Changes in neuropeptide Y protein expression following photothrombotic brain infarction and epileptogenesis.
This study characterized morphological changes in the cortex and hippocampus of Sprague-Dawley rats following photothrombotic infarction and epileptogenesis with emphasis on the distribution of neuropeptide Y (NPY) expression. Animals were lesioned in the left sensorimotor cortex and compared with age-matched naive and sham-operated controls by immunohistochemical techniques at 1, 3, 7, and 180 days post-lesioning (DPL). NPY immunostaining was assessed by light microscopy and quantified by the optical fractionator technique using unbiased stereological methods. At 1, 3, and 7 DPL, the number of NPY-positive somata in the lesioned cortex was increased significantly compared to controls and the contralateral cortex. At 180 DPL, lesioned epileptic animals with frequent seizure activity demonstrated significant increases of NPY expression in the cortex, CA1, CA3, hilar interneurons, and granule cells of the dentate gyrus. In addition to NPY immunostaining, neuronal degeneration, cell death/cell loss, and astroglial response were assessed with cell-specific markers. Nissl and NeuN staining showed reproducible infarctions at each investigated time point. FJB-positive somata were most abundant in the infarct core at 1 DPL, decreased markedly at 3 DPL, and virtually absent by 7 DPL. Activated astroglia were detected in the cortex and hippocampus following lesioning and the development of seizure activity. In summary, NPY protein expression and morphological changes following cortical photothrombosis were time-, region-, and pathologic state-dependent. Alterations in NPY expression may reflect reactive or compensatory responses of the rat brain to acute infarction and to the development and expression of epileptic seizures.


Effect of soil moisture stress on growth and yield of cassava in Nigeria.
Nine cassava genotypes were evaluated for their growth responses and adaptability to soil moisture stress on the field and in the screenhouse in Nigeria. Genotypes were evaluated in three savanna agroecologies in a randomized complete block design with three replicates. Screenhouse evaluation was conducted using three moisture regimes of 75, 50 and 25% Field Capacity (FC) in a two-factor factorial experiment in CRD with three replicates. Morphological and yield data were collected on the field and in the screenhouse. Results showed significant (p < 0.05) difference among genotypes on the field and in the screenhouse. Field moisture stress led to a decline in plant height by 47%, stem girth by 15%, number of tubers by 95% and tuber yield by 87%. Screenhouse moisture condition of 25% FC led to a reduction in plant height by 12.6 and 21.2%, stem girth by 16.3 and 21.7%, number of roots by 94.5 and 88.7% and root weight by 93.3 and 94.9%, respectively at 16 and 30 WAP. Moisture stress therefore resulted into considerable reduction in both vegetative growth and yield of cassava genotypes. Therefore, a concerted effort in breeding cassava for drought tolerance is needed as cassava cultivation is expanding into nontraditional semiarid regions of sub-Saharan Africa. Germplasm introduced from Latin America (especially north-eastern Brazil) is providing a unique source of variability to further broaden the genetic base for drought tolerance in cassava.


Age- and race-based serum thyrotropin reference limits.
TSH reference limits, particularly the upper limit, are controversial. The traditional and prevailing method for setting limits uses TSH distribution of thyroid disease-free individuals. The curve is not Gaussian, but skewed to higher concentrations, even after log-transformation; values in the skewed area are assumed to reflect mild hypothyroidism. The underlying assumption for this traditional approach, which has not previously been tested, is that the limits derived from this curve are applicable to all people. However, recent studies suggest that distinct subpopulations have unique TSH distribution and reference limits that are significantly different from limits established by the traditional approach. A search was focused on articles that provide the basis for current recommendations for setting TSH reference limits as well as articles that suggest that the traditional method does not reflect accurately the TSH distribution and reference limits of distinct subpopulations within the United States. TSH distribution and reference limits shift to higher concentrations with age, even up to centenarians, and are unique for different racial/ethnic groups, being at higher concentrations in Caucasians than either Blacks or Hispanics originating from Puerto Rico or the Dominican Republic. The distribution curve derived by the traditional approach represents a composite of curves from specific subpopulations that do not provide appropriate reference limits for those unique groups. Age- and race-specific TSH distribution and reference limits, possibly influenced by genetic factors, should be employed to provide clinicians accurate limits for specific populations and guidance for further evaluation of thyroid dysfunction.


Changing patterns in asthma morbidity and mortality.
Asthma morbidity and mortality have increased in many countries over the last 10 years or more. In some countries, epidemics of deaths have occurred, while others have shown gradual increases. The New Zealand National Asthma Mortality Study associated mortality with severe asthma, underassessment of severity, undertreatment with corticosteroids, overreliance on bronchodilators, discontinuity of medical care and delay in seeking help. Case-control studies of asthma mortality in New Zealand linked prescription of fenoterol with a higher risk of death from asthma than prescription of salbutamol; this higher risk was not negated by adjustment for markers of severity. A study in Saskatchewan, Canada confirmed the increased risk associated with fenoterol use, but also found a significantly elevated risk associated with salbutamol, especially at higher doses. A randomized, placebo-controlled crossover study of regular versus as-needed beta-agonists undertaken in New Zealand showed increased morbidity from asthma during regular treatment, with increased symptoms, decreased pulmonary function, increased airways responsiveness and overall poorer control of asthma despite constant inhaled corticosteroid treatment. Similar findings were evident in some earlier studies of regular salbutamol. Taken together, several recent studies suggest a deleterious effect of frequent use of inhaled beta-agonists, particularly higher potency preparations. Increased responsiveness to allergen is one possible mechanism for this effect, but whatever the mechanism, frequent use of beta-agonists appears to have caused a shift in the chronic severity of asthma, leading to increased morbidity and mortality.


The influence of early aging on eye movements during motor simulation.
Movement based interventions such as imagery and action observation are used increasingly to support physical rehabilitation of adults during early aging. The efficacy of these more covert approaches is based on an intuitively appealing assumption that movement execution, imagery and observation share neural substrate; alteration of one influences directly the function of the other two. Using eye movement metrics this paper reports findings that question the congruency of the three conditions. The data reveal that simulating movement through imagery and action observation may offer older adults movement practice conditions that are not constrained by the age-related decline observed in physical conditions. In addition, the findings provide support for action observation as a more effective technique for movement reproduction in comparison to imagery. This concern for imagery was also seen in the less congruent temporal relationship in movement time between imagery and movement execution suggesting imagery inaccuracy in early aging.


Expression pattern of PAX3 and PAX6 genes during human embryogenesis.
The expression of human PAX6 and PAX3 genes was investigated in 6 human 6-9 week old conceptuses by in situ hybridization. During human embryonic development (6-8 developmental weeks), PAX6 was expressed in the ventricular zone of telencephalon and diencephalon, and in the ventricular and ventral intermediate zones of medulla oblongata and spinal cord. PAX6 expression was detected in both layers of the optic cup, optic stalk and prospective corneal epithelium. Infundibulum and Rathke's pouch of the pituitary gland showed hybridization signal as well. In the early fetal period (9 developmental weeks) PAX6 expression increased in the spinal cord. In the eye, hybridization signal characterized the corneal and lens epithelium, pigmented and neural retina, while it was missing in the optic disc and nerve. In a 6-week human embryo, transcripts of PAX3 gene were observed in the ventricular zone at the mesencephalic-rhombencephalic border, and in the dorsal part of the ventricular zone and the roof plate of the medulla oblongata and the spinal cord. In the 8-9-week fetus, PAX3 expression increased in dorsal parts of the spinal cord. PAX3 characterized ectomesenchyme of the upper and lower jaw, and tongue. During early human development, PAX6 and PAX3 genes seem to be involved in the brain regionalization and establishment of dorso-ventral polarity of the spinal cord. Additionally, PAX6 participates in organogenesis of the eye and the pituitary gland, and PAX3 in the development of face and neck mesenchyme.


Elucidating mechano-pathology of osteoarthritis: transcriptome-wide differences in mechanically stressed aged human cartilage explants.
Failing of intrinsic chondrocyte repair after mechanical stress is known as one of the most important initiators of osteoarthritis. Nonetheless, insight into these early mechano-pathophysiological processes in age-related human articular cartilage is still lacking. Such insights are needed to advance clinical development. To highlight important molecular processes of osteoarthritis mechano-pathology, the transcriptome-wide changes following injurious mechanical stress on human aged osteochondral explants were characterized. Following mechanical stress at a strain of 65% (65%MS) on human osteochondral explants (n65%MS = 14 versus ncontrol = 14), RNA sequencing was performed. Differential expression analysis between control and 65%MS was performed to determine mechanical stress-specific changes. Enrichment for pathways and protein-protein interactions was analyzed with Enrichr and STRING. We identified 156 genes significantly differentially expressed between control and 65%MS human osteochondral explants. Of note, IGFBP5 (FC = 6.01; FDR = 7.81 × 10-3) and MMP13 (FC = 5.19; FDR = 4.84 × 10-2) were the highest upregulated genes, while IGFBP6 (FC = 0.19; FDR = 3.07 × 10-4) was the most downregulated gene. Protein-protein interactions were significantly higher than expected by chance (P = 1.44 × 10-15 with connections between 116 out of 156 genes). Pathway analysis showed, among others, enrichment for cellular senescence, insulin-like growth factor (IGF) I and II binding, and focal adhesion. Our results faithfully represent transcriptomic wide consequences of mechanical stress in human aged articular cartilage with MMP13, IGF binding proteins, and cellular senescence as the most notable results. Acquired knowledge on the as such identified initial, osteoarthritis-related, detrimental responses of chondrocytes may eventually contribute to the development of effective disease-modifying osteoarthritis treatments.


