Influence of fixation and morphometric technics on capillary basement-membrane thickening prevalence data in diabetes.
Muscle tissue obtained by needle biopsy from 20 diabetic subjects and from 20 age-matched control subjects was divided into two portions, one of which was fixed and processed by our routine procedure (primary glutaraldehyde fixation followed by osmium fixation and embedment in araldite) and the other was fixed initially in osmium tetroxide and embedded in maraglas, the procedure employed by Siperstein et al. Basement-membrane width of capillaries was measured by the 20-point method of Siperstein et al. and by the two-minimum-point technic developed in our own laboratory. Contrary to the experience of Siperstein et al., the prevalence of basement-membrane thickening in diabetic subjects based on mean width values and/or standard deviations in excess of 95 per cent tolerance intervals was highest (65 per cent) in minimum measurements of glutaraldehyde-fixed tissues and lowest (30 per cent) in osmium-fixed tissues (X2 = 4.9123, p less than 0.05). Internal discrepancies in the data of Siperstein et al. indicate that (1) their basement-membrane-width values derived from multiple measurements from control subjects are anomalous (low) and (2) the very high prevalence of basement-membrane thickening they reported in diabetic and in prediabetic subjects and considered as strong support for their conclusion that basement-membrane disease is independent of and precedes glucose intolerance is suspect.


Learned irrelevance and retrospective correlation learning.
In 1973 Mackintosh reported an interference effect that he called learned irrelevance in which exposure to uncorrelated (CS/US) presentation of the unconditional stimulus (US) and the conditioned stimulus (CS) interfered with future Pavlovian conditioning. It has been argued that there is no specific interference effect in learned irrelevance; rather the interference is the sum of independent CS and US exposure effects (CS + US). We review previous research on this question and report two new experiments. We conclude that learned irrelevance is a consequence of a contingency learning and a specific learned irrelevance mechanism. Moreover even the independent exposure controls, used in previous experiments to support the CS and US exposure account, provide support for the correlation learning process.


Phonon-enhanced light matter interaction at the nanometre scale.
Optical near fields exist close to any illuminated object. They account for interesting effects such as enhanced pinhole transmission or enhanced Raman scattering enabling single-molecule spectroscopy. Also, they enable high-resolution (below 10 nm) optical microscopy. The plasmon-enhanced near-field coupling between metallic nanostructures opens new ways of designing optical properties and of controlling light on the nanometre scale. Here we study the strong enhancement of optical near-field coupling in the infrared by lattice vibrations (phonons) of polar dielectrics. We combine infrared spectroscopy with a near-field microscope that provides a confined field to probe the local interaction with a SiC sample. The phonon resonance occurs at 920 cm(-1). Within 20 cm(-1) of the resonance, the near-field signal increases 200-fold; on resonance, the signal exceeds by 20 times the value obtained with a gold sample. We find that phonon-enhanced near-field coupling is extremely sensitive to chemical and structural composition of polar samples, permitting nanometre-scale analysis of semiconductors and minerals. The excellent physical and chemical stability of SiC in particular may allow the design of nanometre-scale optical circuits for high-temperature and high-power operation.


Multi-Domain Variational Autoencoders for Combined Modeling of MRI-Based Biventricular Anatomy and ECG-Based Cardiac Electrophysiology.
Human cardiac function is characterized by a complex interplay of mechanical deformation and electrophysiological conduction. Similar to the underlying cardiac anatomy, these interconnected physiological patterns vary considerably across the human population with important implications for the effectiveness of clinical decision-making and the accuracy of computerized heart models. While many previous works have investigated this variability separately for either cardiac anatomy or physiology, this work aims to combine both aspects in a single data-driven approach and capture their intricate interdependencies in a multi-domain setting. To this end, we propose a novel multi-domain Variational Autoencoder (VAE) network to capture combined Electrocardiogram (ECG) and Magnetic Resonance Imaging (MRI)-based 3D anatomy information in a single model. Each VAE branch is specifically designed to address the particular challenges of the respective input domain, enabling efficient encoding, reconstruction, and synthesis of multi-domain cardiac signals. Our method achieves high reconstruction accuracy on a United Kingdom Biobank dataset, with Chamfer Distances between reconstructed and input anatomies below the underlying image resolution and ECG reconstructions outperforming multiple single-domain benchmarks by a considerable margin. The proposed VAE is capable of generating realistic virtual populations of arbitrary size with good alignment in clinical metrics between the synthesized and gold standard anatomies and Maximum Mean Discrepancy (MMD) scores of generated ECGs below those of comparable single-domain approaches. Furthermore, we observe the latent space of our VAE to be highly interpretable with separate components encoding different aspects of anatomical and ECG variability. Finally, we demonstrate that the combined anatomy and ECG representation improves the performance in a cardiac disease classification task by 3.9% in terms of Area Under the Receiver Operating Characteristic (AUROC) curve over the best corresponding single-domain modeling approach.


Dietary and urinary metabonomic factors possibly accounting for higher blood pressure of black compared with white Americans: results of International Collaborative Study on macro-/micronutrients and blood pressure.
Black compared with non-Hispanic white Americans have higher systolic and diastolic blood pressure and rates of prehypertension/hypertension. Reasons for these adverse findings remain obscure. Analyses here focused on relations of foods/nutrients/urinary metabolites and higher black blood pressure for 369 black compared with 1190 non-Hispanic white Americans aged 40 to 59 years from 8 population samples. Multiple linear regression, standardized data from four 24-hour dietary recalls per person, two 24-hour urine collections, and 8 blood pressure measurements were used to quantitate the role of foods, nutrients, and metabolites in higher black blood pressure. Compared with non-Hispanic white Americans, blacks' average systolic/diastolic pressure was higher by 4.7/3.4 mm Hg (men) and 9.0/4.8 mm Hg (women). Control for higher body mass index of black women reduced excess black systolic/diastolic pressure to 6.8/3.8 mm Hg. Lesser intake of vegetables, fruits, grains, vegetable protein, glutamic acid, starch, fiber, minerals, and potassium, and higher intake of processed meats, pork, eggs, and sugar-sweetened beverages, along with higher cholesterol and higher Na/K ratio, related to in higher black blood pressure. Control for 11 nutrient and 10 non-nutrient correlates reduced higher black systolic/diastolic pressure to 2.3/2.3 mm Hg (52% and 33% reduction in men) and to 5.3/2.8 mm Hg (21% and 27% reduction in women). Control for foods/urinary metabolites had little further influence on higher black blood pressure. Less favorable multiple nutrient intake by blacks than non-Hispanic white Americans accounted, at least in part, for higher black blood pressure. Improved dietary patterns can contribute to prevention/control of more adverse black blood pressure levels.


Imatinib treatment and Aβ42 in humans.
The first-line treatment in chronic myeloid leukemia (CML), imatinib, has been shown to decrease the production of amyloid-β (Aβ) in vitro and in animal studies. However, whether imatinib has this effect in humans is not known. Plasma levels of Aβ42 were analyzed in sequential samples from CML patients treated with imatinib (n=51). The effect of imatinib on Aβ production was also investigated in human embryonic kidney 293 (HEK293) cells overexpressing the amyloid precursor protein (APP) with the Swedish mutation, in mouse primary cortical neurons and in human Down syndrome embryonic stem-cell-derived cortical neurons. Twelve months of imatinib treatment did not lower plasma Aβ42 levels in CML patients, and imatinib treatment did not lead to less Aβ42 production in any of the in vitro models whereas β- and γ-secretase inhibitors did. These data question the previously described role of imatinib in inhibiting amyloidogenic APP processing and as a drug candidate for AD.


Genetic variation within the Hypodontus macropi (Nematoda: Strongyloidea) complex from macropodid marsupial hosts in Australia.
Genetic variation was investigated in the strongylid nematode Hypodontus macropi from macropodid marsupials using the second internal transcribed spacer of ribosomal DNA. A total of 547 specimens from ten species of hosts, representing all of the known hosts of the parasite, from across the Australian continent was examined. Phylogenetic analyses revealed distinct genetic clades in each of Macropus agilis, M. dorsalis, M. rufogriseus, M. bicolor, Petrogale persephone, Thylogale billardierii and T. stigmatica. A further clade contained all specimens from M. robustus and M. rufus, together with two examples of host switching by nematodes into M. fuliginosus. The latter clade was subdivided into three subclades, one comprising specimens occurring in M. robustus erubescens, M. rufus and M. fuliginosus, the second in M. r. woodwardi and the third in M. r. robustus suggesting a relationship between the subclades and the subspecies of M. robustus. The extent of the genetic differences and the fact that several of them occur in broad sympatry suggests that H. macropi as currently defined morphologically may represent as many as ten cryptic species. Limited evidence was found for co-speciation between hosts and parasites; rather most relationships were better explained by host switching.


Common SNPs explain some of the variation in the personality dimensions of neuroticism and extraversion.
The personality traits of neuroticism and extraversion are predictive of a number of social and behavioural outcomes and psychiatric disorders. Twin and family studies have reported moderate heritability estimates for both traits. Few associations have been reported between genetic variants and neuroticism/extraversion, but hardly any have been replicated. Moreover, the ones that have been replicated explain only a small proportion of the heritability (<~2%). Using genome-wide single-nucleotide polymorphism (SNP) data from ~12,000 unrelated individuals we estimated the proportion of phenotypic variance explained by variants in linkage disequilibrium with common SNPs as 0.06 (s.e. = 0.03) for neuroticism and 0.12 (s.e. = 0.03) for extraversion. In an additional series of analyses in a family-based sample, we show that while for both traits ~45% of the phenotypic variance can be explained by pedigree data (that is, expected genetic similarity) one third of this can be explained by SNP data (that is, realized genetic similarity). A part of the so-called 'missing heritability' has now been accounted for, but some of the reported heritability is still unexplained. Possible explanations for the remaining missing heritability are that: (i) rare variants that are not captured by common SNPs on current genotype platforms make a major contribution; and/ or (ii) the estimates of narrow sense heritability from twin and family studies are biased upwards, for example, by not properly accounting for nonadditive genetic factors and/or (common) environmental factors.


