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Introduction Apraxia is a core clinical feature of corticobasal syndrome (CBS). Among the subtypes of apraxia, ideomotor and imitation apraxia are frequently found in CBS. However, little is known about the brain networks that are characteristic of each apraxia subtype or their clinical implication. In this study, we used 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to explore the specific patterns of glucose hypometabolism that are characteristic of apraxia subtypes by focusing on ideomotor and imitation apraxia. Methods We compared the areas of glucose hypometabolism in the brains of 52 patients with CBS and 13 healthy controls, both as a whole and according to apraxia subtypes. In addition, we investigated the relationship between the apraxia subtypes and the clinical phenotype of CBS. Results In patients with CBS, common hypometabolism was observed in the frontal gyrus, precentral gyrus and caudate regardless of apraxia subtypes. In particular, ideomotor apraxia was associated with hypometabolism in the angular gyrus, while imitation apraxia was associated with hypometabolism in the posterior part including the postcentral gyrus, precuneus, and posterior cingulate gyrus. Patients who showed both ideomotor and imitation apraxia were more likely to show the typical features of CBS and progressive supranuclear palsy compared with patients showing only one type of apraxia. Conclusion Group comparison analysis using FDG-PET revealed distinct pathways of ideomotor and imitation apraxia in CBS. These findings add to our understanding of the brain networks underlying apraxia in association with the clinical features of CBS.

Introduction Cognitive impairment is not uncommon in patients with multiple system atrophy (MSA). This study investigated the cortical metabolic changes of MSA and the cortical structure associated with cognitive impairment. Methods The study included probable/definite MSA patients who underwent fluorodeoxyglucose positron emission tomography and cognitive evaluation based on mini-mental status examination (MMSE). Cerebral metabolism of the entire MSA patients (n = 88) was compared with healthy controls (n = 19) by voxel-wise statistical parametric mapping. Eight brain regions of interest (ROIs) were selected accordingly: the dorsolateral prefrontal, medial superior frontal, insular, posterior parietal, precuneus, lateral temporal, medial temporal, and posterior cingulate regions. Using validated population-based norms, MSA patients were divided by MMSE z-scores into MSA with cognitive dysfunction (MSA-D, n = 30) and without cognitive dysfunction (MSA-ND, n = 58). Regional metabolism of the selected ROIs was compared between the MSA-D and MSA-ND groups by logistic regression models. Correlations between the regional metabolism of the selected ROIs and MMSE z-scores were analyzed with a linear regression model. Results Voxel-wise analysis showed hypometabolism in the frontal, temporal, parietal, and limbic areas in MSA patients than in controls. ROI-based comparisons showed that metabolism in the posterior cingulate (P = 0.006) and medial temporal (P = 0.039) regions was significantly lower in the MSA-D than in the MSA-ND group. The degree of posterior cingulate metabolism correlated significantly with MMSE z-score (P = 0.023). Conclusions MSA shows fronto-temporo-parietal cortical involvement. Hypometabolism of the limbic regions is associated with cognitive impairment in MSA.

Boron (B) (1.5 mol %) is introduced into Li[Ni

Pencil-and-paper exercises in public-key cryptography are important in learning the subject. It is desirable that a student doing such an exercise does not get the right answer by a wrong method. We therefore seek exercises that are sound in the sense that a student who makes on of several common errors will get a wrong answer. Such exercises are difficult to construct by hand. This paper considers how to do so automatically, and describes software developed for this purpose, covering several popular cryptosystems (RSA, Diffe-Hellman, Massey-Omura, ElGamal, Knapsack). We also introduce diagnostic exercises, in which all error paths lead to different answers, so that the answer given by the student may suggest the nature of their error. These too can be generated automatically by our software.

Ventilation and mechanics of breathing are an integral part of respiratory physiology that directly affect aerosol transport and deposition in the lung. Although natural breathing pattern varies widely among individuals, breathing pattern is controllable, and by using an appropriate breathing pattern, aerosol deposition can be substantially modified for desired purposes. Effects of breathing pattern have been investigated under carefully controlled inhalation conditions covering a wide range of tidal volumes (V

Although dementia is a contraindication for deep brain stimulation (DBS) in patients with Parkinson's disease (PD), the concept is supported by little scientific evidence. Moreover, it is unclear whether PD with mild cognitive impairment (PD-MCI) or domain-specific cognitive impairments affect the outcome of DBS in non-demented PD patients.To investigate the influence of baseline cognitive profiles of PD on the outcome of DBS.Baseline cognitive levels of patients with PD who underwent DBS were classified into PD with dementia (PDD) (n = 15), PD-MCI (n = 210), and normal cognition (PD-NC) (n = 79). The impact of the cognitive level on key DBS outcome measures [mortality, nursing home admission, progression to HoehnYahr (HY) stage 5 and progression to PDD] were analyzed using Cox regression models. We also investigated whether impairment of a specific cognitive domain could predict these outcomes in non-demented patients.Patients with PDD showed a substantially higher risk of nursing home admission and progression to HY stage 5 compared with patients with PD-MCI [hazard ratio (HR) 4.20, P = .002; HR = 5.29, P .001] and PD-NC (HR 7.50, P .001; HR = 7.93, P .001). MCI did not alter the prognosis in patients without dementia, but those with visuospatial impairment showed poorer outcomes for nursing home admission (P = .015), progression to HY stage 5 (P = .027) and PDD (P = .006).Cognitive profiles may stratify the pre-operative risk and predict long-term outcomes of DBS in PD.