Monitoring and modelling of influent patterns, phase distribution and removal of 20 elements in two primary wastewater treatment plants in Norway.
Many small- or medium-sized communities in Northern Europe employ only primary wastewater treatment plants (WWTPs) and effluent discharges can be a relevant source of pollution. The current study combines monitoring and modelling approaches to investigate concentrations, influent patterns, size distribution and removal of 20 elements for the two primary WWTPs (Ladehammeren, LARA; Høvringen, HØRA) serving Trondheim, the third largest city in Norway. Element concentrations were determined in raw influent wastewater, effluents and biosolids, and diurnal inflow patterns were assessed. The elemental distribution in particulate, colloidal and dissolved fractions of untreated wastewater was characterized using filtration separation and electron microscopy. An influent generator model and multivariate statistical analyses were used to determine release patterns and to predict the (co-)occurrence of selected elements. Raw influent wastewater concentrations for most elements were similar in the two WWTPs, with only Ca, Mn, Fe, Co and Ba being significantly higher (p < 0.05) in HØRA (which receives more household and hospital discharges). Removal efficiencies varied between elements, but in most cases reflected their association with particulates. Nanosized particles of several elements were detected, with Cu/Zn being most common. Measured concentrations of most elements followed typical diurnal wastewater discharge patterns and enrichment factors calculated for biosolids confirmed the importance of anthropogenic sources for P, Cu, Zn, Cd, As, Cr, Ni, Pb, V, Co and Fe. Elemental concentrations generally correlated well with total suspended solid (TSS) concentrations at HØRA, while this was less pronounced in LARA (possibly due to higher industrial contributions). In one of its first applications for WWTP influent pattern examination, principal component analysis was found to be instrumental for source identification of target elements, showing significant differences between LARA and HØRA influents. The combined experimental, statistical and modelling approaches used herein allowed for improved understanding of element sources, patterns of discharge and fate in primary WWTPs.


Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits.
Deep sequence-based imputation can enhance the discovery power of genome-wide association studies by assessing previously unexplored variation across the common- and low-frequency spectra. We applied a hybrid whole-genome sequencing (WGS) and deep imputation approach to examine the broader allelic architecture of 12 anthropometric traits associated with height, body mass, and fat distribution in up to 267,616 individuals. We report 106 genome-wide significant signals that have not been previously identified, including 9 low-frequency variants pointing to functional candidates. Of the 106 signals, 6 are in genomic regions that have not been implicated with related traits before, 28 are independent signals at previously reported regions, and 72 represent previously reported signals for a different anthropometric trait. 71% of signals reside within genes and fine mapping resolves 23 signals to one or two likely causal variants. We confirm genetic overlap between human monogenic and polygenic anthropometric traits and find signal enrichment in cis expression QTLs in relevant tissues. Our results highlight the potential of WGS strategies to enhance biologically relevant discoveries across the frequency spectrum.


The Relationship between the Growth Hormone/Insulin-like Growth Factor System and the Histological Features of Nonalcoholic Fatty Liver Disease.
Objective Growth hormone (GH) deficiency has recently been reported as a cause of nonalcoholic fatty liver disease (NAFLD), and GH supplementation has been shown to improve the histology of NAFLD. The aim of the present study was to clarify the relationship between the histological severity of NAFLD and production of the GH/insulin-like growth factor 1 (IGF-1) axis. Methods A total of 222 Japanese patients with liver biopsy-confirmed NAFLD and 55 patients with hepatitis C virus (HCV)-related chronic liver disease (CLD) were enrolled in the present study. The serum levels of GH, IGF-1, and IGF-binding protein 3 (IGFBP-3) were measured and their relationships with the histological severity of liver disease were assessed. To exclude age- and sex-related differences, the IGF-1 standard deviation score (IGF-1:SDS) was determined for each patient. Results With respect to the stage of fibrosis in patients with NAFLD, the serum GH levels were higher and the serum IGFBP-3 levels and IGF-1:SDSs were lower in patients with cirrhosis (grade F4 fibrosis) than in patients grade F1-F3 fibrosis; moreover, these differences were statistically significant (all p<0.01). The GH, IGF-1, and IGFBP-3 levels were not correlated with fibrosis in patients with HCV-related CLD. Furthermore, the GH levels were lower and the IGFBP-3 levels were significantly higher in patients with severe steatosis (S3) than in patients with mild to moderate steatosis (S1-S2) (p<0.05). Conclusion Increased GH levels and decreased IGF-1 and IGFBP-3 levels might contribute to the progression of NAFLD. The GH/IGF-1 axis may be important in the development of NAFLD, but not in patients with HCV-related CLD.


Data-Driven Rule Mining and Representation of Temporal Patterns in Physiological Sensor Data.
Mining and representation of qualitative patterns is a growing field in sensor data analytics. This paper leverages from rule mining techniques to extract and represent temporal relation of prototypical patterns in clinical data streams. The approach is fully data-driven, where the temporal rules are mined from physiological time series such as heart rate, respiration rate, and blood pressure. To validate the rules, a novel similarity method is introduced, that compares the similarity between rule sets. An additional aspect of the proposed approach has been to utilize natural language generation techniques to represent the temporal relations between patterns. In this study, the sensor data in the MIMIC online database was used for evaluation, in which the mined temporal rules as they relate to various clinical conditions (respiratory failure, angina, sepsis, …) were made explicit as a textual representation. Furthermore, it was shown that the extracted rule set for any particular clinical condition was distinct from other clinical conditions.


Does the frequency of HIV and STI testing among men who have sex with men in primary care adhere with Australian guidelines?
Australian guidelines recommend annual testing for HIV and sexually transmitted infections (STIs) for all men who have sex with men (MSM) and 3-6 monthly testing for those at higher risk as defined by behavioural criteria. We assessed HIV/STI re-testing rates among MSM attending primary care clinics. We conducted a retrospective follow-up of HIV negative MSM tested for HIV or STIs (chlamydia or syphilis) at four primary care clinics in the 9-month period: April to December 2006. Re-testing rates for these infections were calculated over 18 months. Logistic regression was undertaken to identify predictors of guideline adherence. Of the MSM requiring annual HIV testing according to the guidelines, the re-testing rates at 1 y were 35% (762/2163). Among the higher risk MSM, 6-monthly HIV re-testing rates were 15% (283/1862). Within the subgroup who reported 11 or more male sexual partners within the past 6 months, HIV re-testing rates within 6 months were 19%. Independent predictors of HIV re-testing within 6 months in higher-risk MSM were reporting 11 or more male sexual partners in the last 6 months (AOR 3.1, 95% CI 1.8 to 4.8); being born overseas (AOR 2.0, 95% CI 1.2 to 3.4); and previous HIV testing more than 12 months earlier (AOR 3.3, 95% CI 1.9 to 5.5). There is poor adherence to national guidelines that recommend regular re-testing of MSM for STIs, particularly among those at higher risk who require more frequent testing. Clinical strategies are urgently needed to encourage more frequent HIV/STI testing among MSM, especially in the higher risk subgroup.


A multilevel examination of gender differences in the association between features of the school environment and physical activity among a sample of grades 9 to 12 students in Ontario, Canada.
Creating school environments that support student physical activity (PA) is a key recommendation of policy-makers to increase youth PA. Given males are more active than females at all ages, it has been suggested that investigating gender differences in the features of the environment that associate with PA may help to inform gender-focused PA interventions and reduce the gender disparity in PA. The purpose of this cross-sectional study was to explore gender differences in the association between factors of the school environment and students' time spent in PA. Among a sample of 10781 female and 10973 male students in grades 9 to 12 from 76 secondary schools in Ontario, Canada, student- and school-level survey PA data were collected and supplemented with GIS-derived measures of the built environment within 1-km buffers of the 76 schools. Findings from the present study revealed significant differences in the time male and female students spent in PA as well as in some of the school- and student-level factors associated with PA. Results of the gender-specific multilevel analyses indicate schools should consider providing an alternate room for PA, especially for providing flexibility activities directed at female students. Schools should also consider offering daily physical education programming to male students in senior grades and providing PA promotion initiatives targeting obese male students. Although most variation in male and female students' time spent in PA lies between students within schools, there is sufficient between-school variation to be of interest to practitioners and policy-makers. More research investigating gender differentials in environment factors associated with youth PA are warranted.


The immunological basis of endotoxin-induced tumor regression. Requirement for T-cell-mediated immunity.
It was shown that although intravenous administration of bacterial endotoxin caused extensive hemorrhagic necrosis of four different syngeneic murine tumors, only two of these tumors subsequently underwent complete regression: the two that were shown to be immunogeneic as classically defined. An immunologic basis for endotoxin-induced regression was further indicated by the additional findings that regression, but not hemorrhagic necrosis, of the two immunogenic tumors failed to occur in mice that were immunodepressed by whole-body gamma-irradiation, or that were made T-cell deficient by thymectomy and irradiation. That endotoxin-induced regression is T-cell mediated was suggested by the findings that tumor regression was followed by a state of long-lived immunity to a tumor cell challenge implant, and with the possession by the host of T cells that were capable of passively transferring this state of immunity to normal recipients. It is concluded that although parenteral injection of endotoxin causes hemorrhagic necrosis of most solid murine tumors, it is only those tumors that are immunogenic enough to evoke the generation of T-cell-mediated immunity which subsequently go on to completely regress.


Prenatal and postnatal management of hyperprostaglandin E syndrome after genetic diagnosis from amniocytes.
To describe prenatal genetic diagnosis in hyperprostaglandin E syndrome (HPS) and the effect of indomethacin therapy on the course of the disease before birth and in the neonatal period. Mutational analysis of the ROMK channel gene (KCNJ1) from amniocytes by single-strand conformational analysis and direct sequencing. Review of the clinical and laboratory findings during pregnancy and the neonatal period in two siblings affected with HPS. Compound heterozygosity of the fetus in KCNJ1 (D74Y/P110L) confirmed the clinical diagnosis of HPS at 26 weeks of gestation. Indomethacin therapy from 26 to 31 weeks prevented further progression of polyhydramnios without major side effects. In contrast to the elder brother, who had been diagnosed at the age of 2 months, the neonatal course was uncomplicated. Hypovolemic renal failure after excessive renal loss of salt and water could be prevented and severe nephrocalcinosis did not occur. Genetic diagnosis of HPS and subsequent prenatal indomethacin therapy seems to have a beneficial effect on the natural course of HPS, especially progression of polyhydramnios; therefore, extreme prematurity could be prevented. Also, postnatally the early diagnosis allows the effective water and electrolyte substitution before severe volume depletion.