Sweet's syndrome: an unusual cutaneous feature of Crohn's disease or ulcerative colitis. The South West Gastroenterology Group.
Sweet's syndrome is characterized by tender, red inflammatory nodules or papules, usually affecting the upper limbs, face or neck. It is part of the group of acute neutrophilic dermatoses that includes pyoderma gangrenosum, but can be distinguished by its appearance, distribution and histological features. Four patients with Sweet's syndrome and Crohn's disease are reported. A total of 30 cases from the literature suggest that Sweet's syndrome is an unusual extraintestinal manifestation of either Crohn's disease or ulcerative colitis. There is a strong predilection for women (87%), patients with colonic disease (100%) and those with other extraintestinal features (77%). The rash is associated with active disease in 67-80%, but may precede the onset of intestinal symptoms in 21% and has been reported 3 months after proctocolectomy for ulcerative colitis.


Global transgenerational gene expression dynamics in two newly synthesized allohexaploid wheat (Triticum aestivum) lines.
Alteration in gene expression resulting from allopolyploidization is a prominent feature in plants, but its spectrum and extent are not fully known. Common wheat (Triticum aestivum) was formed via allohexaploidization about 10,000 years ago, and became the most important crop plant. To gain further insights into the genome-wide transcriptional dynamics associated with the onset of common wheat formation, we conducted microarray-based genome-wide gene expression analysis on two newly synthesized allohexaploid wheat lines with chromosomal stability and a genome constitution analogous to that of the present-day common wheat. Multi-color GISH (genomic in situ hybridization) was used to identify individual plants from two nascent allohexaploid wheat lines between Triticum turgidum (2n=4x=28; genome BBAA) and Aegilops tauschii (2n=2x=14; genome DD), which had a stable chromosomal constitution analogous to that of common wheat (2n=6x=42; genome BBAADD). Genome-wide analysis of gene expression was performed for these allohexaploid lines along with their parental plants from T. turgidum and Ae. tauschii, using the Affymetrix Gene Chip Wheat Genome-Array. Comparison with the parental plants coupled with inclusion of empirical mid-parent values (MPVs) revealed that whereas the great majority of genes showed the expected parental additivity, two major patterns of alteration in gene expression in the allohexaploid lines were identified: parental dominance expression and non-additive expression. Genes involved in each of the two altered expression patterns could be classified into three distinct groups, stochastic, heritable and persistent, based on their transgenerational heritability and inter-line conservation. Strikingly, whereas both altered patterns of gene expression showed a propensity of inheritance, identity of the involved genes was highly stochastic, consistent with the involvement of diverse Gene Ontology (GO) terms. Nonetheless, those genes showing non-additive expression exhibited a significant enrichment for vesicle-function. Our results show that two patterns of global alteration in gene expression are conditioned by allohexaploidization in wheat, that is, parental dominance expression and non-additive expression. Both altered patterns of gene expression but not the identity of the genes involved are likely to play functional roles in stabilization and establishment of the newly formed allohexaploid plants, and hence, relevant to speciation and evolution of T. aestivum.


Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban.
There is continued debate as to whether a routine, early invasive strategy is superior to a conservative strategy for the management of unstable angina and myocardial infarction without ST-segment elevation. We enrolled 2220 patients with unstable angina and myocardial infarction without ST-segment elevation who had electrocardiographic evidence of changes in the ST segment or T wave, elevated levels of cardiac markers, a history of coronary artery disease, or all three findings. All patients were treated with aspirin, heparin, and the glycoprotein IIb/IIIa inhibitor tirofiban. They were randomly assigned to an early invasive strategy, which included routine catheterization within 4 to 48 hours and revascularization as appropriate, or to a more conservative (selectively invasive) strategy, in which catheterization was performed only if the patient had objective evidence of recurrent ischemia or an abnormal stress test. The primary end point was a composite of death, nonfatal myocardial infarction, and rehospitalization for an acute coronary syndrome at six months. At six months, the rate of the primary end point was 15.9 percent with use of the early invasive strategy and 19.4 percent with use of the conservative strategy (odds ratio, 0.78; 95 percent confidence interval, 0.62 to 0.97; P=0.025). The rate of death or nonfatal myocardial infarction at six months was similarly reduced (7.3 percent vs. 9.5 percent; odds ratio, 0.74; 95 percent confidence interval, 0.54 to 1.00; P<0.05). In patients with unstable angina and myocardial infarction without ST-segment elevation who were treated with the glycoprotein IIb/IIIa inhibitor tirofiban, the use of an early invasive strategy significantly reduced the incidence of major cardiac events. These data support a policy involving broader use of the early inhibition of glycoprotein IIb/IIIa in combination with an early invasive strategy in such patients.


'Mystery big cats' in the Peruvian Amazon: morphometrics solve a cryptozoological mystery.
Two big cat skulls procured from hunters of Yanachaga National Park, Peru, were reported as those of cats informally dubbed the 'striped tiger' and 'anomalous jaguar'. Observations suggested that both skulls were distinct from those of jaguars, associated descriptions of integument did not conform to this species, and it has been implied that both represent members of one or two novel species. We sought to resolve the identity of the skulls using morphometrics. DNA could not be retrieved since both had been boiled as part of the defleshing process. We took 36 cranial and 13 mandibular measurements and added them to a database incorporating nearly 300 specimens of over 30 felid species. Linear discriminant analysis resolved both specimens as part of Panthera onca with high probabilities for cranial and mandibular datasets. Furthermore, the specimens exhibit characters typical of jaguars. If the descriptions of their patterning and pigmentation are accurate, we assume that both individuals were aberrant.


Epidemiology, survival, and costs of localized gastrointestinal stromal tumors.
The aim of this study is to examine the epidemiologic and economic burden in surgically resected localized gastrointestinal stromal tumor (GIST) patients versus age- and gender-matched controls. Two data sources were used to conduct a series of complementary analyses. First, the Surveillance, Epidemiology, and End Results (SEER) cancer registry was used to identify diagnosed GIST patients from 1993 to 2002 and determine incidence, prevalence, and 3-year survival. Second, using the SEER-Medicare linked database, a matched case-control analysis was conducted to determine resource utilization, GIST recurrence, and costs. Because GIST recurrence is not explicitly defined in the database, patterns in resource use were used to identify probable recurrence. Kaplan-Meier Sample Average (KMSA) Estimator technique was used to estimate costs of GIST and recurrence. SEER registry results show over the 10-year time horizon average annual GIST incidence was 0.32 per 100,000 persons in the United States, 15-year limited-duration prevalence was 1.62 per 100,000 persons, and 3-year survival was 73%. A total of 292 GIST patients were included in the SEER-Medicare analyses; 35 were identified with probable recurrence. GIST patients had increased risk of mortality (hazard ratio: 1.23; 95% confidence intervals: 0.94-1.61) compared to controls. Median recurrence-free and postrecurrence survival was 45 and 46 months, respectively. GIST patients incurred significantly higher medical care costs in the first year after initial resection, with $23,221 attributable to GIST. GIST recurrence costs totaled $101,700 over 5 years after initial resection. GIST is associated with substantial medical care costs, estimated recurrence costs more than $100,000; treatments that delay or reduce recurrence could substantially reduce the burden of GIST.


Use of emergency medical service transport among patients with ST-segment-elevation myocardial infarction: findings from the National Cardiovascular Data Registry Acute Coronary Treatment Intervention Outcomes Network Registry-Get With The Guidelines.
Activation of emergency medical services (EMS) is critical for the early triage and treatment of patients experiencing ST-segment-elevation myocardial infarction, yet data regarding EMS use and its association with subsequent clinical care are limited. We performed an observational analysis of 37 634 ST-segment-elevation myocardial infarction patients treated at 372 US hospitals participating in the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines between January 2007 and September 2009, and examined independent patient factors associated with EMS transportation versus patient self-transportation. We found that EMS transport was used in only 60% of ST-segment-elevation myocardial infarction patients. Older patients, those living farther from the hospital, and those with hemodynamic compromise were more likely to use EMS transport. In contrast, race, income, and education level did not appear to be associated with the mode of transport. Compared with self-transported patients, EMS-transported patients had significantly shorter delays in both symptom-onset-to-arrival time (median, 89 versus 120 minutes; P<0.0001) and door-to-reperfusion time (median door-to-balloon time, 63 versus 76 minutes; P<0.0001; median door-to-needle time, 23 versus 29 minutes; P<0.0001). Emergency medical services transportation to the hospital is underused among contemporary ST-segment-elevation myocardial infarction patients. Nevertheless, use of EMS transportation is associated with substantial reductions in ischemic time and treatment delays. Community education efforts are needed to improve the use of emergency transport as part of system-wide strategies to improve ST-segment-elevation myocardial infarction reperfusion care.


Impact of prehospital medical evacuation (MEDEVAC) transport time on combat mortality in patients with non-compressible torso injury and traumatic amputations: a retrospective study.
In combat operations, patients with traumatic injuries require expeditious evacuation to improve survival. Studies have shown that long transport times are associated with increased morbidity and mortality. Limited data exist on the influence of transport time on patient outcomes with specific injury types. The objective of this study was to determine the impact of the duration of time from the initial request for medical evacuation to arrival at a medical treatment facility on morbidity and mortality in casualties with traumatic extremity amputation and non-compressible torso injury (NCTI). We completed a retrospective review of MEDEVAC patient care records for United States military personnel who sustained traumatic amputations and NCTI during Operation Enduring Freedom between January 2011 and March 2014. We grouped patients as traumatic amputation and NCTI (AMP+NCTI), traumatic amputation only (AMP), and neither AMP nor NCTI (Non-AMP/NCTI). Analysis was performed using chi-squared tests, Fisher's exact tests, Cochran-Armitage Trend tests, Shapiro-Wilks tests, Wilcoxon and Kruskal-Wallis techniques and Cox proportional hazards regression modeling. We reviewed 1267 records, of which 669 had an injury severity score (ISS) of 10 or greater and were included in the analysis. In the study population, 15.5% sustained only amputation injuries (n=104, AMP only), 10.8% sustained amputation and NCTI (n=72, AMP+NCTI), and 73.7% did not sustain either an amputation or an NCTI (n=493, Non-AMP/NCTI). AMP+NCTI had the highest mortality (16.7%) with transport time greater than 60 min. While the AMP+NCTI group had decreasing survival with longer transport times, AMP and Non-AMP/NCTI did not exhibit the same trend. A decreased transport time from the point of injury to a medical treatment facility was associated with decreased mortality in patients who suffered a combination of amputation injury and NCTI. No significant association between transport time and outcomes was found in patients who did not sustain NCTI. Priority for rapid evacuation of combat casualties should be given to those with NCTI.


