Towards autonomous neuroprosthetic control using Hebbian reinforcement learning.
Our goal was to design an adaptive neuroprosthetic controller that could learn the mapping from neural states to prosthetic actions and automatically adjust adaptation using only a binary evaluative feedback as a measure of desirability/undesirability of performance. Hebbian reinforcement learning (HRL) in a connectionist network was used for the design of the adaptive controller. The method combines the efficiency of supervised learning with the generality of reinforcement learning. The convergence properties of this approach were studied using both closed-loop control simulations and open-loop simulations that used primate neural data from robot-assisted reaching tasks. The HRL controller was able to perform classification and regression tasks using its episodic and sequential learning modes, respectively. In our experiments, the HRL controller quickly achieved convergence to an effective control policy, followed by robust performance. The controller also automatically stopped adapting the parameters after converging to a satisfactory control policy. Additionally, when the input neural vector was reorganized, the controller resumed adaptation to maintain performance. By estimating an evaluative feedback directly from the user, the HRL control algorithm may provide an efficient method for autonomous adaptation of neuroprosthetic systems. This method may enable the user to teach the controller the desired behavior using only a simple feedback signal.


Echocardiographic ventricular shape analysis in congenital heart disease with right ventricular volume or pressure overload.
In this 2-dimensional (2-D) echocardiographic study, a computerized Fourier analysis technique refined from one that allows quantification of changes in septal shapes in normal fetuses, newborns and infants allowed analysis of left ventricular (LV) shapes in 14 patients with right ventricular (RV) volume overload (atrial septal defects), 5 with volume and pressure overload (total anomalous pulmonary venous connection), and 10 with pressure overload (complete transposition of the great arteries [TGA] with intact ventricular septum). Diastolic shape factors in the 3 groups were significantly different from those of normal subjects (p less than 0.01). Highest diastolic values were found in patients with TGA (mean 4.59 +/- 1.28). Systolic shape factors were similar in patients with atrial septal defect and normal subjects. Significant differences existed between normal subjects and patients with total anomalous pulmonary venous connection, with the greatest differences in systolic shape factor being 5.61 for TGA vs 1.87 (p less than 0.005) for normal subjects. Shape factor correlated well with hemodynamic data for RV/LV systolic pressure ratios (r = 0.93, p less than 0.001) for normalized interventricular pressure differences (r = -0.95, p less than 0.001). The lower the normalized systolic pressure difference or the higher the RV/LV ratio, the more the septum encroached into the LV cavity. Significant but weaker correlations were noted for values during diastole. Quantitative application of Fourier shape factor analysis to LV shapes allows numerical expression of visually interpreted distortions over a wide range of geometric alterations.


Salivary mucin MUC5B could be an important component of in vitro pellicles of human saliva: an in situ ellipsometry and atomic force microscopy study.
This paper describes a combined investigation of the salivary and MUC5B films structure and topography in conditions similar to those found in the oral cavity in terms of ionic strength, pH, and protein concentration. AFM and ellipsometry were successfully used to give a detailed picture of the film structure and topography both on hydrophilic and on hydrophobic substrata. Regardless of the substrata, the salivary film can be described as having a two sublayer structure in which an inner dense layer is decorated by large aggregates. However, the shape and height of these larger aggregates largely depend on the type of substrata used. Additionally, we show that the adsorption of MUC5B is controlled by the type of substrata and the MUC5B film topography is similar to that of the larger aggregates present in the salivary films, especially on hydrophobic substrates. Therefore, we conclude that MUC5B is a major component in the salivary film when formed on hydrophobic substrates. Furthermore, we studied how resistant the salivary and MUC5B films are against elutability by buffer rinsing and addition of SDS solution. We conclude that the adsorbed proteins contain fractions with varying binding strengths to the two types of surfaces. Specifically, we have shown that the large MUC5B biomacromolecules on the hydrophobic substrates are especially resistant to both elution with buffer solution and SDS. Therefore, these large mucins can be responsible for the increased resistance of HWS films on hydrophobic substrates and can protect the intraoral surfaces against surface-active components present in oral health care products.


Projection X-ray Imaging: Radiography, Mammography, Fluoroscopy.
Recent advances in digital detector technology for medical radiography and fluoroscopy have resulted in improved workflow efficiency, operational flexibility, image quality, and diagnostic accuracy. This is attributed to the implementation of portable flat-panel x-ray detector devices able to provide real-time readout, processing, and display of medical images. As a result, digital radiography flat-panel detectors are rapidly replacing computed radiography passive detectors for projection imaging exams and image intensifier detectors for dynamic fluoroscopy exams. Advanced exam capabilities now include digital tomosynthesis and dual-energy radiography; the former is based on rapid acquisition of multiple angle-dependent image projections to synthesize tomographic slabs at selectable depths within the patient, and the latter is based on rapid back-to-back acquisition of the same anatomy at low and high x-ray energies to generate separate soft tissue and bone images. In both situations, superimposition of anatomy is reduced or eliminated, with the possibility of enhanced diagnostic confidence. Increased x-ray absorption efficiency and lower electronic noise of digital radiography detectors compared to computed radiography detectors enable equal image quality at lower patient dose; however, because of a disconnect between image appearance and radiation dose, lower patient dose is not always achieved. Education, training, and implementation of standards such as the International Electrotechnical Commission 62494-1 Digital Radiography Exposure Index are needed to ensure image quality at the lowest appropriate radiation dose. The National Council on Radiation Protection and Measurements can contribute to radiation responsibility in medical imaging by providing guidance on use of digital radiography, including recommendations for acquisition protocols and exposure index standards, for development of radiographic exam diagnostic reference levels, and for oversight of retake and reject analysis.


Association between ATP2B1 gene polymorphism and the onset of cerebral infarction.
The aim of this study was to investigate the correlation between adenosine triphosphate (ATP) 2B1 gene polymorphism in cerebral infarction (CI) patients and the onset of CI. A total of 100 CI patients (CI group) and 88 healthy people who received physical examination (Control group) were enrolled as study subjects. Meanwhile, 4 mL of venous blood was extracted from each subject. The single nucleotide polymorphisms of rs19203, rs13412 and rs28313 in the promoter region of adenosine triphosphate (ATP) 2B1 gene were classified via conformation-difference gel electrophoresis. Chi-square was adopted to test whether the frequency of ATP2B1 genotype distribution conformed to genetic equilibrium law. Meanwhile, the correlations between ATP2B1 alleles and gene polymorphism sites and the onset of CI were analyzed. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the level of vascular endothelial growth factor (VEGF) in the serum of CI patients. Furthermore, the correlation of ATP2B1 gene polymorphism with the expression level of VEGF was analyzed. Hardy-Weinberg equilibrium analysis revealed that the polymorphisms of three ATP2B1 gene loci were in accordance with genetic equilibrium distribution (p>0.05). According to the results of genetic correlation analysis, the polymorphisms and alleles of ATP2B1 rs19203 and rs13412 were statistically correlated with the onset of CI (p<0.05). However, the rs28313 polymorphism and alleles were not correlated with the onset of CI (p>0.05). In addition, a statistically significant correlation between the polymorphisms of rs19203 and rs13412 and the expression level of VEGF was found in CI patients (p<0.05). Rs19203 and rs13412 in the promoter region of the ATP2B1 gene are correlated with the onset of CI. However, rs28313 bears no relationship with CI.


MicroRNA-99a and 100 mediated upregulation of FOXA1 in bladder cancer.
Urothelial cell carcinoma of the bladder (UCC) is a common disease often characterized by FGFR3 dysregulation. Whilst upregulation of this oncogene occurs most frequently in low-grade non-invasive tumors, recent data reveal increased FGFR3 expression characterizes a common sub-type of invasive UCC sharing molecular similarities with breast cancer. These similarities include upregulation of the FOXA1 transcription factor and reduced expression of microRNAs-99a/100. We have previously identified direct regulation of FGFR3 by these two microRNAs and now search for further targets. Using a microarray meta-database we find potential FOXA1 regulation by microRNAs-99a/100. We confirm direct targeting of the FOXA1 3'UTR by microRNAs-99a/100 and also potential indirect regulation through microRNA-485-5p/SOX5/JUN-D/FOXL1 and microRNA-486/FOXO1a. In 292 benign and malignant urothelial samples, we find an inverse correlation between the expression of FOXA1 and microRNAs-99a/100 (r=-0.33 to -0.43, p<0.05). As for FGFR3 in UCC, tumors with high FOXA1 expression have lower rates of progression than those with low expression (Log rank p=0.009). Using global gene expression and CpG methylation profiling we find genotypic consequences of FOXA1 upregulation in UCC. Genetic changes are associated with regional hypomethylation, occur near FOXA1 binding sites, and mirror gene expression changes previously reported in FGFR3 mutant-UCC. These include gene silencing through aberrant hypermethylation (e.g. IGFBP3) and affect genes characterizing breast cancer sub-types (e.g. ERBB2). In conclusion, we have identified microRNAs-99a/100 mediate a direct relationship between FGFR3 and FOXA1 and potentially facilitate cross talk between these pathways in UCC.


A Factor-Graph-Based Approach to Vehicle Sideslip Angle Estimation.
Sideslip angle is an important variable for understanding and monitoring vehicle dynamics, but there is currently no inexpensive method for its direct measurement. Therefore, it is typically estimated from proprioceptive sensors onboard using filtering methods from the family of the Kalman filter. As a novel alternative, this work proposes modeling the problem directly as a graphical model (factor graph), which can then be optimized using a variety of methods, such as whole-dataset batch optimization for offline processing or fixed-lag smoothing for on-line operation. Experimental results on real vehicle datasets validate the proposal, demonstrating a good agreement between estimated and actual sideslip angle, showing similar performance to state-of-the-art methods but with a greater potential for future extensions due to the more flexible mathematical framework. An open-source implementation of the proposed framework has been made available online.


Comparison of digital signal processing modules in gamma-ray spectrometry.
Commercial digital signal-processing modules have been tested for their applicability to gamma-ray spectrometry. The tests were based on the same n-type high purity germanium detector. The spectrum quality was studied in terms of energy resolution and peak area versus shaping parameters, using a Eu-152 point source. The stability of a reference peak count rate versus the total count rate was also examined. The reliability of the quantitative results is discussed for their use in measurement at the metrological level.


