Evaluation of the SVOne Handheld Autorefractor in a Pediatric Population.
The SVOne is a portable, Hartmann-Shack wavefront aberrometer, which can be attached to a smartphone to determine the refractive error of the eye objectively. Previous results have shown the device to provide measurements equivalent to those of standard clinical techniques in young, healthy adults. The aim of the present study was to compare the findings of the SVOne with retinoscopy, subjective refraction, and two commercially available autorefractors (Retinomax-3 and WAM-5500) in a pediatric population. The refractive error of the right eye was assessed both without and with cycloplegia in 40 visually normal children between 5 and 17 years of age (mean age = 11.3 years) using the five techniques described above. Further, to assess repeatability of the instruments, the entire procedure was repeated in a subgroup of five subjects. All data were analyzed in terms of power vectors (M, J0, and J45). No significant difference was observed between the mean values of M (spherical equivalent) for the different techniques. Retinoscopy showed the best agreement with subjective refraction, both without and with cycloplegia, followed by the open-field WAM-5500. The most repeatable procedures, when measured without and with cycloplegia, were the WAM-5500 and retinoscopy, respectively. Measurements with the SVOne showed a decline in repeatability under cycloplegia. The results indicate that the SVOne provides measurements of refractive error in a normal, pediatric population that are not significantly different from other subjective and objective procedures. Accurate alignment along the visual axis, especially when measuring through a dilated pupil, is critical. This instrument is valuable for vision screenings, for examinations taking place outside the clinical office, and a starting point for the refractive assessment.


Rapid Exchange of Stably Bound Protein and DNA Cargo on a DNA Origami Receptor.
Biomolecular complexes can form stable assemblies yet can also rapidly exchange their subunits to adapt to environmental changes. Simultaneously allowing for both stability and rapid exchange expands the functional capacity of biomolecular machines and enables continuous function while navigating a complex molecular world. Inspired by biology, we design and synthesize a DNA origami receptor that exploits multivalent interactions to form stable complexes that are also capable of rapid subunit exchange. The system utilizes a mechanism first outlined in the context of the DNA replisome, known as multisite competitive exchange, and achieves a large separation of time scales between spontaneous subunit dissociation, which requires days, and rapid subunit exchange, which occurs in minutes. In addition, we use the DNA origami receptor to demonstrate stable interactions with rapid exchange of both DNA and protein subunits, thus highlighting the applicability of our approach to arbitrary molecular cargo, an important distinction with canonical toehold exchange between single-stranded DNA. We expect this study to benefit future studies that use DNA origami structures to exploit multivalent interactions for the design and synthesis of a wide range of possible kinetic behaviors.


Origin and Age of Metal Veins in Canyon Diablo Graphite Nodules.
Previous studies attributed the origin of metal veins penetrating graphite nodules in the Canyon Diablo IAB main group iron meteorite to condensation from vapor or melting of host metal. Abundances of 16 siderophile elements measured in kamacite within vein and host meteorite are most consistent with an origin by melting of the host metal followed by fractional crystallization of the liquid. The presence of the veins within graphite nodules may be explained by impact, as peak shock temperatures, and thus the most likely areas to undergo metal melting, are at metal-graphite interfaces. The origin of the veins is constrained by Re-Os chronometry to have occurred early (>4 Ga) in Solar System history.


Neural stem cells for the treatment of disorders of the enteric nervous system: strategies and challenges.
The main goal of this review is to summarize the status of the research in the field of stem cells transplantation, as it is applicable to the treatment of gastrointestinal motility. This field of research has advanced tremendously in the past 10 years, and recent data produced in our laboratories as well as others is contributing to the excitement on the use of neural stem cells (NSC) as a valuable therapeutic approach for disorders of the enteric nervous system characterized by a loss of critical neuronal subpopulations. There are several sources of NSC, and here we describe therapeutic strategies for NSC transplantation in the gut. These include using NSC as a relatively nonspecific cellular replacement strategy in conditions where large populations of neurons or their subsets are missing or destroyed. As with many other recent "breakthroughs" stem cell therapy may eventually prove to be overrated. However, at the present time, it does appear to provide the hope for a true cure for many currently intractable diseases of both the central and the peripheral nervous system. Certainly more extensive research is needed in this field. We hope that our review will encourage new investigators in entering this field of research ad contribute to our knowledge of the potentials of NSC and other cells for the treatment of gastrointestinal dysmotility.


CoCoA: conditional correlation models with association size.
Many scientific questions can be formulated as hypotheses about conditional correlations. For instance, in tests of cognitive and physical performance, the trade-off between speed and accuracy motivates study of the two variables together. A natural question is whether speed-accuracy coupling depends on other variables, such as sustained attention. Classical regression techniques, which posit models in terms of covariates and outcomes, are insufficient to investigate the effect of a third variable on the symmetric relationship between speed and accuracy. In response, we propose a conditional correlation model with association size, a likelihood-based statistical framework to estimate the conditional correlation between speed and accuracy as a function of additional variables. We propose novel measures of the association size, which are analogous to effect sizes on the correlation scale while adjusting for confound variables. In simulation studies, we compare likelihood-based estimators of conditional correlation to semiparametric estimators adapted from genomic studies and find that the former achieves lower bias and variance under both ideal settings and model assumption misspecification. Using neurocognitive data from the Philadelphia Neurodevelopmental Cohort, we demonstrate that greater sustained attention is associated with stronger speed-accuracy coupling in a complex reasoning task while controlling for age. By highlighting conditional correlations as the outcome of interest, our model provides complementary insights to traditional regression modeling and partitioned correlation analyses.


Exercise partially reverses the inhibitory effect of caffeine on liver gluconeogenesis in type 1 diabetic rats with hypoglycemia.
The purpose was to determine the possible effects of exercise and/or caffeine on hypoglycemia and liver gluconeogenesis in diabetic rats. These were divided into four subgroups: (a) intraperitoneal insulin only, (b) exercise bout before insulin, (c) caffeine after insulin, and (d) exercise bout before and caffeine after insulin. The marked glycemic drop 45 min after insulin (0 min = 229.00, 45 min = 75.75) was considerably reduced (p < 0.05) by caffeine or exercise (45 min: exercise = 127.00, caffeine = 104.78). However, this systemic effect was lost (p > 0.05) when they were combined (45 min: exercise + caffeine = 65.44) (Mean, in mg·dL-1). Caffeine alone strongly inhibited liver glucose production from 2 mM lactate 45 min after insulin (without caffeine = 3.05, with caffeine = 0.27; p < 0.05), while exercise + caffeine partially re-established the liver gluconeogenic capacity (exercise + caffeine = 1.61; p < 0.05 relative to the other groups) (Mean, in μmol·g-1). The improved hypoglycemia with caffeine or exercise cannot be explained by their actions on liver gluconeogenesis. As their beneficial effect disappeared when they were combined, such association in diabetic patients should be avoided during the period of hyperinsulinemia due to the risk of severe hypoglycemia.


Carbon-Based Electrode Materials for Microsupercapacitors in Self-Powering Sensor Networks: Present and Future Development.
There is an urgent need to fulfill future energy demands for micro and nanoelectronics. This work outlines a number of important design features for carbon-based microsupercapacitors, which enhance both their performance and integration potential and are critical for complimentary metal oxide semiconductor (CMOS) compatibility. Based on these design features, we present CMOS-compatible, graphene-based microsupercapacitors that can be integrated at the back end of the line of the integrated circuit fabrication. Electrode materials and their interfaces play a crucial role for the device characteristics. As such, different carbon-based materials are discussed and the importance of careful design of current collector/electrode interfaces is emphasized. Electrode adhesion is an important factor to improve device performance and uniformity. Additionally, doping of the electrodes can greatly improve the energy density of the devices. As microsupercapacitors are engineered for targeted applications, device scaling is critically important, and we present the first steps toward general scaling trends. Last, we outline a potential future integration scheme for a complete microsystem on a chip, containing sensors, logic, power generation, power management, and power storage. Such a system would be self-powering.


It's A-bout Time: Detailed Patterns of Physical Activity in Obese Adolescents Participating in a Lifestyle Intervention.
The detailed patterns of physical activity and sedentary behaviors of overweight and obese adolescents are unknown, but may be important for health outcomes and targeted intervention design. Participants completed Curtin University's Activity, Food and Attitudes Program (CAFAP), an 8-week intervention with 12 months of maintenance intervention. Physical activity and sedentary time were assessed at 6 time periods with accelerometers and were analyzed by 1) time and type of day, 2) intensity bout patterns using exposure variation analysis, and 3) individual case analysis. Participants (n = 56) spent a lower percentage of time at baseline in light activity during school days compared with weekend days (24.4% vs 29.0%, P = .004). The majority of time was in long uninterrupted sedentary bouts of greater than 30 minutes (26.7% of total time, 36.8% of sedentary time at baseline). Moderate activity was accumulated in short bouts of less than 5 minutes (3.1% of total time, 76.0% moderate time). Changes varied by individuals. Exposure variation analysis revealed specific changes in activity patterns in overweight and obese adolescents who participated in a lifestyle intervention. A better understanding of these patterns can help to design interventions that meaningfully affect specific behaviors, with unique health consequences.


Identification and characterization of the hemophore-dependent heme acquisition system of Yersinia pestis.
Yersinia pestis possesses a heme-protein acquisition system (Hmu) that allows it to utilize heme and heme-protein complexes as the sole sources of iron. Analysis of the Y. pestis CO92 genomic sequence revealed a second heme-protein acquisition gene cluster that shares homology with the hemophore-dependent heme acquisition system (Has system) of Serratia marcescens. This locus consisted of the hasR(yp) receptor gene, the hasA(yp) hemophore gene, and genes encoding components of the HasA(yp) dedicated ABC transporter factor (hasDE(yp)), as well as a tonB homologue (hasB(yp)). By using a reconstituted secretion system in Escherichia coli, we showed that HasA(yp) is a secreted heme-binding protein and that expression of HasA(yp) is iron regulated in E. coli. The use of a transcriptional reporter fusion showed that the hasRADEB promoter is Fur regulated and has increased activity at 37 degrees C. Hemoglobin utilization via the Has(yp) system was studied with both E. coli and Y. pestis, for which has and has hmu mutant strains were used. No contribution of the Has system to heme utilization was observed in either E. coli or Y. pestis under the conditions we tested. Previously it was shown that a deletion of the Hmu system had no effect on the virulence of Y. pestis in a mouse model of bubonic plague. An Hmu(-) Has(-) double mutant also retained full virulence in this model of infection. This report constitutes the first attempt to investigate the contribution of the hemophore-dependent heme acquisition system in bacterial pathogenicity.


