Nodule formation is stimulated by the ethylene inhibitor aminoethoxyvinylglycine.
Previous researchers found that formation and function of nitrogen-fixing nodules on legume roots were severely inhibited by addition of exogenous ethylene. Nodule formation by Rhizobium meliloti on Medicago sativa was stimulated twofold when the ethylene biosynthesis inhibitor aminoethoxyvinylglycine (AVG) was added with the inoculum. Stimulation of nodule formation by AVG showed a similar concentration dependence as inhibition of ethylene biosynthesis, suggesting that the primary action of AVG is the inhibition of ethylene biosynthesis. When AVG was added 2 to 3 days after inoculation, the number of nodules formed was still increased. On a per plant basis, however, the average nitrogen fixation was unchanged by AVG treatment and was independent of nodule number.


Usefulness of flexible spectral imaging color enhancement (FICE) for the detection of angiodysplasia in the preview of capsule endoscopy.
Flexible spectral imaging color enhancement (FICE) is an image enhancement system that can obtain bright and high-contrast images. FICE for capsule endoscopy (CE) is available during interpretation of Given Imaging, but its usefulness is rarely reported. The aim of this study is to evaluate the preview of angiodysplasia by FICE in comparison with the conventional preview. The accumulated CE data of 50 patients with angiodysplasia were randomly assigned to 2 equally sized groups of conventional reading and FICE reading. One experienced doctor analyzed them for the first time in a quick-view mode and the mean reading time, sensitivity and specificity for detecting angiodysplasia by each method were evaluated for comparisons including suspected blood indicator. The mean reading time was 14min for both conventional reading and FICE reading. The two previews of angiodysplasia were significantly superior to the function of suspected blood indicator (p<0.01). The sensitivity and specificity of conventional reading for detecting angiodysplasia were 80% and 100%, respectively. Those of FICE reading were 91% and 86%, respectively. FICE reading was superior in term of sensitivity, while it resulted in more false positive lesion findings and lower specificity. However, such false-positive findings by FICE reading can be correctly identified at a glance by converting the image to conventional mode. This study demonstrates that FICE enables accurate detection of angiodysplasia in the preview of CE.


Hydrogen peroxide produced by angiopoietin-1 mediates angiogenesis.
Angiopoietin-1 (Ang1) mediates angiogenesis by enhancing endothelial cell survival and migration. It is also known that Ang1 activates Tie2, an endothelial-specific tyrosine kinase receptor, but the molecular mechanism of this process is not clear. In this study, we investigated whether reactive oxygen species (ROS) production plays a role in Ang1-mediated angiogenesis. We found that human umbilical vein endothelial cells treated with Ang1 produce ROS transiently, which was suppressed by NADPH oxidase inhibitor, diphenylene-iodonium chloride, and rotenone. The Ang1-induced ROS was identified as hydrogen peroxide (H2O2) using adenovirus-catalase infection. Removal of H2O2 by adenovirus-catalase significantly suppressed Ang1-induced in vitro endothelial cell migration, in vivo tubule formation and angiogenesis, and activation of p44/42 mitogen-activated protein kinase (MAPK), involved in cell migration, and delayed the deactivation of Akt phosphorylation involved in cell survival. Supporting to in vitro data, Ang1-induced vascular remodeling in catalase (-/-) mice was more prominent than in catalase (+/+) mice: Ang1-induced increases of the diameter of terminal arterioles and the postcapillary venules in catalase (-/-) mice were significant compared with catalase (+/+) mice. These results show that Ang1-induced H2O2 plays an important role in Ang1-mediated angiogenesis by modulating p44/42 MAPK activity.


The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology.
The terminology for human papillomavirus(HPV)–associated squamous lesions of the lower anogenital tract has a long history marked by disparate diagnostic terms derived from multiple specialties. It often does not reflect current knowledge of HPV biology and pathogenesis. A consensus process was convened to recommend terminology unified across lower anogenital sites. The goal was to create a histopathologic nomenclature system that reflects current knowledge of HPV biology, optimally uses available biomarkers, and facilitates clear communication across different medical specialties. The Lower Anogenital Squamous Terminology (LAST) Project was co-sponsored by the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology and included 5 working groups; 3 work groups performed comprehensive literature reviews and developed draft recommendations. Another work group provided the historical background and the fifth will continue to foster implementation of the LAST recommendations. After an open comment period, the draft recommendations were presented at a consensus conference attended by LAST work group members, advisors, and representatives from 35 stakeholder organizations including professional societies and government agencies. Recommendations were finalized and voted on at the consensus meeting. The final, approved recommendations standardize biologically relevant histopathologic terminology for HPV-associated squamous intraepithelial lesions and superficially invasive squamous carcinomas across all lower anogenital tract sites and detail the appropriate use of specific biomarkers to clarify histologic interpretations and enhance diagnostic accuracy. A plan for disseminating and monitoring recommendation implementation in the practicing community was also developed. The implemented recommendations will facilitate communication between pathologists and their clinical colleagues and improve accuracy of histologic diagnosis with the ultimate goal of providing optimal patient care.


The "Seven Pillars" Response to Patient Safety Incidents: Effects on Medical Liability Processes and Outcomes.
To determine whether a communication and resolution approach to patient harm is associated with changes in medical liability processes and outcomes. Administrative, safety, and risk management data from the University of Illinois Hospital and Health Sciences System, from 2002 to 2014. Single health system, interrupted time series design. Using Mann-Whitney U tests and segmented regression models, we compared means and trends in incident reports, claims, event analyses, patient communication consults, legal fees, costs per claim, settlements, and self-insurance expenses before and after the implementation of the "Seven Pillars" communication and resolution intervention. Queried databases maintained by Department of Safety and Risk Management and the Department of Administrative Services at UIH. Extracted data from risk module of the Midas incident reporting system. The intervention nearly doubled the number of incident reports, halved the number of claims, and reduced legal fees and costs as well as total costs per claim, settlement amounts, and self-insurance costs. A communication and optimal resolution (CANDOR) approach to adverse events was associated with long-lasting, clinically and financially significant changes in a large set of core medical liability process and outcome measures.


Tumours and cancers in Graeco-Roman times.
In Graeco-Roman times all tumours (Greek: onkoi, abnormal swellings) were considered to be of inflammatory origin, the result of unfavourable humoural fluxes, and caused by an extravascular outpouring of fluid into tissue spaces. The neoplastic nature of tumours is a more recent concept, barely two centuries old. In Hippocratic literature tumours were mainly classified as karkinômata, phumata, and oidêmata. Phumata included a large variety of tumours, inflammatory and neoplastic in origin, and mostly benign (in modern terms), while oidêmata were soft, painless tumours and even included generalised oedema (dropsy). Although all categories possibly included occasional cancers, the vast majority of what appears to have been malignant tumours were called karkinoi karkinômata (Latin: cancrum/carcinoma). There was, however, no recognition of benign and malignant, primary and secondary tumours, in the modern sense.


Brachial endothelial function is impaired in patients with systemic lupus erythematosus.
To verify if endothelial function is impaired in pre-menopausal women with systemic lupus erythematosus (SLE) and whether endothelial dysfunction is related to disease duration, cumulative prednisone dose, antimalarial use, anticardiolipin antibody (aCL), hypertension, Raynaud's phenomenon, disease activity score, and vasculitis. Using high-resolution ultrasound, we measured the diameter of brachial artery at rest, during reactive hyperemia, and after glyceryl trinitrate (GTN). We compared 69 pre-menopausal female patients with SLE (mean age 29 +/- 8 years) with 35 age and sex-matched controls (mean age 29 +/- 6 years), The mean disease duration was 72 months. There was no significant difference in baseline brachial artery diameter. The flow-mediated dilation (endothelial dependent dilation) was significantly impaired in SLE patients when compared to controls (5.0 +/- 5.0% vs 12.0 +/- 6.0%, p < 0.001), even in the subgroup of patients without coronary artery disease risk factor (4.5 +/- 4.0% vs 12.0 +/- 6.0%, p < 0.001). The GTN induced dilation (endothelial independent dilation) was significantly lower in the aCL positive SLE patients when compared to the controls (11.9 +/- 4.0% vs 16.3 +/- 6.0%, p < 0.05). The endothelium-dependent dilation was not related to disease duration, cumulative prednisone dose, antimalarial use, anticardiolipin antibody, hypertension history, Raynaud's phenomenon, SLE disease activity score or vasculitis. This is the first study using brachial artery ultrasound imaging to evaluate endothelium function in SLE. Patients with SLE presented lower flow mediated dilation (endothelium dependent dilation) than sex and age-matched controls, even in patients without traditional cardiovascular risk factors and this may represent an early atherosclerotic process.


Deletion of Gab1 in the liver leads to enhanced glucose tolerance and improved hepatic insulin action.
Insulin receptor substrate-1 (IRS-1) and IRS-2 are known to transduce and amplify signals emanating from the insulin receptor. Here we show that Grb2-associated binder 1 (Gab1), despite its structural similarity to IRS proteins, is a negative modulator of hepatic insulin action. Liver-specific Gab1 knockout (LGKO) mice showed enhanced hepatic insulin sensitivity with reduced glycemia and improved glucose tolerance. In LGKO liver, basal and insulin-stimulated tyrosine phosphorylation of IRS-1 and IRS-2 was elevated, accompanied by enhanced Akt/PKB activation. Conversely, Erk activation by insulin was suppressed in LGKO liver, leading to defective IRS-1 Ser612 phosphorylation. Thus, Gab1 acts to attenuate, through promotion of the Erk pathway, insulin-elicited signals flowing through IRS and Akt proteins, which represents a novel balancing mechanism for control of insulin signal strength in the liver.