Subaxial cervical synovial cysts: report of 35 histologically confirmed surgically treated cases and review of the literature.
Retrospective study The authors' aim of the present study is to report their experience with subaxial cervical synovial cysts hoping to provide further insight into these lesions including the presenting symptoms, possible mechanisms of cyst development associated with cervical level, surgical treatments and clinical outcomes. Synovial cysts are relatively common in the lumbar spine and very uncommonly identified in the subaxial cervical spine. Several case reports and a few small series have been reported in the literature over the past four decades. The authors retrospectively reviewed the cases of 35 patients who underwent surgical treatment for histologically confirmed symptomatic subaxial cervical synovial cysts between 1993 and 2009. The presenting symptoms, age, sex, cervical level, operation, complications and outcomes were analyzed in this cohort. Preoperative and postoperative neurologic assessments were done by staff neurologists independent of the operating surgeon. This study was approved by the Mayo Clinic institutional review board. Thirty-five patients underwent surgical treatment for their synovial cysts and follow-up for at least 12 months postoperatively. The mean follow-up time was 49 months (range, 12-134). There were no deaths associated with the surgery. There was one postoperative infection in a patient undergoing a decompressive laminectomy and posterior instrumented fusion. Patient outcomes were assessed using the Modified Rankin Score for 12 patients was 0, 17 patients was 1, 4 patients was 2, and 2 patients was 3. This series of 35 patients with subaxial cervical synovial cysts surgically treated over a period of 17 years illustrates the relative rarity of these lesions. Magnetic resonance imaging is currently the optimal radiographic study to identify these lesions. Surgical resection can be an effective treatment.


[Septal stents--a perspective tamponadeless management of patients after septoplasty].
The article deals with pathophysiology of disturbed nasal breathing, tools of surgical correction of deviated nasal septum, features of the course of wound process. Clinical efficacy of stent fixation of the septum and conventional elastic tamponade was compared in 38 patients who had undergone septoplasty and submucous radiowave disintegration of the lower nasal turbinate bones for deviation of the nasal septum and a neurovegetative form of chronic vasomotor rhinitis. Higher efficacy of intranasal stenting is shown. Tamponadeless management of the patients after surgical interevention on the nasal septum is demonstrated.


[Membrane action of ionic surfactants on yeast cells].
Effect of a number of homologous series of cationic and anionic surfactants on yeast cells was examined. It is found that the cellular proteins extraction degree under the surfactants treatment depends on the agents structure. It is established that the highest extraction efficiency among the bisquaternary ammonium compounds is displayed by the decyl derivatives and among sodium alkyl sulfates--by octyl sulfate. The influence of pH, ionic strength and the agent concentration on the proteins extraction degree was studied. It is concluded that the anionic and cationic compounds act on the yeast plasma membrane by the similar way and all the differences observed are just the quantitative ones. It is suggested that the efficiency of the surfactant action on the cell is limited particularly by the ratio of cell wall pore size to the size of micelles formed by the agent in the solution.


[Influence of complex plant polyphenol preparation Eklikit on process of liver functions recovery after alcohol intoxication].
The comparative study was carried out to estimate hepatoprotective activity of the preparation "Eklikit", that represents the extract from the Shizandra chinensis crests and reference hepatoprpotector "Legalon" under acute alcohol intoxication. It was found that "Eklikit" posseses membrane protective and expressed hepatoprotective activity. "Eklikit" exceeds the reference hepatorpotector, "Legalon", in its ability to increase the oxidized form of NAD+ and reduced glutatione, cholesterol ethers and reduce the time of thiopental sleep. In other cases "Eklikit" was equally effective to "Legalon".


Interplay between the amphipathic polyoxometalate interactions in solution and at solid-liquid interfaces: a toolbox for the technical application.
The far-reaching interplay between the speciation of polyoxometalates (POMs) in the liquid phase and the POM adsorption characteristics on substrate surfaces yet remains to be understood. The significance of this interplay is however paramount because it indicates the degree of technical applicability of solvent-processable POM molecules. Herein, we target this fundamentally important issue, shedding light on the "POM-counterion-solvent" and "POM-counterion-solvent-substrate" processes. We effectively combine the results from small-angle X-ray scattering in solution with surface sensitive scanning tunneling microscopy and X-ray photoelectron spectroscopy measurements and present on this basis a semi-quantitative analysis which provides an excellent correlation between both approaches. The MeCN-solution speciation of a tris(alkoxo)-ligated Wells-Dawson-type polyoxoanion - explored as a representative of commonly negatively charged POM-based inorganic-organic nanostructures - is strikingly connected with the growth of porous two-dimensional molecular layers on highly oriented pyrolytic graphite (HOPG). Low water amounts dramatically transform intermolecular relationships toward hierarchical agglomeration that inhibits the layer formation on HOPG. The obtained findings lay the groundwork for a mechanistic study of controlled nucleation and growth of POM nanostructures on weakly interacting surfaces.


Large-Scale Discovery of Disease-Disease and Disease-Gene Associations.
Data-driven phenotype analyses on Electronic Health Record (EHR) data have recently drawn benefits across many areas of clinical practice, uncovering new links in the medical sciences that can potentially affect the well-being of millions of patients. In this paper, EHR data is used to discover novel relationships between diseases by studying their comorbidities (co-occurrences in patients). A novel embedding model is designed to extract knowledge from disease comorbidities by learning from a large-scale EHR database comprising more than 35 million inpatient cases spanning nearly a decade, revealing significant improvements on disease phenotyping over current computational approaches. In addition, the use of the proposed methodology is extended to discover novel disease-gene associations by including valuable domain knowledge from genome-wide association studies. To evaluate our approach, its effectiveness is compared against a held-out set where, again, it revealed very compelling results. For selected diseases, we further identify candidate gene lists for which disease-gene associations were not studied previously. Thus, our approach provides biomedical researchers with new tools to filter genes of interest, thus, reducing costly lab studies.


[The calcium-binding properties of plasma proteins following the allograft of a cadaveric kidney].
The kinetics of calcium binding to plasma proteins in hypo- and hypercalcaemia, induced in vitro, were studied in 60 patients after renal transplantation. Langmuir and Scatchard analysis revealed the normal binding of calcium to plasma proteins in 10 patients (cooperative mechanism of calcium-protein interaction in hypocalcaemic state and existence of one or several sets of calcium binding independent sites in hypercalcaemic state). Cooperative binding with the decreased values of effective Ka, effective n. molar binding ratio (CaPr/A) and specific buffer capacity (beta sp.) were observed in 1/3 patients. Cooperative mechanism of calcium-proteins interaction has not been observed in more than 1/2 patients and the values of n. CaPr/A, beta sp, decreased in most of the patients. The observed changes may be caused by a proteins metabolism deterioration and may result in deterioration of calcium homeostasis.


Biomedical signal acquisition with streaming wireless communication for recording evoked potentials.
Commercial electrophysiology systems for recording evoked potentials always connect patients to the acquisition unit via long wires. Wires guarantee timely transfer of signals for synchronization with the stimuli, but they are susceptible to electromagnetic and electrostatic interferences. Though wireless solutions are readily available (e.g. Bluetooth), they introduce high delay variability that will distort the evoked potential traces. We developed a complete wireless acquisition system with a fixed delay. The system supports up to 4 bipolar channels; each is amplified by 20,000× and digitized to 24 bits. The system incorporates the "driven-right-leg" circuit to lower the common noise. Data are continuously streamed using radio-frequency transmission operating at 915 MHz and then tagged with the stimulus SYNC signal at the receiver. The delay, noise level and transmission error rate were measured. Flash visual evoked potentials were recorded monocularly from both eyes of six adults with normal vision. The signals were acquired via wireless and wired transmissions simultaneously. The recording was repeated on some participants within 2 weeks. The delay was constant at 20 ms. The system noise was white and Gaussian (2 microvolts RMS). The transmission error rate was about one per million packets. The VEPs recorded with wireless transmission were consistent with those with wired transmission. The VEP amplitudes and shapes showed good intra-session and inter-session reproducibility and were consistent across eyes. The wireless acquisition system can reliably record visual evoked potentials. It has a constant delay of 20 ms and very low error rate.


Diagnostic value of VEGF in peri-implantitis and its correlation with titanium particles: A controlled clinical study.
VEGF is prototypic marker of neovascularization, repeatedly proposed as intrinsic characteristic of peri-implantitis. This study aimed to assess pattern of VEGF in peri-implantitis, its correlation with titanium particles (TPs) and capacity as respective biomarker. Pathological specificity of VEGF was assessed in peri-implant granulations using immunohistochemistry, periodontal granulations represented Ti-free positive controls. VEGF was correlated to TPs, identified using scanning electron microscopy coupled with dispersive x-ray spectrometry. Diagnostic accuracy, sensitivity and specificity of VEGF were estimated in PICF specimens from peri-implantitis, peri-implant mucositis (PIM) and healthy peri-implant tissues (HI) using machine learning algorithms. Peri-implantitis exhibited rich neovascular network with expressed density in contact zones toward neutrophil infiltrates without specific pattern variations around TPs, identified in all peri-implantitis specimens (mean particle size 8.9 ± 24.8 µm2; Ti-mass (%) 0.380 ± 0.163). VEGF was significantly more expressed in peri-implantitis (47,065 ± 24.2) compared to periodontitis (31,14 ± 9.15), and positively correlated with its soluble concentrations in PICF (p = 0.01). VEGF was positively correlated to all clinical endpoints and significantly increased in peri-implantitis compared to both PIM and HI, but despite high specificity (96%), its overall diagnostic capacity was average. Two patient clusters were identified in peri-implantitis, one with 8-fold higher VEGF values compared to HI, and second with lower values comparable to PIM. VEGF accurately reflects neovascularization in peri-implantitis that was expressed in contact zones toward implant surface without specific histopathological patter variation around TPs. VEGF answered requests for biomarker of peri-implantitis but further research is necessary to decrypt its exact underlying cause.