Simplifying switch to second-line antiretroviral therapy in sub Saharan Africa: predicted effect of using a single viral load to define efavirenz-based first-line failure.
Many individuals failing first-line antiretroviral therapy (ART) in sub-Saharan Africa never initiate second-line ART or do so after significant delay. For people on ART with a viral load more than 1000 copies/ml, the WHO recommends a second viral load measurement 3 months after the first viral load and enhanced adherence support. Switch to a second-line regimen is contingent upon a persistently elevated viral load more than 1000 copies/ml. Delayed second-line switch places patients at increased risk for opportunistic infections and mortality. To assess the potential benefits of a simplified second-line ART switch strategy, we use an individual-based model of HIV transmission, progression and the effect of ART which incorporates consideration of adherence and drug resistance, to compare predicted outcomes of two policies, defining first-line regimen failure for patients on efavirenz-based ART as either two consecutive viral load values more than 1000 copies/ml, with the second after an enhanced adherence intervention (implemented as per current WHO guidelines) or a single viral load value more than 1000 copies/ml. We simulated a range of setting-scenarios reflecting the breadth of the sub-Saharan African HIV epidemic, taking into account potential delays in defining failure and switch to second-line ART. The use of a single viral load more than 1000 copies/ml to define ART failure would lead to a higher proportion of persons with nonnucleoside reverse-transcriptase inhibitor resistance switched to second-line ART [65 vs. 48%; difference 17% (90% range 14-20%)], resulting in a median 18% reduction in the rate of AIDS-related death over setting scenarios (90% range 6-30%; from a median of 3.1 to 2.5 per 100 person-years) over 3 years. The simplified strategy also is predicted to reduce the rate of AIDS conditions by a median of 31% (90% range 8-49%) among people on first-line ART with a viral load more than 1000 copies/ml in the past 6 months. For a country of 10 million adults (and a median of 880 000 people with HIV), we estimate that this approach would lead to a median of 1322 (90% range 67-3513) AIDS deaths averted per year over 3 years. For South Africa this would represent around 10 215 deaths averted annually. As a step towards reducing unnecessary mortality associated with delayed second-line ART switch, defining failure of first-line efavirenz-based regimens as a single viral load more than 1000 copies/ml should be considered.


Acute Swedish Massage Monotherapy Successfully Remediates Symptoms of Generalized Anxiety Disorder: A Proof-of-Concept, Randomized Controlled Study.
Generalized anxiety disorder (GAD) is a prevalent and costly disorder for which many patients may prefer nontraditional treatment. A proof-of-concept study of was conducted to evaluate the acute effects of Swedish massage therapy (SMT) as a monotherapy for the treatment of subjects with GAD. A randomized, single-masked, clinical trial was conducted between March 2012 and May 2013 at the Mood and Anxiety Disorders Program of Emory University. Forty-seven currently untreated subjects with a DSM-IV diagnosis of GAD were randomly assigned to twice-weekly SMT versus a light touch control condition for 6 weeks. The primary outcome measure was reduction in Hamilton Anxiety Rating Scale (HARS) scores after 6 weeks of treatment for SMT versus light touch, as determined by mixed model repeated-measures analysis of 40 evaluable subjects. Mean HARS baseline scores were 20.05 (SD = 3.34) for SMT and 19.58 (SD = 4.90) for light touch. At week 6, the difference in mean (standard error of the mean [SEM]) HARS score reduction was 3.26 points (SMT: -11.67 [1.09]; light touch: -8.41 [1.01]; t₁₀₆ = -2.19; P = .030; effect size = -0.69). Treatment group differences were significant (P < .05) starting at the end of week 3. This first monotherapy trial suggests that a complementary and alternative manual therapy, SMT, is an effective acute treatment for GAD. ClinicalTrials.gov identifier: NCT01337713.


Cardiovascular haemodynamics and cardiac autonomic control in patients with subclinical and overt hyperthyroidism.
To characterize cardiac structure and function and cardiac autonomic control in patients with subclinical and overt hyperthyroidism. Thirty patients with subclinical hyperthyroidism and 30 with overt disease were selected from patients never previously treated for endocrinological disease in the outpatient clinic of our institution. Twenty normal individuals were studied as control group. Left ventricular structure and function and cardiac autonomic control were evaluated, respectively, by two-dimensional Doppler echocardiography and by 24-h Holter recording with heart rate variability analysis. Patients with overt hyperthyroidism showed greater values of left ventricular end-diastolic volume (P<0.05) and left ventricular mass (P<0.05) than patients with subclinical disease. In addition, the mean velocity of left ventricular fibre shortening (P<0.05) and left ventricular ejection fraction (P<0.05) were greater in patients with overt hyperthyroidism than in patients with subclinical disease. No difference in any of these parameters was detectable between normal subjects and patients with subclinical disease. The isovolumic relaxation period was shorter in patients with subclinical hyperthyroidism than in control individuals (P<0.05) and in patients with overt hyperthyroidism (P<0.05). As regards cardiac autonomic control, all time and frequency domain measures decreased progressively from control individuals to patients with subclinical hyperthyroidism and those with overt disease (P<0.001). Thyrotoxic patients show changes in left ventricular structure and increased echocardiographic indexes of myocardial contractility, whereas the only echocardiographic feature detectable in patients with subclinical hyperthyroidism is an increased velocity of left ventricular relaxation. Cardiac parasympathetic withdrawal is evident in patients with overt hyperthyroidism and in patients with subclinical disease.


Improving AutoDock Vina Using Random Forest: The Growing Accuracy of Binding Affinity Prediction by the Effective Exploitation of Larger Data Sets.
There is a growing body of evidence showing that machine learning regression results in more accurate structure-based prediction of protein-ligand binding affinity. Docking methods that aim at optimizing the affinity of ligands for a target rely on how accurate their predicted ranking is. However, despite their proven advantages, machine-learning scoring functions are still not widely applied. This seems to be due to insufficient understanding of their properties and the lack of user-friendly software implementing them. Here we present a study where the accuracy of AutoDock Vina, arguably the most commonly-used docking software, is strongly improved by following a machine learning approach. We also analyse the factors that are responsible for this improvement and their generality. Most importantly, with the help of a proposed benchmark, we demonstrate that this improvement will be larger as more data becomes available for training Random Forest models, as regression models implying additive functional forms do not improve with more training data. We discuss how the latter opens the door to new opportunities in scoring function development. In order to facilitate the translation of this advance to enhance structure-based molecular design, we provide software to directly re-score Vina-generated poses and thus strongly improve their predicted binding affinity. The software is available at http://istar.cse.cuhk.edu.hk/rf-score-3.tgz and http://crcm. marseille.inserm.fr/fileadmin/rf-score-3.tgz.


Anti-cancer effect and structural characterization of endo-polysaccharide from cultivated mycelia of Inonotus obliquus.
The endo-polysaccharide extracted from mycelia of Inonotus obliquus (Pers.:Fr.) Pil. (Hymenochaetaceae) is a specific activator of B cells and macrophages. However, the in vivo anti-cancer effects and the chemical structure of the endo-polysaccharide are unknown. We purified the endo-polysaccharide, investigated its anti-cancer effects via in vitro and in vivo assays, and performed a structural characterization. The endo-polysaccharide was extracted from I. obliquus mycelia cultivated in a 300-l pilot fermenter, followed by hot water extraction and ethanol precipitation. Purification was achieved by DEAE-cellulose ion-exchange chromatography and gel-permeation chromatography. Chemical analysis revealed that the purified endo-polysaccharide is an alpha-linked fucoglucomannan with a molecular weight of approximately 1,000 kDa. The anti-cancer activities of the endo-polysaccharide against various types of tumor cells were determined. No direct toxicity against either cancer or normal cells was observed. Intraperitoneal administration of the endo-polysaccharide significantly prolonged the survival rate of B16F10-implanted mice, resulting in a 4.07-fold increase in the survival rate at a dose of 30 mg/kg/day. After 60 days of feeding, approximately 67% of the initial number of mice survived with no tumor incidence based on macroscopic examination. These results indicate that the anti-cancer effect of endo-polysaccharide is not directly tumorcidal but rather is immuno-stimulating.


Primary and secondary prevention of liver cancer caused by HBV.
Primary cancer of the liver (hepatocellular carcinoma, HCC) is one of the most common cancers worldwide; HBV is the major cause of HCC. A vaccine that protects against HBV infection was invented in 1969 and is now one of the most commonly used vaccines. National vaccination programs have dramatically reduced the prevalence of HBV infection and carriers, with a concomitant decrease in the incidence of HCC in the vaccine-impacted populations. HBV vaccine is the first widely used cancer prevention vaccine; a second that protects against papilloma virus and cancer of the cervix has recently been introduced. Appropriate treatment of HBV carriers with antivirals can reduce the titers of HBV in their blood and thereby greatly reduce the risk of HCC and chronic liver disease. Further data are required to establish criterion for treatment to enable protocols for medical and prevention programs. There are other viral caused cancers and an understanding of their pathogenesis is an important future direction for research to reduce the human burden of cancer.


Factors influencing nurses' willingness to lead.
To identify factors influencing nurses' willingness to lead. Given the ageing workforce and the projected retirement of nurse leaders, there is a concern about nursing leadership shortages in the next decade. Several studies have shown that nurses are not interested in pursuing leadership positions, but studies investigating nurses' willingness to lead and related predictors remain limited. A workforce survey of 1,201 direct-care nurses was conducted in Oregon. Logistic regression modelling was used to identify factors influencing the likelihood of nurses' willingness to lead. Fifty-three percent of nurses were willing to pursue leadership roles. Years of experience, job burnout, the perception of the work environment, adequacy of leadership preparation, and the amount of salary and compensation were significant predictors of nurses' willingness to lead. Increasing nurses' participation in hospital affairs and providing adequate leadership preparation, parts of the work environment, prior to engaging them in leadership roles is recommended to improve their attitudes about leading. Recruitment of future nursing leaders should not be based solely on demographics such as age and gender. Rather, recruiters should focus on creating more favourable work environments in which to lead.