Objective\ud \ud We aimed to characterize the demographics of adults with dissociative (nonepileptic) seizures, placing emphasis on distribution of age at onset, male:female ratio, levels of deprivation, and dissociative seizure semiology.\ud Methods\ud \ud We collected demographic and clinical data from 698 adults with dissociative seizures recruited to the screening phase of the CODES (Cognitive Behavioural Therapy vs Standardised Medical Care for Adults With Dissociative Non‐Epileptic Seizures) trial from 27 neurology/specialist epilepsy clinics in the UK. We described the cohort in terms of age, age at onset of dissociative seizures, duration of seizure disorder, level of socioeconomic deprivation, and other social and clinical demographic characteristics and their associations.\ud Results\ud \ud In what is, to date, the largest study of adults with dissociative seizures, the overall modal age at dissociative seizure onset was 19 years; median age at onset was 28 years. Although 74% of the sample was female, importantly the male:female ratio varied with age at onset, with 77% of female but only 59% of male participants developing dissociative seizures by the age of 40 years. The frequency of self‐reported previous epilepsy was 27%; nearly half of these epilepsy diagnoses were retrospectively considered erroneous by clinicians. Patients with predominantly hyperkinetic dissociative seizures had a shorter disorder duration prior to diagnosis in this study than patients with hypokinetic seizures (P < .001); dissociative seizure type was not associated with gender. Predominantly hyperkinetic seizures were most commonly seen in patients with symptom onset in their late teens. Thirty percent of the sample reported taking antiepileptic drugs; this was more common in men. More than 50% of the sample lived in areas characterized by the highest levels of deprivation, and more than two‐thirds were unemployed.\ud Significance\ud \ud Females with dissociative seizures were more common at all ages, whereas the proportion of males increased with age at onset. This disorder was associated with socioeconomic deprivation. Those with hypokinetic dissociative seizures may be at risk for delayed diagnosis and treatment.

The Cl35(n,p) and Cl35(n,α) cross sections at incident neutron energies between 2.42 and 2.74 MeV were measured using the Berkeley High Flux Neutron Generator. The cross sections for Cl35(n,p) were more than a factor of 3 to 5 less than all of the values in the neutron absorption data libraries, while the Cl35(n,α) cross sections are in reasonable agreement with the data libraries. The measured energy-differential cross section is consistent with a single resonance with a width of 293(46) keV. This result suggests that, despite the high incident neutron energy, any attempt to model (n,x) cross sections in the vicinity of the N=Z=20 shell gap requires a resolved resonance approach rather than a Hauser-Feshbach approach.

Introduction: Disability increases an individual’s dependence and negatively impacts their physical, mental, and social functioning. The current study aims to establish the prevalence and risk factors of disability in Singapore’s population. Materials and Methods: Data was extracted from the Well-being of the Singapore Elderly (WiSE) study. This cross-sectional study recruited participants aged 60 years and above (n = 2421) who were representative of Singapore’s multiethnic population. We used the World Health Organization Disability Assessment Schedule (WHODAS) 2.0 to assess the severity of disability in our sample while establishing its associations and correlations with cognitive levels, sociodemographic variables, and chronic illness. Results: Cognitive deficits, old age, female gender, Malay and Indian ethnicity, lack of education, retired or homemaker status, presence of chronic illness (specifically stroke, heart problems, depression, and dementia) were found to be significantly associated with disability in Singapore’s elderly population. As hypothesised, participants with deficits in cognition were more likely to indicate higher WHODAS scores. Conclusion: The findings highlighted specific factors associated with disability in this multiethnic population. The identification of these factors would lead the way to the development of appropriate interventions. Key words: Chronic illness, Cognitive decline, Functioning, Old age

Introduction: The current study aimed to establish the prevalence of internet gaming disorder (IGD) and its association with demographic characteristics, game genre, game use (time spent on gaming), as well as psychological distress, social phobia and well-being among current online gamers in Singapore. Materials and Methods: A total of 1251 participants aged 13 to 40 years completed the study which was administered as a web survey. The online questionnaire was designed using QuestionPro, and consisted of 8 sections and 105 questions. The 9-item Internet Gaming Disorder Questionnaire was used to establish the prevalence of IGD in the study. A series of logistic regression models were used to examine the associations between IGD, demographic characteristics and game genre, as well as IGD and psychological distress, social phobia and well-being. Results: The prevalence of IGD established using a cutoff of 5 among those who were current online gamers was 17.7%. Multiple logistic regressions revealed that those meeting criteria of IGD were more likely to be older, reported an earlier age of onset of playing online games, had primary and secondary education versus tertiary education, were currently students versus being currently employed and played massively multiplayer online role-playing games. Distress and social anxiety were higher while satisfaction with life was significantly lower among those who met criteria for IGD than those who did not meet the criteria. Conclusion: The prevalence of IGD and its negative consequences in our sample of current online gamers was significant and point towards the need for further clinical studies and innovative interventions to address the problem. Key words: Gamers, Massively multiplayer online role-playing games, Psychological distress

© Mary Ann Liebert, Inc., publishers 2018. Improvements in cancer therapy for childhood and adolescent and young adult (AYA) survivors have increased in excess of 80% among pediatric patients and in excess of 85% among AYA cancer patients. Our research group explored the late effects consequences of cancer treatment on pregnancy and birth outcomes subsequent to a childhood (0-14 years) or AYA (15-25 years) diagnosis of cancer in female cancer survivors. Embase and Medline databases were searched. There were 17 review (n = 10 matched and n = 7 unmatched) studies that met the inclusion criteria. Subanalyses were conducted on 10 matched studies. The median age for all studies for patients at diagnosis and birth was 11 and 27 years, respectively. In matched cohort studies, female childhood and AYA cancer patients, who received chemotherapy alone, had a pooled estimated rate of 18% of experiencing a live birth compared with 10% of females who received radiotherapy alone and subsequently had a live birth. Females who received surgery alone reported higher pooled estimated rates of 44% for a live birth. For matched retrospective review studies, 79% (n = 973) of women experienced a live birth, of which 22% of these babies were born preterm. This meta-analysis found lower birth rates for survivors. Access to fertility-related information and discussions around fertility preservation options and oncofertility psychosocial support should be offered to all cancer patients and their families before starting cancer treatment.

