salient for both genders. Additionally, cumulative risk across a number of developmental domains places adolescents at particularly high risk of perpetrating partner violence. Implications for prevention include extending existing prevention programs that focus on high risk groups with multiple risks for developmental disruption, as well as focusing on preventing or mitigating identified risk factors across both genders.


Effects of adlay hull extracts on uterine contraction and Ca2+ mobilization in the rat.
Dysmenorrhea is directly related to elevated PGF(2alpha) levels. It is treated with nonsteroid antiinflammatory drugs (NSAIDs) in Western medicine. Since NSAIDs produce many side effects, Chinese medicinal therapy is considered as a feasible alternative medicine. Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf.) has been used as a traditional Chinese medicine for treating dysmenorrhea. However, the relationship between smooth muscle contraction and adlay extracts remains veiled. Therefore, we investigated this relationship in the rat uterus by measuring uterine contraction activity and recording the intrauterine pressure. We studied the in vivo and in vitro effects of the methanolic extracts of adlay hull (AHM) on uterine smooth muscle contraction. The extracts were fractionated using four different solvents: water, 1-butanol, ethyl acetate, and n-hexane; the four respective fractions were AHM-Wa, AHM-Bu, AHM-EA, and AHM-Hex. AHM-EA and its subfractions (175 microg/ml) inhibited uterine contractions induced by PGF(2alpha), the Ca(2+) channel activator Bay K 8644, and high K(+) in a concentration-dependent manner in vitro. AHM-EA also inhibited PGF(2alpha)-induced uterine contractions in vivo; furthermore, 375 microg/ml of AHM-EA inhibited the Ca(2+)-dependent uterine contractions. Thus 375 microg/ml of AHM-EA consistently suppressed the increases in intracellular Ca(2+) concentrations induced by PGF(2alpha) and high K(+). We also demonstrated that naringenin and quercetin are the major pure chemical components of AHM-EA that inhibit PGF(2alpha)-induced uterine contractions. Thus AHM-EA probably inhibited uterine contraction by blocking external Ca(2+) influx, leading to a decrease in intracellular Ca(2+) concentration. Thus adlay hull may be considered as a feasible alternative therapeutic agent for dysmenorrhea.


A comparative pan-genome perspective of niche-adaptable cell-surface protein phenotypes in Lactobacillus rhamnosus.
Lactobacillus rhamnosus is a ubiquitously adaptable Gram-positive bacterium and as a typical commensal can be recovered from various microbe-accessible bodily orifices and cavities. Then again, other isolates are food-borne, with some of these having been long associated with naturally fermented cheeses and yogurts. Additionally, because of perceived health benefits to humans and animals, numerous L. rhamnosus strains have been selected for use as so-called probiotics and are often taken in the form of dietary supplements and functional foods. At the genome level, it is anticipated that certain genetic variances will have provided the niche-related phenotypes that augment the flexible adaptiveness of this species, thus enabling its strains to grow and survive in their respective host environments. For this present study, we considered it functionally informative to examine and catalogue the genotype-phenotype variation existing at the cell surface between different L. rhamnosus strains, with the presumption that this might be relatable to habitat preferences and ecological adaptability. Here, we conducted a pan-genomic study involving 13 genomes from L. rhamnosus isolates with various origins. In using a benchmark strain (gut-adapted L. rhamnosus GG) for our pan-genome comparison, we had focused our efforts on a detailed examination and description of gene products for certain functionally relevant surface-exposed proteins, each of which in effect might also play a part in niche adaptability among the other strains. Perhaps most significantly of the surface protein loci we had analyzed, it would appear that the spaCBA operon (known to encode SpaCBA-called pili having a mucoadhesive phenotype) is a genomic rarity and an uncommon occurrence in L. rhamnosus. However, for any of the so-piliated L. rhamnosus strains, they will likely possess an increased niche-specific fitness, which functionally might presumably be manifested by a protracted transient colonization of the gut mucosa or some similar microhabitat.


Classification systems for distal radius fractures.
Background and purpose - The reliability of conventional radiography when classifying distal radius fractures (DRF) is fair to moderate. We investigated whether reliability increases when additional computed tomography scans (CT) are used. Patients and methods - In this prospective study, we performed pre- and postreduction posterior-anterior and lateral radiographs of 51 patients presenting with a displaced DRF. The case was included when there was a (questionable) indication for surgical treatment and an additional CT was conducted within 5 days. 4 observers assessed the cases using the Frykman, Fernández, Universal, and AO classification systems. The first 2 assessments were performed using conventional radiography alone; the following 2 assessments were performed with an additional CT. We used the intraclass correlation coefficient (ICC) to evaluate reliability. The CT was used as a reference standard to determine the accuracy. Results - The intraobserver ICC for conventional radiography alone versus radiography and an additional CT was: Frykman 0.57 vs. 0.51; Fernández 0.53 vs. 0.66; Universal 0.57 vs. 0.64; AO 0.59 vs. 0.71. The interobserver ICC was: Frykman: 0.45 vs. 0.28; Fernández: 0.38 vs. 0.44; Universal: 0.32 vs. 0.43; AO: 0.46 vs. 0.40. Interpretation - The intraobserver reliability of the classification systems was fair but improved when an additional CT was used, except for the Frykman classification. The interobserver reliability ranged from poor to fair and did not improve when using an additional CT. Additional CT scanning has implications for the accuracy of scoring the fracture types, especially for simple fracture types.


Performance and optical characteristic of InGaN MQWs laser diodes.
The performance of the InGaN multi-quantum wells (MQWs) laser diode structures has been numerically investigated by using ISE TCAD software. We investigated the effect of well numbers, barrier thickness and barrier doping on the output power, threshold current, and slope efficiency. All material parameters used in the model are evaluated based on the recent literature values. We observed the maximum output power and lower threshold current when the well number was two. Effective change in the output power and threshold current was observed with the variations in barriers thickness and doping level. Our results are in agreement with the experimental results observed by [S. Nakamura et al. Jpn. J. Appl. Phys. Part 2, 37, L1020 (1998) and S. Nakamura et al. Appl. Phys. Lett. 76, 22 (2000)].


Polarization multiplexing and demultiplexing for appearance-based modeling.
Polarization has been used in numerous prior studies for separating diffuse and specular reflectance components, but in this work we show that it also can be used to separate surface reflectance contributions from individual light sources. Our approach is called polarization multiplexing and it has a significant impact in appearance modeling where the image as a function of illumination direction is needed. Multiple unknown light sources can illuminate the scene simultaneously, and the individual contributions to the overall surface reflectance are estimated. Polarization multiplexing relies on the relationship between the light source direction and the intensity modulation. Inverting this transformation enables the individual intensity contributions to be estimated. In addition to polarization multiplexing, we show that phase histograms from the intensity modulations can be used to estimate scene properties including the number of light sources.


High-level, lasting antiviral immunity induced by a bimodal AIDS vaccine and boosted by live-virus exposure: prevention of viremia.
To characterize the correlates of protection from systemic infection in a vaccinated rhesus macaque, RAt-9, which had been challenged sequentially with two related clade C simian/human immunodeficiency viruses (SHIV-Cs) yet remained aviremic for more than 5 years despite indirect evidence of cryptic infection. To measure long-term anti-SHIV-C immunity, host genetics and gene-expression patterns for protective correlates. Long-term immune reactivity was evaluated and identification of virus in RAt-9 was attempted by RT-PCR analysis of concentrated plasma and blood transfer to CD8(+) cell-depleted infant macaques. Full MHC genotyping of RAt-9, TRIM5α and KIR3DL allelic expression analysis of PBMC, and microarray gene expression analysis were performed. All attempts to detect/isolate virus, including blood transfer to CD8(+) cell-depleted infant rhesus macaques, were negative, and the animal maintained normal levels of memory CD4(+) T cells in both peripheral blood and gut tissues. However, RAt-9 maintained high levels of anti-SHIV-C humoral and cellular immunity, including reactivity to nonvaccine neoantigens (Nef and Rev), up to 63 months postinitial challenge, suggesting chronic sub-threshold infection. RAt-9 expressed the Mamu A*001 allele negative for B*008 and B*017, had a B13 serotype, and had increased expression of killer-cell immunoglobulin-like receptors (KIRs) previously linked to favorable outcomes of lentiviral infection. Elements of the gene expression profiling coincided with genotyping results. RAt-9 also displayed CD8 cell noncytotoxic antiviral response (CNAR) activity. Monkey RAt-9 is the first example of a virus-exposed, persistently aviremic animal that has maintained long-term, high-level cellular and humoral antiviral immunity in the absence of an identifiable cryptic reservoir.


O-GlcNAcylation is required for mutant KRAS-induced lung tumorigenesis.
Mutant KRAS drives glycolytic flux in lung cancer, potentially impacting aberrant protein glycosylation. Recent evidence suggests aberrant KRAS drives flux of glucose into the hexosamine biosynthetic pathway (HBP). HBP is required for various glycosylation processes, such as protein N- or O-glycosylation and glycolipid synthesis. However, its function during tumorigenesis is poorly understood. One contributor and proposed target of KRAS-driven cancers is a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT). Here we showed in novel autochthonous mouse models that EMT accelerated KrasG12D lung tumorigenesis by upregulating expression of key enzymes of the HBP pathway. We demonstrated that HBP was required for suppressing KrasG12D-induced senescence, and targeting HBP significantly delayed KrasG12D lung tumorigenesis. To explore the mechanism, we investigated protein glycosylation downstream of HBP and found elevated levels of O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins. O-GlcNAcylation suppressed KrasG12D oncogene-induced senescence (OIS) and accelerated lung tumorigenesis. Conversely, loss of O-GlcNAcylation delayed lung tumorigenesis. O-GlcNAcylation of proteins SNAI1 and c-MYC correlated with the EMT-HBP axis and accelerated lung tumorigenesis. Our results demonstrated that O-GlcNAcylation was sufficient and required to accelerate KrasG12D lung tumorigenesis in vivo, which was reinforced by epithelial plasticity programs.