[The feasibility of at-home self-monitoring blood pressure in elderly hypertensive patients].
The goal of the SHEAF study is to determine whether self blood pressure measurement (SBPM) has a better cardiovascular prognostic value than office blood pressure (OBP) among French elderly (> or = 60 y) hypertensive patients (pts) followed-up by general practitioners. Baseline SBPM was performed over a 4-day period: every day a series of 3 consecutive measurements was requested in the morning (8:00 am) and in the evening (8:00 pm), using a validated device OMRON 705 CP. Measurements performed out of predefined morning and evening time (outside the 4:00-12:00 am range or the 4:00-12:00 pm range) were discarded as well as aberrant values. Pts were included in the study only if they exhibited at least 15 valid measurements with at least 6 in the morning and 6 in the evening. 5,649 pts were selected. 186 pts were excluded for age < 60 years. Thus SBPM analysis was performed for 5,463 pts: 2,687 men (49%) and 2,776 women (51%) aged 70 +/- 7 years. Only 252 pts (5%) were excluded for non valid SBPM (207 pts < 15 measurements, 106 pts < 6 measurements in the morning and 205 pts < 6 measurements in the evening). 5,211 pts (95%) with valid SBPM were included. The distribution of pts according to the number of measurements performed is the following: [table: see text] The number of measurements performed in the morning is highly related to the number of measurements performed in the evening. None of the following variables is significantly associated with the poor compliance of measurement protocol: age, gender, CV history, CV risk factors, hypertension duration. In a large cohort of elderly hypertensive living in the community, SBPM is easily performed both in the morning and in the evening by most of the pts. If the SHEAF study demonstrates the prognostic value of SBPM, this would provide the basis for the use of this measurement method by a majority of elderly hypertensives.


Residual lesions on computed tomography after intracerebral hemorrhage.
We investigated the residual abnormalities on computed tomography in a series of patients with proven intracerebral hemorrhage to determine whether the type of lesion is related to the site and size of the initial hematoma. In a partially prospective follow-up study, we studied computed tomographic scans of 42 patients with spontaneous intracerebral hemorrhage after 2-24 (median 9) months. Lobar hemorrhages had occurred in 20 patients; the other 22 hemorrhages were in the basal ganglia or thalamus. No residual lesions were found on seven scans (17%), despite residual handicap in three of these seven patients (slight, moderate, and moderately severe). In five cases, the scan showed only focal atrophy, and in two there were only focal calcifications. There were six patients with slit-like lesions (only after deep hemorrhages), 12 with rounded and isolated hypodense areas, and 10 with rounded hypodense areas connected to the ventricular system. The connection between the residual lesion and the ventricular system depended to a large extent on the size of the initial hematoma, but very little on whether it had initially ruptured into the ventricular system. A retrospective diagnosis of cerebral hemorrhage on radiological grounds can be made with confidence only in a small group of patients with slit-like lesions in the basal ganglia. This diagnosis is impossible in approximately one third of cerebral hemorrhages because the abnormalities are aspecific or have completely disappeared.


Encoding of naturalistic stimuli by local field potential spectra in networks of excitatory and inhibitory neurons.
Recordings of local field potentials (LFPs) reveal that the sensory cortex displays rhythmic activity and fluctuations over a wide range of frequencies and amplitudes. Yet, the role of this kind of activity in encoding sensory information remains largely unknown. To understand the rules of translation between the structure of sensory stimuli and the fluctuations of cortical responses, we simulated a sparsely connected network of excitatory and inhibitory neurons modeling a local cortical population, and we determined how the LFPs generated by the network encode information about input stimuli. We first considered simple static and periodic stimuli and then naturalistic input stimuli based on electrophysiological recordings from the thalamus of anesthetized monkeys watching natural movie scenes. We found that the simulated network produced stimulus-related LFP changes that were in striking agreement with the LFPs obtained from the primary visual cortex. Moreover, our results demonstrate that the network encoded static input spike rates into gamma-range oscillations generated by inhibitory-excitatory neural interactions and encoded slow dynamic features of the input into slow LFP fluctuations mediated by stimulus-neural interactions. The model cortical network processed dynamic stimuli with naturalistic temporal structure by using low and high response frequencies as independent communication channels, again in agreement with recent reports from visual cortex responses to naturalistic movies. One potential function of this frequency decomposition into independent information channels operated by the cortical network may be that of enhancing the capacity of the cortical column to encode our complex sensory environment.


Speeding up biphasic reactions with surface nanodroplets.
Biphasic chemical reactions compartmentalized in small droplets offer advantages, such as streamlined procedures for chemical analysis, enhanced chemical reaction efficiency and high specificity of conversion. In this work, we experimentally and theoretically investigate the rate for biphasic chemical reactions between acidic nanodroplets on a substrate surface and basic reactants in a surrounding bulk flow. The reaction rate is measured by droplet shrinkage as the product is removed from the droplets by the flow. In our experiments, we determine the dependence of the reaction rate on the flow rate and the solution concentration. The theoretical analysis predicts that the life time τ of the droplets scales with Peclet number Pe and the reactant concentration in the bulk flow cre,bulk as τ∝ Pe-3/2cre,bulk-1, in good agreement with our experimental results. Furthermore, we found that the product from the reaction on an upstream surface can postpone the droplet reaction on a downstream surface, possibly due to the adsorption of interface-active products on the droplets in the downstream. The time of the delay decreases with increasing Pe of the flow and also with increasing reactant concentration in the flow, following the scaling same as that of the reaction rate with these two parameters. Our findings provide insight for the ultimate aim to enhance droplet reactions under flow conditions.


Reexamining human origins in light of Ardipithecus ramidus.
Referential models based on extant African apes have dominated reconstructions of early human evolution since Darwin's time. These models visualize fundamental human behaviors as intensifications of behaviors observed in living chimpanzees and/or gorillas (for instance, upright feeding, male dominance displays, tool use, culture, hunting, and warfare). Ardipithecus essentially falsifies such models, because extant apes are highly derived relative to our last common ancestors. Moreover, uniquely derived hominid characters, especially those of locomotion and canine reduction, appear to have emerged shortly after the hominid/chimpanzee divergence. Hence, Ardipithecus provides a new window through which to view our clade's earliest evolution and its ecological context. Early hominids and extant apes are remarkably divergent in many cardinal characters. We can no longer rely on homologies with African apes for accounts of our origins and must turn instead to general evolutionary theory. A proposed adaptive suite for the emergence of Ardipithecus from the last common ancestor that we shared with chimpanzees accounts for these principal ape/human differences, as well as the marked demographic success and cognitive efflorescence of later Plio-Pleistocene hominids.


Comparative Analysis and Refinement of Human PSC-Derived Kidney Organoid Differentiation with Single-Cell Transcriptomics.
Kidney organoids derived from human pluripotent stem cells have great utility for investigating organogenesis and disease mechanisms and, potentially, as a replacement tissue source, but how closely organoids derived from current protocols replicate adult human kidney is undefined. We compared two directed differentiation protocols by single-cell transcriptomics of 83,130 cells from 65 organoids with single-cell transcriptomes of fetal and adult kidney cells. Both protocols generate a diverse range of kidney cells with differing ratios, but organoid-derived cell types are immature, and 10%-20% of cells are non-renal. Reconstructing lineage relationships by pseudotemporal ordering identified ligands, receptors, and transcription factor networks associated with fate decisions. Brain-derived neurotrophic factor (BDNF) and its cognate receptor NTRK2 were expressed in the neuronal lineage during organoid differentiation. Inhibiting this pathway improved organoid formation by reducing neurons by 90% without affecting kidney differentiation, highlighting the power of single-cell technologies to characterize and improve organoid differentiation.


Hippocampal replay of extended experience.
During pauses in exploration, ensembles of place cells in the rat hippocampus re-express firing sequences corresponding to recent spatial experience. Such "replay" co-occurs with ripple events: short-lasting (approximately 50-120 ms), high-frequency (approximately 200 Hz) oscillations that are associated with increased hippocampal-cortical communication. In previous studies, rats exploring small environments showed replay anchored to the rat's current location and compressed in time into a single ripple event. Here, we show, using a neural decoding approach, that firing sequences corresponding to long runs through a large environment are replayed with high fidelity and that such replay can begin at remote locations on the track. Extended replay proceeds at a characteristic virtual speed of approximately 8 m/s and remains coherent across trains of ripple events. These results suggest that extended replay is composed of chains of shorter subsequences, which may reflect a strategy for the storage and flexible expression of memories of prolonged experience.


Engineering Surfaces through Sequential Stop-Flow Photopatterning.
Solution-exchange lithography is a new modular approach to engineer surfaces via sequential photopatterning. An array of lenses reduces features on an inkjet-printed photomask and reproduces arbitrarily complex patterns onto surfaces. In situ exchange of solutions allows successive photochemical reactions without moving the substrate and affords access to hierarchically patterned substrates.


