Psychiatric morbidity among HIV-infected children and adolescents in a resource-poor Kenyan urban community.
The course of HIV/AIDS in children has been transformed from an acute to a chronic one with the advent of Anti-Retroviral Therapy. The aim of this study was to determine the prevalence and pattern of psychiatric morbidity in HIV-infected children and adolescents between 6 and 18 years of age and the relationship between their socio-demographic factors, immune suppression and psychiatric morbidity. The study was conducted at a paediatric HIV clinic in Nairobi, between February and April 2010. One hundred and sixty-two HIV-infected children and adolescents aged between 6 and 18 years and their guardians were interviewed. Seventy-nine (48.8%) of the study participants were found to have psychiatric morbidity. The most prevalent Diagnostic Statistical Manual, 4th Edition TR psychiatric disorders were: Major depression (17.8%), Social phobia (12.8%), Oppositional Defiant Disorder (12.1%) and Attention Deficit Hyperactivity Disorder (12.1%). Twenty-five per cent of the study participants had more than one psychiatric disorder. The prevalence of psychiatric morbidity in HIV-infected children is higher than that found in children in the general population. There is therefore a need to integrate psychiatric services into the routine care of HIV-infected children.


Charge-Induced Force Noise on Free-Falling Test Masses: Results from LISA Pathfinder.
We report on electrostatic measurements made on board the European Space Agency mission LISA Pathfinder. Detailed measurements of the charge-induced electrostatic forces exerted on free-falling test masses (TMs) inside the capacitive gravitational reference sensor are the first made in a relevant environment for a space-based gravitational wave detector. Employing a combination of charge control and electric-field compensation, we show that the level of charge-induced acceleration noise on a single TM can be maintained at a level close to 1.0 fm s^{-2} Hz^{-1/2} across the 0.1-100 mHz frequency band that is crucial to an observatory such as the Laser Interferometer Space Antenna (LISA). Using dedicated measurements that detect these effects in the differential acceleration between the two test masses, we resolve the stochastic nature of the TM charge buildup due to interplanetary cosmic rays and the TM charge-to-force coupling through stray electric fields in the sensor. All our measurements are in good agreement with predictions based on a relatively simple electrostatic model of the LISA Pathfinder instrument.


π-Hydrogen bonding and aromaticity: a systematic interplay study.
Quantum DFT calculations, corrected for long-range interactions, have been carried out on complex models formed between HF as a proton donor and 2-methylene-2H-indene derivatives as proton acceptors. Using various exocyclic X substitutions, mutual effects of the aromaticity and the strength of the resulting π-hydrogen bond (after its evaluation by AIM methodology) have been investigated. The results show that the aromaticity of 6-membered rings and the hydrogen bond strength increase upon increasing the electron-donating character of the X-substituents. Based on some aromaticity indices (HOMA, FLU, SA and NICS(1)zz), it has been shown that the formation of a π-hydrogen bond causes an increase of aromaticity of the 6-membered ring. Also, the strength of the resulting π-hydrogen bond (with an energy of about 4.0 to 7.0 kcal mol-1) depends on the aromaticity of the 6-membered ring and increases with an increase in the aromaticity. In addition, a linear relationship was found between the most negative value of the molecular electrostatic potential (Vmin) and the HOMA, which confirms that the Vmin in the region of the studied ring could be used as a new index to estimate the amount of aromaticity. The electronic properties of the complexes have also been evaluated by means of the molecular electrostatic potential (MEP), the atoms in molecules (AIM) and the natural bond orbital (NBO) analyses.


Quality of life in American Indian women with arthritis or diabetes.
We investigated quality of life (QOL) in American Indian women with different chronic diseases. Sixty American Indian women with diabetes mellitus (DM), rheumatoid arthritis (RA), or both DM and RA (DM + RA), and healthy control women received evaluations of joint motion, hand strength dexterity, pain, activity and participation limitations and QOL. The DM + RA and RA groups had significantly more pain, less joint motion, decreased hand strength, and more activity limitations. Participation was similar for all groups except the DM + RA group. Past and present QOL were similar; however, the DM + RA group reported significantly decreased future QOL. Results suggest that the presence of more than one chronic disease affects activity and participation. Factors that related to QOL were different for each disease group, with the exception of pain. Identification of factors related to QOL can help occupational therapists identify areas for intervention.


World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 1: update 2013 on the acute and continuation treatment of unipolar depressive disorders.
This 2013 update of the practice guidelines for the biological treatment of unipolar depressive disorders was developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The goal has been to systematically review all available evidence pertaining to the treatment of unipolar depressive disorders, and to produce a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. The guidelines are intended for use by all physicians seeing and treating patients with these conditions. The 2013 update was conducted by a systematic update literature search and appraisal. All recommendations were approved by the Guidelines Task Force. This first part of the guidelines (Part 1) covers disease definition, classification, epidemiology, and course of unipolar depressive disorders, as well as the management of the acute and continuation phase treatment. It is primarily concerned with the biological treatment (including antidepressants, other psychopharmacological medications, electroconvulsive therapy, light therapy, adjunctive and novel therapeutic strategies) of adults. To date, there is a variety of evidence-based antidepressant treatment options available. Nevertheless there is still a substantial proportion of patients not achieving full remission. In addition, somatic and psychiatric comorbidities and other special circumstances need to be more thoroughly investigated. Therefore, further high-quality informative randomized controlled trials are urgently needed.


What's in a care pathway? Towards a cultural cartography of the new NHS.
Maps are increasingly understood as socio-cultural and political constructs, rather than mirrors of nature. Drawing on the insights of cultural cartographers, this paper presents a critical analysis of a specific instance of map-making in health policy, namely the growing use of care pathways in care planning and service delivery. Widely regarded to date as devices for ensuring quality of care, equity of treatment, optimal resource allocation and a rational division of labour between healthcare professionals, they have been seen as helpful--and technically neutral--tools for routing patients through the system. By contrast, we argue that the metaphors are misleading: lived experience and its objectification in pathway maps continually re-create one another, as we explore the slippage between map, map-making and mapping. This paper is based on interviews and observations with a variety of healthcare workers in three areas of south eastern England. We trace the development of a series of pathways-in-process, and show how they configure the patient, highlighting some aspects of their experiences, whilst silencing others. We also analyse the role of pathways in the carving up and surveillance of space round the emergence of the 'hybrid professional', particularly new practitioners such as GP specialists, specialist nurses, extended scope therapists and others. In considering the wider implications of care pathways as part of the contemporary discourse on policy, the paper critiques the rationalist, and sometimes evangelical assumptions underpinning their current popularity. In particular, we suggest that a critical and processual understanding of pathways might contribute to a more informed appreciation of their potential (and their limitations) as mechanisms for healthcare policy implementation.


Denning behaviour of the European badger (Meles meles) correlates with bovine tuberculosis infection status.
Heterogeneities in behaviours of individuals may underpin important processes in evolutionary biology and ecology, including the spread of disease. Modelling approaches can sometimes fail to predict disease spread, which may partly be due to the number of unknown sources of variation in host behaviour. The European badger is a wildlife reservoir for bovine tuberculosis (bTB) in Britain and Ireland, and individual behaviour has been demonstrated to be an important factor in the spread of bTB among badgers and to cattle. Radio-telemetry devices were deployed on 40 badgers from eight groups to investigate patterns of den (sett) use in a high-density population, where each group had one or two main and three to eight outlier setts in their territory. Badgers were located at their setts for 28 days per season for 1 year to investigate how patterns differed between individuals. Denning behaviour may have a strong influence on contact patterns and the transmission of disease. We found significant heterogeneity, influenced by season, sex and age. Also, when controlling for these, bTB infection status interacting with season was highly correlated with sett use. Test-positive badgers spent more time away from their main sett than those that tested negative. We speculate that wider-ranging behaviour of test-positive animals may result in them contacting sources of infection more frequently and/or that their behaviour may be influenced by their disease status. Measures to control infectious diseases might be improved by targeting functional groups, specific areas or times of year that may contribute disproportionately to disease spread.


The impact of adolescent binge drinking and sustained abstinence on affective state.
While it is clear that affect is negatively impacted by heavy drinking in adulthood and that it improves with abstinence, little is known about effects of heavy drinking on mood during adolescence. This study examined negative mood states among 2 groups of 16- to 18-year-old high school students; youth with a history of recent heavy episodic drinking (HED; n = 39) and comparison youth with limited lifetime drinking experience (CON; n = 26). Affect was assessed at 3 time points during a 4- to 6-week period of monitored abstinence using the Hamilton Rating Scales for Anxiety and Depression; self-reports were obtained with the state portion of the State-Trait Anxiety Inventory, and experience sampling of current affect was assessed via daily text messages sent at randomly determined times in the morning, afternoon, and evening. Youth with a recent history of HED reported more negative affect compared with nondrinking youth during early stages of abstinence (days since last HED at assessment 1: M = 6.46; SD = 5.06); however, differences in affect were not observed after 4 to 6 weeks of abstinence. Sex differences were evident, with HED girls reporting greater depression and anxiety than HED male peers. Although not significant, response patterns indicated that boys may experience faster resolution of negative emotional states than girls with sustained abstinence. Findings suggest that high-dose drinking is associated with elevated negative affect for adolescents and that negative mood states may take longer to resolve for girls than for boys following heavy drinking episodes. Future research clarifying naturally occurring changes in affective response during early and sustained abstinence is necessary for improving programs designed to promote adolescent decision-making and to reduce risk for relapse.


