Pump RIN-induced impairments in unrepeatered transmission systems using distributed Raman amplifier.
High spectral efficiency modulation format based unrepeatered transmission systems using distributed Raman amplifier (DRA) have attracted much attention recently. To enhance the reach and optimize system performance, careful design of DRA is required based on the analysis of various types of impairments and their balance. In this paper, we study various pump RIN induced distortions on high spectral efficiency modulation formats. The vector theory of both 1st and higher-order stimulated Raman scattering (SRS) effect using Jones-matrix formalism is presented. The pump RIN will induce three types of distortion on high spectral efficiency signals: intensity noise stemming from SRS, phase noise stemming from cross phase modulation (XPM), and polarization crosstalk stemming from cross polarization modulation (XPolM). An analytical model for the statistical property of relative phase noise (RPN) in higher order DRA without dealing with complex vector theory is derived. The impact of pump RIN induced impairments are analyzed in polarization-multiplexed (PM)-QPSK and PM-16QAM-based unrepeatered systems simulations using 1st, 2nd and 3rd-order forward pumped Raman amplifier. It is shown that at realistic RIN levels, negligible impairments will be induced to PM-QPSK signals in 1st and 2nd order DRA, while non-negligible impairments will occur in 3rd order case. PM-16QAM signals suffer more penalties compared to PM-QPSK with the same on-off gain where both 2nd and 3rd order DRA will cause non-negligible performance degradations. We also investigate the performance of digital signal processing (DSP) algorithms to mitigate such impairments.


Parechovirus A Infections in Healthy Australian Children During the First 2 Years of Life: A Community-based Longitudinal Birth Cohort Study.
Hospital-based studies identify parechovirus (PeV), primarily PeV-A3, as an important cause of severe infections in young children. However, few community-based studies have been published and the true PeV infection burden is unknown. We investigated PeV epidemiology in healthy children participating in a community-based, longitudinal birth cohort study. Australian children (n = 158) enrolled in the Observational Research in Childhood Infectious Diseases (ORChID) study were followed from birth until their second birthday. Weekly stool and nasal swabs and daily symptom diaries were collected. Swabs were tested for PeV by reverse-transcription polymerase chain reaction and genotypes determined by subgenomic sequencing. Incidence rate, infection characteristics, clinical associations, and virus codetections were investigated. PeV was detected in 1423 of 11 124 (12.8%) and 17 of 8100 (0.2%) stool and nasal swabs, respectively. Major genotypes among the 306 infection episodes identified were PeV-A1 (47.9%), PeV-A6 (20.1%), and PeV-A3 (18.3%). The incidence rate was 144 episodes (95% confidence interval, 128-160) per 100 child-years. First infections appeared at a median age of 8 (interquartile range, 6.0-11.7) months. Annual seasonal peaks changing from PeV-A1 to PeV-A3 were observed. Infection was positively associated with age ≥6 months, summer season, nonexclusive breastfeeding at age <3 months, and formal childcare attendance before age 12 months. Sole PeV infections were either asymptomatic (38.4%) or mild (32.7%), while codetection with other viruses in stool swabs was common (64.4%). In contrast with hospital-based studies, this study showed that diverse and dynamically changing PeV genotypes circulate in the community causing mild or subclinical infections in children.Parechovirus can cause severe illnesses in children. However, studies focus mainly on hospitalized populations. True disease burden in the community remains largely unknown. From our community-based cohort, we found diverse parechovirus genotypes in the community, causing mild or subclinical infections in children. NCT01304914.


Ethical stumbling blocks in uncovering folate deficiency as a preventable cause of spina bifida.
The year 2016 witnessed the anniversaries of several key events related to the prevention of neural tube defects (NTD) with folate supplementation. However, the road leading up to this achievement was full of stumbling blocks, both in terms of research ethics and researcher ethics. First, the decisions of ethics review boards differed with respect to allowing placebo groups in folate trials, thus reducing the level of evidence obtained from the earliest studies. Second, statisticians insisted on analysing the outcome of a trial by intention-to-treat - which turned out to be non-significant - rather than by treatment received, which was statistically significant. Third, the recognition of positive results was stymied by the reluctance of some researchers to recognise and quote others' contributions. All this needlessly delayed the recognition of the NTD-preventive effects of folate by a decade. The story of the prevention of NTD thus offers insights into research inadequacies that have the potential to impede the advance of medical science, with the ethical aspects having the most immediate impact. Efficient ethics review boards play a major role worldwide and if they play safe, they may risk disallowing high-quality studies of great public health import.


Precision measurements of the optical attenuation profile along the propagation path in thin-film waveguides.
An experimental technique for precision measurements of the optical attenuation profile along a propagation path in thin-film waveguides is reported. The method involves a 100% outcoupling of guided light through immersion of the waveguide into a liquid with an index of refraction slightly higher than that of the film. The measurement is simple and nondestructive. The repeatability and accuracy of the measured attenuation per unit length is typically better than 5%, even with losses below 0.1 dB/cm and less than 1-cm-long guiding paths.


Neurotrophin regulation of ionic currents and cell size depends on cell context.
Trk receptor activation by neurotrophins is often considered to have a defined set of actions on target neurons, including supporting neuronal survival, inducing morphological differentiation, and regulating a host of target genes that specify neuronal phenotype. It is not known if all such regulatory effects are obligatory, or if some may vary depending on the cell context in which the receptors are expressed. We have examined this issue by comparing neurotrophin effects on the regulation of electrical excitability and morphological differentiation in two strains of PC12 cells. We found that while neurotrophins induced neurite extension and increased calcium currents in both PC12 cell types, sodium current levels were regulated in only one of these strains. Moreover, we found little correlation between calcium current levels and the extent of morphological differentiation when compared in individual cells of a single strain. Thus, the regulatory effects of neurotrophins on cell phenotype are not fully determined by the Trk receptors that they activate; rather, they can vary with differences in cell context that arise not only between different cell lineages, but also between individual cells of clonal relation.


Transverse plane pelvic rotation increase (TPPRI) following rotationally corrective instrumentation of adolescent idiopathic scoliosis double curves.
We have occasionally observed clinically noticeable postoperative transverse plane pelvic rotation increase (TPPRI) in the direction of direct thoracolumbar/lumbar rotational corrective load applied during posterior instrumentation and arthrodesis for double (Lenke 3 and 6) adolescent idiopathic scoliosis (AIS) curves. Our purposes were to document this occurrence; identify its frequency, associated variables, and natural history; and determine its effect upon patient outcome. Transverse plane pelvic rotation (TPPR) can be quantified using the left/right hemipelvis width ratio as measured on standing posterior-anterior scoliosis radiographs. Descriptive statistics were done to determine means and standard deviations. Non-parametric statistical tests were used due to the small sample size and non-normally distributed data. Significance was set at P < 0.05. Seventeen of 21 (81%) consecutive patients with double curves (7 with Lenke 3 curves and 10 with Lenke 6) instrumented with lumbar pedicle screw anchors to achieve direct rotation had a complete sequence of measurable radiographs. While 10 of these 17 had no postoperative TPPRI, 7 did all in the direction of the rotationally corrective thoracolumbar instrumentation load. Two preoperative variables were associated with postoperative TPPRI: more tilt of the vertebra below the lower instrumented vertebra (-23° ± 3.1° vs. -29° ± 4.6°, P = 0.014) and concurrent anterior thoracolumbar discectomy and arthrodesis (5 of 10 vs. 7 of 7, P = 0.044). Patients with a larger thoracolumbar/lumbar angle of trunk inclination or larger lower instrumented vertebra plus one to sacrum fractional/hemicurve were more likely to have received additional anterior thoracolumbar discectomy and arthrodesis (c = 0.90 and c = 0.833, respectively).Postoperative TPPRI resolved in 5 of the 7 by intermediate follow-up at 12 months. Patient outcome was not adversely affected by postoperative TPPRI, whether or not it persisted. Our findings suggest that TPPRI is a decompensation caused by extension of the corrective thoracolumbar rotational load into the lumbosacral hemicurve below. As posterior instrumentation of adolescent idiopathic scoliosis becomes increasingly more effective in the transverse plane, postoperative TPPRI may become more widely noticed. This study provides some assurance that recompensation usually occurs, but that in either event TPPRI does not seem to affect clinical outcome.


The anatomy of the professional lapse: bridging the gap between traditional frameworks and students' perceptions.
To support students' developing professionalism, it is necessary to understand the professional challenges and dilemmas they perceive in the clinical setting. This study systematically documented and catalogued students' reports of professional lapses. Six focus groups were conducted with senior medical students (n = 29) at three universities. Using a grounded-theory approach, three researchers analyzed the students' reports of specific lapses in professionalism for recurrent themes. The resulting coding structure was applied using NVivo qualitative data analysis software. A total of 120 pages of text yielded 48 specific incidents of professional lapses, which were analyzed by three researchers using grounded theory. Most incidents were witnessed (n = 34) or known about (n = 4), as opposed to self-reported (n = 10). Six critical "issues" emerged: communicative violations (to or about patients or other health care professionals); role resistance (individuals chafing against constraints or expectations of their perceived roles); objectification of patients (ignoring patients or treating patients as vehicles for learning); accountability (to colleagues or patients, including avoiding patients, failing to disclose information, or failing to treat appropriately); physical harm (to patients or others); and crossfire (being put in the middle of a struggle between superiors). This study explored how students experienced and operationalized professionalism in clinical settings at a variety of universities. Interestingly, the critical issues they reported as salient did not map easily onto standard, abstract definitions of professionalism. This incongruence suggested that the development of effective curricula in this domain must bridge the gap between traditional taxonomies and students' perceptions of professionalism.


Single Cell Proteomics for Molecular Targets in Lung Cancer: High-Dimensional Data Acquisition and Analysis.
In the proteomic and genomic era, lung cancer researchers are increasingly under challenge with traditional protein analyzing tools. High output, multiplexed analytical procedures are in demand for disclosing the post-translational modification, molecular interactions and signaling pathways of proteins precisely, specifically, dynamically and systematically, as well as for identifying novel proteins and their functions. This could be better realized by single-cell proteomic methods than conventional proteomic methods. Using single-cell proteomic tools including flow cytometry, mass cytometry, microfluidics and chip technologies, chemical cytometry, single-cell western blotting, the quantity and functions of proteins are analyzed simultaneously. Aside from deciphering disease mechanisms, single-cell proteomic techniques facilitate the identification and screening of biomarkers, molecular targets and promising compounds as well. This review summarized single-cell proteomic tools and their use in lung cancer.