Multicentre stepped-wedge cluster randomised controlled trial of an antimicrobial stewardship programme in residential aged care: protocol for the START trial.
Antimicrobial resistance is a growing global health threat, driven by increasing inappropriate use of antimicrobials. High prevalence of unnecessary use of antimicrobials in residential aged care facilities (RACFs) has driven demand for the development and implementation of antimicrobial stewardship (AMS) programmes. The Stepped-wedge Trial to increase antibiotic Appropriateness in Residential aged care facilities and model Transmission of antimicrobial resistance (START) will implement and evaluate the impact of a nurse-led AMS programme on antimicrobial use in 12 RACFs. The START trial will implement and evaluate a nurse-led AMS programme via a stepped-wedge cluster randomised controlled trial design in 12 RACFs over 16 months. The AMS programme will incorporate education, aged care-specific treatment guidelines, documentation forms, and audit and feedback strategies that will target aged care staff, general practitioners, pharmacists, and residents and their families. The intervention will primarily focus on urinary tract infections, lower respiratory tract infections, and skin and soft tissue infections. RACFs will transition from control to intervention phases in random order, two at a time, every 2 months, with a 2-month transition, wash-in period. The primary outcome is the cumulative proportion of residents within each facility prescribed an antibiotic during each month and total days of antibiotic use per 1000 occupied bed days. Secondary outcomes include the number of courses of systemic antimicrobial therapy, antimicrobial appropriateness, antimicrobial resistant organisms, Clostridioides difficile infection, change in antimicrobial susceptibility profiles, hospitalisations and all-cause mortality. Analyses will be conducted according to the intention-to-treat principle. Ethics approval has been granted by the Alfred Hospital Human Research Ethics Committee (HREC/18/Alfred/591). Research findings will be disseminated through peer-reviewed publications, conferences and summarised reports provided to participating RACFs. NCT03941509.


Determining optimal planning target volume and image guidance policy for post-prostatectomy intensity modulated radiotherapy.
There is limited information available on the optimal Planning Target Volume (PTV) expansions and image guidance for post-prostatectomy intensity modulated radiotherapy (PP-IMRT). As the prostate bed does not move in a uniform manner, there is a rationale for anisotropic PTV margins with matching to soft tissue. The aim of this study is to find the combination of PTV expansion and image guidance policy for PP-IMRT that provides the best balance of target coverage whilst minimising dose to the organs at risk. The Cone Beam CT (CBCT) images (n = 377) of 40 patients who received PP-IMRT with daily online alignment to bony anatomy (BA) were reviewed. Six different PTV expansions were assessed: 3 published PTV expansions (0.5 cm uniform, 1 cm uniform, and 1 + 0.5 cm posterior) and 3 further anisotropic PTV expansions (Northern Sydney Cancer Centre (NSCC), van Herk, and smaller anisotropic). Each was assessed for size, bladder and rectum coverage and geographic miss. Each CBCT was rematched using a superior soft tissue (SST) and averaged soft tissue (AST) match. Potential geographic miss was assessed using all PTV expansions except the van Herk margin. The 0.5 cm uniform expansion yielded the smallest PTV (median volume = 222.3 cc) and the 1 cm uniform expansion yielded the largest (361.7 cc). The Van Herk expansion includes the largest amount of bladder (28.0 %) and rectum (36.0 %) and the 0.5 cm uniform expansion the smallest (17.1 % bladder; 10.2 % rectum). The van Herk PTV expansion had the least geographic miss with BA matching (4.2 %) and the 0.5 cm uniform margin (28.4 %) the greatest. BA matching resulted in the highest geographic miss rate for all PTVs, followed by SST matching and AST matching. Changing from BA to an AST match decreases potential geographic miss by half to two thirds, depending on the PTV expansion, to <10 % for all PTV expansions. When using the smaller anisotropic PTV expansion, AST matching would reduce the geographic miss rate from 21.0 % with BA matching down to 5.6 %. Our results suggest the optimal PTV expansion and image guidance policy for PP-IMRT is daily average soft tissue matching using CBCT scans with a small anisotropic PTV expansion of 0.5 cm in all directions apart from a 1 cm expansion in the anterior-posterior direction in the upper prostate bed. Care must be taken to ensure adequate training of Radiation Therapists to perform soft tissue matching with CBCT scans.


Expression and Characteristics of Two Glucose-Tolerant GH1 β-glucosidases From Actinomadura amylolytica YIM 77502T for Promoting Cellulose Degradation.
The bioconversion of lignocellulose in various industrial processes, such as biofuel production, requires the degradation of cellulose. Actinomadura amylolytica YIM 77502T is an aerobic, Gram-positive actinomycete that can efficiently degrade crystalline cellulose by extracellular cellulases. Genomic analysis of A. amylolytica identified 9 cellulase and 11 β-glucosidase genes that could potentially encode proteins that digest cellulose. Extracellular proteome characterization of A. amylolytica cell-free culture supernatant by liquid chromatography tandem mass spectrometry analysis revealed that 4 of these cellulases and 2 of these β-glucosidases functioned during cellulose hydrolysis. Thin-layer chromatography analysis revealed extracellular β-glucosidases play a major role in carboxyl methyl cellulose (CMC) degradation of products in culture supernatants. In this study, 2 of the identified secreted β-glucosidases, AaBGL1 and AaBGL2, were functionally expressed in Escherichia coli and found to have β-glucosidase activity with wide substrate specificities, including for p-nitrophenyl β-D-glucopyranoside (pNPG), p-nitrophenyl-beta-D-cellobioside (pNPC), and cellobiose. Moreover, AaBGL1 and AaBGL2 had high tolerances for glucose. After adding these β-glucosidases to commercial cellulases, the degradation rates of CMC, Avicel, birch sawdust, and corncob powder increased by 37, 42, 33, and 9%, respectively. Overall, this work identifies an alternative potential source of β-glucosidases with potential applications in commercial cellulose utilization and the bioenergy industry.


TTK Inhibitors as a Targeted Therapy for CTNNB1 (β-catenin) Mutant Cancers.
The spindle assembly checkpoint kinase TTK (Mps1) is a key regulator of chromosome segregation and is the subject of novel targeted therapy approaches by small-molecule inhibitors. Although the first TTK inhibitors have entered phase I dose escalating studies in combination with taxane chemotherapy, a patient stratification strategy is still missing. With the aim to identify a genomic biomarker to predict the response of tumor cells to TTK inhibitor therapy, we profiled a set of preclinical and clinical TTK inhibitors from different chemical series on a panel of 66 genetically characterized cell lines derived from different tumors (Oncolines). Cell lines harboring activating mutations in the CTNNB1 gene, encoding the Wnt pathway signaling regulator β-catenin, were on average up to five times more sensitive to TTK inhibitors than cell lines wild-type for CTNNB1 The association of CTNNB1-mutant status and increased cancer cell line sensitivity to TTK inhibition was confirmed with isogenic cell line pairs harboring either mutant or wild-type CTNNB1 Treatment of a xenograft model of a CTNNB1-mutant cell line with the TTK inhibitor NTRC 0066-0 resulted in complete inhibition of tumor growth. Mutations in CTNNB1 occur at relatively high frequency in endometrial cancer and hepatocellular carcinoma, which are known to express high TTK levels. We propose mutant CTNNB1 as a prognostic drug response biomarker, enabling the selection of patients most likely to respond to TTK inhibitor therapy in proof-of-concept clinical trials. Mol Cancer Ther; 16(11); 2609-17. ©2017 AACR.


Strain localization in a shear transformation zone model for amorphous solids.
We model a sheared disordered solid using the theory of shear transformation zones (STZs). In this mean-field continuum model the density of zones is governed by an effective temperature that approaches a steady state value as energy is dissipated. We compare the STZ model to simulations by Shi [Phys. Rev. Lett. 98, 185505 (2007)], finding that the model generates solutions that fit the data, exhibit strain localization, and capture important features of the localization process. We show that perturbations to the effective temperature grow due to an instability in the transient dynamics, but unstable systems do not always develop shear bands. Nonlinear energy dissipation processes interact with perturbation growth to determine whether a material exhibits strain localization. By estimating the effects of these interactions, we derive a criterion that determines which materials exhibit shear bands based on the initial conditions alone. We also show that the shear band width is not set by an inherent diffusion length scale but instead by a dynamical scale that depends on the imposed strain rate.


Morphogenesis of the C. elegans hermaphrodite uterus.
We have undertaken electron micrographic reconstruction of the Caenorhabditis elegans hermaphrodite uterus and determined the correspondence between cells defined by their lineage history and differentiated cell types. In this organ, many cells do not move during morphogenesis and the cell lineage may function to put cells where they are needed. Differentiated uterine cell types include the toroidal ut cells that make structural epithelium, and specialized utse and uv cells that make the connection between the uterus and the vulva. A cell fate decision in which the anchor cell (AC) induces adjacent ventral uterine intermediate precursor cells to adopt the pi fate, rather than the ground state rho, has profound consequences for terminal differentiation: all pi progeny are directly involved in making the uterine-vulval connection whereas all rho progeny contribute to ut toroids or the uterine-spermathecal valve. In addition to specifying certain uterine cell fates, the AC also induces the vulva. Its multiple inductions thereby function to coordinate the connection of an internal to an external epithelium. The AC induces the pi cells and ultimately fuses with a subset of their progeny. This is an example of reciprocal cell-cell interaction that can be studied at single cell resolution. The AC is thus a transitory cell type that plays a pivotal role in organizing the morphogenesis of the uterine-vulval connection.


Hypothyroidism with concurrent Lyme disease.
Lyme disease can be seen as localized, disseminated, acute, or chronic and can mimic other, more serious diseases. Even though it is a multisystemic illness, very few spirochetes are present; yet, once established in the host, it can persist for years. The antibody response is slow and variable, and the spirochete is difficult to isolate from clinical specimens, even those obtained from the pathognomonic skin lesion. These variables, together with nonspecific symptoms, make the diagnosis of Lyme disease difficult. The author describes an unusual case of Lyme disease superimposed on severe primary hypothyroidism in which the thyroid disorder was so advanced and pronounced that the diagnosis of Borrelia infection could easily have been missed.