Frasier syndrome, part of the Denys Drash continuum or simply a WT1 gene associated disorder of intersex and nephropathy?
Dysfunction of the Wilms' Tumour gene (WT1), a transcription factor critical for normal development and function of the urogenital tract, can result in both tumourigenesis [corrected] and urogenital abnormalities. The association of WT1 gene mutations with most cases of Denys-Drash syndrome is well described. More recently WT1 mutations have also been described in a related condition, Frasier syndrome. We report a case where genetic analysis showed a WT1 mutation typically associated with Frasier syndrome: a 1228 + 5 guanine to adenine substitution at the 3' alternative splice donor site in intron 9. The case provides a focus for the discussion of recent evidence that Denys Drash and Frasier syndrome form two ends of a spectrum of disorders. In addition, it illustrates the increasing significance of genetic investigation within clinical practice for diagnostic, prognostic and therapeutic purposes and the importance of karyotype analysis in phenotypically normal girls with renal disease.


A minimized rRNA-binding site for ribosomal protein S4 and its implications for 30S assembly.
Primary ribosomal protein S4 is essential for 30S ribosome biogenesis in eubacteria, because it nucleates subunit assembly and helps coordinate assembly with the synthesis of its rRNA and protein components. S4 binds a five-helix junction (5WJ) that bridges the 5' and 3' ends of the 16S 5' domain. To delineate which nucleotides contribute to S4 recognition, sequential deletions of the 16S 5' domain were tested in competitive S4-binding assays based on electrophoretic mobility shifts. S4 binds the minimal 5WJ RNA containing just the five-helix junction as well or better than with affinity comparable to or better than the 5' domain or native 16S rRNA. Internal deletions and point mutations demonstrated that helices 3, 4, 16 and residues at the helix junctions are necessary for S4 binding, while the conserved helix 18 pseudoknot is dispensable. Hydroxyl radical footprinting and chemical base modification showed that S4 makes the same interactions with minimal rRNA substrates as with the native 16S rRNA, but the minimal substrates are more pre-organized for binding S4. Together, these results suggest that favorable interactions with S4 offset the energetic penalty for folding the 16S rRNA.


Sexual distractors boost younger and older adults' visual search RSVP performance.
Do sexual words have high attentional priority? How does the ability to ignore sexual distractors evolve with age? To answer these questions, two experiments using Rapid Serial Visual Presentation (RSVP) were conducted. Experiment 1 showed that both younger and older participants were better at identifying a target (the name of a colour) when it was preceded by 336 ms by a sexual word rather than by a musical word. Strikingly, the sexual-word advantage was more pronounced for older adults than for younger adults. Experiment 2 showed that introducing a variable delay between the distractor and the target eliminated the sexual-word advantage. This finding suggests that the sexual-word advantage found in Experiment 1 was due to learning to utilize the sexual word as a temporal cue with a fixed duration between the distractor and the target. Contrary to previous research [Arnell et al., 2007, Emotion, 7, 465), neither experiment showed that sexual words produce an attentional blink.


Vitamin D status of chronic kidney disease patients living in a sunny country.
Vitamin D nutritional status has been poorly investigated in chronic kidney disease (CKD) patients, especially those inhabiting a subtropical area where the sunlight incidence is abundant all year. The purpose of this study was to evaluate the status of vitamin D and to analyze the relationship of circulating 25-hydroxyvitamin D [25(OH)D] with other serum parameters of mineral metabolism in patients with CKD not yet on dialysis. This cross-sectional study enrolled 144 nondiabetic CKD patients not yet receiving dialysis (stages 2 to 5 of CKD). Fasting blood samples were obtained for measurements of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], intact parathyroid hormone, phosphorus, and calcium. In the entire sample, the serum concentration of 25(OH) was 34.3 +/- 18.3 ng/mL (+/-SD unless otherwise noted). A deficiency of vitamin D, i.e., 25(OH)D <15 ng/mL, was found in only one patient. Fifty-seven patients (39.6%) were considered vitamin D-insufficient (16 to 30 ng/mL). The vitamin D-insufficient group contained more females, a higher degree of proteinuria, and a lower serum concentration of 1,25(OH)(2)D. In multiple regression analysis, 25(OH)D was associated positively with 1,25(OH)(2)D, serum calcium, and proteinuria, whereas 1,25(OH)(2)D was associated only with 25(OH)D and phosphorus. The variables associated with intact parathormone were serum phosphorus and creatinine clearance, but not 1,25(OH)(2)D or 25(OH)D. Despite an elevated prevalence of vitamin D insufficiency, the serum concentration of 25(OH)D was, on average, higher than that found in patients inhabiting higher-latitude regions. This higher serum concentration may have contributed to the differences found in the relationship between vitamin D metabolites and other serum markers of mineral metabolism in our CKD patients.


The relationship between alcohol use and risk of breast cancer by histology and hormone receptor status among women 65-79 years of age.
Alcohol consumption is associated with a moderate increase in breast cancer risk, possibly because alcohol increases estrogen levels in blood. Certain types of breast carcinomas are more hormonally responsive than others, including those that have a lobular histology or are hormone receptor positive, but few studies evaluating alcohol use and breast cancer risk have stratified results by histology or estrogen receptor (ER)/progesterone receptor (PR) status. We conducted a population-based case-control study of women 65-79 years of age in western Washington State. Women (975) diagnosed with invasive breast cancer during 1997-1999 were compared with 1007 controls. Ever-use of alcohol over the past 20 years was associated with a 1.3-fold [95% confidence interval (CI), 1.0-1.5] increased risk of breast cancer, although this increase was primarily limited to women who consumed > or =30.0 g/day of alcohol [odds ratio (OR), 1.7; 95% CI, 1.1-2.6]. Differences in risk by histology were observed: ever-use of alcohol was associated with a 1.8-fold (95% CI, 1.3-2.5) increased risk of lobular cancer but only a 1.2-fold (95% CI, 0.9-1.4) increased risk of ductal cancer. Ever-users of alcohol had an increase in risk of ER+/PR+ tumors (OR, 1.3; 95% CI, 1.1-1.7), but no change in their risks of ER+/PR- or ER-/PR- tumors. Alcohol use appears to be more strongly associated with risk of lobular carcinomas and hormone receptor-positive tumors than it is with other types of breast cancer. These results are consistent with there being an underlying hormonal basis for the known association between alcohol use and breast cancer incidence.


Research progress in the treatment of small cell lung cancer.
Small cell lung cancer (SCLC) accounts for approximately 10-15% of all lung cancers. No significant improvement has been made for patients with SCLC in the past several decades. The main progresses were the thoracic radiation and prophylactic cranial irradiation (PCI) that improved the patient survival rate. For patients with limited disease and good performance status (PS), concurrent chemoradiotherapy (CCRT) followed by PCI should be considered. For extensive disease, the combination of etoposide and platinum-based chemotherapy remains the standard treatment and consolidative thoracic radiotherapy is beneficial for patients who have a significant respond to initial chemotherapy. However, the prognosis still remains poor. Recently, efforts have been focused on molecular targets and immunotherapy. But numerous molecular targets methods have failed to show a significant clinical benefit in patients with SCLC. It is anticipated that further development of research will depend on the on-going trials for molecular targeted therapy and immunotherapy which are promising and may improve the outcomes for SCLC in the next decade.


Strong disorder fixed point in absorbing-state phase transitions.
The effect of quenched disorder on nonequilibrium phase transitions in the directed percolation universality class is studied by a strong disorder renormalization group approach and by density matrix renormalization group calculations. We show that for sufficiently strong disorder the critical behavior is controlled by a strong disorder fixed point and in one dimension the critical exponents are conjectured to be exact: beta=(3-sqrt[5])/2 and nu( perpendicular )=2. For disorder strengths outside the attractive region of this fixed point, disorder dependent critical exponents are detected. Existing numerical results in two dimensions can be interpreted within a similar scenario.


Optomagnetic Effect Induced by Magnetized Nanocavity Plasmon.
We propose a new type of optomagnetic effect induced by a highly confined plasmonic field in a nanocavity. It is shown that a very large dynamic magnetic field can be generated as the result of the inhomogeneity of nanocavity plasmons, which can directly activate spin-forbidden transitions in molecules. The dynamic optomagnetic effects on optical transitions between states of different spin multiplicities are illustrated by first-principles calculations for C60. Remarkably, the intensity of spin forbidden singlet-to-triplet transitions can even be stronger than that of singlet-to-singlet transitions when the spatial distribution of plasmon is comparable with the molecular size. This approach not only offers a powerful optomagnetic means to rationally fabricate molecular excited states with different multiplicities but also provides a groundbreaking concept of the light-matter interaction that could lead to the observation of new physical phenomena and the development of new techniques.


Random prospective study cyclophosphamide, doxorubicin, and methotrexate (CAM) combination chemotherapy versus single-agent sequential chemotherapy in non small cell lung cancer.
A group of 104 patients with unresectable non-small cell lung cancer were randomized to receive combination chemotherapy with cyclophosphamide, doxorubicin, and methotrexate (CAM) or single-agent sequential chemotherapy with the same three agents. CAM combination chemotherapy produced a 22% objective response rate, including two complete remissions, compared to a 9% response rate, including one complete remission, produced by single-agent therapy (P = 0.16). The median survival time was 32 weeks (range, 3-116) for CAM, compared to 25 weeks (range, 4-179 +) for sequential single agents (P = 0.24). Overall survival was 31% (1-year), (16%) (1 1/2-year), and 5% (2-year), with no difference between the study arms. Although there was no statistically significant survival advantage for the CAM arm, both arms had survival superior to that in historical controls, presumably because of better patient selection. This study indicates that cyclophosphamide, doxorubicin, and methotrexate are, at best, marginally active as single agents, and new drugs with more efficacy are needed before combination chemotherapy can be expected to result in any meaningful prolongation of survival in non-small cell lung cancer.