WHO should accelerate, not stall, rectal artesunate deployment for pre-referral treatment of severe malaria.
The recent World Health Organization moratorium on rectal artesunate (RAS) for pre-referral treatment of severe childhood malaria is costing young lives. The decision was based on disappointing findings from a large observational study that provided RAS to community health workers with little training and supervision. This non-randomized, operational research has provided useful information to guide the implementation of RAS but is subject to bias and confounding and cannot be used to assess treatment effects. Parenteral artesunate reduces severe malaria mortality and a large body of evidence also shows RAS has lifesaving efficacy. There is now more than a decade of delay in conducting the necessary engagement and training required for successful deployment of RAS. Further delays will result in more preventable deaths.


Adductor Canal Block With Continuous Infusion Versus Intermittent Boluses and Morphine Consumption: A Randomized, Blinded, Controlled Clinical Trial.
Based on the assumption that relatively large volumes of local anesthetic optimize an adductor canal block (ACB), we theorized that an ACB administered as repeated boluses would improve analgesia without compromising mobility, compared with a continuous infusion. We performed a randomized, blinded, controlled study, including patients scheduled for total knee arthroplasty with spinal anesthesia. Patients received 0.2% ropivacaine via a catheter in the adductor canal administered as either repeated intermittent boluses (21 mL/3 h) or continuous infusion (7 mL/h). The primary outcome was total (postoperative day [POD], 0-2) opioid consumption (mg), administered as patient-controlled analgesia. Pain, ambulation, and quadriceps muscle strength were secondary outcomes. We randomized 110 patients, of whom 107 were analyzed. Total opioid consumption (POD, 0-2) was a median (range) of 23 mg (0-139) in the bolus group and 26 mg (3-120) in the infusion group (estimated median difference, 4 mg; 95% confidence interval [CI], -13 to 5; P = .29). Linear mixed-model analyses revealed no difference in pain during knee flexion (mean difference, 2.6 mm; 95% CI, -2.9 to 8.0) or at rest (mean difference, 1.7 mm; 95% CI, -1.5 to 4.9). Patients in the bolus group had improved quadriceps sparing on POD 2 (median difference, 7.4%; 95% CI, 0.5%-15.5%). However, this difference was not present on POD 1 or reflected in the ambulation tests (P > .05). Changing the mode of administration for an ACB from continuous infusion to repeated intermittent boluses did not decrease opioid consumption, pain, nor mobility.


Genetic architecture of spring and autumn phenology in Salix.
In woody plants from temperate regions, adaptation to the local climate results in annual cycles of growth and dormancy, and optimal regulation of these cycles are critical for growth, long-term survival, and competitive success. In this study we have investigated the genetic background to growth phenology in a Salix pedigree by assessing genetic and phenotypic variation in growth cessation, leaf senescence and bud burst in different years and environments. A previously constructed linkage map using the same pedigree and anchored to the annotated genome of P. trichocarpa was improved in target regions and used for QTL analysis of the traits. The major aims in this study were to map QTLs for phenology traits in Salix, and to identify candidate genes in QTL hot spots through comparative mapping with the closely related Populus trichocarpa. All traits varied significantly among genotypes and the broad-sense heritabilities ranged between 0.5 and 0.9, with the highest for leaf senescence. In total across experiment and years, 80 QTLs were detected. For individual traits, the QTLs explained together from 21.5 to 56.5% of the variation. Generally each individual QTL explained a low amount of the variation but three QTLs explained above 15% of the variation with one QTL for leaf senescence explaining 34% of the variation. The majority of the QTLs were recurrently identified across traits, years and environments. Two hotspots were identified on linkage group (LG) II and X where narrow QTLs for all traits co-localized. This study provides the most detailed analysis of QTL detection for phenology in Salix conducted so far. Several hotspot regions were found where QTLs for different traits and QTLs for the same trait but identified during different years co-localised. Many QTLs co-localised with QTLs found in poplar for similar traits that could indicate common pathways for these traits in Salicaceae. This study is an important first step in identifying QTLs and candidate genes for phenology traits in Salix.


The measure of order and disorder in the distribution of species in fragmented habitat.
Species distribution patterns within naturally fragmented habitat have been found to often exhibit patterns of pronounced nestedness. Highly predictable extinction sequences are implied by these nested species distribution patterns, thus the patterns are important to both the philosophy and practice of conservation biology. A simple thermodynamic measure of the order and disorder apparent in the nested patterns is described. The metric offers (i) a measure of the uncertainty in species extinction order, (ii) a measure of relative populational stabilities, (iii) a means of identifying minimally sustainable population sizes, and (iv) an estimate of the historical coherence of the species assemblage. Four presumptions govern the development of the metric and its theory: (i) the fragmented habitat was once whole and originally populated by a single common source biota, (ii) the islands were initially uniform in their habitat heterogeneity and type mix, and have remained so throughout their post-fragmentation history, (iii) no significant clinal (latitudinal) gradation exists across the archipelago so as to promote species turnover across the archipelago, and (iv) all species of interest are equally isolated on all islands. The violation of these conditions promotes species distributions which are idiosyncratic to the general extinction order expected in fragmentation archipelagos. While some random variation in extinction order is to be expected, idiosyncratic distributional patterns differ from randomness and are readily segregatable from such noise. A method of identifying idiosyncratic species and sites is described.


Daytime measurements of atmospheric temperature profiles (2-15 km) by lidar utilizing Rayleigh-Brillouin scattering.
In this Letter, we report on a novel method for measuring atmospheric temperature profiles by lidar during daytime for heights of 2-15.3 km, with a vertical resolution of 0.3-2.2 km, using Rayleigh-Brillouin scattering. The measurements are performed by scanning a laser (λ=355 nm) over a 12 GHz range and using a Fabry-Pérot interferometer as discriminator. The temperature is derived by using a new analytical line shape model assuming standard atmospheric pressure conditions. Two exemplary temperature profiles resulting from measurements over 14 and 27 min are shown. A comparison with radiosonde temperature measurements shows reasonable agreement. In cloud-free conditions, the temperature difference reaches up to 5 K within the boundary layer, and is smaller than 2.5 K above. The statistical error of the derived temperatures is between 0.15 and 1.5 K.


A randomized trial on screening for social determinants of health: the iScreen study.
There is growing interest in clinical screening for pediatric social determinants of health, but little evidence on formats that maximize disclosure rates on a wide range of potentially sensitive topics. We designed a study to examine disclosure rates and hypothesized that there would be no difference in disclosure rates on face-to-face versus electronic screening formats for items other than highly sensitive items. We conducted a randomized trial of electronic versus face-to-face social screening formats in a pediatric emergency department. Consenting English-speaking and Spanish-speaking adult caregivers familiar with the presenting child's household were randomized to social screening via tablet computer (with option for audio assist) versus a face-to-face interview conducted by a fully bilingual/bicultural researcher. Almost all caregivers (96.8%) reported at least 1 social need, but rates of reporting on the more sensitive issues (household violence and substance abuse) were significantly higher in electronic format, and disclosure was marginally higher in electronic format for financial insecurity and neighborhood and school safety. There was a significant difference in the proportion of social needs items with higher endorsement in the computer-based group (70%) than the face-to-face group (30%). Pediatric clinical sites interested in incorporating caregiver-reported socioeconomic, environmental, and behavioral needs screening should consider electronic screening when feasible, particularly when assessing sensitive topics such as child safety and household member substance use.


A fentanyl-based pain management protocol provides early analgesia for adult trauma patients.
In the past two decades, a number of reports have identified inadequate treatment of pain among emergency department patients. No study has evaluated the frequency or effectiveness of early analgesia in the trauma patient. The objective of this study was to determine the effect of a protocol-driven pain management scheme on time to initiation of analgesia among trauma patients. A fentanyl-based protocol was developed with patients being assigned to one of three treatment arms based on hemodynamics and Glasgow Coma Scale (GCS) score. Using an institutional review board-approved before and after study design, patients over the age of 14 and meeting trauma system activation criteria at the Dartmouth-Hitchcock Medical Center were eligible. Results were compared with a retrospective chart review of eligible patients treated during a matched preprotocol time period in 2002. The primary outcome measure was time to initiation of analgesia. Secondary outcome measures included (1) the proportion of patients receiving their first analgesia dose within 30 minutes, (2) the number of patients receiving multiple doses of analgesia in the trauma bay, and (3) adverse events. Pain level was assessed using either a Numeric Pain Scale (for patients with a GCS score of 15) or a Behavioral Pain Assessment Scale (GCS score <15). Implementation of the protocol resulted in a decrease in the mean time to initiation of analgesia from 53.61 minutes +/- 6.88 minutes to 27.94 minutes +/- 3.34 minutes (p = 0.001). The protocol also increased the percentage of patients receiving analgesia within the first 30 minutes of arrival from 44.4% to 74.6% (p < 0.001). There were no differences between the two groups in terms of baseline characteristics or adverse events. The implementation of a fentanyl-based pain management protocol resulted in a marked reduction in time to initial analgesia among trauma patients. There was no evidence of an increase in adverse events. This tool has the potential to be easily extrapolated and applied to other trauma systems.


Reliability of overbite depth indicator (ODI) and anteroposterior dysplasia indicator (APDI) in the assessment of different vertical and sagittal dental malocclusions: a receiver operating characteristic (ROC) analysis.
Differential diagnosis of skeletal and dental relationships is crucial for planning orthodontic treatment. Overbite depth indicator (ODI) and anteroposterior dysplasia indicator (APDI) had been introduced in the past for assessment of vertical and sagittal jaw relationships, respectively. The objectives of this study were to evaluate the reliability of ODI and APDI in overbite and Angle malocclusions, as well as assess their diagnostic reliability among males and females of different age groups. This study was conducted using pretreatment dental casts and lateral cephalograms of 90 subjects. For ODI, subjects were divided into three groups based on overbite (normal overbite, open bite and deep bite). Likewise, the same subjects were divided for APDI into three groups, based on Angle's malocclusion classification (dental Class I, II and III malocclusions). Mann-Whitney U test was applied for comparison of study parameters regarding sex and different age groups. The mean values of ODI and APDI were compared among study groups by means of Kruskal-Wallis and post-hoc Dunnet T3 tests. The receiver operating characteristic (ROC) curve was applied to test diagnostic reliability. Insignificant differences were found for ODI and APDI angles, particularly in regards to sex and age. Significant intergroup differences were found in different overbite groups and Angle's classification for ODI and APDI, respectively (p < 0.001). ROC showed 91% and 88% constancy with dental pattern in ODI and APDI, respectively. ODI can reliably differentiate deep bite versus normal overbite and deep bite versus open bite. APDI can reliably differentiate dental Class I, II and III malocclusions.