Correction to: Scientific Reports https://doi.org/10.1038/s41598-017-14403-y, published online 22 January 2018 The original version of this Article contained a typographical error in the spelling of the consortium member Patrick Yu-Wai-Man which was incorrectly given as Patrick Yu Wai Man. In addition, a supplementary file containing additional algorithms and analysis was omitted from the original version of this Article. These errors have now been corrected in the HTML and PDF versions of the Article.

Because electric vehicles (EVs) are used intermittently with long resting periods in the fully charged state before driving, calendar aging behavior is an important criterion for the application of Li-ion batteries used in EVs. In this work, Ni-rich Li[Ni

Introduction: Functioning and quality of life (QOL) are negatively impacted as a result of mental illness. This study aimed to determine the: i) socio-demographic and clinical correlates of functioning and; ii) associations between functioning and QOL in a multiethnic sample of psychiatric outpatients. Materials and Methods: This was a cross-sectional study of outpatients receiving treatment from a tertiary psychiatric hospital. Functioning was assessed using the Global Assessment of Functioning (GAF) scale, while QOL was measured using the World Health Organization Quality of Life-BREF (WHOQOL-BREF) which comprises 4 domains: physical health, psychological health, social relationships and environment. Results: Various socio-demographic and clinical correlates were associated with functioning including employment and marital status, education and diagnosis. Depression was the only clinical characteristic which negatively correlated with functioning (P = 0.035). Amongst the whole sample, multiple linear regressions revealed that functioning was positively associated with all 4 QOL domains (physical health [P

Parallel processing and double-flow methods, which are used to increase the speed of turbo-code decoding, cause memory contentions. Although memory contentions due to parallel processing can be resolved by adopting the quadratic polynomial permutation (QPP) interleaver, the double-flow method still causes memory contentions because of its read/write sequences from both ends of the input packets. Thus, we propose a modified architecture to resolve memory contentions for the double-flow method to fit the QPP interleaver. In our experiment, the proposed method has a shorter decoding time and smaller hardware size compared the conventional method. A bit-accurate simulation was performed, and hardware implementation with field-programmable gate arrays (FPGAs) led to a high throughput of 80 Mbps. © 2014 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.

Background Perry syndrome (PS) caused by DCTN1 gene mutation is clinically characterized by autosomal dominant parkinsonism, depression, severe weight loss, and hypoventilation. Previous pathological studies have reported relative sparing of the cerebral cortex in this syndrome. Here, we characterize novel clinical and neuroimaging features in 3 patients with PS. Methods 18 F-fluorinated N -3-fluoropropyl-2-s-carboxymethoxy-3-β-(4-iodophenyl) nortropane ([ 18 F]FP-CIT) PET, [ 18 F]fluorodeoxyglucose PET, or volumetric MRI was performed in probands, and imaging data were analyzed and compared with those of control subjects. Results We identified 2 novel mutations of DCTN1 . Oculogyric crisis that presented before levodopa treatment was observed in 1 case. One patient had supranuclear gaze palsy. In 2 cases, [ 18 F]FP-CIT showed marked loss of dopamine transporter binding with only mild parkinsonism. Areas of hypometabolism or cortical thickness change were observed in dorsolateral frontal, anterior cingulate, lateral temporal, and inferior parietal cortices. Conclusion Oculomotor manifestations are not uncommon in PS. Neuroimaging studies suggest involvement of the frontotemporoparietal cortex, which may be the clinical correlate of apathy and depression, as well as pathological changes in subcortical structures.

This paper provides a design of high-throughput parallel turbo decoder that is able to decode several packets of various length simultaneously. For high-speed communications, designing of Turbo decoder as parallel structures reduces the long decoding time caused by iterative turbo decode way. Also, by employing the double buffer structure for input and output packets improves the decoder throughput by enabling continuous decoding. Because parallel turbo decoder is designed to be able to decode the packet of the longest length, there exist idle PE`s(Processing Element) in the case of decoding packets of short length. The main idea of this paper is to increase the utilization of PE`s in parallel Turbo decoder and to improve the decoder throughput by using the idle PE`s immediately for the subsequent packets decoding. For this, the control is necessary to enable the concurrent decoding of several short packets and we propose the method of this control. Applying the proposed method, we implemented Turbo Decoder with 32 PE`s that can decode packets of 6144 bits maximum. Compared to the conventional Turbo decoder, although the area was increased about 16%, the decoder throughput was improved 28 times for short packets.

The incidence of Crohn disease (CD) has been increasing and surgery needs to be contemplated in a substantial number of cases. The relevant advent of biological treatment has changed but not eliminated the need for surgery in many patients. Despite previous publications on the indications for surgery in CD, there was a need for a comprehensive review of existing evidence on the role of elective surgery and options in pediatric patients affected with CD. We present an expert opinion and critical review of the literature to provide evidence-based guidance to manage these patients. Indications, surgical options, risk factors, and medications in pre- and perioperative period are reviewed in the light of available evidence. Risks and benefits of surgical options are addressed. An algorithm is proposed for the management of postsurgery monitoring, timing for follow-up endoscopy, and treatment options.