Investigating the association between polymorphisms in connective tissue growth factor and susceptibility to colon carcinoma.
There have been numerous studies on the gene expression of connective tissue growth factor (CTGF) in colorectal cancer, however very few have investigated polymorphisms in this gene. The present study aimed to determine whether single nucleotide polymorphisms (SNPs) in the CTGF gene are associated with a higher susceptibility to colon cancer and/or an invasive tumor growth pattern. The CTGF gene was genotyped for seven SNPs (rs6918698, rs1931002, rs9493150, rs12526196, rs12527705, rs9399005 and rs12527379) by pyrosequencing. Formalin‑fixed paraffin‑embedded tissue samples (n=112) from patients diagnosed with colon carcinoma, and an equal number of blood samples from healthy controls, were selected for genomic DNA extraction. The complexity index was measured using images of tumor samples (n=64) stained for cytokeratin‑8. The images were analyzed and correlated with the identified CTGF SNPs and clinicopathological parameters of the patients, including age, gender, tumor penetration, lymph node metastasis, systemic metastasis, differentiation and localization of tumor. It was demonstrated that the frequency of the SNP rs6918698 GG genotype was significantly associated (P=0.05) with an increased risk of colon cancer, as compared with the GC and CC genotypes. The other six SNPs (rs1931002, rs9493150, rs12526196, rs12527705, rs9399005 and rs12527379) exhibited no significant difference in the genotype and allele frequencies between patients diagnosed with colon carcinoma and the normal healthy population. A trend was observed between genotype variation at rs6918698 and the complexity index (P=0.052). The complexity index and genotypes for any of the studied SNPs were not significantly correlated with clinical or pathological parameters of the patients. These results indicate that the rs6918698 GG genotype is associated with an increased risk of developing colon carcinoma, and genetic variations at the rs6918698 are associated with the growth pattern of the tumor. The present results may facilitate the identification of potential biomarkers of the disease in addition to drug targets.


Predicting permeability of compacted clay filtrated with landfill leachate by k-Nearest Neighbors modelling method.
It is important to protect the soil and groundwater from the pollution originating from leachate. Compacted clay soils is a favorable and economic method to protect groundwater and soil against contamination. In this study, compaction tests of leachate was done by using Modified Proctor method. The effects of microbial activity on the permeability of compacted clay soils were analyzed and the obtained data were applied to k-Nearest Neighbors (k-NN) method to predict the permeability of soils in landfill sites. k-NN method, which is a non-parametric distance-based machine learning method and widely used in classification and regression problems was applied to model the relationship between the microorganisms and the permeability. By using k-NN classification method, total heterotrophic bacteria and fungi microorganisms correctly classified the permeability variance as 78.59% and 77.31% success rate, respectively. Also, k-NN modelling was set on regression mode to predict permeability value and produced similar success rates in regression similarity with the actual value. Although, fecal coliforms and fecal streptococci microorganisms had neutral or negative contribution on analyses. For prediction accuracy and regression analysis, the k-NN method was considered for modeling the data. The results of the k-Nearest Neighbors method proved that it is a promising tool for predicting permeability of compacted clay by using microbial activity.


Elucidating the mechanism of posterior reversible encephalopathy syndrome: a case of transient blindness after central venous catheterization.
Posterior reversible encephalopathy syndrome (PRES) is a condition characterized by reversible symptoms including headache, visual disturbances, focal neurological deficits, altered mentation, and seizures. It has been associated with circumstances that may affect the cerebrovascular system, such as hypertension, eclampsia, and immunosuppression with calcineurin inhibitors. The underlying etiology of PRES has remained unclear; however, cerebrovascular autoregulatory dysfunction, hyperperfusion, and endothelial activation have been implicated. We describe a case of a young patient with lung transplant, who presented with headache, acute binocular blindness, and seizure immediately after infusion of saline through a peripherally inserted central catheter line, which inadvertently terminated cephalad in the left internal jugular vein, near the jugular foramen. Subsequent brain magnetic resonance imaging revealed vasogenic edematous lesions in a pattern consistent with PRES--a diagnosis supported by his constellation of symptoms, history of lung transplantation on tacrolimus immunosuppression, and relative hypertension. This is the first reported case describing the development of PRES after the insertion of a peripherally inserted central catheter line. The development of PRES in a typical high-risk patient immediately after cerebral venous outflow obstruction implicates the role of the cerebral venous system and provides potential insight into the mechanism of this disorder that remains of unclear pathogenesis.


Alcoholic cirrhosis and hepatocellular carcinoma.
Hepatocellular carcinoma shows a rising incidence worldwide, and the largest burden of disease in Western countries derives from patients with alcoholic liver disease (ALD) and cirrhosis, the latter being the premier premalignant factor for HCC. The present chapter addresses key issues including the epidemiology of alcohol-associated HCC, and its link to other coexisting non-alcoholic liver diseases, and additional host and environmental risk factors including the underlying genetics. Also discussed are molecular mechanisms of alcohol-associated liver cancer evolution involving the mediators of alcohol toxicity and carcinogenicity, acetaldehyde and reactive oxygen species, as well as the recently described mutagenic adducts which these mediators form with DNA. Specifically, interference of alcohol with retinoids and cofactors of transmethylation processes are outlined. Information presented in this chapter illustrates that the development of HCC in the context of ALD is multifaceted and suggests several molecular targets for prevention and markers for the screening of risk groups.


Hybrid integrated plasmonic-photonic waveguides for on-chip localized surface plasmon resonance (LSPR) sensing and spectroscopy.
We experimentally demonstrate efficient extinction spectroscopy of single plasmonic gold nanorods with exquisite fidelity (SNR > 20dB) and high efficiency light coupling (e. g., 9.7%) to individual plasmonic nanoparticles in an integrated platform. We demonstrate chip-scale integration of lithographically defined plasmonic nanoparticles on silicon nitride (Si3N4) ridge waveguides for on-chip localized surface plasmon resonance (LSPR) sensing. The integration of this hybrid plasmonic-photonic platform with microfluidic sample delivery system is also discussed for on-chip LSPR sensing of D-glucose with a large sensitivity of ∼ 250 nm/RIU. The proposed architecture provides an efficient means of interrogating individual plasmonic nanoparticles with large SNR in an integrated alignment-insensitive platform, suitable for high-density on-chip sensing and spectroscopy applications.


Frictional properties of light-activated antimicrobial polymers in blood vessels.
The adhesion of microbes to catheter surfaces is a serious problem and the resulting infections frequently lead to longer hospitalisation and higher risk for the patient. Several approaches have been developed to produce materials that are less susceptible to microbial colonisation. One such approach is the incorporation of photoactivated compounds, such as Toluidine Blue O (TBO), in the polymeric matrix resulting in 'light-activated antimicrobial materials'. The insertion and removal of catheters can cause tissue damage and patient discomfort through frictional forces; hence the lubricity of a catheter material is also very important. In this work the tribological performance of silicone and polyurethane containing TBO and gold nanoparticles were evaluated using two different surfaces, the inner part of the aorta and the superior vena cava of sheep. Static and kinetic friction coefficients of these materials were measured using a tribometric device developed for in vitro applications using dry materials and those lubricated with blood. It was found that neither the preparation process nor the presence of TBO or gold nanoparticles, had an effect on the friction factors in comparison to those of untreated materials. In all cases, static and kinetic friction coefficients on aorta tissue were higher than those on vena cava due to higher surface roughness of the aorta. The presence of blood as a lubricant resulted in lower friction coefficients.


Effect of high-flow nasal cannula oxygen therapy in adults with acute hypoxemic respiratory failure: a meta-analysis of randomized controlled trials.
Conflicting recommendations exist on whether high-flow nasal cannula (HFNC) oxygen therapy should be administered to adult patients in critical care with acute hypoxemic respiratory failure. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate its effect on intubation rates. We searched electronic databases from inception to April 2016. We included RCTs that compared HFNC oxygen therapy with usual care (conventional oxygen therapy or noninvasive ventilation) in adults with acute hypoxemic respiratory failure. Because of the different methodologies and variation in clinical outcomes, we conducted 2 subgroup analyses according to oxygen therapy used and disease severity. We pooled data using random-effects models. The primary outcome was the proportion of patients who required endotracheal intubation. We included 6 RCTs (n = 1892). Compared with conventional oxygen therapy, HFNC oxygen therapy was associated with a lower intubation rate (risk ratio [RR] 0.60, 95% confidence interval [CI] 0.38 to 0.94; I2 = 49%). We found no significant difference in the rate between HFNC oxygen therapy and noninvasive ventilation (RR 0.86, 95% CI 0.68 to 1.09; I2 = 2%). In the subgroup analysis by disease severity, no significant differences were found in the intubation rate between HFNC oxygen therapy and either conventional oxygen therapy or noninvasive ventilation (interaction p = 0.3 and 0.4, respectively). The intubation rate with HFNC oxygen therapy was lower than the rate with conventional oxygen therapy and similar to the rate with noninvasive ventilation among patients with acute hypoxemic respiratory failure. Larger, high-quality RCTs are needed to confirm these findings.