Octanuclear cubic coordination cages.
Two new bis-bidentate bridging ligands have been prepared, L (naph) and L (anth), which contain two chelating pyrazolyl-pyridine units connected to an aromatic spacer (naphthalene-1,5-diyl and anthracene-9,10-diyl respectively) via methylene connectors. Each of these reacts with transition metal dications having a preference for octahedral coordination geometry to afford {M 8L 12} (16+) cages (for L (anth), M = Cu, Zn; for L (naph), M = Co, Ni, Cd) which have an approximately cubic arrangement of metal ions with a bridging ligand spanning each of the twelve edges, and a large central cavity containing a mixture of anions and/or solvent molecules. The cages based on L (anth) have two cyclic helical {M 4L 4} faces, of opposite chirality, connected by four additional L (anth) ligands as "pillars"; all metal centers have a meridional tris-chelate configuration. In contrast the cages based on L (naph) have (noncrystallographic) S 6 symmetry, with a diagonally opposite pair of corners having a facial tris-chelate configuration with the other six being meridional. An additional significant difference between the two types of structure is that the cubes containing L (anth) do not show significant interligand aromatic stacking interactions. However, in the cages based on L (naph), there are six five-membered stacks of aromatic ligand fragments around the periphery, each based on an alternating array of electron-rich (naphthyl) and electron-deficient (pyrazolyl-pyridine, coordinated to M (2+)) aromatic units. A consequence of this is that the cages {M 8(L (naph)) 12} (16+) retain their structural integrity in polar solvents, in contrast to the cages {M 8(L (anth)) 12} (16+) which dissociate in polar solvents. Consequently, the cages {M 8(L (naph)) 12} (16+) give NMR spectra in agreement with the symmetry observed in the solid state, and their fluorescence spectra (for M = Cd) display (in addition to the normal naphthalene-based pi-pi* fluorescence) a lower-energy exciplex-like emission feature associated with a naphthyl --> pyrazolyl-pyridine charge-transfer excited state arising from the pi-stacking between ligands around the cage periphery.


Swept-frequency feedback interferometry using terahertz frequency QCLs: a method for imaging and materials analysis.
The terahertz (THz) frequency quantum cascade laser (QCL) is a compact source of high-power radiation with a narrow intrinsic linewidth. As such, THz QCLs are extremely promising sources for applications including high-resolution spectroscopy, heterodyne detection, and coherent imaging. We exploit the remarkable phase-stability of THz QCLs to create a coherent swept-frequency delayed self-homodyning method for both imaging and materials analysis, using laser feedback interferometry. Using our scheme we obtain amplitude-like and phase-like images with minimal signal processing. We determine the physical relationship between the operating parameters of the laser under feedback and the complex refractive index of the target and demonstrate that this coherent detection method enables extraction of complex refractive indices with high accuracy. This establishes an ultimately compact and easy-to-implement THz imaging and materials analysis system, in which the local oscillator, mixer, and detector are all combined into a single laser.


In vitro activities of meropenem, PD 127391, PD 131628, ceftazidime, chloramphenicol, co-trimoxazole, and ciprofloxacin against Pseudomonas cepacia.
In a study of 110 Pseudomonas cepacia isolates from patients without cystic fibrosis, the in vitro potencies of three new compounds, meropenem, PD 127391, and PD 131628, were comparable to those of ceftazidime and ciprofloxacin and exceeded those of chloramphenicol and co-trimoxazole. The MICs of ceftazidime, ciprofloxacin, meropenem, and the PD compounds for 90% of strains tested were < or = 4 micrograms/ml, whereas they were 32 micrograms/ml for chloramphenicol and co-trimoxazole. Data for 20 isolates from patients with cystic fibrosis indicated that the isolates were less susceptible to all seven antibiotics tested, with the most active compounds being meropenem and PD 127391.


Thyroid cancer & sarcoidosis.
The association of thyroid cancer and SA has been previously described in individual case reports. We are describing 4 patients with co-existence of papillary thyroid cancer (PTC) and SA who presented a diagnostic and management challenge. One patient (Patient 1) with known history of SA was referred for thyroid nodules and cervical adenopathies; Fine needle aspiration (FNA) showed PTC. At surgery, he was found to have non-necrotizing granulomatous inflammation (NNGI) in lymph nodes in addition to PTC. Another patient (Patient 2) with known history of PTC presented with a palpable LN. FNA showed NNGI. She was subsequently found to have diffuse lymphadenopathies from SA. A third patient (Patient 3) who was totally asymptomatic, without history of PTC or SA, presented with a right thyroid nodule and a right lateral neck adenopathy both of which were positive for PTC. Pathology showed extensive NNGI and PTC in 4 LNs. Subsequent work up revealed diffuse lymphadenopahies throughout the body on positron-emitting tomography/computed tomography with elevated serum angiotensin converting enzyme level. The last patient (Patient 4) who did not have any history of SA or PTC presented with systemic symptoms. Work up revealed a large goiter with substernal extension that required a thyroidectomy. At surgery, suspicious adenopathies were resected and were found to contain NNGI. The thyroid specimen contained PTC. Clinicians should be wary of this association/co-existence of SA and PTC to avoid mismanagement of neck lymphadenopathies in patients with current or history of SA. Although 4% of thyroid cancers may induce a sarcoid reaction in the thyroid gland, SA as a disease may coexist with PTC although causality remains uncertain. Being aware of this association is important in the differential diagnosis of a thyroid mass and/or a LN in a patient with SA. Therefore, patients with known SA who are found to have cervical adenopathies or thyroid nodules should have a thorough work up.


TRPP channels and polycystins.
The founding member of the TRPP family, TRPP2, was identified as one of the disease genes causing autosomal dominant polycystic kidney disease (ADPKD). ADPKD is the most prevalent, potentially lethal, monogenic disorder in humans, with an average incidence of one in 400 to one in 1,000 individuals worldwide. Here we give an overview of TRPP ion channels and Polycystin-1 receptor proteins focusing on more recent studies. We include the Polycystin-1 family since these proteins are functionally linked to TRPP channels.


Implementation experience during an eighteen month intervention to improve paediatric and newborn care in Kenyan district hospitals.
We have conducted an intervention study aiming to improve hospital care for children and newborns in Kenya. In judging whether an intervention achieves its aims, an understanding of how it is delivered is essential. Here, we describe how the implementation team delivered the intervention over 18 months and provide some insight into how health workers, the primary targets of the intervention, received it. We used two approaches. First, a description of the intervention is based on an analysis of records of training, supervisory and feedback visits to hospitals, and brief logs of key topics discussed during telephone calls with local hospital facilitators. Record keeping was established at the start of the study for this purpose with analyses conducted at the end of the intervention period. Second, we planned a qualitative study nested within the intervention project and used in-depth interviews and small group discussions to explore health worker and facilitators' perceptions of implementation. After thematic analysis of all interview data, findings were presented, discussed, and revised with the help of hospital facilitators. Four hospitals received the full intervention including guidelines, training and two to three monthly support supervision and six monthly performance feedback visits. Supervisor visits, as well as providing an opportunity for interaction with administrators, health workers, and facilitators, were often used for impromptu, limited refresher training or orientation of new staff. The personal links that evolved with senior staff seemed to encourage local commitment to the aims of the intervention. Feedback seemed best provided as open meetings and discussions with administrators and staff. Supervision, although sometimes perceived as fault finding, helped local facilitators become the focal point of much activity including key roles in liaison, local monitoring and feedback, problem solving, and orientation of new staff to guidelines. In four control hospitals receiving a minimal intervention, local supervision and leadership to implement new guidelines, despite their official introduction, were largely absent. The actual content of an intervention and how it is implemented and received may be critical determinants of whether it achieves its aims. We have carefully described our intervention approach to facilitate appraisal of the quantitative results of the intervention's effect on quality of care. Our findings suggest ongoing training, external supportive supervision, open feedback, and local facilitation may be valuable additions to more typical in-service training approaches, and may be feasible.


Does HLA-dependent chimerism underlie the pathogenesis of juvenile dermatomyositis?
Juvenile dermatomyositis (JDM) is a multisystem autoimmune disease that at times resembles chronic graft-vs-host disease. This led us to suggest that nonself cells may play a role in the disease process. In this study we examined the relationship between HLA genotype and the presence of maternally derived chimeric cells in JDM patients and healthy controls, and assessed immunologic activity in the chimeric cells. We identified chimeric cells more often in children with JDM (60 of 72) than in their unaffected siblings (11 of 48) or in healthy controls (5 of 29). The presence of chimerism in the JDM patients, their healthy siblings, and unaffected control children was associated with a HLA-DQA1*0501 allele in the mother (p = 0.011). Further, we show that maternally transferred chimeric T cells are responsive to the host's (JDM childs') lymphocytes (33.75 +/- 8.4 IFN-gamma-producing cells from JDM cells vs 5.0 +/- 1.25 from maternal cells), and that this is a memory response. These combined data indicate that chimeric cells play a direct role in the JDM disease process and that the mother's HLA genotype facilitates the transfer and/or persistence of maternal cells in the fetal circulation.


Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study.
This multicenter phase 1/2 trial investigated the combination of bendamustine, lenalidomide, and dexamethasone in repeating 4-week cycles as treatment for relapsed refractory multiple myeloma (MM). Phase 1 established maximum tolerated dose (MTD). Phase 2 assessed overall response rate at the MTD. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). A total of 29 evaluable patients were enrolled. Median age was 63 years (range, 38-80 years). Median number of prior therapies was 3 (range, 1-6). MTD was bendamustine 75 mg/m(2) (days 1 and 2), lenalidomide 10 mg (days 1-21), and dexamethasone 40 mg (weekly) of a 28-day cycle. Partial response rate was 52%, with very good partial response achieved in 24%, and minimal response in an additional 24% of patients. Median follow-up was 13 months; median OS has not been reached. One-year OS is 93% (95% confidence interval [CI], 59%-99%). Median PFS is 6.1 months (95% CI, 3.7-9.4 months) with one-year PFS of 20% (95% CI, 6%-41%). Grade 3/4 adverse events included neutropenia, thrombocytopenia, anemia, hyperglycemia, and fatigue. This first phase 1/2 trial testing bendamustine, lenalidomide, and dexamethasone as treatment of relapsed refractory MM was feasible and highly active. This study is registered at www.clinicaltrials.gov as #NCT01042704.