Mechanisms of motivational interviewing in health promotion: a Bayesian mediation analysis.
Counselor behaviors that mediate the efficacy of motivational interviewing (MI) are not well understood, especially when applied to health behavior promotion. We hypothesized that client change talk mediates the relationship between counselor variables and subsequent client behavior change. Purposeful sampling identified individuals from a prospective randomized worksite trial using an MI intervention to promote firefighters' healthy diet and regular exercise that increased dietary intake of fruits and vegetables (n = 21) or did not increase intake of fruits and vegetables (n = 22). MI interactions were coded using the Motivational Interviewing Skill Code (MISC 2.1) to categorize counselor and firefighter verbal utterances. Both Bayesian and frequentist mediation analyses were used to investigate whether client change talk mediated the relationship between counselor skills and behavior change. Counselors' global spirit, empathy, and direction and MI-consistent behavioral counts (e.g., reflections, open questions, affirmations, emphasize control) significantly correlated with firefighters' total client change talk utterances (rs = 0.42, 0.40, 0.30, and 0.61, respectively), which correlated significantly with their fruit and vegetable intake increase (r = 0.33). Both Bayesian and frequentist mediation analyses demonstrated that findings were consistent with hypotheses, such that total client change talk mediated the relationship between counselor's skills--MI-consistent behaviors [Bayesian mediated effect: αβ = .06 (.03), 95% CI = .02, .12] and MI spirit [Bayesian mediated effect: αβ = .06 (.03), 95% CI = .01, .13]--and increased fruit and vegetable consumption. Motivational interviewing is a resource- and time-intensive intervention, and is currently being applied in many arenas. Previous research has identified the importance of counselor behaviors and client change talk in the treatment of substance use disorders. Our results indicate that similar mechanisms may underlie the effects of MI for dietary change. These results inform MI training and application by identifying those processes critical for MI success in health promotion domains.


EPIDEMIC OF PATHOLOGIC MYOPIA: What Can Laboratory Studies and Epidemiology Tell Us?
To systematically review epidemiologic and laboratory studies on the etiology of high myopia and its links to pathologic myopia. Regular Medline searches have been performed for the past 20 years, using "myopia" as the basic search term. The abstracts of all articles have been scrutinized for relevance, and where necessary, translations of articles in languages other than English were obtained. Systematic review shows that there is an epidemic of myopia and high myopia in young adults in East and Southeast Asia, with similar but smaller trends in other parts of the world. This suggests an impending epidemic of pathologic myopia. High myopia in young adults in East and Southeast Asia is now predominantly associated with environmental factors, rather than genetic background. Recent clinical trials show that the onset of myopia can be reduced by increasing the time children spend outdoors, and methods to slow the progression of myopia are now available. High myopia is now largely associated with environmental factors that have caused the epidemic of myopia in East and Southeast Asia. An important clinical question is whether the pathologic consequences of acquired high myopia are similar to those associated with classic genetic high myopia. Increased time outdoors can be used to slow the onset of myopia, whereas methods for slowing progression are now available clinically. These approaches should enable the current epidemics of myopia and high myopia to be turned around, preventing an explosion of pathologic myopia.


Ultracompact all-optical XOR logic gate in a slow-light silicon photonic crystal waveguide.
We demonstrate an ultracompact, chip-based, all-optical exclusive-OR (XOR) logic gate via slow-light enhanced four-wave mixing (FWM) in a silicon photonic crystal waveguide (PhCWG). We achieve error-free operation (<10⁻⁹) for 40 Gbit/s differential phase-shift keying (DPSK) signals with a 2.8 dB power penalty. Slowing the light to vg = c/32 enables a FWM conversion efficiency, η, of -30 dB for a 396 μm device. The nonlinear FWM process is enhanced by 20 dB compared to a relatively fast mode of vg = c/5. The XOR operation requires ≈ 41 mW, corresponding to a switching energy of 1 pJ/bit. We compare the slow-light PhCWG device performance with experimentally demonstrated XOR DPSK logic gates in other platforms and discuss scaling the device operation to higher bit-rates. The ultracompact structure suggests the potential for device integration.


Variability in Mass Spectrometry-based Quantification of Clinically Relevant Drug Transporters and Drug Metabolizing Enzymes.
Many different methods are used for mass-spectrometry-based protein quantification in pharmacokinetics and systems pharmacology. It has not been established to what extent the results from these various methods are comparable. Here, we compared six different mass spectrometry-based proteomics methods by measuring the expression of clinically relevant drug transporters and metabolizing enzymes in human liver. Mean protein concentrations were in general quantified to similar levels by methods using whole tissue lysates. Methods using subcellular membrane fractionation gave incomplete enrichment of the proteins. When the enriched proteins were adjusted to levels in whole tissue lysates, they were on average 4-fold lower than those quantified directly in whole tissue lysates. The differences in protein levels were propagated into differences in predictions of hepatic clearance. In conclusion, caution is needed when comparing and applying quantitative proteomics data obtained with different methods, especially since membrane fractionation is common practice for protein quantification used in drug clearance predictions.


A smartphone platform for the quantification of vitamin D levels.
Vitamin D deficiency has been linked to a number of diseases and adverse outcomes including: osteoporosis, infections, diabetes, cardiovascular diseases, and even cancer. At present the vast majority of vitamin D testing is performed in large-scale laboratories at the request of a physician as part of an annual panel of blood tests. Here we present a system for rapid quantification of vitamin D levels on a smartphone. The system consists of a smartphone accessory, an app, and a test strip that allows the colorimetric detection of 25-hydroxyvitamin D using a novel gold nanoparticle-based immunoassay. We show that the system can be used to accurately measure physiological levels of 25-hydroxyvitamin D with accuracy better than 15 nM and a precision of 10 nM. We compare our system with well-established ELISA test kits for serum samples of unknown concentration and demonstrate equivalency of the results. We envision this as the first step towards the development of the NutriPhone, a comprehensive system for the analysis of multiple vitamins and micronutrients on a smartphone.


Validation of the NITI Endoluminal Compression Anastomosis Ring (EndoCAR) device and comparison to the traditional circular stapled colorectal anastomosis in a porcine model.
The purpose of this study was to determine whether the characteristics of compression anastomoses created by a new device are comparable to existing stapler technology. A total of 18 pigs were studied, and each served as its own control using a 27-mm compression device and a 29-mm stapler. Anastomoses were randomized to proximal and distal positions along the rectum and were separated by 10 cm. Six nonsurvival pigs were sacrificed at zero time to failure test the anastomoses. Twelve pigs were sacrificed at 14 days. Failure pressures, circumferences, and radiographic leak rates were determined. Anastomotic tissue was processed for matrix metalloproteinase, collagen, and elastin levels. The compression anastomoses had higher mean failure pressures than stapled anastomoses at zero time (103 vs 29.9 mm Hg). At 2 weeks, there was no difference between failure pressures (256 vs 250 mm Hg). During burst testing, 3 of the compression anastomoses failed at the anastomosis at 2 weeks, whereas none of the stapled anastomoses failed. The mean anastomotic circumference of the compression anastomoses was narrower than the stapled anastomoses (9.63 vs 11.25 cm, P = .001). There were no clinical leaks or radiographic leaks by barium enema at 2 weeks. There was no difference between matrix metalloproteinase, collagen, or elastin content based on tissue analysis. There were dense adhesions to 7 of 12 (58.3%) of the stapled anastomoses, whereas only 1 of 12 (8.3%) of the compression anastomoses had flimsy adhesions. A new compression anastomosis technique using a nickel-titanium alloy may be an advance in technology by reducing leaks and eliminating foreign material in the anastomosis.


Tentative interpretive criteria for the diffusion susceptibility test using 30-microgram netilmicin disks.
The disk diffusion inhibitory zone diameters for 10-microgram and 30-microgram netilmicin disks were correlated with minimum inhibitory concentrations against 471 clinical strains tested in cation-supplemented Mueller-Hinton broth. Regression line and error-rate bounded analysis favored the use of 30-microgram netilmicin disks utilizing zone size breakpoints of greater than or equal to 17 mm to indicate susceptibility (less than or equal to 8 microgram/ml) and less than or equal to 13 mm to indicate resistance (greater than 32 microgram/ml). Significant minor interpretive errors may be expected when testing populations of Pseudomonas that have netilmicin minimum inhibitory concentrations near the intermediate range (16 microgram/ml).


Consistent Divisions or Methodological Decisions? Assessing the U.S. Racial Hierarchy Across Outcomes.
Scholars have offered a range of perspectives on the twenty-first century racial landscape with little consensus about either the current state of the U.S. racial hierarchy or its future trajectory. We offer a more comprehensive assessment, using data from the National Longitudinal Study of Adolescent to Adult Health (Add Health) to study racial stratification across a number of socioeconomic outcomes. We pay particular attention to the robustness of results across different categorization schemes that account for self-identification and interviewer classification, as well as racial fluidity. Although we observe that White and Asian Americans generally have the best socioeconomic outcomes, on average, while Black Americans and American Indians have the worst, we also find meaningful differences in patterns of stratification both across outcomes and depending on how race is operationalized. These differences in stratification are reflected in the estimated number of strata as well as the rank order of racial categories. Our results suggest that ongoing debates about the nature of the U.S. racial hierarchy can be partly explained by methodological decisions about which outcomes to study and how best to measure race. The online version contains supplementary material available at 10.1007/s12552-021-09351-2.


A comparison between use of spray and freeze drying techniques for preparation of solid self-microemulsifying formulation of valsartan and in vitro and in vivo evaluation.
The objective of the present study was to develop self micro emulsifying formulation (SMEF) of valsartan to improve its oral bioavailability. The formulations were screened on the basis of solubility, stability, emulsification efficiency, particle size and zeta potential. The optimized liquid SMEF contains valsartan (20% w/w), Capmul MCM C8 (16% w/w), Tween 80 (42.66% w/w) and PEG 400 (21.33% w/w) as drug, oil, surfactant and co-surfactant, respectively. Further, Liquid SMEF was adsorbed on Aerosol 200 by spray and freeze drying methods in the ratio of 2 : 1 and transformed into free flowing powder. Both the optimized liquid and solid SMEF had the particle size <200 nm with rapid reconstitution properties. Both drying methods are equally capable for producing stable solid SMEF and immediate release of drug in in vitro and in vivo conditions. However, the solid SMEF produced by spray drying method showed high flowability and compressibility. The solid state characterization employing the FTIR, DSC and XRD studies indicated insignificant interaction of drug with lipid and adsorbed excipient. The relative bioavailability of solid SMEF was approximately 1.5 to 3.0 folds higher than marketed formulation and pure drug. Thus, the developed solid SMEF illustrates an alternative delivery of valsartan as compared to existing formulations with improved bioavailability.