Water dissociation on K2O-pre-adsorbed transition metals: a systematic theoretical study.
It is imperative to regulate O-H bond cleavage on metal surfaces with a pre-adsorbed K2O promoter in heterogeneous catalysis. Density functional theory (DFT) calculations have been performed to explore the adsorption and dissociation of water on K2O-pre-adsorbed transition metal surfaces (Au, Ag, Cu, Ni, Pt, Rh, Ir, Pd, Ru, Co and Fe) as compared with those on clean and K-pre-adsorbed metal surfaces. The calculation results indicate that the presence of K2O species significantly promotes water dissociation and the promoting effect depends on the adsorption strength of K2O, namely, the more strongly K2O binds to the metal surface, the less promoting effect it has on the water O-H bond cleavage. Based on geometrical and electronic analysis, the stronger promoting effect of K2O than K on water dissociation on the given metal surfaces can be attributed to stronger attractive electrostatic interactions between OH and the dissociating H of H2O at the TSs as well as between O of H2O and K of K2O at the ISs on K2O-pre-adsorbed surfaces compared with those on K-pre-covered surfaces. Moreover, the additional hydrogen bond interaction between H and Oad of K2O at the ISs on Cu/Ag/Au and Fe/Co/Ni metals would be responsible for the much greater promoting effect of K2O than K on these metal surfaces, while there is a slightly greater promoting effect of K2O on the remaining metal surfaces. From the above analysis, we expect our studies can provide profound understanding of the nature of the promoting effect of K2O on O-H bond scission.


Reflections on the biology, morphology and ecology of the Macrochelidae.
The Macrochelidae is a cosmopolitan family of predatory mesostigmatic mites, many of which occupy specialized and often unstable habitats. Most known species have adapted to life in dung deposits where prey is plentiful and the potential exists for rapid population growth. Phoresy on co-occurring flying insects plays a vital role in assuring niche continuity for macrochelids in these ephemeral substrates. A brief general review of some of the earlier highlights of macrochelid research is presented, followed by a discussion of the emergence of phoresy as a major survival strategy in the Macrochelidae associated with dung beetles. Special emphasis is placed on the behavioural and chemical mechanisms that mediate phoretic specificity of macrochelid species in the unique n-dimensional universes of their scarab hosts. Phylogenetic analysis of selected phoretic and non-phoretic macrochelid taxa has shown a strong correlation between phoretic state and evolutionary position, indicating that an increasing commitment to phoresy in the Macrochelidae is correlated with an advance from early derivative to terminal taxa. Laboratory and field observations have confirmed the importance of chemical, behavioural and ecological factors in maintaining the integrity of the relationship between phoretically specific macrochelids and their dung beetle hosts.


Perirhinal cortex ablation impairs configural learning and paired-associate learning equally.
Combined damage to the perirhinal and entorhinal cortex has been implicated in the formation of stimulus-stimulus associative memories. We show in this article that relative to three normal controls three cynomolgus monkeys with ablations restricted to the perirhinal cortex were impaired on a visual paired associate learning task in which subjects had to learn which of two visual stimuli were associated with a cue stimulus. The subjects with perirhinal cortex ablations also showed an impairment of a similar magnitude on a visual configural learning task in which they had to learn which of two configurations of visual stimuli were associated with food-reward. The stimuli in both tasks were comprised of alphanumeric characters presented upon a touch-screen. Both groups made fewer errors on the configural learning task than on the paired associate learning task. We suggest that performance on both tasks relies critically on the perirhinal cortex due to the specialization of the perirhinal cortex in processing knowledge about objects. We argue that the specializations of this system and of other memory systems such as the hippocampal-fornix spatial/episodic memory system, are conferred by the specialization of their anatomical connections to other structures. We reject the notion that there are specific memory processes such as the hippocampal based configural associative system that was proposed to be critical for configural associative learning.


Fractionation of polymeric procyanidins from lowbush blueberry and quantification of procyanidins in selected foods with an optimized normal-phase HPLC-MS fluorescent detection method.
The polymeric procyanidins were fractionated from lowbush blueberry on a Sephadex LH-20 column. The degree of polymerization (DP) for the polymers was determined by thiolysis to be in a range of 19.9 to 114.1. Normal-phase HPLC analysis indicated that the polymeric procyanidins did not contain oligomeric procyanidins with DP < 10. The polymers eluted as a single peak at the end of the chromatogram. The normal-phase HPLC gradient was modified to improve the separation of procyanidin monomers through decamers and to elute all the polymers beyond those as a distinct peak. Monomers through decamers were quantified individually. All the polymers (DP > 10) were quantified using a mixture of purified polymers as an external standard. Polymers were found to be the dominant procyanidins in brown sorghum bran, cranberry, and blueberry. Thiolysis of the polymer peaks indicated that epicatechin was present as extension units in these foods, however, the composition of terminal units varied considerably between catechin and epicatechin, or an A-type dimer linkage in the case of cranberry.


Masticatory muscle activity during deliberately performed oral tasks.
The aim of this study was to investigate masticatory muscle activity during deliberately performed functional and non-functional oral tasks. Electromyographic (EMG) surface activity was recorded unilaterally from the masseter, anterior temporalis and suprahyoid muscles in 11 subjects (5 men, 6 women; age = 34.6 +/- 10.8 years), who were accurately instructed to perform 30 different oral tasks under computer guidance using task markers. Data were analyzed by descriptive statistics, repeated measurements analysis of variance (ANOVA) and hierarchical cluster analysis. The maximum EMG amplitude of the masseter and anterior temporalis muscles was more often found during hard chewing tasks than during maximum clenching tasks. The relative contribution of masseter and anterior temporalis changed across the tasks examined (F 5.2; p < or = 0.001). The masseter muscle was significantly (p < or = 0.05) more active than the anterior temporalis muscle during tasks involving incisal biting, jaw protrusion, laterotrusion and jaw cupping, the difference being statistically significant (p < or = 0.05). The anterior temporalis muscle was significantly (p < or = 0.01) more active than the masseter muscle during tasks performed in intercuspal position, during tooth grinding, and during hard chewing on the working side. Based upon the relative contribution of the masseter, anterior temporalis, and suprahyoid muscles, the investigated oral tasks could be grouped into six separate clusters. The findings provided further insight into muscle- and task-specific EMG patterns during functional and non-functional oral behaviors.


Response of leaf ontogeny and photosynthetic activity to reproductive growth in cotton.
This study was conducted to determine if reproductive growth in cotton (Gossypium hirsutum L.) affects concurrent leaf development. Apparent photosynthesis (AP), stomatal conductance (Cs), soluble protein (SP), ribulose bisphosphate carboxylase (RuBisCO), and chlorophyll (Chl) were monitored in four main-stem cotton leaves which emerged at approximately 2 week intervals. The leaf which emerged during vegetative growth (48 days after planting) had higher AP, SP, and RuBisCO levels than that present in any leaves which emerged during fruit development. The last leaf studied (89 days after planting) was still present after boll maturation was completed and exhibited a rejuvenation in AP, SP, RuBisCO, and Chl starting at 30 days after leaf emergence. At 96 days after planting, the P700 Chl a-protein complex (PSI) was virtually absent from the leaves that emerged at 48 and 62 days after planting. The light harvesting Chl a/b complex was still present in these leaves, indicating greater degradation of PSI. The data emphasize the influence of developing fruit on concurrently developing leaves, an effect which was alleviated after boll maturation was completed. The declining AP per unit leaf area and smaller leaf size at the top of the plant results in a reduced photosynthetic potential of successively later emerging leaves. This reduction in leaf AP is consistent with earlier reported seasonal canopy photosynthesis patterns.


A nonribosomal landscape in the nucleolus revealed by the stem cell protein nucleostemin.
Nucleostemin is a p53-interactive cell cycle progression factor that shuttles between the nucleolus and nucleoplasm, but it has no known involvement in ribosome synthesis. We found the dynamic properties of nucleostemin differed strikingly from fibrillarin (a protein directly involved in rRNA processing) both in response to rRNA transcription inhibition and in the schedule of reentry into daughter nuclei and the nucleolus during late telophase/early G1. Furthermore, nucleostemin was excluded from the nucleolar domains in which ribosomes are born--the fibrillar centers and dense fibrillar component. Instead it was concentrated in rRNA-deficient sites within the nucleolar granular component. This finding suggests that the nucleolus may be more subcompartmentalized than previously thought. In support of this concept, electron spectroscopic imaging studies of the nitrogen and phosphorus distribution in the nucleolar granular component revealed regions that are very rich in protein and yet devoid of nucleic acid. Together, these results suggest that the ultrastructural texture of the nucleolar granular component represents not only ribosomal particles but also RNA-free zones populated by proteins or protein complexes that likely serve other functions.


Sharing sensitive health information through social media in the Arab world.
Sharing daily activities on social media has become a part of our lifestyle, but little is known about sharing sensitive health information in the Arab world. The objective of this study is to explore how social media users in the Arab world share sensitive health information through Facebook. A retrospective qualitative analysis was used in the study. A total of 110 Facebook groups, related to HIV, sickle cell and depression were screened between 5 June and 1 December 2014. Forty four Facebook groups met the inclusion criteria. 28 471 posts were extracted, of which 649 met inclusion criteria. Forty two percent of health information exchanged were related to HIV, 34% to depression and 24% to sickle cell diseases. The majority of postings were from Egypt 21.1%, Saudi Arabia 20%, Algeria 10% and Libya 9.2%. Male posts were 54.2% while 45.8% were posted by females. Individuals utilized Facebook groups to share personal experiences of their disease 31%, in addition to being used for seeking queries 13.6%, offering explicit advice 8.3%, reporting signs and symptoms of the disease 7.3% and posting their communication with the health-care provider 6.6%. Users in the Arab world use social media to exchange sensitive health information, which could have serious implications regarding the privacy of the information shared with other members of the group. On the other hand, sharing health information could have positive effects for patients, such as sharing disease experiences and peer support. However, more work is needed to ensure that Facebook users in the Arab world are aware of the potential consequences of sharing sensitive health information through social media.