New fungal genera, Tectonidula gen. nov. for Calosphaeria-like fungi with holoblastic-denticulate conidiogenesis and Natantiella gen. nov. for three species segregated from Ceratostomella.
Two morphologically similar groups of ascomycetes with globose to subglobose perithecia, elongate necks, unitunicate asci floating freely at maturity, and hyaline ascospores currently placed in Calosphaeria s. lat. and Ceratostomella s. lat., respectively, are studied. The Calosphaeria-like fungi have groups of perithecia growing between cortex and wood, arranged in circular groups with converging necks and piercing the cortex in a common point; the asci with a shallow apical ring and U- to horseshoe-shaped hyaline ascospores are compared with Calosphaeria pulchella, the type species of the genus. Conidiogenesis of the investigated Calosphaeria-like fungi is holoblastic-denticulate; ramichloridium-like and sporothrix-like conidiophores and conidia were formed in vitro. Ascospore and ascus morphology, structure of the ascal apex, ascogenous system, mode of conidiogenesis and the large subunit rRNA sequences of this group differ considerably from C. pulchella and both groups are unrelated. Thus a new genus, Tectonidula, is described with two accepted species, T. hippocrepida and T. fagi; they are separated by ascospore and ascus morphology and holoblastic-denticulate conidiogenesis from the core species of Calosphaeria. The placement of Tectonidula among perithecial ascomycetes is discussed. The relationship of Tectonidula with Barbatosphaeria and two ramichloridium-like hyphomycetous genera Rhodoveronaea and Myrmecridium is investigated. Three species formerly attributed to Ceratostomella are studied. The revision of the herbarium type specimen and fresh material of Ceratostomella ligneola revealed that it is conspecific with Ceratostomella ampullasca and Ceratostomella similis. The LSU phylogeny clearly separated C. ligneola from Ceratostomella s. str. and morphologically similar Lentomitella. On the basis of molecular sequence data and detailed comparison of morphology of asci, ascospores and ascogenous system the genus Natantiella is described for C. ligneola with C. ampullasca and C. similis as its synonyms. Natantiella produced sterile mycelium in vitro.


Deletion of murine choline dehydrogenase results in diminished sperm motility.
Choline dehydrogenase (CHDH) catalyzes the conversion of choline to betaine, an important methyl donor and organic osmolyte. We have previously identified single nucleotide polymorphisms (SNPs) in the human CHDH gene that, when present, seem to alter the activity of the CHDH enzyme. These SNPs occur frequently in humans. We created a Chdh(-/-) mouse to determine the functional effects of mutations that result in decreased CHDH activity. Chdh deletion did not affect fetal viability or alter growth or survival of these mice. Only one of eleven Chdh(-/-) males was able to reproduce. Loss of CHDH activity resulted in decreased testicular betaine and increased choline and PCho concentrations. Chdh(+/+) and Chdh(-/-) mice produced comparable amounts of sperm; the impaired fertility was due to diminished sperm motility in the Chdh(-/-) males. Transmission electron microscopy revealed abnormal mitochondrial morphology in Chdh(-/-) sperm. ATP content, total mitochondrial dehydrogenase activity and inner mitochondrial membrane polarization were all significantly reduced in sperm from Chdh(-/-) animals. Mitochondrial changes were also detected in liver, kidney, heart, and testis tissues. We suggest that men who have SNPs in CHDH that decrease the activity of the CHDH enzyme could have decreased sperm motility and fertility.


The evolution of relative brain size in marsupials is energetically constrained but not driven by behavioral complexity.
Evolutionary increases in mammalian brain size relative to body size are energetically costly but are also thought to confer selective advantages by permitting the evolution of cognitively complex behaviors. However, many suggested associations between brain size and specific behaviors - particularly related to social complexity - are possibly confounded by the reproductive diversity of placental mammals, whose brain size evolution is the most frequently studied. Based on a phylogenetic generalized least squares analysis of a data set on the reproductively homogenous clade of marsupials, we provide the first quantitative comparison of two hypotheses based on energetic constraints (maternal investment and seasonality) with two hypotheses that posit behavioral selection on relative brain size (social complexity and environmental interactions). We show that the two behavioral hypotheses have far less support than the constraint hypotheses. The only unambiguous associates of brain size are the constraint variables of litter size and seasonality. We also found no association between brain size and specific behavioral complexity categories within kangaroos, dasyurids, and possums. The largest-brained marsupials after phylogenetic correction are from low-seasonality New Guinea, supporting the notion that low seasonality represents greater nutrition safety for brain maintenance. Alternatively, low seasonality might improve the maternal support of offspring brain growth. The lack of behavioral brain size associates, found here and elsewhere, supports the general 'cognitive buffer hypothesis' as the best explanatory framework of mammalian brain size evolution. However, it is possible that brain size alone simply does not provide sufficient resolution on the question of how brain morphology and cognitive capacities coevolve.


Australia's rural medical workforce: Supply from its medical schools against career stage, gender and rural-origin.
The aim of this study was to explore the association between career stage and rural medical workforce supply among Australian-trained medical graduates. Descriptive analysis using the national Medicine in Australia: Balancing Employment and Life (MABEL) longitudinal study. Australian-trained GPs and other specialists who participated in the MABEL study, 2008-2013. Proportions of GPs and specialists working in rural locations, according to career stage (establishing, early, mid and late), gender and childhood-origin type (rural versus metropolitan). Logistic regression models revealed that establishing- and early-career GPs had significantly higher likelihood (OR 1.67 and 1.38, respectively) of working rurally, but establishing and early-career doctors were significantly less likely (OR 0.34 and 0.43, respectively) to choose general practice, contributing proportionally fewer rural GPs overall (OR 0.77 and 0.75, respectively) compared to late-career doctors. For specialists, there were no significant associations between career cohorts and rural practice. Overall, there was a significantly lower likelihood (OR 0.83) of establishing-career doctors practising rurally. Women were similarly likely to be rural GPs but less likely to be rural specialists, while rural-origin was consistently associated with higher odds of rural practice. The supply of Australia's rural medical workforce from its medical schools continues to be challenging, with these data highlighting both their source and associations with doctors at different career stages. Despite large investments through rural medical training and rural workforce recruitment and retention policies, these data confirm continued reliance on internationally trained medical graduates for large proportions of rural supply is likely.


Positive predictive value of specific mammographic findings according to reader and patient variables.
To evaluate the risk of cancer (positive predictive value [PPV]) associated with specific findings (mass, calcifications, architectural distortion, asymmetry) in mammographic examinations with abnormal results, to determine the distribution of these findings in examinations in which the patients received a diagnosis of cancer and examinations in which the patients did not, and to analyze PPV variation according to radiologist and patient factors. HIPAA-compliant institutional review board approval was obtained. PPV of mammographic findings was evaluated in a prospective cohort of 10,262 women who underwent 10,641 screening or diagnostic mammographic examinations with abnormal results between January 1998 and December 2002 in the San Francisco Mammography Registry. The cohort was linked with the Surveillance Epidemiology and End Results program to determine cancer status among these women. PPVs were calculated for each finding and were stratified according to patient characteristics, cancer type, and radiologist reader. Cases of breast cancer (n = 1552) were identified (invasive, n = 1287; ductal carcinoma in situ, n = 270); in five, both kinds of breast cancer were recorded. Overall, of the number of interpretations, masses were most frequently noted in 56%, followed by calcifications in 29%, asymmetry in 12%, and architectural distortion in 4%. Masses, calcifications, architectural distortion, and developing asymmetry demonstrated similar PPVs in screening examinations (9.7%, 12.7%, 10.2%, and 7.4%, respectively), whereas one-view-only and focal asymmetry demonstrated lower PPVs (3.6% and 3.7%, respectively) and were a frequent reason for an abnormal result (42%). Overall, one (5%) in 20 invasive cancers was identified with asymmetry, one (6%) in 16 invasive cancers was identified with architectural distortion, one (21%) in five invasive cancers was identified with calcifications, and two (68%) in three invasive cancers were identified with a mass. Five percent of invasive cancers were identified with asymmetry, and asymmetry is more weakly associated with cancer in screening examinations than are mass, calcifications, and architectural distortion.


Comparison of PC and iPad administrations of the Cogstate Brief Battery in the Mayo Clinic Study of Aging: Assessing cross-modality equivalence of computerized neuropsychological tests.
Objective: Computerized neuropsychological assessments are increasingly used in clinical practice, population studies of cognitive aging and clinical trial enrichment. Subtle, but significant, performance differences have been demonstrated across different modes of test administration and require further investigation. Method: Participants included cognitively unimpaired adults aged 50 and older from the Mayo Clinic Study of Aging who completed the Cogstate Brief Battery and Cogstate's Groton Maze Learning Test (GMLT) on an iPad or a personal computer (PC) in the clinic. Mode of administration differences and test-retest reliability coefficients were examined across 3 cohorts: a demographically matched test-retest cohort completing PC and iPad administrations the same day (N = 168); a test naïve cohort comparing baseline PC (n = 1820) and iPad (n =605) performance; and a demographically matched longitudinal cohort completing 3 Cogstate visits over 15 months on either the PC (n =63) or iPad (n =63). Results: Results showed a small but statistically significant and consistent finding for faster performance on PC relative to iPad for several Cogstate Brief Battery measures. Measures of accuracy generally did not differ or differences were very small. The GMLT showed faster performance and higher total errors on iPad. Most Cogstate variables showed no difference in the rate of change across PC and iPad administrations. Conclusions: There are small, but significant, differences in performance when giving the same cognitive tests on a PC or an iPad. Future studies are needed to better understand if these small differences impact the clinical interpretation of results and research outcomes.


Microfluidic enhancement of self-assembly systems.
Dynamic, kinetically-controlled, self-assembly processes are commonly observed in nature and are capable of creating intricate, functional architectures from simple precursors. However, notably, much of the research into molecular self-assembly has been performed using conventional bulk techniques where the resultant species are dictated by thermodynamic stability to yield relatively simple assemblies. Whereas, the environmental control offered by microfluidic systems offers methods to achieve non-equilibrium reaction conditions capable of increasingly sophisticated self-assembled structures. Alterations to the immediate microenvironment during the assembly of the molecules is possible, providing the basis for kinetically-controlled assembly. This review examines the key mechanism offered by microfluidic systems and the architectures required to access them. The mechanisms include diffusion-led mixing, shear gradient alignment, spatial and temporal confinement, and structural templates in multiphase systems. The works are selected and categorised in terms of the microfluidic approaches taken rather than the chemical constructs which are formed.


Which patient requires neuroendocrine assessment following traumatic brain injury, when and how?
Traumatic brain injury (TBI) is an important public health problem, particularly among young adults in industrialized countries. Hypopituitarism is a common occurrence among survivors of TBI and may contribute to the associated morbidity seen in the acute and chronic phases following injury. The available data suggest that survivors of moderate to severe TBI should undergo screening for hypopituitarism particularly in the first year after injury. This requires a close liaison between endocrinologists, neurosurgeons, neuropsychologists, intensive care and rehabilitation physicians. Patients who suffer milder forms of TBI should also be considered for endocrine evaluation if they exhibit any clinical features of pituitary hormone deficiencies.