In vitro evaluation of sun protection factors of sunscreen agents using a novel UV spectrophotometric technique.
A method for the in vitro determination of low- and high-value sun protection factors (SPF) of sunscreens using artificial substrates and a novel pseudo double beam (PDB) mode of operation of a standard double beam UV spectrophotometer is described. The method allows transmittance to be calculated from detector responses of reference and sample beams measured at different gain levels and facilitates the accurate quantification of low levels of electromagnetic radiation transmitted through highly absorbing samples. The spectrophotometer was modified to hold quartz diffusing plates on which a substrate [Transpore adhesive tape or human stratum corneum obtained from a skin surface biopsy (SSB)] and the sunscreens to be tested were applied. The PDB mode of operation increased the effective linear range of the detector response of the spectrophotometer by a factor of approximately 20000-fold, enabling the in vitro SPF determination technique to be applied to both high and low SPF value sunscreens. Eight commercial sunscreens with known SPF values ranging from 4 to 77, previously determined by in vivo methods, were tested in vitro using both test substrates and correlations between the in vivo and in vitro values were determined. SPF values determined using the in vitro method correlated well with the known in vivo results (Transpore tape, R(2) = 0.611; SSB, R(2) = 0.7928). The in vitro SPF obtained for one of the tested products differed substantially from the cited in vivo SPF value. Independent in vitro and in vivo re-evaluation of the SPF of this product matched the value predicted by the present method much more closely than the originally cited in vivo value. All determined SPFs were ordered correctly in comparison to in vivo ranking and the technique appeared to correctly identify a sunscreen that had a labelled SPF value that was significantly higher than its true SPF.


The burden of seasonal respiratory infections on a national telehealth service in England.
Seasonal respiratory illnesses present a major burden on primary care services. We assessed the burden of respiratory illness on a national telehealth system in England and investigated the potential for providing early warning of respiratory infection. We compared weekly laboratory reports for respiratory pathogens with telehealth calls (NHS 111) between week 40 in 2013 and week 29 in 2015. Multiple linear regression was used to identify which pathogens had a significant association with respiratory calls. Children aged <5 and 5-14 years, and adults over 65 years were modelled separately as were time lags of up to 4 weeks between calls and laboratory specimen dates. Associations with respiratory pathogens explained over 83% of the variation in cold/flu, cough and difficulty breathing calls. Based on the first two seasons available, the greatest burden was associated with respiratory syncytial virus (RSV) and influenza, with associations found in all age bands. The most sensitive signal for influenza was calls for 'cold/flu', whilst for RSV it was calls for cough. The best-fitting models showed calls increasing a week before laboratory specimen dates. Daily surveillance of these calls can provide early warning of seasonal rises in influenza and RSV, contributing to the national respiratory surveillance programme.


'I'm calling in regard to my son': Entitlement, obligation, and opportunity to seek help for others.
From mundane acts like lending a hand to high-stakes incidents like calling an ambulance, help is a ubiquitous part of the human experience. Social relations shape who we help and how. This paper presents a discursive psychology study of an understudied form of help - seeking help for others. Drawing on a corpus of recorded calls to a victim support helpline, I analysed how social relations were demonstrably relevant when callers sought help for others. I used membership categorization analysis and sequential conversation analysis to document how participants used categories to build and interpret requests for help on behalf of others. Categorical relationships between help-seekers, help-recipients, and potential help-providers were consequential in determining whether callers' requests were justified and if help could be provided. The findings show that different categorical relationships configured seeking help for others as a matter of entitlement, obligation, or opportunity. Analysing the categories participants use in naturally occurring social interaction provides an emic perspective on seeking help for others. This kind of help-seeking offers a fruitful area for discursive psychology to develop new conceptualizations of help and social relations.


Venous thromboembolic events in patients with brain metastases: the PICOS score.
Venous thromboembolic events (VTEs) are significant complications in patients with systemic malignancies. Thrombosis risk is poorly defined for patients with brain metastasis, and available risk calculation scores are not validated for these patients. We identified 811 patients with brain metastasis followed at our institution and reviewed electronic charts retrospectively for the occurrence of VTEs, along with candidate risk factors. Risk factors were tested in univariate and multivariate analyses and finally integrated in a score model for risk estimation. An independent cohort of 346 patients with brain metastasis was available for validation. VTEs were documented in 97 of 811 patients (12.0%). Primary tumours with high thrombogenicity (p = 0.02, hazard ratio 1.7, 95% confidence interval (CI) = 1.1-2.8), dexamethasone (p = 0.011, hazard ratio 2.27, 95% CI = 1.5-4.5), chemotherapy (p = 0.005, hazard ratio 3.4, 95% CI = 1.6-7.5), body mass index > 35 kg/m2 (p = 0.002, hazard ratio 3.4, 95% CI = 1.6-7.5) and immobilisation (p = 0.003, hazard ratio 2.4, 95% CI = 1.3-4.3) were confirmed to be independently associated with VTEs. We derived a score model for VTE risk estimation, the thrombogenic primary, immobilization, chemotherapy, obesity, steroid (PICOS) score (0-7 points). Receiver-operating characteristic curve analysis demonstrated its prognostic accuracy (area under the curve [AUC] = 0.71, 95% CI = 0.64-0.77), and its value for the evaluation of VTE risk was superior to that of other scores such as the Khorana (AUC = 0.51) or CONKO (AUC = 0.52) scores. The potential value of the PICOS score was confirmed in the validation cohort (AUC = 0.72, 95% CI = 0.63-0.82). The PICOS score may become a helpful tool for the identification of patients with brain metastasis at high risk for VTEs and for stratification in controlled studies.


Polymer gel dosimetry using x-ray computed tomography: a feasibility study.
A new three-dimensional dosimetry technique using x-ray computed tomography (CT) to analyse polymer gels is proposed. The CT imaging is sensitive to radiation-induced density changes that occur within irradiated polyacrylamide gel (PAG). In this preliminary study, a CT imaging protocol is developed to optimize CT images of PAG; the response of PAG CT number to dose (N(CT)-dose response) and the reproducibility of the response are investigated, and the use of CT to analyse PAG is compared with MRI. Experiments were conducted using two 1.5 l cylindrical PAG phantoms (3% acrylamide, 3% bis and 5% gelatin by weight), one irradiated with four intersecting 10 MV photon beams and the other with 10 sets of 6 MV parallel opposed circular radiosurgery fields. The final imaging protocol involves using optimum CT parameters (120 kVp and 200 mAs for our GE HiSpeed CT/i scanner), image averaging and background subtraction. The N(CT)-dose response is reproducible, linear up to 800-1000 cGy and is relatively insensitive to the gel temperature during imaging. The dose resolution is approximately 50 cGy for an image thickness of 10 mm. Despite the low dose resolution, preliminary results indicate that this CT technique provides accurate localization of high dose gradients such as those observed in stereotactic radiosurgery. Thus, given the availability and speed of CT scanners, the technique has the potential to be a valuable and practical 3D dose verification tool in radiation therapy.


Compressive sensing of full wave field data for structural health monitoring applications.
Numerous nondestructive evaluations and structural health monitoring approaches based on guide waves rely on analysis of wave fields recorded through scanning laser Doppler vibrometers (SLDVs) or ultrasonic scanners. The informative content which can be extracted from these inspections is relevant; however, the acquisition process is generally time-consuming, posing a limit in the applicability of such approaches. To reduce the acquisition time, we use a random sampling scheme based on compressive sensing (CS) to minimize the number of points at which the field is measured. The CS reconstruction performance is mostly influenced by the choice of a proper decomposition basis to exploit the sparsity of the acquired signal. Here, different bases have been tested to recover the guided waves wave field acquired on both an aluminum and a composite plate. Experimental results show that the proposed approach allows a reduction of the measurement locations required for accurate signal recovery to less than 34% of the original sampling grid.


New thermooptical measurement method and a comparison with other methods.
A simple and sensitive method of measuring the thermally induced index changes arising from absorption of a laser beam in a low-loss material is described. The sample is placed outside the laser cavity, but at the position of minimum radius of curvature of the wavefront, which is a confocal distance behind the waist. It is estimated that the method is sensitive enough to measure absorption coefficients of the order of 5 x 10(_6) cm(_1) and it is shown experimentally to have good accuracy on low-loss materials. A detailed comparison of sensitivity and accuracy estimates is given for the various published thermal-lens methods for measuring low absorption coefficients.Although the method is illustrated for the thermal effect, it is applicable to other nonlinear index changes induced by laser beams.


Structurally Diverse Alkaloids from the Seeds of Peganum harmala.
Investigation of the alkaloids from Peganum harmala seeds yielded two pairs of unique racemic pyrroloindole alkaloids, (±)-peganines A-B (1-2); two rare thiazole derivatives, peganumals A-B (3-4); six new β-carboline alkaloids, pegaharmines F-K (5-10); and 12 known analogues. Their structures, including stereochemistry, were elucidated through spectroscopic analyses, quantum chemistry calculations, and single-crystal X-ray diffraction. Notably, the incorporation of pyrrole and indole moieties in peganines A-B, thiazole fragments in peganumals A-B, and a C-1 α,β-unsaturated ester motif in pegaharmine F (5) are all rare, and their presence in the genus Peganum were demonstrated for the first time. All isolates were tested for antiproliferative activities against the HL-60, PC-3, and SGC-7901 cancer cell lines, and compounds 9, 11, 12, and 13 exhibited moderate cytotoxicity against HL-60 cancer cell lines with IC50 values in the range of 4.36-9.25 μM.


Development of bioactive photocrosslinkable fibrous hydrogels.
Three-dimensional (3D) fibrous hydrogels were fabricated by blending two photoactive polymers, poly(ethylene glycol) diacrylate (PEGDA) and poly(vinyl alcohol) (PVA), and the resulting solution was electrospun. PEGDA is a commonly used hydrogel material for tissue engineering applications since its interaction with cells can be tuned by crosslinking in a variety of bioactive molecules including peptides and proteins. The PVA in these materials aids in fiber formation and stabilizes the fibrous network when hydrated. The average dry fiber diameter in the hydrogels was 1.02 μm and upon swelling, the fiber diameter increased approximately six-fold. Fibers were stable under cell culture conditions for up to 5 days. The adhesive ligand, RGDS, was readily incorporated into the fibrous network via the conjugation of RGDS to PEG-monoacrylate which was then crosslinked with the fibers. The bioactivity of the fibrous hydrogels was compared with peptide-modified PEGDA-based hydrogels. The two hydrogel materials had similar cell adhesion and viability. Cell morphology on the fibrous hydrogels was dendritic showing a more in vivo like representation, as compared to spread cell morphology on the PEGDA gels. The ability to generate 3D fibrous architectures in hydrogel systems opens up new areas of investigation in cell-material interactions and tissue formation.