Am I my brother's (or customer's or tenant's) keeper? Economic and ethical aspects to the California Supreme Court's struggle with the issue of landowner's standard of care.
The Supreme Court of California has ruled on several cases involving the question of to what extent a possessor of land is liable for the harm to customers or tenants occurring when a third party commits a criminal act against the customers or tenants present on the land. This paper reviews the historical development of this aspect of negligence law and analyzes the ethical and economic efficiency implications of ascribing legal responsibility for such crimes to: a) local government, b) the possessor of land, c) the customer, and d) the criminal. For example, is there an effort by the judicial system to substitute deterrence from criminal acts provided by possessors of land (i.e., specific deterrence) for the general deterrence traditionally provided through the use of police powers by local government? Analysis indicates that specific deterrence may be more effective in changing the location of criminal acts than in reducing the level of criminal activities. Also, the expense of complying with the legal responsibilities of protecting customers and clients may be especially high in high-crime, low-income areas, thus forcing commercial establishments to move or go out of business. Thus, we have a troubling tradeoff: compensating individual crime victims in a high-crime area could ultimately deprive the residents of basic economic opportunities.


Cost of coils for intracranial aneurysms: clinical decision analysis for implementation of a capitation model.
OBJECTIVE The price of coils used for intracranial aneurysm embolization has continued to rise despite an increase in competition in the marketplace. Coils on the US market range in list price from $500 to $3000. The purpose of this study was to investigate potential cost savings with the use of a price capitation model. METHODS The authors built a clinical decision analytical tree and compared their institution's current expenditure on endovascular coils to the costs if a capped-price model were implemented. They retrospectively reviewed coil and cost data for 148 patients who underwent coil embolization from January 2015 through September 2016. Data on the length and number of coils used in all patients were collected and analyzed. The probabilities of a treated aneurysm being ≤/> 10 mm in maximum dimension, the total number of coils used for a case being ≤/> 5, and the total length of coils used for a case being ≤/> 50 cm were calculated, as was the mean cost of the currently used coils for all possible combinations of events with these probabilities. Using the same probabilities, the authors calculated the expected value of the capped-price strategy in comparison with the current one. They also conducted multiple 1-way sensitivity analyses by applying plausible ranges to the probabilities and cost variables. The robustness of the results was confirmed by applying individual distributions to all studied variables and conducting probabilistic sensitivity analysis. RESULTS Ninety-five (64%) of 148 patients presented with a rupture, and 53 (36%) were treated on an elective basis. The mean aneurysm size was 6.7 mm. A total of 1061 coils were used from a total of 4 different providers. Companies A (72%) and B (16%) accounted for the major share of coil consumption. The mean number of coils per case was 7.3. The mean cost per case (for all coils) was $10,434. The median total length of coils used, for all coils, was 42 cm. The calculated probability of treating an aneurysm less than 10 mm in maximum dimension was 0.83, for using 5 coils or fewer per case it was 0.42, and for coil length of 50 cm or less it was 0.89. The expected cost per case with the capped policy was calculated to be $4000, a cost savings of $6564 in comparison with using the price of Company A. Multiple 1-way sensitivity analyses revealed that the capped policy was cost saving if its cost was less than $10,500. In probabilistic sensitivity analyses, the lowest cost difference between current and capped policies was $2750. CONCLUSIONS In comparison with the cost of coils from the authors' current provider, their decision model and probabilistic sensitivity analysis predicted a minimum $407,000 to a maximum $1,799,976 cost savings in 148 cases by adapting the capped-price policy for coils.


A Bayesian model of shape and appearance for subcortical brain segmentation.
Automatic segmentation of subcortical structures in human brain MR images is an important but difficult task due to poor and variable intensity contrast. Clear, well-defined intensity features are absent in many places along typical structure boundaries and so extra information is required to achieve successful segmentation. A method is proposed here that uses manually labelled image data to provide anatomical training information. It utilises the principles of the Active Shape and Appearance Models but places them within a Bayesian framework, allowing probabilistic relationships between shape and intensity to be fully exploited. The model is trained for 15 different subcortical structures using 336 manually-labelled T1-weighted MR images. Using the Bayesian approach, conditional probabilities can be calculated easily and efficiently, avoiding technical problems of ill-conditioned covariance matrices, even with weak priors, and eliminating the need for fitting extra empirical scaling parameters, as is required in standard Active Appearance Models. Furthermore, differences in boundary vertex locations provide a direct, purely local measure of geometric change in structure between groups that, unlike voxel-based morphometry, is not dependent on tissue classification methods or arbitrary smoothing. In this paper the fully-automated segmentation method is presented and assessed both quantitatively, using Leave-One-Out testing on the 336 training images, and qualitatively, using an independent clinical dataset involving Alzheimer's disease. Median Dice overlaps between 0.7 and 0.9 are obtained with this method, which is comparable or better than other automated methods. An implementation of this method, called FIRST, is currently distributed with the freely-available FSL package.


A high-density genetic map and molecular sex-typing assay for gerbils.
We constructed a high-density genetic map for Mongolian gerbils (Meriones unguiculatus). We genotyped 137 F2 individuals with a genotype-by-sequencing (GBS) approach at over 10,000 loci and built the genetic map using a two-step approach. First, we chose the highest-quality set of 485 markers to construct a robust map of 1239 cM with 22 linkage groups as expected from the published karyotype. Second, we added an additional 5449 markers onto the map based on their genotype similarity with the original markers. We used the final marker set to assemble 1140 genomic scaffolds (containing ~ 20% of annotated genes) into a chromosome-level assembly. We used both genetic linkage and relative sequencing coverage in males and females to identify X- and Y-chromosome scaffolds and from these we designed a robust and internally-controlled PCR assay to determine sex. This assay will facilitate early stage sex-typing of embryonic and young gerbils which is difficult using current visual methods. Accession ID: Meriones unguiculatus: 10047.


Personalized therapy based on image for esophageal or gastroesophageal junction adenocarcinoma.
Preoperative therapy is the gold standard for esophageal or gastroesophageal junction adenocarcinoma. Positron emission tomography (PET) is not only essential for tumor staging, but changes in glucose consumption correspond with response to therapy and correlated with prognosis. Therefore, with further refinement, PET parameter can serve as a tool for personalized therapy. For instance, the Municon trials suggested the possibility of PET-response guided therapy for esophageal adenocarcinoma (EAC) patients, however there are limitations. New PET parameters such as total lesion glycolysis (TLG) or magnetic resonance imaging (MRI) may provide better response prediction. Furthermore, PET parameters combined with genomic profiling might enhance better treatment selection, prediction, and prognostication. Here, we summarized the current state of understanding and future possibilities.


Case-control study of postmenopausal hormone replacement therapy and endometrial cancer.
This study evaluated recent inconsistent findings that adding progestins to postmenopausal estrogen replacement therapy protects against endometrial cancer. Using a population-based case-control study, the authors compared 511 endometrial cancer cases aged 50-79 years in the Philadelphia, Pennsylvania, region during 1999-2002 with 1,412 random-digit-dialing controls regarding postmenopausal hormone replacement therapy (HRT) use. Telephone interviews were performed with memory aids mailed in advance. An increased risk of endometrial cancer was observed among postmenopausal women using only unopposed estrogen for 3 or more years, compared with women who never used HRT (adjusted odds ratio = 3.4, 95% confidence interval (CI): 1.4, 8.3). Using combination HRT (of any duration) was associated with a substantial reduction in risk (odds ratio = 0.8, 95% CI: 0.6, 1.1). Comparing women using only combined estrogen and progestin for 3 or more years with women using only unopposed estrogen for 3 or more years, the authors found that the adjusted odds ratio was 0.2 (95% CI: 0.1, 0.6). Long-term use of unopposed estrogen is associated with increased risk for endometrial cancer, whereas combined estrogen plus progestin hormone therapy is not. Thus, if HRT is to be used in women with an intact uterus, this study confirms the benefit of adding progestins to the regimen.


Evaluation of adnexal masses with three-dimensional ultrasonography.
To estimate whether three-dimensional ultrasonography and three-dimensional power Doppler investigation can contribute to the differentiation between benign and malignant ovarian masses. Women scheduled for surgical treatment of an adnexal mass were included in a multicenter prospective study. All women underwent two-dimensional and three-dimensional ultrasonographic examination in the week before surgery. All parameters were compared in women with benign tumors, borderline tumors, and malignant tumors using receiver operating characteristic analysis and likelihood ratios. We included 181 women; 144 had a benign mass, 26 had a malignancy, and 11 had a borderline tumor. At three-dimensional ultrasonography, the most striking difference was found in the presence of central vessels in an adnexal mass. Central vessels assessed by three-dimensional ultrasonography were present in 15% (21 of 144) of the benign masses, 69% (18 of 26) of the malignant masses, and 27% (3 of 11) of the masses of borderline malignancy. The likelihood ratios for presence of central vessels for a mass being malignant and/or borderline was 4.9 (95% confidence interval 2.1-12). Mean gray index and flow index were also significantly different between the groups, but other features were not. The central localization of vessels in an adnexal mass, as observed by three-dimensional ultrasonography, the mean gray index, and the flow index are potentially important parameters for distinguishing benign from malignant adnexal masses. II-2.


Molecular assessment of Pocillopora verrucosa (Scleractinia; Pocilloporidae) distribution along a depth gradient in Ludao, Taiwan.
It can be challenging to identify scleractinian corals from the genus Pocillopora Lamarck 1816 in the field because of their large range of inter- and intra-specific morphological variation that co-occur with changes in the physical environment. This task is made more arduous in the context of a depth gradient, where light and water current could greatly affect the morphology of the corallum. Pocillopora verrucosa (Ellis & Solander 1786) in Taiwan was previously reported exclusively from shallow waters (<10 m in depth), but a recent observation of this species in the mesophotic zone (>40 m in depth) questions this bathymetric distribution. We used the mitochondrial open reading frame and the histone 3 molecular markers to investigate the vertical and horizontal spatial distribution of P. verrucosa around Ludao (Green Island), Taiwan. We genotyped 101 P. verrucosa-like colonies collected from four depth zones, ranging from 7 to 45 m, at three sites around the island. Of the 101 colonies sampled, 85 were genotyped as P. verrucosa, 15 as P. meandrina, and one specimen as an undescribed Pocillopora species. P. verrucosa was found at all depths, while P. meandrina and the undescribed Pocillopora specimen were limited to 15 m depth. P. verrucosa has a large bathymetric distribution around Ludao and could benefit from the refuge that the mesophotic zone offers. This study illustrates the difficulty of identifying Pocillopora corals in the field and emphasizes the relevance of molecular taxonomy as an important and complementary tool to traditional taxonomy for clarifying vertical and horizontal species distribution. Our results also illustrate the need in conservation biology to target species genetic diversity rather than just species diversity.