Linking the response properties of cells in auditory cortex with network architecture: cotuning versus lateral inhibition.
The frequency-intensity receptive fields (RF) of neurons in primary auditory cortex (AI) are heterogeneous. Some neurons have V-shaped RFs, whereas others have enclosed ovoid RFs. Moreover, there is a wide range of temporal response profiles ranging from phasic to tonic firing. The mechanisms underlying this diversity of receptive field properties are yet unknown. Here we study the characteristics of thalamocortical (TC) and intracortical connectivity that give rise to the individual cell responses. Using a mouse auditory TC slice preparation, we found that the amplitude of synaptic responses in AI varies non-monotonically with the intensity of the stimulation in the medial geniculate nucleus (MGv). We constructed a network model of MGv and AI that was simulated using either rate model cells or in vitro neurons through an iterative procedure that used the recorded neural responses to reconstruct network activity. We compared the receptive fields and firing profiles obtained with networks configured to have either cotuned excitatory and inhibitory inputs or relatively broad, lateral inhibitory inputs. Each of these networks yielded distinct response properties consistent with those documented in vivo with natural stimuli. The cotuned network produced V-shaped RFs, phasic-tonic firing profiles, and predominantly monotonic rate-level functions. The lateral inhibitory network produced enclosed RFs with narrow frequency tuning, a variety of firing profiles, and robust non-monotonic rate-level functions. We conclude that both types of circuits must be present to account for the wide variety of responses observed in vivo.


Encapsulation of superparamagnetic iron oxide nanoparticles in poly-(lactide-co-glycolic acid) microspheres for biomedical applications.
Magnetic microspheres were prepared using a single step coaxial electrohydrodynamic atomization technique at ambient temperature and pressure, with poly(lactic-co-glycolic acid) as the coating and iron oxide (Fe3O4) nanoparticles dispersed in polyethylene glycol as the encapsulated material. The morphology and particle size distributions of the prepared magnetic microspheres were investigated by scanning electron microscopy. The particles were spherical with mean diameters ranging from ~2 μm to 18 μm, depending on the combination of processing parameters (flow rate and applied voltage). Analysis by infrared spectroscopy and focused ion-beam sectioning confirmed incorporation of iron oxide nanoparticles into the microspheres and the prepared samples were shown to be responsive to an applied magnetic field. This study demonstrates a convenient method for the preparation of nanoparticle loaded microspheres, which could be used potentially as transverse relaxation contrast agents in magnetic resonance imaging, as well as for magnetically guided drug delivery.


Hierarchical community classification and assessment of aquatic ecosystems using artificial neural networks.
Benthic macroinvertebrate communities in stream ecosystems were assessed hierarchically through two-level classification methods of unsupervised learning. Two artificial neural networks were implemented in combination. Firstly, the self-organizing map (SOM) was used to reduce the dimension of community data, and secondly, the adaptive resonance theory (ART) was subsequently applied to the SOM to further classify the groups in different scales. Hierarchical grouping in community data efficiently reflected the impact of the environmental factors such as topographic conditions, levels of pollution, and sampling location and time across different scales. New community data not included in the training process were used to test the trained network model. The input data were appropriately grouped at different hierarchical levels by the trained networks, and correspondingly revealed the impact of environmental disturbances and temporal dynamics of communities. The hierarchical clusters based on a two-level classification method could be useful for assessing ecosystem quality and community variations caused by environmental disturbances.


Activity-dependent constraints on catecholamine signaling.
Catecholamine signaling is thought to modulate cognition in an inverted-U relationship, but the mechanisms are unclear. We measured norepinephrine and dopamine release, postsynaptic calcium responses, and interactions between tonic and phasic firing modes under various stimuli and conditions. High tonic activity in vivo depleted catecholamine stores, desensitized postsynaptic responses, and decreased phasic transmission. Together this provides a clearer understanding of the inverted-U relationship, offering insights into psychiatric disorders and neurodegenerative diseases with impaired catecholamine signaling.


Neighborhood-Level Drinking Norms and Alcohol Intervention Outcomes in HIV Patients Who Are Heavy Drinkers.
Heavy alcohol consumption can be harmful, particularly for individuals with HIV. There is substantial variability in response to interventions that aim to reduce drinking. Neighborhood drinking norms may explain some of this variability among HIV-infected patients. Therefore, we investigated whether neighborhood-level drinking norms modified response to alcohol intervention among HIV-infected heavy drinkers. Heavily-drinking HIV comprehensive care patients (n = 230) completed 1 of 3 brief alcohol interventions (an educational intervention, a motivational interviewing [MI] intervention, or an MI intervention with a technological enhancement called HealthCall). Drinking was reported at baseline and end of treatment (60 days). Neighborhood-level drinking norms were obtained from a separate general population study. Patients' reductions in drinks per drinking day in response to MI (as compared with the educational control) were more pronounced in neighborhoods with more permissive drinking norms. In contrast, patients' reductions in drinks per drinking day in response to MI plus HealthCall did not significantly vary between neighborhoods with different drinking norms. Norms did not evidence significant interactions with intervention condition for 3 other exploratory drinking outcomes (drinking frequency, binge frequency, and maximum quantity). Neighborhood-level drinking norms help explain differential response to an alcohol MI intervention among HIV-infected patients. This study suggests the utility of considering neighborhood context as an effect modifier of alcohol interventions.


[The correcting role of autonomous 3'-->5' exonucleases in mammalian multienzyme DNA polymerase complexes].
A study was made of the correcting role of autonomous 3'-->5' exonucleases (AE) contained in multienzyme DNA polymerase complexes of rat hepatocytes or calf thymocytes. DNA was synthesized on phage psi X174 amber3 or M13mp2 primer-templates, and used to transfect Escherichia coli spheroplasts. Frequencies were estimated for direct and reverse mutations resulting from mistakes made in the course of in vitro DNA synthesis. The mistake rate of the hepatocytic complex was estimated at 3 x 10(-6) with equimolar dNTP, and increased tenfold when proteins accounting for 70% of the total 3'-->5' exonuclease activity of the complex were removed. The fidelity of DNA synthesis was completely restored in the presence of exogenous AE (epsilon subunit of E. coli DNA polymerase III). Nuclear (Pol delta n) and cytosolic (Pol delta c) forms of DNA polymerase delta were isolated from calf thymocytes. The former was shown to contain an AE (TREX2) absent from the latter. As compared with Pol delta c, Pol delta n had a 20-fold higher exo/pol ratio and allowed 4-5 times higher fidelity of DNA synthesis. The mistake rate of DNA polymerase complexes changed when dNTP were used in nonequimolar amounts.


Estimated dietary intake of polyphenols in European adolescents: the HELENA study.
Knowledge about polyphenols intakes and their determinants among adolescents might be helpful for planning targeted prevention strategies at an early age. In the European multicenter cross-sectional HELENA study of 2006-2007, 2428 subjects (47% boys) had data on dietary intake of polyphenols from 2 non-consecutive 24 h recalls via linking with the Phenol-Explorer database. Differences by sex, age, country, BMI, maternal education, paternal education, family affluence, smoking status, alcohol use, and physical activity were explored by linear regression. Median, lower and upper quartiles of polyphenol intakes were 326, 167 and 564 mg/day, respectively. Polyphenol intake was significantly higher in the oldest (16-17.49 years), girls, non-Mediterranean countries, lowest BMI, highest paternal education, and alcohol consumers. Main food contributors were fruit (23%, mainly apple and pear, i.e., 16.3%); chocolate products (19.2%); and fruit and vegetable juices (15.6%). Main polyphenol classes were flavonoids (75-76% of total) and phenolic acids (17-19% of total). The three most consumed polyphenols were proanthocyanidin polymers (> 10 mers), hesperidin, and proanthocyanidin 4-6 oligomers. The current study provided for the first time numbers on the total polyphenol intake and their main food sources in a heterogeneous group of European adolescents. Major differences with adult populations are the lower polyphenol consumption and the major food sources, such as chocolate and biscuits. The discussed determinants and polyphenol types already point to some important population groups that need to be targeted in future public health initiatives.


Emotional communication in close relationships.
Emotional communication patterns characterizing interactions between partners in close relationships were investigated by asking 29 couples who were married or living together to engage in a videotaped discussion of a problem they were having in their relationship. In a later experimental session, partners identified specific communications that they believed had an important influence on the discussion and then rated the communications in terms of the feelings the communicator intended to convey and the recipient's reactions. Partners attempted to reciprocate both the positive and negative feelings that they perceived their partner to express toward them. However, only negative feelings were actually reciprocated. This was because subjects were sensitive to differences in the negative feelings their partners reported expressing and interpreted those feelings correctly, but they were inaccurate in perceiving their partners' expressions of positive feelings. Men (but not women) interpreted their partners' failures to express love as an indication of hostility, whereas women (but not men) interpreted their partners' lack of hostility as an indication of love. These and other results were conceptualized in terms of a general model of emotional communication. Parameters of the model pertaining to the hostility of partners' communications were often related to women's satisfaction with their relationship and their beliefs about relationships in general. However, they were unrelated to men's satisfaction and general beliefs. This suggested that women are generally more adversely affected by overt expression of hostility than are men.


Leveraging Agriculture for Nutrition Impact through the Feed the Future Initiative.
Nutrition is a multisectoral problem; current state of empirical evidence for agricultural interventions' impacts on nutrition is weak. In the past 10 years, both agriculture and nutrition have risen on the global policy agenda. Several recent international movements have created great momentum for nutrition among global political leaders and policymakers. The 2008 world food price crisis prompted larger investment pledges to agricultural development. The U.S. Government launched the Feed the Future initiative in 2009 to address global hunger and food security, with a primary goal to reduce poverty and undernutrition by simultaneously promoting inclusive agriculture sector growth and improved nutritional status for women and children. With operations in 19 focus countries, Feed the Future provides an important laboratory of learning where efforts can be effective and, once proven, taken to scale to make agriculture work for nutrition. The Strengthening Partnerships, Results, and Innovations in Nutrition Globally (SPRING) project has been conducting a series of research on the Feed the Future initiative. This chapter will first provide a review of the nutrition narrative in relation to food and nutrition, introduce the current understanding of linkages between agriculture and nutrition and the Feed the Future initiative's efforts to strengthen the nutritional impact of agricultural and economic growth activities, and describe an extensive review of how the design and early implementation of Feed the Future activities linked agriculture and nutrition. Finally, the chapter presents an updated framework that incorporates ways to improve nutrition outcomes of agricultural programming in the broader context of food system.