Dark matter universe.
Most of the mass in the universe is in the form of dark matter--a new type of nonbaryonic particle not yet detected in the laboratory or in other detection experiments. The evidence for the existence of dark matter through its gravitational impact is clear in astronomical observations--from the early observations of the large motions of galaxies in clusters and the motions of stars and gas in galaxies, to observations of the large-scale structure in the universe, gravitational lensing, and the cosmic microwave background. The extensive data consistently show the dominance of dark matter and quantify its amount and distribution, assuming general relativity is valid. The data inform us that the dark matter is nonbaryonic, is "cold" (i.e., moves nonrelativistically in the early universe), and interacts only weakly with matter other than by gravity. The current Lambda cold dark matter cosmology--a simple (but strange) flat cold dark matter model dominated by a cosmological constant Lambda, with only six basic parameters (including the density of matter and of baryons, the initial mass fluctuations amplitude and its scale dependence, and the age of the universe and of the first stars)--fits remarkably well all the accumulated data. However, what is the dark matter? This is one of the most fundamental open questions in cosmology and particle physics. Its existence requires an extension of our current understanding of particle physics or otherwise point to a modification of gravity on cosmological scales. The exploration and ultimate detection of dark matter are led by experiments for direct and indirect detection of this yet mysterious particle.


Linear and nonlinear operation of a time-to-space processor.
The operational characteristics of a time-to-space processor based on three-wave mixing for instantaneous imaging of ultrafast waveforms are investigated. We assess the effects of various system parameters on the processor's important attributes: time window of operation and signal conversion efficiency. Both linear and nonlinear operation regimes are considered, with use of a Gaussian pulse profile and a Gaussian spatial mode model. This model enables us to define a resolution measure for the processor, which is found to be an important characteristic. When the processor is operated in the linear interaction regime, we find that the conversion efficiency of a temporal signal to a spatial image is inversely proportional to the resolution measure. In the nonlinear interaction regime, nonuniform signal conversion due to fundamental wave depletion gives rise to a phenomenon that can be used to enhanced the imaging operation. We experimentally verify this nonlinear operation.


Human echolocation: pitch versus loudness information.
Blind persons emit sounds to detect objects by echolocation. Both perceived pitch and perceived loudness of the emitted sound change as they fuse with the reflections from nearby objects. Blind persons generally are better than sighted at echolocation, but it is unclear whether this superiority is related to detection of pitch, loudness, or both. We measured the ability of twelve blind and twenty-five sighted listeners to determine which of two sounds, 500 ms noise bursts, that had been recorded in the presence of a reflecting object in a room with reflecting walls using an artificial head. The sound pairs were original recordings differing in both pitch and loudness, or manipulated recordings with either the pitch or the loudness information removed. Observers responded using a 2AFC method with verbal feedback. For both blind and sighted listeners the performance declined more with the pitch information removed than with the loudness information removed. In addition, the blind performed clearly better than the sighted as long as the pitch information was present, but not when it was removed. Taken together, these results show that the ability to detect pitch is a main factor underlying high performance in human echolocation.


Changing intestinal connective tissue interactions alters homeobox gene expression in epithelial cells.
In segmented organs, homeobox genes are involved in axial patterning and cell identity. Much less is known about their role in non-segmented endoderm derivatives such as the digestive epithelium. Using a xenograft model of fetal intestinal anlagen implanted under the skin of nude mice, we have investigated whether the expression of five homeobox genes (HoxA-4, HoxA-9, HoxC-8, Cdx-1 and Cdx-2) is modified when intestinal epithelium undergoes normal development or displays heterodifferentiation in association with heterotopic mesenchyme. In homotypic associations of fetal endoderm and mesenchyme that recapitulate normal development, the overall pattern of homeobox gene expression was maintained: HoxA-9 and HoxC-8 were the highest in the colon and ileum, respectively, and HoxA-4 was expressed all along the intestine; Cdx-1 and Cdx-2 exhibited an increasing gradient of expression from small intestine to colon. Yet, grafting per se caused a faint upregulation of HoxA-9 and HoxC-8 in small intestinal regions in which these genes are not normally expressed, while the endoderm-mesenchyme dissociation-association step provoked a decay of Cdx-1 in the colon. In heterotopic associations of colonic endoderm with small intestinal mesenchyme, the colonic epithelium exhibited heterodifferentiation to a small intestinal-like phenotype. In this case, we observed a decay of HoxA-9 expression and an upregulation of HoxC-8. Additionally, heterodifferentiation of the colonic epithelium was accompanied by a downregulation of Cdx-1 and Cdx-2 to a level similar to that found in the normal small intestine. To demonstrate that mesenchyme-derived cells can influence Cdx-1 and Cdx-2 expression in the bowel epithelium, fetal jejunal endoderm was associated with intestinal fibroblastic cell lines that either support small intestinal-like or colonic-like morphogenesis. A lower expression of both homeobox genes was shown in grafts presenting the small intestinal phenotype than in those showing glandular colonic-like differentiation. Taken together, these results suggest that homeobox genes participate in the control of the positional information and/or cell differentiation in the intestinal epithelium. They also indicate that the level of Cdx-1 and Cdx-2 homeobox gene expression is influenced by epithelial-mesenchymal cell interactions in the intestinal mucosa.


GBSS-BINDING PROTEIN, encoding a CBM48 domain-containing protein, affects rice quality and yield.
The percentage of amylose in the endosperm of rice (Oryza sativa) largely determines grain cooking and eating qualities. Granule-bound starch synthase I (GBSSI) and GBSSII are responsible for amylose biosynthesis in the endosperm and leaf, respectively. Here, we identified OsGBP, a rice GBSS-binding protein that interacted with GBSSI and GBSSII in vitro and in vivo. The total starch and amylose contents in osgbp mutants were significantly lower than those of wild type in leaves and grains, resulting in reduced grain weight and quality. The carbohydrate-binding module 48 (CBM48) domain present in the C-terminus of OsGBP is crucial for OsGBP binding to starch. In the osgbp mutant, the extent of GBSSI and GBSSII binding to starch in the leaf and endosperm was significantly lower than wild type. Our data suggest that OsGBP plays an important role in leaf and endosperm starch biosynthesis by mediating the binding of GBSS proteins to developing starch granules. This elucidation of the function of OsGBP enhances our understanding of the molecular basis of starch biosynthesis in rice and contributes information that can be potentially used for the genetic improvement of yield and grain quality.


Synaptic dynamics contribute to long-term single neuron response fluctuations.
Firing rate variability at the single neuron level is characterized by long-memory processes and complex statistics over a wide range of time scales (from milliseconds up to several hours). Here, we focus on the contribution of non-stationary efficacy of the ensemble of synapses-activated in response to a given stimulus-on single neuron response variability. We present and validate a method tailored for controlled and specific long-term activation of a single cortical neuron in vitro via synaptic or antidromic stimulation, enabling a clear separation between two determinants of neuronal response variability: membrane excitability dynamics vs. synaptic dynamics. Applying this method we show that, within the range of physiological activation frequencies, the synaptic ensemble of a given neuron is a key contributor to the neuronal response variability, long-memory processes and complex statistics observed over extended time scales. Synaptic transmission dynamics impact on response variability in stimulation rates that are substantially lower compared to stimulation rates that drive excitability resources to fluctuate. Implications to network embedded neurons are discussed.


Assessment of Tongue Position and Laryngeal Height in Two Professional Voice Populations.
Purpose To advance our current knowledge of singer physiology by using ultrasonography in combination with acoustic measures to compare physiological differences between musical theater (MT) and opera (OP) singers under controlled phonation conditions. Primary objectives addressed in this study were (a) to determine if differences in hyolaryngeal and vocal fold contact dynamics occur between two professional voice populations (MT and OP) during singing tasks and (b) to determine if differences occur between MT and OP singers in oral configuration and associated acoustic resonance during singing tasks. Method Twenty-one singers (10 MT and 11 OP) were included. All participants were currently enrolled in a music program. Experimental procedures consisted of sustained phonation on the vowels /i/ and /ɑ/ during both a low-pitch task and a high-pitch task. Measures of hyolaryngeal elevation, tongue height, and tongue advancement were assessed using ultrasonography. Vocal fold contact dynamics were measured using electroglottography. Simultaneous acoustic recordings were obtained during all ultrasonography procedures for analysis of the first two formant frequencies. Results Significant oral configuration differences, reflected by measures of tongue height and tongue advancement, were seen between groups. Measures of acoustic resonance also showed significant differences between groups during specific tasks. Both singer groups significantly raised their hyoid position when singing high-pitched vowels, but hyoid elevation was not statistically different between groups. Likewise, vocal fold contact dynamics did not significantly differentiate the two singer groups. Conclusions These findings suggest that, under controlled phonation conditions, MT singers alter their oral configuration and achieve differing resultant formants as compared with OP singers. Because singers are at a high risk of developing a voice disorder, understanding how these two groups of singers adjust their vocal tract configuration during their specific singing genre may help to identify risky vocal behavior and provide a basis for prevention of voice disorders.