Lower-Extremity Edema Is Common after Transjugular Intrahepatic Portosystemic Shunt Creation and Is Associated with Lower Survival: A Two-Institution Study.
Background Transjugular intrahepatic portosystemic shunt (TIPS) creation is an accepted treatment of portal hypertension. Lower-extremity edema (LEE) is an underreported complication of TIPS creation. Purpose To assess the epidemiologic findings of LEE after TIPS creation and their association with patient survival. Materials and Methods The medical records of patients who underwent TIPS creation between January 2003 and April 2019 at Oregon Health and Science University and patients who underwent TIPS creation between January 2006 and December 2016 at University of Minnesota were retrospectively reviewed. Clinical, laboratory, and technical parameters, development and outcome of edema, and survival data were collected. LEE was defined as new-onset or worsened edema up to 1 year after TIPS creation. Cardiac ventricular function was evaluated with transthoracic echocardiography. Risk factors for LEE were evaluated with logistic regression analysis, and critical P values were additionally assessed by using the false discovery rate. Survival curves were compared by using the log-rank test. Results Three hundred thirty-four patients were included (mean age, 55 years ± 11 [standard deviation]; 208 men). TIPS creation was primarily performed for ascites (159 of 334 patients, 48%), gastrointestinal bleeding (127 of 334 patients, 38%), or a combination of bleeding and ascites (38 of 334 patients, 11%). One hundred seventy of the 334 patients (51%) developed LEE (new onset, 120; worsened edema, 50). Three of 170 patients (2%) had abnormal left ventricular ejection fraction. Multivariable analysis showed TIPS creation for ascites (odds ratio, 1.7; 95% CI: 1.04, 2.7; P = .03) and hepatic hydrothorax (odds ratio, 2.2; 95% CI: 1.1, 4.2; P = .02) was likely associated with LEE; however, it did not reach significance at a critical P value of .009. Among 164 patients with data on the outcome of LEE, LEE eventually improved in 94 (57%). The median survival of patients with LEE was lower than that of patients without LEE (38 months vs 71 months, respectively; P = .02). Conclusion Lower-extremity edema developed in more than 50% of study patients who underwent transjugular intrahepatic portosystemic shunt (TIPS) creation, regardless of left ventricular function. There was suggestion that TIPS creation for ascites might be an underlying risk factor. Lower-extremity edema portends worse survival. © RSNA, 2020 Online supplemental material is available for this article.


Laparoscopic-assisted nephrectomy with inferior vena cava tumor thrombectomy: preliminary results.
To evaluate the feasibility and outcome of laparoscopic-assisted radical nephrectomy and inferior vena cava (IVC) tumor thrombectomy in patients with renal cell carcinoma and level I IVC tumor thrombus. The clinical, operative, and pathologic data were retrospectively obtained from patients undergoing the above-mentioned procedure for renal tumors involving the IVC. This approach involved laparoscopic dissection of the kidney and renal vasculature/IVC. After renal artery ligation, an 8 to 12-cm incision was made from the tip of the 11th rib extending anteriorly toward the midline. Through this incision, a Satinsky vascular clamp was placed on the IVC in such a way as to include all the caval thrombus. The tumor thrombus was removed en bloc with the kidney and the cavotomy repaired with a running suture. Four obese patients underwent transperitoneal laparoscopic-assisted right nephrectomy with inferior vena cava (IVC) thrombectomy. The mean tumor size was 9 cm (range 6 to 13), with the thrombus extending 2 cm into the IVC in all cases. Patients had a mean body mass index of 32.8 (range 30.5 to 37.2) and a mean American Society of Anesthesiologists score of 2.8 (range 2 to 3). The mean operative time was 248 minutes (range 225 to 274). The mean estimated blood loss was 517 mL (range 250 to 900). No intraoperative or postoperative complications occurred. The mean hospital stay was 6.2 days (range 4 to 11, median 5). Laparoscopic-assisted nephrectomy and IVC thrombectomy is a difficult but feasible procedure. This approach allows a smaller incision than a typical open approach. Additional studies are needed to examine the advantages of this approach over a pure open approach.


The reference epigenome and regulatory chromatin landscape of chronic lymphocytic leukemia.
Chronic lymphocytic leukemia (CLL) is a frequent hematological neoplasm in which underlying epigenetic alterations are only partially understood. Here, we analyze the reference epigenome of seven primary CLLs and the regulatory chromatin landscape of 107 primary cases in the context of normal B cell differentiation. We identify that the CLL chromatin landscape is largely influenced by distinct dynamics during normal B cell maturation. Beyond this, we define extensive catalogues of regulatory elements de novo reprogrammed in CLL as a whole and in its major clinico-biological subtypes classified by IGHV somatic hypermutation levels. We uncover that IGHV-unmutated CLLs harbor more active and open chromatin than IGHV-mutated cases. Furthermore, we show that de novo active regions in CLL are enriched for NFAT, FOX and TCF/LEF transcription factor family binding sites. Although most genetic alterations are not associated with consistent epigenetic profiles, CLLs with MYD88 mutations and trisomy 12 show distinct chromatin configurations. Furthermore, we observe that non-coding mutations in IGHV-mutated CLLs are enriched in H3K27ac-associated regulatory elements outside accessible chromatin. Overall, this study provides an integrative portrait of the CLL epigenome, identifies extensive networks of altered regulatory elements and sheds light on the relationship between the genetic and epigenetic architecture of the disease.


Magnetic structures of the low temperature phase of Mn3(VO4)2 - towards understanding magnetic ordering between adjacent Kagomé layers.
In this article we report on a detailed analysis of the magnetic structures of the magnetic phases of the low temperature (lt-) phase of Mn3(VO4)2 (=Mn3V2O8) with a Kagomé staircase structure determined by means of powder neutron diffraction. Two magnetic transitions were found at ∼25 K (HT1 phase, Cmc'a') and ∼17 K (LT1 phase, Pmc'a'), in excellent agreement with previous reports. The LT1 phase is characterized by commensurate magnetic ordering of the magnetic moments on two magnetic sites of the Mn1a/b (2a + 2d) and Mn2 (8i) ions of the nuclear structure (where for the latter site two different overall orientations of magnetic moments within the ab-plane (Mn2a and Mn2b) can be distinguished. This results in mainly antiferromagnetic interactions between edge-sharing Mn-octahedra within the Kagomé planes. The HT1 phase is characterised by strong spin frustration resulting from the loss of ordering of the magnetic moments of Mn2a/b ions along the b-axis. Both magnetic structures are in agreement with the previously reported ferrimagnetic properties of lt-Mn3(VO4)2 and shed light on the magnetic phase diagram of the compound reported previously. The magnetic structures are discussed with respect to superexchange interaction pathways within the Kagomé layers, which appear to be predominantly antiferromagnetic. The magnetic structures of Mn3(VO4)2 are different compared to those reported for Ni3(VO4)2 and Co3(VO4)2 and represent an unique commensurate way out of spin frustration for compounds with strong antiferromagnetic superexchange interactions within the Kagomé layers. Additionally, we derive a superexchange model, which will be called redox-mediated M-M(')(d(0))-M superexchange and which can help to understand the exclusively ferromagnetic ordering of adjacent Kagomé layers found only for lt-Mn3(VO4)2.


SPECT brain imaging in epilepsy: a meta-analysis.
A meta-analysis of SPECT brain imaging in epilepsy was performed to derive the sensitivity and specificity of interictal, postictal or ictal rCBF patterns to identify a seizure focus in medically refractory patients. Papers were obtained by pooling all published articles identified by two independent literature searches: (a) Dialnet (EMBASE) or Radline by CD-ROM and (b) Current Contents searched manually. Literature inclusion criteria were: (a) patients had a localization-related epileptic syndrome; (b) more than six patients were reported; and (c) patients had at least an interictal EEG-documented epileptiform abnormality. Of 46 papers meeting these criteria, 30 contained extractable data. SPECT results were compared to localization by standard diagnostic evaluation and surgical outcome. Meta-analytic sensitivities for SPECT localization in patients with temporal lobe seizures relative to diagnostic evaluation were 0.44 (interictal), 0.75 (postictal) and 0.97 (ictal). Similar results were obtained relative to surgical outcome. False-positive rates were low relative to diagnostic evaluation (7.4% for interictal and 1.5% for postictal studies) and surgical outcome (4.4% for interictal and 0.0% for postictal studies). The results were not dependent on tracer used (or dose), the presence of CT-identified structural abnormalities, blinding of image interpretation or camera quality (although data were more variable with low-resolution cameras). There were insufficient data for conclusions regarding extratemporal-seizure or pediatric epilepsy populations. Insights gained from reviewing this literature yielded recommendations for minimal information that should be provided in future reports. Additional recommendations regarding the nature and focus of future studies also are provided. The most important of these is that institutions using SPECT imaging in epilepsy should perform ictal, preferably, or postictal scanning in combination with interictal scanning.


Finding and Verifying Enhancers for Endothelial-Expressed Genes.
Identification and analysis of enhancers for endothelial-expressed genes can provide crucial information regarding their upstream transcriptional regulators. However, enhancer identification can be challenging, particularly for people with limited access or experience of bioinformatics, and transgenic analysis of enhancer activity patterns can be prohibitively expensive. Here we describe how to use publicly available datasets displayed on the UCSC Genome Browser to identify putative endothelial enhancers for mammalian genes. Furthermore, we detail how to utilize mosaic Tol2-mediated transgenesis in zebrafish to verify whether a putative enhancer is capable of directing endothelial-specific patterns of gene expression.