Examining the effect of peer helping in a coping skills intervention: a randomized controlled trial for advanced gastrointestinal cancer patients and their family caregivers.
At the end of life, spiritual well-being is a central aspect of quality of life for many patients and their family caregivers. A prevalent spiritual value in advanced cancer patients is the need to actively give. To address this need, the current randomized trial examined whether adding a peer helping component to a coping skills intervention leads to improved meaning in life and peace for advanced gastrointestinal cancer patients and their caregivers. Feasibility and acceptability outcomes were also assessed. Advanced gastrointestinal cancer patients and caregivers (n = 50 dyads) were randomly assigned to a 5-session, telephone-based coping skills intervention or a peer helping + coping skills intervention. One or both dyad members had moderate-severe distress. Peer helping involved contributing to handouts on coping skills for other families coping with cancer. Patients and caregivers completed measures of meaning in life/peace, fatigue, psychological symptoms, coping self-efficacy, and emotional support. Patient pain and caregiver burden were also assessed. Small effects in favor of the coping skills group were found regarding meaning in life/peace at 1 and 5 weeks post-intervention. Other outcomes did not vary as a function of group assignment, with both groups showing small decreases in patient and caregiver fatigue and caregiver distress and burden. High recruitment and retention rates supported feasibility, and high participant satisfaction ratings supported acceptability. Although a telephone-based intervention is feasible and acceptable for this population, peer helping in the context of a coping skills intervention does not enhance spiritual well-being relative to coping skills alone.


Multimodal integration of fMRI and EEG data for high spatial and temporal resolution analysis of brain networks.
Two major non-invasive brain mapping techniques, electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), have complementary advantages with regard to their spatial and temporal resolution. We propose an approach based on the integration of EEG and fMRI, enabling the EEG temporal dynamics of information processing to be characterized within spatially well-defined fMRI large-scale networks. First, the fMRI data are decomposed into networks by means of spatial independent component analysis (sICA), and those associated with intrinsic activity and/or responding to task performance are selected using information from the related time-courses. Next, the EEG data over all sensors are averaged with respect to event timing, thus calculating event-related potentials (ERPs). The ERPs are subjected to temporal ICA (tICA), and the resulting components are localized with the weighted minimum norm (WMNLS) algorithm using the task-related fMRI networks as priors. Finally, the temporal contribution of each ERP component in the areas belonging to the fMRI large-scale networks is estimated. The proposed approach has been evaluated on visual target detection data. Our results confirm that two different components, commonly observed in EEG when presenting novel and salient stimuli, respectively, are related to the neuronal activation in large-scale networks, operating at different latencies and associated with different functional processes.


Method-Specific Attributes that Influence Choice of Future Contraception Among Married Women in Nairobi's Informal Settlements.
Despite an extensive evidence base on contraceptive method choice, it remains uncertain which factors are most influential in predisposing women toward certain methods and against others. This paper addresses this gap in knowledge by making use of rarely-measured perceptions about specific methods, perceived social network experience of methods, and women's own past experiences using specific methods. We draw on baseline data from the project, "Improving Measurement of Unintended Pregnancy and Unmet Need for Family Planning." Using conditional logit analysis, we ascertain which perceived method-specific attributes, including past experience of methods by women themselves and by their friends, predict preferred future contraceptive method among 317 women living in Nairobi slums who are using no method but intend to start in the next 12 months. Results show that satisfaction with past use, positive experience of use by a woman's social network, husband/partner's approval, lack of interference with menses, and perception of safety for long term use were all associated with choice of a future method.


Immunomodulatory properties and molecular effects in inflammatory diseases of low-dose x-irradiation.
Inflammatory diseases are the result of complex and pathologically unbalanced multicellular interactions. For decades, low-dose X-irradiation therapy (LD-RT) has been clinically documented to exert an anti-inflammatory effect on benign diseases and chronic degenerative disorders. By contrast, experimental studies to confirm the effectiveness and to reveal underlying cellular and molecular mechanisms are still at their early stages. During the last decade, however, the modulation of a multitude of immunological processes by LD-RT has been explored in vitro and in vivo. These include leukocyte/endothelial cell adhesion, adhesion molecule and cytokine/chemokine expression, apoptosis induction, and mononuclear/polymorphonuclear cell metabolism and activity. Interestingly, these mechanisms display comparable dose dependences and dose-effect relationships with a maximum effect in the range between 0.3 and 0.7 Gy, already empirically identified to be most effective in the clinical routine. This review summarizes data and models exploring the mechanisms underlying the immunomodulatory properties of LD-RT that may serve as a prerequisite for further systematic analyses to optimize low-dose irradiation procedures in future clinical practice.


Altered K+ channel expression in abnormal T lymphocytes from mice with the lpr gene mutation.
The observation that voltage-dependent K+ channels are required for activation of human T lymphocytes suggests that pathological conditions involving abnormal mitogen responses might be reflected in ion channel abnormalities. Gigaohm seal techniques were used to study T cells from MRL/MpJ-lpr/lpr mice; these mice develop generalized lymphoproliferation of functionally and phenotypically abnormal T cells and a disease resembling human systemic lupus erythematosus. The number and predominant type of K+ channels in T cells from these mice differ dramatically from those in T cells from control strains and a congenic strain lacking the lpr gene locus. Thus an abnormal pattern of ion channel expression has now been associated with a genetic defect in cells of the immune system.


Etiological yield of SNP microarrays in idiopathic intellectual disability.
Intellectual disability (ID) has a prevalence of 3% and is classified according to its severity. An underlying etiology cannot be determined in 75-80% in mild ID, and in 20-50% of severe ID. After it has been shown that copy number variations involving short DNA segments may cause ID, genome-wide SNP microarrays are being used as a tool for detecting submicroscopic copy number changes and uniparental disomy. This study was performed to investigate the presence of copy number changes in patients with ID of unidentified etiology. Affymetrix(®) 6.0 SNP microarray platform was used for analysis of 100 patients and their healthy parents, and data were evaluated using various databases and literature. Etiological diagnoses were made in 12 patients (12%). Homozygous deletion in NRXN1 gene and duplication in IL1RAPL1 gene were detected for the first time. Two separate patients had deletions in FOXP2 and UBE2A genes, respectively, for which only few patients have recently been reported. Interstitial and subtelomeric copy number changes were described in 6 patients, in whom routine cytogenetic tools revealed normal results. In one patient uniparental disomy type of Angelman syndrome was diagnosed. SNP microarrays constitute a screening test able to detect very small genomic changes, with a high etiological yield even in patients already evaluated using traditional cytogenetic tools, offer analysis for uniparental disomy and homozygosity, and thereby are helpful in finding novel disease-causing genes: for these reasons they should be considered as a first-tier genetic screening test in the evaluation of patients with ID and autism.


A novel mutation in KCNQ3-related benign familial neonatal epilepsy: electroclinical features and neurodevelopmental outcome.
Benign familial neonatal epilepsy (BFNE) is caused, in about 5% of families, by mutations in the KCNQ3 gene encoding voltage-gated potassium channel subunits. Usually, newborns with BFNE show a normal neurological outcome, but recently, refractory seizures and/or developmental disability have been reported suggesting phenotype variability associated with KCNQ3-related BFNE. Here, we describe a proband from a BFNE family carrying a novel variant in the KCNQ3 gene. Regarding the paucity of data in the literature, we describe the presented case with a view to further establishing: (1) a genotype/phenotype correlation in order to define a BFNE phenotype associated with favourable outcome; (2) an electroclinical pattern associated with BFNE based on video-EEG recording; (3) appropriate first-line AEDs; and (4) the duration of AED treatment. The presented case from Day 3 exhibited a cluster of ictal events, identified as epileptic seizures on Day 10 based on continuous video-EEG polygraphy. The seizures were characterized by asymmetric tonic posturing, associated with a generalized decrease in EEG amplitude, and followed by bilateral asynchronous clonic movements associated with bicentral sharp-wave discharges. The seizures were refractory to intravenous pyridoxine, whereas levetiracetam resulted in rapid total seizure control which has remained to date. This study demonstrates that the novel heterozygous KCNQ3 (c.<strike> </strike>914A>T; p.Asp305Val) variant, affecting residues in the pore region, is associated with a specific electroclinical pattern and favourable neurodevelopmental outcome. [Published with video sequence on www.epilepticdisorders.com].


An SINS/GNSS Ground Vehicle Gravimetry Test Based on SGA-WZ02.
In March 2015, a ground vehicle gravimetry test was implemented in eastern Changsha to assess the repeatability and accuracy of ground vehicle SINS/GNSS gravimeter-SGA-WZ02. The gravity system developed by NUDT consisted of a Strapdown Inertial Navigation System (SINS), a Global Navigation Satellite System (GNSS) remote station on test vehicle, a GNSS static master station on the ground, and a data logging subsystem. A south-north profile of 35 km along the highway in eastern Changsha was chosen and four repeated available measure lines were obtained. The average speed of a vehicle is 40 km/h. To assess the external ground gravity disturbances, precise ground gravity data was built by CG-5 precise gravimeter as the reference. Under relative smooth conditions, internal accuracy among repeated lines shows an average agreement at the level of 1.86 mGal for half wavelengths about 1.1 km, and 1.22 mGal for 1.7 km. The root-mean-square (RMS) of difference between calculated gravity data and reference data is about 2.27 mGal/1.1 km, and 1.74 mGal/1.7 km. Not all of the noises caused by vehicle itself and experiments environments were eliminated in the primary results. By means of selecting reasonable filters and improving the GNSS observation conditions, further developments in ground vehicle gravimetry are promising.