Evaluation of the US Army Special Forces Tactical Human Optimization, Rapid Rehabilitation, and Reconditioning Program.
We sought to assess the rehabilitation process, training, performance, and injury rates among those participating and not participating in the Tactical Human Optimization, Rapid Rehabilitation, and Reconditioning (THOR3) program and determine injury risk factors. A survey inquiring about personal characteristics, injuries, physical performance, and THOR3 participation during the previous 12 months was administered to Army Special Operations Forces (SOF) Soldiers. Based on responses to physical training, Soldiers were categorized into three groups: a traditional physical training (TPT) group, a cross-training (CT) group, and a THOR3 group. To identify potential injury risk factors, risk ratios and 95% confidence intervals (95% CIs) were calculated. Backward- stepping multivariable logistic regression models were used to assess key factors associated with injury risk. The survey was completed by 328 male Soldiers. Most of the Soldiers (62%) who scheduled an appointment with the physical therapist were seen within 1 day. Self-reported injury rates for the TPT, CT, and THOR3 groups were 70%, 52%, and 48%, respectively. When controlling for personal characteristics, unit training, and fitness, the TPT group had a marginally higher risk of being injured than the THOR3 group (odds ratio [OR], 2.72; 95% CI, 0.86-8.59; p = .09). Soldiers who did not perform any unit resistance training (ORnone/90-160 min, 3.62; 95% CI, 1.05-12.53; p = .04) or the greatest amount of resistance training (OR>160 min/90-160 min, 3.44; 95% CI, 1.64-7.20; p < .01) were more likely to experience an injury than the moderate-resistance training group. THOR3 appears to offer human performance optimization/injury prevention advantages over other SOF human performance programs.


Arabidopsis EF-Tu receptor enhances bacterial disease resistance in transgenic wheat.
Perception of pathogen (or microbe)-associated molecular patterns (PAMPs/MAMPs) by pattern recognition receptors (PRRs) is a key component of plant innate immunity. The Arabidopsis PRR EF-Tu receptor (EFR) recognizes the bacterial PAMP elongation factor Tu (EF-Tu) and its derived peptide elf18. Previous work revealed that transgenic expression of AtEFR in Solanaceae confers elf18 responsiveness and broad-spectrum bacterial disease resistance. In this study, we developed a set of bioassays to study the activation of PAMP-triggered immunity (PTI) in wheat. We generated transgenic wheat (Triticum aestivum) plants expressing AtEFR driven by the constitutive rice actin promoter and tested their response to elf18. We show that transgenic expression of AtEFR in wheat confers recognition of elf18, as measured by the induction of immune marker genes and callose deposition. When challenged with the cereal bacterial pathogen Pseudomonas syringae pv. oryzae, transgenic EFR wheat lines had reduced lesion size and bacterial multiplication. These results demonstrate that AtEFR can be transferred successfully from dicot to monocot species, further revealing that immune signalling pathways are conserved across these distant phyla. As novel PRRs are identified, their transfer between plant families represents a useful strategy for enhancing resistance to pathogens in crops.


Surface roughness average and scanning electron microscopic observations of resin luting agents.
The objective of this work was to evaluate the surface roughness changes of three current resin cements after tooth brushing simulation, as well as discuss its relation with scanning electron microscopic observations. The materials employed were Enforce Sure Cure (Dentsply), Rely X (3M-ESPE) and Variolink II (Vivadent). They were subjected to brushing abrasion (100,000 strokes for each specimen) and the surface roughness alterations (before and after strokes) were detected. For each roughness test condition, specimens were coated with gold-palladium and observed on a DSM 900 Zeiss scanning electron microscope. Roughness changes values (Ra) were statistically increased after brushing strokes. Based on the microscopic observations and roughness changes analysis, all cements studied became rougher after brushing strokes.


S100B and Inflammatory Cytokine Levels in Blood as Potential Markers of Blood-Brain Barrier Damage and Psychiatric Impairment in Comorbid Hepatitis C Viral Infection and Alcohol Use Disorder.
Hepatitis C virus (HCV) infection and alcohol use disorder (AUD) both adversely affect the immune system resulting in alterations in immune cell signaling and inflammatory processes. The aim of this study was to investigate how comorbid AUD contributes to abnormalities in inflammatory mediators and psychiatric impairments in adults with HCV. Alcohol use, mood, and inflammatory factors were evaluated at 3 time points (baseline, week 4, and week 12) in Veterans with HCV, with (n = 42) and without (n = 13) comorbid AUD. Peripheral indices of immune activation, blood-brain barrier (BBB) damage (S100 calcium-binding protein B [S100B]), liver function, and viral load were measured using immunoassays and polymerase chain reaction assays. Comorbid AUD was associated with increased symptoms of depression and anxiety, elevated levels of liver enzymes, and altered expression of inflammatory factors. Alcohol consumption was positively correlated with the severity of psychiatric symptoms. Univariate analysis identified significant group differences in interleukin (IL)-8 (p = 0.006), IL-10 (p = 0.03), and S100B (p = 0.048), with increased levels in participants with AUD, which persisted over time despite reductions in alcohol use and no significant change in HCV viral load. Statistically significant effects of study group or time were not found for the other immune factors assessed. Exploratory receiver operating characteristic curve analysis evaluated the ability of IL-8, IL-10, and S100B to differentiate between levels of alcohol consumption and generated biomarker cutoff values used to identify low risk and unhealthy alcohol use groups. These results demonstrate that HCV and comorbid AUD are associated with greater psychiatric impairments, potentially resulting from increased inflammation, dysregulated cytokine expression, and compromised BBB function. Alcohol-induced BBB damage may increase the risk of neuropathological consequences within the context of chronic HCV infection.


GABA(A) receptors modulate ethanol-induced conditioned place preference and taste aversion in mice.
GABA(A) receptor antagonists have been shown to reduce ethanol self-administration and ethanol-induced conditioned taste aversion (CTA) in rats, suggesting a role for the GABA(A) receptor in modulating ethanol's motivational effects. The present experiments examined the effects of the GABA(A) receptor antagonists, bicuculline and picrotoxin, on the acquisition of ethanol-induced conditioned place preference (CPP) and CTA in male DBA/2J mice. Mice in the CPP experiments received four pairings of ethanol (2 g/kg) with a distinctive floor stimulus for a 5-min conditioning session (CS+ sessions). During CS+ sessions, mice also received bicuculline (0, 1.0, 3.0, or 5.0 mg/kg) or picrotoxin (2.0 mg/kg) before an injection of ethanol. On intervening days (CS- sessions), the pretreatment injection was always vehicle followed by saline injections that were paired with a different floor type. For the preference test, all mice received saline injections and were placed on a half grid and half hole floor for a 60-min session. For the CTA experiments, mice were adapted to a 2-h per day water restriction regimen followed by five conditioning trials every 48 h. During conditioning trials, subjects received an injection of vehicle, bicuculline (0.5 and 2.0 mg/kg), or picrotoxin (0.75 and 2.5 mg/kg) before injection of 2 g/kg ethanol or saline following 1-h access to a saccharin solution. Both picrotoxin and the lowest dose of bicuculline (1.0 mg/kg) significantly increased the magnitude of CPP relative to vehicle-treated controls. Picrotoxin alone did not produce place conditioning. Ethanol-stimulated locomotor activity was significantly reduced during conditioning trials with picrotoxin and the higher doses of bicuculline (3.0 and 5.0 mg/kg). Bicuculline did not alter ethanol-induced CTA; however, picrotoxin dose-dependently increased the magnitude of ethanol-induced CTA. Bicuculline and picrotoxin did not produce CTA when administered alone. Overall, these results suggest that blockade of GABA(A) receptors with bicuculline and picrotoxin enhances ethanol's motivational effects in the CPP paradigm; however, only picrotoxin enhances ethanol's motivational effects in the CTA paradigm.


Heterologous deoxyribonucleic acid uptake and complexing with cellular constituents in competent Bacillus subtilis.
With competent cultures of Bacillus subtilis the uptake of Escherichia coli deoxyribonucleic acid (DNA) is about 50% that for homologous DNA. Uptake of phage T6 DNA, if any, is of the order of 7%, while nonglucosylated phage T6 (T6) DNA is taken up almost as effectively as homologous DNA. Both T6 and T4 DNA interfere only minimally with uptake of homologous DNA; by contrast, T6 DNA competes with homologous DNA as effectively as the latter itself. These results indicate that the glucose residues in the T-even phage DNA, located in the large groove of the DNA helix, reduce affinity for cellular receptors, leading to low binding of T6 DNA. The latter DNA is considerably less degraded by extracellular nucleases than homologous DNA, thus excluding enzymatic hydrolysis as the source of poor uptake. Affinity of DNA for competent cells was also evaluated by the formation, and detection in a CsCl density gradient, of complexes of DNA with cellular constituent(s). Such comlexes, similar to those previously observed with transforming DNA, are formed by E. coli DNA and T6 DNA; in reconstruction experiments the denatured forms of these same DNA samples form complexes when added to the cells before lysis. T6 DNA, on the other hand, does not form such a complex. The possible role of such complexes in transport of DNA to the cell interior is discussed.


The Gut Microbiome, Lactobacillus acidophilus; Relation with Type 2 Diabetes Mellitus.
Symbiotic interactions of microorganisms are widespread in nature, and support fundamentally important processes linking health and disease to the bacterial ecology. Intestinal microbiota is the largest source of microbial stimulation that exerts both harmful and beneficial effects on human health. It participates in the development of the postnatal immune system as well as oral tolerance and immunity. The recently explored impact of the microbiota on energy metabolism, gut hormone regulation and the gut-brain axis was judged to be a fascinating topic and of great value in the future, and can have a clinical role in the management of obesity and diabetes. To assess the impact of the gut microbe, Lactobacillus acidophilus, in patients with type 2 Diabetes Mellitus (controlled and uncontrolled) compared to healthy individuals, as a preliminary approach to future treatment with probiotics, prebiotics or diet modulation. A case control study was conducted on 30 diabetic patients and 10 control individuals. All patients were subjected to full history, thorough clinical examination, and laboratory measurement of fasting blood sugar, 2 hours post prandial, Glycosylated Hemoglobin (HbA1C), CRP (C-Reactive Protein), Lipid profile, and Identification of stool Lactobacillus acidophilus by PCR (polymerase chain reaction) technique. Significantly lower Stool Lactobacillus acidophilus PCR count among diabetic patients when compared to healthy control individuals. Stool Lactobacillus acidophilus PCR count was lower among type 2 diabetic patients, which may show relationship of lactobacillus with type 2 diabetes mellitus. However, further studies are needed to determine correlation or causation of this relationship.