Emotional memory in bipolar disorder.
Cognitive impairment has been well documented in bipolar disorder. However, specific aspects of cognition such as emotional memory have not been examined. To investigate episodic emotional memory in bipolar disorder, as indicated by performance on an amygdala-related cognitive task. Twenty euthymic patients with bipolar disorder and 20 matched controls were recruited. Participants were shown a slide show of an emotionally neutral story, or a closely matched emotionally arousing story. One week later, participants were assessed on a memory-recall test. In contrast with the pattern observed in controls, patients with bipolar disorder had no enhancement of memory for the emotional content of the story (F=14.7, d.f.=1,36, P<0.001). The subjective perception of the emotional impact of the emotional condition was significantly different from that of the neutral condition in controls but not in people with bipolar disorder. Our data suggest that the physiological pattern of enhanced memory retrieval for emotionally bound information is blunted in bipolar disorder.


When Harvard said no to eugenics: the J. Ewing Mears Bequest, 1927.
James Ewing Mears (1838-1919) was a founding member of the Philadelphia Academy of Surgery. His 1910 book, The Problem of Race Betterment, laid the groundwork for later authors to explore the uses of surgical sterilization as a eugenic measure. Mears left $60,000 in his will to Harvard University to support the teaching of eugenics. Although numerous eugenic activists were on the Harvard faculty, and two of its Presidents were also associated with the eugenics movement, Harvard refused the Mears gift. The bequest was eventually awarded to Jefferson Medical College in Philadelphia. This article explains why Harvard turned its back on a donation that would have supported instruction in a popular subject. Harvard's decision illustrates the range of opinion that existed on the efficacy of eugenic sterilization at the time. The Mears case also highlights a powerful irony: the same week Harvard turned down the Mears legacy, the U.S. Supreme Court endorsed eugenic sterilization in the landmark case of Buck v. Bell. Justice Oliver Wendell Holmes, Jr., graduate of Harvard and former member of its law faculty wrote the opinion in that case, including the famous conclusion: "Three generations of imbeciles are enough."


Inhibition of iron uptake is responsible for differential sensitivity to V-ATPase inhibitors in several cancer cell lines.
Many cell lines derived from tumors as well as transformed cell lines are far more sensitive to V-ATPase inhibitors than normal counterparts. The molecular mechanisms underlying these differences in sensitivity are not known. Using global gene expression data, we show that the most sensitive responses to HeLa cells to low doses of V-ATPase inhibitors involve genes responsive to decreasing intracellular iron or decreasing cholesterol and that sensitivity to iron uptake is an important determinant of V-ATPase sensitivity in several cancer cell lines. One of the most sensitive cell lines, melanoma derived SK-Mel-5, over-expresses the iron efflux transporter ferroportin and has decreased expression of proteins involved in iron uptake, suggesting that it actively suppresses cytoplasmic iron. SK-Mel-5 cells have increased production of reactive oxygen species and may be seeking to limit additional production of ROS by iron.


Pharmacogenomics and the Yin/Yang actions of ginseng: anti-tumor, angiomodulating and steroid-like activities of ginsenosides.
In Chinese medicine, ginseng (Panax ginseng C.A. Meyer) has long been used as a general tonic or an adaptogen to promote longevity and enhance bodily functions. It has also been claimed to be effective in combating stress, fatigue, oxidants, cancer and diabetes mellitus. Most of the pharmacological actions of ginseng are attributed to one type of its constituents, namely the ginsenosides. In this review, we focus on the recent advances in the study of ginsenosides on angiogenesis which is related to many pathological conditions including tumor progression and cardiovascular dysfunctions. Angiogenesis in the human body is regulated by two sets of counteracting factors, angiogenic stimulators and inhibitors. The 'Yin and Yang' action of ginseng on angiomodulation was paralleled by the experimental data showing angiogenesis was indeed related to the compositional ratio between ginsenosides Rg1 and Rb1. Rg1 was later found to stimulate angiogenesis through augmenting the production of nitric oxide (NO) and vascular endothelial growth factor (VEGF). Mechanistic studies revealed that such responses were mediated through the PI3K-->Akt pathway. By means of DNA microarray, a group of genes related to cell adhesion, migration and cytoskeleton were found to be up-regulated in endothelial cells. These gene products may interact in a hierarchical cascade pattern to modulate cell architectural dynamics which is concomitant to the observed phenomena in angiogenesis. By contrast, the anti-tumor and anti-angiogenic effects of ginsenosides (e.g. Rg3 and Rh2) have been demonstrated in various models of tumor and endothelial cells, indicating that ginsenosides with opposing activities are present in ginseng. Ginsenosides and Panax ginseng extracts have been shown to exert protective effects on vascular dysfunctions, such as hypertension, atherosclerotic disorders and ischemic injury. Recent work has demonstrates the target molecules of ginsenosides to be a group of nuclear steroid hormone receptors. These lines of evidence support that the interaction between ginsenosides and various nuclear steroid hormone receptors may explain the diverse pharmacological activities of ginseng. These findings may also lead to development of more efficacious ginseng-derived therapeutics for angiogenesis-related diseases.


Relationship between the Hamilton Depression Rating Scale and the Montgomery-Asberg Depression Rating Scale in depressed elderly: a meta-analysis.
To determine whether the sensitivity of the Hamilton Depression Rating Scale (HDRS) and Montgomery-Asberg Depression Rating Scale (MADRS) to treatment effects are comparable in geriatric antidepressant randomized controlled trials by developing and validating an equation that links between the two instruments. Literature search for this meta-analysis was based on three sources: MEDLINE, a recent related meta-analysis, and experts in geriatric antidepressant trials. The search resulted in 11 relevant geriatric antidepressant trial studies that administered both instruments for symptom ratings. The authors used baseline ratings as a model-building sample and postrandomization ratings as a validation sample. HDRS scores were prorated into HDRS17, a 17-item HDRS, for analysis. The development and validation was based on a total number of 1,874 subjects. The correlations were high between baseline mean HDRS17 and MADRS ratings (r = 0.80; Fisher's z = 1.09, N = 25, p <0.0001) and between postrandomization ratings (r = 0.88, Fisher's z = 1.39, N = 65, p <0.0001). The following equation was derived: HDRS17 = -1.58 + 0.86 x MADRS. The difference between observed and estimated HDRS17 in a validation sample consisting of postrandomization follow-up means did not depend on magnitudes of HDRS17. Although generalizability of findings into a broader population could be limited, and the authors could not assess concordance of changes of particular item constructs between HDRS and MADRS ratings, both ratings are comparable in assessing changes in overall depressive symptom severity in response to antidepressants in depressed elderly at aggregated group mean levels.


[Brief history of recent hemp cultivation in Switzerland and subsequent medico-legal problems resulting from hemp cultivation].
In March 1995, a decision about cultivation of cannabis was issued by the Swiss Federal Offices of Public Health, Police and Agriculture in order to satisfy the growing interest of farmers and other people in hemp farming. It pointed out that 1)... each hemp plant contains THC and must be therefore considered a drug, 2)... no permission is required for those who grow hemp without the intention to produce drugs ... meaning that the choice of the plant variety was not restricted to those which are characterized by a low THC concentration and grown in a few countries belonging to the European Union. Claiming that natural hemp must contain significant amounts of THC and thanks to the Swiss legislation, areas dedicated to hemp cultivation develop considerably. Most hemp plants which are submitted to our laboratories by the police for THC quantification belong to the drug-type. Nowadays, a great deal of goods (food and beverages, cosmetics, drugs) made of hemp are marketed in Switzerland. Strong suspicions exist however that several of these products could be used as a screen for the illegal market of cannabis. For instance, despite financial support from the state, fiber hemp cultivation remains unsuccessful. No advantage with regard to seed productivity, edible seed and essential oils qualities and yields have been found for drug hemp over fiber hemp by agricultural research stations up to now. Several clues about the possible illicit use of hemp goods rich in THC, especially hemp tea made of flower tops and "therapeutic" pillows filled with cannabis exist. Recently, two Federal edits were issued in order to restrict the selling of hemp seedlings and of hemp foods and beverages to those containing only low amounts of THC. However, the marketing of hemp plants used for decorating remains free partly explaining the recent success of these "beautiful" plants. Broadly speaking, the Swiss and European legislations about hemp have approached mutually during the last years.


Effects of noise and acoustics in schools on vocal health in teachers.
Previous studies on the influence of noise and acoustics in the classroom on voice symptoms among teachers have exclusively relied on self-reports. Since self-reported physical conditions may be biased, it is important to determine the role of objective measurements of noise and acoustics in the presence of voice symptoms. To assess the association between objectively measured and self-reported physical conditions at school with the presence of voice symptoms among teachers. In 12 public schools in Bogotα, we conducted a cross-sectional study among 682 Colombian school workers at 377 workplaces. After signed the informed consent, participants filled out a questionnaire on individual and work-related conditions and the nature and severity of voice symptoms in the past month. Short-term environmental measurements of sound levels, temperature, humidity, and reverberation time were conducted during visits at the workplaces, such as classrooms and offices. Logistic regression analysis was used to determine associations between work-related factors and voice symptoms. High noise levels outside schools (odds ratio [OR] = 1.83; 95% confidence interval [CI]: 1.12-2.99) and self-reported poor acoustics at the workplace (OR = 2.44; 95% CI: 1.88-3.53) were associated with voice symptoms. We found poor agreement between the objective measurements and self-reports of physical conditions at the workplace. This study indicates that noise and acoustics may play a role in the occurrence of voice symptoms among teachers. The poor agreement between objective measurements and self-reports of physical conditions indicate that these are different entities, which argue for inclusion of physical measurements of the working environment in studies on the influence of noise and acoustics on vocal health.