Δ133p53 represses p53-inducible senescence genes and enhances the generation of human induced pluripotent stem cells.
p53 functions to induce cellular senescence, which is incompatible with self-renewal of pluripotent stem cells such as induced pluripotent stem cells (iPSC) and embryonic stem cells (ESC). However, p53 also has essential roles in these cells through DNA damage repair for maintaining genomic integrity and high sensitivity to apoptosis for eliminating severely damaged cells. We hypothesized that Δ133p53, a physiological inhibitory p53 isoform, is involved in the balanced regulation of self-renewing capacity, DNA damage repair and apoptosis. We examined 12 lines of human iPSC and their original fibroblasts, as well as three ESC lines, for endogenous protein levels of Δ133p53 and full-length p53 (FL-p53), and mRNA levels of various p53 target genes. While FL-p53 levels in iPSC and ESC widely ranged from below to above those in the fibroblasts, all iPSC and ESC lines expressed elevated levels of Δ133p53. The p53-inducible genes that mediate cellular senescence (p21WAF1, miR-34a, PAI-1 and IGFBP7), but not those for apoptosis (BAX and PUMA) and DNA damage repair (p53R2), were downregulated in iPSC and ESC. Consistent with these endogenous expression profiles, overexpression of Δ133p53 in human fibroblasts preferentially repressed the p53-inducible senescence mediators and significantly enhanced their reprogramming to iPSC. The iPSC lines derived from Δ133p53-overexpressing fibroblasts formed well-differentiated, benign teratomas in immunodeficient mice and had fewer numbers of somatic mutations than an iPSC derived from p53-knocked-down fibroblasts, suggesting that Δ133p53 overexpression is non- or less oncogenic and mutagenic than total inhibition of p53 activities. Overexpressed Δ133p53 prevented FL-p53 from binding to the regulatory regions of p21WAF1 and miR-34a promoters, providing a mechanistic basis for its dominant-negative inhibition of a subset of p53 target genes. This study supports the hypothesis that upregulation of Δ133p53 is an endogenous mechanism that facilitates human somatic cells to become self-renewing pluripotent stem cells with maintained apoptotic and DNA repair activities.


Tai chi Qigong improves lung functions and activity tolerance in COPD clients: a single blind, randomized controlled trial.
To evaluate the effectiveness of a Tai chi Qigong (TCQ) program in enhancing respiratory functions and activity tolerance in clients with chronic obstructive pulmonary disease (COPD). A single-blind, randomized controlled trial. Five general outpatient clinics in Hong Kong. In total, 206 COPD clients were randomly assigned into one of the three groups, namely, TCQ, exercise, and control group. Subjects in the TCQ group received a TCQ program consisting of two 60-min sessions each week for three months. Subjects in the exercise group were taught to practice breathing techniques combined with walking as an exercise. Subjects in the control group were instructed to maintain their usual activities. Data collection was performed at baseline and at the 6-week and 3-month marks. Lung functions, 6-min walk test, and COPD exacerbation rate. Results of repeated measures of analysis of covariance demonstrated that there were significant interaction effects between time and group in forced vital capacity (p=.002, η(2)=.06), forced expiratory volume in 1s (p<.001, η(2)=.02), walking distance (p<.001), and exacerbation rate (p=.006, η(2)=.06) at 3 months. Improvements were noted in the TCQ group. No changes were observed in the exercise group, while a decline in lung functions was noticed in the control group. Tai chi Qigong was able to improve respiratory functions and activity tolerance level in COPD clients. The breathing and walking exercise helped maintain lung functions and slow down disease progression.


BAG3 Suppresses Loading of Ago2 to IL6 mRNA in Pancreatic Ductal Adenocarcinoma.
Pancreatic stellate cells (PSCs) are a subset of pancreatic cancer-associated fibroblasts, which play a critical role in pancreatic fibrosis, a characteristic feature of pancreatic cancer. The interplay between PSCs and pancreatic cancer cells is vital for promotion of tumor progression and metastasis. BAG3 is correlated with poor prognostics in patients with pancreatic ductal adenocarcinoma (PDAC), however, the exact mechanisms remain largely unknown. In this study, we demonstrated that BAG3 downregulation decreased IL6 release by PDACs, and IL6 reduction was, at least partially, responsible for suppression of PSCs activation by PDACs with BAG3 downmodulation. Importantly, BAG3 expression positively correlated with fibrosis in pancreatic cancer tissue. With regard to the underlying mechanism, we demonstrated that BAG3 knockdown facilitated recruitment of Agonaute 2 (Ago2) to IL6 mRNA, resulting in destabilization of IL6 mRNA. In addition, the current study demonstrated that phosphorylation at Serine (Ser) 387 site was required for recruitment of Ago2-containing miRISC to IL6 mRNA and BAG3 knockdown facilitated Ago2 loading to IL6 mRNA via increasing its phosphorylation at Ser 387. This study shed new light on the tumor-promoting role of BAG3 in PDAC tumors, suggesting BAG3 might represent an interesting therapeutic opportunity to PDAC patients.


Evaluation of a school-based program aimed at preventing depressive symptoms in adolescents.
The aim of this pilot study was to evaluate the implementation of a universal school-based cognitive behavioral program whose target is to prevent depressive symptoms in adolescents. The study had a quasi-experimental design with pretest, posttest, and a 1-year follow-up and provides an illustrative calculation for the implementation costs of the intervention. Sixty-two students (aged 14) and seven tutors participated. A majority of the students and all of the tutors were satisfied with the intervention. The students, both females and males, rated their depressed symptoms as significantly lower after the course; and for the females, this was maintained 1-year postintervention. The implementation costs for the initial 2 years were about US$300 per student. Positive effects of a universal school-based cognitive behavioral intervention aiming at preventing depressive symptoms in adolescents were found, especially among females.


Waveguide coupled photodiode using reflector and metal coplanar waveguide for optical triplexing applications.
The monitoring photodiode is the key building block for an optical triplexer at wavelengths of 1310, 1490, and 1550 nanometers. The InGaAs/InP photodetectors were proposed and fabricated to be monolithi-cally integrated with AlGaAs/GaAs optical waveguides using total internal reflection coupling. The metal coplanar waveguides on top of the polyimide planarization and passivation layer were then connected to illustrate the high speed monitoring functions. The full width half maximum of the temporal response and 3-dB bandwidth for the optical waveguide coupled photodiodes demonstrated 29.5 ps and 11 GHz, respectively. The bit error rate performance of this integrated photodiode at 10 Gbit/s with 2(7)-1 long pseudo-random bit sequence NRZ input data also showed error-free operation.


Relative importance of microplastics as a pathway for the transfer of hydrophobic organic chemicals to marine life.
It has been hypothesised that, if ingested, plastic debris could act as vector for the transfer of chemical contaminants from seawater to organisms, yet modelling suggest that, in the natural environment, chemical transfer would be negligible compared to other routes of uptake. However, to date, the models have not incorporated consideration of the role of gut surfactants, or the influence of pH or temperature on desorption, whilst experimental work has shown that these factors can enhance desorption of sorbed contaminants several fold. Here, we modelled the transfer of sorbed organic contaminants dichlorodiphenyltrichloroethane (DDT), phenanthrene (Phe) and bis-2-ethylhexyl phthalate (DEHP) from microscopic particles of polyvinylchloride (PVC) and polyethylene (PE) to a benthic invertebrate, a fish and a seabird using a one-compartment model OMEGA (Optimal Modelling for EcotoxicoloGical Applications) with different conditions of pH, temperature and gut surfactants. Environmental concentrations of contaminants at the bottom and the top of published ranges were considered, in combination with ingestion of either 1 or 5% by weight of plastic. For all organisms, the combined intake from food and water was the main route of exposure for Phe, DEHP and DDT with a negligible input from plastic. For the benthic invertebrate, predictions including the presence of contaminated plastic resulted in very small increases in the internal concentrations of DDT and DEHP, while the net change in the transfer of Phe was negligible. While there may be scenarios in which the presence of plastic makes a more important contribution, our modelling study suggests that ingestion of microplastic does not provide a quantitatively important additional pathway for the transfer of adsorbed chemicals from seawater to biota via the gut.


Recombinant antigen-based avidin-biotin microtiter enzyme-linked immunosorbent assay for serodiagnosis of invasive amebiasis.
An immunoscreening approach was used to isolate a strongly positive cDNA clone from an Entamoeba histolytica HK-9 cDNA expression library in the phage vector lambda ZAP-II. The 1.85-kb cDNA insert was found to be truncated and encoded the cysteine-rich, immunodominant domain of the antigenic 170-kDa subunit of the amebal galactose-N-acetylgalactosamine binding lectin. This domain was expressed as a glutathione S-transferase fusion protein in Escherichia coli. Inclusion bodies of the recombinant protein were solubilized with Sarkosyl, and the protein was enriched from the crude bacterial extract by thiol-affinity chromatography. The recombinant protein was used to develop a rapid, sensitive, and specific avidin-biotin microtiter enzyme-linked immunosorbent assay (ELISA) for invasive amebiasis. Sera from 38 individuals suffering from invasive amebiasis, 12 individuals with noninvasive amebiasis, 44 individuals with other infections, and 27 healthy subjects were screened by the recombinant antigen-based ELISA. The sensitivity and specificity of the assay were 90.4 and 94.3%, respectively, which correlated well with those of an ELISA developed with crude amebal antigen (r = 0.94; P < 0.0001), as well as with those of a commercially available serodiagnostic ELISA (r = 0.92; P < 0.0001). Thus, the bacterially expressed recombinant lectin can replace the crude amebal extract as an antigen in the serodiagnosis of invasive amebiasis by using avidin-biotin microtiter ELISA.


Symptoms of emotional distress in a family planning service: stability over a four-week period.
The 25-item Hopkins Symptom Checklist ( HSCL -25) was used on two occasions four weeks apart to identify self-reported symptoms of anxiety and depression in patients attending a family planning service. Only 28 per cent of patients classified as anxious to start with remained so four weeks later, but 62 per cent of those with high depression scores and 74 per cent of those with high depression and high anxiety scores maintained significant levels of depression. The implications of these findings for routine screening are discussed.


