A household-based study of acute viral respiratory illnesses in Andean children.
Few community studies have measured the incidence, severity and etiology of acute respiratory illness (ARI) among children living at high-altitude in remote rural settings. We conducted active, household-based ARI surveillance among children aged <3 years in rural highland communities of San Marcos, Cajamarca, Peru from May 2009 through September 2011 (RESPIRA-PERU study). ARI (defined by fever or cough) were considered lower respiratory tract infections if tachypnea, wheezing, grunting, stridor or retractions were present. Nasal swabs collected during ARI episodes were tested for respiratory viruses by real-time, reverse-transcriptase polymerase chain reaction. ARI incidence was calculated using Poisson regression. During 755.1 child-years of observation among 892 children in 58 communities, 4475 ARI were observed, yielding an adjusted incidence of 6.2 ARI/child-year (95% confidence interval: 5.9-6.5). Families sought medical care for 24% of ARI, 4% were classified as lower respiratory tract infections and 1% led to hospitalization. Of 5 deaths among cohort children, 2 were attributed to ARI. One or more respiratory viruses were detected in 67% of 3957 samples collected. Virus-specific incidence rates per 100 child-years were: rhinovirus, 236; adenovirus, 73; parainfluenza virus, 46; influenza, 37; respiratory syncytial virus, 30 and human metapneumovirus, 17. Respiratory syncytial virus, metapneumovirus and parainfluenza virus 1-3 comprised a disproportionate share of lower respiratory tract infections compared with other etiologies. In this high-altitude rural setting with low-population density, ARI in young children were common, frequently severe and associated with a number of different respiratory viruses. Effective strategies for prevention and control of these infections are needed.


Number of inner-sphere water molecules in Gd3+ and Eu3+ complexes of DTPA-amide and -ester conjugates.
The inner-sphere water coordination number for Eu3+ and Gd3+ complexed with five DTPA analogs, in which one or two terminal carboxylate groups are functionalized as propyl amides or propyl esters, have been studied using phosphorescence lifetime and nuclear magnetic relaxation dispersion (NMRD) measurements. Both methods show that the water coordination number does not increase above that observed for the analogous DTPA complexes. The phosphorescence lifetime results indicate that all five Eu3+ complexes have one inner-sphere water molecule at 25 degrees C. The NMRD profiles for three of the Gd3+ complexes at 25 degrees C are also consistent with one inner-sphere water molecule, whereas two complexes have profiles consistent only with a mixture of complexes, 50% containing a single water molecule and 50% with none. Lowering the temperature alters the population of these species such that all five Gd3+ complexes have significantly less bound water on average at 5 degrees C. These results explain the anomalous temperature dependencies of the NMRD curves reported previously for the Gd(DTPA)-protein conjugates. We suggest that the Gd(DTPA)-conjugate systems have a fluxional coordination sphere whereby the amount of inner-sphere coordinated water varies from near zero at 5 degrees C to a high of two near 37 degrees C.


Number of embryos transferred after in vitro fertilization and good perinatal outcome.
To assess the association between number of embryos transferred and a measure of assisted reproductive technology success that emphasizes good perinatal outcome. We analyzed assisted reproductive technology cycles initiated in 2011 that progressed to fresh embryo transfer among women using autologous oocytes and reported to the U.S. National Assisted Reproductive Technology Surveillance System (n=82,508). Percentages of good perinatal outcome (live birth of a term [at or after 37 weeks of gestation], normal birth weight [2,500 g or greater] singleton) were stratified by prognosis (favorable, average, less favorable), age, embryo stage (day 3, day 5), and number of embryos transferred. Differences in the percentages by number of embryos transferred were evaluated using Fisher's exact test with Bonferroni correction. Among patients younger than 35 years with a favorable prognosis, chances of a good perinatal outcome were higher with transferring a single (compared with double) day 5 (43% compared with 27%) or day 3 embryo (36% compared with 30%). Likewise, a higher chance of a good perinatal outcome was observed with transferring a single day 5 embryo in patients 35-37 years old with a favorable prognosis (39% compared with 28%) or patients younger than 35 years old with an average prognosis (35% compared with 26%). A higher chance of good perinatal outcome was associated with transferring two (compared with one) day 3 embryos among patients aged 40 years or younger with an average prognosis or patients younger than 35 years old with a less favorable prognosis. The association between number of embryos transferred and the birth of a term, normal birth weight singleton is described. Among patients younger than 35 years of age undergoing in vitro fertilization with a favorable prognosis, the highest chance of good perinatal outcome is associated with a single embryo transfer. II.


Lateral growth of ZnO nanorod arrays in polyhedral structures for high on-current field-effect transistors.
Lateral growth of one-dimensional nanostructures is crucial for high performance field-effect transistors (FETs) which can drive a high on-current that is proportional to the number of nanorods (NRs) aligned between electrodes. Hence, it is strongly required to laterally and directly grow a large number of NRs between electrodes. For the first time, we propose a polyhedral-type FET (PH-FET) based on laterally-grown ZnO NRs, which includes circle, square and triangle configurations. The PH-FET structure not only provides a larger contact area than that of the planar parallel-type FET so that a great number of ZnO NRs are aligned between electrodes, but also generates a high on-current in the mA range (i.e., 5.5-6.8 mA). The high on-current PH-FET opens up a new range of applications for power devices where large currents have to be switched.


Prevalence of abnormal urinary albumin excretion in elderly people: a Spanish survey.
HERMEX is a population-based study, which tries to evaluate the prevalence of cardiovascular risk factors in the population of Extremadura, Spain. This report provides the data concerning albuminuria in the elderly people recruited in the survey. 3,402 subjects were randomly selected from the database of the Health Care System of Extremadura. The final sample included 2,813 subjects (mean age 51.2 years, 53.5 % female). Urinary albumin excretion rate (UAER) in the first morning urine sample was analyzed. Albuminuria was diagnosed when UAER (albumin-to-creatinine ratio) was ≥ 22 mg/g in men or ≥ 31 mg/g in women. The prevalence of abnormal UAER in the elderly population was 10.9 % (microalbuminuria: 8.9 %; overt proteinuria: 1.8 %). The younger subjects showed a lower prevalence of microalbuminuria (3.4 %, p < 0.001). Elderly patients showed a higher prevalence of cardiovascular risk factors than the younger ones. The elderly had higher systolic blood pressure and pulse pressure than the younger ones. Furthermore, the elderly subjects had lower plasma levels of HDL cholesterol, but higher triglycerides, glucose, creatinine, and glycosylated hemoglobin; no differences were found for total and LDL cholesterol. When the prevalence of causes of microalbuminuria was compared between age groups, we found a sharp increase in diabetic and, especially, hypertensive patients in the elderly group. The multivariate analysis showed an independent association of microalbuminuria with systolic blood pressure and plasma creatinine. A high prevalence of abnormal UAER in elderly people was detected in a randomly selected sample of Spanish general population. In most elderly patients, microalbuminuria was associated with high blood pressure and, less frequently, with diabetes mellitus.


Do older manual workers benefit in vitality after retirement? Findings from a 3-year follow-up panel study.
Vitality is the feeling of physical and mental aliveness. Vitality benefits individual, organizational and societal well-being. However, we know much less about the dynamics in the levels of vitality and its' precursors. This study investigates the effects of retirement on vitality and how this effect differs between manual and non-manual workers and by baseline levels of vitality. We used two waves of the NIDI Pension Panel Survey, collected in the Netherlands in 2015 and 2018. Data from 4156 older workers (N = 4156), of whom 1934 (46.5%) retired between waves, were analysed. Vitality is assessed in three ways, as: (1) a composite measure of vitality, and its subcomponents (2) energy and (3) fatigue. Conditional Change OLS Regression models demonstrated that retirement is associated with improved vitality and decreased fatigue. Older workers who retire from manual work at wave 1 experienced the largest gains in vitality and highest declines in fatigue at wave 2, compared to those who remained employed. Retirement was more advantageous for older workers who experienced poor vitality and high fatigue at wave 1. No such effects were found for energy. Older workers in manual work, those experiencing low vitality and high fatigue at wave 1, may benefit most from early retirement. Since opportunities for early retirement are highly restrictive, it is essential to provide these groups of workers with effective work accommodations and interventions that may not only improve their vitality and quality of working life, but also extend their participation in the labour market.


Reproductive Life Planning and Contraceptive Action Planning for Privately Insured Women: The MyNewOptions Study.
Although reproductive life planning (RLP) is recommended in federal and clinical guidelines and may help insured women make personalized contraceptive choices, it has not been systematically evaluated for effectiveness. In 2014, some 984 privately insured women aged 18-40 who were not intending to become pregnant in the next year were randomly assigned to receive RLP, RLP with contraceptive action planning (RLP+) or information only (the control group). Women's contraceptive use, prescription contraceptive use, method adherence, switching to a more effective method, method satisfaction and contraceptive self-efficacy were assessed at six-month intervals during the two-year follow-up period. Differences between groups were identified using binomial logistic regression, linear regression and generalized estimating equation models. During the follow-up period, the proportion of women using any contraceptive method increased from 89% to 96%, and the proportion using a long-acting reversible contraceptive or sterilization increased from 8% to 19%. Contraceptive adherence was high (72-76%) in all three groups. In regression models, the sole significant finding was that women in the RLP+ group were more likely than those in the RLP group to use a prescription method (odds ratio, 1.3). No differences were evident between the intervention groups and the control group in overall contraceptive use, contraceptive adherence, switching to a more effective method, method satisfaction or contraceptive self-efficacy. The study does not provide evidence that web-based RLP influences contraceptive behaviors in insured women outside of the clinical setting. Further research is needed to identify strategies to help women of reproductive age identify contraceptive methods that meet their needs and preferences.