[Epidemiology of patients harboring extended-spectrum beta-lactamase-producing enterobacteriaceae (ESBLE), on admission].
The incidence of extended-spectrum beta-lactamase-producing enterobacteria (ESBLE) has regularly increased over the last few years. However, little is known about epidemiology of ESBLE carriers in France. The objective of this study was to determine the ESBLE carriers or infected patients profile, identified within 48 hours following hospital admission. This retrospective study included all patients admitted in 2006 and 2007 at the Necker-Enfants-Malades (NEM) teaching hospital, carrying or infected with ESBLE isolated within 48 hours following admission. The pediatric and adult populations were compared. There was no significant difference between pediatric and adult populations. Escherichia coli and Klebsiella pneumoniae were the two main species isolated, accounting respectively for 59.6 and 21.1 % of the 114 isolated strains. Among the 114 analyzed files, 24 patients (21 %) were known to be EBLSE carriers, 37 (32 %) were transferred from another hospital, including 16 from another country. Concerning the 54 (47 %) other patients, five (4 %) came from a country with high prevalence, and 44 (39 %) were treated for a chronic illness. Only five patients (4 %) carrying ESBLE did not have any usual risk factor for multidrug resistance (MDR) bacterial carriage. In our study, 4 % of patients carrying ESBLE admitted had no usual risk factor for MDR bacteria. Targeted screening of previous carriers, patients with chronic illness, transferred patients, or patients coming from country with high prevalence, would help to limit the spread of ESBLE.


Relations between respiratory symptoms and sickness among workers in the animal feed industry.
The survey aimed at studying the associations between prevalent respiratory symptoms in an occupational population and sickness absence due to respiratory disorders. A cross sectional survey among male workers in an animal feed mill was conducted. A total of 303 production workers and 102 office clerks completed a questionnaire on respiratory complaints, smoking habits, and occupational history. The questionnaire was used to identify workers with respiratory symptoms in the past 12 months. During this period all spells of sickness absence were recorded. Causes of sickness were classified in broad categories encompassing respiratory symptoms, influenza, musculoskeletal disorders, and others. Logistic regression analysis showed that workers with respiratory complaints experienced a higher sickness absence than those without respiratory complaints. Adjusted for age and smoking the odds ratio (OR) for sickness prevalence was 1.9 among office clerks and 2.6 among blue collar workers. Smoking increased the risk on sickness absence with ORs of 2.4 and 1.6, respectively. When restricting the analysis to sickness due to respiratory complaints, subjects with respiratory complaints had significantly higher risks for absence prevalence and absence rate than those without respiratory complaints. There were no differences in sickness absence between workers with asthma like complaints and those with chronic bronchitis like complaints. The clear associations between respiratory complaints and prevalence and rate of respiratory sickness absence indicate that workers with respiratory complaints are at risk of temporary disability and, thus, may experience a reduced ability to cope with routine activities at work.


Pancreatic beta-cell responses to GLP-1 after near-normalization of blood glucose in patients with type 2 diabetes.
This study investigated the effects of strict glycaemic control on beta-cell function in nine obese subjects with type 2 diabetes (T2DM), using graded glucose infusions together with infusions of saline or GLP-1 before (HbA(1)c: 8.0+/-0.4%) and after four weeks of near-normalization of blood glucose (BG) using insulin (mean diurnal BG: 6.4+/-0.3 mmol/l; HbA(1)c: 6.6+/-0.3%). Nine matched healthy subjects acted as controls. In controls, area-under-curve (AUC) for amylin, C-peptide and proinsulin were higher with GLP-1 than saline (P<0.001). The AUC amylin/C-peptide ratio was similar on both days, while AUC proinsulin/C-peptide ratio was higher with GLP-1 (P=0.02). In the patients, amylin, C-peptide and proinsulin AUCs were unaltered by near-normoglycaemia per se. Proinsulin responses to GLP-1 were unchanged, but amylin and C-peptide AUCs increased (P<0.05) after insulin treatment, and AUC amylin/C-peptide ratios rose to control levels. Near-normoglycaemia tended to reduce AUC proinsulin/C-peptide ratio, which was significant (P=0.04) with GLP-1, but still higher than with saline (P=0.004). In conclusion, amylin, C-peptide and proinsulin responses to glucose were unaffected by four weeks of near-normoglycaemia, whereas GLP-1 increased amylin and C-peptide secretion and amylin/C-peptide ratio. Near-normoglycaemia reduced proinsulin/C-peptide ratio during stimulation with GLP-1, suggesting that strict glycaemic control might ameliorate some of the disturbances in beta-cell function characterizing T2DM.


The societal burden of osteoporosis.
Osteoporosis currently affects 10 million Americans and is responsible for more than 1.5 million fractures annually. The financial burden of osteoporosis is substantial, with annual direct medical costs estimated at 17 to 20 billion dollars. Most of these costs are related to the acute and rehabilitative care following osteoporotic fractures, particularly hip fractures. The societal burden of osteoporosis includes these direct medical costs and the monetary (eg, caregiver time) and nonmonetary costs of poor health. The aging of the US population is expected to increase the prevalence of osteoporosis and the number of osteoporotic fractures. Growth of the older adult population will pose significant challenges to Medicare and Medicaid, which bear most of the cost of osteoporosis. Efforts to address the looming financial burden must focus on reducing the prevalence of osteoporosis and the incidence of costly fragility fractures.


When good deeds leave a bad taste. Negative inferences from ethical food claims.
Consumer research has demonstrated halo effects arising from advertising claims on food packaging (e.g., "organic," "no cholesterol") that promote misperceiving products more positively on other dimensions (e.g., low-calorie, low-fat). However, little research has explored the conditions under which such claims might give rise to more negative rather than positive evaluations. This paper highlights two domains of judgment in which an ethical or values-based claim ("organic") can promote negative impressions. In Study 1, participants judged organic foods relative to conventional foods on healthfulness and expected taste quality. Results suggest that whereas organics are perceived as more healthful than conventional foods (consistent with previous findings), they are also perceived as less tasty, especially among participants low in environmental concern. In Study 2, participants judged the effectiveness of a formula drink intended to help alleviate malnourishment that was described as organic or not, depending on experimental condition. Results showed that participants high in environmental concern (who typically evaluate organic products positively) judged the drink more negatively (i.e., as less effective) when it was described as "organic." Discussion focuses on possible mechanisms for these effects, as well as the moderating role of judgment type and perceivers' values in halo effects more broadly.


Reliability, Validity, and Sensitivity of a Novel Smartphone-Based Eccentric Hamstring Strength Test in Professional Football Players.
To evaluate the test-retest reliability, sensitivity, and concurrent validity of a smartphone-based method for assessing eccentric hamstring strength among male professional football players. A total of 25 healthy male professional football players performed the Chinese University of Hong Kong (CUHK) Nordic break-point test, hamstring fatigue protocol, and isokinetic hamstring strength test. The CUHK Nordic break-point test is based on a Nordic hamstring exercise. The Nordic break-point angle was defined as the maximum point where the participant could no longer support the weight of his body against gravity. The criterion for the sensitivity test was the presprinting and postsprinting difference of the Nordic break-point angle with a hamstring fatigue protocol. The hamstring fatigue protocol consists of 12 repetitions of the 30-m sprint with 30-s recoveries between sprints. Hamstring peak torque of the isokinetic hamstring strength test was used as the criterion for validity. A high test-retest reliability (intraclass correlation coefficient = .94; 95% confidence interval, .82-.98) was found in the Nordic break-point angle measurements. The Nordic break-point angle significantly correlated with isokinetic hamstring peak torques at eccentric action of 30°/s (r = .88, r2 = .77, P < .001). The minimal detectable difference was 8.03°. The sensitivity of the measure was good enough that a significance difference (effect size = 0.70, P < .001) was found between presprinting and postsprinting values. The CUHK Nordic break-point test is a simple, portable, quick smartphone-based method to provide reliable and accurate eccentric hamstring strength measures among male professional football players.


Antecedents of perceived coach autonomy supportive and controlling behaviors: coach psychological need satisfaction and well-being.
Within the self-determination theory (Deci & Ryan, 2000) framework, research has considered the consequences of coaches' autonomy supportive and controlling behaviors on various athlete outcomes (e.g., motivation and performance). The antecedents of such behaviors, however, have received little attention. Coaches (N = 443) from a variety of sports and competitive levels completed a self-report questionnaire to assess their psychological need satisfaction, well-being and perceived interpersonal behaviors toward their athletes. Structural equation modeling demonstrated that coaches' competence and autonomy need satisfaction positively predicted their levels of psychological well-being, as indexed by positive affect and subjective vitality. In turn, coaches' psychological well-being positively predicted their perceived autonomy support toward their athletes, and negatively predicted their perceived controlling behaviors. Overall, the results highlight the importance of coaching contexts that facilitate coaches' psychological need satisfaction and well-being, thereby increasing the likelihood of adaptive coach interpersonal behavior toward athletes.


Crime and memory.
The conflict between knowing and not knowing, speech and silence, remembering and forgetting, is the central dialectic of psychological trauma. This conflict is manifest in the individual disturbances of memory, the amnesias and hypermnesias, of traumatized people. It is manifest also on a social level, in persisting debates over the historical reality of atrocities that have been documented beyond any reasonable doubt. Social controversy becomes particularly acute at moments in history when perpetrators face the prospect of being publicly exposed or held legally accountable for crimes long hidden or condoned. This situation obtains in many countries emerging from dictatorship, with respect to political crimes such as murder and torture. It obtains in this country with regard to the private crimes of sexual and domestic violence. This article examines a current public controversy, regarding the credibility of adult recall of childhood abuse, as a classic example of the dialectic of trauma.


Finding and appraising evidence.
Surgeons have tended to regard evidence-based medicine with a degree of skepticism. A variety of reasons for this have been proposed,ranging from the surgical personality to the nature of the research questions that occur when studying surgical treatment. The relative paucity of randomized trials of surgical treatment has been noted by many investigators, and there has been considerable debate about whether this reflects poorly on the scientific education of the surgical community or points to special problems in applying this methodology in this discipline. This debate has matured over the last 10 years, and there is now greater understanding of the factors that make surgical operations difficult subjects for randomized trials; on the other hand, such trials are being done now more than ever before.