The transport of the histidine-rich protein I from Plasmodium falciparum is insensitive to brefeldin A.
During its intraerythrocytic development, Plasmodium falciparum synthesizes several proteins that are exported beyond its membrane. Some of these secreted antigens are involved in the formation of protuberances or knobs, a major virulence factor, at the erythrocyte membrane. Various secreted malarial polypeptides, the transport of which is sensitive to brefeldin A, are translocated in vitro into dog pancreatic microsomes. We present evidence that the histidine-rich protein I (PfHRPI) is secreted by the parasite via a novel pathway, independent of the ER/Golgi apparatus. The secretion of PfHRPI was not blocked by incubation of parasite cultures at 15 degrees C and 20 degrees C or 37 degrees C in the presence of brefeldin A. PfHRPI was not translocated into microsomes in an in vitro translation-translocation cell-free system. Unlike other polypeptides from eukaryotic cells that bypass the ER/Golgi pathway and do not have a signal peptide, PfHRPI has an atypical signal sequence consisting of 21 amino acids, including eight positively charged residues followed by 11 hydrophobic residues. We also found that the unusually charged PfHRPI signal sequence diverts Exp-1, which is usually exported, away from the translocation machinery of microsomal membranes.


Attitudes of patients with schizophrenia and depression to psychiatric research: a study in seven European countries.
Relatively few studies have examined how patients with schizophrenia and depression view psychiatric research and what influences their readiness to participate. A total of 763 patients (48% schizophrenia, 52% depression) from 7 European countries were examined using a specifically designed self-report questionnaire ["Hamburg Attitudes to Psychiatric Research Questionnaire" (HAPRQ)]. Most patients (98%) approved of psychiatric research, in general, at least "a little". There was a tendency to approve psychosocial rather than biological research topics (e.g. research on the role of the family by 91% of patients compared to 79% in genetics). Reasons to participate were mainly altruistic. Only a minority (28%) considered monetary incentives important. Patients wanted extensive background information and a feedback of the results; both were significantly more expressed by schizophrenia as compared to depressive patients, although these findings need to be interpreted with care because of age and gender differences between the diagnostic groups. While patients expressed discerning views of psychiatric research, only few differences were apparent between the two diagnostic groups. Patients' research priorities are not the same as those of many professionals and funding bodies. Their demonstrated critical appraisal should inform future research ensuring an increased patient role in the research process.


A vast-range speed control microchip for retention of all cell types.
This Technical Note is the first description of a large-scale logarithmic flow-rate damping system designed to retain cells of different adherence, different suspensibility and different motility. The chamber, which can easily retain and cultivate many types of cells, including high-motility cells and swimming cells, via a series of "speed bumps", readily facilitates cell retention for complex heterogeneous cultures. Yeast cells, red blood cells, rabbit bone marrow aspirate and dinoflagellate swimming cells were introduced into the chip for multi-cell retention, multi-cell culture and observation. Here, we show that the chamber creates a flow field with a ratio of end/start speeds as low as 0.01. The logarithmic distribution of flow-rate within the chamber is controlled precisely by pressure, all of the cell types that we tested were retained easily within the chamber. Many cell-cell interactions were observed, predicting a high potential for the success of on-chip heterogeneous cell experiments.


Incipient stem cell niche conversion in tissue culture: using a systems approach to probe early events in WUSCHEL-dependent conversion of lateral root primordia into shoot meristems.
Adventitious shoot organogenesis contributes to the fitness of diverse plant species, and control of this process is a vital step in plant transformation and in vitro propagation. New shoot meristems (SMs) can be induced by the conversion of lateral root primorida/meristems (LRP/LRMs) or callus expressing markers for this identity. To study this important and fascinating process we developed a high-throughput methodology for the synchronous initiation of LRP by auxin, and subsequent cytokinin-induced conversion of these LRP to SMs. Cytokinin treatment induces the expression of the shoot meristematic gene WUSCHEL (WUS) in converting LRP (cLRP) within 24-30 h, and WUS is required for LRP → SM conversion. Subsequently, a transcriptional reporter for CLAVATA3 (CLV3) appeared 32-48 h after transfer to cytokinin, marking presumptive shoot stem cells at the apex of cLRP. Thus the spatial expression of these two components (WUS and CLV3) of a regulatory network maintaining SM stem cells already resembles that seen in a vegetative shoot apical meristem (SAM), suggesting the very rapid initiation and establishment of the new SMs. Our high-throughput methodology enabled us to successfully apply a systems approach to the study of plant regeneration. Herein we characterize transcriptional reporter expression and global gene expression changes during LRP → SM conversion, elaborate the role of WUS and WUS-responsive genes in the conversion process, identify and test putative functional targets, perform a comparative analysis of domain-specific expression in cLRP and SM tissue, and develop a bioinformatic tool for examining gene expression in diverse regeneration systems.


Inflammatory cytokines in atherosclerosis: current therapeutic approaches.
The notion of atherosclerosis as a chronic inflammatory disease has intensified research on the role of cytokines and the way these molecules act and interact to initiate and sustain inflammation in the microenvironment of an atherosclerotic plaque. Cytokines are expressed by all types of cells involved in the pathogenesis of atherosclerosis, act on a variety of targets exerting multiple effects, and are largely responsible for the crosstalk among endothelial, smooth muscle cells, leucocytes, and other vascular residing cells. It is now understood that widely used drugs such as statins, aspirin, methotrexate, and colchicine act in an immunomodulatory way that may beneficially affect atherogenesis and/or cardiovascular disease progression. Moreover, advancement in pharmaceutical design has enabled the production of highly specific antibodies against key molecules involved in the perpetuation of the inflammatory cascade, raising hope for advances in the treatment of atherosclerosis. This review describes the actions and effects of these agents, their potential clinical significance, and future prospects.


The suitability of caffeinated drinks for children: a systematic review of randomised controlled trials, observational studies and expert panel guidelines.
The increased availability of caffeinated drinks raises questions about the level of caffeine that is appropriate for children, as well as the benefits and risks associated with their consumption. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, this systematic review evaluates evidence from randomised controlled trials investigating the effects of caffeine on cognition, behaviour, mood and exercise performance in children. Observational studies and expert panel guidelines are also discussed. One hundred and nine studies were found, with 11 randomised controlled trials and 13 observational studies meeting the criteria. High caffeine intakes (e.g. >5 mg kg(-1) body weight day(-1)) were associated with an increased risk of anxiety and withdrawal symptoms. However, smaller amounts were not linked with such effects and may benefit cognitive function and sports performance based on adult studies. The evidence suggests that children and adolescents should limit daily caffeine consumption to 2.5 mg kg(-1) body weight day(-1), equating to one or two cups of tea or one small cup of coffee. Lower contributors of caffeine, such as tea, may be more appropriate for children because they contribute to daily fluid intakes and provide flavonoids. By contrast, caffeinated soft drinks may be less suitable options for children as a result of their acidity, higher caffeine content, presence of added sugar (in some cases) and absence of bioactive compounds. More studies are needed to determine the intakes that represent a risk and whether there may be benefits for alertness and sports performance with moderate intakes of caffeine.


Limited spatial clustering of individual Plasmodium falciparum alleles in field isolates from coastal Kenya.
We describe Plasmodium falciparum genetic diversity in coastal Kenya, typing S-antigen and the merozoite surface proteins 1 and 2 (MSP-1 and MSP-2) in field isolates by the polymerase chain reaction (PCR). Malaria in coastal Kenya is characterized by low seasonal transmission, and a relatively high incidence of severe disease, which tends to occur in time-space clusters. We chose the highly polymorphic S-antigen as a marker for localized parasite diversity because it has been shown to vary in serotype prevalence in time and space. A total of 261 children (up to nine years of age) in two neighboring locations with different transmission rates were sampled for blood-stage parasites in cross-sectional surveys before and after the main transmission period in 1991, and also in a concomitant one-year longitudinal survey tracing clinical infections. Six major sequence types of S-antigen were identified, which were subdivided into 70 alleles; however, only 50% of isolates were typeable. The S-antigen sequence types varied qualitatively between locations, over time, and between asymptomatic and clinical disease infections, but not between different age groups. The MSP-1 and MSP-2 sequence type prevalences, in contrast, did not differ in any of these comparisons. We describe the use of the Mantel test for assessing clustering of individual parasite alleles at the household level, and demonstrate low-level clustering of MSP-1 and MSP-2 alleles and S-antigen sequence types, at the end of a long period of low transmission.


Suprachoroidally Delivered DNA Nanoparticles Transfect Retina and Retinal Pigment Epithelium/Choroid in Rabbits.
This study evaluated ocular tolerability and transfectability of nonviral DNA nanoparticles (DNPs) after microneedle-based suprachoroidal (SC) administration, in comparison to subretinal (SR) administration. The DNPs consisted of a single copy of plasmid DNA with a polyubiquitin C/luciferase transcriptional cassette compacted with 10 kDa PEG-substituted lysine 30-mer peptides (CK30PEG10k). New Zealand White rabbits (n = 4 per group) received a unilateral SC injection (0.1 mL via a microneedle technique) of ellipsoid-shaped DNPs, rod-shaped DNPs, or saline (negative control). A cohort of rabbits (n = 4) also received a single unilateral SR injection (0.05 mL via a transvitreal approach) of rod-shaped DNPs. At day 7, luciferase activity was measured in the retina and retinal pigment epithelium (RPE)-choroid via bioluminescence assay. A cohort of rabbits received a SC injection of analogous DNPs to assess spread of DNP injectate in the suprachoroidal space (SCS) via optical coherent tomography and histology. Suprachoroidal injection of DNPs resulted in reversible opening of the SCS circumferentially and posteriorly and was generally well tolerated, with no significant ocular examination score changes, intraocular pressure abnormalities, or changes in electroretinography amplitudes on day 7 compared to the baseline. High luciferase activity was observed in the retina and RPE-choroid of eyes that received SC DNPs (rod and ellipsoid shape) and SR DNPs (rod shape) compared to controls. The mean luciferase activity in RPE-choroid and retina was comparable between SC and SR administrations. Transfection in the RPE-choroid was approximately 10-fold higher than in the retina after either SC or SR administration of DNPs. Suprachoroidal and SR administration of DNPs resulted in comparable transfection of retina and RPE-choroid. Suprachoroidal delivery of DNPs offers the potential to precisely target chorioretinal tissues while avoiding surgical risks associated with SR injection, and it may offer an office-based nonsurgical gene therapy option for the treatment of retinal diseases.