Voluntary Sleep Choice and Its Effects on Bayesian Decisions.
This study examines whether voluntary sleep restriction at commonly experienced levels impacts decision making in a Bayesian choice task. Participants recruited were largely traditional age college students from a regional state university (n = 100) and a federal military academy (n = 99; n = 56 and 43, respectively, used in final analysis). Sleep was measured by actigraphy over a one-week period, followed by performance of a decision task. The task involved two sources of information, base rate odds and sample evidence, with subjects asked to make a probability judgment. Results found that subjects with nightly sleep < 6 hr (sleep deprived = SD), relative to those with > 7 hr, placed less decision weight on new evidence, relative to base rate information, in making difficult choices. This result is strongest among female subjects. For easier choices, voluntary SD did not affect relative decision weights placed on the two sources of available information.


Genome-wide analysis of basic/helix-loop-helix transcription factor family in rice and Arabidopsis.
The basic/helix-loop-helix (bHLH) transcription factors and their homologs form a large family in plant and animal genomes. They are known to play important roles in the specification of tissue types in animals. On the other hand, few plant bHLH proteins have been studied functionally. Recent completion of whole genome sequences of model plants Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa) allows genome-wide analysis and comparison of the bHLH family in flowering plants. We have identified 167 bHLH genes in the rice genome, and their phylogenetic analysis indicates that they form well-supported clades, which are defined as subfamilies. In addition, sequence analysis of potential DNA-binding activity, the sequence motifs outside the bHLH domain, and the conservation of intron/exon structural patterns further support the evolutionary relationships among these proteins. The genome distribution of rice bHLH genes strongly supports the hypothesis that genome-wide and tandem duplication contributed to the expansion of the bHLH gene family, consistent with the birth-and-death theory of gene family evolution. Bioinformatics analysis suggests that rice bHLH proteins can potentially participate in a variety of combinatorial interactions, endowing them with the capacity to regulate a multitude of transcriptional programs. In addition, similar expression patterns suggest functional conservation between some rice bHLH genes and their close Arabidopsis homologs.


NFATc4 Regulates Sox9 Gene Expression in Acinar Cell Plasticity and Pancreatic Cancer Initiation.
Acinar transdifferentiation toward a duct-like phenotype constitutes the defining response of acinar cells to external stress signals and is considered to be the initial step in pancreatic carcinogenesis. Despite the requirement for oncogenic Kras in pancreatic cancer (PDAC) development, oncogenic Kras is not sufficient to drive pancreatic carcinogenesis beyond the level of premalignancy. Instead, secondary events, such as inflammation-induced signaling activation of the epidermal growth factor (EGFR) or induction of Sox9 expression, are required for tumor formation. Herein, we aimed to dissect the mechanism that links EGFR signaling to Sox9 gene expression during acinar-to-ductal metaplasia in pancreatic tissue adaptation and PDAC initiation. We show that the inflammatory transcription factor NFATc4 is highly induced and localizes in the nucleus in response to inflammation-induced EGFR signaling. Moreover, we demonstrate that NFATc4 drives acinar-to-ductal conversion and PDAC initiation through direct transcriptional induction of Sox9. Therefore, strategies designed to disrupt NFATc4 induction might be beneficial in the prevention or therapy of PDAC.


Knocking out P2X receptors reduces transmitter secretion in taste buds.
In response to gustatory stimulation, taste bud cells release a transmitter, ATP, that activates P2X2 and P2X3 receptors on gustatory afferent fibers. Taste behavior and gustatory neural responses are largely abolished in mice lacking P2X2 and P2X3 receptors [P2X2 and P2X3 double knock-out (DKO) mice]. The assumption has been that eliminating P2X2 and P2X3 receptors only removes postsynaptic targets but that transmitter secretion in mice is normal. Using functional imaging, ATP biosensor cells, and a cell-free assay for ATP, we tested this assumption. Surprisingly, although gustatory stimulation mobilizes Ca(2+) in taste Receptor (Type II) cells from DKO mice, as from wild-type (WT) mice, taste cells from DKO mice fail to release ATP when stimulated with tastants. ATP release could be elicited by depolarizing DKO Receptor cells with KCl, suggesting that ATP-release machinery remains functional in DKO taste buds. To explore the difference in ATP release across genotypes, we used reverse transcriptase (RT)-PCR, immunostaining, and histochemistry for key proteins underlying ATP secretion and degradation: Pannexin1, TRPM5, and NTPDase2 (ecto-ATPase) are indistinguishable between WT and DKO mice. The ultrastructure of contacts between taste cells and nerve fibers is also normal in the DKO mice. Finally, quantitative RT-PCR show that P2X4 and P2X7, potential modulators of ATP secretion, are similarly expressed in taste buds in WT and DKO taste buds. Importantly, we find that P2X2 is expressed in WT taste buds and appears to function as an autocrine, positive feedback signal to amplify taste-evoked ATP secretion.


Resistance to falciparum malaria among adults in central Sudan.
Adults claiming resistance to malaria were identified in the Sennar region of central Sudan, where P. falciparum is hyperendemic but seasonal in transmission. Indirect fluorescent antibody (IFA) titers of sera from these individuals were comparable to those of malaria patients with positive blood films, indicating equal exposure, while in vitro antiparasitic activity of their sera tended to be higher, indicating an effective immunological response to falciparum malaria. Hemoglobin S (Hb S) was significantly more prevalent in adults resistant to malaria. This trait offers protection at the erythrocyte level and it is also possible that it could enhance the ability of carrier adults to acquire protective immunity. Erythrocyte 6-phosphogluconate dehydrogenase A (PGDA) and phosphoglucomutase 1 (PGM1), phenotypes of unknown relevance to protection against falciparum malaria, were also significantly more prevalent in those claiming resistance to malaria. A trend of higher prevalence for erythrocyte glucose-6-phosphate dehydrogenase deficiency (G6PD-), Kell (+) and transferrin D (TfD) was detected among resistant individuals and higher KP(a+) and P2 among malaria patients, but the numbers evaluated in this study did not allow determination of statistical significance. No association was found with erythrocyte glyoxalases, ABO and Duffy blood groups and serum haptoglobins.


Embedding the International Classification of Functioning, Disability and Health in Health Professions Curricula to Enable Interprofessional Education and Collaborative Practice.
The World Health Organization's International Classification of Functioning, Disability and Health (WHO-ICF) is a comprehensive and highly adaptable framework that provides a universal language and shared health concepts to articulate human functioning across the lifespan and from individual to population health settings. It provides a global, biopsychosocial, and holistic structure for conceptualising the human experience of health and health service provision. Consequently, the ICF framework offers hope for a universal map for health service providers that bridges professional, cultural, economic, and geographical variations. While the use of the ICF is typically mandated by health professions accreditation bodies, integration of the ICF in medical and health professional education programmes has been slow. In addition, its potential for scaffolding interprofessional education for collaborative practice has not been maximised. In this Perspective paper, we draw on our extensive experience in developing curricula and teaching within a range of health professions programmes (medicine, occupational therapy, physiotherapy, and speech-language pathology) to provide advice on conceptual, theoretical, and practical dimensions of embedding the ICF framework within curricula to support interprofessional education and collaborative practice.


Gangliosides enhance the membrane actions of ethanol and pentobarbital.
The physical properties of vesicles containing phosphatidylcholine (PC) and gangliosides were evaluated by the fluorescent probes 1,6-diphenyl-1,3,5-hexatriene, trans- parinarate (probes of the lower acyl regions), and 1-(4- trimethylammoniumphenyl )-6-phenyl-1,3,5-hexatriene (a probe of the glycerol backbone and upper acyl regions). Exposure of PC vesicles to ethanol produced a decrease in polarization of fluorescence of these probes, but large concentrations (200-600 mM) were required. Incorporation of 10 mole% rat brain synaptic gangliosides into the PC vesicles enhanced the effect of ethanol by several-fold. Synaptic gangliosides also enhanced the effect of ethanol on vesicles containing cholesterol in addition to PC. Comparison of mono-, di-, tri-, and asialogangliosides , sphingosine, and sphingomyelin indicated the importance of the oligosaccharide moiety, but not the sialic acid residues, in the enhancement of ethanol action by gangliosides. Variation of assay temperature and the acyl composition of the PC demonstrated that gangliosides increased the effects of ethanol only if the lipids were near the phase transition temperature. Gangliosides also produced a marked enhancement of the effect of pentobarbital on fluorescence polarization of probes in PC vesicles. The membrane partioning of pentobarbital was increased by gangliosides, but it was not clear that this increase in drug concentration in the membrane was sufficient to account for the large change in fluorescence polarization. These results suggest that ganglioside content may be an important determinant of the effects of alcohols and barbiturates on biomembranes. In particular, the high drug sensitivity of neuronal membranes may be related to the enrichment of gangliosides in these membranes.


Drivers for OSH interventions in small and medium-sized enterprises.
The debate concerning occupational safety and health (OSH) interventions has recently focused on the need of improving the evaluation of interventions, and in particular on the need for providing information about why the intervention worked or not, under what circumstances and in which context. Key concepts in the analysis of the context are the drivers, i.e., those factors enabling, fostering or facilitating OSH interventions. However, the concept of driver for an OSH intervention is both confused and contested. Although the term is widely used, there is little consensus on how drivers should be understood, how important they are in different contexts and how they can facilitate interventions. This exploratory study based on interviews with the owner-managers and the safety officers of small and medium-sized enterprises (SMEs) gives an overview of the most characteristic drivers for OSH interventions. The results will be used to make an initial evaluation of SMEs' needs, and will help orient interventions and future research.