Identifying the content area for the 51-item National Eye Institute Visual Function Questionnaire: results from focus groups with visually impaired persons.
To identify the content area for a questionnaire designed to measure vision-targeted health-related quality of life and to determine whether problems with vision-related functioning are qualitatively similar across different common eye diseases. Twenty-six condition-specific focus groups were conducted with 246 patients from 5 geographic regions to identify the content area for a questionnaire for use among persons with diabetic retinopathy, glaucoma, macular degeneration, cytomegalovirus retinitis, and cataract. A standard protocol was used to structure each focus group discussion. Sessions were audiotaped, transcribed, and coded in preparation for a content analysis. Five university-based ophthalmology practices and 1 nonprofit eye care foundation. Eligible participants had to have 1 of the following eye conditions: age-related cataracts, age-related macular degeneration, diabetic retinopathy, primary open angle glaucoma, cytomegalovirus retinitis, or low vision from any cause. All eligible persons were older than 21 years, spoke English, and had sufficient cognitive function to provide informed consent. Among the 246 participants, 2623 problems with vision-related functioning were mentioned. The mean number of problems per person ranged from 13.5 for those with diabetic retinopathy to 7.9 for persons with glaucoma. For the sample overall, reading problems were mentioned most frequently, followed by driving, general problems with seeing clearly, and mental health complaints caused by vision. Although the proportion of persons who reported each problem varied by condition, at least some persons with each eye disease reported each problem. The 3 most common descriptors associated with each problem were difficulty or ease of performance (13%), psychological distress associated with performance of the activity (11%), and complete inability to participate in a visual activity (11%). An item-generation strategy for a new questionnaire using a standardized focus group method identified content areas and aspects of visual disability that are not included in currently available vision-specific instruments that assess the impact of common eye diseases on visual functioning in every-day life. Although participants mentioned problems that were unique to their disease, across conditions the problems mentioned were similar. These findings provide empirical evidence of content validity for a vision-targeted, health-related quality-of-life survey designed for use across conditions.


Serum Lipid and Serum Metabolite Components in relation to anthropometric parameters in EPIC-Potsdam participants.
Lipidomic and metabolomic techniques become more and more important in human health research. Recent developments in analytical techniques enable the investigation of high amounts of substances. The high numbers of metabolites and lipids that are detected with among others mass spectrometric techniques challenge in most cases the statistical processes to bring out stable and interpretable results. This study targets to use the novel non-established statistical method treelet transform (TT) to investigate high numbers of metabolites and lipids and to compare the results with the established method principal component analysis (PCA). Serum lipid and metabolite profiles are investigated regarding their association to anthropometric parameters associated to obesity. From 226 participants of the EPIC (European Prospective Investigation into Cancer and Nutrition)-Potsdam study blood samples were investigated with an untargeted metabolomics approach regarding serum metabolites and lipids. Additionally, participants were surveyed anthropometrically to assess parameters of obesity, such as body mass index (BMI), waist-to-hip-ratio (WHR) and body fat mass. TT and PCA are used to generate treelet components (TCs) and factors summarizing serum metabolites and lipids in new, latent variables without too much loss of information. With partial correlations TCs and factors were associated to anthropometry under the control for relevant parameters, such as sex and age. TT with metabolite variables (p=121) resulted in 5 stable and interpretable TCs explaining 18.9% of the variance within the data. PCA on the same variables generated 4 quite complex, less easily interpretable factors explaining 37.5% of the variance. TT on lipidomic data (p=353) produced 3 TCs as well as PCA on the same data resulted in 3 factors; the proportion of explained variance was 17.8% for TT and 39.8% for PCA. In both investigations TT ended up with stable components that are easier to interpret than the factors from the PCA. In general, the generated TCs and factors were similar in their structure when the factors are considered regarding the original variables loading high on them. Both TCs and factors showed associations to anthropometric measures. TT is a suitable statistical method to generate summarizing, latent variables in data sets with more variables than observations. In the present investigation it resulted in similar latent variables compared to the established method of PCA. Whereby less variance is explained by the summarizing constructs of TT compared to the factors of PCA, TCs are easier to interpret. Additionally the resulting TCs are quite stable in bootstrap samples.


Evidence for Top Quark Production in Nucleus-Nucleus Collisions.
Ultrarelativistic heavy ion collisions recreate in the laboratory the thermodynamical conditions prevailing in the early universe up to 10^{-6} sec, thereby allowing the study of the quark-gluon plasma (QGP), a state of quantum chromodynamics (QCD) matter with deconfined partons. The top quark, the heaviest elementary particle known, is accessible in nucleus-nucleus collisions at the CERN LHC, and constitutes a novel probe of the QGP. Here, we report the first evidence for the production of top quarks in nucleus-nucleus collisions, using lead-lead collision data at a nucleon-nucleon center-of-mass energy of 5.02 TeV recorded by the CMS experiment. Two methods are used to measure the cross section for top quark pair production (σ_{tt[over ¯]}) via the selection of charged leptons (electrons or muons) and bottom quarks. One method relies on the leptonic information alone, and the second one exploits, in addition, the presence of bottom quarks. The measured cross sections, σ_{tt[over ¯]}=2.54_{-0.74}^{+0.84} and 2.03_{-0.64}^{+0.71} μb, respectively, are compatible with expectations from scaled proton-proton data and QCD predictions.


Signet-ring cell lymphoma of bone marrow.
A case of signet-ring cell lymphoma affecting bone marrow is reported. The tumour presented as multiple lytic lesions in the lumbosacral spine. A bone biopsy specimen showed the typical appearances of signet-ring cell lymphoma, and the cells stained positively with antiserum to CD20, though neither immunoglobulin light or heavy chains could be shown within the vacuoles. The patient subsequently responded to chemotherapy.


Anaesthetic induction and recovery characteristics of a diazepam-ketamine combination compared with propofol in dogs.
Induction of anaesthesia occasionally has been associated with undesirable behaviour in dogs. High quality of induction of anaesthesia with propofol has been well described while in contrast variable induction and recovery quality has been associated with diazepam-ketamine. In this study, anaesthetic induction and recovery characteristics of diazepam-ketamine combination with propofol alone were compared in dogs undergoing elective orchidectomy. Thirty-six healthy adult male dogs were used. After habitus scoring (simple descriptive scale [SDS]), the dogs were sedated with morphine and acepromazine. Forty minutes later a premedication score (SDS) was allocated and general anaesthesia was induced using a combination of diazepam-ketamine (Group D/K) or propofol (Group P) and maintained with isoflurane. Scores for the quality of induction, intubation and degree of myoclonus were allocated (SDS). Orchidectomy was performed after which recovery from anaesthesia was scored (SDS) and times to extubation and standing were recorded. Data were analysed using descriptive statistics and Kappa Reliability and Kendall Tau B tests. Both groups were associated with acceptable quality of induction and recovery from anaesthesia. Group P, however, was associated with a poorer quality of induction (p = 0.014), prolonged induction period (p = 0.0018) and more pronounced myoclonus (p = 0.003), but had better quality of recovery (p = 0.000002) and shorter recovery times (p = 0.035) compared with Group D/K. Diazepam-ketamine and propofol are associated with acceptable induction and recovery from anaesthesia. Propofol had inferior anaesthetic induction characteristics, but superior and quicker recovery from anaesthesia compared with diazepam-ketamine.


Memory Binding Test Distinguishes Amnestic Mild Cognitive Impairment and Dementia from Cognitively Normal Elderly.
We aimed to assess reliability and cross-sectional discriminative validity of the Memory Binding Test (MBT) to distinguish persons with amnestic cognitive impairment (aMCI) and dementia from cognitively normal elderly controls. The MBT was administered to 20 participants with dementia, 31 with aMCI and 246 controls, who received the first administration of the MBT from May 2003 to December 2007, as a substudy of the community-based Einstein Aging Study (age range: 70+). The optimal index resulted from comparing the partial area under the receiver operating characteristic curves (ROC AUC) of four major MBT indices for specificities ≥0.70. Optimal cut-score of the optimal index was selected by maximizing the sum of sensitivity and specificity. Age and education effects were assessed using stratified cut-scores and adjusted logistic regression. Reliability was computed as intraclass correlation between scores at baseline and 1-year follow-up for participants who remained cognitively normal. Total number of Items recalled in the Paired condition (TIP) was elected the optimal index. TIP cut-score was ≤22 for differentiating aMCI alone (sensitivity = 0.74, specificity = 0.73) and aMCI and dementia combined (sensitivity = 0.84, specificity = 0.73) from controls. It was ≤17 for differentiating dementia from aMCI and controls (sensitivity = 0.95, specificity = 0.87). Age and education adjustments did not materially improve discriminative validity. The reliability of TIP was 0.77. MBT achieved moderate to good reliability. TIP had superior cross-sectional discriminative validity than the other MBT indices. We recommend using the empirical cut-score of TIP ≤22 for discriminating aMCI and dementia and ≤17 for discriminating dementia alone.


Sub-specialization or super-specialization in surgery?
A special centre for prosthetic hip replacement set up 10 years ago has been successful in its primary objectives, producing high quality work at low cost and stimulating research. The project has not yet been successful in achieving a permanent staffing structure, but this is the effect of certain British ideologies in surgical training, with the result that craftsmanship and technology cannot be reconciled with pure intellectual attainment.The success of the project suggests the importance of isolating elective surgery from emergency surgery in the interests of cost-effectiveness. Problems of isolation from teaching hospitals are not insurmountable, but isolation to some degree is essential to achieve the minimum size necessary for efficiency and to ensure unbroken professional team-work among all levels of staff. While maximum efficiency in this field can be achieved only in special centres, too many primary operations will be required every year to insist that total hip replacement should be done only in special centres. A special feature of this field is the need for a permanent staffing structure to hand on technical expertise as an unbroken tradition.


Characterization of Antigenic MHC-Class-I-Restricted T Cell Epitopes in the Glycoprotein of Ebolavirus.
Ebolavirus causes highly lethal hemorrhagic fever in humans. The envelope-displayed viral glycoprotein (GP) is the primary target of humoral immunity induced by natural exposure and vaccination. No T cell epitopes in the GP have been characterized in humans. A phase I clinical trial of a heterologous prime-boost vaccination regime with viral vectors encoding filovirus antigens elicits humoral and T cell responses in vaccinees. The most frequently recognized peptide pools are deconvoluted to identify the minimal epitopes recognized by antigen-specific T cells. We characterize nine immunogenic epitopes on the Ebolavirus GP. Histocompatibility leukocyte antigen (HLA) typing with in silico epitope analysis determines the likely MHC class I restriction elements. Thirteen HLA-A and -B alleles are predicted to present the identified CD8+ T cell epitopes, suggesting promiscuous recognition and a broad immune response. Delivery of the Ebolavirus GP antigen by using a heterologous prime-boost approach is immunogenic in genetically diverse human populations, with responses against multiple epitopes.