Loss of skeletal muscle in cancer: biochemical mechanisms.
Patients with cancer often undergo a specific loss of skeletal muscle mass, while the visceral protein reserves are preserved. This condition known as cachexia reduces the quality of life and eventually results in death through erosion of the respiratory muscles. Nutritional supplementation or appetite stimulants are unable to restore the loss of lean body mass, since protein catabolism is increased mainly as a result of the activation of the ATP-ubiquitin-dependent proteolytic pathway. Several mediators have been proposed. An enhanced protein degradation is seen in skeletal muscle of mice administered tumour necrosis factor (TNF), which appears to be mediated by oxidative stress. There is some evidence that this may be a direct effect and is associated with an increase in total cellular-ubiquitin-conjugated muscle proteins. Another cytokine, interleukin-6 (IL-6), may play a role in muscle wasting in certain animal tumours, possibly through both lysosomal (cathepsin) and non-lysosomal (proteasome) pathways. A tumour product, proteolysis-inducing factor (PIF) is produced by cachexia-inducing murine and human tumours and initiates muscle protein degradation directly through activation of the proteasome pathway. The action of PIF is blocked by eicosapentaenoic acid (EPA), which has been shown to attenuate the development of cachexia in pancreatic cancer patients. When combined with nutritional supplementation EPA leads to accumulation of lean body mass and prolongs survival. Further knowledge on the biochemical mechanisms of muscle protein catabolism will aid the development of effective therapy for cachexia.


Identification and management of Lynch syndrome in the Middle East and North African countries: outcome of a survey in 12 countries.
Lynch syndrome (LS), the most common inherited form of colorectal cancer (CRC), is responsible for 3% of all cases of CRC. LS is caused by a mismatch repair gene defect and is characterized by a high risk for CRC, endometrial cancer and several other cancers. Identification of LS is of utmost importance because colonoscopic surveillance substantially improves a patient's prognosis. Recently, a network of physicians in Middle Eastern and North African (ME/NA) countries was established to improve the identification and management of LS families. The aim of the present survey was to evaluate current healthcare for families with LS in this region. A questionnaire was developed that addressed the following issues: availability of clinical management guidelines for LS; attention paid to family history of cancer; availability of genetic services for identification and diagnosis of LS; and assessment of knowledge of LS surveillance. Members of the network and authors of recent papers on LS from ME/NA and neighbouring countries were invited to participate in the survey and complete the online questionnaire. A total of 55 individuals were invited and 19 respondents from twelve countries including Algeria, Azerbaijan, Cyprus, Egypt, Iran, Jordan, Kuwait, Lebanon, Morocco, Palestine, Tunisia, and Turkey completed the questionnaire. The results showed that family history of CRC is considered in less than half of the surveyed countries. Guidelines for the management of LS are available in three out of twelve countries. The identification and selection of families for genetic testing were based on clinical criteria (Amsterdam criteria II or Revised Bethesda criteria) in most countries, and only one country performed universal screening. In most of the surveyed countries genetic services were available in few hospitals or only in a research setting. However, surveillance of LS families was offered in the majority of countries and most frequently consisted of regular colonoscopy. The identification and management of LS in ME/NA countries are suboptimal and as a result most LS families in the region remain undetected. Future efforts should focus on increasing awareness of LS amongst both the general population and doctors, and on the improvement of the infrastructure in these countries.


The effect of mechanical interlocking on crystal packing: predictions and testing.
The first statistical analyses of the X-ray crystal structures of mechanically interlocked molecular architectures, the first molecular mechanics-based solid-state calculations on such structures and atomic force microscopy (AFM) experiments are used in combination to predict and test which types of benzylic amide macrocycle-containing rotaxanes possess mobile components in the crystalline phase and thus could form the basis of solid-state devices that function through mechanical motion at the molecular level. The statistical studies and calculations show that crystals formed by rotaxanes possess similarities and unanticipated differences with respect to the crystal packing of noninterlocked molecules. Trends in the rotaxane series correlate quantities related to crystal packing, molecular size, stoichiometry, and H-bonding. In accordance with the findings of Gavezzotti et al. for conventional molecular architectures, a principal component analysis (PCA) showed that three vectors related to the size, packing parameters, and stoichiometry are sufficient to describe the crystal properties of benzylic amide macrocycle-containing rotaxanes. When hydrogen bond-related quantities are included in a second PCA, they combine with the size and the stoichiometry vectors but not with packing-related parameters, indicating that the intramolecular "saturation" of the H-bonds (between the interlocked components) takes precedence over crystal assembly (i.e., intermolecular packing) in these systems. However, cluster analyses also suggest a major role for the energy of interaction between the macrocycle and its crystal environment. The identification of such a "privileged" interaction is of fundamental importance to the development of rotaxanes with in-crystal mobility of one or more of their interlocked components, a prerequisite for the exploitation of molecular level mechanical motion in the solid state. The set of trends found, together with the calculated energies, was used to propose guidelines for which benzylic amide macrocycle-containing rotaxanes are best suited to become building blocks for systems with mobile submolecular units in the crystalline phase. An experimental test of the predictive power of such guidelines was carried out using AFM on a rotaxane and its thread, identified by the study as a promising candidate for solid-state mobility. Intuitively, the rotaxane should be less mobile in the solid state since it has multiple sets of both hydrogen bond donors and acceptors that can form strong inter- and intramolecular H-bonds. Conversely, the thread has no hydrogen bond donors and cannot form such bonds. The AFM experiments, however, confirm the statistical analysis prediction that the rotaxane is considerably more mobile in the solid than the thread.


In Silico Analysis of Green Tea Polyphenols as Inhibitors of AChE and BChE Enzymes in Alzheimer's Disease Treatment.
Alzheimer's disease (AD) is the most frequent cause of dementia, especially in the elderly. AD is the most common progressive neurodegenerative disorder, which involves the loss of structure and function of cholinergic neurons. Moreover, if these neuronal changes cannot be compensated, this may ultimately lead to neurodegenerative processes. Therefore, most of the drug therapies are based on the cholinergic hypothesis, which suggests that AD begins as a deficiency in the production of the neurotransmitter acetylcholine. In this context, many inhibitors play an important role in AD treatment among which acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have more potential in the treatment process of AD. In this study, we selected tea polyphenols of green tea which are reported as AChE and BChE inhibitors used in the treatment of AD. The molecular docking results revealed that polyphenols exhibit interactions and inhibit by binding with AChE and BChE. The amount of energy to bind with AChE and BChE needed by Epigallocatechin-3-gallate was lowest at about -14.45 and -13.30 kcal/mol, respectively. All compounds showed binding energy values ranging between -14.45 to -9.75 kcal/mol for both types of enzymes. The present docking study suggests that tea polyphenols inhibit AChE as well as BChE and enhance the cholinergic neurotransmission by prolonging the time. However, AChE molecules remain in the synaptic cleft. In consideration to these findings, cholinesterase inhibitors are suggested as the standard drugs for the treatment of AD.


Relationship of dynamic seat ratings to real-world neck injury rates.
The Insurance Institute for Highway Safety assigns consumer safety ratings to passenger vehicle seats based on laboratory sled tests that simulate rear-end collisions. The purpose of this research was to determine how well these ratings correlate to driver neck injury risk in real-world crashes. Insurance claims for cars and SUVs struck in the rear by the front of another passenger vehicle were examined for evidence of driver neck injury. Logistic regression was used to compare neck injury rates for vehicles with different seat ratings while controlling for other important variables. Driver neck injury rates were 15% lower for vehicles with seats rated good compared with vehicles with seats rated poor. Rates of driver neck injuries lasting 3 months or more were 35% lower for vehicles with seats rated good compared with vehicles with seats rated poor. Seat/head restraints that perform better in dynamic sled tests have lower risk of neck injury than seats that rate poor, especially when considering long-term injuries. However, the relationship of dynamic seat ratings to neck injury rates is not linear. Further research is needed to determine whether the criteria for rating seats can be amended so as to be more uniformly predictive of real-world neck injury.


A universal approach for the synthesis of mesoporous gold, palladium and platinum films for applications in electrocatalysis.
High-surface-area mesoporous materials expose abundant functional sites for improved performance in applications such as gas storage/separation, catalysis, and sensing. Recently, soft templates composed of amphiphilic surfactants and block copolymers have been used to introduce mesoporosity in various materials, including metals, metal oxides and carbonaceous compounds. In particular, mesoporous metals are attractive in electrocatalysis because their porous networks expose numerous unsaturated atoms on high-index facets that are highly active in catalysis. In this protocol, we describe how to create mesoporous metal films composed of gold, palladium, or platinum using block copolymer micelle templates. The amphiphilic block copolymer micelles are the sacrificial templates and generate uniform structures with tunable pore sizes in electrodeposited metal films. The procedure describes the electrodeposition in detail, including parameters such as micelle diameters, deposition potentials, and deposition times to ensure reproducibility. The micelle diameters can be controlled by swelling the micelles with different solvent mixtures or by using block copolymer micelles with different molecular weights. The deposition potentials and deposition times allow further control of the mesoporous structure and its thickness, respectively. Procedures for example applications are included: glucose oxidation, ethanol oxidation and methanol oxidation reactions. The synthetic methods for preparation of mesoporous metal films will take ~4 h; the subsequent electrochemical tests will take ~5 h for glucose sensing and ~3 h for alcohol oxidation reaction.


Bragg stack-functionalized counter electrode for solid-state dye-sensitized solar cells.
A highly reflective counter electrode is prepared through the deposition of alternating layers of organized mesoporous TiO(2) (om-TiO(2)) and colloidal SiO(2) (col-SiO(2)) nanoparticles. We present the effects of introducing this counter electrode into dye-sensitized solar cells (DSSCs) for maximizing light harvesting properties. The om-TiO(2) layers with a high refractive index are prepared by using an atomic transfer radical polymerization and a sol-gel process, in which a polyvinyl chloride-g-poly(oxyethylene) methacrylate graft copolymer is used as a structure-directing agent. The col-SiO(2) layers with a low refractive index are prepared by spin-coating commercially available silica nanoparticles. The properties of the Bragg stack (BS)-functionalized counter electrode in DSSCs are analyzed by using a variety of techniques, including spectroscopic ellipsometry, SEM, UV/Vis spectroscopy, incident photon-to-electron conversion efficiency, electrochemical impedance spectroscopy, and intensity modulated photocurrent/voltage spectroscopy measurements, to understand the critical factors contributing to the cell performance. When incorporated into DSSCs that are used in conjunction with a polymerized ionic liquid as the solid electrolyte, the energy conversion efficiency of this solid-state DSSC (ssDSSC) approaches 6.6 %, which is one of the highest of the reported N719 dye-based ssDSSCs. Detailed optical and electrochemical analyses of the device performance show that this assembly yields enhanced light harvesting without the negative effects of charge recombination or electrolyte penetration, which thus, presents new possibilities for effective light management.