Conducting Event-Related Potential (ERP) Research with Young Children: A Review of Components, Special Considerations and Recommendations for Research on Cognition and Emotion.
There has been an unprecedented increase in the number of research studies employing event-related potential (ERP) techniques to examine dynamic and rapidly-occurring neural processes with children during the preschool and early childhood years. Despite this, there has been little discussion of the methodological and procedural differences that exist for studies of young children versus older children and adults. That is, reviewers, editors, and consumers of this work often expect developmental studies to simply apply adult techniques and procedures to younger samples. Procedurally, this creates unrealistic expectations for research paradigms, data collection, and data reduction and analyses. Scientifically, this leads to inappropriate measures and methods that hinder drawing conclusions and advancing theory. Based on ERP work with preschoolers and young children from 10 laboratories across North America, we present a summary of the most common ERP components under study in the area of emotion and cognition in young children along with 13 realistic expectations for data collection and loss, laboratory procedures and paradigms, data processing, ERP averaging, and typical challenges for conducting this type of work. This work is intended to supplement previous guidelines for work with adults and offer insights to aid researchers, reviewers, and editors in the design and evaluation of developmental research using ERPs. Here we make recommendations for researchers who plan to conduct or who are conducting ERP studies in children between ages 2 and 12, focusing on studies of toddlers and preschoolers. Recommendations are based on both data and our cumulative experience and include guidelines for laboratory setup, equipment and recording settings, task design, and data processing.


Achilles tendinopathy: A prospective study on the effect of active rehabilitation and steroid injections in a clinical setting.
In published efficacy studies on Achilles tendinopathy (AT) exercise alone results in improvement in 60-90% of the cases. However, this high success rate cannot be expected in usual clinical practice. We prospectively investigated the effectiveness of a treatment regimen consisting of home-based exercises (concentric, eccentric, and stretching) and optional glucocorticosteroid (GCS) injections in patients with (AT) in a usual clinical setting. Patients unable to commence or progress in exercise were offered GCS, hypothesizing that the GCS would facilitate exercise. Ninety-three consecutive patients with AT referred to two outpatient rheumatology clinics were registered, and seen at five visits over a 6-month period. Exercises seemed to have a slow, but long-lasting effect with GCS having a dramatic short-term effect on symptoms. Twenty-six percent of the patients could proceed with training alone, the remainder received one to three supplementary GCS. There were significant improvements on all outcome variables over time (P ≤ 0.001). At follow-up, 42 had no more symptoms, 29 good result, 16 slightly improved, 4 unchanged, and 2 slightly worse. Overall, 94% of the patients had improved, and we thus recommend the use of GCS injections in AT patients if training alone does not lead to improvement.


Inhibition of CYP2E1 with natural agents may be a feasible strategy for minimizing the hepatotoxicity of ethanol.
CYP2E1, induced in hepatocytes by heavy consumption of ethanol and certain other drugs, is a potent generator of superoxide, and is thereby thought to mediate the gravest aspects of alcoholic hepatotoxicity. Certain drugs such as the sedative chlormethiazole are effective inhibitors of CYP2E1, and may have clinical potential in the treatment of alcoholics. A number of phytochemicals can also potently inhibit CYP2E1 - most notably certain isothiocyanates found in crucifera, such as sulforaphane and phenethylisothiocyanate. Preparation of these compounds from crucifera seeds or sprouts should enable commercial production of supplements that would protect the livers of social drinkers while concurrently reducing risk for carcinogen-induced cancers.


Germ-free and microbiota-associated mice yield small intestinal epithelial organoids with equivalent and robust transcriptome/proteome expression phenotypes.
Intestinal epithelial organoids established from gut tissue have become a widely used research tool. However, it remains unclear how environmental cues, divergent microbiota composition and other sources of variation before, during and after establishment confound organoid properties, and how these properties relate to the original tissue. While environmental influences cannot be easily addressed in human organoids, mice offer a controlled assay-system. Here, we probed the effect of donor microbiota differences, previously identified as a confounding factor in murine in vivo studies, on organoids. We analysed the proteomes and transcriptomes of primary organoid cultures established from two colonised and one germ-free mouse colony of C57BL/6J genetic background, and compared them to their tissue of origin and commonly used cell lines. While an imprint of microbiota-exposure was observed on the proteome of epithelial samples, the long-term global impact of donor microbiota on organoid expression patterns was negligible. Instead, stochastic culture-to-culture differences accounted for a moderate variability between independently established organoids. Integration of transcriptome and proteome datasets revealed an organoid-typic expression signature comprising 14 transcripts and 10 proteins that distinguished organoids across all donors from murine epithelial cell lines and fibroblasts and closely mimicked expression patterns in the gut epithelium. This included the inflammasome components ASC, Naip1-6, Nlrc4 and Caspase-1, which were highly expressed in all organoids compared to the reference cell line m-ICc12 or mouse embryonic fibroblasts. Taken together, these results reveal that the donor microbiota has little effect on the organoid phenotype and suggest that organoids represent a more suitable culture model than immortalised cell lines, in particular for studies of intestinal epithelial inflammasomes.


Isolation of Zika Virus Imported from Tonga into Australia.
The globally emergent Zika virus (ZIKV) is a threat to Australia, given the number of imported cases from epidemic regions and the presence of competent mosquito vectors. We report the isolation of ZIKV from a female traveler who recently returned from Tonga to Brisbane, Queensland, Australia in 2016. A specific TaqMan real-time reverse transcriptase polymerase chain reaction assay (RT-PCR) assay was used to detect ZIKV in serum and urine samples. Conventional cell culture techniques and suckling mice were employed in an attempt to isolate ZIKV from serum and urine. A ZIKV isolate (TS17-2016) was recovered from the serum sample after one passage in suckling mouse brains and harvested 11 days post inoculation. Phylogenetic analysis of complete envelope (E) gene sequences demonstrated TS17-2016 shared 99.9% nucleotide identity with other contemporary sequences from Tonga 2016, Brazil 2015 and French Polynesia 2013 within the Asian lineage. This is the first known report of successful isolation of ZIKV from a human clinical sample in Australia and the first from a traveler from Tonga. This study highlights the potential difficulties in isolating ZIKV from acute clinical samples using conventional cell culture techniques, particularly in non-endemic countries like Australia where access to samples of sufficient viral load is limited. The successful isolation of TS17-2016 will be essential for continued investigations of ZIKV transmission and pathogenicity and will enable the advancement of new preventative control measures extremely relevant to the Australian and Pacific region.


Food and nutrient intakes of a population sample of 7-year-old children in the south-west of England in 1999/2000 - what difference does gender make?
To describe the diet of schoolchildren aged 7 years, and identify gender differences in food and nutrient intakes. A cohort of children resident in the south-west of England in 1999/2000. Diet was assessed using three 1-day unweighed food diaries. Nutrient intakes were compared with dietary reference values for this age group, and with children aged 7-10 years in the British National Diet and Nutrition Survey. Food and nutrient intakes were contrasted between boys and girls. Median nutrient intakes exceeded the reference nutrient intake (RNI) for most nutrients. Median intakes of iron and zinc were below the RNI. Median sodium intake was greater than the maximum set by the Scientific Advisory Committee on Nutrition. The mean energy intake for boys and girls, respectively, were 7.3 and 6.8 MJ, this is below the estimated average requirement. The percentage of energy from fat was 35.3% for boys and 36.1% for girls. Boys had higher iron intakes than girls, even after adjustment for energy intake. There were differences in the types of foods eaten between boys and girls; girls ate more fruit and vegetables (P = 0.001) and boys ate more breakfast cereals (P = 0.016). The dietary intakes of these 7-year-old children were adequate for most nutrients. However, a reduction in the sodium content of the diet would be advantageous. Fruit and vegetable consumption should be encouraged particularly among boys.


Deficient adaptation to centrosome duplication defects in neural progenitors causes microcephaly and subcortical heterotopias.
Congenital microcephaly (MCPH) is a neurodevelopmental disease associated with mutations in genes encoding proteins involved in centrosomal and chromosomal dynamics during mitosis. Detailed MCPH pathogenesis at the cellular level is still elusive, given the diversity of MCPH genes and lack of comparative in vivo studies. By generating a series of CRISPR/Cas9-mediated genetic KOs, we report here that - whereas defects in spindle pole proteins (ASPM, MCPH5) result in mild MCPH during development - lack of centrosome (CDK5RAP2, MCPH3) or centriole (CEP135, MCPH8) regulators induces delayed chromosome segregation and chromosomal instability in neural progenitors (NPs). Our mouse model of MCPH8 suggests that loss of CEP135 results in centriole duplication defects, TP53 activation, and cell death of NPs. Trp53 ablation in a Cep135-deficient background prevents cell death but not MCPH, and it leads to subcortical heterotopias, a malformation seen in MCPH8 patients. These results suggest that MCPH in some MCPH patients can arise from the lack of adaptation to centriole defects in NPs and may lead to architectural defects if chromosomally unstable cells are not eliminated during brain development.


Scaling metagenome sequence assembly with probabilistic de Bruijn graphs.
Deep sequencing has enabled the investigation of a wide range of environmental microbial ecosystems, but the high memory requirements for de novo assembly of short-read shotgun sequencing data from these complex populations are an increasingly large practical barrier. Here we introduce a memory-efficient graph representation with which we can analyze the k-mer connectivity of metagenomic samples. The graph representation is based on a probabilistic data structure, a Bloom filter, that allows us to efficiently store assembly graphs in as little as 4 bits per k-mer, albeit inexactly. We show that this data structure accurately represents DNA assembly graphs in low memory. We apply this data structure to the problem of partitioning assembly graphs into components as a prelude to assembly, and show that this reduces the overall memory requirements for de novo assembly of metagenomes. On one soil metagenome assembly, this approach achieves a nearly 40-fold decrease in the maximum memory requirements for assembly. This probabilistic graph representation is a significant theoretical advance in storing assembly graphs and also yields immediate leverage on metagenomic assembly.