The effect of midlife physical activity on cognitive function among older adults: AGES--Reykjavik Study.
There are few studies on the long-term associations of physical activity (PA) to cognition. Here, we examine the association of midlife PA to late-life cognitive function and dementia. The sample consisted of a population-based cohort of men and women (born in 1907-1935) participating in the Age Gene/Environment Susceptibility-Reykjavik Study. The interval between the midlife ascertainment of PA and late-life cognitive function was 26 years. Composite scores of speed of processing, memory, and executive function were assessed with a battery of neuropsychological tests, and dementia was diagnosed according to international guidelines. There were 4,761 nondemented participants and 184 (3.7%) with a diagnosis of dementia, with complete data for the analysis. Among the participants, no midlife PA was reported by 68.8%, ≤ 5 hours PA by 26.5%, and >5 hours PA by 4.5%. Excluding participants with dementia compared with the no PA group, both PA groups had significantly faster speed of processing (≤ 5 hours, β = .22; >5 hours, β = .32, p trend < .0001), better memory (≤ 5 hours, β = .15; >5 hours, β = .18, p trend < .0001), and executive function (≤ 5 hours, β = .09; >5 hours, β = .18, p trend< .0001), after controlling for demographic and cardiovascular factors. The ≤ 5 hours PA group was significantly less likely to have dementia in late life (odds ratio: 0.6, 95% confidence interval: 0.40-0.88) after adjusting for confounders. Midlife PA may contribute to maintenance of cognitive function and may reduce or delay the risk of late-life dementia.


Financial appraisal of wet mesophilic AD technology as a renewable energy and waste management technology.
Anaerobic digestion (AD) has the potential to support diversion of organic waste from landfill and increase renewable energy production. However, diffusion of this technology has been uneven, with countries such as Germany and Sweden taking the lead, but limited diffusion in other countries such as the UK. In this context, this study explores the financial viability of AD in the UK to offer reasons why it has not been more widely used. This paper presents a model that calculates the Internal Rate of Return (IRR) on a twenty year investment in a 30,000 tonnes per annum wet mesophilic AD plant in the UK for the treatment of source separated organic waste, which is judged to be a suitable technology for the UK climate. The model evaluates the financial significance of the different alternative energy outputs from this AD plant and the resulting economic subsidies paid for renewable energy. Results show that renewable electricity and renewable heat sales supported by renewable electricity and renewable heat tariffs generates the greatest IRR (31.26%). All other uses of biogas generate an IRR in excess of 15%, and are judged to be a financially viable investment. Sensitivity analysis highlights the financial significance of: economic incentive payments and a waste management gate fee; and demonstrates that the fate of the digestate by-product is a source of financial uncertainty for AD investors.


Why and how to quantify minimal residual disease in acute lymphoblastic leukemia?
Several studies have demonstrated that monitoring of minimal residual disease (MRD) in childhood and adult acute lymphoblastic leukemia (ALL) significantly correlates with clinical outcome. MRD detection is particularly useful for evaluation of early treatment response and consequently for improved front-line therapy stratification. MRD information is also significant for children undergoing allogeneic hematopoietic stem cell transplantation and those with relapsed ALL. Currently, three highly specific and sensitive methodologies for MRD detection are available, namely multiparameter flow cytometric immunophenotyping, real-time quantitative polymerase chain reaction (RQ-PCR)-based detection of fusion gene transcripts or breakpoints, and RQ-PCR-based detection of clonal immunoglobulin and T-cell receptor gene rearrangements. In this review, characteristics, pitfalls, advantages and disadvantages of each MRD technique are critically discussed. The special emphasis is put on interlaboratory standardization, especially in view of the results obtained within the European collaborative BIOMED-1, BIOMED-2, and Europe Against Cancer projects and recent developments by European Study Group on MRD detection in ALL and EuroFlow Consortium. Standardized MRD techniques form the basis for stratification of patients into the risk groups in new treatment protocols mainly in childhood ALL. Only the results of these studies can answer the question whether MRD-based treatment intervention is associated with improved outcome.


Can Routine Histopathology Distinguish Between Vulvar Cutaneous Candidosis and Dermatophytosis?
This study aimed to determine if vulvar cutaneous candidosis and dermatophytosis can be distinguished by routine histopathology. Twenty-four cases of periodic acid-Schiff-stained vulvar biopsies with a diagnosis of cutaneous mycosis were reviewed and histopathological characteristics on both periodic acid-Schiff and hematoxylin and eosin were recorded. Data were collected on age, clinical impression, microbiological results, and treatment, and all specimens underwent multiplex polymerase chain reaction analysis. The mean age was 60 years, and all but 3 women had at least 1 risk factor for mycosis including 15 (62.5%) with lichen sclerosus and/or planus managed with topical corticosteroids. A clinical suspicion of tinea or candidosis was documented in 12 (50%) of the cases. Vulvovaginal swabs showed Candida species in 9 women; one skin scraping was positive for Trichophyton rubrum. Microbiology was not obtained in 8 patients, 5 had a negative swab, and 1 had negative skin scrapings. No histopathological or morphological features distinguished Candida species from dermatophytes. Organisms appeared as basophilic structures in the stratum corneum in 15 (62.5%) hematoxylin and eosin-stained slides. Polymerase chain reaction results were positive for Candida species in 5 (21%) and for dermatophytes in 3 (13%), negative in 13, and unassessable in 3 cases. Vulvar cutaneous candidosis and dermatophytosis cannot be reliably distinguished by routine histopathology or specific polymerase chain reaction. A high index of suspicion combined with adequate microbiological testing remains the best approach to differentiating between the 2, which impacts on counseling, treatment, and prognosis.


[Use of laser scalpel in the surgical treatment of injuries of the liver].
An analysis of the 10-years clinical use of CO2-laser scalpel in surgery of traumas of the liver in 41 patients was performed. In 55 patients wounds of the liver were treated by the routine surgical method. Laser coagulation is especially effective for treatment of great area flat wounds. A pronounced hemo- and cholestatic effect of the defocused laser radiation was noted which allowed 3, 5 times more often performing the radical treatment of wounds of the liver. Lethality was reduced from 31% to 24%.


Xnr3 affects brain patterning via cell migration in the neural-epidermal tissue boundary during early Xenopus embryogenesis.
Neural induction and anteroposterior neural patterning occur simultaneously during Xenopus gastrulation by the inhibition of BMP and Wnt signaling, respectively. However, other processes might be necessary for determining the neural-epidermal boundary. Xenopus nodal-related-3 (Xnr3) is expressed in dorsal blastula and plays a role in neural formation. In this study, we analyzed how Xnr3 affects neural patterning to identify novel mechanisms of neural-epidermal-boundary determination. In situ hybridization revealed that ventro-animal injection with Xnr3 shifted the lateral krox20 expression domain anteriorly and reduced Otx2 expression. The mature region of Xnr3 is necessary for these effects to occur, and the pro-region accelerated them. Phalloidin labeling revealed that cells around the neural-epidermal boundary lost their slender shape following Xnr3 injection. Moreover, we analyzed the cell migration of ectodermal cells and found specific Xnr3-induced effects at the neural-epidermal boundary. These findings together suggested that Xnr3 affects anterior ectoderm migration around the neural-epidermal boundary to induce a specific neural pattern abnormality. Change of the shape of surrounding ectodermal cells and the specific migratory pattern might therefore reflect the novel mechanism of neural-epidermal boundary.


[Radiation therapy of malignant neoplasms of the middle ear after nonradical surgical interventions].
The paper is concerned with the short- and long-term results of gamma-beam therapy and chemo- and radiotherapy in 109 patients with malignant middle ear tumors after nonradical surgical interventions. A single focal dose was 2-2.5 Gy, a summary dose varied within 60-80 Gy with relation to the degree of dissemination, growth type and tumor histological structure. A 3-year survival rate was 41.1%, a 5-year survival rate was 21%.


Cats and dogs: two neglected species in this era of embryo production in vitro?
During the last decades, in vitro fertilization (IVF) has become a routine technique in most domestic animals. However, in the dog the technique has lagged behind, with to date not a single pup born after IVF. In cats, healthy kittens have been born, but in fewer numbers than in cattle and horses. In pet animals, research in reproduction has mainly been focused on contraception, although recently, the introduction of new drugs especially marketed for cats and dogs will probably expand fertility research in carnivores towards the previously neglected area of assisted reproduction. In particular, the dog remains a real challenge for the reproductive biologist, due to the low meiotic capacity of canine follicular oocytes. In cats, oocyte maturation is less of a problem and embryo production rates comparable to those of cattle can be achieved. The domestic cat is a valuable model for endangered felids and it can even be used as a recipient for wild felid embryos. In this short review, we list some of the problems associated with the implementation of IVF in dogs and cats in relation to their reproductive characteristics, and we discuss the state-of-the-art of IVF in several other domestic species such as cattle, horses and pigs.


Prevalence and associated factors of moderate to severe erectile dysfunction among adult men in Malaysia.
Erectile dysfunction (ED) is a pervasive problem among men, often shrouded in silence and stigma. This manuscript analysed the National Health and Morbidity Survey 2019 data to identify the prevalence of moderate to severe ED among men aged 18 and above in Malaysia and describe its associated factors. Self-administered questionnaire on ED utilised a locally validated International Index of Erectile Function. Variables on sociodemographics, risky lifestyles and comorbidities were obtained via an interviewer-administered questionnaire. The prevalence was determined using complex sampling analysis, and logistic regression was used to determine the associated factors of ED. A sample of 2403 men aged ≥ 18 participated, with a moderate to severe ED prevalence was 31.6% (95% CI 28.8, 34.6). The mean (± SD) of the total score of IIEF-5 for overall respondents was 18.16 (± 4.13). Multiple logistic regression analysis revealed a significant association between moderate to severe ED among men aged 60 years and above, single or divorcee, men without formal, primary, and secondary education, non-government employees, unemployed, and retiree, as well as physically inactive men. Focused public health interventions are necessary to improve education in sexual health, increase health promotion programs, and promote healthy ageing across the population.