Single-cell genetic analysis reveals insights into clonal development of prostate cancers and indicates loss of PTEN as a marker of poor prognosis.
Gauging the risk of developing progressive disease is a major challenge in prostate cancer patient management. We used genetic markers to understand genomic alteration dynamics during disease progression. By using a novel, advanced, multicolor fluorescence in situ hybridization approach, we enumerated copy numbers of six genes previously identified by array comparative genomic hybridization to be involved in aggressive prostate cancer [TBL1XR1, CTTNBP2, MYC (alias c-myc), PTEN, MEN1, and PDGFB] in six nonrecurrent and seven recurrent radical prostatectomy cases. An ERG break-apart probe to detect TMPRSS2-ERG fusions was included. Subsequent hybridization of probe panels and cell relocation resulted in signal counts for all probes in each individual cell analyzed. Differences in the degree of chromosomal and genomic instability (ie, tumor heterogeneity) or the percentage of cells with TMPRSS2-ERG fusion between samples with or without progression were not observed. Tumors from patients that progressed had more chromosomal gains and losses, and showed a higher degree of selection for a predominant clonal pattern. PTEN loss was the most frequent aberration in progressers (57%), followed by TBL1XR1 gain (29%). MYC gain was observed in one progresser, which was the only lesion with an ERG gain, but no TMPRSS2-ERG fusion. According to our results, a probe set consisting of PTEN, MYC, and TBL1XR1 would detect progressers with 86% sensitivity and 100% specificity. This will be evaluated further in larger studies.


A general linear model-based approach for inferring selection to climate.
Many efforts have been made to detect signatures of positive selection in the human genome, especially those associated with expansion from Africa and subsequent colonization of all other continents. However, most approaches have not directly probed the relationship between the environment and patterns of variation among humans. We have designed a method to identify regions of the genome under selection based on Mantel tests conducted within a general linear model framework, which we call MAntel-GLM to Infer Clinal Selection (MAGICS). MAGICS explicitly incorporates population-specific and genome-wide patterns of background variation as well as information from environmental values to provide an improved picture of selection and its underlying causes in human populations. Our results significantly overlap with those obtained by other published methodologies, but MAGICS has several advantages. These include improvements that: limit false positives by reducing the number of independent tests conducted and by correcting for geographic distance, which we found to be a major contributor to selection signals; yield absolute rather than relative estimates of significance; identify specific geographic regions linked most strongly to particular signals of selection; and detect recent balancing as well as directional selection. We find evidence of selection associated with climate (P < 10-5) in 354 genes, and among these observe a highly significant enrichment for directional positive selection. Two of our strongest 'hits', however, ADRA2A and ADRA2C, implicated in vasoconstriction in response to cold and pain stimuli, show evidence of balancing selection. Our results clearly demonstrate evidence of climate-related signals of directional and balancing selection.


RNF112-mediated FOXM1 ubiquitination suppresses the proliferation and invasion of gastric cancer.
Forkhead box M1 (FOXM1) plays a critical role in development physiologically and tumorigenesis pathologically. However, insufficient efforts have been dedicated to exploring the regulation, in particular the degradation of FOXM1. Here, the ON-TARGETplus siRNA library targeting E3 ligases was used to screen potential candidates to repress FOXM1. Of note, mechanism study revealed that RNF112 directly ubiquitinates FOXM1 in gastric cancer, resulting in a decreased FOXM1 transcriptional network and suppressing the proliferation and invasion of gastric cancer. Interestingly, the well-established small-molecule compound RCM-1 significantly enhanced the interaction between RNF112 and FOXM1, which further promoted FOXM1 ubiquitination and subsequently exerted promising anticancer effects in vitro and in vivo. Altogether, we demonstrate that RNF112 suppresses gastric cancer progression by ubiquitinating FOXM1 and highlight the RNF112/FOXM1 axis serves as both prognosis biomarker and therapeutic target in gastric cancer.


Mechanisms controlling anaemia in Trypanosoma congolense infected mice.
Trypanosoma congolense are extracellular protozoan parasites of the blood stream of artiodactyls and are one of the main constraints on cattle production in Africa. In cattle, anaemia is the key feature of disease and persists after parasitaemia has declined to low or undetectable levels, but treatment to clear the parasites usually resolves the anaemia. The progress of anaemia after Trypanosoma congolense infection was followed in three mouse strains. Anaemia developed rapidly in all three strains until the peak of the first wave of parasitaemia. This was followed by a second phase, characterized by slower progress to severe anaemia in C57BL/6, by slow recovery in surviving A/J and a rapid recovery in BALB/c. There was no association between parasitaemia and severity of anaemia. Furthermore, functional T lymphocytes are not required for the induction of anaemia, since suppression of T cell activity with Cyclosporin A had neither an effect on the course of infection nor on anaemia. Expression of genes involved in erythropoiesis and iron metabolism was followed in spleen, liver and kidney tissues in the three strains of mice using microarrays. There was no evidence for a response to erythropoietin, consistent with anaemia of chronic disease, which is erythropoietin insensitive. However, the expression of transcription factors and genes involved in erythropoiesis and haemolysis did correlate with the expression of the inflammatory cytokines Il6 and Ifng. The innate immune response appears to be the major contributor to the inflammation associated with anaemia since suppression of T cells with CsA had no observable effect. Several transcription factors regulating haematopoiesis, Tal1, Gata1, Zfpm1 and Klf1 were expressed at consistently lower levels in C57BL/6 mice suggesting that these mice have a lower haematopoietic capacity and therefore less ability to recover from haemolysis induced anaemia after infection.


Enzyme mediated silicon-oxygen bond formation; the use of Rhizopus oryzae lipase, lysozyme and phytase under mild conditions.
The potential for expanding the variety of enzymic methods for siloxane bond formation is explored. Three enzymes, Rhizopus oryzae lipase (ROL), lysozyme and phytase are reported to catalyse the condensation of the model compound, trimethylsilanol, formed in situ from trimethylethoxysilane, to produce hexamethyldisiloxane in aqueous media at 25 °C and pH 7. Thermal denaturation and reactant inhibition experiments were conducted to better understand the catalytic role of these enzyme candidates. It was found that enzyme activities were significantly reduced following thermal treatment, suggesting a potential key-role of the enzyme active sites in the catalysis. Similarly, residue-specific modification of the key-amino acids believed to participate in the ROL catalysis also had a significant effect on the silicon bio-catalysis, indicating that the catalytic triad of the lipase may be involved during the enzyme-mediated formation of the silicon-oxygen bond. E. coli phytase was found to be particularly effective at catalysing the condensation of trimethylsilanol in a predominantly organic medium consisting of 95% acetonitrile and 5% water. Whereas the use of enzymes in silicon chemistry is still very much a developing and frontier activity, the results presented herein give some grounds for optimism that the variety of enzyme mediated reactions will continue to increase and may one day become a routine element in the portfolio of the synthetic silicon chemist.


Nonlinear effects in acousto-optic imaging.
Acousto-optic (AO) imaging is a promising technique that is able to reveal optical properties in the millimeter range inside scattering media by tagging the photon paths with an ultrasonic beam. To increase both the contrast and the resolution of the AO images, we have explored the possibility of using the nonlinear response of the speckle modulation. Variation of the second-harmonic signal as the square of the ultrasonic amplitude has been found, and strong reduction of the tagged zone size has been demonstrated.


Spatiotopic neural representations develop slowly across saccades.
One of the long-standing unsolved mysteries of visual neuroscience is how the world remains apparently stable in the face of continuous movements of eyes, head and body. Many factors seem to contribute to this stability, including rapid updating mechanisms that temporarily remap the visual input to compensate for the impending saccade. However, there is also a growing body of evidence pointing to more long-lasting spatiotopic neural representations, which remain solid in external rather than retinal coordinates. In this study, we show that these spatiotopic representations take hundreds of milliseconds to build up robustly.


Bone formation induced by a novel form of mechanical loading on joint tissue.
Because of insufficient mechanical loading, exposure to weightlessness in space flight reduces bone mass. In order to maintain bone mass in a weightless condition, we investigated a novel form of mechanical loading--joint loading. Since some part of gravity-induced loading to our skeletal system is absorbed by viscoelastic deformation of joint tissues, we hypothesized that deformation of joint tissues would generate fluid flow in bone and stimulate bone formation in diaphyseal cortical bone. In order to test the hypothesis, we applied directly oscillatory loading to an elbow joint of mice and conducted bone histomorphometry on the diaphysis of ulnae. Using murine femurs ex vivo, streaming potentials were measured to evaluate a fluid flow induced by joint loading. Bone histomorphometry revealed that compared to no loading control, elbow loading increased mineralizing surface, mineral apposition rate, and bone formation rate 3.2-fold, 3.0-fold, and 7.9-fold, respectively. We demonstrated that joint loading generated a streaming potential in a medullar cavity of femurs. The results support a novel mechanism, in which joint loading stimulates effectively bone formation possibly by generating fluid flow, and suggest that a supportive attachment to joints, driven passively or actively, would be useful to maintain bone mass of astronauts during an exposure to weightlessness.


Clinical characteristics of Japanese patients with anti-PL-7 (anti-threonyl-tRNA synthetase) autoantibodies.
The clinical and laboratory features of seven Japanese patients with anti-aminoacyl-tRNA synthetase (ARS) autoantibodies against PL-7 (anti-threonyl-tRNA synthetase) were analyzed and compared with previously published findings. Serum samples from 1,135 Japanese patients with various autoimmune diseases were screened for anti-PL-7 antibodies using RNA and protein immunoprecipitation assays. The patients whose sera contained anti-PL-7 antibodies were assessed regarding clinical symptoms and clinical course. Sera from seven patients were found to have anti-PL-7 antibodies. These autoantibodies were associated with polymyositis/dermatomyositis (PM/DM) and/or interstitial lung disease (ILD). The clinical diagnoses of these seven patients were PM - systemic sclerosis (SSc) overlap (5 patients), DM (1 patient) and idiopathic pulmonary fibrosis (IPF) (1 patient). All patients had ILD with a chronic course and six also had arthritis (85%) and five sclerodactyly (71%). These results indicate that anti-PL-7 autoantibodies are closely associated with PM-SSc overlap as well as ILD, arthritis and sclerodactyly in our series of Japanese patients.