Arterial catheters as a source of bloodstream infection: a systematic review and meta-analysis.
Catheter-related bloodstream infections are associated with significant costs and adverse consequences. Arterial catheters are commonly used in the critical care setting and are among the most heavily manipulated vascular access devices. We sought to evaluate the prevalence of arterial catheter-related bloodstream infection. PubMed, CinAHL, EMBASE, and Web of Science. Included studies reported prevalence rate of catheter-related bloodstream infection for arterial catheters used for critical illness or postoperative monitoring. For the purposes of this study, catheter-related bloodstream infection was defined as positive blood culture collected from an arterial catheter and from the periphery with the same organism in a patient demonstrating systemic signs of sepsis. The study population, site of insertion, antiseptic preparation, catheter days, and prevalence of catheter-related bloodstream infection were abstracted. When data were not available, authors were contacted for further information. Forty-nine studies met criteria including 222 cases of arterial catheter-related bloodstream infection in 30,841 catheters. Pooled incidence was 3.40/1,000 catheters or 0.96/1,000 catheter days. Prevalence was considerably higher in the subgroup of studies that cultured all catheters (1.26/1,000 catheter days) compared with those studies that cultured only when the arterial catheter was suspected as the source for the catheter-related bloodstream infection (0.70/1,000 catheter days). Pooled data also found a significantly increased risk of infection for femoral site of insertion compared with radial artery for arterial catheter placement (relative risk, 1.93; 95% CI, 1.32-2.84; p = 0.001) CONCLUSIONS: Arterial catheters are an underrecognized cause of catheter-related bloodstream infection. Pooled incidence when catheters were systematically cultured and correlated to blood culture results indicated a substantial burden of arterial catheter-related bloodstream infection. Selection of a radial site over a femoral site will help reduce the risk of arterial catheter-related bloodstream infection. Future studies should evaluate technologies applied to preventing central venous catheter-related bloodstream infection to arterial catheters as well.


New insights into heparan sulphate biosynthesis from the study of mutant mice.
Heparan sulphate (HS) is an essential co-receptor for a number of growth factors, morphogens and adhesion proteins. The biosynthetic modifications involved in the generation of a mature HS chain may determine the strength and outcome of HS-ligand interactions. These modifications are catalysed by a complex family of enzymes, some of which occur as multiple gene products. Various mutant mice have now been generated, which lack the function of isolated components of the HS biosynthetic pathway. In this discussion, we outline the key findings of these studies, and use them to put into context our own work concerning the structure of the HS generated by the Hs2st -/- mice.


A novel tumor necrosis factor-mediated mechanism of direct epithelial sodium channel activation.
Alveolar liquid clearance is regulated by Na(+) uptake through the apically expressed epithelial sodium channel (ENaC) and basolaterally localized Na(+)-K(+)-ATPase in type II alveolar epithelial cells. Dysfunction of these Na(+) transporters during pulmonary inflammation can contribute to pulmonary edema. In this study, we sought to determine the precise mechanism by which the TIP peptide, mimicking the lectin-like domain of tumor necrosis factor (TNF), stimulates Na(+) uptake in a homologous cell system in the presence or absence of the bacterial toxin pneumolysin (PLY). We used a combined biochemical, electrophysiological, and molecular biological in vitro approach and assessed the physiological relevance of the lectin-like domain of TNF in alveolar liquid clearance in vivo by generating triple-mutant TNF knock-in mice that express a mutant TNF with deficient Na(+) uptake stimulatory activity. TIP peptide directly activates ENaC, but not the Na(+)-K(+)-ATPase, upon binding to the carboxy-terminal domain of the α subunit of the channel. In the presence of PLY, a mediator of pneumococcal-induced pulmonary edema, this binding stabilizes the ENaC-PIP2-MARCKS complex, which is necessary for the open probability conformation of the channel and preserves ENaC-α protein expression, by means of blunting the protein kinase C-α pathway. Triple-mutant TNF knock-in mice are more prone than wild-type mice to develop edema with low-dose intratracheal PLY, correlating with reduced pulmonary ENaC-α subunit expression. These results demonstrate a novel TNF-mediated mechanism of direct ENaC activation and indicate a physiological role for the lectin-like domain of TNF in the resolution of alveolar edema during inflammation.


Music therapy for patients who have undergone hematopoietic stem cell transplant.
Objectives. This study examines the short- and long-term QOL benefits of a music therapy intervention for patients recovering from hematopoietic stem cell transplantation (HSCT). Methods. Ninety allogeneic HSCT patients, after transplant, were randomized to receive ISO-principle (i.e., mood matching) based music therapy (MT; n = 29), unstructured music (UM; n = 30), or usual care (UC; n = 31) for four weeks. The ISO principle posits that patients may shift their mood from one state to another by listening to music that is "equal to" the individual's initial mood state and subsequently listening to music selections that gradually shift in tempo and mood to match the patient's desired disposition. Participants in MT and UM groups developed two audio CDs to help them feel more relaxed and energized and were instructed to use the CDs to improve their mood as needed. Short-term effects on mood and long-term effects on QOL were examined. Results. MT and UM participants reported improved mood immediately after listening to CDs; the within-group effect was greater for UM participants compared to MT participants. Participant group was not associated with long-term QOL outcomes. Conclusions. Music listening improves mood acutely but was not associated with long-term benefits in this study.


Microarrays.
Microarrays are revolutionizing genetics by making it possible to genotype hundreds of thousands of DNA markers and to assess the expression (RNA transcripts) of all of the genes in the genome. Microarrays are slides the size of a postage stamp that contain millions of DNA sequences to which single-stranded DNA or RNA can hybridize. This miniaturization requires little DNA or RNA and makes the method fast and inexpensive; multiple assays of each target make the method highly accurate. DNA microarrays with hundreds of thousands of DNA markers have made it possible to conduct systematic scans of the entire genome to identify genetic associations with complex disorders or dimensions likely to be influenced by many genes of small effect size. RNA microarrays can provide snapshots of gene expression across all of the genes in the genome at any time in any tissue, which has far-reaching applications such as structural and functional 'genetic neuroimaging' and providing a biological basis for understanding environmental influence.


Optofluidic transport and manipulation of plasmonic nanoparticles by thermocapillary convection.
Optothermal control of fluid motion has been suggested as a powerful way of controlling nanomaterials in micro- or nanofluidic samples. Methods based on merely thermal convection, however, often rely on high temperature for achieving fluid velocities suitable for most practical uses. Here, we demonstrate an optofluidic approach based on Marangoni or thermocapillary convection to steer and manipulate nano-objects with high accuracy at an air/liquid interface. By experiments and numerical simulations, we show that the fluid velocities achieved by this approach are more than three orders of magnitude stronger compared to natural convection and that it is possible to control the transport and position of single plasmonic nanoparticles over micrometer distances with high accuracy.


Investigation of the corneal filament in filamentary keratitis.
To date, no studies have elucidated the composition of the corneal filament in detail. In this study, an immunohistochemical technique was used to clarify the exact composition of the corneal filament in filamentary keratitis. In addition, the mechanisms responsible for filament formation were identified. Filaments were obtained from 13 patients with filamentary keratitis with a background of penetrating keratoplasty, aqueous tear deficiency, and severe ocular surface disorders, who were receiving treatment at an outpatient facility. From those tissues, transverse and longitudinal frozen sections were prepared and subjected to an indirect fluorescent immunohistochemical analysis with primary antibodies, including cytokeratins (CK1, -4, -6, -10, -12, and -13), mucins (MUC1, -4, -5AC, and -16), keratinization-related proteins (transglutaminase [TGase]-1 and filaggrin), cell proliferation marker Ki67, and markers of infiltration cells (HLA-DR and neutrophil-elastase). TUNEL staining was used for the detection of apoptosis. Fluorescent images of the sections were inspected with a fluorescence microscope. The filaments were composed of CK12-positive cells and had a roll-formed central core. They were covered with MUC5AC- and -16-positive mucins including CK4- and -13-positive cells and neutrophil-elastase-positive cells. The filaments also included broken cells and DNA fiber-form postlesional nuclei that were positive for TUNEL staining. However, those areas stained weakly for CK6 and HLA-DR; faintly for CK1, CK10, MUC1, and MUC4; and not at all for Ki67, TGase-1, and filaggrin. The results of this research have the potential to open new pathways toward understanding the mechanism that generates the filament in filamentary keratitis, as well as new treatments in the future.


Impaired DNA repair in mouse monocytes compared to macrophages and precursors.
Previously we showed that human monocytes isolated from peripheral blood display downregulation of several DNA repair proteins, including XRCC1, ligase III, PARP-1 and DNA-PKCS, resulting in a deficiency of DNA repair, while in macrophages derived from monocytes the repair protein expression and DNA repair is restored. To see whether this is a specific phenomenon of human monocytes and macrophages, we assessed the expression of these repair genes in mice. We also addressed the question at which differentiation step in bone marrow cells downregulation of DNA repair gene expression occurs. The study revealed that mouse monocytes, similar to human, lack the expression of XRCC1, ligase III, PARP-1 and DNA-PKCS. If mice were treated with total body irradiation, they showed significant apoptosis in bone marrow monocytes, but not in peritoneal macrophages. This was also observed after treatment with the methylating anticancer drug temozolomide, resulting in high death rate of monocytes, but not macrophages. Monocytes arise from hematopoietic stem cells. Even the early stem cell fraction (LT-HSC) expressed detectable amounts of XRCC1, which was transiently upregulated, achieving the highest expression level in CMP (common myeloid progenitor) and, during the subsequent differentiation process, downregulated up to a non-detectable level in monocytes. The immediate monocyte precursor GMP also expressed ligase III, PARP-1 and DNA-PKCS. All these repair genes lacking in monocytes were upregulated again in macrophages. The sensitivity of monocytes, macrophages and precursor cells roughly correlated with their XRCC1 expression level. Monocytes, but not macrophages, also displayed strong γH2AX focal staining, indicating the presence of non-repaired DNA double-strand breaks following total body irradiation. Overall, the data revealed that murine monocytes exhibit the same DNA repair-impaired phenotype and high sensitivity compared to macrophages as observed in human. Therefore, the repair deficiency previously described for human monocytes appears to be a general property of this cell type.