Gluteal-sparing approach for posterior iliac crest bone graft: description of a new technique and assessment of morbidity in ninety-two patients after spinal fusion.
Retrospective clinical series. Description of alternative technique for the harvesting of posterior iliac crest bone graft (ICBG) and assessment of associated morbidity. Although posterior ICBG operations are common, they are often reported to result in significant morbidity. A recent emphasis on the morbidity of ICBG has helped to fuel the costly growth in clinical use of alternatives, such as bone morphogenetic protein-2. Many studies have reported a variety of complications related to iliac crest donor sites, but the most common reported morbidity is pain and/or decreased sensation over the ICBG site. This study is a retrospective review of all patients in the practice of the senior author (T.F.A.) during the study period who received a lumbar fusion with autogenous bone harvested from the posterior iliac crest and accessed by the surgical approach described. Outcomes were assessed by a pain questionnaire determining the site of pain and its magnitude on visual analog scale. Pain on the harvested side was compared with that on the contralateral side, and overall procedure satisfaction was assessed. Statistical analysis was performed using analysis of variance, the Pearson chi2 test, and the Student t test. Any value of P < 0.05 was considered significant. Of 120 patients eligible for the study, 92 patients (77%) were available for follow-up. The patients were interviewed on an average of 24 months (+/-14 months) after their operation. The vast majority of patients (88%, n = 81) had no significant difference in pain or had less pain over the ICBG site than the contralateral side. Eleven patients (12%) experienced significantly greater pain at the ICBG site than over the contralateral side (visual analog scale difference >1). There were 7 patients (8%) in the series with significantly greater pain over the contralateral iliac crest than at the ICBG site. The likelihood of significant pain over the harvested ICBG site was not statistically greater than the likelihood of contralateral iliac crest pain (P = 0.23). One patient (1%) had sensory loss in the superior cluneal nerve distribution. There was 1 patient with an infection that involved the ICBG site and required irrigation and debridement and intravenous antibiotics. Seventy-two patients (78%) stated that they were very satisfied with the operation, 13 (14%) were somewhat satisfied, and 7 (8%) were not satisfied. Although it is difficult to directly compare our results to those reported in other studies, we conclude that the rate of significant chronic sequelae related to this method of harvesting bone from the posterior iliac crest is low. Our findings may be due to the avoidance in this technique of disruption of the gluteal musculature and preservation of the lateral wall of the ilium. The methods used in other studies to estimate the prevalence of chronic pain related to posterior iliac crest bone grafting after lumbar spinal surgery may grossly overestimate this prevalence.


[Asynchronism and right ventricular pacing].
In patients with congenital heart block (CHB), dual-chamber pacing restores physiological heart rate and atrio-ventricular synchronization. However, patients with narrow QRS junctional escape rhythm may be deleteriously affected by long-term, permanent, apical ventricular pacing. We assessed the impact of apical ventricular pacing on echocardiographic ventricular dyssynchrony and hemodynamic parameters. Fourteen CHB adults (23 +/- years, 58% male), with a DDD transvenous pacemaker and a junctional escape rhythm (QRS<120 ms) before implantation, were studied. Echocardiography coupled with tissue Doppler imaging (TDI) and Strain rate was performed in spontaneous rhythm (VVI mode 30/mn) and during atrio-synchronized ventricular pacing. The heart rate (43 +/- 09 vs 68 +/- 07: p<0.01), cardiac output (2.9 +/- 0.7 vs 3.7 +/- 0.6 L/min) and left ventricular filling time (325 +/- 38 vs 412 +/- 51 ms; p<0.01) were significantly less in the escape spontaneous rhythm compared with atrio-ventricular synchronized apical pacing. However, interventricular dyssynchrony (28 +/- 12 vs 59 +/- 25 ms, p<0.05), intra-left ventricular dyssynchrony (36 +/- 11 vs 57 +/- 29 ms; p<0.05), extent of left ventricular myocardium displaying delayed longitudinal contraction (26 +/- 10 vs 39 +/- 17%: p<0.05) were significantly less in the escape rhythm compared with paced rhythm. Once implanted with a DDD pacemaker, CHB patients present with increased cardiac output secondary to the restoration of physiological heart rate and improved diastolic function. However, the apical site is not optimal, as it creates detrimental ventricular dyssynchrony in patients with previous nearly physiological ventricular activation. Alternative pacing sites should be investigated.


Marijuana, tetrahydrocannabinol, and pulmonary antibacterial defenses.
Although marijuana is now consumed extensively, little is known of its biologic effects on the lung. To study this problem, the intrapulmonary inactivation of an aerosolized challenge of Staphylococcus aureus was quantified in rats exposed to graded amounts of fresh marijuana smoke. Controls inactivated 85.1 percent +/- 0.3 percent of the bacteria six hours after inoculation. Following an in vivo accumulative exposure to smoke from progressively increasing numbers of marijuana cigarettes for periods of ten minutes each hour for five consecutive hours, intrapulmonary bacterial inactivation was impaired in a dose-dependent manner. Evaluation of the effects of parenterally administered delta-9-tetrahydrocannabinol (THC) or of exposure to fresh smoke from THC-extracted marijuana placebo cigarettes indicated that the cytotoxin in marijuana was not related to the primary psychomimetic component. Thus, marijuana smoke is toxic to the lung and impairs the pulmonary antibacterial defense system in a dose-dependent manner.


Microbiability and microbiome-wide association analyses of feed efficiency and performance traits in pigs.
The objective of the present study was to investigate how variation in the faecal microbial composition is associated with variation in average daily gain (ADG), backfat thickness (BFT), daily feed intake (DFI), feed conversion ratio (FCR), and residual feed intake (RFI), using data from two experimental pig lines that were divergent for feed efficiency. Estimates of microbiability were obtained by a Bayesian approach using animal mixed models. Microbiome-wide association analyses (MWAS) were conducted by single-operational taxonomic units (OTU) regression and by back-solving solutions of best linear unbiased prediction using a microbiome covariance matrix. In addition, accuracy of microbiome predictions of phenotypes using the microbiome covariance matrix was evaluated. Estimates of heritability ranged from 0.31 ± 0.13 for FCR to 0.51 ± 0.10 for BFT. Estimates of microbiability were lower than those of heritability for all traits and were 0.11 ± 0.09 for RFI, 0.20 ± 0.11 for FCR, 0.04 ± 0.03 for DFI, 0.03 ± 0.03 for ADG, and 0.02 ± 0.03 for BFT. Bivariate analyses showed a high microbial correlation of 0.70 ± 0.34 between RFI and FCR. The two approaches used for MWAS showed similar results. Overall, eight OTU with significant or suggestive effects on the five traits were identified. They belonged to the genera and families that are mainly involved in producing short-chain fatty acids and digestive enzymes. Prediction accuracy of phenotypes using a full model including the genetic and microbiota components ranged from 0.60 ± 0.19 to 0.78 ± 0.05. Similar accuracies of predictions of the microbial component were observed using models that did or did not include an additive animal effect, suggesting no interaction with the genetic effect. Our results showed substantial associations of the faecal microbiome with feed efficiency related traits but negligible effects with growth traits. Microbiome data incorporated as a covariance matrix can be used to predict phenotypes of animals that do not (yet) have phenotypic information. Connecting breeding environment between training sets and predicted populations could be necessary to obtain reliable microbiome predictions.


Kaempferol derivatives as antiviral drugs against the 3a channel protein of coronavirus.
The protein coded by the open-reading-frame 3a of SARS coronavirus has been demonstrated to form a cation-selective channel that may become expressed in the infected cell. The activity of the channel is involved in the mechanism of virus release. Drugs that inhibit the ion channel can, therefore, inhibit virus release, and they could be a source for development of novel therapeutic antiviral agents. Various drugs found in Chinese herbs that are well known as anticancer agents also have an antiviral potency. Here we tested the flavonols kaempferol, kaempferol glycosides, and acylated kaempferol glucoside derivatives with respect to their potency to block the 3a channel. We used the Xenopus oocyte with a heterologously expressed 3a protein as a model system to test the efficacy of the flavonols. Some of these drugs turned out to be potent inhibitors of the 3a channel. The most effective one was the glycoside juglanin (carrying an arabinose residue) with an IC50 value of 2.3 µM for inhibition of the 3a-mediated current. Kaempferol derivatives with rhamnose residue also seem to be quite effective. We suggest that viral ion channels, in general, may be a good target for the development of antiviral agents, and that, in particular, kaempferol glycosides are good candidates for 3a channel proteins of coronaviruses.


Coronavirus disease-19 and headache; impact on pre-existing and characteristics of de novo: a cross-sectional study.
Coronavirus disease-19 is caused by the severe acute respiratory syndrome coronavirus 2 Headache is a common symptom during and after Coronavirus disease-19. We aimed to study headache character in relation to COVID-19. This was a cross-sectional study. Patients who had Coronavirus disease-19, confirmed by reverse transcription polymerase chain reaction technique and presented to the headache clinic within 3 months after the onset of infections were identified to the study. Study included patients diagnosed as primary headache disorders according to The International Classification of Headache Disorders, 3rd edition. Participants were grouped into categories according to having previous or de novo headache. Descriptive data, paired sample t-test and the chi-squared test (X2) were used for statistical analyses of the data. A total of 121 patients were included in this study. Their mean age was 35.29 + 9.54 and most of them were females (83.5%). Prior to Coronavirus disease-19 infections, 78 (64.5%) had migraine and 11(9.1%) experienced a tension-type headache while 32 (26.4) reported de novo headache post Coronavirus disease-19. Patient had significant increase in headache days 11.09 ± 8.45 post Coronavirus disease-19 compared with 8.66 ± 7.49 headache days before Coronavirus disease-19 infection (p < 0.006). Post Coronavirus disease-19, the usage of analgesic increased significantly by the patient with migraine (2.31 ± 1.65 vs 3.05 ± 2.09, p = 0.002) while the patient with tension type headache had statistically significant increase in severity (5.556 ± 1.86 vs 7 ± 2.25, p = 0.033) and frequency (7 ± 6.29 vs 12.72 ± 7.96, p = 0.006) of headache attacks. Bi-frontal and temporal headache are the most reported (40.6% each) headache site among de novo headache group. Patients younger than 40 years had longer duration of the headache attack (18.50 ± 16.44 vs 5.5 ± 9.07, p = 0.045) post COVID-19. Male patients compared to females (8.66 ± 1.15 versus 5.93 ± 2.01 p = 0.04) had more severe headache post Coronavirus disease-19. De novo headache resolved within 1 month in most of patients (65.3%). Primary headache get worse after Coronavirus disease-19. De novo primary headache is frequent post Coronavirus disease-19 and resolve within 1 month. Headaches related to Coronavirus disease-19 are severe, present as migraine phenotype. Young male patients with Coronavirus disease-19 tend to have worse headache.