Optical characterization of nonimaging dish concentrator for the application of dense-array concentrator photovoltaic system.
Optimization of the design of a nonimaging dish concentrator (NIDC) for a dense-array concentrator photovoltaic system is presented. A new algorithm has been developed to determine configuration of facet mirrors in a NIDC. Analytical formulas were derived to analyze the optical performance of a NIDC and then compared with a simulated result obtained from a numerical method. Comprehensive analysis of optical performance via analytical method has been carried out based on facet dimension and focal distance of the concentrator with a total reflective area of 120 m2. The result shows that a facet dimension of 49.8 cm, focal distance of 8 m, and solar concentration ratio of 411.8 suns is the most optimized design for the lowest cost-per-output power, which is US$1.93 per watt.


[Anterior versus posterior decompression for the treatment of thoracolumbar fractures with spinal cord injury:a Meta-analysis].
To systematically evaluate the efficacy and safety of anterior decompression and posterior decompression in the treatment of thoracolumbar fractures with spinal cord injury, so as to provide a good scientific basis for more effective treatment of thoracolumbar fractures with spinal cord injury. A clinical data about comparative study of anterior decompression and posterior decompression in the treatment of thoracolumbar fractures with spinal cord injury was searched and collected. The databases of Pubmed, Embase, Cochrane Library, CNKI, CBM, Wanfang Medical Network were searched by computer. Artificially collected journals included Spine, European Spine Journal, The Journal of Bone and Joint Surgery. Two spine surgeons independently screened the literature according to established inclusion and exclusion criteria and assessed the quality of the included studies. Meta-analysis was performed on the data using Review Manager 5.3 software, the indicators included operative time, intraoperative blood loss, postoperative tactile score, postoperative motor score, postoperative vertebral height, hospitalization time, neurological function recovery, efficiency of treatment, postoperative complications. Fifteen randomized controlled trials (RCTs) were enrolled in a total of 1 360 patients, including 680 anterior decompression and 680 posterior decompression. The results of Meta-analysis showed that the anterior decompression group had longer operation time [MD=80.09, 95% CI(36.83, 123.34), P=0.000 3], more intraoperative blood loss [MD=225.21, 95%CI(171.07, 279.35), P<0.000 01], longer hospitalization time [MD=2.31, 95% CI(0.32, 4.31), P=0.02]. And the postoperative tactile score [MD=13.39, 95% CI(9.86, 16.92), P<0.000 01], postoperative motor score [MD=13.15, 95% CI(7.02, 19.29), P<0.000 1], vertebral height [MD=1.36, 95% CI(0.79, 1.92), P<0.000 01] in anterior decompression were higher than that in posterior decompression. There was no statistically significant differences in the efficacy of treatment [OR=1.14, 95% CI(0.56, 2.31), P=0.72], neurological recovery [OR=0.87, 95% CI(0.57, 1.33), P=0.52] between two groups. Compared with posterior decompression, the anterior decompression has the advantages of longer operating time, more intraoperative blood loss, longer hospitalization time, higher postoperative tactile score, higher postoperative motor score, and higher injury vertebral height, But there was no significant difference in the treatment efficiency and nerve function recovery between two groups.


Safety and Treatment Effectiveness of a Single Autologous Protein Solution Injection in Patients with Knee Osteoarthritis.
Osteoarthritis (OA) is a common degenerative condition characterized by pain and loss of function. A pathological biochemical environment with excess inflammatory and catabolic proteins is a major contributor to OA. nSTRIDE(®) Autologous Protein Solution (APS) is a new therapy under development for the treatment of OA. This therapy is formed from a patient's blood and contains high concentrations of anti-inflammatory and anabolic proteins. This study assessed the safety and treatment effects of APS. Eleven subjects with early to moderate OA were injected with APS. Subjects were closely monitored for adverse events (AE) following the injection. Treatment outcome measures were obtained before injection. AE and clinical outcomes were assessed at 1 and 2 weeks postinjection and 1, 3, and 6 months postinjection. There were no serious AE or AE that were reported by the investigator as greater than mild in severity. There were no AE that were related to the device. There were minor AE related to the injection procedure, including injection site discomfort (1/11), injection site joint pain (1/11), and procedural nausea (1/11), which resolved quickly and did not require treatment. Mean Western Ontario and McMaster Universities Arthritis Index (WOMAC) composite scores and pain, stiffness, and function subscale scores all showed significant improvement compared to baseline by 2 weeks postinjection. The data presented here suggest that the treatment is safe and show a complication profile that is mild and consistent with similar treatments. A single injection of APS for treatment of early to moderate knee OA led to symptom improvement over the study course. Based on these results, an adequately powered, well-controlled, randomized multicenter study to establish clinical efficacy is warranted.


Adjunctive granulocyte colony-stimulating factor for treatment of septic shock due to melioidosis.
Melioidosis, caused by the intracellular pathogen Burkholderia pseudomallei, is endemic in northern Australia and Southeast Asia. Risk factors for this infection have also been associated with functional neutrophil defects. Because of this, granulocyte colony-stimulating factor (G-CSF) was adopted for use in patients with septic shock due to melioidosis in December 1998. We compared the mortality rates from before and after the introduction of G-CSF therapy at the Royal Darwin Hospital (Darwin, Australia) during the period of 1989-2002. The mortality rate decreased from 95% to 10% after the introduction of G-CSF. Risk factors, the duration of illness before presentation, and the severity of illness were similar in both groups. A smaller decrease in mortality among patients in the intensive care unit who did not have melioidosis was observed, suggesting that other changes in management did not account for the magnitude of the benefit seen. We conclude that G-CSF may have contributed to the reduction in the mortality rate among patients with septic shock due to melioidosis.


Identification of blood meal sources in the main African malaria mosquito vector by MALDI-TOF MS.
The identification of blood meal sources in malaria vectors is critical to better understanding host/vector interactions and malaria epidemiology and control. Currently, the identification of mosquito blood meal origins is based on time-consuming and costly techniques such as precipitin tests, ELISA and molecular tools. Although these tools have been validated to identify the blood meal and trophic preferences of female Anopheles mosquitoes, they present several limitations. Recently, matrix-assisted, laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was successfully used as a quick and accurate tool for arthropod identification, including mosquitoes. The aim of the present work was to test whether MALDI-TOF MS could also be applied to identification of blood meal sources from engorged mosquitoes. Abdomen proteins extracted from Anopheles gambiae (stricto sensu, S molecular form) that were either unengorged or artificially engorged on seven distinct types of vertebrate blood (human, horse, sheep, rabbit, mouse, rat, dog) were submitted for MALDI-TOF MS. The comparison of mass spectrometry (MS) spectra from mosquito abdomens collected 1 h post-feeding, were able to discriminate blood meal origins. Moreover, using Aedes albopictus specimens, abdominal protein MS spectra from engorged mosquitoes were found specific to host blood source and independent of the mosquito species. A sequential analysis revealed stability of mosquito abdominal protein spectra up to 24 h post-feeding. These results indicate that MALDI-TOF MS could determine feeding patterns of freshly engorged mosquitoes up to 24 h post-blood meal. The MALDI-TOF MS technique appears to be an efficient tool for large epidemiological surveillance of vector-borne diseases and outbreak source identification.


Consensus clustering based on a new Probabilistic Rand Index with application to subtopic retrieval.
We introduce a probabilistic version of the well-known Rand Index (RI) for measuring the similarity between two partitions, called Probabilistic Rand Index (PRI), in which agreements and disagreements at the object-pair level are weighted according to the probability of their occurring by chance. We then cast consensus clustering as an optimization problem of the PRI value between a target partition and a set of given partitions, experimenting with a simple and very efficient stochastic optimization algorithm. Remarkable performance gains over input partitions as well as over existing related methods are demonstrated through a range of applications, including a new use of consensus clustering to improve subtopic retrieval.


Discovery of a small molecule that inhibits bacterial ribosome biogenesis.
While small molecule inhibitors of the bacterial ribosome have been instrumental in understanding protein translation, no such probes exist to study ribosome biogenesis. We screened a diverse chemical collection that included previously approved drugs for compounds that induced cold sensitive growth inhibition in the model bacterium Escherichia coli. Among the most cold sensitive was lamotrigine, an anticonvulsant drug. Lamotrigine treatment resulted in the rapid accumulation of immature 30S and 50S ribosomal subunits at 15 °C. Importantly, this was not the result of translation inhibition, as lamotrigine was incapable of perturbing protein synthesis in vivo or in vitro. Spontaneous suppressor mutations blocking lamotrigine activity mapped solely to the poorly characterized domain II of translation initiation factor IF2 and prevented the binding of lamotrigine to IF2 in vitro. This work establishes lamotrigine as a widely available chemical probe of bacterial ribosome biogenesis and suggests a role for E. coli IF2 in ribosome assembly.


Validation of uromodulin as a candidate gene for human essential hypertension.
A recent genome-wide association study identified a locus on chromosome 16 in the promoter region of the uromodulin (UMOD) gene that is associated with hypertension. Here, we examined the hypertension signal with functional studies in Umod knockout (KO) mice. Systolic blood pressure was significantly lower in KO versus wild-type (WT) mice under basal conditions (KO: 116.6±0.3 mm Hg versus WT: 136.2±0.4 mm Hg; P<0.0001). Administration of 2% NaCl did not alter systolic blood pressure in KO mice, whereas it increased in WT mice by ≈33%, P<0.001. The average 24-hour urinary sodium excretion in the KO was greater than that of WT mice (P<0.001). Chronic renal function curves demonstrate a leftward shift in KO mice, suggesting that the relationship between UMOD and blood pressure is affected by sodium. Creatinine clearance was increased during salt loading with 2% NaCl in the KO mice, leading to augmented filtered Na(+) excretion and further Na(+) loss. The difference in sodium uptake that exists between WT and KO strains was explored at the molecular level. Urinary tumor necrosis factor-α levels were significantly higher in KO mice compared with WT mice (P<0.0001). Stimulation of primary thick ascending limb of the loop of Henle cells with exogenous tumor necrosis factor-α caused a reduction in NKCC2A expression (P<0.001) with a concurrent rise in the levels of UMOD mRNA (P<0.001). Collectively, we demonstrate that UMOD regulates sodium uptake in the thick ascending limb of the loop of Henle by modulating the effect of tumor necrosis factor-α on NKCC2A expression, making UMOD an important determinant of blood pressure control.