White blood cell (WBC) count is a common clinical measure used as a predictor of certain aspects of human health, including immunity and infection status. WBC count is also a complex trait that varies among individuals and ancestry groups. Differences in linkage disequilibrium structure and heterogeneity in allelic effects are expected to play a role in the associations observed between populations. Prior genome-wide association study (GWAS) meta-analyses have identified genomic loci associated with WBC and its subtypes, but much of the heritability of these phenotypes remains unexplained. Using GWAS summary statistics for over 50 000 individuals from three diverse populations (Japanese, African-American and European ancestry), a Bayesian model methodology was employed to account for heterogeneity between ancestry groups. This approach was used to perform a trans-ethnic meta-analysis of total WBC, neutrophil and monocyte counts. Ten previously known associations were replicated and six new loci were identified, including several regions harboring genes related to inflammation and immune cell function. Ninety-five percent credible interval regions were calculated to narrow the association signals and fine-map the putatively causal variants within loci. Finally, a conditional analysis was performed on the most significant SNPs identified by the trans-ethnic meta-analysis (MA), and nine secondary signals within loci previously associated with WBC or its subtypes were identified. This work illustrates the potential of trans-ethnic analysis and ascribes a critical role to multi-ethnic cohorts and consortia in exploring complex phenotypes with respect to variants that lie outside the European-biased GWAS pool.

Introduction: Depression is a significant public health issue across all sociodemographic groups and is identified as a common and serious mental health problem particularly among the older adult population. The aims of the current study were to determine the prevalence of depression and subsyndromal depression among older adults in Singapore. Materials and Methods: The Well-being of the Singapore Elderly (WiSE) study was a comprehensive single phase, cross-sectional survey. Stage 1 Geriatric Mental State-Automated Geriatric Examination for Computer Assisted Taxonomy (GMS-AGECAT) depression syndrome was used for this analysis. Association of depression and subsyndromal depression with sociodemographic characteristics, social support as well as comorbidity with chronic physical illnesses and quality of life was assessed. Results: The prevalence of GMS-AGECAT depression and subsyndromal depression was 3.7% and 13.4%, respectively. The odds of depression were significantly higher among those aged 75 to 84 (2.1) as compared to those aged 60 to 74 years and in those who had a history of depression diagnosis by a doctor (4.1). The odds of depression were higher among those of Indian and Malay ethnicities (5.2 and 3.2 times, respectively) as compared to those of Chinese ethnicity. Those with depression and subsyndromal depression were associated with more disability, poorer life satisfaction, and medical comorbidities. Conclusion: Our study suggests that the prevalence of depression seems to have decreased as compared to a decade ago wherein the prevalence of depression was estimated to be 5.5%. This positive trend can be ascribed to concerted efforts across various disciplines and sectors, which need to be continually strengthened, monitored and evaluated. Key words: Comorbidity, GMS-AGECAT, Social support, Subsyndromal depression

A human exposure-response (E-R) model previously demonstrated to accurately predict population mean FEV₁ response to ozone exposure has been proposed as the foundation for future risk assessments for ambient ozone.Fit the original and related models to a larger data set with a wider range of exposure conditions and assess agreement between observed and population mean predicted values.Existing individual E-R data for 23 human controlled ozone exposure studies with a wide range of concentrations, activity levels, and exposure patterns have been obtained. The data were fit to the original model and to a version of the model that contains a threshold below which no response occurs using a statistical program for fitting nonlinear mixed models.Mean predicted FEV₁ responses and the predicted proportions of individuals experiencing FEV₁ responses greater than 10, 15, and 20% were found to be in agreement with observed responses across a wide range of exposure conditions for both models. The threshold model, however, provided a better fit to the data than the original, particularly at the lowest levels of exposure.The models identified in this manuscript predict population FEV₁ response characteristics for 18-35-year-old individuals exposed to ozone over a wide range of conditions and represent a substantial improvement over earlier E-R models. Because of its better fit to the data, particularly at low levels of exposure, the threshold model is likely to provide more accurate estimates of risk in future risk assessments of ozone-induced FEV₁ effects.

Introduction: This study aims to assess the prevalence rates of mental disorders and chronic medical conditions in the Singapore resident population, and examine their association and respective impact on the quality of life. Materials and Methods: A household survey was carried out on a nationally representative sample of the adult (18 years and above) resident population. The main instrument used to establish the diagnosis of mental disorders is the World Mental Health Composite International Diagnostic Interview (WMH-CIDI). The mental disorders included in study were major depressive disorder, bipolar disorder, generalised anxiety disorder, obsessive compulsive disorder, alcohol abuse and alcohol dependence. Respondents were asked if they had any of the chronic medical conditions from a list of 15 conditions. Health-related quality of life was assessed with the EQ-5D. Results: Of the 6616 respondents, the lifetime prevalence of mental disorders was 12.0%, and that of chronic medical disorders were 42.6% and those with comorbid mental and medical disorders was 6.1%. The prevalence of any physical disorder in this population was high (42.6%). Among those with chronic physical disorders, 14.3% also had a mental disorder, and among those with mental disorders, more than half (50.6%) had a medical disorder. Most of the mental disorders were not treated. Males, Indians, older people, and those who were separated or divorced were more likely to have comorbidity. The health-related quality of life was significant worse in those with both mental and medical disorders compared to those with either mental or medical disorder. Conclusion: Our study re-emphasised the common occurrence of mental and medical disorders and the importance for an integrated care system with the capability to screen and treat both types of disorders. It also identified certain subpopulations which are more likely to have comorbidity for which a more targeted intervention could be planned. Key words: Chronic conditions, Ethnicity, Health-related quality of life, Marital status

Anal canal cancer is a rare cancer with incidence that continues to rise. This has been in large part due to increased prevalence of immunosuppressed conditions such as organ transplantation and human immunodeficiency virus along with transmission of the human papillomavirus. Identification of high-risk groups and close monitoring of these groups can help to detect earlier stages of cancer. Chemoradiation therapy remains the mainstay of treatment with excellent outcomes. Surgery for anal canal carcinoma remains as a salvage technique for failed chemoradiation or recurrent disease.