Apple consumption is related to better sexual quality of life in young women.
Even if some evidence exists of a positive correlation between regular intake of phytoestrogens, polyphenols, antioxidants and women's sexual health, there is not a study addressing the potential correlation between daily apple consumption and women's sexual function. We aim to assess whether there is a tie between daily apple intake and sexual function in a sample of healthy young sexually active Italian women, not complaining of any sexual disorders. Seven hundred and thirty-one women (mean age 31.9, range 18-43) were enrolled in this cross-sectional study (from September 2011 to April 2012). All participants completed anonymously the Female Sexual Function Index (FSFI) and were asked to report on their amount of daily apple consumption and their eating habits. On the basis of apple consumption all women were split into two groups: Group A--regular daily apple consumption, Group B--no regular apple consumption (<1 apple/day). The main outcome measure was the FSFI questionnaire result. Three hundred and forty-three women reported a regular daily apple intake and were classified in Group A, while 388 were included in Group B. Group A had a significantly higher total (p = 0.001; Cohen's d = 3.39) and lubrication domain (p = 0.001; Cohen's d = 3.02) FSFI scores than participants in Group B. Multivariate analysis demonstrated that daily apple intake must be considered as an independent parameter (p = 0.002) in predicting a better score at questionnaire examination. This study suggests a potential relationship between regular daily apple consumption and better sexuality in our young women population.


COX-2-dependent and independent effects of COX-2 inhibitors and NSAIDs on proatherogenic changes in human monocytes/macrophages.
It is the second decade of controversy regarding the cardiovascular effects of cyclo-oxygenase-2 (COX-2) inhibitors. At this time, celecoxib is the only available COX-2-specific inhibitor for treatment of pain and inflammation. Therefore, the present study was designed primarily to determine the impact of celecoxib on cholesterol handling (uptake via scavenger receptors and efflux from the cells) and foam cell formation in human THP-1 macrophages, followed by comparison to rofecoxib and other non-steroidal anti-inflammatory drugs (NSAIDs). THP-1 human macrophages and peripheral blood mononuclear cells were incubated with: celecoxib, rofecoxib, naproxen (at 5, 10, 25 µM) and acetaminophen (0.5 mM, 1 mM)±oxidized low-density lipoprotein (oxLDL, 25 µg/mL). Scavenger receptors: CD36, LOX-1, SR-A1, and CXCL16 and cholesterol efflux proteins: ATP-binding cassette transporter (ABC) A1 and G1, and 27-hydroxylase were detected. The adhesion of monocytes to cultured endothelial cells with/ without COX-2 inhibitors/NSAIDs was also analyzed. The presence of celecoxib and rofecoxib (at high concentrations) significantly decreased expression of 27-hydroxylase and ABCA1, interfering with normal cholesterol outflow from macrophages. Acetaminophen and the non-specific COX inhibitor naproxen had no significant effect on these proteins. Only celecoxib had a profound effect on the class B scavenger receptor CD36 and the class E receptor LOX1. We demonstrate that in contrast to celecoxib, rofecoxib and naproxen increased adhesive properties of monocytes to endothelial cells. This work might contribute to our understanding of multiple mechanisms underlying elevated cardiovascular risk upon the use of COX-2 inhibitors and uncover new possibilities to enhance the safety profile of existing COX-2 inhibitors.


Impact of the fungicide carbendazim in freshwater microcosms. II. Zooplankton, primary producers and final conclusions.
Effects of chronic application of the fungicide Derosal(R) (active ingredient carbendazim) were studied in indoor macrophyte-dominated freshwater microcosms. The concentrations (0, 3.3, 33, 100, 330 and 1000 µg/l) were kept at a constant level for 4 weeks. This paper is the second of a series of two; it describes the effects on zooplankton and primary producers and presents an overall discussion. The zooplankton community was negatively affected by the three highest treatment levels (NOEC(community)=33 µg/l). At higher treatment levels Cladocera taxa were completely eliminated, while Copepod numbers were reduced. Rotatoria taxa decreased (Keratella quadrata and Lecane sp.) or increased in abundance (Testudinella parva) at the highest treatment level only. Due to the reduced grazing pressure, the abundance of some phytoplankton taxa and the chlorophyll-a content of the phytoplankton increased at the three highest treatment levels (NOEC(community)=33 µg/l). This effect was not observed for the periphyton, most probably because the reduced grazing pressure was compensated by the increased abundance of some snail species such as Lymnaea stagnalis and Physella acuta. At the end of the experimental period the biomass of the macrophyte Elodea nuttallii was significantly elevated at the two highest treatment levels. It is hypothesised that carbendazim might have caused, directly or indirectly, the removal of pathogene organisms from the macrophyte.


Reasons for non-vaccination against HPV and future vaccination intentions among 19-26 year-old women.
Despite CDC recommendations regarding universal catch-up vaccination against human papillomavirus (HPV), only about ten percent of young adult women in the United States have been vaccinated. The purpose of this study was to better understand reasons for non-vaccination among insured 19-26 year-old women and to evaluate future vaccination intentions. We used an administrative claims database from a large US managed care plan to identify women aged 19-26 for receipt of a mailed survey. From a sample of 1,375 women with no evidence of HPV vaccination from June 1, 2006 through April 30, 2007, 222 completed surveys were received, of which 185 were eligible for this analysis. The main outcome measures were unvaccinated women's attitudes and vaccine awareness, likelihood of future action regarding the vaccine, and reasons for inaction. Among the 185 non-vaccinees, 25.4% were married, 83.2% were white, and 89.2% had a college or higher level education. The vaccine was described as very important by 32.4% of subjects, and 30.1% had discussed the vaccine with a doctor and received a doctor's recommendation. Half or fewer of respondents were "very" or "extremely" likely to discuss the vaccine with their doctor (50.0%), do additional research on the vaccine (42.6%), ask a doctor to get the vaccine (37.5%), or make an appointment to get the vaccine (27.8%), while 48.0% were "somewhat", "very", or "extremely" likely to do nothing to get the vaccine. Among the latter, reasons for taking no action included being married or in a monogamous relationship (54.9%), belief that the vaccine is too new (35.4%), not having enough information about the vaccine (31.7%), concerns about side effects (24.4%), and uncertainty about insurance coverage (24.4%). Educational interventions may be needed to enhance HPV vaccination rates among 19-26 year-old women, particularly regarding information about vaccine safety, vaccine efficacy, insurance coverage, and the value of vaccination to women in monogamous relationships.


Receptor tyrosine kinase signaling favors a protumorigenic state in breast cancer cells by inhibiting the adaptive immune response.
Using transgenic mouse models of breast cancer that ablate Src homology and collagen A (ShcA) expression or oncogene-coupled ShcA signaling, we previously showed that this adaptor is critical for mammary tumor onset and progression. We now provide the first evidence that ShcA regulates mammary tumorigenesis, in part, through its ability to regulate the adaptive immune response. Inactivation of ShcA signaling within tumor cells results in extensive CD4(+) T-cell infiltration and induction of a humoral immune response in mammary tumors. This is associated with a robust CTL response in preneoplastic lesions that are deficient in ShcA signaling. Moreover, mammary tumor progression of ShcA-deficient hyperplasias is accelerated in a T cell-deficient background. We also uncover a clinically relevant correlation between high ShcA expression and low CTL infiltration in human breast cancers. Finally, we define a novel ShcA-regulated immune signature that functions as an independent prognostic marker of survival in human epidermal growth factor receptor 2(+) and basal breast cancers. We reveal a novel role for tumor cell-derived ShcA in the establishment and maintenance of an immunosuppressive state.


Influence of protein deposition on bacterial adhesion to contact lenses.
The aim of the study is to determine the adhesion of Gram positive and Gram negative bacteria onto conventional hydrogel (CH) and silicone hydrogel (SH) contact lens materials with and without lysozyme, lactoferrin, and albumin coating. Four lens types (three SH-balafilcon A, lotrafilcon B, and senofilcon A; one CH-etafilcon A) were coated with lysozyme, lactoferrin, or albumin (uncoated lenses acted as controls) and then incubated in Staphylococcus aureus (Saur 31) or either of two strains of Pseudomonas aeruginosa (Paer 6294 and 6206) for 24 h at 37 °C. The total counts of the adhered bacteria were determined using the H-thymidine method and viable counts by counting the number of colony-forming units on agar media. All three strains adhered significantly lower to uncoated etafilcon A lenses compared with uncoated SH lenses (p < 0.05). Lysozyme coating on all four lens types increased binding (total and viable counts) of Saur 31 (p < 0.05). However, lysozyme coating did not influence P. aeruginosa adhesion (p > 0.05). Lactoferrin coating on lenses increased binding (total and viable counts) of Saur 31 (p < 0.05). Lactoferrin-coated lenses showed significantly higher total counts (p < 0.05) but significantly lower viable counts (p < 0.05) of adhered P. aeruginosa strains. There was a significant difference between the total and viable counts (p < 0.05) that were bound to lactoferrin-coated lenses. Albumin coating of lenses increased binding (total and viable counts) of all three strains (p < 0.05). Lysozyme deposited on contact lenses does not possess antibacterial activity against certain bacterial strains, whereas lactoferrin possess an antibacterial effect against strains of P. aeruginosa.


Perceptual deficits and the activity of the color-opponent and broad-band pathways at isoluminance.
The deficits in texture, motion, and depth perception incurred in monkeys at isoluminance were compared with the responses of neurons of the color-opponent and broad-band systems in the lateral geniculate nucleus. Texture perception, assumed to be carried by the color-opponent system, and motion and depth perception, ascribed to the broad-band pathway, were all found to be compromised but not abolished at isoluminance. Correspondingly, both the color-opponent and the broad-band systems were affected at isoluminance, but the activity of the neurons in neither system was abolished. These results suggest that impairment of visual capacities at isoluminance cannot be uniquely attributed to either of these systems and that isoluminant stimuli are inappropriate for the psychophysical isolation of these pathways.