The crystal structure of yeast thiamin pyrophosphokinase.
Thiamin pyrophosphokinase (TPK) catalyzes the transfer of a pyrophosphate group from ATP to vitamin B1 (thiamin) to form the coenzyme thiamin pyrophosphate (TPP). Thus, TPK is important for the formation of a coenzyme required for central metabolic functions. TPK has no sequence homologs in the PDB and functions by an unknown mechanism. The TPK structure has been determined as a significant step toward elucidating its catalytic action. The crystal structure of Saccharomyces cerevisiae TPK complexed with thiamin has been determined at 1.8 A resolution. TPK is a homodimer, and each subunit consists of two domains. One domain resembles a Rossman fold with four alpha helices on each side of a 6 strand parallel beta sheet. The other domain has one 4 strand and one 6 strand antiparallel beta sheet, which form a flattened sandwich structure containing a jelly-roll topology. The active site is located in a cleft at the dimer interface and is formed from residues from domains of both subunits. The TPK dimer contains two compound active sites at the subunit interface. The structure of TPK with one substrate bound identifies the location of the thiamin binding site and probable catalytic residues. The structure also suggests a likely binding site for ATP. These findings are further supported by TPK sequence homologies. Although possessing no significant sequence homology with other pyrophospokinases, thiamin pyrophosphokinase may operate by a mechanism of pyrophosphoryl transfer similar to those described for pyrophosphokinases functioning in nucleotide biosynthesis.


The European artificial intelligence strategy: implications and challenges for digital health.
In February, 2020, the European Commission published a white paper on artificial intelligence (AI) as well as an accompanying communication and report. The paper sets out policy options to facilitate a secure and trustworthy development of AI and considers health to be one of its most important areas of application. We illustrate that the European Commission's approach, as applied to medical AI, presents some challenges that can be detrimental if not addressed. In particular, we discuss the issues of European values and European data, the update problem of AI systems, and the challenges of new trade-offs such as privacy, cybersecurity, accuracy, and intellectual property rights. We also outline what we view as the most important next steps in the Commission's iterative process. Although the European Commission has done good work in setting out a European approach for AI, we conclude that this approach will be more difficult to implement in health care. It will require careful balancing of core values, detailed consideration of nuances of health and AI technologies, and a keen eye on the political winds and global competition.


Inbreeding and experience affect response to climate change by endangered woodpeckers.
In recent decades, female red-cockaded woodpeckers (Picoides borealis) have laid eggs increasingly earlier in response to a changing climate, as has been observed in several other bird species breeding at north temperate latitudes. Within each year, females that lay earlier are more productive than females that lay later. However, inexperienced females, experienced females who change mates and inbred birds have not adjusted to the changing climate by laying earlier, and have suffered reproductive costs as a result. Failure to respond to global climate change may be a further example of the reduced ability of inbred animals to respond to environmental challenges.


Non-disclosed men who have sex with men in UK HIV transmission networks: phylogenetic analysis of surveillance data.
Patients who do not disclose their sexuality, including men who do not disclose same-sex behaviour, are difficult to characterise through traditional epidemiological approaches such as interviews. Using a recently developed method to detect large networks of viral sequences from time-resolved trees, we localised non-disclosed men who have sex with men (MSM) in UK transmission networks, gaining crucial insight into the behaviour of this group. For this phylogenetic analysis, we obtained HIV pol sequences from the UK HIV Drug Resistance Database (UKRDB), a central repository for resistance tests done as part of routine clinical care throughout the UK. Sequence data are linked to demographic and clinical data held by the UK Collaborative HIV Cohort study and the national HIV/AIDS reporting system database. Initially, we reconstructed maximum likelihood phylogenies from these sequences, then sequences were selected for time-resolved analysis in BEAST if they were clustered with at least one other sequence at a genetic distance of 4·5% or less with support of at least 90%. We used time-resolved phylogenies to create networks by linking together nodes if sequences shared a common ancestor within the previous 5 years. We identified potential non-disclosed MSM (pnMSM), defined as self-reported heterosexual men who clustered only with men. We measured the network position of pnMSM, including betweenness (a measure of connectedness and importance) and assortativity (the propensity for nodes sharing attributes to link). 14 405 individuals were in the network, including 8452 MSM, 1743 heterosexual women and 1341 heterosexual men. 249 pnMSM were identified (18·6% of all clustered heterosexual men) in the network. pnMSM were more likely to be black African (p<0·0001), less likely to be infected with subtype B (p=0·006), and were slightly older (p=0·002) than the MSM they clustered with. Mean betweenness centrality was lower for pnMSM than for MSM (1·31, 95% CI 0·48-2·15 in pnMSM vs 2·24, 0·98-3·51 in MSM; p=0·002), indicating that pnMSM were in peripheral positions in MSM clusters. Assortativity by risk group was higher than expected (0·037 vs -0·037, p=0·01) signifying that pnMSM were linked to each other. We found that self-reported heterosexual men were more likely to link MSM and heterosexual women than heterosexual women were to link MSM and heterosexual men (Fisher's exact test p=0·0004; OR 2·24) but the number of such transmission chains was small (only 54 in total vs 32 in women). pnMSM are a subgroup distinct from both MSM and from heterosexual men. They are more likely to choose sexual partners who are also pnMSM and might exhibit lower-risk sexual behaviour than MSM (eg, choosing low-risk partners or consistently using condoms). Heterosexual men are the group most likely to be diagnosed with late-stage disease (ie, low CD4 counts) and non-disclosed MSM might put female partners at higher risk than heterosexual men because non-disclosed MSM have male partners. Hence, pnMSM require specific consideration to ensure they are included in public health interventions. National Institutes of Health.


A functional assay to measure postsynaptic gamma-aminobutyric acidB responses in cultured spinal cord neurons: heterologous regulation of the same K+ channel.
The stimulation of postsynaptic gamma-aminobutyric acid (GABA)B receptors leads to slow inhibitory postsynaptic potentials due to the influx of K(+)-ions. This was studied biochemically, in vitro in mammalian cultured spinal cord neurons by using 86Rb as a substitute for K+. (-)-Baclofen, a GABAB receptor agonist, produced a concentration-dependent increase in the 86Rb-influx. This effect was stereospecific and blocked by GABAB receptor antagonists like CGP 35 348 (3-aminopropyl-diethoxymethyl-phosphonic acid) and phaclofen. Apart from the GABAB receptors, both adenosine via adenosine1 receptors and 5-hydroxytryptamine (5-HT) via 5-HT1 alpha agonists also increased the 86Rb-influx. These agonists failed to show any additivity between them when they were combined in their maximal concentration. In addition, their effect was antagonized specifically by their respective antagonists without influencing the others. These findings suggest the presence of GABAB, adenosine1 and 5-HT1 alpha receptors in the cultured spinal cord neurons, which exhibit a heterologous regulation of the same K(+)-channel. The effect of these agonists were antagonized by phorbol 12,13-didecanoate, an activator of protein kinase C, and pretreatment with pertussis toxin. This suggests that these agonists by acting on their own receptors converge on the same K(+)-channel through the Gi/Go proteins. In summary, we have developed a biochemical functional assay for studying and characterizing GABAB synaptic pharmacology in vitro, using spinal cord neurons.


Population density and distribution of wheat bugs infesting durum wheat in Sardinia, Italy.
Wheat is a very important crop in Italy, and is infested by wheat bugs belonging to the genera Eurygaster (Hemiptera: Scutellaridae) and Aelia (Hemiptera: Pentatomidae). Many wheat bug infestations have been reported in the north, south, and center of Italy, both in the past as well as recently. The present study was carried out in Sardinia, Italy, during two years (2007 and 2008). The objective of this study was to determine the species and distribution of wheat bugs in durum wheat fields in Sardinia, and to estimate their population density in order to know the incidence of the pest on the island. Sampling took place twice a year (May and June) in three zones, representative of durum wheat cropping in the island. Four species of wheat bugs were found; the predominant species was Eurygaster austriaca (Schrank), followed by Aelia germari (Kuster), Eurygaster maura L., and Aelia acuminata L. The average density of wheat bugs was low (1.1 individuals/m²), but in certain areas it was above the damage threshold (4 individuals/m²). For this reason, the conclusion of the study is that this pest should be monitored in order to control outbreaks and prevent their further spread.


Contractile properties of single motor units in human toe extensors assessed by intraneural motor axon stimulation.
1. Single motor axons innervating human toe extensor muscles were selectively stimulated through a tungsten microelectrode inserted percutaneously into the peroneal nerve. Twitch and tetanic forces were measured from a strain gauge over the proximal phalanx of the toe generating the greatest force. Twitch data were obtained from 19 single motor units in nine subjects: 8 motor units supplied extensor hallucis longus (EHL), 5 motor units supplied extensor digitorum longus (EDL), and 6 motor units supplied extensor digitorum brevis (EDB). Unpotentiated twitch forces ranged from 6.3 to 78.1 mN (20.0 +/- 4.0 mN, mean +/- SE), with the distribution highly skewed toward small forces. Twitch contraction and half-relaxation times were 74.8 +/- 3.9 and 78.6 +/- 6.0 ms, respectively. Compared with motor units in human thenar muscles, those in human toe extensor muscles were stronger but slower. However, as in thenar motor units, twitch force and contraction time were not related. 2. Force-frequency relationships were determined for 13 units (5 EDL, 5 EHL, 3 EDB) by stimulating each unit with short trains (1.0-5.0 s) of constant frequency (2-100 Hz). Peak force was related to stimulus frequency in a sigmoid fashion. The steep region of the curve extended from 5.5 +/- 0.7 (SE) Hz to 16.3 +/- 1.1 Hz for all units, and the stimulus frequency required to generate half-maximal force (9.6 +/- 0.6 Hz) was close to the center of the steep range. This frequency, which was inversely related to twitch contraction time, was lower than the frequency required to develop half-maximal force of human thenar motor units (12 +/- 4 Hz, mean +/- SD). The slopes of the regression lines relating force to frequency, computed over the steep range for each unit, were also lower for the toe extensors (3.7 +/- 0.7 mN/Hz) than for the thenar muscles (6 +/- 1 mN/Hz). 3. Maximal tetanic forces ranged from 29.9 to 188.1 mN (89.0 +/- 16.5 mN, mean +/- SE), and were generated at stimulus frequencies from 15 to 100 Hz (median 50 Hz). The stimulation frequency required for fused tetani (absence of noticeable force fluctuation) was generally less than that required for maximum tetanic force. The mean twitch-tetanus ratio, calculated for unpotentiated twitches, was 0.22 +/- 0.02 (range 0.15-0.41). This ratio was higher than for human thenar motor units (0.14 +/- 0.06, mean +/- SE). After twitch potentiation of 10 units, the mean twitch-tetanus ratio increased to 0.28 +/- 0.04. 4. The effects of preceding each stimulus train with a short interstimulus interval (10 ms) on force production at each frequency were examined in nine motor units. Peak forces at the onset of each contraction were higher when such an "initial doublet" preceded stimulus trains of < or = 20 Hz, but the mean force at the end of each stimulus train was not significantly affected at any frequency. 5. Eight units were stimulated with a train that increased in frequency continuously from 2 to 80 Hz, and then decreased symmetrically. This pattern resulted in peak forces that were higher on the descending limb of the stimulus train, the force-frequency relationship tracing a hysteresis loop. Hysteresis was exhibited because damping in the neuromuscular system causes the mechanical output of muscle to lag behind neural input. Thus, in non-steady-state conditions (as in most forms of natural activity), somewhat higher firing rates may be required to attain a particular level of force; once attained, force output will be transiently unresponsive to diminution of firing rate. 6. We conclude that there are differences in the contractile properties of single motor units in human toe extensor muscles (involved in posture and locomotion) and thenar muscles (involved in prehension and manipulation). Twitch-tetanus ratios were greater for motor units in the toe extensors, and this property accounted for the lower force sensitivity of these units to increases in frequency. (ABSTRACT TRUNCATED)