Objective: To investigate in vivo the impact of age on nigrostriatal dopamine dysfunction in Parkinson's disease (PD). Methods: PD patients (n = 78) and healthy control subjects (n = 35) underwent longitudinal positron emission tomography assessments using 3 presynaptic dopamine markers: (1) [11C](±)dihydrotetrabenazine (DTBZ), to estimate the density of the vesicular monoamine transporter type 2; (2) [11C]d-threo-methylphenidate, to estimate the density of the plasma membrane dopamine transporter; and (3) 6-[18F]-fluoro-L-dopa, to estimate the activity of the enzyme dopa-decarboxylase. Results: The study comprised 438 PD scans and 241 control scans (679 scans in total). At symptom onset, the loss of putamen DTBZ binding was substantially greater in younger compared to older PD patients (p = 0.015). Remarkably, however, the rate of progression of DTBZ binding loss was significantly slower in younger patients (p< 0.05). The estimated presymptomatic phase of the disease spanned more than 2 decades in younger patients, compared to 1 decade in older patients. Interpretation: Our results suggest that, compared to older patients, younger PD patients progress more slowly and are able to endure more damage to the dopaminergic system before the first motor symptoms appear. These observations suggest that younger PD patients have more efficient compensatory mechanisms. Ann Neurol 2011

A representative human tracheobronchial tree has been geometrically represented with adjustable triple-bifurcation units (TBUs) in order to effectively simulate local and global micron particle depositions. It is the first comprehensive attempt to compute micron-particle transport in a (Weibel Type A) 16-generation model with realistic inlet conditions. The CFD modeling predictions are compared to experimental observations as well as analytical modeling results. Based on the findings with the validated computer simulation model, the following conclusions can be drawn: (i) Surprisingly, simulated inspiratory deposition fractions for the entire tracheobronchial region (say, G0–G15) with repeated TBUs in parallel and in series agree rather well with those calculated using analytical/semi-empirical expressions. However, the predicted particle-deposition fractions based on such analytical formulas differ greatly from the present simulation results for most local bifurcations, due to the effects of local geometry and resulting local flow features and particle distributions. Clearly, the effects of realistic geometries, flow structures and particle distributions in different individual bifurcations accidentally cancel each other so that the simulated deposition efficiencies during inspiration in a relatively large airway region may agree quite well with those obtained from analytical expressions. Furthermore, with the lack of local resolution, analytical models do not provide any physical insight to the air–particle dynamics in the tracheobronchial region. (ii) The maximum deposition enhancement factors (DEF) may be in the order of 10 2 to 10 3 for micron particles in the tracheobronchial airways, implying potential health effects when the inhaled particles are toxic. (iii) The presence of sedimentation for micron particles in lower bronchial airways may change the local impaction-based deposition patterns seen for larger airways and hence reduces the maximum DEF values. (iv) Rotation of an airway bifurcation cause a significant impact on distal bifurcations rather than on the proximal ones. Such geometric effects are minor when compared to the effects of airflow and particle transport/deposition history, i.e., upstream effects.

A nonaqueous dispersion of poly(3,4-ethylenedioxythiophene) (PEDOT) was prepared with the use of polymeric ionic liquid (PIL) as a polymerization template and phase transfer medium. A detailed investigation was performed to understand the role of PIL in the course of polymerization and phase transfer reaction. On the basis of our findings from X-ray photoelectric spectroscopy (XPS), we propose a mechanism by which the PIL leads to the nanostructured PEDOT colloids in various organic solvents and thus facilitating smoother surface morphologies of the PEDOT-PIL films. In addition, the enhancement of charge transport was observed for PEDOT-PIL complex when compared with PEDOT without PIL. Raman spectroscopy indicates that there is a reduced interaction between the charge carriers on the PEDOT and the counter ions bound to PIL, thus promoting charge carrier hopping rates.

Focusing on relatively small airways in terms of the medium-size bronchial generations G6–G9, the interplay of impaction and sedimentation on micron particle transport and deposition has been simulated. A commercial finite-volume code, enhanced with user-supplied programs, has been employed. Although impaction is still a dominant deposition mechanism for microparticle in medium-size airways under normal breathing conditions (say, Q in = 15 – 30 L / min ), sedimentation may play a role as well. In turn, that can influence the local particle deposition patterns, efficiencies and fractions for a realistic range of Stokes numbers ( 0.001 ⩽ St ⩽ 0.33 ) . However, deposition due to sedimentation is significantly amplified during slow inhalation; for example, the gravitational deposition may become dominant in the ninth bifurcation (i.e., generations G8–G9) for relatively large microparticles (say, d p > 5 μ m ) at Q in = 3.75 L / min . The occurrence of sedimentation changes the location of the deposition “hot spots” and reduces the order of the maximum deposition enhancement factor. The use of analytical formulas based on inclined tube models for predicting gravitational deposition in local bronchial airway segments as well as the combination of deposition by sedimentation and impaction has to be carefully examined. As shown, more prudent is the use of curve-fitted correlations generated from experimentally validated computer simulation results as a function of Stokes number and sedimentation parameter.