Enhanced endothelial cell functions on rosette nanotube-coated titanium vascular stents.
One of the main problems with current vascular stents is a lack of endothelial cell interactions, which if sufficient, would create a uniform healthy endothelium masking the underlying foreign metal from inflammatory cell interference. Moreover, if endothelial cells from the arterial wall do not adhere to the stent, the stent can become loose and dislodge. Therefore, the objective of this in vitro study was to design a novel biomimetic nanostructured coating (that does not contain drugs) on conventional vascular stent materials (specifically, titanium) for improving vascular stent applications. Rosette nanotubes (RNTs) are a new class of biomimetic nanotubes that self-assemble from DNA base analogs and have been shown in previous studies to sufficiently coat titanium and enhance osteoblast cell functions. RNTs have many desirable properties for use as vascular stent coatings including spontaneous self-assembly in body fluids, tailorable surface chemistry for specific implant applications, and nanoscale dimensions similar to those of the natural vascular extracellular matrix. Importantly, the results of this study provided the first evidence that RNTs functionalized with lysine (RNT-K), even at low concentrations, significantly increase endothelial cell density over uncoated titanium. Specifically, 0.01 mg/mL RNT-K coated titanium increased endothelial cell density by 37% and 52% compared to uncoated titanium after 4 h and three days, respectively. The excellent cytocompatibility properties of RNTs (as demonstrated here for the first time for endothelial cells) suggest the need for the further exploration of these novel nanostructured materials for vascular stent applications.


[Carcinoma of the parathyroids. Surgical experience in 3 cases].
Parathyroid carcinoma is a rare cause of hyperparathyroidism (rate of occurrence of 0.5% of all parathyroid neoplasms). In this report we describe three cases of parathyroid carcinoma seen in our Institution and we analyse the clinical, diagnostic, therapeutic and pathological findings of this disease. The three patients were 14, 22 and 45 year old respectively. Familial history was negative for endocrine diseases. The laboratory and instrumental findings of thyroid and adrenal glands were negative. Predominant symptoms were in all cases weakness, lethargy, bone and muscular pain, nausea, vomiting. The two young patients presented fractures of the inferior limb and of the forearm respectively, five years and one year before the diagnosis. X-ray examination and MNR easily demonstrated the "brown tumors". In two cases a symptomatic nephrolithiasis was present. The 14 year old child presented polyuria and polydipsia. In all cases a mass was palpable in the neck (two in the right side and one in the left one). The elevated serum calcium concentration (15, 18, and 20.2 mg/dl respectively) and the elevated serum PTH (480, 651, and 680 pg/ml respectively) allowed the diagnosis of hyperparathyroidism. Ultrasound scan and thallium-technetium scanning identified in all cases a mass adjacent the thyroid. A radical resection of the malignant parathyroid gland and the ipsilateral thyroid lobe was performed in two cases, while only a resection of the involved parathyroid gland in one case. The diagnosis of parathyroid cancer was established using pathologic criteria.(ABSTRACT TRUNCATED AT 250 WORDS)


Spinal MRI in patients with suspected multiple sclerosis and negative brain MRI.
Although MRI detects the white matter lesions of multiple sclerosis within the brain with high sensitivity, a minority of patients have normal brain MRI. We describe 20 patients, selected from over 170 who had undergone brain imaging with minimal (n = 12) or no (n = 8) abnormalities (median number of lesions = I, range, 0-3) but in whom spinal MRI was abnormal. Twelve had clinically definite or laboratory supported definite multiple sclerosis according to the Poser criteria; one had clinically probable disease and seven, not fulfilling the Poser criteria, were classified as possible multiple sclerosis. All had presented with symptoms and signs referable to the spinal cord or optic nerves. Eleven had a primary progressive course, eight relapsing-remitting and only one secondary progressive. Moderate or severe disability was the rule in the primary progressive cases; all the relapsing-remitting patients had minimal disability. All had at least one lesion visible in the spinal cord (median 2; range 1-6). In patients in whom the diagnosis of multiple sclerosis is not supported by abnormalities on brain MRI, imaging of the spinal cord can be of considerable value.


Reducing harm in drinking environments: a systematic review of effective approaches.
Drinking environments, including bars, nightclubs and their surrounds are associated with high levels of acute alcohol-related harms. This systematic review examined the effectiveness of interventions implemented in drinking environments to reduce alcohol use and associated harms. The findings of the review were limited by the methodological shortcomings of the included studies. However, three studies indicated that multicomponent programmes combining community mobilisation, RBS training, house policies and stricter enforcement of licensing laws may be effective in reducing assaults, traffic crashes, and underage sales depending on the focus of the intervention. The effectiveness of other intervention approaches was limited. Future studies of interventions in drinking environments should focus on using appropriate and robust study designs.


Interventions for enhancing medication adherence.
People who are prescribed self administered medications typically take only about half their prescribed doses. Efforts to assist patients with adherence to medications might improve the benefits of prescribed medications. The primary objective of this review is to assess the effects of interventions intended to enhance patient adherence to prescribed medications for medical conditions, on both medication adherence and clinical outcomes. We updated searches of The Cochrane Library, including CENTRAL (via http://onlinelibrary.wiley.com/cochranelibrary/search/), MEDLINE, EMBASE, PsycINFO (all via Ovid), CINAHL (via EBSCO), and Sociological Abstracts (via ProQuest) on 11 January 2013 with no language restriction. We also reviewed bibliographies in articles on patient adherence, and contacted authors of relevant original and review articles. We included unconfounded RCTs of interventions to improve adherence with prescribed medications, measuring both medication adherence and clinical outcome, with at least 80% follow-up of each group studied and, for long-term treatments, at least six months follow-up for studies with positive findings at earlier time points. Two review authors independently extracted all data and a third author resolved disagreements. The studies differed widely according to medical condition, patient population, intervention, measures of adherence, and clinical outcomes. Pooling results according to one of these characteristics still leaves highly heterogeneous groups, and we could not justify meta-analysis. Instead, we conducted a qualitative analysis with a focus on the RCTs with the lowest risk of bias for study design and the primary clinical outcome. The present update included 109 new RCTs published since the previous update in January 2007, bringing the total number of RCTs to 182; we found five RCTs from the previous update to be ineligible and excluded them. Studies were heterogeneous for patients, medical problems, treatment regimens, adherence interventions, and adherence and clinical outcome measurements, and most had high risk of bias. The main changes in comparison with the previous update include that we now: 1) report a lack of convincing evidence also specifically among the studies with the lowest risk of bias; 2) do not try to classify studies according to intervention type any more, due to the large heterogeneity; 3) make our database available for collaboration on sub-analyses, in acknowledgement of the need to make collective advancement in this difficult field of research. Of all 182 RCTs, 17 had the lowest risk of bias for study design features and their primary clinical outcome, 11 from the present update and six from the previous update. The RCTs at lowest risk of bias generally involved complex interventions with multiple components, trying to overcome barriers to adherence by means of tailored ongoing support from allied health professionals such as pharmacists, who often delivered intense education, counseling (including motivational interviewing or cognitive behavioral therapy by professionals) or daily treatment support (or both), and sometimes additional support from family or peers. Only five of these RCTs reported improvements in both adherence and clinical outcomes, and no common intervention characteristics were apparent. Even the most effective interventions did not lead to large improvements in adherence or clinical outcomes. Across the body of evidence, effects were inconsistent from study to study, and only a minority of lowest risk of bias RCTs improved both adherence and clinical outcomes. Current methods of improving medication adherence for chronic health problems are mostly complex and not very effective, so that the full benefits of treatment cannot be realized. The research in this field needs advances, including improved design of feasible long-term interventions, objective adherence measures, and sufficient study power to detect improvements in patient-important clinical outcomes. By making our comprehensive database available for sharing we hope to contribute to achieving these advances.


Neurobiological studies on the relationship between toxoplasmosis and neuropsychiatric diseases.
Toxoplasma gondii is a widespread protozoan parasite infecting approximately one third of the world population. After proliferation of tachyzoites during the acute stage, the parasite forms tissue cysts in various anatomical sites including the Central Nervous tissue, and establishes a chronic infection. Clinical spectrum normally ranges from a completely asymptomatic infection to severe multi-organ involvement. Many studies have suggested T. gondii infection as a risk factor for the development of some neuropsychiatric disorders, particularly schizophrenia. During the last years, a potential link with other neurobiological diseases such as Parkinson disease and Alzheimer disease has also been suggested. This review will focus on neurobiological and epidemiological data relating infection with T. gondii to neuropsychiatric diseases.


Efficiency of functional brain networks and intellectual performance.
Our brain is a complex network in which information is continuously processed and transported between spatially distributed but functionally linked regions. Recent studies have shown that the functional connections of the brain network are organized in a highly efficient small-world manner, indicating a high level of local neighborhood clustering, together with the existence of more long-distance connections that ensure a high level of global communication efficiency within the overall network. Such an efficient network architecture of our functional brain raises the question of a possible association between how efficiently the regions of our brain are functionally connected and our level of intelligence. Examining the overall organization of the brain network using graph analysis, we show a strong negative association between the normalized characteristic path length lambda of the resting-state brain network and intelligence quotient (IQ). This suggests that human intellectual performance is likely to be related to how efficiently our brain integrates information between multiple brain regions. Most pronounced effects between normalized path length and IQ were found in frontal and parietal regions. Our findings indicate a strong positive association between the global efficiency of functional brain networks and intellectual performance.


Psychological comorbidities in Chinese patients with acute-on-chronic liver failure.
Patients with acute-on-chronic liver failure (ACLF) experience long-term chronic liver diseases plus an acute liver function decompensation. This study aimed to determine whether psychological symptoms in patients with hepatitis B virus (HBV)-related ACLF differ from those with other chronic liver diseases and to identify which factors could predict psychological impairment in liver patients. This was a paired case-control study. A total of 120 inpatients, including 40 cases for HBV-related ACLF, 40 paired controls for HBV-related cirrhosis and 40 paired controls for chronic hepatitis B (CHB), as well as 40 paired healthy controls were studied. A high proportion of patients with HBV-related ACLF were classified as Child's stage C. The prevalence of depression in patients with HBV-related ACLF was significantly higher than in CHB patients and healthy controls, but was equivalent to patients with HBV-related cirrhosis. Patients with HBV-related ACLF had significantly higher level of self-esteem than those with HBV-related cirrhosis. However, there was no significant difference among the three liver patient groups and healthy controls in anxiety and suicide intent. Lower education level, anxiety, poor sleep quality and greater severity of disease were associated with elevated depression. Patients with HBV-related ACLF and cirrhosis are at higher risk of depression. It appears that severity of liver disease measured by Child-Pugh class, rather than additional acute liver function decompensation, significantly predicted depression among liver patients.


Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion.
Concerns regarding the safety of transfused blood have led to the development of a range of interventions to minimise blood loss during major surgery. Anti-fibrinolytic drugs are widely used, particularly in cardiac surgery, and previous reviews have found them to be effective in reducing blood loss, the need for transfusion, and the need for re-operation due to continued or recurrent bleeding. In the last few years questions have been raised regarding the comparative performance of the drugs. The safety of the most popular agent, aprotinin, has been challenged, and it was withdrawn from world markets in May 2008 because of concerns that it increased the risk of cardiovascular complications and death. To assess the comparative effects of the anti-fibrinolytic drugs aprotinin, tranexamic acid (TXA), and epsilon aminocaproic acid (EACA) on blood loss during surgery, the need for red blood cell (RBC) transfusion, and adverse events, particularly vascular occlusion, renal dysfunction, and death. We searched: the Cochrane Injuries Group's Specialised Register (July 2010), Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 3), MEDLINE (Ovid SP) 1950 to July 2010, EMBASE (Ovid SP) 1980 to July 2010. References in identified trials and review articles were checked and trial authors were contacted to identify any additional studies. The searches were last updated in July 2010. Randomised controlled trials (RCTs) of anti-fibrinolytic drugs in adults scheduled for non-urgent surgery. Eligible trials compared anti-fibrinolytic drugs with placebo (or no treatment), or with each other. Two authors independently assessed trial quality and extracted data. This review summarises data from 252 RCTs that recruited over 25,000 participants. Data from the head-to-head trials suggest an advantage of aprotinin over the lysine analogues TXA and EACA in terms of reducing perioperative blood loss, but the differences were small. Compared to control, aprotinin reduced the probability of requiring RBC transfusion by a relative 34% (relative risk [RR] 0.66, 95% confidence interval [CI] 0.60 to 0.72). The RR for RBC transfusion with TXA was 0.61 (95% CI 0.53 to 0.70) and was 0.81 (95% CI 0.67 to 0.99) with EACA. When the pooled estimates from the head-to-head trials of the two lysine analogues were combined and compared to aprotinin alone, aprotinin appeared more effective in reducing the need for RBC transfusion (RR 0.90; 95% CI 0.81 to 0.99).Aprotinin reduced the need for re-operation due to bleeding by a relative 54% (RR 0.46, 95% CI 0.34 to 0.62). This translates into an absolute risk reduction of 2% and a number needed-to-treat (NNT) of 50 (95% CI 33 to 100). A similar trend was seen with EACA (RR 0.32, 95% CI 0.11 to 0.99) but not TXA (RR 0.80, 95% CI 0.55 to 1.17). The blood transfusion data were heterogeneous and funnel plots indicate that trials of aprotinin and the lysine analogues may be subject to publication bias.When compared with no treatment aprotinin did not increase the risk of myocardial infarction (RR 0.87, 95% CI 0.69 to 1.11), stroke (RR 0.82, 95% CI 0.44 to 1.52), renal dysfunction (RR 1.10, 95% CI 0.79 to 1.54) or overall mortality (RR 0.81, 95% CI 0.63 to 1.06). Similar trends were seen with the lysine analogues, but data were sparse. These data conflict with the results of recently published non-randomised studies, which found increased risk of cardiovascular complications and death with aprotinin. There are concerns about the adequacy of reporting of uncommon events in the small clinical trials included in this review.When aprotinin was compared directly with either, or both, of the two lysine analogues it resulted in a significant increase in the risk of death (RR 1.39, 95% CI 1.02, 1.89), and a non-significant increase in the risk of myocardial infarction (RR 1.11 95% CI 0.82, 1.50). Most of the data contributing to this added risk came from a single study - the BART trial (2008). Anti-fibrinolytic drugs provide worthwhile reductions in blood loss and the receipt of allogeneic red cell transfusion. Aprotinin appears to be slightly more effective than the lysine analogues in reducing blood loss and the receipt of blood transfusion. However, head to head comparisons show a lower risk of death with lysine analogues when compared with aprotinin. The lysine analogues are effective in reducing blood loss during and after surgery, and appear to be free of serious adverse effects.


[Effects of isorhamnetin on CYP3A4 and herb-drug interaction].
The study is to report the investigation of the effects of isorhamnetin on CYP3A4 and herb-drug interaction. A reporter gene assay is used to test pregnane X receptor transactivation action, qRT-PCR and a luminescence-based assay were applied to determine mRNA induction and enzyme activity of CYP3A4 after isorhamnetin treatment. The interaction of irinotecan and isorhamnetin was assessed by inhibition assay of cell proliferation. Isorhamnetin at 1, 10 and 25 micromol x L(-1) transactivated the CYP3A4 reporter construct and upregulated CYP3A4 mRNA as well in a dose-dependent manner. However, isorhamnetin had no effect on enzyme activity of CYP3A4 and irinotecan HepG2 cytotoxicity. In conclusion, activation of PXR by isorhamnetin played a role in the upregulation of CYP3A4 mRNA. Moreover, joint action of isorhamnetin with other drugs may not be associated with the herb-drug interaction.


Complementary phosphorylation sites in the adaptor protein SLP-76 promote synergistic activation of natural killer cells.
The cytotoxic effects of natural killer (NK) cells and their ability to secrete cytokines require synergistic signals from specific pairs of co-activation receptors, such as CD314 (also known as NKG2D) and CD244 (2B4), which bind to distinct ligands present on target cells. These signals are required to overcome inhibition mediated by the E3 ubiquitin ligase c-Cbl of the guanine nucleotide exchange factor Vav1, which promotes activation of NK cells. Here, we showed that the adaptor protein SLP-76 (Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons) was required for this synergy and that distinct tyrosine residues in SLP-76 were phosphorylated by each member of a pair of synergistic receptors. Selective phosphorylation of tyrosine 113 or tyrosine 128 in SLP-76 enabled binding of SLP-76 to Vav1. Selective phosphorylation of SLP-76 at these residues was restricted to receptors that stimulated ligand-dependent target cell killing; antibody-dependent stimulation of the Fc receptor CD16 promoted phosphorylation at both sites. Knockdown and reconstitution experiments with SLP-76 mutant proteins showed the distinct role of each tyrosine in the synergistic mobilization of Ca2+, revealing an unexpected degree of selectivity in the phosphorylation of SLP-76 by NK cell co-activation receptors. Together, these data suggest that combined phosphorylation of separate tyrosine residues in SLP-76 forms the basis of synergistic NK cell activation.


Petroleum hydrocarbon persistence following the Deepwater Horizon oil spill as a function of shoreline energy.
An important aspect of oil spill science is understanding how the compounds within spilled oil, especially toxic components, change with weathering. In this study we follow the evolution of petroleum hydrocarbons, including n-alkanes, polycyclic aromatic hydrocarbons (PAHs) and alkylated PAHs, on a Louisiana beach and salt marsh for three years following the Deepwater Horizon spill. Relative to source oil, we report overall depletion of low molecular weight n-alkanes and PAHs in all locations with time. The magnitude of depletion, however, depends on the sampling location, whereby sites with highest wave energy have highest compound depletion. Oiled sediment from an enclosed bay shows high enrichment of high molecular weight PAHs relative to 17α(H),21β(H)-hopane, suggesting the contribution from sources other than the Deepwater Horizon spill, such as fossil fuel burning. This insight into hydrocarbon persistence as a function of hydrography and hydrocarbon source can inform policy and response for future spills.


Cutaneous or respiratory exposures to peanut allergens in mice and their impacts on subsequent oral exposure.
Recent data suggested that non-gastrointestinal exposure can lead to sensitisation to food allergens. We thus assessed the immune impact of respiratory or cutaneous exposure to peanut proteins on non-altered epithelium and investigated the effect of such pre-exposure on subsequent oral administration of peanut. BALB/cJ mice were exposed to purified Ara h 1 or to a non-defatted roasted peanut extract (PE) by simple deposit of allergens solutions on non-altered skin or in the nostrils. Exposures were performed 6 times at weekly intervals. Pre-exposed mice then received intra-gastric administrations of PE alone or in the presence of the Th2 mucosal adjuvant cholera toxin (CT). The specific humoral and cellular immune response was assessed throughout the protocol. Both cutaneous and respiratory exposures led to the production of specific IgG1. Local and systemic IL-5 and IL-13 production were also evidenced, demonstrating activation of specific Th2 cells. This effect was dose-dependent and most efficient via the respiratory route. Moreover, these pre-exposures led to the production of specific IgE antibodies after gavage with PE, whatever the presence of CT. Cutaneous or respiratory exposures to peanut induce Th2 priming in mice. Moreover, pre-exposures promote further sensitisation via the oral route without the use of CT; this proposes a new adjuvant-free experimental model of sensitisation to food that may reflect a realistic exposure pattern in infants. These results also suggest that non-gastrointestinal peanut exposure should be minimised in high-risk infants, even those with non-altered skin, to potentially reduce allergic sensitisation to this major food allergen.


Impaired manganese metabolism causes mitotic misregulation.
Manganese is an essential trace element, whose intracellular levels need to be carefully regulated. Mn(2+) acts as a cofactor for many enzymes and excess of Mn(2+) is toxic. Alterations in Mn(2+) homeostasis affect metabolic functions and mutations in the human Mn(2+)/Ca(2+) transporter ATP2C1 have been linked to Hailey-Hailey disease. By deletion of the yeast orthologue PMR1 we have studied the impact of Mn(2+) on cell cycle progression and show that an excess of cytosolic Mn(2+) alters S-phase transit, induces transcriptional up-regulation of cell cycle regulators, bypasses the need for S-phase cell cycle checkpoints and predisposes to genomic instability. On the other hand, we find that depletion of the Golgi Mn(2+) pool requires a functional morphology checkpoint to avoid the formation of polyploid cells.