"We have been working overnight without sleeping": traditional birth attendants' practices and perceptions of post-partum care services in rural Tanzania.
In many low-income countries, formal post-partum care utilization is much lower than that of skilled delivery and antenatal care. While Traditional Birth Attendants (TBAs) might play a role in post-partum care, research exploring their attitudes and practices during this period is scarce. Therefore, the aim of this study was to explore TBAs' practices and perceptions in post-partum care in rural Tanzania. Qualitative in-depth interview data were collected from eight untrained and three trained TBAs. Additionally, five multiparous women who were clients of untrained TBAs were also interviewed. Interviews were conducted in February 2013. Data were digitally recorded and transcribed verbatim. Qualitative content analysis was used to analyze data. Our study found that TBAs take care of women during post-partum with rituals appreciated by women. They report lacking formal post-partum care training, which makes them ill-equipped to detect and handle post-partum complications. Despite their lack of preparation, they try to provide care for some post-partum complications which could put the health of the woman at risk. TBAs perceive that utilization of hospital-based post-partum services among women was only important for the baby and for managing complications which they cannot handle. They are poorly linked with the health system. This study found that the TBAs conducted close follow-ups and some of their practices were appreciated by women. However, the fact that they were trying to manage certain post-partum complications can put women at risk. These findings point out the need to enhance the communication between TBAs and the formal health system and to increase the quality of the TBA services, especially in terms of prompt referral, through provision of training, mentoring, monitoring and supervision of the TBA services.


Regulation of histidine and proline degradation enzymes by amino acid availability in Bacillus subtilis.
The first enzymes of the histidine (hut) and proline degradative pathways, histidase and proline oxidase, could not be induced in Bacillus subtilis cells growing in glucose minimal medium containing a mixture of 16 amino acids. Addition of the 16-amino-acid mixture to induced wild-type cells growing in citrate minimal medium repressed histidase synthesis 25- to 250-fold and proline oxidase synthesis 16-fold. A strain containing a transcriptional fusion of the hut promoter to the beta-galactosidase gene was isolated from a library of Tn917-lacZ transpositions. Examination of histidase and beta-galactosidase expression in extracts of a hut-lacZ fusion strain grown in various media showed that induction, catabolite repression, and amino acid repression of the hut operon were mediated at the level of transcription. This result was confirmed by measurement of the steady-state level of hut RNA in cells grown in various media. Since amino acid repression was not defective in B. subtilis mutants deficient in nitrogen regulation of glutamine synthetase and catabolite repression, amino acid repression appears to be mediated by a system that functions independently of these regulatory systems.


Aging and resistance to oxidative damage in Caenorhabditis elegans.
The dauer larva state and the age-1 mutation, both of which extend life-span in Caenorhabditis elegans, were tested for hyperresistance to cellular damage that may be relevant to aging. The age-1 strain TJ401 displayed hyperresistance to oxidative stress relative to its parental strain. The activities of two enzymes that protect cells from oxidative damage, superoxide dismutase (SOD) and catalase, showed an age-dependent increase in mutant animals, which was not seen in the parental strain. These increases in activities paralleled the time course of the hyperresistance. The results are consistent with the age-1 gene product functioning as a negative regulator of SOD and catalase activities. In wild-type and age-1 dauer larvae, elevated levels of SOD activity, but not of catalase activity, were present when compared with young adults. The common increase in SOD activity prompted cloning the C. elegans Cu/Zn SOD gene. Its position on the physical map of the genome was in the region to which the age-1 gene has been genetically mapped, but it is unlikely that a mutation at the SOD locus confers the Age phenotype. Results support the free radical theory of aging by suggesting that the increased resistance to oxidative stress may be among the causes of increased longevity in both strain TJ401 and in the dauer larva.


RhoA as a Signaling Hub Controlling Glucagon Secretion From Pancreatic α-Cells.
Glucagon hypersecretion from pancreatic islet α-cells exacerbates hyperglycemia in type 1 diabetes (T1D) and type 2 diabetes. Still, the underlying mechanistic pathways that regulate glucagon secretion remain controversial. Among the three complementary main mechanisms (intrinsic, paracrine, and juxtacrine) proposed to regulate glucagon release from α-cells, juxtacrine interactions are the least studied. It is known that tonic stimulation of α-cell EphA receptors by ephrin-A ligands (EphA forward signaling) inhibits glucagon secretion in mouse and human islets and restores glucose inhibition of glucagon secretion in sorted mouse α-cells, and these effects correlate with increased F-actin density. Here, we elucidate the downstream target of EphA signaling in α-cells. We demonstrate that RhoA, a Rho family GTPase, plays a key role in this pathway. Pharmacological inhibition of RhoA disrupts glucose inhibition of glucagon secretion in islets and decreases cortical F-actin density in dispersed α-cells and α-cells in intact islets. Quantitative FRET biosensor imaging shows that increased RhoA activity follows directly from EphA stimulation. We show that in addition to modulating F-actin density, EphA forward signaling and RhoA activity affect α-cell Ca2+ activity in a novel mechanistic pathway. Finally, we show that stimulating EphA forward signaling restores glucose inhibition of glucagon secretion from human T1D donor islets.


Conditions for increased insemination rates in caged Aedes triseriatus (Diptera: Culicidae) reared from field-collected eggs.
Primarily in order to facilitate future studies on venereal transmission of La Crosse encephalitis virus by Aedes triseriatus, tests were conducted to identify conditions that maximize insemination rates in caged populations of Ae. triseriatus derived from field-collected eggs. All tests were conducted at 21 degrees C +/- 1 degree C, which is approximately the mean temperature during July and August in southwestern Wisconsin where La Crosse virus is endemic. Non-bloodfed females exposed on their 5th through 8th day of adult life showed little sexual receptivity to either 5- to 6-day-old males or 8- to 9-day-old males. F1 females were no more receptive than their mothers had been at a similar age. Mean insemination rates did not exceed 32.6% in any of these age combinations at sex ratios ranging from 4 males: 1 female-1 male: 4 females. Mean insemination rates ranged as high as 89.0% when non-bloodfed females were exposed on their 9th through 12th day of adult life to 5- to 6-day-old males in a 4 male: 1 female ratio. In females given a bloodmeal on their 4th day of life and exposed on their 5th through 8th day to 5- to 6-day-old males, mean insemination rates ranged as high as 91.7% at a ratio of 2 males: 1 female.


Inhibition of lysosomal protease cathepsin D reduces renal fibrosis in murine chronic kidney disease.
During chronic kidney disease (CKD) there is a dysregulation of extracellular matrix (ECM) homeostasis leading to renal fibrosis. Lysosomal proteases such as cathepsins (Cts) regulate this process in other organs, however, their role in CKD is still unknown. Here we describe a novel role for cathepsins in CKD. CtsD and B were located in distal and proximal tubular cells respectively in human disease. Administration of CtsD (Pepstatin A) but not B inhibitor (Ca074-Me), in two mouse CKD models, UUO and chronic ischemia reperfusion injury, led to a reduction in fibrosis. No changes in collagen transcription or myofibroblasts numbers were observed. Pepstatin A administration resulted in increased extracellular urokinase and collagen degradation. In vitro and in vivo administration of chloroquine, an endo/lysosomal inhibitor, mimicked Pepstatin A effect on renal fibrosis. Therefore, we propose a mechanism by which CtsD inhibition leads to increased collagenolytic activity due to an impairment in lysosomal recycling. This results in increased extracellular activity of enzymes such as urokinase, triggering a proteolytic cascade, which culminates in more ECM degradation. Taken together these results suggest that inhibition of lysosomal proteases, such as CtsD, could be a new therapeutic approach to reduce renal fibrosis and slow progression of CKD.


Contribution of UDP-glucuronosyltransferase 1A1 and 1A8 to morphine-6-glucuronidation and its kinetic properties.
The metabolic conversion of morphine to morphine-6-glucuronide (M6G) seems to play a significant role in mediation of the clinical effect of morphine because of the superior analgesic effect of M6G. Therefore, it would be of great interest to clarify the specificity of morphine-6-glucuronidation by UDP glucuronosyltransferase (UGT) isozymes. We investigated the specificity of morphine-6-glucuronidation catalyzed by recombinant human UGT isozymes in microsomes from baculovirus-infected insect cells. The morphine glucuronidation activity of recombinant human UGT isozymes incubated with morphine and UDP-glucuronic acid was determined by high-performance liquid chromatography with a fluorescence detector. Not only UGT2B7, which is well known to catalyze morphine-6-glucuronidation, but also UGT1A1 and 1A8 effectively catalyzed morphine-6-glucuronidation at relatively low morphine concentrations (<100 muM). The kinetics of both isozymes at the low substrate concentrations showed hyperbolic Michaelis-Menten kinetics. However, as the morphine concentration approached 100 muM, morphine-6-glucuronidation activity gradually decreased, and the kinetics closely resembled substrate inhibition Michaelis-Menten kinetic behavior. The K(m) values were 67.9 and 68.1 muM and the K(si) values were 218.9 and 88.0 muM for UGT1A1 and 1A8, respectively. These kinetics are basically different from that of morphine-6-glucuronidation by UGT2B7, which suggested biphasic Michaelis-Menten kinetic behavior. Furthermore, to estimate the contribution of these UGT isozymes in M6G formation in vivo, the expression levels of UGT1A1 and 1A8 mRNA in human liver and intestine were determined by reverse transcription real-time polymerase chain reaction. The results strongly suggest that UGT1A1 and UGT1A8 are isozymes involved in morphine-6-glucuronidation in vivo, as is UGT2B7 in humans.