The behavioral ecology of cultural psychological variation.
Recent work has documented a wide range of important psychological differences across societies. Multiple explanations have been offered for why such differences exist, including historical philosophies, subsistence methods, social mobility, social class, climactic stresses, and religion. With the growing body of theory and data, there is an emerging need for an organizing framework. We propose here that a behavioral ecological perspective, particularly the idea of adaptive phenotypic plasticity, can provide an overarching framework for thinking about psychological variation across cultures and societies. We focus on how societies vary as a function of six important ecological dimensions: density, relatedness, sex ratio, mortality likelihood, resources, and disease. This framework can: (a) highlight new areas of research, (b) integrate and ground existing cultural psychological explanations, (c) integrate research on variation across human societies with research on parallel variations in other animal species, (d) provide a way for thinking about multiple levels of culture and cultural change, and (e) facilitate the creation of an ecological taxonomy of societies, from which one can derive specific predictions about cultural differences and similarities. Finally, we discuss the relationships between the current framework and existing perspectives. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Smoking among Lebanese medical students: Prevalence and attitudes.
The tobacco epidemic is a major public health threat facing the world. Tobacco dependence is recognized as the greatest preventable cause of disease and death. Medical students are in key position influencing future tobacco cessation programs. The primary objective of this study is to evaluate the prevalence of smoking among medical students across Lebanon and their smoking attitudes. It also investigates their attitude toward smoking, showing where they really stand on this major public health issue. This study helps better tackle anti-smoking campaigns among both physicians and patients. This cross-sectional study was conducted by sending a questionnaire to currently enrolled medical students at all seven medical schools in Lebanon. The 32-item questionnaire was used, comprised three sections assessing sociodemographic characteristics, smoking habits, and attitudes toward smoking among Lebanese medical students. The questionnaire was launched online on Limesurvey to retain anonymity. The data were then transferred to Statistical Package for Social Sciences for analysis. Data were expressed as percentages for discrete variables and as mean ± standard deviation for continuous variables. One hundred sixty-three complete responses remained of the 182 obtained responses. Forty-two of the total 163 students identified themselves as either daily or occasional smokers yielding a prevalence of 25.8%. Smokers were less likely to ask patients about their smoking habit and to counsel them about smoking cessation. Almost one-third of smokers felt that they had no obligations toward the society. Approximately 1 in 4 Lebanese medical students is a smoker. Students who smoke are less likely to ask patients about their smoking habits and to counsel them on smoking cessation. This is a major drawback in the fight against tobacco. This calls for better education of our future doctors on smoking cessation to decrease the smoking burden on our Lebanese society and worldwide.


Mammography Screening Beliefs and Knowledge among a Multi-ethnic Sample of Low-income, Uninsured Women.
The purpose of this study was to examine screening mammography prevalence and its associated beliefs among a multi-ethnic sample of low-income, uninsured women. Data pertaining to the sample's demographic characteristics, mammography screening history and beliefs, and knowledge on recommended screening age were analyzed (n=533). Overall, 22.1% of the participants had never been screened. Black women were more likely than others to have never been screened, White women were more likely to be overdue, and Hispanic women were more likely to report recent screening. Fear of not knowing what will be done during mammography consistently predicted screening among the racial/ethnic groups. Concerns about "people doing mammograms being rude to women" had the highest negative correlation with mammography among Hispanic women. A majority of the sample believed that screening should begin at age 40. Interventions to increase screening mammography must incorporate information about the screening procedure and be sensitive to cultural differences in screening barriers.


Incorporating uncertainty of management costs in sensitivity analyses of matrix population models.
The importance of accounting for economic costs when making environmental-management decisions subject to resource constraints has been increasingly recognized in recent years. In contrast, uncertainty associated with such costs has often been ignored. We developed a method, on the basis of economic theory, that accounts for the uncertainty in population-management decisions. We considered the case where, rather than taking fixed values, model parameters are random variables that represent the situation when parameters are not precisely known. Hence, the outcome is not precisely known either. Instead of maximizing the expected outcome, we maximized the probability of obtaining an outcome above a threshold of acceptability. We derived explicit analytical expressions for the optimal allocation and its associated probability, as a function of the threshold of acceptability, where the model parameters were distributed according to normal and uniform distributions. To illustrate our approach we revisited a previous study that incorporated cost-efficiency analyses in management decisions that were based on perturbation analyses of matrix population models. Incorporating derivations from this study into our framework, we extended the model to address potential uncertainties. We then applied these results to 2 case studies: management of a Koala (Phascolarctos cinereus) population and conservation of an olive ridley sea turtle (Lepidochelys olivacea) population. For low aspirations, that is, when the threshold of acceptability is relatively low, the optimal strategy was obtained by diversifying the allocation of funds. Conversely, for high aspirations, the budget was directed toward management actions with the highest potential effect on the population. The exact optimal allocation was sensitive to the choice of uncertainty model. Our results highlight the importance of accounting for uncertainty when making decisions and suggest that more effort should be placed on understanding the distributional characteristics of such uncertainty. Our approach provides a tool to improve decision making.


Effects of porous media preparation on bacteria transport through laboratory columns.
Bacterial and colloid transport experiments related to environmental systems are typically performed in the laboratory, with sand often used as the porous media. In order to prepare the sand, mechanical sieving is frequently used to tighten the sand grain size distribution. However, mechanical sieving has been reported to provide insufficient repeatability between identical colloidal transport experiments. This work examined the deficiencies of mechanical sieving with respect to bacterial transport through sand columns. It was found that sieving with standard brass sieves (1) contaminates the sand with copper and zinc as a linear function of sieving time and (2) inefficiently sizes sand grains below 300 microm (the largest size examined in this study) due to rapid clogging of the sieves. A procedure was developed that allows utilization of brass sieves for sizing the sand grains and removes the metal contamination introduced from the sieves. Bacterial transport experiments utilizing this column preparation procedure gave repeatable breakthrough curves. Further examination of the effects of these treatments on bacterial transport showed interesting results. First, it was found that the metal contamination did not affect the clean-bed bacterial transport. Second. it was found that variations of the column flushing procedure did not alter the clean-bed breakthrough of the bacteria, but did alter the inter-particle blocking. Finally, it was found that the shape of the sand grains (oblong vs. rounded) significantly alters the bacterial transport. with the transport being dominated by the smallest dimension of the oblong grains.


Substance use service availability in HIV treatment programs: Data from the global IeDEA consortium, 2014-2015 and 2017.
Substance use is common among people living with HIV and has been associated with suboptimal HIV treatment outcomes. Integrating substance use services into HIV care is a promising strategy to improve patient outcomes. We report on substance use education, screening, and referral practices from two surveys of HIV care and treatment sites participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. HIV care and treatment sites participating in IeDEA are primarily public-sector health facilities and include both academic and community-based hospitals and health facilities. A total of 286 sites in 45 countries participated in the 2014-2015 survey and 237 sites in 44 countries participated in the 2017 survey. We compared changes over time for 147 sites that participated in both surveys. In 2014-2015, most sites (75%) reported providing substance use-related education on-site (i.e., at the HIV clinic or the same health facility). Approximately half reported on-site screening for substance use (52%) or referrals for substance use treatment (51%). In 2017, the proportion of sites providing on-site substance use-related education, screening, or referrals increased by 9%, 16%, and 8%, respectively. In 2017, on-site substance use screening and referral were most commonly reported at sites serving only adults (compared to only children/adolescents or adults and children/adolescents; screening: 86%, 37%, and 59%, respectively; referral: 76%, 47%, and 46%, respectively) and at sites in high-income countries (compared to upper middle income, lower middle income or low-income countries; screening: 89%, 76%, 68%, and 45%, respectively; referral: 82%, 71%, 57%, and 34%, respectively). Although there have been increases in the proportion of sites reporting substance use education, screening, and referral services across IeDEA sites, gaps persist in the integration of substance use services into HIV care, particularly in relation to screening and referral practices, with reduced availability for children/adolescents and those receiving care within resource-constrained settings.


A systematic review of population-based studies of infective endocarditis.
We sought to summarize and critically appraise the literature on the epidemiology of infective endocarditis (IE) in the general population. We retrieved population-based IE surveys by searching MEDLINE and EMBASE. Two reviewers independently extracted relevant data. We performed a metaregression to determine if temporal trends of IE characteristics exist. Fifteen population-based investigations with 2,371 IE cases from seven countries (Denmark, France, Italy, the Netherlands, Sweden, United Kingdom, and United States) from 1969 to 2000 were eligible. Different case definitions and procedures were used to capture all IE cases, including census of existing diagnoses, record-linkage system, and direct contact survey. In the unadjusted regression, there was a decline in the proportion of IE patients with underlying rheumatic heart disease (RHD; 12%; 95% confidence interval [CI], - 21 to - 3%; p = 0.01) and an increase in the proportion of patients undergoing valve surgery (9%; 95% CI, 3 to 16%) per decade. After adjusting for country, the decline in IE cases with underlying RHD became nonsignificant, but the proportions of IE patients undergoing valve surgery increased 7% per decade (95% CI, - 4 to 14%; p = 0.06), and those with underlying prosthetic valve increased 7% per decade (95% CI, - 1 to 16%; p = 0.07). There were no significant temporal trends in the causative organisms. Evidence from well-planned, representative IE epidemiologic surveys is scarce in many countries. Available studies suggest a changing distribution of underlying valvular heart disease in patients with IE and an increase in its surgical treatment.


Characterizing Long COVID: Deep Phenotype of a Complex Condition.
Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or "long COVID"), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies. The Human Phenotype Ontology (HPO) is a widely used standard for exchange and analysis of phenotypic abnormalities in human disease but has not yet been applied to the analysis of COVID-19. We identified 303 articles published before April 29, 2021, curated 59 relevant manuscripts that described clinical manifestations in 81 cohorts three weeks or more following acute COVID-19, and mapped 287 unique clinical findings to HPO terms. We present layperson synonyms and definitions that can be used to link patient self-report questionnaires to standard medical terminology. Long COVID clinical manifestations are not assessed consistently across studies, and most manifestations have been reported with a wide range of synonyms by different authors. Across at least 10 cohorts, authors reported 31 unique clinical features corresponding to HPO terms; the most commonly reported feature was Fatigue (median 45.1%) and the least commonly reported was Nausea (median 3.9%), but the reported percentages varied widely between studies. Translating long COVID manifestations into computable HPO terms will improve analysis, data capture, and classification of long COVID patients. If researchers, clinicians, and patients share a common language, then studies can be compared/pooled more effectively. Furthermore, mapping lay terminology to HPO will help patients assist clinicians and researchers in creating phenotypic characterizations that are computationally accessible, thereby improving the stratification, diagnosis, and treatment of long COVID. U24TR002306; UL1TR001439; P30AG024832; GBMF4552; R01HG010067; UL1TR002535; K23HL128909; UL1TR002389; K99GM145411.