Thigh and Psoas Major Muscularity and Its Relation to Running Mechanics in Sprinters.
We aimed to examine the morphological characteristics of the thigh and psoas major muscles in sprinters as well as interrelations among their muscularity, hip joint mechanics, and running speed during maximal running. T1-weighted magnetic resonance images of the thigh and trunk were obtained from 15 male sprinters (best 100-m sprint times, 10.63-11.57 s) and 12 untrained men. From the magnetic resonance images, the volumes of each of the quadriceps femoris and hamstrings, total adductors, sartorius, tensor fasciae latae, gracilis, and psoas major were determined. For sprinters, the kinetic and kinematic data were measured using a three-dimensional motion capture system and force plates during maximal running. The data for one step from the foot strike of the stance leg to that of the swing leg were analyzed. The center of gravity (CG) velocity and hip joint kinetics were quantified. Compared with untrained men, sprinters had significantly greater thigh muscle volumes of the hip flexors and extensors, total adductors, gracilis, and psoas major, whereas the monoarticular knee extensor and flexor thigh muscle volumes were similar between the two groups. The CG velocity was positively correlated with the hip flexion angular impulse. Only the rectus femoris volume was significantly correlated with the CG velocity and peak hip flexion moment for the swing leg (r = 0.66-0.69). The sprinters in this study presented greater muscularity of the thigh and psoas major but not the monoarticular knee extensor or flexor muscles. The rectus femoris, in particular, may play an important role during the swing phase of sprinting.


Characterization of the rotavirus assembly pathway in situ using cryoelectron tomography.
Rotavirus assembly is a complex process that involves the stepwise acquisition of protein layers in distinct intracellular locations to form the fully assembled particle. Understanding and visualization of the assembly process has been hampered by the inaccessibility of unstable intermediates. We characterize the assembly pathway of group A rotaviruses observed in situ within cryo-preserved infected cells through the use of cryoelectron tomography of cellular lamellae. Our findings demonstrate that the viral polymerase VP1 recruits viral genomes during particle assembly, as revealed by infecting with a conditionally lethal mutant. Additionally, pharmacological inhibition to arrest the transiently enveloped stage uncovered a unique conformation of the VP4 spike. Subtomogram averaging provided atomic models of four intermediate states, including a pre-packaging single-layered intermediate, the double-layered particle, the transiently enveloped double-layered particle, and the fully assembled triple-layered virus particle. In summary, these complementary approaches enable us to elucidate the discrete steps involved in forming an intracellular rotavirus particle.


Recombinant human retinol-binding protein refolding, native disulfide formation, and characterization.
Human retinol-binding protein (RBP) is a monomeric 21-kDa protein that is currently the subject of numerous studies owing to its role in the cellular uptake and utilization of retinol. When the RBP gene is overexpressed in Escherichia coli, inclusion bodies of aggregated RBP are found in the cells. These inclusion bodies are solubilized in 5.0 M GdmCl containing 10 mM DTT. Refolding of RBP is carried out in the presence of vitamin A by diluting denatured and reduced RBP into a redox refolding buffer consisting of 3 mM cysteine/0.3 mM cystine at 4 degreesC. Ion exchange chromatography (HPLC) is utilized to purify refolded RBP to homogeneity as demonstrated by SDS-PAGE and electrospray MS. The native structure of refolded RBP was established by its ability to bind to vitamin A and the plasma protein transthyretin. The reconstitution of RBP outlined within affords a 50-60% overall yield, i.e., 73 mg of pure RBP/L of E. coli culture.


Bortezomib in late antibody-mediated kidney transplant rejection (BORTEJECT Study): study protocol for a randomized controlled trial.
Despite major advances in transplant medicine, improvements in long-term kidney allograft survival have not been commensurate with those observed shortly after transplantation. The formation of donor-specific antibodies (DSA) and ongoing antibody-mediated rejection (AMR) processes may critically contribute to late graft loss. However, appropriate treatment for late AMR has not yet been defined. There is accumulating evidence that the proteasome inhibitor bortezomib may substantially affect the function and integrity of alloantibody-secreting plasma cells. The impact of this agent on the course of late AMR has not so far been systematically investigated. The BORTEJECT Study is a randomized controlled trial designed to clarify the impact of intravenous bortezomib on the course of late AMR. In this single-center study (nephrological outpatient service, Medical University Vienna) we plan an initial cross-sectional DSA screening of 1,000 kidney transplant recipients (functioning graft at ≥180 days; estimated glomerular filtration rate (eGFR) >20 ml/minute/1.73 m2). DSA-positive recipients will be subjected to kidney allograft biopsy to detect morphological features consistent with AMR. Forty-four patients with biopsy-proven AMR will then be included in a double-blind placebo-controlled intervention trial (1:1 randomization stratified for eGFR and the presence of T-cell-mediated rejection). Patients in the active group will receive two cycles of bortezomib (4 × 1.3 mg/m2 over 2 weeks; 3-month interval between cycles). The primary end point will be the course of eGFR over 24 months (intention-to-treat analysis). The sample size was calculated according to the assumption of a 5 ml/minute/1.73 m2 difference in eGFR slope (per year) between the two groups (alpha: 0.05; power: 0.8). Secondary endpoints will be DSA levels, protein excretion, measured glomerular filtration rate, transplant and patient survival, and the development of acute and chronic morphological lesions in 24-month protocol biopsies. The impact of anti-humoral treatment on the course of late AMR has not yet been systematically investigated. Based on the hypothesis that proteasome inhibition improves the outcome of DSA-positive late AMR, we suggest that our trial has the potential to provide solid evidence towards the treatment of this type of rejection. Clinicaltrials.gov: NCT01873157.


Effect of torcetrapib on the progression of coronary atherosclerosis.
Levels of high-density lipoprotein (HDL) cholesterol are inversely related to cardiovascular risk. Torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, increases HDL cholesterol levels, but the functional effects associated with this mechanism remain uncertain. A total of 1188 patients with coronary disease underwent intravascular ultrasonography. After treatment with atorvastatin to reduce levels of low-density lipoprotein (LDL) cholesterol to less than 100 mg per deciliter (2.59 mmol per liter), patients were randomly assigned to receive either atorvastatin monotherapy or atorvastatin plus 60 mg of torcetrapib daily. After 24 months, disease progression was measured by repeated intravascular ultrasonography in 910 patients (77%). After 24 months, as compared with atorvastatin monotherapy, the effect of torcetrapib-atorvastatin therapy was an approximate 61% relative increase in HDL cholesterol and a 20% relative decrease in LDL cholesterol, reaching a ratio of LDL cholesterol to HDL cholesterol of less than 1.0. Torcetrapib was also associated with an increase in systolic blood pressure of 4.6 mm Hg. The percent atheroma volume (the primary efficacy measure) increased by 0.19% in the atorvastatin-only group and by 0.12% in the torcetrapib-atorvastatin group (P=0.72). A secondary measure, the change in normalized atheroma volume, showed a small favorable effect for torcetrapib (P=0.02), but there was no significant difference in the change in atheroma volume for the most diseased vessel segment. The CETP inhibitor torcetrapib was associated with a substantial increase in HDL cholesterol and decrease in LDL cholesterol. It was also associated with an increase in blood pressure, and there was no significant decrease in the progression of coronary atherosclerosis. The lack of efficacy may be related to the mechanism of action of this drug class or to molecule-specific adverse effects. (ClinicalTrials.gov number, NCT00134173 [ClinicalTrials.gov].).


Changes in race-specific virulence in Pseudomonas syringae pv. phaseolicola are associated with a chimeric transposable element and rare deletion events in a plasmid-borne pathogenicity island.
Virulence for bean and soybean is determined by effector genes in a plasmid-borne pathogenicity island (PAI) in race 7 strain 1449B of Pseudomonas syringae pv. phaseolicola. One of the effector genes, avrPphF, confers either pathogenicity, virulence, or avirulence depending on the plant host and is absent from races 2, 3, 4, 6, and 8 of this pathogen. Analysis of cosmid clones and comparison of DNA sequences showed that the absence of avrPphF from strain 1448A is due to deletion of a continuous 9.5-kb fragment. The remainder of the PAI is well conserved in strains 1448A and 1449B. The left junction of the deleted region consists of a chimeric transposable element generated from the fusion of homologs of IS1492 from Pseudomonas putida and IS1090 from Ralstonia eutropha. The borders of the deletion were conserved in 66 P. syringae pv. phaseolicola strains isolated in different countries and representing the five races lacking avrPphF. However, six strains isolated in Spain had a 10.5-kb deletion that extended 1 kb further from the right junction. The perfect conservation of the 28-nucleotide right repeat of the IS1090 homolog in the two deletion types and in the other 47 insertions of the IS1090 homolog in the 1448A genome strongly suggests that the avrPphF deletions were mediated by the activity of the chimeric mobile element. Our data strongly support a clonal origin for the races of P. syringae pv. phaseolicola lacking avrPphF.


Coffee consumption and risk of endometrial cancer: a dose-response meta-analysis of prospective cohort studies.
This is a dose-response (DR) meta-analysis to evaluate the association of coffee consumption on endometrial cancer (EC) risk. A total 1,534,039 participants from 13 published articles were added in this meta-analysis. The RR of total coffee consumption and EC were 0.80 (95% CI: 0.74-0.86). A stronger association between coffee intake and EC incidence was found in patients who were never treated with hormones, 0.60 (95% CI: 0.50-0.72), and subjects with a BMI ≥25 kg/m(2), 0.57 (95% CI: 0.46-0.71). The overall RRs for caffeinated and decaffeinated coffee were 0.66 (95% CI: 0.52-0.84) and 0.77 (95% CI: 0.63-0.94), respectively. A linear DR relationship was seen in coffee, caffeinated coffee, decaffeinated coffee and caffeine intake. The EC risk decreased by 5% for every 1 cup per day of coffee intake, 7% for every 1 cup per day of caffeinated coffee intake, 4% for every 1 cup per day of decaffeinated intake of coffee, and 4% for every 100 mg of caffeine intake per day. In conclusion, coffee and intake of caffeine might significantly reduce the incidence of EC, and these effects may be modified by BMI and history of hormone therapy.