Fibromyalgia in women with ankylosing spondylitis.
Fibromyalgia (FM), pre-dominantly found in women, may accompany other pre-existing rheumatic diseases. The association between FM and ankylosing spondylitis (AS) is uncertain. We evaluated FM in women with AS. Eighteen women with AS were compared with 18 men with AS (controls) for age, duration of symptoms, time to diagnosis, degree of sacroiliac involvement, history of peripheral arthritis, patient global assessment, Health Assessment Questionnaire, Fibromyalgia Impact Questionnaire, level of diffuse pain, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Functional Index (BASFI). Physical examination included the number of tender points and enthesitis sites, Schober test, distance between occiput and wall, chest expansion, lateral spinal flexion, and intermalleolar distance. Inflammatory activity was measured by the erythrocyte sedimentation rate (ESR). Of all tested parameters, the ones with significant differences between the groups were time between symptom onset and AS diagnosis (longer for women), FM incidence and the number of tender points and enthesitis sites (higher for women), BASDAI (higher in women and correlated with FM and the number of tender points but not with ESR), and BASFI and BASDAI scores (increased in FM patients). FM was present in 50% of women with AS and associated with higher disease activity indices (BASDAI and BASFI) and not related to severity of physical findings or ESR. The reliability of well-accepted assessment tools of AS, such as BASDAI and BASFI, in evaluating AS activity in women may be called into question due to a confounding effect of FM.


Revealing calcium fluxes by analyzing inhibition dynamics in action potential clamp.
In cardiac excitation-contraction coupling (ECC), calcium enters the cytosol via L-type Ca2+ channels (LTCC) and reverse Na+/Ca2+-exchange (NCXrev), or is released from the sarcoplasmic reticulum (SR) by Ca2+-induced Ca2+-release (CICR). The magnitude of Ca2+ influx via the different pathways varies with the state of the cell and is difficult to assess quantitatively, because changes in Ca2+ influx through one pathway affect the others. In rainbow trout ventricular myocytes, the role of the SR has been uncertain for decades. The aim of this work was therefore two-fold: 1) to develop a method to quantify the Ca2+ influx pathways, and 2) to determine the role of CICR from the SR in trout ventricular myocytes. The novelty of our developed method lies in the mathematical analysis of measured transsarcolemmal Ca2+ currents and their impact on the corresponding Ca2+ transient during gradual inhibition of the currents in action potential (AP) clamp. We tested the developed method using an excitation-contraction model and showed that the method was able to recover calcium fluxes from noisy synthetic data. We applied the approach to trout ventricular myocytes and quantified the relative contributions of different Ca2+ influx pathways in ECC and determined the kinetics of these fluxes. Under baseline conditions, NCXrev is the main transmembrane Ca2+ influx pathway contributing 29 ± 6% (of the Ca2+ influx), LTCC 18 ± 7%, and CICR 53 ± 10% to overall Ca2+ transient. Thus, NCXrev is an important regulator of contractility and probably plays a role in the negative force-frequency relationship of trout ventricular preparations. These results demonstrate that trout and neonatal mammalian cardiomyocytes resemble each other not only in terms of morphology and energetics but ECC as well. In summary, the developed method resolves the major problem how to separate highly interconnected fluxes in AP clamp and allows to study Ca2+ fluxes in cardiomyocytes under conditions close to in vivo.


Estimating DNA coverage and abundance in metagenomes using a gamma approximation.
Shotgun sequencing generates large numbers of short DNA reads from either an isolated organism or, in the case of metagenomics projects, from the aggregate genome of a microbial community. These reads are then assembled based on overlapping sequences into larger, contiguous sequences (contigs). The feasibility of assembly and the coverage achieved (reads per nucleotide or distinct sequence of nucleotides) depend on several factors: the number of reads sequenced, the read length and the relative abundances of their source genomes in the microbial community. A low coverage suggests that most of the genomic DNA in the sample has not been sequenced, but it is often difficult to estimate either the extent of the uncaptured diversity or the amount of additional sequencing that would be most efficacious. In this work, we regard a metagenome as a population of DNA fragments (bins), each of which may be covered by one or more reads. We employ a gamma distribution to model this bin population due to its flexibility and ease of use. When a gamma approximation can be found that adequately fits the data, we may estimate the number of bins that were not sequenced and that could potentially be revealed by additional sequencing. We evaluated the performance of this model using simulated metagenomes and demonstrate its applicability on three recent metagenomic datasets. Supplementary data are available at Bioinformatics online.


Body size drives allochthony in food webs of tropical rivers.
Food web subsidies from external sources ("allochthony") can support rich biological diversity and high secondary and tertiary production in aquatic systems, even those with low rates of primary production. However, animals vary in their degree of dependence on these subsidies. We examined dietary sources for aquatic animals restricted to refugial habitats (waterholes) during the dry season in Australia's wet-dry tropics, and show that allochthony is strongly size dependent. While small-bodied fishes and invertebrates derived a large proportion of their diet from autochthonous sources within the waterhole (phytoplankton, periphyton, or macrophytes), larger animals, including predatory fishes and crocodiles, demonstrated allochthony from seasonally inundated floodplains, coastal zones or the surrounding savanna. Autochthony declined roughly 10% for each order of magnitude increase in body size. The largest animals in the food web, estuarine crocodiles (Crocodylus porosus), derived ~80% of their diet from allochthonous sources. Allochthony enables crocodiles and large predatory fish to achieve high biomass, countering empirically derived expectations for negative density vs. body size relationships. These results highlight the strong degree of connectivity that exists between rivers and their floodplains in systems largely unaffected by river regulation or dams and levees, and how large iconic predators could be disproportionately affected by these human activities.


A phase of I trial of 4'-epi-Adriamycin.
4'-epi-adriamycin was administered intravenously on an every-3-week schedule to 34 patients with advanced malignant tumors. Patients were treated at five dosage levels, ranging from 40 mg/m2 to 100 mg/m2. Hematologic toxicity was dose limiting. No cardiac, renal, or hepatic toxicity was observed; there were no drug-related deaths. Partial alopecia developed in all patients receiving a cumulative dose of 200 mg/m2; mild nausea and vomiting occurred in 13 patients. Although major therapeutic responses were not seen in this phase I trial, 2 of 15 patients with objectively measurable disease showed minor responses; 7 patients had stabilization of previously progressing cancer for 3 to 5+ months. A dose of 85 mg/m2 of epi-Adriamycin every 3 weeks seems an appropriate initial dose for phase II studies in patients having a performance status of 70 or higher. A starting dose of 70 mg/m2 is recommended for patients having a lower performance status.


Impact of comorbidities and drug therapy on development of renal impairment in a predominantly African American and Hispanic HIV clinic population.
Renal impairment in human immunodeficiency virus (HIV)-infected patients could potentially be caused by many factors. HIV-related renal impairment risks have been little studied in African Americans and Hispanics. We investigated the impact of HIV itself, highly active antiretroviral therapy (HAART), comorbidities, and non-HIV-related drug treatment on glomerular filtration rate in a predominantly African American/Hispanic HIV-infected population who had received HAART for at least one year. This study was a retrospective electronic medical record database evaluation of renal impairment risks in a largely African American/Hispanic HIV population obtaining medical care at an HIV clinic in Dallas, Texas. Proportional hazards models were used to investigate an association between an estimated glomerular filtration rate decrease >25% from baseline (ie, renal impairment) and demographics, antiretroviral/nonantiretroviral medications, comorbidities (hypertension, diabetes mellitus, hepatitis C virus [HCV] infection, hepatitis B virus [HBV] infection), CD4+ counts, viral load, and duration patients were monitored at the clinic (time on study). In total, 323 patients were evaluated: 82% males; 61% African American/12% Hispanic/19% Caucasian; mean age 37.9 years (standard deviation [SD] 8.5); 6% HBV-positive; 34% HCV-positive; 29% hypertensive; 3% diabetic; 52% tenofovir-treated; mean weight 75.4 kg (SD, 15.4); mean estimated glomerular filtration 114.5 mL/min/1.73 m(2) (SD, 36.7) using the Modification of Diet in Renal Disease (MDRD) calculation method; mean creatinine clearance (from which estimated glomerular filtration was extrapolated) by the Cockcroft-Gault calculation method 120.6 mL/min/1.73 m(2) (SD, 41.2); mean time on study 2.7 years (SD, 1.0 year). An estimated glomerular filtration rate decrease of >25% from baseline was significantly associated with time on study (P = 0.0017; hazards ratio [HR] = 0.999) and hypertension (HR = 1.706; P = 0.0158) by the MDRD method, and with age (HR = 1.039; P = 0.0077), weight (HR = 0.987; P = 0.0023), and time on study (HR = 0.999; P = 0.0043) by extrapolation of Cockcroft-Gault creatinine clearance calculation. No specific HAART agent was associated with significant renal impairment risk by the definition used in this study. This retrospective database study showed time on study, hypertension, weight, and age to be the only significant predictors of an estimated glomerular filtration rate decrease >25% from baseline.


Follow-up survey of participants attending the Advanced Trauma Operative Management (ATOM) Course.
The ATOM Course was developed to educate surgeons about the surgical management of penetrating injuries. Its goals are to improve knowledge, self-confidence, and technical competence. ATOM participants completed a 25-item questionnaire to assess self-efficacy (SE) for advanced trauma operative management before and immediately after taking the ATOM course. On follow-up, questionnaires were sent to ATOM participants. One was a 7-item survey to assess the value of the ATOM course to surgical practice. Another was the 25-item questionnaire to assess SE. Four items on the survey to assess the value of ATOM had mean scores > or = 4.0 and 3 had mean scores > 3.6. All had modes of 4.0 or greater. For all items, most respondents selected the agree options indicating positive assessments of the ATOM course to their surgical practice. For SE, the pre-ATOM mean SE score was 3.88 and the immediate post ATOM mean SE score was 4.57 (p < 0.05). The follow-up mean SE score was 4.47 indicating maintenance of SE (p > 0.05). Follow-up data from ATOM participants indicate that respondents believe the ATOM course improved their ability to identify and repair traumatic injuries. They report they use the techniques and knowledge learned in ATOM and confidence remains high after the ATOM course. ATOM is well received as an effective teaching strategy for surgical education for the management of penetrating injuries.