Fimbrial and non-fimbrial haemagglutinins in Enterobacter aerogenes.
Ten strains of Enterobacter aerogenes were examined for their ability to produce haemagglutinins and fimbriae. Nine strains formed a mannose-sensitive (MS) haemagglutinin associated with thin (4 nm) non-channelled fimbriae. These thin fimbriae of E. aerogenes were antigenically different from the thin fimbriae of other fimbriate strains of Enterobacter and Klebsiella and probably represent a new kind of fimbria not previously described in Enterobacteriaceae. Eight of these same nine strains also formed a non-fimbrial mannose-resistant, proteus-like (MR/P) haemagglutinin. The formation of thin fimbriae associated with MS haemagglutinin and of non-fimbrial MR/P haemagglutinin are properties not associated with other strains of Enterobacter and Klebsiella. E. aerogenes strain NCIB11460 was unusual among the strains examined in this series in that it alone produced mannose-resistant, Klebsiella-like (MR/K) haemagglutinin and type-3 fimbriae which, as judged by immunoelectronmicroscopy, were antigenically like those of type-3 fimbriate Klebsiella strains. The identifying characters of this exceptional strain of E. aerogenes are discussed in detail. All ten strains also produced thick fimbriae which by immunoelectronmicroscopy behaved like the type-1 fimbriae of Klebsiella strains. However, correlation between their presence and the production of MS haemagglutinin in E. aerogenes was not established. The findings are discussed in the light of the present difficult taxonomic status of E. aerogenes within the tribe Klebsielleae.


Quantification of alternatively spliced FGFR2 RNAs using the RNA invasive cleavage assay.
The regulated splicing of fibroblast growth factor receptor-2 (FGFR2) transcripts leads to tissue-specific expression of distinct receptor isoforms. These isoforms contain two different versions of the ligand binding Ig-like domain III, which are encoded by exon IIIb or exon IIIc. The mutually exclusive use of exon IIIb and exon IIIc can be recapitulated in tissue culture using DT3 and AT3 rat prostate carcinoma cells. We used this well-characterized system to evaluate the precision and accuracy of the RNA invasive cleavage assay to specifically measure FGFR2 alternative splicing outcomes. Experiments presented here demonstrated that the RNA invasive cleavage assay could specifically detect isoforms with discrimination levels that ranged from 1 in 5 x 10(3) to 1 in 10(5). Moreover the assay could detect close to 0.01 amole of FGFR2 RNAs. The assay detected the expected levels of transcripts containing either exon IIIb or IIIc, but, surprisingly, it detected high levels of IIIb-IIIc double inclusion transcripts. This finding, which has important implications for the role of exon silencing and of mRNA surveillance mechanisms, had been missed by RT-PCR. Additionally, we used the RNA invasive cleavage assay to demonstrate a novel function for the regulatory element IAS2 in repressing exon IIIc inclusion. We also show here that purification of RNA is not necessary for the invasive cleavage assay, because crude cell lysates could be used to accurately measure alternative transcripts. The data presented here indicate that the RNA invasive cleavage assay is an important addition to the repertoire of techniques available for the study of alternative splicing.


Initial evaluation of nivolumab in patients with post-operative recurrence of malignant pleural mesothelioma.
Limited options exist for treating post-recurrence patients with malignant pleural mesothelioma (MPM). This study aimed to evaluate the efficacy and feasibility of nivolumab in patients with post-operative recurrence of MPM in a real-world setting. This study included 35 patients with post-operative recurrence of MPM. Treatment consisted of 240-mg intravenous nivolumab administration every 2 weeks until progressive disease (PD) or serious adverse events (AEs). Additional post-treatment data were evaluated, including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), post-treatment survival and AEs. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors. Survival analysis was performed using the Kaplan-Meier method. The feasibility analysis including AEs was performed with the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Of the 35 patients who received nivolumab, median follow-up was 6 months. The median treatment duration was 3 months (range: 1-14 months), and median of 8 cycles (range: 2-32 cycles) was administered. Best overall responses were follows: 1 patient had complete response, 6 had partial response, 18 had stable disease and 8 had PD. The ORR was 20.0%, and the DCR was 77.1%. The median overall survival and PFS were 13.1 and 4.4 months, respectively. There were grade-3 AEs in four patients (11.4%). No grade-4 or -5 AEs were observed. Nivolumab treatment in patients with post-operative recurrence of MPM seems safe and clinical efficacy.


AAV-mediated expression of BAG1 and ROCK2-shRNA promote neuronal survival and axonal sprouting in a rat model of rubrospinal tract injury.
A lesion to the rat rubrospinal tract is a model for traumatic spinal cord lesions and results in atrophy of the red nucleus neurons, axonal dieback, and locomotor deficits. In this study, we used adeno-associated virus (AAV)-mediated over-expression of BAG1 and ROCK2-shRNA in the red nucleus to trace [by co-expression of enhanced green fluorescent protein (EGFP)] and treat the rubrospinal tract after unilateral dorsal hemisection. We investigated the effects of targeted gene therapy on neuronal survival, axonal sprouting of the rubrospinal tract, and motor recovery 12 weeks after unilateral dorsal hemisection at Th8 in rats. In addition to the evaluation of BAG1 and ROCK2 as therapeutic targets in spinal cord injury, we aimed to demonstrate the feasibility and the limits of an AAV-mediated protein over-expression versus AAV.shRNA-mediated down-regulation in this traumatic CNS lesion model. Our results demonstrate that BAG1 and ROCK2-shRNA both promote neuronal survival of red nucleus neurons and enhance axonal sprouting proximal to the lesion.


First results of triple-modality treatment combining radiotherapy, chemotherapy, and hyperthermia for the treatment of patients with stage IIB, III, and IVA cervical carcinoma.
Patients with advanced cervical carcinoma are treated routinely with radiotherapy and cisplatin-containing chemotherapy. It has been shown that hyperthermia can improve the results of both radiotherapy and cisplatin. In the current study, the feasibility and efficacy of the combination of all three modalities was studied in previously untreated patients with cervical carcinoma. Patients with advanced cervical carcinoma were registered prospectively in the U.S., Norway, and the Netherlands. External-beam radiotherapy and brachytherapy were administered for a biologically effective dose > or = 86.7 gray. At least 4 courses of weekly cisplatin (40 mg/m(2)) and 4 sessions of weekly locoregional hyperthermia were added to radiotherapy. Sixty-eight patients with a median age of 45 years were enrolled. Full-dose radiotherapy was delivered to all patients according to plan. At least 4 courses of chemotherapy were received by 97% of patients, and at least 4 courses of hyperthermia treatment were received by 93% of patients. Toxicity was fully comparable to that described for chemoradiotherapy alone, and the median total treatment time was 45 days. Complete remission was achieved by 61 patients (90%). After a median follow-up of 538 days, 74% of patients remained alive without signs of recurrence, and the overall survival rate was 84%. The combination of full-dose radiotherapy, chemotherapy, and hyperthermia was feasible and effective in a multicenter international setting among patients with advanced cervical carcinoma. A Phase III study comparing this novel triplet with standard chemoradiation, designed to show at least a 15% improvement in overall survival, has been launched.


Six-minute walk distance in patients with chronic obstructive pulmonary disease: Which reference equations should we use?
The use of different 6-min walk distance (6MWD) reference equations probably results in different predicted 6MWD reference values. We wished to investigate the impact of several 6MWD reference equations for adults in patients with chronic obstructive pulmonary disease (COPD) and factors accountable for different 6MWD% predicted values. Twenty-two 6MWD reference equations were applied to a data set of 2757 patients with COPD. The predicted 6MWD reference value of Troosters and colleagues was used as the point of reference. Four out of 21 remaining equations resulted in comparable 6MWD% predicted, 16 equations resulted in significantly higher 6MWD% predicted and 1 equation resulted in a significantly lower 6MWD% predicted. Similar differences in 6MWD% predicted were observed after stratification by sex. Body mass index and global initiative for chronic obstructive lung disease (GOLD) stage classification demonstrated varying results within and between the groups; 9 out of 21 equations resulted in comparable 6MWD% predicted in underweight patients but only 1 equation demonstrated comparable result in obese. Eight equations in GOLD I, whilst 5 out of 21 equations in GOLD IV resulted in comparable 6MWD% predicted. Existing 6MWD reference equations will give varying results. The choice of 6MWD reference equation should consider the consistency of 6-min walk test operating procedures and at least be specific for the country/region of origin.


Cancer-preventive activities of tocopherols and tocotrienols.
The cancer-preventive activity of vitamin E has been studied. Whereas some epidemiological studies have suggested a protective effect of vitamin E against cancer formation, many large-scale intervention studies with alpha-tocopherol (usually large doses) have not demonstrated a cancer-preventive effect. Studies on alpha-tocopherol in animal models also have not demonstrated robust cancer prevention effects. One possible explanation for the lack of demonstrable cancer-preventive effects is that high doses of alpha-tocopherol decrease the blood and tissue levels of delta-tocopherols. It has been suggested that gamma-tocopherol, due to its strong anti-inflammatory and other activities, may be the more effective form of vitamin E in cancer prevention. Our recent results have demonstrated that a gamma-tocopherol-rich mixture of tocopherols inhibits colon, prostate, mammary and lung tumorigenesis in animal models, suggesting that this mixture may have a high potential for applications in the prevention of human cancer. In this review, we discuss biochemical properties of tocopherols, results of possible cancer-preventive effects in humans and animal models and possible mechanisms involved in the inhibition of carcinogenesis. Based on this information, we propose that a gamma-tocopherol-rich mixture of tocopherols is a very promising cancer-preventive agent and warrants extensive future research.