Polymorphisms of human nonmetastatic clone 23 type 1 gene and neoplastic lesions of uterine cervix.
Single-nucleotide polymorphisms (SNP) in promoter of human nonmetastatic clone 23 type 1 (nm23-H1) may affect their binding with transcription factors and affect promoter activity as well as gene transcription. Therefore, we investigated the impact of the nm23-H1 gene polymorphisms on the neoplastic lesions of uterine cervix in mid-Taiwan women (women who live in the central area of Taiwan). We expected that women with different genotypes in nm23-H1 polymorphisms, such as rs34214448, rs16949649, or rs2302254, may have different incidences of cervical neoplasia. In total, 366 blood samples were collected from 244 healthy women and 122 patients with cervical neoplasia to analyze 3 nm23-H1 gene single-nucleotide polymorphisms (rs34214448, rs16949649, and rs2302254). The heterozygous genotypes, TG in rs34214448 or TC in rs16949649, were differentially distributed between patients with cervical neoplasia and normal women (Hommel adjusted P = .0440 and .0435, respectively) as compared to their homozygotes. Moreover, compared to those with wild-type homozygotes and heterozygotes, women with variant homozygotes TT in rs34214448 or CC in rs16949649 exert different distributions between patients with cervical neoplasia and normal women (P = .058 and .058). Interestingly, we found the genotype distribution of rs34214448 has significant association with that of rs16949649 with high consistency. Mid-Taiwan women with the polymorphic heterozygotes TG in rs34214448 or TC in rs16949649 of human nonmetastatic clone 23 type 1 promoter have the tendency to develop cervical neoplasia while compared to their homozygous counterparts. However, women with variant homozygotes TT in rs34214448 or CC in rs16949649 exhibit less tendency as compared to those with wild-type homozygotes and heterozygotes.


Leaching from waste incineration bottom ashes treated in a rotary kiln.
Leaching from municipal solid waste incineration bottom ash treated in a rotary kiln was quantified using a combination of lab-scale leaching experiments and geochemical modelling. Thermal treatment in the rotary kiln had no significant effect on the leaching of Al, Ba, Ca, Mg, Si, Sr, Zn, sulfate and inorganic carbon. Leaching of these elements from the treated residues remained unchanged and was, in general, controlled by solubility of the same minerals as in the untreated residues. Leaching of Cd, Co, Ni, Ti, Be, Bi, and Sn from both untreated and treated residues was found to be close to or below their detection limits; no effects of the thermal treatment on leachability of these metals were observed. The leaching of Cl, dissolved organic carbon (DOC), Cu and Pb decreased by at least one order of magnitude after the thermal treatment. This could be explained by evaporation (Cl) and by a better burnout of organic matter which then limited metal-DOC complexation and mobility. At the same time, leaching of Mo and Cr appeared to increase by a factor of 4 and more than two orders of magnitude, respectively. The large changes in Cr leaching may be explained by decreases in Al reduction capacity after the thermal treatment. Overall, rotary kiln thermal treatment of bottom ashes can be recommended to reduce the leaching of Cu, Pb, Cl and DOC; however, increased leaching of Cr and Mo should be expected.


Insights into LRRK2 function and dysfunction from transgenic and knockout rodent models.
Mutations in the LRRK2 (leucine-rich repeat kinase 2) gene on chromosome 12 cause autosomal dominant PD (Parkinson's disease), which is indistinguishable from sporadic forms of the disease. Numerous attempts have therefore been made to model PD in rodents via the transgenic expression of LRRK2 and its mutant variants and to elucidate the function of LRRK2 by knocking out rodent Lrrk2. Although these models often only partially recapitulate PD pathology, they have helped to elucidate both the normal and pathological function of LRRK2. In particular, LRRK2 has been suggested to play roles in cytoskeletal dynamics, synaptic machinery, dopamine homoeostasis and autophagic processes. Our understanding of how these pathways are affected, their contribution towards PD development and their interaction with one another is still incomplete, however. The present review summarizes the findings from LRRK2 rodent models and draws potential connections between the apparently disparate cellular processes altered, in order to better understand the underlying mechanisms of LRRK2 dysfunction and illuminate future therapeutic interventions.


Lumbar Plexus Block as an Effective Alternative to Subarachnoid Block for Intertrochanteric Hip Fracture Surgeries in the Elderly.
Elderly patients with hip fractures pose a medical challenge for the anesthesiologist and are often associated with a high incidence of perioperative morbidity and mortality. We aimed to compare the efficacy of lumbar plexus block (LPB) with subarachnoid block (SAB) in elderly patients undergoing closed reduction and internal fixation for hip fractures. In this observational study, 50 patients with femoral intertrochanteric fracture were divided into LPB group and SAB group of 25 each by convenient sampling. Patients in the LPB group were given 20-25 ml of 0.5% bupivacaine to block the ipsilateral lumbar plexus with nerve stimulator assistance, whereas the patients in the SAB group received 0.5% bupivacaine intrathecally. Student's t-test was used for comparing the time for performing block, the time to achieving block, the time to the first request for analgesia, and the hemodynamic variables. Lumbar plexus blockade took a longer time for performing and achieving block (P < 0.001). The time for the first request for analgesia was significantly longer in the LPB group (P < 0.001). A statistically significant reduction in blood pressures was noted in the SAB group. Lumbar plexus blockade offered more stable intraoperative hemodynamics and longer duration of postoperative analgesia in elderly patients undergoing hip fracture surgery.


Histopathology of the inner ear in patients with xeroderma pigmentosum and neurologic degeneration.
Xeroderma pigmentosum (XP) is a rare autosomal recessive disease caused by mutations resulting in defective repair of DNA damage. XP patients have a markedly increased risk of ultraviolet-induced neoplasms and premature aging of sun-exposed tissue. Approximately 25% of XP patients in the United States have neurologic abnormalities including progressive sensorineural hearing loss (SNHL). To describe the temporal bone histopathology in 2 individuals with XP (XPA and XPD) with neurologic degeneration and to discuss the possible causes of deafness in these patients. Temporal bones were removed at autopsy and studied using light microscopy. In the case with XPD, the organ of Corti was missing throughout the cochlea, whereas the case with XPA demonstrated scattered presence of sensory cells in the middle and apical turns. In both cases, there was moderate-to-severe patchy atrophy of the stria vascularis in all turns, and cochlear neurons were severely atrophied compared with age-matched controls, with loss of both peripheral dendrites and central axons. There was severe degeneration of Scarpa's ganglion in the case with XPA. Two cases of XP with neurologic degeneration are reported. The case with XPD demonstrated a more severe audiologic phenotype than XPA, although both had similar findings such as atrophy of the organ of Corti, stria vascularis, and spiral ganglia leading to severe or profound SNHL by the third decade of life. It is not clear if the neuronal degeneration in the inner ear was primary or secondary to loss of neuroepithelial cells.


Network-Based Predictors of Progression in Head and Neck Squamous Cell Carcinoma.
The heterogeneity in head and neck squamous cell carcinoma (HNSCC) has made reliable stratification extremely challenging. Behavioral risk factors such as smoking and alcohol consumption contribute to this heterogeneity. To help elucidate potential mechanisms of progression in HNSCC, we focused on elucidating patterns of gene interactions associated with tumor progression. We performed de-novo gene co-expression network inference utilizing 229 patient samples from The Cancer Genome Atlas (TCGA) previously annotated by Bornstein et al. (2016). Differential network analysis allowed us to contrast progressor and non-progressor cohorts. Beyond standard differential expression (DE) analysis, this approach evaluates changes in gene expression variance (differential variability DV) and changes in covariance, which we denote as differential wiring (DW). The set of affected genes was overlaid onto the co-expression network, identifying 12 modules significantly enriched in DE, DV, and/or DW genes. Additionally, we identified modules correlated with behavioral measures such as alcohol consumption and smoking status. In the module enriched for differentially wired genes, we identified network hubs including IL10RA, DOK2, APBB1IP, UBASH3A, SASH3, CELF2, TRAF3IP3, GIMAP6, MYO1F, NCKAP1L, WAS, FERMT3, SLA, SELPLG, TNFRSF1B, WIPF1, AMICA1, PTPN22; the network centrality and progression specificity of these genes suggest a potential role in tumor evolution mechanisms related to inflammation and microenvironment. The identification of this network-based gene signature could be further developed to guide progression stratification, highlighting how network approaches may help improve clinical research end points and ultimately aid in clinical utility.


A Pilot Study of Intervention With a Mobile Application Visualizing the Macronutrient Content for Type 2 Diabetes at a Japanese Center.
Estimating the nutritional content of food is essential for self-management in people with type 2 diabetes mellitus, but it is a difficult skill to learn. The aim of this study was to investigate how diabetes management was impacted by the ability of patients to search for items they ate from a database of 26,300 different foods, and to visualize nutritional intake using the Japanese mobile application (app) "Calomeal." This was a single-arm, single-center, pilot study. Eighteen outpatients with type 2 diabetes mellitus used the "Calomeal" app for 3 months. The primary endpoint was change in hemoglobin A1c (HbA1c). Secondary endpoints were changes in body weight (BW), lipid parameters, and quality of life scores. The baseline characteristics of the study subjects were as follows: age: 53.4 ± 7.8 years; male/female ratio: 11/7; HbA1c: 7.9 (7.58 - 8.23)%; and body mass index (BMI): 25.17 (21.63 - 28.59) kg/m2. Significant reductions in HbA1c and BMI were observed over 3 months (HbA1c: 7.9 (7.58 - 8.23)% to 7.6 (7.3 - 8.23)%, P = 0.0410; BMI: 25.17 (21.63 - 28.59) to 24.54 (21.57 - 27.81) kg/m2, P = 0.0057). Reductions in HbA1c and BMI both correlated with decreased carbohydrate intake estimated by the mobile app. Japanese patients who used their smartphones to visualize their nutritional intake using the "Calomeal" app demonstrated improved short-term glycemic control and BMI. Although the validity of the results should be tested in future randomized controlled trials, this approach may be a clinical option for improving self-management in Japanese patients with type 2 diabetes mellitus.