Combined technique of elastic magnetorheological finishing and HF etching for high-efficiency improving of the laser-induced damage threshold of fused silica optics.
The inadequate laser-induced damage threshold (LIDT) of optical elements limits the future development of high-power laser systems. With the aim of raising the LIDT, the elastic passivating treatment mechanism and parameter optimization of a combined magnetorheological finishing (MRF) and HF etching process are investigated. The relationships among the width/depth ratio of defects and parameters of the passivating treatment process (MRF and HF etching), relative intensity (RI), and LIDT of fused silica (FS) optics are revealed through a set of simulations and experiments. For high-efficiency improvement of LIDT, in an elastic passivating treatment process, scratches or other defects need not be wiped off entirely, but only passivated or enlarged to an acceptable profile. This combined process can be applied in polishing high-power-laser-irradiated components with high efficiency, low damage, and high LIDT. A 100 mm×100 mm×10 mm FS optic window is treated, and the width/depth ratio rises from 3 to 11, RI decreases from 4 to 1.2, and LIDT is improved from 7.8 to 17.8 J/cm2 after 385 min of MRF elastic polishing and 60 min of HF etching. Comparing this defect-carrying sample to the defect-free one, the MRF polishing time is shortened, obviously, from 1100 to 385 min, and the LIDT is merely decreased from 19.4 to 17.8 J/cm2. Due to the optimized technique, the fabricating time was shortened by a factor of 2.6, while the LIDT decreased merely 8.2%.


Influence of carrying a backpack on pelvic tilt, rotation, and obliquity in female college students.
The purpose of this investigation was to examine the influence of different methods of backpack carriage on pelvic tilt, obliquity and rotation of college-age females. Thirty subjects (mean age 22.4 years) participated in three conditions: walking without a backpack, carrying a backpack unilaterally, and carrying a backpack over both shoulders. The backpack was loaded with material that comprised 15% of the subject's body weight. Gait was analyzed using the Oxford Metrics VICON Clinical Manager system while the subject walked with no backpack, with a backpack unilaterally and bilaterally. Repeated measures analysis of variance was used to determine differences in angular motion and range of motion in pelvic tilt, rotation, and obliquity in three complete trials during the three walking conditions. Angular pelvic tilt was greatest with bilateral backpack carriage compared to unilateral carriage or walking without a backpack. Angles of pelvic obliquity and rotation were not changed across the three walking conditions. Range of motion for pelvic obliquity and rotation was significantly decreased when walking with a backpack. These results suggest that backpack carriage could cause permanent posture deviations in young female college students. More study is required to evaluate compressive forces during various walking conditions.


Long range chromosome organization in Escherichia coli: The position of the replication origin defines the non-structured regions and the Right and Left macrodomains.
The Escherichia coli chromosome is organized into four macrodomains (Ori, Ter, Right and Left) and two non-structured regions. This organization influences the segregation of sister chromatids, the mobility of chromosomal DNA, and the cellular localization of the chromosome. The organization of the Ter and Ori macrodomains relies on two specific systems, MatP/matS for the Ter domain and MaoP/maoS for the Ori domain, respectively. Here by constructing strains with chromosome rearrangements to reshuffle the distribution of chromosomal segments, we reveal that the difference between the non-structured regions and the Right and Left lateral macrodomains relies on their position on the chromosome. A change in the genetic location of oriC generated either by an inversion within the Ori macrodomain or by the insertion of a second oriC modifies the position of Right and Left macrodomains, as the chromosome region the closest to oriC are always non-structured while the regions further away behave as macrodomain regardless of their DNA sequence. Using fluorescent microscopy we estimated that loci belonging to a non-structured region are significantly closer to the Ori MD than loci belonging to a lateral MD. Altogether, our results suggest that the origin of replication plays a prominent role in chromosome organization in E. coli, as it determines structuring and localization of macrodomains in growing cell.


Immune effects of targeted radiation therapy for cancer.
Radiation therapy plays an important role in the treatment of the majority of cancers, and is commonly used to treat both localized and metastatic disease. Immunotherapy has recently been firmly integrated into the treatment of metastatic melanoma, and holds significant promise in treating a variety of other cancers. Although large field radiation has historically been appreciated for its immunosuppressive ability, targeted radiation can induce substantial changes in the tumor microenvironment beyond cellular cytotoxicity that evoke innate and adaptive immune responses. Previous studies have highlighted radiation-induced changes in proinflammatory cytokines, chemokines, effector, and immunosuppressive T cell subsets, as well as in immune receptors on tumor cells. Some of these changes in localized and systemic immune mediators have been linked to expansion of tumor-reactive T cells, improved clinical responses, and increased overall survival in preclinical and clinical models. Taken together, this evidence suggests that targeted radiation therapy can impact anti-tumor immune responses, and may potentially be combined with immunotherapy for synergistic effect.


Central line associated blood stream infection rate after intervention and comparing outcome with national healthcare safety network and international nosocomial infection control consortium data.
Benchmarking of central line associated blood stream infection (CLABSI) rates remains a problem in developing countries due to the variations in surveillance practices and/or infection risk as non-availability of national data. The aim of the following study was to find out the CLABSI rate before and after central line (CL) bundle intervention and compare the outcome with international surveillance data. This prospective longitudinal cohort study on adult intensive care unit patients was conducted at Hera General Hospital, Makkah Saudi Arabia from January 1 to December 31, 2012. Five key components of bundle were selected; hand hygiene, maximal barrier precautions upon insertion, skin antisepsis, optimum site selection and daily review of line necessity with prompt removal of unnecessary lines. Post-intervention CLABSI rate was compared with National Healthcare Safety Network (NHSN) and International Nosocomial Infection Control Consortium (INICC) rates. Statistical Package for the Social Sciences (SPSS) 14.0 software (SPSS Inc., 233 South Wacker Drive, 11(th) floor Chicago, USA) was used for statistical analysis included regression analysis for correlation. Statistical significance was set at P < 0.05. CLABSI rate was reduced from 10.1 to 6.5 per 1000 CL days after interventions and had significant correlation with overall bundle compliance rate 87.6% (P = 0.02) On benchmarking, CLABSI rate after the intervention was similar to mean pool value of INICC (6.8) while higher than NHSN (3.1). The most common microorganisms isolated were; methicillin-resistant Staphylococcus aureus (30.8%), Acinetobacter baumanii (23.3%) and Enterococcus faecalis (15.4%). We found that INICC data was a better benchmarking tool comparative to NHSN because it represents the countries that are developing the surveillance system. A multicenter national study is recommended.


Final height, target height and the community.
Height varies with age, and it varies with historic time. Final height is determined by endocrine parameters and genetics, by nutrition and health, by environmental factors, by birth weight, early growth, BMI, and developmental tempo. European populations of the 19th century were short, but their shortness did not result from growth impairment at all ages. In those days, shortness was mainly due to a significantly blunted adolescent growth spurt. New modelling approaches suggest an independent regulation of adolescent growth and final height: the target for growth and final height appears to be set by the community. In order to test this hypothesis, we formed a geographic network of Switzerland consisting of 169 nodes (district capitals) and 335 connecting edges (roads), and investigated military conscript data obtained between 2004 and 2009. Average height of Swiss military conscripts was 178.2 cm (SD 6.5 cm). But conscripts from first order neighbouring districts were more similar in height than expected. Short stature districts have short, tall stature districts have tall neighbours. We found significant height correlations between 1st (r=0.58), 2nd (r=0.64), 3rd (r=0.45) and even 4th order neighbours (r=0.42). It appears that tall stature communities generate tall people, short stature communities generate short people, and migrants orientate towards the new height target of their host population (community effect on growth).


Ecology of Anaplasma phagocytophilum and Borrelia burgdorferi in the western United States.
We discuss the ecology of Anaplasma phagocytophilum and Borrelia burgdorferi in the western U.S. These agents, while emerging in the eastern U.S., remain stable or rare in the west. In the western U.S., tick vectors and mammalian hosts for B. burgdorferi and A. phagocytophilum are distinct from those in the eastern U.S. and considerably more variable. Spatial complexity, local extinctions, and low levels of movement among foci may determine the distribution and prevalence of these agents. High-prevalence A. phagocytophilum patches may be transient, possibly as host individuals become immune. Thus, A. phagocytophilum in California could exist in a metapopulation of interacting patches. Local dynamics are sensitive to host population sizes and minimum tick infestation levels. Determining critical values for these key factors and their interactions will be important for predicting the level and distribution of future infections in the western U.S.


Leukocyte telomere length variation due to DNA extraction method.
Telomere length is indicative of biological age. Shorter telomeres have been associated with several disease and health states. There are inconsistencies throughout the literature amongst relative telomere length measured by quantitative PCR (qPCR) and different extraction methods or kits used. We quantified whole-blood leukocyte telomere length using the telomere to single copy gene (T/S) ratio by qPCR in 20 young (18-25 yrs) men after extracting DNA using three common extraction methods: Lahiri and Nurnberger (high salt) method, PureLink Genomic DNA Mini kit (Life Technologies) and QiaAmp DNA Mini kit (Qiagen). Telomere length differences of DNA extracted from the three extraction methods was assessed by one-way analysis of variance (ANOVA). DNA purity differed between extraction methods used (P=0.01). Telomere length was impacted by the DNA extraction method used (P=0.01). Telomeres extracted using the Lahiri and Nurnberger method (mean T/S ratio: 2.43, range: 1.57-3.02) and PureLink Genomic DNA Mini Kit (mean T/S ratio: 2.57, range: 2.24-2.80) did not differ (P=0.13). Likewise, QiaAmp and Purelink-extracted telomeres were not statistically different (P=0.14). The Lahiri-extracted telomeres, however, were significantly shorter than those extracted using the QiaAmp DNA Mini Kit (mean T/S ratio: 2.71, range: 2.32-3.02; P=0.003). DNA purity was associated with telomere length. There are discrepancies between the length of leukocyte telomeres extracted from the same individuals according to the DNA extraction method used. DNA purity could be responsible for the discrepancy in telomere length but this will require validation studies. We recommend using the same DNA extraction kit when quantifying leukocyte telomere length by qPCR or when comparing different cohorts to avoid erroneous associations between telomere length and traits of interest.