Induction of cytochromes P450.
The induction of cytochromes P450 (CYPs) has been appreciated for some time but an understanding of the mechanisms involved has been poorly understood until recently. The discovery of the role of nuclear receptors such as the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) has provided a major trigger for research in this area. This work has provided an explanation for species differences in hepatic induction. The production of a PXR crystal structure in the presence and absence of known high affinity ligands has offered the possibility of predicting structures which may bind to the receptor and hence act as inducing agents in man. An improvement in the technology of hepatocyte culture, access to good quality human hepatocytes and the miniaturisation of cultured preparations has meant that the potential of this technique to predict induction in man has been realised. Molecular biological techniques have also proved essential in both the science and the quantitation of CYP induction. The use of transient transfection cell based systems coupled with reporter gene assays have meant that dose response curves can be generated for many chemicals. Assays have been developed to measure the increase of the corresponding CYP mRNAs in primary hepatocytes and some cell lines with a high degree of sensitivity and specificity (allowing the quantitation of closely related CYPs). Although CYP induction is not usually considered as a major drawback in drug development, the aim should be to eliminate or reduce the inducing effects of a new drug to a minimum. Thus, it is essential to increase our understanding of the complex mechanisms that regulate induction and to pay attention to both the dose and the physicochemical and structural properties of CYP inducing agents.


The failure of radical treatments to cure cancer: can less deliver more?
All too often attempts to deliver improved cancer cure rates by increasing the dose of a particular treatment are not successful enough to justify the accompanying increase in toxicity and reduction in quality of life suffered by a significant number of patients. In part, this drive for using higher levels of treatment derives from the nature of the process for testing and incorporation of new protocols. Indeed, new treatment regimens must now consider the key role of immunity in cancer control, a component that has been largely ignored until very recently. The recognition that some drugs developed for cytotoxicity at higher doses can display alternative anticancer activities at lower doses including through modulation of immune responses is prompting a significant re-evaluation of treatment protocol development. Given that tumours are remarkably heterogeneous and with inherent genetic instability it is probably only the adaptive immune response with its flexibility and extensive repertoire that can rise to the challenge of effecting significant control and ultimately elimination of a patient's cancer. This article discusses some of the elements that have limited higher levels of treatment outcomes and where too much proved less effective. We explore observations that less can often be as effective, if not more effective especially with some chemotherapy regimens, and discuss how this can be exploited in combination with immunotherapies to deliver nontoxic improved tumour responses.


Photoconversion of purified fluorescent proteins and dual-probe optical highlighting in live cells.
Photoconvertible fluorescent proteins (pc-FPs) are a class of fluorescent proteins with "optical highlighter" capability, meaning that the color of fluorescence can be changed by exposure to light of a specific wavelength. Optical highlighting allows noninvasive marking of a subpopulation of fluorescent molecules, and is therefore ideal for tracking single cells or organelles. Critical parameters for efficient photoconversion are the intensity and the exposure time of the photoconversion light. If the intensity is too low, photoconversion will be slow or not occur at all. On the other hand, too much intensity or too long exposure can photobleach the protein and thereby reduce the efficiency of photoconversion. This protocol describes a general approach how to set up a confocal laser scanning microscope for pc-FP photoconversion applications. First, we describe a procedure for preparing purified protein droplet samples. This sample format is very convenient for studying the photophysical behavior of fluorescent proteins under the microscope. Second, we will use the protein droplet sample to show how to configure the microscope for photoconversion. And finally, we will show how to perform optical highlighting in live cells, including dual-probe optical highlighting with mOrange2 and Dronpa.


Predictable patterns of disruptive selection in stickleback in postglacial lakes.
Disruptive selection is often assumed to be relatively rare, because it is dynamically unstable and hence should be transient. However, frequency-dependent interactions such as intraspecific competition may stabilize fitness minima and make disruptive selection more common. Such selection helps explain the maintenance of genetic variation and may even contribute to sympatric speciation. There is thus great interest in determining when and where disruptive selection is most likely. Here, we show that there is a general trend toward weak disruptive selection on trophic morphology in three-spine stickleback (Gasterosteus aculeatus) in 14 lakes on Vancouver Island. Selection is inferred from the observation that, within a lake, fish with intermediate gill raker morphology exhibited slower growth than phenotypically extreme individuals. Such selection has previously been shown to arise from intraspecific competition for alternate resources. However, not all environments are equally conducive to disruptive selection, which was strongest in intermediate-sized lakes where both littoral and pelagic prey are roughly balanced. Also, consistent with theory, we find that sexual dimorphism in trophic traits tends to mitigate disruptive selection. These results suggest that it may be possible to anticipate the kinds of environments and populations most likely to experience disruptive selection.


Prosthetic heart valve evaluation by magnetic resonance imaging.
To evaluate the potential of magnetic resonance imaging (MRI) for evaluation of velocity fields downstream of prosthetic aortic valves. Furthermore, to provide comparative data from bileaflet aortic valve prostheses in vitro and in patients. A pulsatile flow loop was set up in a 7.0 Tesla MRI scanner to study fluid velocity data downstream of a 25 mm aortic bileaflet heart valve prosthesis. Three dimensional surface plots of velocity fields were displayed. In six NYHA class I patients blood velocity profiles were studied downstream of their St. Jude Medical aortic valves using a 1.5 Tesla MRI whole-body scanner. Blood velocity data were displayed as mentioned above. Fluid velocity profiles obtained from in vitro studies 0.25 valve diameter downstream of the valve exhibited significant details about the cross sectional distribution of fluid velocities. This distribution completely reflected the valve design. Blood velocity profiles in humans were considerably smoother and in some cases skewed with the highest velocities toward the anterior-right ascending aortic wall. Display and interpretation of fluid and blood velocity data obtained downstream of prosthetic valves is feasible both in vitro and in vivo using the MRI technique. An in vitro model with a straight tube and the test valve oriented orthogonally to the long axis of the test tube does not entail fluid velocity profiles which are compatible to those obtained from humans, probably due to the much more complex human geometry, and variable alignment of the valve with the ascending aorta. With the steadily improving quality of MRI scanners this technique has significant potential for comparative in vitro and in vivo hemodynamic evaluation of heart valves.


Mitochondria as potential targets of flavonoids: focus on adipocytes and endothelial cells.
Obesity is a major public health problem, resulting from an excess of energy storage and/or a default of energy expenditure leading to the increased occurrence of cardiovascular risk factors that favour the development of vascular complications. As a consequence, many studies are interested to find novel therapeutic chemical including flavonoids that appear to be promising natural compounds to treat obesity and its complications. Several in vitro studies addressed the mechanisms involved that might explain their beneficial effects, on adipocytes and endothelial cells, two cell types that play major role in obesity and its vascular complications. Besides the well-described antioxidant properties of flavonoids, at least a part of their beneficial effects on these cell types might be explained by their action on the regulation of mitochondrial function. In this review, we will therefore focus on the pathophysiological role of mitochondria in regulating endothelial and adipocyte functions. In addition, we will present some of the more promising flavonoids, important in human diet, including flavanols, flavonols, isoflavones, anthocyanins, flavanones and flavones; and their potential effects to improve endothelial or adipocyte functions via the mitochondria.


Learning to reproduce a list and memory for the learning.
The ability to reproduce from memory a short list of verbal items immediately following presentation is known to improve over successive trials on that list, even if these trials are embedded in a sequence of trials on other lists of the same sort (Hebb, 1961). Less clear is whether this "Hebb effect" arises without the list repetition being noticed. This question has long been pondered and has recently taken on particular theoretical significance, but the available evidence is scant and inconsistent. Two experiments are described in which, in essence, a sequence of immediate reproduction trials was followed by tests that called for list recognition (Experiments 1 and 2) and/or estimates of list presentation frequency (Experiment 1). These tests provided quantitative measures of repetition awareness. Typical Hebb effects were found, but there was no evidence that the effects occurred without the subjects' being aware of the repetition; effect-size analyses indicated that both the recognition and frequency responses were more sensitive to repetition than were the reproduction responses. Therefore, not only could the recognition and frequency responses not have been made solely on the basis of how readily the test lists were reproduced, but the Hebb effect could have required an awareness of repetition.


Absence of toll-like receptor 7 ameliorates survival and reduces intestinal injury in mice after Clostridium difficile infection.
Clostridioides difficile (CD) is a major cause of antibiotic-associated diarrhea and pseudomembranous enteritis. C. difficile infection (CDI) is increasingly present in the community and represents a significant burden on the healthcare system. Identification of novel immune-based therapeutic targets from a better understanding of their molecular pathogenesis is urgently required. Toll-like receptor 7 (TLR7) is an important pattern recognition receptor and function as an immune sensor that can trigger host defenses against pathogens, but the relationship between TLR7 and CDI remains unknown. Here, we reported that the expression levels of TLR7 increased significantly in patients and mice with CDI. Absence of TLR7 in mice with CDI demonstrated enhanced bacterial clearance of intestinal contents and reduced intestinal inflammation, edema, injury and prolonged the survival. TLR7 loss decreased the concentrations of tumor necrosis factor (TNF)-α, interferon (IFN)-γ and IFN-α1 in the intestine and improved tissue damage and inflammation. Flow cytometry and immunofluorescence results indicated that TLR7 enhanced leukocyte recruitment in the infected intestine. In-vitro results have shown that TLR7 impairs the phagocytosis and killing ability of macrophages to CD, prompts reactive oxygen species (ROS) production and accelerates apoptosis. To our knowledge, our study first identified TLR7 as a critical factor that contributes to the immunopathology of CDI, suggesting that targeting TLR7 might serve as a potential treatment for CDI.


The biology of cancer stem cells.
Cancers originally develop from normal cells that gain the ability to proliferate aberrantly and eventually turn malignant. These cancerous cells then grow clonally into tumors and eventually have the potential to metastasize. A central question in cancer biology is, which cells can be transformed to form tumors? Recent studies elucidated the presence of cancer stem cells that have the exclusive ability to regenerate tumors. These cancer stem cells share many characteristics with normal stem cells, including self-renewal and differentiation. With the growing evidence that cancer stem cells exist in a wide array of tumors, it is becoming increasingly important to understand the molecular mechanisms that regulate self-renewal and differentiation because corruption of genes involved in these pathways likely participates in tumor growth. This new paradigm of oncogenesis has been validated in a growing list of tumors. Studies of normal and cancer stem cells from the same tissue have shed light on the ontogeny of tumors. That signaling pathways such as Bmi1 and Wnt have similar effects in normal and cancer stem cell self-renewal suggests that common molecular pathways regulate both populations. Understanding the biology of cancer stem cells will contribute to the identification of molecular targets important for future therapies.