Effect of deacetylation on property of electrospun chitosan/PVA nanofibrous membrane and removal of methyl orange, Fe(III) and Cr(VI) ions.
In this study, effect of degree of deacetylation on property and adsorption capacity of chitosan/polyvinyl Alcohol electrospun membrane has been investigated. Resulting nanofibers were characterized by FESEM, FTIR, XRD, TGA, tensile testing, weight loss test and adsorption test. FESEM result shows, finer nanofiber was fabricated from 42h hydrolyzed chitosan and PVA blend solution. FTIR and XRD result showed a strong interaction between chitosan and polyvinyl alcohol. Higher tensile strength was observed for the nanofiber having 42h hydrolyzed chitosan. Blend solution of chitosan/PVA having low DD chitosan had higher viscosity. The nanofibrous membrane was stable in distilled water, acidic and basic medium. The isotherm study shows that the adsorption capacity (qm) of nanofiber containing higher DD chitosan was higher for Cr(VI). In contrary, the membrane containing chitosan with lower DD showed the higher adsorption capacity for Fe(III) and methyl orange. Moreover, the effect of DD on removal percentage of adsorbate was dependent on the initial concentration of the adsorbate.


Disability type, depression, and antidepressants use among older adults in the United States.
Objectives: The study aimed to estimate the prevalence of depression and antidepressant use among older adults with different types of disability.Methods: The study sample consisted of 32,193 adults 50 years and older who participated in the Adult Functioning and Disability supplement of the National Health Interview Survey from 2010-2014. Logistic regression was used to estimate depressive symptoms and self-reported antidepressant use by disability type.Results: One in ten participants reported feeling depressed daily or weekly, and less than half of them reported using antidepressants. Adults with a disability in cognition (odds ratio [OR] = 5.55), mobility (OR = 1.92), vision (OR = 1.91), hearing (OR = 1.88), and self-care (OR = 1.66) were more likely to often feel depressed. Antidepressant use was higher among those with cognition and self-care disability compared with no disabilities. A dose-response association existed between the number of disabilities and depression (AOR = 2.3) and antidepressant use (AOR = 1.39).Conclusions: Various forms of disability are strongly associated with depression in older adults. Antidepressants may be underutilized among older adults with certain impairments, including vision, hearing, and mobility. Future research needs should elucidate the mechanisms linking different disabilities to depression and aim to develop treatments tailored to the needs of older adults with disabilities.


Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future.
Major progress has been made toward our understanding of the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway (referred to as the PD pathway). mAbs are already being used to block the PD pathway to treat human cancers (anti-PD therapy), especially advanced solid tumors. This therapy is based on principles that were discovered through basic research more than a decade ago, but the great potential of this pathway to treat a broad spectrum of advanced human cancers is just now becoming apparent. In this Review, we will briefly review the history and development of anti-PD therapy, from the original benchwork to the most up-to-date clinical results. We will then focus the discussion on three basic principles that define this unique therapeutic approach and highlight how anti-PD therapy is distinct from other immunotherapeutic approaches, namely tumor site immune modulation, targeting tumor-induced immune defects, and repairing ongoing (rather than generating de novo) tumor immunity. We believe that these fundamental principles set the standard for future immunotherapies and will guide our efforts to develop more efficacious and less toxic immune therapeutics to treat human cancers.


Deposition of Quantum Dots in a Capillary Tube.
The ability to assemble nanomaterials, such as quantum dots, enables the creation of functional devices that present unique optical and electronic properties. For instance, light-emitting diodes with exceptional color purity can be printed via the evaporative-driven assembly of quantum dots. Nevertheless, current studies of the colloidal deposition of quantum dots have been limited to the surfaces of a planar substrate. Here, we investigate the evaporation-driven assembly of quantum dots inside a confined cylindrical geometry. Specifically, we observe distinct deposition patterns, such as banding structures along the length of a capillary tube. Such coating behavior can be influenced by the evaporation speed as well as the concentration of quantum dots. Understanding the factors governing the coating process can provide a means to control the assembly of quantum dots inside a capillary tube, ultimately enabling the creation of novel photonic devices.


Serum thyroxine concentrations in larval and metamorphosing anadromous sea lamprey, Petromyzon marinus L.
Thyroxine (T4) concentrations in samples of fresh sera taken from fed and unfed larval (ammocoetes) and metamorphosing anadromous sea lamprey (Petromyzon marinus) were measured by means of radioimmunoassay. T4 levels in unfed ammocoetes after a 1-month period were not significantly different from those of the fed ammocoetes. Nutritional state of ammocoetes therefore does not seem to affect their serum T4 levels. Serum T4 concentrations decreased abruptly at the onset of metamorphosis and declined to levels observed in spawing adults (Leloup and Hardy, '76; Packard et al., '76) by the middle (stage 3) of metamorphosis. No significant change in serum T4 levels occurred between stage 3 to the end of metamorphosis. The possible significance of decline in serum T4 levels to the metamorphic event in lamprey is discussed.


Large benefits to marine fisheries of meeting the 1.5°C global warming target.
Translating the Paris Agreement to limit global warming to 1.5°C above preindustrial level into impact-related targets facilitates communication of the benefits of mitigating climate change to policy-makers and stakeholders. Developing ecologically relevant impact-related targets for marine ecosystem services, such as fisheries, is an important step. Here, we use maximum catch potential and species turnover as climate-risk indicators for fisheries. We project that potential catches will decrease by more than 3 million metric tons per degree Celsius of warming. Species turnover is more than halved when warming is lowered from 3.5° to 1.5°C above the preindustrial level. Regionally, changes in maximum catch potential and species turnover vary across ecosystems, with the biggest risk reduction in the Indo-Pacific and Arctic regions when the Paris Agreement target is achieved.


Correction of NR2E3 Associated Enhanced S-cone Syndrome Patient-specific iPSCs using CRISPR-Cas9.
Enhanced S-cone syndrome (ESCS) is caused by recessive mutations in the photoreceptor cell transcription factor NR2E3. Loss of NR2E3 is characterized by repression of rod photoreceptor cell gene expression, over-expansion of the S-cone photoreceptor cell population, and varying degrees of M- and L-cone photoreceptor cell development. In this study, we developed a CRISPR-based homology-directed repair strategy and corrected two different disease-causing NR2E3 mutations in patient-derived induced pluripotent stem cells (iPSCs) generated from two affected individuals. In addition, one patient's iPSCs were differentiated into retinal cells and NR2E3 transcription was evaluated in CRISPR corrected and uncorrected clones. The patient's c.119-2A>C mutation caused the inclusion of a portion of intron 1, the creation of a frame shift, and generation of a premature stop codon. In summary, we used a single set of CRISPR reagents to correct different mutations in iPSCs generated from two individuals with ESCS. In doing so we demonstrate the advantage of using retinal cells derived from affected patients over artificial in vitro model systems when attempting to demonstrate pathophysiologic mechanisms of specific mutations.


Persistently low cardiac output predicts high mortality in newborns with cardiogenic shock.
Cardiogenic shock is an acute "unstable" state of circulatory dysfunction. To evaluate the haemodynamic aspects of 45 newborn infants affected by cardiogenic shock, in relation to etiologies and the mortality rate. Retrospective, correlation study of etiologies, mortality rate and haemodynamic measurements by Doppler ultrasound parameters. 45 newborn infants with cardiogenic shock, Gestational Age (GA) 37 (34-41), Birth Weight (BW) 2750 (1600-3600) g and and a control group of 20 neonates [GA 38 (34-40) wks, BW 2960 (1750-3800) g]. Left ventricular Cardiac Output (CO) was measured by a duplex scanner with pulsed Doppler and color flow mapping echocardiography in the first 48 hours of life. In healthy newborns CO was 240 mL/min/kg (210-280), in newborns with cardiogenic shock CO was 170 mL/min/kg (f130-200), p < 0.01. The Stroke Volume was 1.80 mL/kg (1.70-1.90) in the control group and 1.20 (1.15-1.80) in the shocked group (p < 0.05); Heart Rate was 146 beats/min (130-160) and 160 beats/mm (140-194), (p < 0.01) respectively. Twenty-nine infants with cardiogenic shock had CO < or = 150 mL/min/kg and 5 of them (17.2%) died; 16 neonates had CO > 150 mL/min/kg and only one (6.2%) died (p < .01). Twenty-six of 36 newborns with perinatal asphyxia had CO < or = mL/min/kg and 5 of them died, while only one of 10 infants with CO > 150 mL/min/kg died. Our results show that persistently low CO (< or = mL/min/kg) during the first 48 hours life, in newborns with cardiogenic shock due to perinatal asphyxia is associated with a significantly higher mortality.


An ERAS-based survey evaluating demographics, United States Medical Licensing Examination Performance, and research experience between American medical graduates and United States citizen international medical graduates: is the bar higher on the continent?
To provide an assessment and comparison of the demographics, medical school academic performance, United States Medical Licensing Examination (USMLE) performance, and research experience between American Medical Graduate (AMG) and United States International Medical Graduate (USIMG) candidates who applied for and successfully matched into categorical general surgery residency programs. Data were obtained through the Electronic Residency Application Service (ERAS) and a post-match survey distributed to all applicants. The study was conducted at a community-based, university-affiliated hospital. All United States citizen graduates of allopathic American medical schools or international medical schools, who were applying for a general surgery residency position at our institution. A total of 854 candidates applied, including 143 AMGs and 223 USIMGs. Seventy-two AMGs (50.3%) and 41 USIMGs (18.4%) were invited to interview (p < 0.0001). Mean USMLE step 1 scores were higher among USIMG applicants overall (USIMG: 212.1 ± 14.9 vs AMG: 206.9 ± 15.5; p < 0.0005) and among those invited to interview (USIMG: 227.8 ± 16.2 vs AMG: 215.5 ± 16.2; p < 0.0001). Seventy percent of AMGs matched into a categorical surgery residency compared with 31.6% of USIMGs (p < 0.001). Compared with AMGs, USIMGs applied to more programs (USIMG: 90.3 ± 42.8 vs AMG: 52.1 ± 26.4; p < 0.002), were offered fewer interviews (USIMG: 9.0 ± 6.9 vs AMG: 20.9 ± 13.7; p < 0.0001), and subsequently ranked fewer programs (USIMG: 7.5 ± 4.5 vs AMG: 12.5 ± 6.1; p < 0.0008). USIMGs require higher USMLE scores than their AMG counterparts to be considered for categorical general surgery residency positions. However, excellence on the USMLE neither ensures an invitation to interview nor categorical match success. A well-rounded application in conjunction with a practical application strategy is critical for USIMGs to achieve success in attaining a general surgery residency position.