Vestibulo-ocular reflex in patients with superior semicircular canal benign paroxysmal positional vertigo (BPPV).
The function of all the semicircular canals in patients with idiopathic benign paroxysmal positional vertigo (BPPV) in whom otoconial debris is located in the superior semicircular canal (SSC) is normal. BPPV of SSC is an infrequent entity in which otoconial debris evokes vertigo and nystagmus in the head-hanging position and during anterior flexion of the patient. We studied the vestibulo-ocular reflex (VOR) in 12 patients with this particular type of BPPV. The reflex was evoked by rapid head impulses in the plane of the three semicircular canals in the affected and the normal ear. The reflex was evaluated with a video system that analyzes the head and eye velocity: the gain (the relation between both magnitudes) was the objective measure. The mean gain of VOR was within normal limits for the six semicircular canals and there were no significant differences between the same canals on each side of patients with BPPV in whom canalolithiasis was located in the SSC. However, gain asymmetry was different for each pair of canals.


Offshore fresh groundwater reserves as a global phenomenon.
The flow of terrestrial groundwater to the sea is an important natural component of the hydrological cycle. This process, however, does not explain the large volumes of low-salinity groundwater that are found below continental shelves. There is mounting evidence for the global occurrence of offshore fresh and brackish groundwater reserves. The potential use of these non-renewable reserves as a freshwater resource provides a clear incentive for future research. But the scope for continental shelf hydrogeology is broader and we envisage that it can contribute to the advancement of other scientific disciplines, in particular sedimentology and marine geochemistry.


Anxiety sensitivity in adolescence and young adulthood: the role of stressful life events, 5HTTLPR and their interaction.
Cognitive biases have long been hypothesized to influence the development and maintenance of symptoms of internalizing problems. Anxiety sensitivity represents one such bias and refers to sensitivity to the physical and emotional symptoms of anxiety and the belief that these are harmful. Twin studies indicate a role for both environmental and genetic influences on anxiety sensitivity. However, little work has been done specifying environments or genes involved in this phenotype. In light of this, we looked at the association between stressful life events, the serotonin transporter gene polymorphism (5HTTLPR), and anxiety sensitivity in a longitudinal sample of adolescents. Stressful life events and anxiety sensitivity were measured in over 1,500 individuals at three time points (mean ages 15, 17, and 20 years). 5HTTLPR was genotyped in 1,109 participants. There was consistent evidence for an association between stressful life events and both anxiety sensitivity and change in anxiety sensitivity over time. Although the effect of independent stressful life events was relatively short lived, dependent stressful life events were associated with anxiety sensitivity over time. There was no evidence for a main effect of 5HTTLPR on anxiety sensitivity. 5HTTLPR genotype did not moderate the effect of stressful life events on anxiety sensitivity. The current study extends previous work by showing that stressful life events, independent of the individual, explained change in cognitions associated with anxiety and depression. This effect does not, however, appear to be moderated by genotype.


Oxygen therapy for acute myocardial infarction.
Oxygen (O2) is widely used in people with acute myocardial infarction (AMI). Previous systematic reviews concluded that there was insufficient evidence to know whether oxygen reduced, increased or had no effect on heart ischaemia or infarct size. Our first Cochrane review in 2010 also concluded there was insufficient evidence to know whether oxygen should be used. Since 2010, the lack of evidence to support this widely used intervention has attracted considerable attention, prompting further trials of oxygen therapy in myocardial infarction patients. It is thus important to update this Cochrane review. To assess the effects of routine use of inhaled oxygen for acute myocardial infarction (AMI). We searched the following bibliographic databases on 6 June 2015: the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE (OVID), Embase (OVID), CINAHL (EBSCO) and Web of Science (Thomson Reuters). LILACS (Latin American and Caribbean Health Sciences Literature) was last searched in September 2016. We also contacted experts to identify eligible studies. We applied no language restrictions. Randomised controlled trials in people with suspected or proven AMI (ST-segment elevation myocardial infarction (STEMI) or non-STEMI) within 24 hours after onset, in which the intervention was inhaled oxygen (at normal pressure) compared to air, regardless of co-therapies provided to participants in both arms of the trial. Two authors independently reviewed the titles and abstracts of identified studies to see if they met the inclusion criteria and independently undertook the data extraction. We assessed the quality of studies and the risk of bias according to guidance in the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome was death. The measure of effect used was the risk ratio (RR) with a 95% confidence interval (CI). We used the GRADE approach to evaluate the quality of the evidence and the GRADE profiler (GRADEpro) to import data from Review Manager 5 and create 'Summary of findings' tables. The updated search yielded one new trial, for a total of five included studies involving 1173 participants, 32 of whom died. The pooled risk ratio (RR) of all-cause mortality in the intention-to-treat analysis was 0.99 (95% CI 0.50 to 1.95; 4 studies, N = 1123; I2 = 46%; quality of evidence: very low) and 1.02 (95% CI 0.52 to 1.98; 4 studies, N = 871; I2 = 49%; quality of evidence: very low) when only analysing participants with confirmed AMI. One trial measured pain directly, and two others measured it by opiate usage. The trial showed no effect, with a pooled RR of 0.97 for the use of opiates (95% CI 0.78 to 1.20; 2 studies, N = 250). The result on mortality and pain are inconclusive. There is no clear effect for oxygen on infarct size (the evidence is inconsistent and low quality). There is no evidence from randomised controlled trials to support the routine use of inhaled oxygen in people with AMI, and we cannot rule out a harmful effect. Given the uncertainty surrounding the effect of oxygen therapy on all-cause mortality and on other outcomes critical for clinical decision, well-conducted, high quality randomised controlled trials are urgently required to inform guidelines in order to give definitive recommendations about the routine use of oxygen in AMI.


Designing an ordered template of cylindrical arrays based on a simple flat plate confinement of block copolymers: a coarse-grained molecular dynamics study.
In this paper we study the morphology formed by asymmetric di-block copolymers (di-BCPs) under various confinements using a large-scale coarse-grained molecular dynamics (CGMD) framework. We start with a simple flat plate confinement with the bottom and the top substrate attractive to the minor phase. Studies at a lower confinement length of 17σ have shown that there exists a critical chain length above which a transition from a three-domain morphology to a two-domain morphology is observed. Increasing the confinement length to 42σ, where the chains experience considerably lower confinement effects, also revealed the existence of a critical chain length - a transition from a multi-domain morphology (>3) to a three-domain morphology. The results obtained from the flat plate study with two confinement dimensions were used to design a topography of silica pillars with and without a bottom substrate to form ordered cylindrical BCP arrays. The least and highest radial separation lengths between adjacent pillars are kept at 17σ and 42σ, respectively. A direct correlation was observed in the number of continuous micro-domains of the maximum and minimum confinement dimensions with the 17σ and 42σ flat plate trials. With the optimum chain length employed, the surfaces with affinity to the minor phase can direct the BCP self-assembly to form ordered arrays of minor phase cylinders. The current study thus elucidates a useful tool to predict the morphology formed in an intricate nano-lithographic template by using simple length scale arguments derived from a flat plate confinement study.


Methodological assessment of skin and limb blood flows in the human forearm during thermal and baroreceptor provocations.
Skin blood flow responses in the human forearm, assessed by three commonly used technologies-single-point laser-Doppler flowmetry, integrated laser-Doppler flowmetry, and laser-Doppler imaging-were compared in eight subjects during normothermic baseline, acute skin-surface cooling, and whole body heat stress (Δ internal temperature=1.0±0.2 degrees C; P<0.001). In addition, while normothermic and heat stressed, subjects were exposed to 30-mmHg lower-body negative pressure (LBNP). Skin blood flow was normalized to the maximum value obtained at each site during local heating to 42 degrees C for at least 30 min. Furthermore, comparisons of forearm blood flow (FBF) measures obtained using venous occlusion plethysmography and Doppler ultrasound were made during the aforementioned perturbations. Relative to normothermic baseline, skin blood flow decreased during normothermia+LBNP (P<0.05) and skin-surface cooling (P<0.01) and increased during whole body heating (P<0.001). Subsequent LBNP during whole body heating significantly decreased skin blood flow relative to control heat stress (P<0.05). Importantly, for each of the aforementioned conditions, skin blood flow was similar between the three measurement devices (main effect of device: P>0.05 for all conditions). Similarly, no differences were identified across all perturbations between FBF measures using plethysmography and Doppler ultrasound (P>0.05 for all perturbations). These data indicate that when normalized to maximum, assessment of skin blood flow in response to vasoconstrictor and dilator perturbations are similar regardless of methodology. Likewise, FBF responses to these perturbations are similar between two commonly used methodologies of limb blood flow assessment.


De novo transcriptome assembly from fat body and flight muscles transcripts to identify morph-specific gene expression profiles in Gryllus firmus.
Wing polymorphism is a powerful model for examining many aspects of adaptation. The wing dimorphic cricket species, Gryllus firmus, consists of a long-winged morph with functional flight muscles that is capable of flight, and two flightless morphs. One (obligately) flightless morph emerges as an adult with vestigial wings and vestigial flight muscles. The other (plastic) flightless morph emerges with fully-developed wings but later in adulthood histolyzes its flight muscles. Importantly both flightless morphs have substantially increased reproductive output relative to the flight-capable morph. Much is known about the physiological and biochemical differences between the morphs with respect to adaptations for flight versus reproduction. In contrast, little is known about the molecular genetic basis of these morph-specific adaptations. To address this issue, we assembled a de novo transcriptome of G. firmus using 141.5 million Illumina reads generated from flight muscles and fat body, two organs that play key roles in flight and reproduction. We used the resulting 34,411 transcripts as a reference transcriptome for differential gene expression analyses. A comparison of gene expression profiles from functional flight muscles in the flight-capable morph versus histolyzed flight muscles in the plastic flight incapable morph identified a suite of genes involved in respiration that were highly expressed in pink (functional) flight muscles and genes involved in proteolysis highly expressed in the white (histolyzed) flight muscles. A comparison of fat body transcripts from the obligately flightless versus the flight-capable morphs revealed differential expression of genes involved in triglyceride biosynthesis, lipid transport, immune function and reproduction. These data provide a valuable resource for future molecular genetics research in this and related species and provide insight on the role of gene expression in morph-specific adaptations for flight versus reproduction.