Gradenigo syndrome: unusual consequence of otitis media.
In 1904, Giuseppe Gradenigo published his case series on the triad of ipsilateral abducens nerve palsy, facial pain in the trigeminal nerve distribution, and suppurative otitis media, which would subsequently be referred to as Gradenigo syndrome. Our patient was a 36-year-old female, 23 weeks pregnant, with a 6-day history of right-sided otalgia and hearing loss and a 4-day history of purulent otorrhea, who presented with severe, holocephalic headache, meningeal signs, fever, photophobia, and mental status decline. Lumbar puncture yielded a white blood cell count of 1,559 cells/mm(3) with 95% polymorphonuclear leukocytes, a red blood cell count of 111 cells/mm(3), a protein level of 61 mg/dl, and a glucose level of <40 mg/dl. Cerebrospinal fluid Gram stain showed Gram-positive diplococci, which were subsequently identified as Streptococcus pneumoniae and treated with ceftriaxone. On the second hospital day, she developed horizontal diplopia due to right abducens nerve palsy and right mydriasis. Both symptoms resolved on the third hospital day. Erosion of temporal bone and opacification of mastoid air cells was shown on CT scan. A CT venogram showed an irregularity of the left transverse and superior sagittal sinuses. She was treated with enoxaparin for possible sinus thrombosis. This case demonstrates rare but serious sequelae of otitis media and Gradenigo syndrome. Holocephalic headache from meningitis masked trigeminal pain. Involvement of the ipsilateral petrous apex and surrounding structures on imaging and clinical improvement with antibiotic treatment supports Gradenigo syndrome over intracranial hypertension due to venous sinus thrombosis as the cause of the abducens nerve palsy.


Conservation of sequences adjacent to the telomeric C4A2 repeats of ciliate macronuclear ribosomal RNA gene molecules.
We sequenced and compared the telomeric regions of linear rDNAs from vegetative macronuclei of several ciliates in the suborder Tetrahymenina. All telomeres consisted of tandemly repeated C4A2 sequences, including the 5' telomere of the 11 kb rDNA from developing macronuclei of Tetrahymena thermophila. Our sequence of the 11 kb 5' telomeric region shows that each one of a previously described pair of inverted repeats flanking the micronuclear rDNA (Yao et al., Mol. Cell. Biol. 5: 1260-1267, 1985) is 29 bp away from the positions to which telomeric C4A2 repeats are joined to the ends of excised 11 kb rDNA. In general we found that the macronuclear rDNA sequences adjacent to C4A2 repeats are not highly conserved. However, in the non-palindromic rDNA of Glaucoma, we identified a single copy of a conserved sequence, repeated in inverted orientation in Tetrahymena spp., which all form palindromic rDNAs. We propose that this sequence is required for a step in rDNA excision common to both Tetrahymena and Glaucoma.


In vivo quantitative photoacoustic microscopy of gold nanostar kinetics in mouse organs.
We developed a high-resolution photoacoustic microscopy (PAM) system with a near-infrared (NIR) laser to noninvasively monitor the distribution of gold nanostar (GNS) in blood vessels, liver and spleen in mice. Photoacoustic images of organs at deep depths were continuously acquired in vivo every 30 minutes after a single dose of GNS by tail vein injection. The experimental results showed that GNS accumulated significantly in both liver and spleen from blood circulation after administration, which was qualitatively validated by fluorescence imaging. Our studies demonstrate that PAM might be potentially used for noninvasive tracing the kinetics of exogenous nanoparticles in biological system.


Laparoscopic Technique for Serial Collection of Liver and Mesenteric Lymph Nodes in Macaques.
The mesenteric lymph nodes (MLN) and the liver are exposed to microbes and microbial products from the gastrointestinal (GI) tract, making them immunologically unique. The GI tract and associated MLN are sites of early viral replication in human immunodeficiency virus (HIV) infection and the MLN are likely important reservoir sites that harbor latently-infected cells even after prolonged antiretroviral therapy (ART). The liver has been shown to play a significant role in immune responses to lentiviruses and appears to play a significant role in clearance of virus from circulation. Nonhuman primate (NHP) models for HIV and Acquired Immunodeficiency Syndrome (AIDS) closely mimic these aspects of HIV infection and serial longitudinal sampling of primary sites of viral replication and the associated immune responses in this model will help to elucidate critical events in infection, pathogenesis, and the impact of various intervention strategies on these events. Current published techniques to sample liver and MLN together involve major surgery and/or necropsy, which limits the ability to investigate these important sites in a serial fashion in the same animal. We have previously described a laparoscopic technique for collection of MLN. Here, we describe a minimally invasive laparoscopic technique for serial longitudinal sampling of liver and MLN through the same two port locations required for the collection of MLN. The use of the same two ports minimizes the impact to the animals as no additional incisions are required. This technique can be used with increased sampling frequency compared to major abdominal surgery and reduces the potential for surgical complications and associated local and systemic inflammatory responses that could complicate interpretation of results. This procedure has potential to facilitate studies involving NHP models while improving animal welfare.


Genomic tools for evolution and conservation in the chimpanzee: Pan troglodytes ellioti is a genetically distinct population.
In spite of its evolutionary significance and conservation importance, the population structure of the common chimpanzee, Pan troglodytes, is still poorly understood. An issue of particular controversy is whether the proposed fourth subspecies of chimpanzee, Pan troglodytes ellioti, from parts of Nigeria and Cameroon, is genetically distinct. Although modern high-throughput SNP genotyping has had a major impact on our understanding of human population structure and demographic history, its application to ecological, demographic, or conservation questions in non-human species has been extremely limited. Here we apply these tools to chimpanzee population structure, using ∼700 autosomal SNPs derived from chimpanzee genomic data and a further ∼100 SNPs from targeted re-sequencing. We demonstrate conclusively the existence of P. t. ellioti as a genetically distinct subgroup. We show that there is clear differentiation between the verus, troglodytes, and ellioti populations at the SNP and haplotype level, on a scale that is greater than that separating continental human populations. Further, we show that only a small set of SNPs (10-20) is needed to successfully assign individuals to these populations. Tellingly, use of only mitochondrial DNA variation to classify individuals is erroneous in 4 of 54 cases, reinforcing the dangers of basing demographic inference on a single locus and implying that the demographic history of the species is more complicated than that suggested analyses based solely on mtDNA. In this study we demonstrate the feasibility of developing economical and robust tests of individual chimpanzee origin as well as in-depth studies of population structure. These findings have important implications for conservation strategies and our understanding of the evolution of chimpanzees. They also act as a proof-of-principle for the use of cheap high-throughput genomic methods for ecological questions.


Immunoglobulin E as a Biomarker for the Overlap of Atopic Asthma and Chronic Obstructive Pulmonary Disease.
Asthma-COPD overlap (ACO) is a common clinical syndrome, yet there is no single objective definition. We hypothesized that immunoglobulin E (IgE) measurements could be used to refine the definition of ACO. In baseline plasma samples from 2870 participants in the COPD Genetic Epidemiology (COPDGene®) study, we measured total IgE levels and specific IgE levels to 6 common allergens. Compared to usual chronic obstructive pulmonary disease (COPD), participants with ACO (based on self-report of asthma) had higher total IgE levels (median 67.0 versus 42.2 IU/ml) and more frequently had at least one positive specific IgE (43.5% versus 24.5%). We previously used a strict definition of ACO in participants with COPD, based on self-report of a doctor's diagnosis of asthma before age 40. This strict ACO definition was refined by the presence of atopy, determined by total IgE > 100 IU/ml or at least one positive specific IgE, as was the broader definition of ACO based on self-reported asthma history. Participants with all 3 ACO definitions were younger (mean age 60.0-61.3 years), were more commonly African American (36.8%-44.2%), had a higher exacerbation frequency (1.0-1.2 in the past year), and had more airway wall thickening on quantitative analysis of chest computed tomography (CT) scans. Among participants with ACO, 37%-46% did not have atopy; these individuals had more emphysema on chest CT scan. Based on associations with exacerbations and CT airway disease, IgE did not clearly improve the clinical definition of ACO. However, IgE measurements could be used to subdivide individuals with atopic and non-atopic ACO, who might have different biologic mechanisms and potential treatments.


Optical filters with fractal transmission spectra based on diffractive optics.
The duality between the axial irradiance distribution originated by any circularly symmetric diffracting aperture under monochromatic illumination and its diffracted spectral intensity at a fixed on-axis point under broadband illumination is highlighted and experimentally investigated. Two applications are derived from this basic result. On the one hand, we suggest the use of a broadband source and a spectrometer for a single-shot measurement of the axial response of pupil filters. Second, we implement a spectral filter having a transmission spectrum with a fractal structure of frequencies. Experimental results and potential applications in synthetic spectra designs are provided.


Effect of self-administered foot reflexology for symptom management in healthy persons: a systematic review and meta-analysis.
Self-administered foot reflexology is unrestricted by time and space, economical, and practical because it is easy to learn and apply. This study estimated the effectiveness of self-foot reflexology for symptom management in healthy persons through a systematic review and meta-analysis. The participants were healthy persons not diagnosed with a specific disease. The intervention was foot reflexology administered by participants, not by practitioners or healthcare providers. The comparative studies either between groups or within group comparison were included. Our search utilized core databases (MEDLINE, EMBASE, Cochrane, and CINAHL). We also searched Chinese (CNKI), Japanese (J-STAGE), and Korean databases (KoreaMed, KMbase, KISS, NDSL, KISTI, and OASIS). The search was used MeSH terminology and key words (foot reflexology, foot massage, and self). Analysis of three non-randomized trials and three before-and-after studies showed that self-administered foot reflexology resulted in significant improvement in subjective outcomes such as perceived stress, fatigue, and depression. However, there was no significant improvement in objective outcomes such as cortisol levels, blood pressure, and pulse rate. We did not find any randomized controlled trial. This study presents the effectiveness of self-administered foot reflexology for healthy persons' psychological and physiological symptoms. While objective outcomes showed limited results, significant improvements were found in subjective outcomes. However, owing to the small number of studies and methodological flaws, there was insufficient evidence supporting the use of self-performed foot reflexology. Well-designed randomized controlled trials are needed to assess the effect of self-administered foot reflexology in healthy people.