Orangutans (Pongo abelii) seek information about tool functionality in a metacognition tubes task.
Nonhuman primates appear to engage in metacognition by knowing when they need to search for relevant information for solving the tubes task. The task involves presenting subjects with a number of tubes with only 1 having food hidden inside. Before choosing, subjects look inside the tubes more often when they do not know which 1 contains the food (hidden trials) compared to when they do know this information (visible trials). It is argued, however, that nonmetacognitive general food searching strategies can explain this looking behavior. To address this issue, 3 orangutans were tested with a novel tubes task in which they were only required to seek information about tool functionality. The results showed that subjects had the ability to search for tool functionality but no subject looked significantly more in hidden trials compared to visible trials. Subjects were retested with the same condition and given a second condition in which the cost of a wrong choice was increased. In both conditions, 2 subjects looked significantly more inside the hidden trials compared to the visible trials. Subjects were also tested with the traditional tubes task in which food was hidden inside 1 tube. All subjects looked inside the tubes significantly more in the hidden trials compared to the visible trials. However, subjects conducted more excessive looks compared to when looking for tool functionality. I suggest that excessive searches may be caused by food being a strong stimulus and discuss the relevance of this possibility for metacognitive research involving the tubes task. (PsycINFO Database Record


Immune dysregulation in autism spectrum disorder.
Autism spectrum disorder (ASD) is a common and severe neuro-developmental disorder in early childhood which is defined by social and communication deficits and repetitive and stereotypic behaviours. The aetiology of ASD remains poorly understood. Susceptibility to development of ASD has significant environmental components, in addition to the profound genetic heritability. Few genes have been associated to the risk for ASD development. There is substantial evidence implicating chronic neurological inflammation and immune dysregulation leading to upregulation of inflammatory cytokines in the ASD brain, probably due to altered blood-brain barrier function. The immune system is characterized by excessive and skewed cytokine responses, modulated T cell reactivity, decreased regulation and production of immunosuppressive cytokines, modified NK function and increased autoantibody production. The perinatal environment generates vulnerability to chronic neuro-inflammation in the brain associated with profound modulation and dysregulation in the immune system leading to the rapid development of ASD in genetically susceptible children.


Transposable elements and genome organization: a comprehensive survey of retrotransposons revealed by the complete Saccharomyces cerevisiae genome sequence.
We conducted a genome-wide survey of Saccharomyces cerevisiae retrotransposons and identified a total of 331 insertions, including 217 Ty1, 34 Ty2, 41 Ty3, 32 Ty4, and 7 Ty5 elements. Eighty-five percent of insertions were solo long terminal repeats (LTRs) or LTR fragments. Overall, retrotransposon sequences constitute >377 kb or 3.1% of the genome. Independent evolution of retrotransposon sequences was evidenced by the identification of a single-base pair insertion/deletion that distinguishes the highly similar Ty1 and Ty2 LTRs and the identification of a distinct Ty1 subfamily (Ty1'). Whereas Ty1, Ty2, and Ty5 LTRs displayed a broad range of sequence diversity (typically ranging from 70%-99% identity), Ty3 and Ty4 LTRs were highly similar within each element family (most sharing >96% nucleotide identity). Therefore, Ty3 and Ty4 may be more recent additions to the S. cerevisiae genome and perhaps entered through horizontal transfer or past polyploidization events. Distribution of Ty elements is distinctly nonrandom: 90% of Ty1, 82% of Ty2, 95% of Ty3, and 88% of Ty4 insertions were found within 750 bases of tRNA genes or other genes transcribed by RNA polymerase III. tRNA genes are the principle determinant of retrotransposon distribution, and there is, on average, 1.2 insertions per tRNA gene. Evidence for recombination was found near many Ty elements, particularly those not associated with tRNA gene targets. For these insertions, 5'- and 3'-flanking sequences were often duplicated and rearranged among multiple chromosomes, indicating that recombination between retrotransposons can influence genome organization. S. cerevisiae offers the first opportunity to view organizational and evolutionary trends among retrotransposons at the genome level, and we hope our compiled data will serve as a starting point for further investigation and for comparison to other, more complex genomes.


Detection of West Nile virus in stable flies (Diptera: Muscidae) parasitizing juvenile American white pelicans.
Stable flies, Stomoxys calcitrans (L.) (Diptera: Muscidae), an economically important pest of livestock and humans, were observed parasitizing prefledged American white pelicans, Pelecanus erythrorhynchos (Pelecaniformes: Pelecanidae), in a pelican breeding colony in northeastern Montana where die-offs attributed to West Nile virus (family Flaviviridae, genus Flavivirus, WNV) have occurred since 2002. Engorged and unengorged flies were collected off nine moribund chicks. Of 29 blood-engorged flies testing positive for vertebrate DNA, all 29 contained pelican DNA. Virus isolation was performed on 60 pools (1,176 flies) of unengorged flies using Vero cell plaque assay. Eighteen pools were positive for WNV for an estimated infection rate of 18.0 per 1,000 flies. Fifty-four percent (36/67) of abdomens from blood-engorged flies tested positive for WNV. Pelican viremia levels from the blood-engorged fly abdomens revealed that at least one of the ill pelicans circulated a viremia capable of infecting Culex mosquito vectors. Stable flies may be involved in WNV transmission within the pelican breeding colony by serving as either a mechanical vector or as a source for oral infection if ingested by predators.


Do staff nurse perceptions of nurse leadership behaviors influence staff nurse job satisfaction? The case of a hospital applying for Magnet® designation.
Nurse managers leadership behaviors influence the job satisfaction of staff nurses. Transformational leadership is 1 of the 5 components associated with the Magnet Recognition Program®. The aim of this study was to examine the relationship between staff nurse perception of nurse manager leadership behavior and staff nurse job satisfaction in a hospital on the Magnet® journey and the influence of nurse manager leadership style on staff nurse job satisfaction. A descriptive, correlational design using a self-report survey with convenience sampling was used for this quantitative research study. Staff nurses completed the Multifactor Leadership Questionnaire 5X Short Form, the Abridged Job Descriptive Index survey, and a demographic questionnaire. Pearson correlations and regression analyses were completed to explore the relationship and influence of nurse manager leadership style on staff nurse job satisfaction. Transformational and transactional leadership styles of nurse managers were positively related to staff nurse overall job satisfaction and satisfaction with opportunity for promotion. Passive-avoidant leadership style of nurse managers was negatively related to staff nurse satisfaction with work, promotion, supervision, and coworker. Satisfaction with nurse manager leadership was a positive influence on overall nurse job satisfaction when separately controlling for the influence of each leadership style. Transformational and transactional leadership styles should be taught and encouraged among nurse managers to positively influence the job satisfaction of staff nurses.


Surface waves and atomic force microscope probe-particle near-field coupling: discrete dipole approximation with surface interaction.
Evanescent waves on a surface form due to the collective motion of charges within the medium. They do not carry any energy away from the surface and decay exponentially as a function of the distance. However, if there is any object within the evanescent field, electromagnetic energy within the medium is tunneled away and either absorbed or scattered. In this case, the absorption is localized, and potentially it can be used for selective diagnosis or nanopatterning applications. On the other hand, scattering of evanescent waves can be employed for characterization of nanoscale structures and particles on the surface. In this paper we present a numerical methodology to study the physics of such absorption and scattering mechanisms. We developed a MATLAB implementation of discrete dipole approximation with surface interaction (DDA-SI) in combination with evanescent wave illumination to investigate the near-field coupling between particles on the surface and a probe. This method can be used to explore the effects of a number of physical, geometrical, and material properties for problems involving nanostructures on or in the proximity of a substrate under arbitrary illumination.


Maternal inheritance of mitochondria in Eucalyptus globulus.
It is important to verify mitochondrial inheritance in plant species in which mitochondrial DNA (mtDNA) will be used as a source of molecular markers. We used a polymerase chain reaction (PCR)/restriction fragment length polymorphism (RFLP) approach to amplify mitochondrial introns from subunits 1, 4, 5, and 7 of NADH dehydrogenase (nad) and cytochrome oxidase subunit II (cox2) in Eucalyptus globulus. PCR fragments were then either sequenced or cut with restriction enzymes to reveal polymorphism. Sequencing cox2 showed that eucalypts lack the intron between exons 1 and 2. One polymorphism was found in intron 2-3 of nad7 following restriction digests with HphI. Fifty-four F1 progeny from seven families with parents distinguishable in their mitochondrial nad7 were screened to show that mitochondria were maternally inherited in E. globulus. These results constitute the first report of mitochondrial inheritance in the family Myrtaceae.