Study Objective To investigate safety issues associated with the reuse of sterilized endotracheal tubes (ETTs). Design Prospective, randomized study. Setting Laboratory in vivo testing. Intervention Staphylococcus aureus , Escherichia coli, and Pseudomonas aeruginosa were inoculated onto ETT cuffs. Following inoculation, ETTs were sterilized with either ethylene oxide or glutaraldehyde. Cuffs were then swabbed and cultured for 24 hours. To examine changes in the physical integrities of sterilized ETT cuffs, ETTs were sterilized with ethylene oxide gas once, twice, or three times (the E1, E2, and E3 groups, respectively). Alternatively, ETTs were soaked in glutaraldehyde for 150, 300, 450, or 600 minutes (the G1, G2, G3, and G4 groups, respectively). Measurements Endotracheal tube cuffs were considered nonsterile if a visible colony of test organisms was cultured, and sterile if no colony was cultured. Changes in the physical integrity of sterilized ETT cuffs were determined by measuring changes in intracuff pressure or tensile strength. Main Results No growth of bacteria was observed in sterilized tubes. Endotracheal tube cuffs of the E1 and E2 groups showed almost the same physical integrity as those of the control group, whereas E3 group cuffs were softer than those of the untreated controls. Endotracheal tube cuffs of the G1 and G2 groups were harder than untreated controls; than of those of the G3 and G4 groups were similar to the controls. Conclusions Endotracheal tubes can be reused sterilized safely. The physical integrity of ETT cuffs may be compromised by glutaraldehyde or ethylene oxide sterilization treatments.

Based on recent directed evolution of P450 2B1, six P450 2B11 mutants at three positions were created in an N-terminal modified construct termed P450 2B11dH and characterized for enzyme catalysis using five substrates. Mutant I209A demonstrated a 3.2-fold enhanced k(cat)/K(m) for 7-ethoxy-4-trifluoromethylcourmarin O-deethylation, largely due to a dramatic decrease in K(m) (0.72 microM vs. 18 microM). I209A also demonstrated enhanced selectivity for testosterone 16beta-hydroxylation over 16alpha-hydroxylation. In contrast, V183L showed a 4-fold increased k(cat) for 7-benzyloxyresorufin debenzylation and a 4.7-fold increased k(cat)/K(m) for testosterone 16alpha-hydroxylation. V183L also displayed a 1.7-fold higher k(cat)/K(m) than P450 2B11dH with the anti-cancer prodrugs cyclophosphamide and ifosfamide, resulting from a approximately 4-fold decrease in K(m). Introduction of the V183L mutation into full-length P450 2B11 did not enhance the k(cat)/K(m). Overall, the re-engineered P450 2B11dH enzymes exhibited enhanced catalytic efficiency with several substrates including the anti-cancer prodrugs.

BACKGROUND: Cancer of unknown primary origin (CUP) is defined by the presence of pathologically identified metastatic disease without clinical or radiological evidence of a primary tumour. Our objective was to identify incident cases of CUP in Ontario, Canada, and determine the influence of histology and sites of metastases on overall survival (OS). MATERIAL AND METHODS: We used the Ontario Cancer Registry (OCR) and the Same-Day Surgery and Discharge Abstract Database (SDS/DAD) to identify patients diagnosed with CUP in Ontario between 1 January 2000, and 31 December 2005. Patient diagnostic information, including histology and survival data, was obtained from the OCR. We cross-validated CUP diagnosis and obtained additional information about metastasis through data linkage with the SDS/DAD database. OS was assessed using Cox regression models adjusting for histology and sites of metastases. RESULTS: We identified 3564 patients diagnosed with CUP. Patients without histologically confirmed disease (n = 1821) had a one-year OS of 10.9%, whereas patients with confirmed histology (n = 1743) had a one-year OS of 15.6%. The most common metastatic sites were in the respiratory or digestive systems (n = 1603), and the most common histology was adenocarcinoma (n = 939). Three-year survival rates were 3.5%, 5.3%, 41.6% and 3.6% among adenocarcinoma, unspecified carcinoma, squamous cell carcinoma and undifferentiated histology, respectively. Three-year survival rates were 40%, 2.4%, 8.0% and 4.6% among patients with metastases localised to lymph nodes, the respiratory or digestive systems, other specified sites, and unspecified sites, respectively. CONCLUSION: CUP patients in Ontario have a poor prognosis. Some subgroups may have better survival rates, such as patients with metastases localised to lymph nodes and patients with squamous cell histology.

Multi-channel seismic reflection data from the eastern Northern South Yellow Sea Basin identify various igneous and related features such as stocks, laccoliths, sills, dikes, volcanic edifices, and hydrothermal vent systems. The stocks are tall, vertical intrusives, characterized by a seismically dead zone with upturned host rocks and uplifted overburden. The laccoliths form broad, low-relief mounds with tapering edges. The sills are imaged as concordant, high-amplitude reflections with a distinct lateral extent. The dikes are characterized by steeply inclined, cross-cutting reflections. The volcanic edifices, observed on the top of the shallow, eroded basement, consist of mounds and peaks, probably representing volcanoes and/or their remnants (or necks). The hydrothermal vent systems consist of a shallow crater-like vent, a vertical conduit that appears as a seismic chimney, and deeper sills. The stocks and the laccoliths can provide hydrocarbon traps similar to those associated with salt diapirs. The dikes, if injected into tilted or deformed strata, can form fault-like traps. The sills may form seals and also enhance the maturation of source rocks by high heat and insulation. The volcanic edifices, if weathered and/or fractured, can provide reservoirs. The hydrothermal vents may form focused conduits for fluid migration.