Serum thyroglobulin concentrations and whole-body radioiodine scan in follow-up of differentiated thyroid cancer after thyroid ablation.
Measurement of serum thyroglobulin (Tg) concentrations and whole-body radioiodine scan were performed simultaneously during follow-up of 32 patients with differentiated thyroid cancer who had undergone thyroid ablation by operation and radioiodine. Almost all patients in whom serum Tg was undetectable had normal scans. Concentrations exceeding 50 ng/ml were invariably associated with residual or metastatic tumour uptake in the scan. Out of 21 observations of detectable values below 50 ng/ml, 14 were in patients whose scans showed subclinical or sub-radiological tumour uptake and seven in patients with normal scans. The sensitivity of serum Tg as a tumour marker compared favourably to that of the whole-body scan. A scan is unnecessary when serum Tg is undetectable, but in patients with detectable serum Tg concentrations, particularly if these are below 50 ng/ml, a scan is important to assess and localise tumour uptake of iodine before advising treatmet with iodine-131.


Telemedicine and prostate cancer survivorship: a narrative review.
Prostate cancer survivors have unique needs that encompass diagnosis and treatment-related side effects. The provision of services for prostate cancer survivors is often limited by resources, time constraints in traditional clinic visits, payment, and patient and provider comfort with discussion of sensitive topics including sexual and urinary health, both of which are largely impacted by treatment. Telemedicine, the remote delivery of health care services using telephone, mobile, web, and video platforms, allows for potential cost savings, in addition to ease and comfort as patients can engage in telemedicine-based resources in the comfort of their homes. Furthermore, survivors prefer to seek information online making telemedicine approaches for prostate cancer survivorship care an ideal combination. A majority of the telemedicine-based interventions used the web, followed by telephone, mobile, and video platforms. In limited studies, telemedicine delivery of survivorship care has equal efficacy to traditional care delivery. In addition, although older patients did not use the Internet regularly, they were willing to adapt to Internet usage if it had the potential to increase their quality of life. Telemedicine delivery of prostate cancer survivorship care is acceptable, feasible, cost-effective, and potentially preferred by prostate cancer survivors. Additionally, it emphasizes knowledge, self-management and self-monitoring serving to increase self-efficacy. This specialized care allows for greater access and reaches a wider catchment area compared to traditional clinic visits. This is especially important as the number of prostate cancer survivors increases and healthcare systems incorporate alternatives to traditional in-person care.


Arteries of the thumb originating from the superficial palmar arch: five cases.
Five cases are described where the first web space of the hand received arteries only from the superficial palmar arch. None of these branches was large enough to deserve the name "princeps pollicis artery". These variations must be taken into account during surgical dissections of the hand.


Secondary chronic venous disorders.
Secondary chronic venous disorders (CVD) usually follow an episode of acute deep venous thrombosis (DVT). Most occluded venous segments recanalize over the first 6 to 12 months after an episode of acute DVT, leading to chronic luminal changes and a combination of partial obstruction and reflux. Such morphological changes produce venous hypertension with the highest levels of ambulatory venous pressure occurring in patients with combined outflow obstruction and distal reflux. The clinical manifestations of secondary CVD, including pain, venous claudication, edema, skin changes, and ulceration are commonly referred to as the post-thrombotic syndrome. Such sequelae are best avoided by early and aggressive treatment of proximal DVT. The diagnostic evaluation of secondary CVD is similar to primary CVD and is based upon duplex ultrasound. However, the definition of hemodynamically significant venous stenosis remains obscure and there are no reliable tests to confirm the presence of such lesions. Diagnosis depends more on anatomic rather than hemodynamic criteria, and IVUS is superior to venography in estimating the morphological degree and extent of iliac vein stenosis. The fundamental role of compression in the treatment of CVD is well recognized. Compliance with compression is essential to heal ulcers and minimize recurrence. The efficacy of various adjuncts to ulcer treatment, including complex wound dressings and medications have been variable. Although superficial venous surgery has not been demonstrated to improve ulcer healing rates, it does decrease ulcer recurrence. Deep venous valve reconstruction is performed in only a few specialized centers, and the results are better for primary than for secondary CVD. Treatment of incompetent perforating veins remains controversial. Although artificial venous valves are promising, most early experimental models have failed. With respect to venous obstruction, iliocaval angioplasty and stenting has emerged as the primary treatment for proximal iliofemoral venous obstruction with surgical bypass assuming a secondary role.


Biowire Model of Interstitial and Focal Cardiac Fibrosis.
Myocardial fibrosis is a severe global health problem due to its prevalence in all forms of cardiac diseases and direct role in causing heart failure. The discovery of efficient antifibrotic compounds has been hampered due to the lack of a physiologically relevant disease model. Herein, we present a disease model of human myocardial fibrosis and use it to establish a compound screening system. In the Biowire II platform, cardiac tissues are suspended between a pair of poly(octamethylene maleate (anhydride) citrate) (POMaC) wires. Noninvasive functional readouts are realized on the basis of the deflection of the intrinsically fluorescent polymer. The disease model is constructed to recapitulate contractile, biomechanical, and electrophysiological complexities of fibrotic myocardium. Additionally, we constructed a heteropolar integrated model with fibrotic and healthy cardiac tissues coupled together. The integrated model captures the regional heterogeneity of scar lesion, border zone, and adjacent healthy myocardium. Finally, we demonstrate the utility of the system for the evaluation of antifibrotic compounds. The high-fidelity in vitro model system combined with convenient functional readouts could potentially facilitate the development of precision medicine strategies for cardiac fibrosis modeling and establish a pipeline for preclinical compound screening.


Phase 1 clinical trial of the novel proteasome inhibitor marizomib with the histone deacetylase inhibitor vorinostat in patients with melanoma, pancreatic and lung cancer based on in vitro assessments of the combination.
Combining proteasome and histone deacetylase (HDAC) inhibition has been seen to provide synergistic anti-tumor activity, with complementary effects on a number of signaling pathways. The novel bi-cyclic structure of marizomib with its unique proteasome inhibition, toxicology and efficacy profiles, suggested utility in combining it with an HDAC inhibitor such as vorinostat. Thus, in this study in vitro studies assessed the potential utility of combining marizomib and vorinostat, followed by a clinical trial with the objectives of assessing the recommended phase 2 dose (RP2D), pharmacokinetics (PK), pharmacodynamics (PD), safety and preliminary anti-tumor activity of the combination in patients. Combinations of marizomib and vorinostat were assessed in vitro. Subsequently, in a Phase 1 clinical trial patients with melanoma, pancreatic carcinoma or Non-small Cell Lung Cancer (NSCLC) were given escalating doses of weekly marizomib in combination with vorinostat 300 mg daily for 16 days in 28 day cycles. In addition to standard safety studies, proteasome inhibition and pharmacokinetics were assayed. Marked synergy of marizomib and vorinostat was seen in tumor cell lines derived from patients with NSCLC, melanoma and pancreatic carcinoma. In the clinical trial, 22 patients were enrolled. Increased toxicity was not seen with the combination. Co-administration did not appear to affect the PK or PD of either drug in comparison to historical data. Although no responses were demonstrated using RECIST criteria, 61% of evaluable patients demonstrated stable disease with 39% having decreases in tumor measurements. Treatment of multiple tumor cell lines with marizomib and vorinostat resulted in a highly synergistic antitumor activity. The combination of full dose marizomib with vorinostat is tolerable in patients with safety findings consistent with either drug alone.


Fatty diabetic lung: functional impairment in a model of metabolic syndrome.
The Zucker diabetic fatty (ZDF fa/fa) rat with genetic leptin insensitivity develops obesity and Type 2 diabetes mellitus (T2DM) with age accompanied by hyperplastic changes in the distal lung (Am J Physiol Lung Cell Mol Physiol 298: L392-L403, 2010). To determine the functional consequences of structural changes, we developed a rebreathing (RB) technique to simultaneously measure lung volume, pulmonary blood flow, lung diffusing capacity (Dl(CO)), membrane diffusing capacity (Dm(CO)), pulmonary capillary blood volume (Vc), and septal tissue volume in anesthetized tracheostomized male ZDF fa/fa and matched lean (+/+) control animals at 4, 8, and 12 mo of age. Results obtained by RB technique were compared with that measured by a single-breath (SB) technique and to that expected in a wide range of species. In fa/fa animals compared with +/+, lung volumes and compliance were 13-35% lower at different ages, and the normal age-related increase in lung compliance was no longer evident. Mean pulmonary blood flow declined with age in fa/fa but not in +/+ animals. Dl(CO) measured at a given pulmonary blood flow was 20-43% lower at different ages due to reductions in both Dm(CO) and Vc. Septal tissue volume was also reduced in older fa/fa rats. We conclude that obese rats with T2DM develop significant restrictive pulmonary defects with diffusion impairment in a pattern similar to that previously reported in obese human subjects with T2DM. Functional impairment became exaggerated with age and duration of T2DM. In both fa/fa and +/+ animals, Dl(CO) measured by RB was systematically higher than by SB technique whereas lung volume was similar, a finding consistent with heterogeneous distribution of ventilation in the rat lung.


Alcohol screening and brief intervention for adolescents: the how, what and where of reducing alcohol consumption and related harm among young people.
The aim of the study was to explore the evidence base on alcohol screening and brief intervention for adolescents to determine age appropriate screening tools, effective brief interventions and appropriate locations to undertake these activities. A review of existing reviews (2003-2013) and a systematic review of recent research not included in earlier reviews. The CRAFFT and AUDIT tools are recommended for identification of 'at risk' adolescents. Motivational interventions delivered over one or more sessions and based in health care or educational settings are effective at reducing levels of consumption and alcohol-related harm. Further research to develop age appropriate screening tools needs to be undertaken. Screening and brief intervention activity should be undertaken in settings where young people are likely to present; further assessment at such venues as paediatric emergency departments, sexual health clinics and youth offending teams should be evaluated. The use of electronic (web/smart-phone based) screening and intervention shows promise and should also be the focus of future research.


Use of photoacoustic excitation and laser vibrometry to remotely detect trace explosives.
In this paper, we examine a laser-based approach to remotely initiate, measure, and differentiate acoustic and vibrational emissions from trace quantities of explosive materials against their environment. Using a pulsed ultraviolet laser (266 nm), we induce a significant (>100 Pa) photoacoustic response from small quantities of military-grade explosives. The photoacoustic signal, with frequencies predominantly between 100 and 500 kHz, is detected remotely via a wideband laser Doppler vibrometer. This two-laser system can be used to rapidly detect and discriminate explosives from ordinary background materials, which have significantly weaker photoacoustic response. A 100 ng/cm2 limit of detection is estimated. Photoablation is proposed as the dominant mechanism for the large photoacoustic signals generated by explosives.