Classification of genomic islands using decision trees and their ensemble algorithms.
Genomic islands (GIs) are clusters of alien genes in some bacterial genomes, but not be seen in the genomes of other strains within the same genus. The detection of GIs is extremely important to the medical and environmental communities. Despite the discovery of the GI associated features, accurate detection of GIs is still far from satisfactory. In this paper, we combined multiple GI-associated features, and applied and compared various machine learning approaches to evaluate the classification accuracy of GIs datasets on three genera: Salmonella, Staphylococcus, Streptococcus, and their mixed dataset of all three genera. The experimental results have shown that, in general, the decision tree approach outperformed better than other machine learning methods according to five performance evaluation metrics. Using J48 decision trees as base classifiers, we further applied four ensemble algorithms, including adaBoost, bagging, multiboost and random forest, on the same datasets. We found that, overall, these ensemble classifiers could improve classification accuracy. We conclude that decision trees based ensemble algorithms could accurately classify GIs and non-GIs, and recommend the use of these methods for the future GI data analysis. The software package for detecting GIs can be accessed at http://www.esu.edu/cpsc/che_lab/software/GIDetector/.


Darwin and the scientific method.
There is a contradiction between Darwin's methodology and how he described it for public consumption. Darwin claimed that he proceeded "on true Baconian [inductive] principles and without any theory collected facts on a wholesale scale." He also wrote, "How odd it is that anyone should not see that all observation must be for or against some view if it is to be of any service!" The scientific method includes 2 episodes. The first consists of formulating hypotheses; the second consists of experimentally testing them. What differentiates science from other knowledge is the second episode: subjecting hypotheses to empirical testing by observing whether or not predictions derived from a hypothesis are the case in relevant observations and experiments. A hypothesis is scientific only if it is consistent with some but not other possible states of affairs not yet observed, so that it is subject to the possibility of falsification by reference to experience. Darwin occupies an exalted place in the history of Western thought, deservedly receiving credit for the theory of evolution. In The Origin of Species, he laid out the evidence demonstrating the evolution of organisms. More important yet is that he discovered natural selection, the process that accounts for the adaptations of organisms and their complexity and diversification. Natural selection and other causal processes of evolution are investigated by formulating and testing hypotheses. Darwin advanced hypotheses in multiple fields, including geology, plant morphology and physiology, psychology, and evolution, and subjected them to severe empirical tests.


Experts see it all: configural effects in action observation.
Biological motion perception is influenced by observers' familiarity with the observed action. Here, we used classical dance as a means to investigate how visual and motor experience modulates perceptual mechanism for configural processing of actions. Although some ballet moves are performed by only one gender, male and female dancers train together and acquire visual knowledge of all ballet moves. Twenty-four expert ballet dancers (12 female) and matched non-expert participants viewed pairs of upright and inverted point light female and common dance movements. Visual discrimination between different exemplars of the same movement presented upright was significantly better in experts than controls, whilst no differences were found when the same stimuli were presented upside down. These results suggest expertise influences configural action processing. Within the expert group, effects were stronger for female participants than for males, whilst no differences were found between movement types. This observer gender effect could suggest an additional role for motor familiarity in action perception, over and above the visual experience. Our results are consistent with a specific motor contribution to configural processing of action.


The influence of social capital on health in eight former Soviet countries: why does it differ?
Previous research has identified the role of social capital in explaining variations in health in the countries of the former Soviet Union. This study explores whether the benefits of social capital vary among these countries and why. The impact of micro social capital (trust, membership and social isolation) on individual health was estimated in each of eight former Soviet republics using instrumental variables to overcome methodological hazards such as endogeneity and reverse causality. Interactions with institutional variables (voice and accountability, effectiveness of the legal system, informal economy) and social protection variables (employment protection, old age and disability benefits, sickness and health benefits) were examined. Most social capital indicators, in most countries, are associated with better health but the magnitude and significance of the impact differ between countries. Some of this variation can be explained by interacting social capital indicators with measures of institutional quality, with membership of organisations bringing greater benefit for health in countries where civil liberties are stronger, whereas social isolation has more adverse consequences where there is a large informal economy. A lesser amount is explained by the interaction of social capital indicators with selected measures of social protection. When considering interventions to improve social capital as a means of improving population health, it seems advisable to take into account the influence of macrocontextual variables, in order not to overstate or understate the likely impact of the intervention.


Noninvasive and minimally invasive techniques for the diagnosis and management of allergic diseases.
Allergic diseases of the (upper and lower) airways, the skin and the gastrointestinal tract, are on the rise, resulting in impaired quality of life, decreased productivity, and increased healthcare costs. As allergic diseases are mostly tissue-specific, local sampling methods for respective biomarkers offer the potential for increased sensitivity and specificity. Additionally, local sampling using noninvasive or minimally invasive methods can be cost-effective and well tolerated, which may even be suitable for primary or home care sampling. Non- or minimally invasive local sampling and diagnostics may enable a more thorough endotyping, may help to avoid under- or overdiagnosis, and may provide the possibility to approach precision prevention, due to early diagnosis of these local diseases even before they get systemically manifested and detectable. At the same time, dried blood samples may help to facilitate minimal-invasive primary or home care sampling for classical systemic diagnostic approaches. This EAACI position paper contains a thorough review of the various technologies in allergy diagnosis available on the market, which analytes or biomarkers are employed, and which samples or matrices can be used. Based on this assessment, EAACI position is to drive these developments to efficiently identify allergy and possibly later also viral epidemics and take advantage of comprehensive knowledge to initiate preventions and treatments.


Membrane pores--from biology to track-etched membranes.
Flow of ions through narrow pores, either induced in biological membranes or created in synthetic membrane filters, exhibits, under appropriate conditions: 1) rapid switching of ion current between high and low conducting states; 2) selectivity between different ions; 3) inhibition by protons or divalent cations with an order of efficacy usually H(+)> Zn(2+)>Ca(2+)>Mg(2+). It seems reasonable to conclude that these common properties arise from a common cause-the nature of the flow of ions close to a charged surface.


Coping Well with Advanced Cancer: A Serial Qualitative Interview Study with Patients and Family Carers.
To understand successful strategies used by people to cope well when living with advanced cancer; to explore how professionals can support effective coping strategies; to understand how to support development of effective coping strategies for patients and family carers. Qualitative serial (4-12 week intervals) interview study with people with advanced cancer and their informal carers followed by focus groups. The iterative design had a novel focus on positive coping strategies. Interview analysis focused on patients and carers as individuals and pairs, exploring multiple dimensions of their coping experiences. Focus group analysis explored strategies for intervention development. 26 people with advanced (stage 3-4) breast, prostate, lung or colorectal cancer, or in receipt of palliative care, and 24 paired nominated informal/family carers. Participants recruited through outpatient clinics at two tertiary cancer centres in Merseyside and Manchester, UK, between June 2012 and July 2013. 45 patient and 41 carer interviews were conducted plus 4 focus groups (16 participants). People with advanced cancer and their informal/family carers develop coping strategies which enable effective management of psychological wellbeing. People draw from pre-diagnosis coping strategies, but these develop through responding to the experience of living with advanced cancer. Strategies include being realistic, indulgence, support, and learning from others, which enabled participants to regain a sense of wellbeing after emotional challenge. Learning from peers emerged as particularly important in promoting psychological wellbeing through the development of effective 'everyday', non-clinical coping strategies. Our findings challenge current models of providing psychological support for those with advanced cancer which focus on professional intervention. It is important to recognise, enable and support peoples' own resources and coping strategies. Peer support may have potential, and could be a patient-centred, cost effective way of managing the needs of a growing population of those living with advanced cancer.


Single-trial classification of event-related potentials in rapid serial visual presentation tasks using supervised spatial filtering.
Accurate detection of single-trial event-related potentials (ERPs) in the electroencephalogram (EEG) is a difficult problem that requires efficient signal processing and machine learning techniques. Supervised spatial filtering methods that enhance the discriminative information in EEG data are commonly used to improve single-trial ERP detection. We propose a convolutional neural network (CNN) with a layer dedicated to spatial filtering for the detection of ERPs and with training based on the maximization of the area under the receiver operating characteristic curve (AUC). The CNN is compared with three common classifiers: 1) Bayesian linear discriminant analysis; 2) multilayer perceptron (MLP); and 3) support vector machines. Prior to classification, the data were spatially filtered with xDAWN (for the maximization of the signal-to-signal-plus-noise ratio), common spatial pattern, or not spatially filtered. The 12 analytical techniques were tested on EEG data recorded in three rapid serial visual presentation experiments that required the observer to discriminate rare target stimuli from frequent nontarget stimuli. Classification performance discriminating targets from nontargets depended on both the spatial filtering method and the classifier. In addition, the nonlinear classifier MLP outperformed the linear methods. Finally, training based AUC maximization provided better performance than training based on the minimization of the mean square error. The results support the conclusion that the choice of the systems architecture is critical and both spatial filtering and classification must be considered together.


Compensatory and non-compensatory multidimensional randomized item response models.
Randomized response (RR) models are often used for analysing univariate randomized response data and measuring population prevalence of sensitive behaviours. There is much empirical support for the belief that RR methods improve the cooperation of the respondents. Recently, RR models have been extended to measure individual unidimensional behaviour. An extension of this modelling framework is proposed to measure compensatory or non-compensatory multiple sensitive factors underlying the randomized item response process. A confirmatory multidimensional randomized item response theory model (MRIRT) is proposed for the analysis of multivariate RR data by modelling the response process and specifying structural relationships between sensitive behaviours and background information. A Markov chain Monte Carlo algorithm is developed to estimate simultaneously the parameters of the MRIRT model. The model extension enables the computation of individual true item response probabilities, estimates of individuals' sensitive behaviour on different domains, and their relationships with background variables. An MRIRT analysis is presented of data from a college alcohol problem scale, measuring alcohol-related socio-emotional and community problems, and alcohol expectancy questionnaire, measuring alcohol-related sexual enhancement expectancies. Students were interviewed via direct or RR questioning. Scores of alcohol-related problems and expectancies are significantly higher for the group of students questioned using the RR technique. Alcohol-related problems and sexual enhancement expectancies are positively moderately correlated and vary differently across gender and universities.