Integration of NLP2FHIR Representation with Deep Learning Models for EHR Phenotyping: A Pilot Study on Obesity Datasets.
HL7 Fast Healthcare Interoperability Resources (FHIR) is one of the current data standards for enabling electronic healthcare information exchange. Previous studies have shown that FHIR is capable of modeling both structured and unstructured data from electronic health records (EHRs). However, the capability of FHIR in enabling clinical data analytics has not been well investigated. The objective of the study is to demonstrate how FHIR-based representation of unstructured EHR data can be ported to deep learning models for text classification in clinical phenotyping. We leverage and extend the NLP2FHIR clinical data normalization pipeline and conduct a case study with two obesity datasets. We tested several deep learning-based text classifiers such as convolutional neural networks, gated recurrent unit, and text graph convolutional networks on both raw text and NLP2FHIR inputs. We found that the combination of NLP2FHIR input and text graph convolutional networks has the highest F1 score. Therefore, FHIR-based deep learning methods has the potential to be leveraged in supporting EHR phenotyping, making the phenotyping algorithms more portable across EHR systems and institutions.


[Influence of space flight factors on peripheral red blood cells in humans].
Investigations of cosmonauts' peripheral red blood prior to and on days 1, 7 and 14 post long-term MIR-19 and -20 missions dealt with the morphological composition of blood, indices of iron exchange, correlation of erythrocyte shapes, and the lipid and phospholipid profiles of the erythrocyte membrane. To this avail, methods of light electron microscopy, radioimmune analysis, and thin-layer microscopy were used. Among the unidirectional shifts in the crewmembers of these missions were changes in ion exchange indices and the lipid and phospholipid profiles of erythrocyte membrane which were indicative of increased microviscosity of the lipid layer. Number of erythrocytes and hemoglobin content were reduced; transformed erythrocytes were present. It was also discovered that the fraction of normal erythrocytes (diskocytes) was partially replaced by spherocytes, cnisocytes in flight and typically by echinocytosis post flight. By and large, the observed shifts do not have any clinical implications and are most likely the blood system reaction to the stress of readaptation to the terrestrial conditions.


Anaesthesia for total knee arthroplasty: efficacy of single-injection or continuous lumbar plexus associated with sciatic nerve blocks--a randomized controlled study.
Total knee arthroplasty (TKA) often results in marked postoperative pain. We compared in a randomized controlled study tramadol consumption, postoperative pain and patient satisfaction after primary TKA in patients who received a single injection lumbar plexus and sciatic nerve blocks or a continuous lumbar plexus and sciatic nerve blocks. Forty-four patients scheduled for unilateral total knee arthroplasty were allocated to the single shot group (group A) or to the catheter group (group B). All patients (in both groups) reported being satisfied with their anaesthetic management. Although pain scores and tramadol consumption appeared lower in the active infusion group, the differences did not reach statistical significance. This study confirms that either single injection or continuous infusion of Ropivacaine in lumbar plexus provides reliable and long-acting anaesthesia and analgesia.


Development and psychometric evaluation of a chronic liver disease-specific quality of life questionnaire.
There has been no reliable and valid instrument to measure health-related quality of life for Asian patients with chronic liver disease. The aim of the present study was to develop and evaluate a chronic liver disease-specific quality of life (CLD-QOL) questionnaire for Korean patients with chronic liver disease. Content-validated items were evaluated psychometrically in 271 patients with chronic liver disease recruited from seven university hospitals in Korea. The participants were asked to complete a preliminary questionnaire comprising the content-validated items and the Short Form-36 Health Survey. The Child-Pugh classification was used to classify the severity of liver cirrhosis. Factor analysis extracted a five-factor solution from 27 preliminary items, which were generated by an expert panel and a pilot study, but factor and a multidimensional scaling analysis revealed that four items were not loaded significantly on any factor, suggesting that the four items might be heterogeneous. After deletion of these four items, a multiscaling analysis strongly supported item convergence and discriminant validity. The CLD-QOL was associated significantly with the Child-Pugh classification and the type of patient status (inpatient/outpatient) and was moderately correlated with the subscales of the Short Form-36 Health Survey. The values of Cronbach's alpha for the subscales of the novel CLD-QOL questionnaire were all greater than 0.70. The novel CLD-QOL questionnaire we developed is an easily applicable tool that exhibits excellent psychometric properties for Korean patients with chronic liver disease. It is recommended for the CLD-QOL to apply for Asian patients with chronic liver disease.


Immunization with a mouse mammary tumour virus envelope protein epitope protects against tumour formation without inhibition of the virus infection.
BALB/c mice were immunized with the EP3 surface epitope of the mouse mammary tumour virus (MMTV) gp52 envelope protein before systemic infection with MMTV(C3H) or MMTV(SW). Analysis of the successive stages of the virus infection showed that although these mice were protected against mammary tumour formation, earlier stages of the infection were not inhibited, as reflected by the persisting superantigen-induced activation and deletion of Vbeta-specific T cells. Transplacental transfer of maternal anti-EP3 immunoglobulins to newborns did not protect them from infection through the Peyer's patches. Preincubation of the MMTVs with an anti-EP3 serum before injection, however, successfully inhibited the early stages of the infection. Results from this study show that to inhibit infection by MMTV efficiently, the virus must be neutralized before its interaction with the cell membrane, and that the affinity of the virus-membrane interaction is higher than that of the virus-antibody interaction.


Colorectal cancer incidence and mortality disparities in new Mexico.
Background. Previous analyses indicated that New Mexican Hispanics and American Indians (AI) did not experience the declining colorectal cancer (CRC) incidence and mortality rates observed among non-Hispanic whites (NHW). We evaluated more recent data to determine whether racial/ethnic differences persisted. Methods. We used New Mexico Surveillance Epidemiology and End Results data from 1995 to 2009 to calculate age-specific incidence rates and age-adjusted incidence rates overall and by tumor stage. We calculated mortality rates using National Center for Health Statistics' data. We used joinpoint regression to determine annual percentage change (APC) in age-adjusted incidence rates. Analyses were stratified by race/ethnicity and gender. Results. Incidence rates continued declining in NHW (APC -1.45% men, -1.06% women), while nonsignificantly increasing for AI (1.67% men, 1.26% women) and Hispanic women (0.24%). The APC initially increased in Hispanic men through 2001 (3.33%, P = 0.06), before declining (-3.10%, P = 0.003). Incidence rates declined in NHW and Hispanics aged 75 and older. Incidence rates for distant-stage cancer remained stable for all groups. Mortality rates declined significantly in NHW and Hispanics. Conclusions. Racial/ethnic disparities in CRC persist in New Mexico. Incidence differences could be related to risk factors or access to screening; mortality differences could be due to patterns of care for screening or treatment.


Bilateral dens evaginatus (talon cusp) in permanent maxillary lateral incisors: a rare developmental dental anomaly with great clinical significance.
Talon cusp is an accessory cusp-like structure which projects from the cingulum area or cementoenamel junction. It is important for dentists to be aware of the potential complications that may occur with talon cusp. Early diagnosis and treatment is important, especially to prevent pulpal complications in permanent teeth which may be in developing stage in paediatric patients. The purpose of this paper is to report a case of bilateral talon cusp in permanent maxillary lateral incisors. Associated dental anomalies and clinical problems are discussed along with successful management of the case with conservative therapy.


Single Atomic Vacancy Catalysis.
Single atom catalysts provide exceptional activity. However, measuring the intrinsic catalytic activity of a single atom in real electrochemical environments is challenging. Here, we report the activity of a single vacancy for electrocatalytically evolving hydrogen in two-dimensional (2D) MoS2. Surprisingly, we find that the catalytic activity per vacancy is not constant but increases with its concentration, reaching a sudden peak in activity at 5.7 × 1014 cm-2 where the intrinsic turn over frequency and Tafel slope of a single atomic vacancy was found to be ∼5 s-1 and 44 mV/dec, respectively. At this vacancy concentration, we also find a local strain of ∼3% and a semiconductor to metal transition in 2D MoS2. Our results suggest that, along with increasing the number of active sites, engineering the local strain and electrical conductivity of catalysts is essential in increasing their activity.


Mediators of daily stress and perceived health status in adolescent girls.
A causal model based on the transactional cognitive theory of psychological stress and coping was tested in a middle adolescent female population to determine the effects of daily stress, introspectiveness, and coping efforts on perceived health status. Daily stress was hypothesized to affect perceived health status both directly and through the mediating variables of introspectiveness and coping efforts. A sample of 159 female adolescents completed the Hassles Scale, the Ways of Coping Checklist-Revised, the Introspectiveness Scale for Adolescents and the General Health Rating Index. The causal model was tested using the LISREL VI program. Findings indicated that the model fit the data, indicating a plausible representation of the relationships among the variables identified (x2 = 15.76, df = 12, p less than .203). Daily stress was significantly negatively related to perceived health status through the mediating variables of introspection and problem-focused coping but not emotion-focused coping. Introspectiveness had a significant direct effect on perceived health status. Problem-focused coping was found to have a direct positive effect on perceived health status.


Dose calculations for arbitrarily shaped electron beams.
A method for the calculation of absorbed dose distributions of arbitrarily shaped electron beams is described. Isodose distributions and the output factor of a newly designed treatment field can be predicted with good accuracy, without the need for any dose measurement in the actual field. Two different Gaussian pencil beams are used as building elements for the treatment beams of each electron energy. The dose distributions of the pencil beams are derived from measurements of broad beam dose distributions; in this way the influence of electrons scattered by the applicator walls is taken into account. The contribution to the dose by electrons scattered from a high Z metal frame which defines the treatment field contour is calculated separately and added. This calculation is based on experimentally derived data. The method has been tested for electron beams with 6, 10, 14 and 20 MeV nominal energy. The distance between calculated and measured isodose lines with values between 90 and 10 per cent of the maximum dose did not exceed a limit of 0.3 cm. The difference between calculated and measured output factors remained within 2 per cent.