Cortico-Brainstem Mechanisms of Biased Perceptual Decision-Making in the Context of Pain.
Prior expectations can bias how we perceive pain. Using a drift diffusion model, we recently showed that this influence is primarily based on changes in perceptual decision-making (indexed as shift in starting point). Only during unexpected application of high-intensity noxious stimuli, altered information processing (indexed as increase in drift rate) explained the expectancy effect on pain processing. Here, we employed functional magnetic resonance imaging to investigate the neural basis of both these processes in healthy volunteers. On each trial, visual cues induced the expectation of high- or low-intensity noxious stimulation or signaled equal probability for both intensities. Participants categorized a subsequently applied electrical stimulus as either low- or high-intensity pain. A shift in starting point towards high pain correlated negatively with right dorsolateral prefrontal cortex activity during cue presentation underscoring its proposed role of "keeping pain out of mind". This anticipatory right dorsolateral prefrontal cortex signal increase was positively correlated with periaqueductal gray (PAG) activity when the expected high-intensity stimulation was applied. A drift rate increase during unexpected high-intensity pain was reflected in amygdala engagement and increased functional connectivity between amygdala and PAG. Our findings suggest involvement of the PAG in both decision-making bias and altered information processing to implement expectancy effects on pain. PERSPECTIVE: Modulation of pain through expectations has been linked to changes in perceptual decision-making and altered processing of afferent information. Our results suggest involvement of the dorsolateral prefrontal cortex, amygdala, and periaqueductal gray in these processes.


Cadherin-23, myosin VIIa and harmonin, encoded by Usher syndrome type I genes, form a ternary complex and interact with membrane phospholipids.
Cadherin-23 is a component of early transient lateral links of the auditory sensory cells' hair bundle, the mechanoreceptive structure to sound. This protein also makes up the upper part of the tip links that control gating of the mechanoelectrical transduction channels. We addressed the issue of the molecular complex that anchors these links to the hair bundle F-actin core. By using surface plasmon resonance assays, we show that the cytoplasmic regions of the two cadherin-23 isoforms that do or do not contain the exon68-encoded peptide directly interact with harmonin, a submembrane PDZ (post-synaptic density, disc large, zonula occludens) domain-containing protein, with unusually high affinity. This interaction involves the harmonin Nter-PDZ1 supramodule, but not the C-terminal PDZ-binding motif of cadherin-23. We establish that cadherin-23 directly binds to the tail of myosin VIIa. Moreover, cadherin-23, harmonin and myosin VIIa can form a ternary complex, which suggests that myosin VIIa applies tension forces on hair bundle links. We also show that the cadherin-23 cytoplasmic region, harmonin and myosin VIIa interact with phospholipids on synthetic liposomes. Harmonin and the cytoplasmic region of cadherin-23, both independently and as a binary complex, can bind specifically to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)), which may account for the role of this phospholipid in the adaptation of mechanoelectrical transduction in the hair bundle. The distributions of cadherin-23, harmonin, myosin VIIa and PI(4,5)P(2) in the growing and mature auditory hair bundles as well as the abnormal locations of harmonin and myosin VIIa in cadherin-23 null mutant mice strongly support the functional relevance of these interactions.


Development and evaluation of the Supportive and Palliative Care Indicators Tool (SPICT): a mixed-methods study.
To refine and evaluate a practical, clinical tool to help multidisciplinary teams in the UK and internationally, to identify patients at risk of deteriorating and dying in all care settings. We used a participatory research approach to refine the 2010 Supportive and Palliative Care Indicators Tool (SPICT) and evaluate its use in clinical practice. We conducted an ongoing peer review process for 18 months via an open access webpage, and engaged over 30 clinicians from the UK and internationally in developing an effective tool. Secondly, we carried out a prospective case-finding study in an acute hospital in SE Scotland. Four multidisciplinary teams identified 130 patients with advanced kidney, liver, cardiac or lung disease following an unplanned hospital admission. The SPICT was refined and updated to consist of readily identifiable, general indicators relevant to patients with any advanced illness, and disease-specific indicators for common advanced conditions. Hospital clinicians used the SPICT to identify patients at risk of deteriorating and dying. Patients who died had significantly more unplanned admissions, persistent symptoms and increased care needs. By 12 months, 62 (48%) of the identified patients had died. 69% of them died in hospital, having spent 22% of their last 6 months there. The SPICT can support clinical judgment by multidisciplinary teams when identifying patients at risk of deteriorating and dying. It helped identify patients with multiple unmet needs who would benefit from earlier, holistic needs assessment, a review of care goals, and anticipatory care planning.


Rescue of Long-Term Spatial Memory by 7,8-Dihydroxyflavone in Mice with Reduced Oligodendrogenesis.
Oligodendrogenesis is the process by which new oligodendrocytes are produced in the CNS. Oligodendrocytes form myelin, which has a vital role in neural signal transmission and integration. Here we tested mice with reduced adult oligodendrogenesis in the Morris water maze, a test of spatial learning. These mice were found to have impaired long-term (28 d) spatial memory. However, when 7,8-dihydroxyflavone (7,8-DHF) was administered immediately after each training session, their long-term spatial memory impairment was rescued. An increase in the number of newly formed oligodendrocytes in the corpus callosum was also observed. 7,8-DHF has previously been shown to improve spatial memory in animal models of Alzheimer's disease, post-traumatic stress disorder, Wolfram syndrome and Down syndrome, as well as in normal aging. Understanding the underlying mechanisms of the effect of this drug on spatial memory is therefore helpful in assessing it for clinical relevance and development.


Smoking-related deaths averted due to three years of policy progress.
To evaluate the global impact of adopting highest-level MPOWER tobacco control policies in different countries and territories from 2007 to 2010. Policy effect sizes based on previously-validated SimSmoke models were applied to determine the reduction in the number of smokers as a result of policy adoption during this period. Based on previous research suggesting that half of all smokers die from smoking, we also derived the estimated smoking-attributable deaths (SADs) averted due to MPOWER policy implementation. The results from use of this simple yet powerful method are consistent with those predicted by using previously validated SimSmoke models. In total, 41 countries adopted at least one highest-level MPOWER policy between 2007 and 2010. As a result of all policies adopted during this period, the number of smokers is estimated to have dropped by 14.8 million, with a total of 7.4 million SADs averted. The largest number of SADs was averted as a result of increased cigarette taxes (3.5 million), smoke-free air laws (2.5 million), health warnings (700,000), cessation treatments (380,000), and bans on tobacco marketing (306,000). From 2007 to 2010, 41 countries and territories took action that will collectively prevent nearly 7.5 million smoking-related deaths globally. These findings demonstrate the magnitude of the actions already taken by countries and underscore the potential for millions of additional lives to be saved with continued adoption of MPOWER policies.


Causative classification of river flood events.
A wide variety of processes controls the time of occurrence, duration, extent, and severity of river floods. Classifying flood events by their causative processes may assist in enhancing the accuracy of local and regional flood frequency estimates and support the detection and interpretation of any changes in flood occurrence and magnitudes. This paper provides a critical review of existing causative classifications of instrumental and preinstrumental series of flood events, discusses their validity and applications, and identifies opportunities for moving toward more comprehensive approaches. So far no unified definition of causative mechanisms of flood events exists. Existing frameworks for classification of instrumental and preinstrumental series of flood events adopt different perspectives: hydroclimatic (large-scale circulation patterns and atmospheric state at the time of the event), hydrological (catchment scale precipitation patterns and antecedent catchment state), and hydrograph-based (indirectly considering generating mechanisms through their effects on hydrograph characteristics). All of these approaches intend to capture the flood generating mechanisms and are useful for characterizing the flood processes at various spatial and temporal scales. However, uncertainty analyses with respect to indicators, classification methods, and data to assess the robustness of the classification are rarely performed which limits the transferability across different geographic regions. It is argued that more rigorous testing is needed. There are opportunities for extending classification methods to include indicators of space-time dynamics of rainfall, antecedent wetness, and routing effects, which will make the classification schemes even more useful for understanding and estimating floods. This article is categorized under:Science of Water > Water ExtremesScience of Water > Hydrological ProcessesScience of Water > Methods.


Treatment of acute otitis media of infancy with cefaclor.
The emergence of ampicillin-resistant Haemophilus as a clinical problem in otitis media necessitates a search for alternative, effective therapy. An orally absorbable cephalosporin derivative, cefaclor, is equally effective in vitro against ampicillin-susceptible and -resistant Haemophilus and against other bacteria that cause acute otitis media. Two dosage schedules of cefaclor (40 and 60 mg/kg/day) were evaluated in 95 infants with acute otitis media. Bacterial origin was determined by a culture of tympanocentesis fluid. Success rates using the smaller dosage were inferior to those using the larger dosage. Results of therapy for pneumococcal and Haemophilus infection with 60 mg/kg/day were comparable to those previously found with amoxicillin trihydrate or with combinations of trisulfapyrimadines with erythromycin or penicillin V. One patient with an ampicillin-resistant Haemophilus infection responded well to cefaclor and did not have a relapse. Cefaclor was well tolerated and caused an acceptably low incidence of minor, adverse effects. Cefaclor deserves further testing as a candidate for preferred status as a single-drug treatment of acute otitis media.


Hepatoprotective Potential of Prosopis farcta Beans Extracts against Acetaminophen-induced Hepatotoxicity in Wister Rats.
Hepatotoxicity by acetaminophen is the most frequent cause of acute liver failure in many countries. Prosopis farcta beans extract (PFE) has some antioxidant property and may alleviate hepatotoxicity. Therefore, the aim of this study was to evaluate effects of PFE against acetaminophen-induced hepatotoxicity. Thirty-six male Wistar albino rats weighing 220 ± 30 g were distributed into six groups. Two groups were pretreated with PFE (50 and 75 mg/kg) for 7 days before administration of acetaminophen (600 mg/kg). Two were given acetaminophen or PFE (50 and 75 mg/kg) alone, and the control received normal saline. One day after acetaminophen, administration blood samples were collected by cardiac puncture to determine liver function enzymes markers; aspartate aminotransferase and alanine aminotransferase (AST and ALT), cholesterol, triglyceride (TG), high, low, and very low density lipoproteins (LDL and VLDL). In acetaminophen-treated rat plasma AST (314 ± 18.54 vs. 126.37 ± 4.13), ALT (304 ± 49.24 vs. 187.33 ± 3.71), cholesterol, TG, LDL, and VLDL were increased by 149, 160, 37, 92, 60, and 94%, respectively. PFE at both doses significantly (P < 0.05) attenuated the above biochemical indices to near normal. Prosopis farcta beans extract (50 and 75 mg/kg) exhibited hepatoprotective activity against APAP.