Resisting control of neglected tropical diseases: dilemmas in the mass treatment of schistosomiasis and soil-transmitted helminths in north-west Uganda.
A strong case has recently been made by academics and policymakers to develop national programmes for the integrated control of Africa's 'neglected tropical diseases'. Uganda was the first country to develop a programme for the integrated control of two of these diseases: schistosomiasis and soil-transmitted helminths. This paper discusses social responses to the programme in Panyimur, north-west Uganda. It shows that adults are increasingly rejecting free treatment. Resistance is attributed to a subjective fear of side-effects; divergence between biomedical and local understandings of schistosomiasis/bilharzia; as well as inappropriate and inadequate health education. In addition, the current procedures for distributing drugs at a district level are problematic. Additional research was carried out in neighbouring areas to explore the generalizability of findings. Comparable problems have arisen. It is concluded that the national programme will not fulfil its stated objectives of establishing a local demand for mass treatment unless it can establish more effective delivery strategies and promote behavioural change in socially appropriate ways. To do so will require new approaches to social, economic and political aspects of distribution. There are reasons why populations infected with the 'neglected tropical diseases' are themselves neglected. Those reasons cannot just be wished away.


The association of overweight and obesity with spirometric values in minority children referred for asthma evaluation.
Overweight, obesity, and asthma are more prevalent in minority children; yet, the association of overweight and obesity with spirometric values in asthmatic minorities is not well characterized. To study the relationship between weight, ethnicity, and spirometric values in children referred for asthma evaluation to a large inner-city hospital in Bronx, NY. Retrospective review of spirometry done at the first pulmonary clinic visit of 980 asthmatic children, aged 7-20 years, was conducted. Linear regression analysis was performed to elucidate the association of overweight and obesity with pulmonary function among Whites, African Americans, and Hispanics compared with their normal weight counterparts. More African Americans (58%) and Hispanics (65.4%) were overweight and obese than Whites (51.2%) (p < .05). Compared with their normal weight counterparts, percent forced expiratory volume in the 1st second (FEV(1))/forced vital capacity (FVC) ratio was lower in both overweight and obese African Americans (2.99%, p < .05 and 3.56%, p < .01, respectively) and Hispanics (2.64%, p < .05 and 2.36%, p < .05, respectively); these differences were found in obese (3.73%, p < .05) but not in overweight (0.68%, p = .7) Whites. FEV(1)/FVC ratio was lower in both overweight and obese African American and Hispanic children, while this association was present only among obese Whites compared with their normal weight counterparts. These results suggest that spirometric measures of lower airway obstruction decrease with smaller weight increments in minority children when compared with White children. In the context of the higher prevalence of overweight and obesity among African Americans and Hispanics, our findings offer one potential explanation for increased asthma among minority children.


Intraarterial Thrombolysis as Rescue Therapy for Large Vessel Occlusions.
Background and Purpose- Mechanical thrombectomy (MT) devices have led to improved reperfusion and clinical outcomes in acute ischemic stroke patients with emergent large vessel occlusions; however, less than one-third of patients achieve complete reperfusion. Use of intraarterial thrombolysis in the context of MT may provide an opportunity to enhance these results. Here, we evaluate the use of intraarterial rtPA (recombinant tissue-type plasminogen activator) as rescue therapy (RT) after failed MT in the North American Solitaire Stent-Retriever Acute Stroke registry. Methods- The North American Solitaire Stent-Retriever Acute Stroke registry recruited sites within North America to submit data on acute ischemic stroke patients treated with the Solitaire device. After restricting the population of 354 patients to use of RT and anterior emergent large vessel occlusions, we compared patients who were treated with and without intraarterial rtPA after failed MT. Results- A total of 37 and 44 patients was in the intraarterial rtPA RT and the no intraarterial rtPA RT groups, respectively. Revascularization success (modified Thrombolysis in Cerebral Infarction ≥2b) was achieved in more intraarterial rtPA RT patients (61.2% versus 46.6%; P=0.13) with faster times to recanalization (100±85 versus 164±235 minutes; P=0.36) but was not statistically significant. The rate of symptomatic intracranial hemorrhage (13.9% versus 6.8%; P=0.29) and mortality (42.9% versus 44.7%; P=0.87) were similar between the groups. Good functional outcome (modified Rankin Scale score of ≤2) was numerically higher in intraarterial rtPA patients (22.9% versus 18.4%; P=0.64). Further restriction of the RT population to M1 occlusions only and time of onset to groin puncture ≤8 hours, resulted in significantly higher successful revascularization rates in the intraarterial rtPA RT cohort (77.8% versus 38.9%; P=0.02). Conclusions- Intraarterial rtPA as RT demonstrated a similar safety and clinical outcome profile, with higher reperfusion rates achieved in patients with M1 occlusions. Prospective studies are needed to delineate the role of intraarterial thrombolysis in MT.


Multimodal transition and stochastic antiresonance in squid giant axons.
The experimental data of Takahashi [Physica D 43, 318 (1990)], on the response of squid giant axons stimulated by periodic sequence of short current pulses is interpreted within the Hodgkin-Huxley model. The minimum of the firing rate as a function of the stimulus amplitude I0 in the high-frequency regime is due to the multimodal transition. Below this singular point only odd multiples of the driving period remain and the system is sensitive to noise. The coefficient of variation has a maximum and the firing rate has a minimum as a function of the noise intensity, which is an indication of the stochastic coherence antiresonance. The model calculations reproduce the frequency of occurrence of the most common modes in the vicinity of the transition. A linear relation of output frequency vs I0 above the transition is also confirmed.


Distributed Dynamic Event-Triggered Leader-Following Consensus for Nonlinear Multiagent Systems Over Fading Channel.
This article investigates the leader-following consensus problem of discrete-time nonlinear multiagent systems (MASs) over fading channels. With the consideration of the transmission among followers maybe affected by the fading networks, the nonidentical fading channels model is constructed. To reduce the transmission network burden, the dynamical event-triggered mechanism (DETM) is developed. Different from most of existing event-triggered strategies, the threshold parameter in the developed dynamical event-triggering condition is dynamically adjusted according to a dynamic rule. Based on the DETM, a distributed consensus control protocol is designed under fading channels. Then, sufficient criteria are provided to ensure that MASs can achieve the leaser-following consensus, and satisfy the H∞ performance index in the presence of fading channels. The desired controller parameters can be derived in terms of solutions of matrix inequalities that are lightly solvable. In the end, simulation results show that the designed dynamical event transmission policy is capable of diminishing communication burden more promptly and effectively than some existing ones.


Multivariate analysis of ultrasound-recorded dorsal strain sequences: Investigation of dynamic neck extensions in women with chronic whiplash associated disorders.
Whiplash Associated Disorders (WAD) refers to the multifaceted and chronic burden that is common after a whiplash injury. Tools to assist in the diagnosis of WAD and an increased understanding of neck muscle behaviour are needed. We examined the multilayer dorsal neck muscle behaviour in nine women with chronic WAD versus healthy controls during the entire sequence of a dynamic low-loaded neck extension exercise, which was recorded using real-time ultrasound movies with high frame rates. Principal component analysis and orthogonal partial least squares were used to analyse mechanical muscle strain (deformation in elongation and shortening). The WAD group showed more shortening during the neck extension phase in the trapezius muscle and during both the neck extension and the return to neutral phase in the multifidus muscle. For the first time, a novel non-invasive method is presented that is capable of detecting altered dorsal muscle strain in women with WAD during an entire exercise sequence. This method may be a breakthrough for the future diagnosis and treatment of WAD.


Risk Classification with an Adaptive Naive Bayes Kernel Machine Model.
Genetic studies of complex traits have uncovered only a small number of risk markers explaining a small fraction of heritability and adding little improvement to disease risk prediction. Standard single marker methods may lack power in selecting informative markers or estimating effects. Most existing methods also typically do not account for non-linearity. Identifying markers with weak signals and estimating their joint effects among many non-informative markers remains challenging. One potential approach is to group markers based on biological knowledge such as gene structure. If markers in a group tend to have similar effects, proper usage of the group structure could improve power and efficiency in estimation. We propose a two-stage method relating markers to disease risk by taking advantage of known gene-set structures. Imposing a naive bayes kernel machine (KM) model, we estimate gene-set specific risk models that relate each gene-set to the outcome in stage I. The KM framework efficiently models potentially non-linear effects of predictors without requiring explicit specification of functional forms. In stage II, we aggregate information across gene-sets via a regularization procedure. Estimation and computational efficiency is further improved with kernel principle component analysis. Asymptotic results for model estimation and gene set selection are derived and numerical studies suggest that the proposed procedure could outperform existing procedures for constructing genetic risk models.


Physical model of the immune response of bacteria against bacteriophage through the adaptive CRISPR-Cas immune system.
Bacteria and archaea have evolved an adaptive, heritable immune system that recognizes and protects against viruses or plasmids. This system, known as the CRISPR-Cas system, allows the host to recognize and incorporate short foreign DNA or RNA sequences, called 'spacers' into its CRISPR system. Spacers in the CRISPR system provide a record of the history of bacteria and phage coevolution. We use a physical model to study the dynamics of this coevolution as it evolves stochastically over time. We focus on the impact of mutation and recombination on bacteria and phage evolution and evasion. We discuss the effect of different spacer deletion mechanisms on the coevolutionary dynamics. We make predictions about bacteria and phage population growth, spacer diversity within the CRISPR locus, and spacer protection against the phage population.


The Community College Effect Revisited: The Importance of Attending to Heterogeneity and Complex Counterfactuals.
Community colleges are controversial educational institutions, often said to simultaneously expand college opportunities and diminish baccalaureate attainment. We assess the seemingly contradictory functions of community colleges by attending to effect heterogeneity and to alternative counterfactual conditions. Using data on postsecondary outcomes of high school graduates of Chicago Public Schools, we find that enrolling at a community college penalizes more advantaged students who otherwise would have attended four-year colleges, particularly highly selective schools; however, these students represent a relatively small portion of the community college population, and these estimates are almost certainly biased. On the other hand, enrolling at a community college has a modest positive effect on bachelor's degree completion for disadvantaged students who otherwise would not have attended college; these students represent the majority of community college goers. We conclude that discussions among scholars, policymakers, and practitioners should move beyond considering the pros and cons of community college attendance for students in general to attending to the implications of community college attendance for targeted groups of students.