Parkinson disease is a neurodegenerative disease characterized by loss of midbrain dopaminergic neurons resulting in movement disorder. Neural stem cells (NSC) of the CNS have recently aroused a great deal of interest, not only because of their importance in basic research of neural development, but also for their therapeutic potential in neurological disorders. We have recently generated an immortalized human NSC cell line, HB1.F3, via retrovirus-mediated v-myc transfer. This line is capable of self-renewal, is multipotent, and expresses cell specific markers for NSC, ATP-binding cassettes transporter (ABCG2) and nestin. Next, we co-transduced the F3 NSC line with genes encoding tyrosine hydroxylase (TH) and GTP cyclohydrolase 1 (GTPCH1) in order to generate dopamine-producing NSC. The F3.TH.GTPCH human NSC line expresses TH and GTPCH phenotypes as determined by RT-PCR, western blotting and immunocytochemistry, and shows a 800 to 2000-fold increase in production of L-dihydroxyphenyl alanine in HPLC analysis. A marked improvement in amphetamine-induced turning behavior was observed in parkinsonian rats implanted with F3.TH.GTPCH cells, but not in control rats receiving F3 NSC. In the animals showing functional improvement, a large number of TH-positive F3.TH.GTPCH NSC were found at injection sites. These results indicate that human NSC, genetically transduced with TH and GTPCH1 genes, have great potential in clinical utility for cell replacement therapy in patients suffering from Parkinson disease.

The fundamentals of 3-D airflow as well as heat and water vapor transport and droplet vaporization (or hygroscopicity) are described for a human upper airway model under steady laminar-transitional-turbulent inspiratory flow conditions. Water vapor distributions from the mouth to the first four generations of the tracheobronchial tree are given in terms of relative humidity or mass fraction. The mass transfer coefficients of water vapor are correlated as a function of local flow rate and temperature-dependent diffusivity, which can be readily used for estimating the regional water loss or moisture variations in the human upper airways. Furthermore, the dynamics of hygroscopicity and deposition of isotonic saline droplets have been simulated as an example, applying the basic theory. Specifically, droplet evaporation rates and deposition pattern are analyzed and the effects of inhalation flow rates and thermodynamic air properties are discussed.

Potential human exposure to vapors of methyl tertiary-butyl ether (MTBE) and ethanol is of increasing concern because these materials are widely used as gasoline additives. In this study we analyzed numerically the transport and deposition of MTBE and ethanol vapors in a model of the human upper respiratory airway, consisting of an oral airway and the first four generations of the tracheobronchial tree. Airflow characteristics and mass transfer processes were analyzed at different inspiratory flow conditions using a three-dimensional computational fluid and particle dynamics method. The deposition data were analyzed in terms of regional deposition fractions (DF = regional uptake/mouth concentration) and deposition enhancement factors (DEF = local DF/average DF) at local micro surface areas. Results show that DF in the entire upper airway model is 21.9%, 12.4%, and 6.9% for MTBE and 67.5%, 51.5%, and 38.5% for ethanol at a flow rate of 15, 30, and 60 L/min, respectively. Of the total DF, 65-70% is deposited in the oral airway for both vapors. Deposition is localized at various sites within the upper airway structure, with a maximum DEF of 1.5 for MTBE and 7.8 for ethanol. Local deposition patterns did not change with inhalation conditions, but DF and the maximum DEF increased with diffusivity, solubility, and the degree of airway wall absorption of vapors, as shown by a greater deposition of ethanol than MTBE. The vapor deposition efficiency as expressed by the dimensionless mass transfer coefficient correlated well with a product of Reynolds (Re) and Schmidt (Sc) numbers. In conclusion, MTBE and ethanol vapors deposit substantially in the upper airway structure with a marked enhancement of dose at local sites, and the deposition dose may be reasonably estimated by a functional relationship with dimensionless fluid flow and diffusion parameters.

A short, practical, and validated quality of life (QoL) scale for hemifacial spasm (HFS) is not currently available.To examine the reliability and validity of a short self-rating scale (HFS-7) by comparing HFS patients with healthy controls. We also evaluated the correlation of HFS-7 with the physical and mental domains of SF-36, a generic QoL scale.Seven self-rating items (HFS-7) were administered to HFS patients and healthy controls. In addition, HFS patients answered the SF-36 questionnaire. The validity and reliability of HFS-7 were analysed and correlation between HFS-7 and SF-36 examined.A total of 178 subjects were enrolled in the study, including 85 HFS patients with mean age of 54.8 (SD 11.0) years, of whom 52 (61.2%) were women, and 93 controls with mean age of 51.4 (SD 10.0) years, of whom 59 (63.4%) were women. The test-retest intraclass correlation coefficient for the seven items was between 0.75 and 0.90 and Cronbach's coefficient of reliability for the HFS-7 scale was 0.88. Every item in HFS-7 discriminated between disease and controls (p0.0001). The HFS-7 summary index correlated with the SF-36 summary score (Spearman's correlation r = -0.28, p = 0.009), in particular the mental health summary score (r = -0.416, p0.0001) and the emotional domain (r = -0.466, p0.00001).HFS-7 could prove useful as a simple clinical tool to assess and monitor QoL measures in HFS patients.