Complex physical and mental health needs of rural incarcerated women.
Despite the growing numbers of incarcerated women, there still remain few systematic analyses of their unique physical and mental health needs. A descriptive design was used in a convenience sample of 30 incarcerated female offenders in a rural detention center to investigate the complex health care needs of this population and formulate appropriate community-based nursing interventions. The participants received a detailed physical and mental health assessment, as well as screening for alcohol and drug abuse. Sixty-three percent of the women reported drug problems and 80% reported alcohol problems, while 84% reported physical or sexual abuse. Serious health problems were identified, including AIDS, STDs, and delirium tremens. Scores on the Global Severity Index of the Brief Symptom Inventory showed that 70% percent of the women were in the clinical range for mental health problems. The scores on the Multidimensional Scale of Perceived Social Support were negatively correlated with the Global Severity Index on the BSI (r = -.377, p = .04) which may indicate some protective effect of social support with regards to psychiatric distress. The data demonstrate a need to develop a brief objective mental health screening test for this specific population to identify psychiatric problems that require immediate attention during the incarceration period. The results also highlight incarceration as an excellent opportunity for the advanced practice nurse to initiate focused health care interventions and other strategies which can foster incarcerated women's re-entry into the community. More research is needed in this underserved group, particularly concerning issues of maternal incarceration, STD prevention, detoxification, psychiatric treatment, and sources of social support.


Osseous Metaplasia Mimicking Long Bone in Intramuscular Vascular Malformation.
We describe a case of intramuscular vascular malformation with extensive ossification within the posterior compartment muscles of leg which grossly mimicked long bone leading to equinus deformity of foot. Phleboliths and calcifications are characteristic of vascular malformations, while massive ossification is rare. To our knowledge, no extensive ossified vascular malformation within the leg muscle has been reported. Intramuscular vascular lesions occur with an incidence of 0.8%, most frequent in upper and lower extremities. Most are venous malformations. The diagnosis is rarely made before surgery and requires a definitive histological analysis, as there are no pathognomonic clinical or radiographic findings, especially with extensive ossification. Spontaneous regression does not occur, and excision of lesion is due to aesthetic and functional disturbances.


Immigrant Families, Children With Special Health Care Needs, and the Medical Home.
Immigrant children in the United States historically experience lower-quality health care. Such disparities areconcerning for immigrant children with special health care needs (CSHCNs). Our study assesses the medical home presence for CSHCN by immigrant family type and evaluates which medical home components are associated with disparities. We used the 2011 National Survey of Children's Health, comparing the prevalence and odds of a parent-reported medical home and 5 specific medical home components by immigrant family types using bivariate and multivariate logistic regression. Foreign-born CSHCNs were less likely than CSHCNs with US-born parents to have a medical home (adjusted odds ratio = 0.40, 95% confidence interval 0.19-0.85). The adjusted prevalence of having a medical home was 28% among foreign-born CSHCNs (P < .05) and 37% among CSHCNs with a foreign-born parent (P < .001), compared with 49% among CSHCNs with US-born parents. Foreign-born children without special needs also had a lower odds of a medical home, compared with children with US-born parents (adjusted odds ratio = 0.62, 0.46-0.83). The medical home component most frequently absent for immigrant children without special needs and CSHCNs with a foreign-born parent was family-centered care. In contrast, foreign-born CSHCNs most often lacked care coordination (adjusted prevalence = 37% versus 56% for CSHCNs with US-born parents; P < .05). Disparities in medical home presence for CSHCNs appear to be exacerbated by immigrant family type. Efforts focused on improving family-centered care and care coordination may provide the greatest benefit for immigrant CSHCNs.


Modeling the Cellular Response of Lung Cancer to Radiation Therapy for a Broad Range of Fractionation Schedules.
Purpose: To demonstrate that a mathematical model can be used to quantitatively understand tumor cellular dynamics during a course of radiotherapy and to predict the likelihood of local control as a function of dose and treatment fractions.Experimental Design: We model outcomes for early-stage, localized non-small cell lung cancer (NSCLC), by fitting a mechanistic, cellular dynamics-based tumor control probability that assumes a constant local supply of oxygen and glucose. In addition to standard radiobiological effects such as repair of sub-lethal damage and the impact of hypoxia, we also accounted for proliferation as well as radiosensitivity variability within the cell cycle. We applied the model to 36 published and two unpublished early-stage patient cohorts, totaling 2,701 patients.Results: Precise likelihood best-fit values were derived for the radiobiological parameters: α [0.305 Gy-1; 95% confidence interval (CI), 0.120-0.365], the α/β ratio (2.80 Gy; 95% CI, 0.40-4.40), and the oxygen enhancement ratio (OER) value for intermediately hypoxic cells receiving glucose but not oxygen (1.70; 95% CI, 1.55-2.25). All fractionation groups are well fitted by a single dose-response curve with a high χ2 P value, indicating consistency with the fitted model. The analysis was further validated with an additional 23 patient cohorts (n = 1,628). The model indicates that hypofractionation regimens overcome hypoxia (and cell-cycle radiosensitivity variations) by the sheer impact of high doses per fraction, whereas lower dose-per-fraction regimens allow for reoxygenation and corresponding sensitization, but lose effectiveness for prolonged treatments due to proliferation.Conclusions: This proposed mechanistic tumor-response model can accurately predict overtreatment or undertreatment for various treatment regimens. Clin Cancer Res; 23(18); 5469-79. ©2017 AACR.


Schizophrenia-like symptoms in narcolepsy type 1: shared and distinctive clinical characteristics.
The occurrence of psychotic symptoms in narcolepsy type 1 (NT1) has been reported as responsible for delayed diagnosis due to the misdiagnosis of schizophrenia. This study aimed to identify shared and distinctive clinical characteristics between NT1 and schizophrenia, with the focus on psychotic symptoms. A total of 28 NT1 and 21 schizophrenia patients were included. Hallucination characteristics and PANSS (Positive and Negative Syndrome Scale), HRSD (Hamilton Rating Scale for Depression), DES (Dissociative Experiences Scale), and STAI (State-Trait Anxiety Inventory) scores were collected. Symptom overlap was investigated by χ(2), Fisher's or t tests and multiple logistic regression models. Hallucinations and illusions frequently occurred in both diseases. Unimodal hallucinations were more common in schizophrenia (p = 6.30e-07) and multimodal hallucinations in NT1, but no clear difference was identified in their sensory modality. Hypnagogic/hypnopompic hallucinations were typical of NT1 (p = 5.22e-07), and 25% of NT1 patients exhibited some degree of insight deficit. Hypnagogic/hypnopompic hallucinations, unimodal hallucinations and PANSS score were the most distinctive clinical characteristics. Clinical overlap was found in the dissociative and anxiety domains, while higher depressive scores were observed in schizophrenia. The overlap between NT1 and schizophrenia should be further investigated under a clinical and pathogenetic point of view to improve diagnostic and therapeutic approaches.


National and International Dimensions of Human Immunodeficiency Virus-1 Sequence Clusters in a Northern California Clinical Cohort.
Recent advances in high-throughput molecular epidemiology are transforming the analysis of viral infections. Human immunodeficiency virus (HIV)-1 pol sequences from a Northern Californian cohort (NCC) of 4553 antiretroviral-naive individuals sampled between 1998 and 2016 were analyzed together with 140 000 previously published global pol sequences. The HIV-TRAnsmission Cluster Engine (HIV-TRACE) was used to infer a transmission network comprising links between NCC and previously published sequences having a genetic distance ≤1.5%. Twenty-five percent of NCC sequences were included in 264 clusters linked to a published sequence, and approximately one third of these (8.0% of the total) were linked to 1 or more non-US sequences. The largest cluster, containing 512 NCC sequences (11.2% of the total), comprised the subtype B lineage that traced its origin to the earliest North American sequences. Approximately 5 percent of NCC sequences belonged to a non-B subtype, and these were more likely to cluster with a non-US sequence. Twenty-two NCC sequences belonged to 1 of 4 large clusters containing sequences from rapidly growing regional epidemics: CRF07_BC (East Asia), subtype A6 (former Soviet Union), a Japanese subtype B lineage, and an East/Southeast Asian CRF01_AE lineage. Bayesian phylogenetics suggested that most non-B sequences resulted from separate introductions but that local spread within the largest CRF01_AE cluster occurred twice. The NCC contains national and international links to previously published sequences including many to the subtype B strain that originated in North America and several to rapidly growing Asian epidemics. Despite their rapid regional growth, the Asian epidemic strains demonstrated limited NCC spread.


Reduction of thromboembolic events in meningioma surgery: a cohort study of 724 consecutive patients.
Meningiomas are associated with the highest postoperative rate of venous thromboembolic events (VTE) among all intracranial tumors. The aim of this study is to compare two entirely different VTE prophylaxis regimens in 724 consecutive patients undergoing meningioma surgery. Two cohorts at a single institution treated with different regimens to prevent VTE were reviewed retrospectively. Cohort A (n = 482; 314 females, mean age 57 years, range: 11-87 years) received our institutional regimen during the years 1999-2006, consisting of low-molecular-weight heparin (LMWH) and compression stockings. For cohort B (n = 242; 163 females, mean age 56.8 years, range: 16-90 years), during the years 2008-2010, the management included intraoperative 10°-20° leg elevation with intermittent pneumatic compression (IPC), heparin and LMWH administration. We compared the incidence of the endpoints pulmonary embolism (PE), deep venous thrombosis (DVT), hemorrhage and death, taking into account several known associated risk factors. For all endpoints, we observed a more favorable outcome with the new regimen. The difference in incidence of PEs (cohort A: 38/482, 8%; cohort B: 6/242, 2.5%) reached statistical significance (p = 0.002). In general, patients with skull base meningiomas had a higher risk for PE (OR 2.77). Regarding VTE prophylaxis, an adjusted subgroup analysis suggests that the new regimen is particularly beneficial for patients with skull base meningiomas. We recommend perioperative prophylaxis using a management composed of intraoperative leg-elevation, IPC, early heparin administration and LMWH to reduce the risk for PE.