Diabetes mellitus associated with atypical antipsychotic medications: new case report and review of the literature.
Since the introduction of atypical antipsychotic medications, beginning with clozapine in 1990, several case reports in the psychiatric literature have suggested that they might be associated with new onset of diabetes mellitus as well as with diabetic ketoacidosis. We report the case of a 38-year-old patient with schizophrenia who suddenly developed diabetes mellitus and ketoacidosis 12 months after starting olanzapine. Similar cases in the literature were found through a MEDLINE-assisted search using the key words "schizophrenia," "diabetes mellitus," "ketoacidosis," and "adverse drug reaction." Including this case, 30 patients have been reported in the literature to have developed diabetes or have lost diabetic control after starting clozapine, olanzapine, or quetiapine. Twelve of these 30 developed diabetic ketoacidosis. Two limited quantitative studies have added evidence toward this association. Although a causal relation has not been definitively proved, the number of cases reported in the literature suggests there might be an association between atypical antipsychotic medications and diabetes mellitus. Primary care physicians who care for patients with schizophrenia should be aware of this possible association.


Forced expression of the interferon regulatory factor 2 oncoprotein causes polyploidy and cell death in FDC-P1 myeloid hematopoietic progenitor cells.
The IFN regulatory factor-2 (IRF-2) oncoprotein controls the cell cycle-dependent expression of histone H4 genes during S phase and may function as a component of an E2F-independent mechanism to regulate cell growth. To investigate the role of IRF-2 in control of cell proliferation, we have constructed a stable FDC-P1 cell line (F2) in which expression of IRF-2 is doxycycline (DOX)-inducible, and a control cell line (F0). Both the F2 and F0 cell lines were synchronized in the G1 phase by isoleucine deprivation, and IRF-2 was induced by DOX on release of cells from the cell cycle block. Flow cytometric analyses indicated that forced expression of IRF-2 has limited effects on cell cycle progression before the first mitosis. However, continued cell growth in the presence of elevated IRF-2 levels results in polyploidy (>4n) or genomic disintegration (<2n) and cell death. Western blot analyses revealed that the levels of the cell cycle regulatory proteins cyclin B1 and the cyclin-dependent kinase (CDK)-inhibitory protein p27 are selectively increased. These changes occur concomitant with a significant elevation in the levels of the FAS-L protein, which is the ligand of the FAS (Apo1/CD95) receptor. We also found a subtle change in the ratio of the apoptosis-promoting Bax protein and the antiapoptotic Bcl-2 protein. Hence, IRF-2 induces a cell death response involving the Fas/FasL apoptotic pathway in FDC-P1 cells. Our data suggest that the IRF-2 oncoprotein regulates a critical cell cycle checkpoint that controls progression through G2 and mitosis in FDC-P1 hematopoietic progenitor cells.


A new perspective on management of open calcaneus fractures.
The treatment protocol of closed calcaneal fractures has been described in the literature extensively. However, treatment of open calcaneal fractures has not been discussed in detail. Various treatment alternatives have been suggested including external fixator, primary subtalar distraction arthrodesis, and partial calcanectomy according to the type of fracture. We have retrospectively reviewed 36 adult patients with 39 open calcaneal fractures who were treated with our new philosophy. Average follow-up time was 9.29 years (range, 1.25-28 years). The American Orthopaedic Foot and Ankle Society (AOFAS) scoring system was used in functional evaluation. The average score was 77.9 (range, 67-92). All of the patients had limited subtalar movement. We propose an algorithm for the management of open calcaneus fractures, although treatment largely depends on the physical status of the patient, type of the fracture, localisation of the open wound and the surgeon's choice.


The relationship between multidimensional poverty, income poverty and youth depressive symptoms: cross-sectional evidence from Mexico, South Africa and Colombia.
Whereas monetary poverty is associated with increased risk of depressive symptoms in young people, poverty is increasingly understood as a multidimensional problem. However, it is yet to be understood how the associations between different dimensions of poverty and youth mental health differ across countries. We examine the relationship between multidimensional, as well as income poverty, and depressive symptoms in young people (age 11-25 years) across three middle-income countries. Based on harmonised data from surveys in Colombia, Mexico and South Africa (N=16 173) we constructed a multidimensional poverty index that comprised five deprivations We used Poisson regression to examine relationships between different forms of poverty with depressive symptoms across the countries. Multidimensional poverty was associated with higher rates of depressive symptoms in the harmonised dataset (IRR (incidence rate ratio)=1.25, 95% CI 1.10 to 1.42), in Mexico (IRR=1.34, 95% CI 1.11 to 1.64) and Colombia (IRR=2.01, 95% CI 1.30 to 3.10) but not in South Africa, a finding driven by a lack of associations between child labour and health insurance coverage with depressive symptoms. There was only an association with income poverty and depressive symptoms in South Africa, not in Colombia or Mexico. Depressive symptoms were associated with individual deprivations such as school lag, child labour and lack of access to health services in the harmonised dataset, but not with household deprivations, such as parental unemployment and housing conditions, though the opposite pattern was observed in South Africa. Our findings suggest that the importance of specific dimensions of poverty for mental health varies across countries, and a multidimensional approach is needed to gain insights into the relationship between youth depression and poverty.


Relational similarity and the nonindependence of features in similarity judgments.
Four experiments examined the hypothesis that simple attributional features and relational features operate differently in the determination of similarity judgments. Forced choice similarity judgments ("Is X or Y more similar to Z?") and similarity rating tasks demonstrate that making the same featural change in two geometric stimuli unequally affects their judged similarity to a third stimulus (the comparison stimulus). More specifically, a featural change that causes stimuli to be more superficially similar and less relationally similar increases judged similarity if it occurs in stimuli that already share many superficial attributes, and decreases similarity if it occurs in stimuli that do not share as many superficial attributes. These results argue against an assumption of feature independence which asserts that the degree to which a feature shared by two objects affects similarity is independent of the other features shared by the objects. The MAX hypothesis is introduced, in which attributional and relational similarities are separately pooled, and shared features affect similarity more if the pool they are in is already relatively large. The results support claims that relations and attributes are psychologically distinct and that formal measures of similarity should not treat all types of matching features equally.


Guidelines for colonoscopy surveillance after cancer resection: a consensus update by the American Cancer Society and US Multi-Society Task Force on Colorectal Cancer.
Patients with resected colorectal cancer are at risk for recurrent cancer and metachronous neoplasms in the colon. This joint update of guidelines by the American Cancer Society (ACS) and US Multi-Society Task Force on Colorectal Cancer addresses only the use of endoscopy in the surveillance of these patients. Patients with endoscopically resected Stage I colorectal cancer, surgically resected Stage II and III cancers, and Stage IV cancer resected for cure (isolated hepatic or pulmonary metastasis) are candidates for endoscopic surveillance. The colorectum should be carefully cleared of synchronous neoplasia in the perioperative period. In nonobstructed colons, colonoscopy should be performed preoperatively. In obstructed colons, double contrast barium enema or computed tomography colonography should be done preoperatively, and colonoscopy should be performed 3 to 6 months after surgery. These steps complete the process of clearing synchronous disease. After clearing for synchronous disease, another colonoscopy should be performed in 1 year to look for metachronous lesions. This recommendation is based on reports of a high incidence of apparently metachronous second cancers in the first 2 years after resection. If the examination at 1 year is normal, then the interval before the next subsequent examination should be 3 years. If that colonoscopy is normal, then the interval before the next subsequent examination should be 5 years. Shorter intervals may be indicated by associated adenoma findings (see Postpolypectomy Surveillance Guideline). Shorter intervals are also indicated if the patient's age, family history, or tumor testing indicate definite or probable hereditary nonpolyposis colorectal cancer. Patients undergoing low anterior resection of rectal cancer generally have higher rates of local cancer recurrence, compared with those with colon cancer. Although effectiveness is not proven, performance of endoscopic ultrasound or flexible sigmoidoscopy at 3- to 6-month intervals for the first 2 years after resection can be considered for the purpose of detecting a surgically curable recurrence of the original rectal cancer.


Transcranial direct current stimulation enhances verbal working memory training performance over time and near transfer outcomes.
Studies attempting to increase working memory (WM) capacity show promise in enhancing related cognitive functions but have also raised criticism in the broader scientific community given the inconsistent findings produced by these studies. Transcranial direct current stimulation (tDCS) has been shown to enhance WM performance in a single session [Fregni, F., Boggio, P., Nitsche, M., Bermpohl, F., Anatal, A., Feredoes, E., et al. Anodal transcranial direct current stimulation of prefrontal cortex enhances working memory. Experimental Brain Research, 166, 23-30, 2005]; however, the extent to which tDCS might enhance learning on a WM training regime and the extent to which learning gains might transfer outside the training task remains largely unknown. To this end, participants engaged in an adaptive WM training task [previously utilized in Richmond, L., Morrison, A., Chein, J., & Olson, I. Working memory training and transfer in older adults. Psychology & Aging, 26, 813-822, 2011; Chein, J., & Morrison, A. Expanding the mind's workspace: Training and transfer effects with a complex working memory span task. Psychonomic Bulletin & Review, 17, 193-199, 2010] for 10 sessions over 2 weeks, concurrent with either active or sham stimulation of dorsolateral pFC. Before and after training, a battery of tests tapping domains known to relate to WM abilities was administered. Results show that tDCS enhanced learning on the verbal portion of the training task by 3.65 items. Furthermore, tDCS was shown to enhance near transfer to other untrained WM tasks in comparison with a no-contact control group. These results lend support to the idea that tDCS might bolster training and transfer gains in populations with compromised WM abilities.


Age-related differences in everyday prospective memory tasks: the role of planning and personal importance.
The aim of the present studies was to investigate whether age-related improvement found in naturalistic but experimenter-given prospective memory (PM) tasks can be generalized to real-life intentions. In Study 1, younger, middle-aged, and older adults generated a list of intended activities for the following week; one week later they marked the tasks that they had performed. The participants were also asked to rate the importance of each listed intention and to describe the circumstances of completion that were already known to them. We found that, compared with younger adults, older adults attributed a higher degree of importance to their intentions and had the circumstances of their completion better planned. However, the age-related benefit in the PM performance for all listed intentions was not present for the very important and well-planned tasks. In Study 2 we manipulated whether younger adults engaged or not in the detailed planning of when their intentions could be completed. It was demonstrated that younger adults who had to perform detailed planning completed their intended activities more often than those who did not plan for their intentions. The results support explanations of the age-related benefit in everyday PM that highlight the role of importance and planning.