[Dietary exposure assessment of some important Fusarium toxins in cereal-based products in China].
To elucidate the dietary exposure of Chinese populations to deoxynivalenol (DON), nivalenol (NIV) and zearalenone (ZEN). Ten Fusarium toxins including DON, NIV, ZEN in domestic wheat flour and corn-based products harvested and collected in 2009 were analyzed by UPLC-MS/MS. Dietary intake assessments of human exposure to DON, NIV and ZEN were carried out in combination of national food consumption data with toxin concentration data by deterministic estimate method. (1) There are 2.5% adults and 10% children with the dietary exposure to DON exceeding the tolerable daily intake (TDI) on the basis of the average food consumption. At the 75th percentile food consumption level, the dietary exposure of populations to DON was higher than its TDI, 1.72 and 2.02 times (adults) as well as 1.19 and 1.09 times higher than TDI (children), respectively, based on the higher DON exposure (adults : P90 for wheat flour and P97. 5 for corn-based products, children: P50 for wheat flour and P75 for corn-based products). At the average toxin concentration, children with the high consumption level (90th, 97. 5th and 99th percentile) of either wheat flour or corn-based products, the dietary exposure to DON exceed the TDI, 1.81 to 3.17 times (wheat flour) and 1.47 - 3.97 times (corn-based products) higher than TDI, respectively. The dietary exposure of adults to ZEN exceed the TDI, based on the average food consumption data and higher ZEN level (P99), the 75th consumption data combined with P97. 5th toxin concentration, as well as 90th percentile of both food consumption data and ZEN concentration, respectively. There are 1%, 2.5%, 25%, 25% and 50% populations of children exposed ZEN higher than TDI, respectively at the 50th, 75th, 90th, 97. 5th and 99th percentile of food consumption data. (2) The level of concern (LOC) of DON in wheat flour calculated with high consumption data (90th, 97. 5th and 99th percentile) for all populations as well as DON and ZEN in corn-based products calculated with high consumption data (adults: 99th percentile, children: 97. 5th and 99th percentile) were lower than their average concentrations in above cereals. (3) No matter adults or children, the maximum daily safe intake of both wheat flour and corn-based products with high concentration of DON (97. 5th and 99th percentile, and 90th else for children) were lower than their own average food consumption data. For adults, the maximum daily safe intake of corn-based products with high ZEN contamination level (99th percentile) was lower than the average amount of corn-based products consumption. While, the maximum daily safe intake of both wheat flour and corn-based products derived from high ZEN concentration (97.5th and 99th percentile) for children were lower than their own average food consumption. Children dietary exposure to DON, NIV and ZEN was higher than adults. Children are the populations at the high risk of dietary exposure to these three mycotoxins. The risk to health caused by long-term consumption of wheat flour and corn-based products heavily contaminated with such high concentration of DON and ZEN was relatively high. The present tolerance limit for DON and ZEN in foods implemented in China should be revised on the basis of assessment results.


Evaluation of age-specific causes of death in the context of the Italian longevity transition.
In many low-mortality countries, life expectancy at birth increased steadily over the last century. In particular, both Italian females and males benefited from faster improvements in mortality compared to other high-income countries, especially from the 1960s, leading to an exceptional increase in life expectancy. However, Italy has not become the leader in longevity. Here, we investigate life expectancy trends in Italy during the period 1960-2015 for both sexes. Additionally, we contribute to the existing literature by complementing life expectancy with an indicator of dispersion in ages at death, also known as lifespan inequality. Lifespan inequality underlies heterogeneity over age in populating health improvements and is a marker of uncertainty in the timing of death. We further quantify the contributions of different age groups and causes of death to recent trends in life expectancy and lifespan inequality. Our findings highlight the contributions of cardiovascular diseases and neoplasms to the recent increase in life expectancy but not necessarily to the decrease in lifespan inequality. Our results also uncover a more recent challenge across Italy: worsening mortality from infectious diseases and mortality at older age.


A phase II study of sorafenib in patients with chemo-naive castration-resistant prostate cancer.
The purpose of this trial was to evaluate the antitumor activity of sorafenib, a multikinase inhibitor of cell proliferation and angiogenesis, in patients with castration-resistant prostate cancer. This was a multicenter, two-stage, phase II study. Sorafenib 400 mg was administered orally twice daily continuously. Primary end point was prostate-specific antigen (PSA) 'response' defined as a > or =50% decrease for > or =4 weeks. In all, 28 patients were enrolled. Eastern Cooperative Oncology Group performance status was zero or one in 19 and 9 patients. Two patients had no metastases, and 26 had bone and/or lymph node disease. A median of two cycles (range 1-8) was delivered. Adverse events were typical for sorafenib. The PSA response rate was 3.6% [95% confidence interval (CI) 0.1% to 18.3%] with response occurring in one patient (baseline = 10 000 and nadir = 1643 microg/l). No measurable disease responses occurred in eight patients. Time to PSA progression was 2.3 months (95% CI 1.8-6.4). Of 16 patients who discontinued sorafenib and then did not receive any immediate therapy, 10 had postdiscontinuation PSA declines of 7%-52%. Sorafenib has limited activity using current PSA criteria. The declines in PSA observed on treatment discontinuation indicate an effect on PSA production/secretion. Further study may be warranted but needs to consider the limitations of PSA as an indicator of progression and response.


Metoclopramide for acute migraine: a dose-finding randomized clinical trial.
Intravenous metoclopramide is effective as primary therapy for acute migraine, but the optimal dose of this medication is not yet known. The objective of this study is to compare the efficacy and safety of 3 different doses of intravenous metoclopramide for the treatment of acute migraine. This was a randomized, double-blind, dose-finding study conducted on patients who presented to our emergency department (ED) meeting International Classification of Headache Disorders criteria for migraine without aura. We randomized patients to 10, 20, or 40 mg of intravenous metoclopramide. We coadministered diphenhydramine to all patients to prevent extrapyramidal adverse effects. The primary outcome was improvement in pain on an 11-point numeric rating scale at 1 hour. Secondary outcomes included sustained pain freedom at 48 hours and adverse effects. In this study, 356 patients were randomized. Baseline demographics and headache features were comparable among the groups. At 1 hour, those who received 10 mg of intravenous metoclopramide improved by a mean of 4.7 numeric rating scale points (95% confidence interval [CI] 4.2 to 5.2 points); those who received 20 mg improved by 4.9 points (95% CI 4.4 to 5.4 points), and those who received 40 mg improved by 5.3 points (95% CI 4.8 to 5.9 points). Rates of 48-hour sustained pain freedom in the 10-, 20-, and 40-mg groups were 16% (95% CI 10% to 24%), 20% (95% CI 14% to 28%), and 21% (95% CI 15% to 29%), respectively. The most commonly occurring adverse event was drowsiness, which impaired function in 17% (95% CI 13% to 21%) of the overall study population. Akathisia developed in 33 patients. Both drowsiness and akathisia were evenly distributed across the 3 arms of the study. One month later, no patient had developed tardive dyskinesia. Twenty milligrams or 40 mg of metoclopramide is no better for acute migraine than 10 mg of metoclopramide.


Spatial modeling of households' knowledge about arsenic pollution in Bangladesh.
Arsenic in drinking water is an important public health issue in Bangladesh, which is affected by households' knowledge about arsenic threats from their drinking water. In this study, spatial statistical models were used to investigate the determinants and spatial dependence of households' knowledge about arsenic risk. The binary join matrix/binary contiguity matrix and inverse distance spatial weight matrix techniques are used to capture spatial dependence in the data. This analysis extends the spatial model by allowing spatial dependence to vary across divisions and regions. A positive spatial correlation was found in households' knowledge across neighboring districts at district, divisional and regional levels, but the strength of this spatial correlation varies considerably by spatial weight. Literacy rate, daily wage rate of agricultural labor, arsenic status, and percentage of red mark tube well usage in districts were found to contribute positively and significantly to households' knowledge. These findings have policy implications both at regional and national levels in mitigating the present arsenic crisis and to ensure arsenic-free water in Bangladesh.


Socioeconomic inequality in the prevalence of noncommunicable diseases in low- and middle-income countries: results from the World Health Survey.
Noncommunicable diseases are an increasing health concern worldwide, but particularly in low- and middle-income countries. This study quantified and compared education- and wealth-based inequalities in the prevalence of five noncommunicable diseases (angina, arthritis, asthma, depression and diabetes) and comorbidity in low- and middle-income country groups. Using 2002-04 World Health Survey data from 41 low- and middle-income countries, the prevalence estimates of angina, arthritis, asthma, depression, diabetes and comorbidity in adults aged 18 years or above are presented for wealth quintiles and five education levels, by sex and country income group. Symptom-based classification was used to determine angina, arthritis, asthma and depression rates, and diabetes diagnoses were self-reported. Socioeconomic inequalities according to wealth and education were measured absolutely, using the slope index of inequality, and relatively, using the relative index of inequality. Wealth and education inequalities were more pronounced in the low-income country group than the middle-income country group. Both wealth and education were inversely associated with angina, arthritis, asthma, depression and comorbidity prevalence, with strongest inequalities reported for angina, asthma and comorbidity. Diabetes prevalence was positively associated with wealth and, to a lesser extent, education. Adjustments for confounding variables tended to decrease the magnitude of the inequality. Noncommunicable diseases are not necessarily diseases of the wealthy, and showed unequal distribution across socioeconomic groups in low- and middle-income country groups. Disaggregated research is warranted to assess the impact of individual noncommunicable diseases according to socioeconomic indicators.