Nonlinear sensors: an approach to the residence time detection strategy.
The monitoring of the residence time difference in bistable sensors has been recently proposed as a valid scheme for improving the detection capabilities of sensors as diverse as fluxgate magnetometers, ferroelectric sensors and mechanical sensors. In this paper we propose an approach to the residence time based detection strategy based on the measurement of the slope m of the sensor output integral. We demonstrate that such a method, far from degrading the detection performances can provide an easier way to realize fast and reliable sensors without the computationally demanding task related with the computation of the residence time difference. We introduce the receiver operating characteristic curve as a quantitative estimator for the comparison of the two methods and show that the detector performances increase with increasing the periodic bias amplitude A up to a maximum value. This condition has potentially relevant consequences in the future detectors design.


Oestrogenic activity of p-hydroxybenzoic acid (common metabolite of paraben esters) and methylparaben in human breast cancer cell lines.
This paper addresses the question of whether p-hydroxybenzoic acid, the common metabolite of parabens, possesses oestrogenic activity in human breast cancer cell lines. The alkyl esters of p-hydroxybenzoic acid (parabens) are used widely as preservatives in consumer products to which the human population is exposed and have been shown previously to possess oestrogenic activity and to be present in human breast tumour tissue, which is an oestrogen-responsive tissue. Recent work has shown p-hydroxybenzoic acid to give an oestrogenic response in the rodent uterotrophic assay. We report here that p-hydroxybenzoic acid possesses oestrogenic activity in a panel of assays in human breast cancer cell lines. p-Hydroxybenzoic acid was able to displace [(3)H]oestradiol from cytosolic oestrogen receptor of MCF7 human breast cancer cells by 54% at 5 x 10(6)-fold molar excess and by 99% at 10(7)-fold molar excess. It was able to increase the expression of a stably integrated oestrogen responsive reporter gene (ERE-CAT) at a concentration of 5 x 10(-4) M in MCF7 cells after 24 h and 7 days, which could be inhibited by the anti-oestrogen ICI 182 780 (Faslodex, fulvestrant). Proliferation of two human breast cancer cell lines (MCF7, ZR-75-1) could be increased by 10(-5) M p-hydroxybenzoic acid. Following on from previous studies showing a decrease in oestrogenic activity of parabens with shortening of the linear alkyl chain length, this study has compared the oestrogenic activity of p-hydroxybenzoic acid where the alkyl grouping is no longer present with methylparaben, which has the shortest alkyl group. Intrinsic oestrogenic activity of p-hydroxybenzoic acid was similar to that of methylparaben in terms of relative binding to the oestrogen receptor but its oestrogenic activity on gene expression and cell proliferation was lower than that of methylparaben. It can be concluded that removal of the ester group from parabens does not abrogate its oestrogenic activity and that p-hydroxybenzoic acid can give oestrogenic responses in human breast cancer cells.


An adaptive regional input-output model and its application to the assessment of the economic cost of Katrina.
This article proposes a new modeling framework to investigate the consequences of natural disasters and the following reconstruction phase. Based on input-output tables, its originalities are (1) the taking into account of sector production capacities and of both forward and backward propagations within the economic system; and (2) the introduction of adaptive behaviors. The model is used to simulate the response of the economy of Louisiana to the landfall of Katrina. The model is found consistent with available data, and provides two important insights. First, economic processes exacerbate direct losses, and total costs are estimated at $149 billion, for direct losses equal to $107 billion. When exploring the impacts of other possible disasters, it is found that total losses due to a disaster affecting Louisiana increase nonlinearly with respect to direct losses when the latter exceed $50 billion. When direct losses exceed $200 billion, for instance, total losses are twice as large as direct losses. For risk management, therefore, direct losses are insufficient measures of disaster consequences. Second, positive and negative backward propagation mechanisms are essential for the assessment of disaster consequences, and the taking into account of production capacities is necessary to avoid overestimating the positive effects of reconstruction. A systematic sensitivity analysis shows that, among all parameters, the overproduction capacity in the construction sector and the adaptation characteristic time are the most important.


The bHLH-PAS protein Spineless is necessary for the diversification of dendrite morphology of Drosophila dendritic arborization neurons.
Dendrites exhibit a wide range of morphological diversity, and their arborization patterns are critical determinants of proper neural connectivity. How different neurons acquire their distinct dendritic branching patterns during development is not well understood. Here we report that Spineless (Ss), the Drosophila homolog of the mammalian aryl hydrocarbon (dioxin) receptor (Ahr), regulates dendrite diversity in the dendritic arborization (da) sensory neurons. In loss-of-function ss mutants, class I and II da neurons, which are normally characterized by their simple dendrite morphologies, elaborate more complex arbors, whereas the normally complex class III and IV da neurons develop simpler dendritic arbors. Consequently, different classes of da neurons elaborate dendrites with similar morphologies. In its control of dendritic diversity among da neurons, ss likely acts independently of its known cofactor tango and through a regulatory program distinct from those involving cut and abrupt. These findings suggest that one evolutionarily conserved role for Ahr in neuronal development concerns the diversification of dendrite morphology.


Gangrenous cholecystitis: a contemporary review.
Despite the established superiority of laparoscopic cholecystectomy (LC) for acute cholecystitis, gangrenous cholecystitis (GC) is commonly treated with open cholecystectomy (OC). This study aimed to characterize outcomes of GC in the modern era and between LC or OC surgical approach. Patients with a diagnosis of GC were identified using the 2005-2011 National Surgical Quality Improvement Project Participant User File. Baseline patient and operative characteristics and 30-d outcomes were established for all patients. Patients were stratified by surgical approach (LC or OC), and groups were propensity matched with a nearest-neighbor matching algorithm. Primary outcomes were 30-d mortality and any 30-d complication. A nonparsimonious multiple logistic regression model was used in the matched subset to adjust for patient comorbidities, demographics, and laboratory values. A total of 141,970 cholecystectomies were identified with 7017 having a diagnosis of GC. Overall 30-d mortality for the entire cohort was 0.8% (n = 239) and overall 30-d complication rate was 8.0% (n = 2485). For GC patients, the 30-d mortality was 1.2% (n = 84) and overall complication rate was 10.8% (n = 761). The multivariate logistic regression model demonstrated a significant decrease in overall (odds ratio = 0.46; P < 0.001) complication rates for LC patients but did not reveal a significant difference in 30-d mortality (odds ratio = 0.59; P = 0.12). GC is associated with increased morbidity and mortality compared with that of acute cholecystitis. A LC approach is a safe option for patients with GC and is associated with decreased 30-d morbidity. Although LC should be used when possible for GC to minimize postoperative complications, OC should not be avoided if necessary to ensure patient safety.


Effects of small-scale, home-like facilities in dementia care on residents' behavior, and use of physical restraints and psychotropic drugs: a quasi-experimental study.
Small-scale, home-like care environments are increasingly implemented in institutional nursing care as a model to promote resident-directed care, although evidence on its effects is sparse. This study focuses on the effects of small-scale living facilities on the behavior of residents with dementia and use of physical restraints and psychotropic drugs. A quasi-experimental study was conducted comparing residents in two types of long-term institutional nursing care (i.e., small-scale living facilities and traditional psychogeriatric wards) on three time points: at baseline and follow-ups after six and 12 months. Residents were matched at baseline on cognitive and functional status to increase comparability of groups at baseline. Nurses assessed neuropsychiatric and depressive symptoms, agitation, social engagement, and use of physical restraints using questionnaires. Psychotropic drug use was derived from residents' medical records. In total, 259 residents were included: 124 in small-scale living facilities and 135 controls. Significantly fewer physical restraints and psychotropic drugs were used in small-scale living facilities compared with traditional wards. Residents in small-scale living facilities were significantly more socially engaged, at baseline and after six months follow-up, and displayed more physically non-aggressive behavior after 12 months than residents in traditional wards. No other differences were found. This study suggests positive effects of small-scale living facilities on the use of physical restraints and psychotropic drugs. However, the results for behavior were mixed. More research is needed to gain an insight on the relationship between dementia care environment and other residents' outcomes.


Clinical practice guideline recommendation summaries for pediatric oncology health care professionals: A qualitative study.
To develop a summary format of clinical practice guideline (CPG) recommendations to improve understandability among health care professionals. We developed a summary format based on current research and used the "Think Aloud" technique in one-on-one cognitive interviews to iteratively improve it. Interviews of health care professionals from Children's Oncology Group-member, National Cancer Institute Community Oncology Research Program sites were conducted. After every five interviews (a round), responses were reviewed, and changes made to the format until it was well understood and no new, substantive suggestions for revision were raised. We took a directed (deductive) approach to content analysis of the interview notes to identify concerns related to recommendation summary usability, understandability, validity, applicability and visual appeal. During seven rounds of interviews with 33 health care professionals, we identified important factors that influenced understandability. Participants found understanding weak recommendations more challenging than strong recommendations. Understanding was improved when the term 'conditional' recommendation was used instead of 'weak' recommendation. Participants found a Rationale section to be very helpful but desired more information when a recommendation entailed a practice change. In the final format, the recommendation strength is clearly indicated in the title, highlighted, and defined within a text box. The rationale for the recommendation is in a column on the left, with supporting evidence on the right. In a bulleted list, the Rationale section describes the benefits and harms and additional factors, such as implementation, that were considered by the CPG developers. Each bullet under the supporting evidence section indicates the level of evidence with an explanation and the supporting studies with hyperlinks when applicable. A summary format to present strong and conditional recommendations was created through an iterative interview process. The format is straightforward, making it easy for organizations and CPG developers to use it to communicate recommendations clearly to intended users.