In summary, in this work, we demonstrated the application of the grating-coupled SPR for the fabrication of an EO light modulator. SPR-based EO modulators reported to date have mostly used the Kretchmann configuration. To the best of authors’ knowledge, this work reports the first fabrication and demonstration of a grating-coupled EO modulator. By switching on and off of the applied voltage of 5 V, the subsequent variation of SPR was observed clearly. It should be mentioned that currently our study was limited to show the feasibility of our concept. For practical applications, further optimization of SPR signal will be required, which is a subject of our ongoing research.

Cytochrome P450 2B1 has been subjected to directed evolution to investigate the role of amino acid residues outside of the active site and to engineer novel, more active P450 catalysts. A high throughput screening system was developed to measure H(2)O(2)-supported oxidation of the marker fluorogenic substrate 7-ethoxy-4-trifluoromethylcoumarin (7-EFC). Random mutagenesis by error-prone polymerase chain reaction and activity screening were optimized using the L209A mutant of P450 2B1 in an N-terminally modified construct with a C-terminal His tag (P450 2B1dH). Two rounds of mutagenesis and screening and one subcloning step yielded the P450 2B1 quadruple mutant V183L/F202L/L209A/S334P, which demonstrated a 6-fold higher k(cat) than L209A. Further random or site-directed mutagenesis did not improve the activity. When assayed in an NADPH-supported reconstituted system, V183L/L209A demonstrated lower 7-EFC oxidation than L209A. Therefore, F202L/L209A/S334P was generated, which showed a 2.5-fold higher k(cat)/K(m) for NADPH-dependent 7-EFC oxidation than L209A. F202L/L209A/S334P also showed enhanced catalytic efficiency with 7-benzyloxyresorufin, benzphetamine, and testosterone, and a 10-fold increase in stereoselectivity for testosterone 16alpha-versus 16beta-hydroxylation compared with 2B1dH. Enhanced catalytic efficiency of F202L/L209A/S334P was also retained in the full-length P450 2B1 background with 7-EFC and testosterone as substrates. Finally, the individual mutants were tested for metabolism of the anti-cancer prodrugs cyclophosphamide and ifosfamide. Several of the mutants showed increased metabolism via the therapeutically beneficial 4-hydroxylation pathway, with L209A/S334P showing 2.8-fold enhancement of k(cat)/K(m) with cyclophosphamide and V183L/L209A showing 3.5-fold enhancement with ifosfamide. Directed evolution can thus be used to enhance P450 2B1 catalytic efficiency across a panel of substrates and to identify functionally important residues distant from the active site.

Simulation results of microparticle and nanoparticle deposition patterns, local concentrations, and segmental averages are contrasted for a human upper airway model starting from the mouth to planar airway generation G3 under different inspiratory flow conditions. Specifically, using a commercial finite-volume software with user-supplied programs as a solver, the Euler–Euler (nanoparticles) or the Euler–Lagrange (microparticles) approach was employed with a low-Reynolds-number k – ω model for laminar-to-turbulent airflow and submodels for particle-phase randomization. The results show that depositions of both micro- and nano-size particles vary measurably in the human upper airways; however, the deposition distributions are much more uniform for nanoparticles. The maximum deposition enhancement factor, which is defined as the ratio of local to average deposition concentrations, ranges from about 40 to 2400 for microparticles and about 2 to 11 for nanoparticles with inspiratory flow rates in the range of 15 ⩽ Q in ⩽ 60 l/min. In addition, some airway bifurcations in generations G0 to G3 subjected to high inlet flow rates (say, Q in = 60 l / min ) may receive only very small amounts of large micro-size particles (say, with aerodynamic diameter d ae ⩾ 10 μ m ) due to largely preferred upstream deposition. It has been hypothesized that, uniformly deposited nanoparticles of similar concentrations may have greater toxicity effects when compared to microparticles of the same material.

Transport and deposition of ultrafine particles in straight, bent and bifurcating tubes are considered for different inlet Reynolds numbers, velocity profiles, and particle sizes, i.e., 1 nm⩽dp⩽150 nm. A commercial finite-volume code with user-supplied programs was validated with analytical correlations and experimental data sets for nanoparticle depositions, considering a straight tube, a tubular 90° bend, and a G3-G5 double bifurcation with both planar and nonplanar configurations. The focus is on the airflow structures as well as nanoparticle deposition patterns and deposition efficiencies, which were analyzed for planar and nonplanar bifurcating lung airway models representing part of the upper bronchial tree. Deposition takes place primarily by Brownian diffusion, and thus deposition efficiencies increase with decreasing nanoparticle size and lower inlet Reynolds numbers. Deposition in the nonplanar configuration differs only slightly from that in the planar configuration. When compared with axisymme...

Ultrafine particles are ubiquitous in the ambient air, and their unique physicochemical characteristics may pose a potential health hazard. Accurate lung dose information is essential to assess a potential health risk from exposure to these particles. In the present study, we measured total respiratory tract deposition fraction (TDF) of inert ultrafine aerosols (NMD = 0.04, 0.06, 0.08, and 0.10 μm and σg 1.3) in a group of young healthy adults (11 males and 11 females). A fast-response ultrafine condensation particle counter was used for continuous monitoring of inhaling aerosols breath by breath. Six different breathing patterns were used: three different tidal volumes (Vt = 500, 750, and 1000 ml) and two different flow rates for each Vt. The mean respiratory time (Tm) ranged from 2 to 4 s. The measured data showed that TDF increased with a decrease in particle size, thereby an increase in diffusion coefficient (D), and with an increase in Tm and Vt. For a given particle size both Tm and Vt were almost e...