The health and well-being of Indigenous drug and alcohol workers: results from a national Australian survey.
The increasing demand for alcohol and other drug (AOD) treatment services among the Australian Indigenous population, complex organisational challenges and limitations, and high unemployment rates are likely to negatively impact Indigenous AOD workers' health and well-being. Building the capacity of Indigenous AOD workers is vital, as they play a crucial role in the delivery of treatment services and offer essential support to their communities. A national online survey was conducted to examine organisational, workplace and individual factors that might contribute to levels of stress and well-being among workers who provide services to Indigenous clients. A total of 294 eligible surveys were completed; 184 (63%) from Indigenous and 108 (37%) from non-Indigenous AOD workers. Multiple regression models were conducted to assess the significant predictors of mental health and well-being, job satisfaction, emotional exhaustion, and turnover intention. Indigenous AOD workers typically experienced above average levels of job satisfaction and relatively low levels of emotional exhaustion. However, 1 in 10 reported high levels of emotional exhaustion, a key predictor of turnover intention. Indigenous workers also experienced significantly lower levels of mental health and well-being and greater work/family imbalance, which was a significant contributor to emotional exhaustion. The findings highlight the importance of implementing workforce development strategies that focus on achieving culturally appropriate, equitable and supportive organisational conditions for Indigenous AOD workers. Preventing or managing levels of stress, ensuring adequate and equitable salaries and benefits, and providing more opportunities for career and personal growth may increase job satisfaction and reduce turnover intention among Indigenous workers in the drug and alcohol field.


Double-blind review favours increased representation of female authors.
Double-blind peer review, in which neither author nor reviewer identity are revealed, is rarely practised in ecology or evolution journals. However, in 2001, double-blind review was introduced by the journal Behavioral Ecology. Following this policy change, there was a significant increase in female first-authored papers, a pattern not observed in a very similar journal that provides reviewers with author information. No negative effects could be identified, suggesting that double-blind review should be considered by other journals.


Systematic evidence synthesis of treatments for ADHD in children and adolescents: indirect treatment comparisons of lisdexamfetamine with methylphenidate and atomoxetine.
Systematically review and synthesize the clinical evidence of treatments for attention deficit hyperactivity disorder (ADHD) by indirectly comparing established treatments in the UK with a drug recently approved in Europe (lisdexamfetamine [LDX]). children and adolescents. Europe. Comparators: methylphenidate (MPH), atomoxetine (ATX), and dexamphetamine (DEX). Electronic databases and relevant conference proceedings were searched for randomized, controlled clinical trials evaluating efficacy and safety of at least one of the comparators and LDX. Quality assessments for each included trial were performed using criteria recommended by the Centre for Reviews and Dissemination. Network meta-analysis methods for dichotomous outcomes were employed to evaluate treatment efficacy. Response, as defined by either a reduction from baseline of at least 25% in the ADHD Rating Scale [ADHD-RS] total score or, separately, as assessed on the Clinical Global Impression-Improvement [CGI-I] scale, and safety (all-cause withdrawals and withdrawal due to adverse events). The systematic review found 32 trials for the meta-analysis, including data on LDX, ATX, and different formulations of MPH. No trials for DEX meeting the inclusion criteria were found. Sufficient data were identified for each outcome: ADHD-RS, 16 trials; CGI-I, 20 trials; all-cause withdrawals, 28 trials; and withdrawals due to adverse events, 27 trials. The relative probability of treatment response for CGI-I (95% confidence intervals [CI]) for ATX versus LDX was 0.65 (0.53-0.78); for long-acting MPH versus LDX, 0.82 (0.69-0.97); for intermediate release MPH versus LDX, 0.51 (0.40-0.65); and for short-acting MPH versus LDX, 0.62 (0.51-0.76). The relative probabilities of ADHD-RS treatment response also favored LDX. For the treatment of ADHD, the synthesis of efficacy data showed statistically significant better probabilities of response with LDX than for formulations of MPH or ATX. The analysis of safety data proved inconclusive due to low event rates. These results may be limited by the studies included, which only investigated the short-term efficacy of medications in patients without comorbid disorders.


Glomerular filtration rate in conscious unrestrained starlings under dehydration.
Glomerular filtration rate (GFR) was measured in conscious unrestrained starlings, Sturnis vulgaris. Alzet osmotic minipumps were inserted into the peritoneal cavity under lidocaine local anesthesia and served to infuse the GFR marker [14C]sodium ferrocyanide. GFR was measured in hydrated birds and again after a 24-h period of water deprivation. GFR in dehydrated birds was 1.15 +/- 0.09 ml.min-1.kg-1, significantly lower (P less than 0.001) than the 2.71 +/- 0.31 ml.min-1.kg-1 in fully hydrated animals. In addition, the GFR of the hydrated birds was significantly lower (P less than 0.01) than values of 4.43 +/- 0.24 ml.min-1.kg-1 measured in hydrated anesthetized birds during micropuncture studies. A 24-h period of water deprivation caused significant increases in plasma osmolality and concentration of sodium, chloride, and phosphate. The osmolality and concentrations of calcium, magnesium, and phosphate were significantly elevated in both cloacal urine supernatant and in ureteral urine of dehydrated birds. In both hydrated and dehydrated states, the concentration of magnesium, phosphate, potassium, and total osmolality were significantly higher in cloacal urine than in ureteral urine.


Tactile frequency discrimination is enhanced by circumventing neocortical adaptation.
Neocortical responses typically adapt to repeated sensory stimulation, improving sensitivity to stimulus changes, but possibly also imposing limitations on perception. For example, it is unclear whether information about stimulus frequency is perturbed by adaptation or encoded by precise response timing. We addressed this question in rat barrel cortex by comparing performance in behavioral tasks with either whisker stimulation, which causes frequency-dependent adaptation, or optical activation of cortically expressed channelrhodopsin-2, which elicits non-adapting neural responses. Circumventing adaption by optical activation substantially improved cross-hemispheric discrimination of stimulus frequency. This improvement persisted when temporal precision of optically evoked spikes was reduced. We were able to replicate whisker-driven behavior only by applying adaptation rules mimicking sensory-evoked responses to optical stimuli. Conversely, in a change-detection task, animals performed better with whisker than optical stimulation. Our results directly demonstrate that sensory adaptation critically governs the perception of stimulus patterns, decreasing fidelity under steady-state conditions in favor of change detection.


Molecularly imprinted polymer for selective determination of Δ9-tetrahydrocannabinol and 11-nor-Δ9-tetrahydrocannabinol carboxylic acid using LC-MS/MS in urine and oral fluid.
The use of molecularly imprinted polymers (MIPs) for solid phase extraction (MISPE) allows a rapid and selective extraction compared with traditional methods. Determination of Δ(9)-tetrahydrocannabinol (THC) and 11-nor-Δ(9)-tetrahydrocannabinol carboxylic acid (THC-COOH) in oral fluid (OF) and urine was performed using homemade MISPEs for sample clean-up and liquid chromatography tandem mass spectrometry (LC-MS/MS). Cylindrical MISPE shaped pills were synthesized using catechin as a mimic template. MISPEs were added to 0.5 mL OF or urine sample and sonicated 30 min for adsorption of analytes. For desorption, the MISPE was transfered to a clean tube, and sonicated for 15 min with 2 mL acetone:acetonitrile (3:1, v/v). The elution solvent was evaporated and reconstituted in mobile phase. Chromatographic separation was performed using a SunFire C18 (2.5 μm; 2.1 × 20 mm) column, and formic acid 0.1% and acetonitrile as mobile phase, with a total run time of 5 min. The method was fully validated including selectivity (no endogenous or exogenous interferences), linearity (1-500 ng/mL in OF, and 2.5-500 ng/mL in urine), limit of detection (0.75 and 1 ng/mL in OF and urine, respectively), imprecision (%CV <12.3%), accuracy (98.2-107.0% of target), extraction recovery (15.9-53.5%), process efficiency (10.1-46.2%), and matrix effect (<-55%). Analytes were stable for 72 h in the autosampler. Dilution 1:10 was assured in OF, and Quantisal™ matrix effect showed ion suppression (<-80.4%). The method was applied to the analysis of 20 OF and 11 urine specimens. This is the first method for determination of THC and THC-COOH in OF using MISPE technology.


Survey of antipsychotic medication curriculum content in Australian university nursing programmes.
Antipsychotic medication has long been one of the first-line interventions for people with serious mental illness, with outcomes including reductions in symptoms and relapse rates. More recently, however, questions have been raised about the efficacy of antipsychotic medications, especially in light of their side-effect profile. Such questions have implications for the nurses administering antipsychotic medications, particularly in relation to their knowledge of the antipsychotic medication, its efficacy, and side-effect profile. Also important is the education of nursing students about antipsychotic medications, their use, and management. The present study reports findings of research that explored current curriculum content concerning psychopharmacological treatment in Australian undergraduate and postgraduate nursing programmes. Using a survey design, the research examined the content and modes of delivery of this content to gauge how well students are prepared for administering antipsychotic medication to people with serious mental illness. Findings of the research suggested the need for improvement in preparing nursing students to administer antipsychotic medication, including indications, contraindications, as well as recognition and management of side-effects.