Upper-limb kinematics of the presumed-to-be-unaffected side after brain injury.
The purpose of this pilot study was to investigate the kinematics of the presumed-to-be-unaffected upper limbs of people with brain injury (BI) compared with people without brain injury (WBI) during reaching. Seventeen people with BI with no apparent motor deficit and 17 people WBI were measured and compared. A six-camera motion analysis system was used to determine movement duration, average speed, and smoothness during reaching. The group of people with BI was found to be significantly longer in movement duration (p < .0001), were slower in average speed (p < .0001), and had decreased smoothness (p < .0001) during reaching than the group of people WBI. The results suggest that people with BI may have undetected motor deficit in their presumed-to-be-unaffected upper extremities. Further research is needed to explore the upper-limb motor performance and the impact on function and safety.


Role of Insulin-Stimulated Adipose Tissue Perfusion in the Development of Whole-Body Insulin Resistance.
After food ingestion, macronutrients are transported to and stored in the skeletal muscle and adipose tissue. They can be subsequently used as an energy source in times of energy deprivation. Uptake of these nutrients in myocytes and adipocytes depends largely on adequate tissue perfusion. Interestingly, insulin is able to dilate skeletal muscle arterioles, which facilitates the delivery of macronutrients and insulin itself to muscle tissue. Insulin-stimulated skeletal muscle perfusion is impaired in several insulin-resistant states and is believed to contribute to impaired skeletal muscle glucose uptake and consequently impaired whole-body glucose disposal. Insulin-resistant individuals also exhibit blunted postprandial adipose tissue perfusion. However, the relevance of this impairment to metabolic dysregulation is less clear. In this review, we provide an overview of adipose tissue perfusion in healthy and insulin-resistant individuals, its regulation among others by insulin, and the possible influences of impaired adipose tissue perfusion on whole-body insulin sensitivity. Finally, we propose a novel hypothesis that acute overfeeding impacts distribution of macronutrients by reducing skeletal muscle perfusion, while adipose tissue perfusion remains intact. An online visual overview is available for this article.


Modelling the Impact of Condom Distribution on the Incidence and Prevalence of Sexually Transmitted Infections in an Adult Male Prison System.
To determine the effects of 1) a condom distribution program and 2) a condom distribution program combined with opt-out sexually transmitted infection (STI) screening on the transmission and prevalence of STIs in a prison system. Using data from an implementation evaluation of a state-wide prison condom program and parameter estimates from available literature, a deterministic model was developed to quantify the incidence and prevalence of sexually transmitted HIV, hepatitis B, chlamydia, syphilis and gonorrhoea across 14 Victorian prisons. The model included individual prison populations (by longer (>2 years) or shorter sentence lengths) and monthly prisoner transfers. For each STI, simulations were compared: without any intervention; with a condom distribution program; and with a combined condom and opt-out STI screening at prison reception intervention program. Condoms reduced the annual incidence of syphilis by 99% (N = 66 averted cases); gonorrhoea by 98% (N = 113 cases); hepatitis B by 71% (N = 5 cases); chlamydia by 27% (N = 196 cases); and HIV by 50% (N = 2 cases every 10 years). Condom availability changed the in-prison epidemiology of gonorrhoea and syphilis from self-sustaining to levels unlikely to result in infection outbreaks; however, condoms did not reduce chlamydia prevalence below a self-sustaining level due to its high infectiousness, high prevalence and low detection rate. When combined with a screening intervention program, condoms reduced chlamydia prevalence further, but not below a self-sustaining level. The low prevalence of HIV and hepatitis B in Australian prisons meant the effects of condoms were predicted to be small. Condoms are predicted to effectively reduce the incidence of STIs in prison and are predicted to control syphilis and gonorrhoea transmission, however even combined with a screening on arrival program may be insufficient to reduce chlamydia prevalence below self-sustaining levels. To control chlamydia transmission additional screening of the existing prison population would be required.


The challenges to scaling up antiretroviral therapy in Papua New Guinea.
This study used a qualitative interview methodology to explore the barriers to scaling up access to antiretroviral therapy (ART) in Papua New Guinea (PNG). Key informants were selected purposively from organizations active in HIV/AIDS (human immunodeficiency virus/acquired immune deficiency syndrome) work throughout PNG. Interviews were taped, transcribed and analyzed thematically. Predicted barriers likely to impede the delivery of ART by the health services included shortages of skilled and experienced personnel; lack of sustainable funding; weak services at the rural periphery; lack of capacity for the management of chronic illness; inadequacies of basic services for people living with HIV/AIDS (PLWHAs); the difficulty of finding the most appropriate method and venue of delivery for ART; and the complexities of establishing social criteria for deciding who to treat. Barriers likely to impede the acceptance of treatment by the community included the cost of treatment to the patient; the low socioeconomic status of PLWHAs; the effects of stigma, particularly in the case of women; and sociocultural factors affecting public perceptions of ART. The study concluded that, given the range of potential barriers, scaling up ART in PNG and other developing countries will be a complex process, requiring careful decisions to be made over how best to utilize available resources.


Changing Clinician Practices and Attitudes Regarding the Use of Antiretroviral Therapy for HIV Treatment and Prevention.
As part of the HPTN 065 study in the Bronx, New York and Washington, the authors, we surveyed clinicians to assess for shifts in their practices and attitudes around HIV treatment and prevention. Antiretroviral therapy (ART)-prescribing clinicians at 39 HIV care sites were offered an anonymous Web-based survey at baseline (2010-2011) and at follow-up (2013). The 165 respondents at baseline and 141 respondents at follow-up had similar characteristics-almost 60% were female, median age was 47 years, two-thirds were physicians, and nearly 80% were HIV specialists. The percentage who reported recommending ART irrespective of CD4 count was higher at follow-up (15% versus 68%), as was the percentage who would initiate ART earlier for patients having unprotected sex with partners of unknown HIV status (64% versus 82%), and for those in HIV-discordant partnerships (75% versus 87%). In line with changing HIV treatment guidelines during 2010 to 2013, clinicians increasingly supported early ART for treatment and prevention.


Risk factors associated with severe and recurrent angioedema: an epidemic linked to ACE-inhibitors.
To evaluate the etiology and risk factors for severe manifestation and recurrent episodes of angioedema; to evaluate efficacy of short-term and long-term management strategies for angioedema among a high-risk population. Institutional review board-approved retrospective review of a large, urban population. Data from 875 adult patients treated from January 2008 to December 2013 with the diagnosis of angioedema were obtained using the Clinical Looking Glass utility and review of medical records. Demographic and clinicopathologic risk factors were recorded. The major outcomes evaluated were hospital admission, need for airway intervention, and recurrent episodes of angioedema following the first presentation. Initial treatment strategy and follow-up recommendations were also recorded. The most common cause of angioedema was angiotensin converting enzyme inhibitor (ACEi)-induced (496 [56.6%]). Significant risk factors for severe cases of angioedema included older age, Hispanic race, ACEi-induced angioedema type, American Society of Anesthesiologists class III or above, coexistent cardiopulmonary disease, and a positive smoking history. A total of 17.2% of patients experienced recurrent attacks of angioedema; of those patients, 25.9% were still taking an ACEi at subsequent presentation. Risk factors for recurrent episodes included older age, idiopathic angioedema type, and coexistent cardiopulmonary disease. Only 54.1% of patients who experienced ACEi-induced angioedema had electronic medical record documentation of these allergies. Knowledge of risk factors for severe and recurrent episodes of angioedema and improved education for both healthcare providers and patients, specifically related to ACEi use and allergy documentation, may significantly decrease the burden and morbidity of angioedema among high risk populations. 2b.


The relationship between sleep problems and daytime behavior in children of different ages with autism spectrum disorders.
The purpose of the current study was to evaluate the relationships among sleep problems and daytime behaviors in a large, well-defined cohort of children with autism spectrum disorder (ASD). Out of a registry population of 3452 children with ASDs, a subset of 1193 children aged 4 to 10 years of age from 14 centers across the country was used to evaluate the relationship between varying levels of sleep problems and daytime behavior. Measures included Children's Sleep Habits Questionnaire, Vineland Adaptive Behavior Scales, Survey Interview Form, Second Edition, and Child Behavior Checklist. Multiple analysis of covariance was used to assess the association between sleep and behavior. Results suggest that sleep problems, as identified by parent report by use of the Children's Sleep Habits Questionnaire, have a negative relationship with daytime behavior. More specifically, children with ASDs and sleep problems had more internalizing and externalizing behavior problems, as measured by the Child Behavior Checklist, and poorer adaptive skill development, as measured by the Vineland Adaptive Behavior Scales, than children with ASDs and no sleep problems. Children with moderate to severe sleep problems had greater behavior difficulties, but not necessarily poorer adaptive functioning, than children with mild to moderate sleep problems. Both preschool- and school-aged children demonstrated a negative relationship between behavior and sleep, whereas the relationship between sleep and adaptive functioning was much more variable. These results suggest that, although sleep has a negative relationship with internalizing and externalizing behavior, it may have a different relationship with the acquisition of adaptive skills.


Prevalence of depression among older Americans: the Aging, Demographics and Memory Study.
Previous studies have attempted to provide estimates of depression prevalence in older adults. The Aging, Demographics and Memory Study (ADAMS) is a population-representative study that included a depression assessment, providing an opportunity to estimate the prevalence of depression in late life in the U.S.A. The ADAMS sample was drawn from the larger Health and Retirement Study. A total of 851 of 856 ADAMS participants aged 71 and older had available depression data. Depression was measured using the Composite International Diagnostic Interview - Short Form (CIDI-SF) and the informant depression section of the Neuropsychiatric Inventory (NPI). We estimated the national prevalence of depression, stratified by age, race, sex, and cognitive status. Logistic regression analyses were performed to examine the association of depression and previously reported risk factors for the condition. When combining symptoms of major or minor depression with reported treatment for depression, we found an overall depression prevalence of 11.19%. Prevalence was similar for men (10.19%) and women (11.44%). Whites and Hispanics had nearly three times the prevalence of depression found in African-Americans. Dementia diagnosis and pain severity were associated with increased depression prevalence, while black race was associated with lower rates of depression. The finding of similar prevalence estimates for depression in men and women was not consistent with prior research that has shown a female predominance. Given the population-representativeness of our sample, similar depression rates between the sexes in ADAMS may result from racial, ethnic and socioeconomic diversity.