Enhanced sensitivity to punctate painful stimuli in female patients with chronic low back pain.
Chronic low back pain (CLBP) has been shown to be associated with various pathophysiological changes at several level of the sensorimotor system, pointing to a general hypersensitivity in CLBP patients. The aim of the present study was to investigate signs of generalized mechanical pain hypersensitivity in CLBP patients on the hand and on the painful site of the back. Pinprick stimulation according to a validated standardized quantitative sensory testing protocol was used in 14 female CLBP patients and 14 healthy controls (HC) matched for sex and age. Stimulus response functions to pinprick stimulation on the skin were examined at the affected back and reference sites (hand palmar and hand dorsum). Data from CLBP patients were compared with HC and with reference data from the German Research Network on Neuropathic Pain. We found significant differences in the stimulus response functions between CLBP patients and HC. Pain ratings to the pinpricks were increased for low and moderate pinprick stimuli in CLBP patients. Importantly, this kind of specific pinprick hyperalgesia was found not only for the affected body site (back), but also for the remote reference sites (hand dorsum and hand palmar). We interpret our results as pointing to changes in the nociceptive processing in CLBP at higher levels of the neuraxis, possibly thalamus and/or attentional control, rather than changes of spinal processing. Alternatively, there might be a higher vulnerability to noxious stimulation in CLBP patients.


Modification of penicillin-binding protein 5 associated with high-level ampicillin resistance in Enterococcus faecium.
High-level ampicillin resistance in Enterococcus faecium has been shown to be associated with the synthesis of a modified penicillin-binding protein 5 (PBP 5) which had apparently lost its penicillin-binding capability (R. Fontana, M. Aldegheri, M. Ligozzi, H. Lopez, A. Sucari, and G. Satta. Antimicrob. Agents Chemother. 38:1980-1983, 1994). The pbp5 gene of the highly resistant strain E. faecium 9439 was cloned and sequenced. The deduced amino acid sequence showed 77 and 54% homologies with the PBPs 5 of Enterococcus hirae and Enterococcus faecalis, respectively. A gene fragment coding for the C-terminal part of PBP 5 containing the penicillin-binding domain was also cloned from several E. faecium strains with different levels of ampicillin resistance. Sequence comparison revealed a few point mutations, some of which resulted in amino acid substitutions between SDN and KTG motifs in PBPs 5 of highly resistant strains. One of these converted a polar residue (the T residue at position 562 or 574) of PBP 5 produced by susceptible and moderately resistant strains into a nonpolar one (A or I). This alteration could be responsible for the altered phenotype of PBP 5 in highly resistant strains.


Prevention of biofilm formation by methacrylate-based copolymer films loaded with rifampin, clarithromycin, doxycycline alone or in combination.
This study reports the incorporation of the antibiotics rifampin, doxycycline and clarithromycin in poly(styrene-co-methyl methacrylate films and their effect on biofilm prevention. Invasive procedures in patients such as surgical device, or intravenous or urinary catheter implantation, often results in complicated hospital-acquired nosocomial infections. Biofilm formation is essential to establish these infections on these devices and novel antibiotic delivery approaches are needed for more effective management. The films were evaluated in vitro for drug release and for their ability to prevent biofilm formation by methicillin susceptible and methicillin resistant Staphylococcus aureus. Surface tension components, obtained from contact angle measurements, and the morphology of the films evaluated by scanning electron microscopy were also investigated. In this study, antibiotic-loaded methacrylic copolymer films that effectively released rifampin, clarithromycin and doxycycline for up to 21 days prevented biofilm formation when tested in an in vitro bioreactor model. These drug loaded copolymer films provided the advantage by coating materials with a novel surface that was unsuitable for resettling of biofilms once the antibiotic was dissolved from the polymer surface. A combination of rifampin and clarithromycin released from the polymer film provided >99.9% kill of an MRSA inoculate for up to 72 h. Results showed that combining multiple drugs in copolymer films with unique surface properties, initial hydrophilicity and increase in roughness, can be an effective way to prevent biofilm formation.


Treatment policy change to dihydroartemisinin-piperaquine contributes to the reduction of adverse maternal and pregnancy outcomes.
In Papua, Indonesia, maternal malaria is prevalent, multidrug resistant and associated with adverse outcomes for mother and baby. In March 2006, anti-malarial policy was revised for the second and third trimester of pregnancy to dihydroartemisinin-piperaquine (DHP) for all species of malaria. This study presents the temporal analysis of adverse outcomes in pregnancy and early life following this policy change. From April 2004 to May 2010, a standardized questionnaire was used to collect information from all pregnant women admitted to the maternity ward. A physical examination was performed on all live birth newborns. The relative risks (RR) and the associated population attributable risks (PAR) of adverse outcomes in women with a history of malaria treatment to the risk in those without a history of malaria during the current pregnancy were examined to evaluate the temporal trends before and after DHP deployment. Of 6,556 women enrolled with known pregnancy outcome, 1,018 (16%) reported prior anti-malarial treatment during their pregnancy. The proportion of women with malaria reporting treatment with DHP rose from 0% in 2004 to 64% (121/189) in 2010. In those with history of malaria during pregnancy, the increasing use of DHP was associated with a 54% fall in the proportion of maternal malaria at delivery and a 98% decrease in congenital malaria (from 7.1% prior to 0.1% after policy change). Overall policy change to more effective treatment was associated with an absolute 2% reduction of maternal severe anaemia and absolute 4.5% decrease in low birth weight babies. Introduction of highly effective treatment in pregnancy was associated with a reduction of maternal malaria at delivery and improved neonatal outcomes. Ensuring universal access to arteminisin combination therapy (ACT) in pregnancy in an area of multidrug resistance has potential to impact significantly on maternal and infant health.


Breastfeeding and coffee consumption in children younger than 2 years in Boston, Massachusetts, USA.
Although introduction of inappropriate foods and liquids in early childhood and their association with breastfeeding is commonly reported in US children, coffee use in very young US children and its association with breastfeeding is not. This study aimed to determine the proportion of 1- and 2-year-olds in an urban population consuming coffee, their rate of consumption, and predictors of consumption, including breastfeeding status. We used data from a prospective cohort study on infant weight gain and diet, and body mass index at age 2. We used bivariate analyses to examine variables associated with coffee consumption at 1 and 2 years and multivariate logistic regression to control for variables of interest. This study included 315 mother-infant dyads. At 1 year, the rate of coffee consumption reported was 2.5%; at 2 years, it was 15.2% and average daily consumption was 1.09 oz (range, 0.01- 4.00 oz). The only characteristic associated with coffee consumption at 1 year was breastfeeding at 1 year (P = .0275), which did not remain significant after controlling for confounding variables. Variables significantly associated with coffee consumption at year 2 were lower maternal education (P = .0016), non-US maternal place of birth (P = .0015), maternal Hispanic ethnicity (P < .0001), infant female sex (P = .0495), and receiving any breast milk at 1 year of age (P = .0189). After multivariate logistic regression, maternal Hispanic ethnicity (P = .0139) and infant female sex (P = .0371) remained significant. Coffee consumption is not uncommon among toddlers in Boston, Massachusetts, USA. After controlling for possible confounding factors, maternal ethnicity and infant sex were significantly associated with this practice.


Equilibration of 6-[18F]fluoro-L-m-tyrosine between plasma and erythrocytes.
Intracranial or intraventricular blood pools have been suggested as noninvasive sources of an input function for quantitative PET. These techniques measure the concentration of the tracer in whole blood, but the concentration in plasma depends on the equilibration of the tracer between plasma and erythrocytes. FDG, 6-[18F]fluoro-L-m-tyrosine (FmT), or its major metabolite, 6-[18F]fluoro-3-hydroxyphenylacetic acid (FHPAA), was added to blood samples obtained from healthy fasting volunteers along with radioiodinated human serum albumin (RIHSA). Samples were incubated at 37 degrees C for times between 10 s and 2 h and then plunged into an ice bath and centrifuged. Whole blood and plasma were counted for 18F and 125I activities. The resulting time courses were fit to successively more complex models, evaluated using an F test. All radioactivity associated with RIHSA remained in the plasma, whereas FDG equilibrated instantaneously between plasma and erythrocytes. FmT took about 1 h to equilibrate between plasma and erythrocytes; this time course could be described by a single exponential with a half-life of 10 min. FHPAA equilibrated within the first 5 min of the study. Our results show that, unlike FDG, the partitioning of FmT between plasma and erythrocytes is a relatively slow process. We present an analytic correction that may be applied to the measured time course of radioactivity in whole blood to obtain the time course of the tracer in plasma.


Cross-talk between gibberellin and auxin in development of Populus wood: gibberellin stimulates polar auxin transport and has a common transcriptome with auxin.
Both indole acetic acid (IAA) and gibberellins (GAs) stimulate cell and organ growth. We have examined GA/IAA cross-talk in cambial growth of hybrid aspen (Populus tremulaxtremuloides). Decapitated trees were fed with IAA and GA, alone and in combination. Endogenous hormone levels after feeding were measured, by mass spectrometry, in the stem tissues below the point of application. These stem tissues with defined hormone balances were also used for global transcriptome analysis, and the abundance of selected transcripts was measured by real-time reverse-transcription polymerase chain reaction. By feeding isotope-labeled IAA, we demonstrated that GA increases auxin levels in the stem by stimulating polar auxin transport. This finding adds a new dimension to the concept that the endogenous GA/IAA balance in plants is determined by cross-talk between the two hormones. We also show that GA has a common transcriptome with auxin, including many transcripts related to cell growth. This finding provides molecular support to physiological experiments demonstrating that either hormone can induce growth if the other hormone is absent/deficient because of mutations or experimental treatments. It also highlights the potential for extensive cross-talk between GA- and auxin-induced responses in vegetative growth of the intact plant. The role of endogenous IAA and GA in wood development is discussed.