Global gene expression profiling in early-stage polycystic kidney disease in the Han:SPRD Cy rat identifies a role for RXR signaling.
Han:SPRD Cy is a spontaneous rat model of polycystic kidney disease (PKD) caused by a missense mutation in Pkdr1. Cystogenesis in this model is not clearly understood. In the current study, we performed global gene expression profiling in early-stage PKD cyst development in Cy/Cy kidneys and normal (+/+) kidneys at 3 and 7 days of postnatal age. Expression profiles were determined by microarray analysis, followed by validation with real-time RT-PCR. Genes were selected with over 1.5-fold expression changes compared with age-matched +/+ kidneys for canonical pathway analysis. We found nine pathways in common between 3- and 7-day Cy/Cy kidneys. Three significantly changed pathways were designated "Vitamin D Receptor (VDR)/Retinoid X Receptor (RXR) Activation," "LPS/IL-1-Mediated Inhibition of RXR Function," and "Liver X Receptor (LXR)/RXR Activation." These results suggest that RXR-mediated signaling is significantly altered in developing kidneys with mutated Pkdr1. In gene ontology analysis, the functions of these RXR-related genes were found to be involved in regulating cell proliferation and organ morphogenesis. With real-time RT-PCR analysis, the upregulation of Ptx2, Alox15b, OSP, and PCNA, major markers of cell proliferation associated with the RXR pathway, were confirmed in 3- and 7-day Cy/Cy kidneys compared with 3-day +/+ kidneys. The increased RXR protein was observed in both the nucleus and cytoplasm of cystic epithelial cells in early-stage Cy/Cy kidneys, and the RXR-positive cells were strongly positive for PCNA staining. Taken together, cell proliferation and organ morphogenesis signals transduced by RXR-mediated pathways may have important roles for cystogenesis in early-stage PKD in this Pkdr1-mutated Cy rat.


The OpenScience Slovenia metadata dataset.
The OpenScience Slovenia metadata dataset contains metadata entries for Slovenian public domain academic documents which include undergraduate and postgraduate theses, research and professional articles, along with other academic document types. The data within the dataset was collected as a part of the establishment of the Slovenian Open-Access Infrastructure which defined a unified document collection process and cataloguing for universities in Slovenia within the infrastructure repositories. The data was collected from several already established but separate library systems in Slovenia and merged into a single metadata scheme using metadata deduplication and merging techniques. It consists of text and numerical fields, representing attributes that describe documents. These attributes include document titles, keywords, abstracts, typologies, authors, issue years and other identifiers such as URL and UDC. The potential of this dataset lies especially in text mining and text classification tasks and can also be used in development or benchmarking of content-based recommender systems on real-world data.


Role of hydroxyapatite coating in resisting wear particle migration and osteolysis around acetabular components.
The main problem facing the longevity of total joint replacements is wear particle-induced osteolysis, particularly around the acetabular component. Ovine Total Hip Replacement surgery was performed with roughened femoral heads in order to enhance wear debris generation in vivo. The resistance to aseptic loosening of acetabular components with different surface coatings was investigated. Implants remained in vivo for 1 year. Sheep were randomly assigned to one of six experimental groups where the acetabular cup was fixed utilising an: (a) cemented polyethylene acetabular cup, (b) metal backed grit blasted surface, (c) metal backed plasma sprayed titanium porous coating, (d) metal backed sintered beaded coating, (e) Hydroxyapatite (HA)-coated grit blasted surface (f) and HA-coated porous components. Ground Reaction Force (GRF) was used to asses the functional performance of the implants and data was collected pre-operatively and at 12, 24, 36 and 52 weeks post op. Wear debris generated was analysed and radiographs taken prior to preparation of thin sections. Fibrous tissue (FT) thickness and bone contact at 1 mm intervals along the acetabular bone-implant interface was calculated. GRF data demonstrated significant differences between experimental groups. In all groups there was an increase in the function of the hip after surgery and up to 24 weeks but thereafter the function of the group with the grit blasted surface reduced whereas the function of the other groups did not significantly change. Average wear particles generated were <1 microm in size. The cemented group demonstrated a significantly thicker average FT layer (2.69 mm) when compared with all other groups (p<0.05 in all cases) except the grit blasted group (1.56 mm). HA porous coated cups demonstrated significantly least fibrous tissue adjacent to its interface when compared with all other groups (cemented p<0.05, grit blasted p=0.029, porous p<0.05, sintered beads p<0.05 and HA grit blasted p<0.05). Significantly increased bone contact to HA-coated porous cups (73.33%) when compared with all groups was identified except HA-coated grit blasted cups where no significant difference was demonstrated. Radiographic signs of loosening were visible in all groups except the HA-coated porous group. Results demonstrated that HA porous coated acetabular components significantly enhanced bone ingrowth in the presence of wear particles, preventing their migration and reducing osteolysis. Non-HA-coated porous and sintered beaded components provided a more effective seal against the ingress of wear debris when compared with cemented cups.


Dissolution and transport of insensitive munitions formulations IMX-101 and IMX-104 in saturated soil columns.
Military training exercises can result in deposition of energetic residues on range soils, which ultimately can contaminate groundwater with munitions constituents. Column experiments followed by HYDRUS-1D modeling were conducted to evaluate dissolution and transport of energetic constituents from the new insensitive munitions (IM) formulations IMX-101, a mixture of 3-nitro-1,2,4-triazol-5-one (NTO), nitroguanidine (NQ), and 2, 4-dinitroanisole (DNAN), and IMX-104, a mixture of NTO, 1,3,5-hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and DNAN. NTO and DNAN are emerging contaminants associated with the development of insensitive munitions as replacements for traditional munitions. Flow interruption experiments were performed to investigate dissolution kinetics and sorption non-equilibrium between soil and solution phases. The results indicated that insensitive munitions compounds dissolved in order of their aqueous solubility, consistent with prior dissolution studies conducted in the absence of soil. Initial elution of the high concentration pulse of highly soluble NTO and NQ was followed by lower concentrations, while DNAN had generally lower and more constant concentrations in leachate. The sorption of NTO and NQ was low, while RDX, 1,3,5,7-octahydro-1,3,5,7-tetranitrotetrazocine (HMX, an impurity in technical grade RDX), and DNAN all exhibited appreciable sorption. DNAN transformation was observed, with formation of amino-reduction products 2-ANAN (2-amino-4-nitroanisole) and 4-ANAN (4-amino-2-nitroanisole). HYDRUS-1D model, incorporating one-dimensional advective-dispersive transport with particle dissolution and first-order solute transformation was used to simulate the measured breakthrough curves. Optimized dissolution parameters varied widely but were correlated between compounds in the same formulation. Determined adsorption coefficients generally agreed with values determined from batch and column studies conducted with pure NTO and DNAN, while mass-loss rate coefficients were in better agreement with ones from batch than column studies possibly due to suppression of microbial transformation during elution of high concentrations of explosives. Even in the low organic matter soils selected in this study DNAN experienced significant retardation and transformation, indicating potential for its natural attenuation.


Disorder-specific predictive classification of adolescents with attention deficit hyperactivity disorder (ADHD) relative to autism using structural magnetic resonance imaging.
Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder, but diagnosed by subjective clinical and rating measures. The study's aim was to apply Gaussian process classification (GPC) to grey matter (GM) volumetric data, to assess whether individual ADHD adolescents can be accurately differentiated from healthy controls based on objective, brain structure measures and whether this is disorder-specific relative to autism spectrum disorder (ASD). Twenty-nine adolescent ADHD boys and 29 age-matched healthy and 19 boys with ASD were scanned. GPC was applied to make disorder-specific predictions of ADHD diagnostic status based on individual brain structure patterns. In addition, voxel-based morphometry (VBM) analysis tested for traditional univariate group level differences in GM. The pattern of GM correctly classified 75.9% of patients and 82.8% of controls, achieving an overall classification accuracy of 79.3%. Furthermore, classification was disorder-specific relative to ASD. The discriminating GM patterns showed higher classification weights for ADHD in earlier developing ventrolateral/premotor fronto-temporo-limbic and stronger classification weights for healthy controls in later developing dorsolateral fronto-striato-parieto-cerebellar networks. Several regions were also decreased in GM in ADHD relative to healthy controls in the univariate VBM analysis, suggesting they are GM deficit areas. The study provides evidence that pattern recognition analysis can provide significant individual diagnostic classification of ADHD patients and healthy controls based on distributed GM patterns with 79.3% accuracy and that this is disorder-specific relative to ASD. Findings are a promising first step towards finding an objective differential diagnostic tool based on brain imaging measures to aid with the subjective clinical diagnosis of ADHD.


Antitumor Perspectives of Oleuropein and Its Metabolite Hydroxytyrosol: Recent Updates.
Olive fruit is a significant and promising source of potential bioactive compounds such as oleuropein and hydroxytyrosol. Oleuropein is the ester of elenolic acid and 3,4-dihydroxyphenyl ethanol (HT). It is the main glycoside in olives, the degradation of which results in the formation of hydroxytyrosol in olive oil. Both plays a significant role in the reduction of coronary heart diseases and a certain type of cancers. Both olive oil phenols have an effective role counter to cell proliferation, cell growth, migration, invasion, and angiogenesis. They down regulate the expression of BCL-2 and COX-2 proteins, and reduced DNA damage. Hydroxytyrosol and oleuropein inhibited the multiple stages in colon carcinogenesis; initiation, promotion, and metastasis. They also provide protection against various human cancers including colorectal, skin, breast, thyroid, digestive, lung, brain, blood, and cervical. This review article discusses the anticancer perspectives and mechanisms of oleuropein and hydroxytyrosol in cell cultures and animal and human studies.


MEMS compatible micro-GRIN lenses for fiber to chip coupling of light.
Graded-Index (GRIN) lenses with a diameter of 125 mum are presented. This diameter enables the assembly of the GRIN lenses onto an optical micro-system using the same passive alignment grooves as used for the light carrying optical fibers. In contrast to refractive lenses, GRIN lenses have flat endfaces and the focal distance of a GRIN lens is defined by its length. Therefore, GRIN lenses can be diced from a selected multimode optical fiber with a regular wafer dicing machine. The effects of the resulting surface roughness are reduced by immersing the optical parts into index matching oil, which can not be applied for refractive lenses. This has a further advantage since an anti-reflective coating becomes dispensable. The coupling efficiency of a collimator set-up using the GRIN lenses is studied using paraxial ray calculations. The calculated minimal coupling losses of less than 0.3 dB are in excellent agreement with the measured results. Losses smaller than 2 dB over a coupling length of 2 mm have been measured.