Giant prostatic hyperplasia: report of a previously asymptomatic man presenting with gross hematuria and hypovolemic shock.
Giant prostatic hyperplasia is a rare condition characterized by very high volume benign prostatic enlargement (>500g). Few cases have been reported so far and most of them are associated with severe lower urinary symptoms. We report the first case of asymptomatic giant prostatic hyperplasia in an elderly man who had a 720g prostate adenoma, sudden gross hematuria and hypovolemic shock. The patient was successfully treated with open transvesical prostatectomy and had an uneventful postoperative recovery.


The effects of display size on performance.
We examined the systematic effects of display size on task performance as derived from a standard perceptual and cognitive test battery. Specifically, three experiments examined the influence of varying viewing conditions on response speed, response accuracy and subjective workload at four differing screen sizes under three different levels of time pressure. Results indicated a ubiquitous effect for time pressure on all facets of response while display size effects were contingent upon the nature of the viewing condition. Thus, performance decrement and workload elevation were evident only with the smallest display size under the two most restrictive levels of time pressure. This outcome generates a lower boundary threshold for display screen size for this order of task demand. Extrapolations to the design and implementation of all display sizes and forms of cognitive and psychomotor demand are considered.


Visual Presence: Viewing Geometry Visual Information of UHD S3D Entertainment.
To maximize the presence experienced by humans, visual content has evolved to achieve a higher visual presence in a series of high definition (HD), ultra HD (UHD), 8K UHD, and 8K stereoscopic 3D (S3D). Several studies have introduced visual presence delivered from content when viewing UHD S3D from a content analysis perspective. Nevertheless, no clear definition has been presented for visual presence, and only a subjective evaluation has been relied upon. The main reason for this is that there is a limitation to defining visual presence via the use of content information itself. In this paper, we define the visual presence for each viewing environment, and investigate a novel methodology to measure the experienced visual presence when viewing both 2D and 3D via the definition of a new metric termed volume of visual information by quantifying the influence of the viewing geometry between the display and viewer. To achieve this goal, the viewing geometry and display parameters for both flat and atypical displays are analyzed in terms of human perception by introducing a novel concept of pixel-wise geometry. In addition, perceptual weighting through analysis of content information is performed in accordance with monocular and binocular vision characteristics. In the experimental results, it is shown that the constructed model based on the viewing geometry, content, and perceptual characteristics has a high correlation of about 84% with subjective evaluations.


Preservation of viscoelastic properties of rabbit vocal folds after implantation of hyaluronic Acid-based biomaterials.
To compare the rheological characteristics of structurally different hyaluronic acid (HA)-based biomaterials that are presently used for phonosurgery and to investigate their influence on the viscoelastic properties of vocal folds after implantation in an in vivo rabbit model. In vitro and in vivo rheometric investigation. Experimental laboratory, Inha and Seoul National Universities. Viscoelastic shear properties of 3 HA-based biomaterials (Rofilan, Restylane, and Reviderm) were measured with a strain-controlled rheometer. These biomaterials were injected into the deep layers of rabbit vocal folds, and viscoelastic moduli of the injected vocal folds were determined 2 months after the injection. The vocal fold specimens were observed using a light microscope and a transmission electron microscope. All HA-based biomaterials showed similar levels of shear viscosity, which were slightly higher than that of human vocal folds reported in previous studies. Compared with noninjected control vocal folds, there were no significant differences in the magnitudes of both elastic shear modulus (G') and viscous modulus (G") of injected vocal folds among all of the materials. Light microscopic images showed that all materials were observed in the deep layers of vocal folds and electron scanning images revealed that injected HA particles were homogeneously distributed in regions of collagenous fibers. HA-based biomaterials could preserve the viscoelastic properties of the vocal folds, when they were injected into vocal folds in an in vivo rabbit model. However, further studies on the influence of the biomaterials on the viscoelasticity of human vocal folds in ECM surroundings are still needed.


Recommendations of the International Medical Informatics Association (IMIA) on education in health and medical informatics.
The International Medical Informatics Association (IMIA) agreed on international recommendations in health informatics / medical informatics education. These should help to establish courses, course tracks or even complete programs in this field, to further develop existing educational activities in the various nations and to support international initiatives concerning education in health and medical informatics (HMI), particularly international activities in educating HMI specialists and the sharing of courseware. The IMIA recommendations centre on educational needs for health care professionals to acquire knowledge and skills in information processing and information and communication technology. The educational needs are described as a three-dimensional framework. The dimensions are: 1) professionals in health care (physicians, nurses, HMI professionals, ...), 2) type of specialisation in health and medical informatics (IT users, HMI specialists) and 3) stage of career progression (bachelor, master, ...). Learning outcomes are defined in terms of knowledge and practical skills for health care professionals in their role (a) as IT user and (b) as HMI specialist. Recommendations are given for courses/course tracks in HMI as part of educational programs in medicine, nursing, health care management, dentistry, pharmacy, public health, health record administration, and informatics/computer science as well as for dedicated programs in HMI (with bachelor, master or doctor degree). To support education in HMI, IMIA offers to award a certificate for high quality HMI education and supports information exchange on programs and courses in HMI through a WWW server of its Working Group on Health and Medical Informatics Education (http://www.imia.org/wg1).


Self-Aware SGD: Reliable Incremental Adaptation Framework For Clinical AI Models.
Healthcare is dynamic as demographics, diseases, and therapeutics constantly evolve. This dynamic nature induces inevitable distribution shifts in populations targeted by clinical AI models, often rendering them ineffective. Incremental learning provides an effective method of adapting deployed clinical models to accommodate these contemporary distribution shifts. However, since incremental learning involves modifying a deployed or in-use model, it can be considered unreliable as any adverse modification due to maliciously compromised or incorrectly labelled data can make the model unsuitable for the targeted application. This paper introduces self-aware stochastic gradient descent (SGD), an incremental deep learning algorithm that utilises a contextual bandit-like sanity check to only allow reliable modifications to a model. The contextual bandit analyses incremental gradient updates to isolate and filter unreliable gradients. This behaviour allows self-aware SGD to balance incremental training and integrity of a deployed model. Experimental evaluations on the Oxford University Hospital datasets highlight that self-aware SGD can provide reliable incremental updates for overcoming distribution shifts in challenging conditions induced by label noise.


Reduced {001}-TiO2-x photocatalysts: noble-metal-free CO2 photoreduction for selective CH4 evolution.
The preparation of reduced TiO2 photocatalysts with high Ti3+ concentration is a great challenge due to their instability in air. Here we report a new approach for the synthesis of reduced TiO2 with {001} facets exposed via a hydrothermal process. By the introduction of fluoride atoms, {001} and {101} facets are formed, which act as hole and electron collectors, respectively, for charge separation. By adjusting the volume of HF added, a rutile-anatase transition is observed for the first time. EPR spectra confirm the generation of Ti3+ species in the bulk of TiO2, and Ti3+ signals are studied in the anatase and rutile phases separately. The quantified EPR shows that reduced TiO2 samples present 14 000-fold more spins compared to the pristine TiO2, and the intensity can reach as high as 24.6 × 1019 spins per g. The obtained samples also have a unique disordered layer with a thickness of 1-2 nm on their surfaces, which contributes to the stabilization of the formed Ti3+ species by preventing their oxidation in air. In addition, the synthesized reduced TiO2 samples also exhibit wide-spectrum solar light absorption, especially in the near-infrared region. Owing to their enhanced solar light absorption, improved electron-hole separation and special facet exposure, these samples exhibit enhanced photocatalytic CO2 reduction performance and high CH4 selectivity under solar light irradiation, in the absence of a noble metal Pt as a co-catalyst.


Study protocol for a pilot study to explore the determinants of knowledge use in a medical education context.
While the science of knowledge translation (KT) has been growing steadily for the past decade in relation to understanding processes and actions which are embedded within clinical practice settings, little is known about how empirical knowledge is used within the medical education system. Despite an increase of research in this domain, we know very little about the contribution of this evidence in the development of medical students into effective physicians. This pilot study aims to: provide a synthesis of the evidence for educational strategies within medical education; explore the perceptions and experiences of faculty in undergraduate (UG) medical education in relation to their use of evidence in their educational practices; and illuminate how medical education evidence is formally integrated into a UG medical curriculum. The study will involve three phases. First, a scoping review of the medical education research literature will be undertaken to generate insight into the evidence available for curriculum development, teaching and assessment activities within this domain. Second, a content analysis of undergraduate courses at the University of Toronto will be undertaken to generate an additional insight into the extent that medical education research has been formally integrated into the UG curriculum for medical students at the University. Finally, a purposeful sample of 30-40 medical education leaders from a single large university, selected as it aims to deliver a rigorous research-oriented medical curriculum, will be interviewed to understand how they use the available evidence in their education practices. This study will lay the grounds to generate initial data into the determinants of knowledge use in a medical education context. In doing so, the findings will also inform the development of a larger, pan-Canadian study at medical schools that will generate a comprehensive account of the processes and challenges related to KT within an educational context. This larger study will also begin to explore the relevance of the Knowledge-to-Action model to a medical education context.


Expression and localization of aquaporin-4 in sensory ganglia.
Aquaporin-4 (AQP4) is a water channel protein that is predominantly expressed in astrocytes in the CNS. The rapid water flux through AQP4 may contribute to electrolyte/water homeostasis and may support neuronal activities in the CNS. On the other hand, little is known about the expression of AQP4 in the peripheral nervous system (PNS). Using AQP4(-/-) mice as a negative control, we demonstrated that AQP4 is also expressed in sensory ganglia, such as trigeminal ganglia and dorsal root ganglia in the PNS. Immunohistochemistry revealed that AQP4 is exclusively localized to satellite glial cells (SGCs) surrounding the cell bodies of the primary afferent sensory neurons in the sensory ganglia. Biochemical analyses revealed that the expression levels of AQP4 in sensory ganglia were considerably lower than those in astrocytes in the CNS. Consistently, behavioral analyses did not show any significant difference in terms of mechanical and cold sensitivity between wild type and AQP4(-/-) mice. Overall, although the pathophysiological relevance of AQP4 in somatosensory perception remains unclear, our findings provide new insight into the involvement of water homeostasis in the peripheral sensory system.