As clozapine is under-prescribed in persons with treatment-resistant schizophrenia (TRS), it is necessary to better identify the determinants of health inequalities in access to clozapine use.
To ...identify mental health professionals' characteristics or attitudes and institutional characteristics facilitating or limiting clozapine prescribing.
We systematically searched multiple electronic databases for articles reporting: (i) mental health professionals' attitudes and characteristics favoring or limiting clozapine prescribing; (ii) institutional characteristics associated with variations in clozapine prescribing; (iii) interventions aimed at enhancing clozapine prescribing. Data were synthesized narratively.
A total of 31 articles reporting findings of 29 studies published from 1993 to 2017 in 11 countries fulfilled our inclusion criteria. The main prescriber-related barriers to clozapine prescribing are lack of personal prescribing experience and concern with pharmacological characteristics of clozapine (blood monitoring and adverse effects). Lack of knowledge about the effectiveness of clozapine does not appear as a major determinant of under-prescription. Institutional-related characteristics favoring clozapine prescribing are prescribers' adherence to evidence-based medicine principles and learning by modelling from experienced clozapine prescribers.
Effective strategies to increase access to clozapine in persons with TRS include implementation of integrated clozapine clinics, simplification of blood monitoring, education for prescribers and contact with experienced prescribers. Programs addressing barriers in clozapine prescription need to be disseminated more broadly to ensure persons with TRS have access to evidenced based treatments such as clozapine. Inequality in access to clozapine care should be more systematically handled by mental health facilities and health regulatory agencies.
Motivation: Mathematical description of biological reaction networks by differential equations leads to large models whose parameters are calibrated in order to optimally explain experimental data. ...Often only parts of the model can be observed directly. Given a model that sufficiently describes the measured data, it is important to infer how well model parameters are determined by the amount and quality of experimental data. This knowledge is essential for further investigation of model predictions. For this reason a major topic in modeling is identifiability analysis. Results: We suggest an approach that exploits the profile likelihood. It enables to detect structural non-identifiabilities, which manifest in functionally related model parameters. Furthermore, practical non-identifiabilities are detected, that might arise due to limited amount and quality of experimental data. Last but not least confidence intervals can be derived. The results are easy to interpret and can be used for experimental planning and for model reduction. Availability: An implementation is freely available for MATLAB and the PottersWheel modeling toolbox at http://web.me.com/andreas.raue/profile/software.html. Contact: andreas.raue@me.com Supplementary information: Supplementary data are available at Bioinformatics online.
Is rocking motion predictable? Bachmann, J. A.; Strand, M.; Vassiliou, M. F. ...
Earthquake engineering & structural dynamics,
February 2018, 2018-02-00, 20180201, Letnik:
47, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Summary
An argument of engineers and researchers against the use of rocking as a seismic response modification technique is that the rocking motion of a structure is chaotic and the existing models ...are incapable of predicting it well. This argument is supported by the documented inability of rocking models to predict the motion of a specimen excited by a single ground motion. A statistical comparison of the experimental and the numerical responses of a rigid rocking oscillator not to a specific ground motion, but to ensembles of ground motions that have the same statistical properties, is presented. It is shown that the simple analytical model proposed by Housner in 1963 is capable of predicting the statistics of seismic response of a rigid rocking oscillator.
Attention-deficit/hyperactivity disorder (ADHD) sometimes persists into adulthood. There have been no studies from Germany until the present time on the diagnosis and treatment of ADHD over the ...course of patients' lives, in particular during the transition from adolescence to early adulthood.
We used nationwide routine data of the AOK statutory healthinsurance fund to determine the frequency of ADHD diagnoses and prescriptions of medication for ADHD. We additionally analyzed the care of a transition cohort of initially 15-year-old ADHD patients over a period of six years.
From 2009 to 2014, the prevalence of a diagnosis of ADHD rose from 5.0% to 6.1% in persons aged 0 to 17 years (with a maximum of 13.9% in 9-year-old boys) and from 0.2% to 0.4% in persons aged 18 to 69 years. The amount of ADHD medication prescribed to adults with ADHD increased over time, while the amount prescribed to children and adolescents fell. Methylphenidate was the most commonly prescribed drug, followed by atomoxetine and lisdexamfetamine. Only 31.2% of the patients in the transition cohort still carried the diagnosis of ADHD at the end of the six-year period, at age 21. The percentage of patients taking ADHD medication in this group fell from 51.8% at age 15 to 6.6% at age 21.
The administrative prevalence of a diagnosis of ADHD among adults and the degree of medication use for ADHD by adults have risen in recent years. This can be interpreted as an indication of the sensitization of physicians and patients to the possibility of adult ADHD. Nonetheless, the prevalence of diagnosed ADHD remains less than the prevalence revealed by epidemiologic studies. This may indicate that adults with ADHD are currently underdiagnosed and undertreated. The low rate of use of ADHD medications among adolescents with ADHD who are on the verge of adulthood leads us to the question of whether specific transitional concepts need to be developed for this age group.
Prediction, prevention and treatment of virus infections require understanding of cell-to-cell variability that leads to heterogenous disease outcomes, but the source of this heterogeneity has yet to ...be clarified. To study the multimodal response of single human cells to herpes simplex virus type 1 (HSV-1) infection, we mapped high-dimensional viral and cellular state spaces throughout the infection using multiplexed imaging and quantitative single-cell measurements of viral and cellular mRNAs and proteins. Here we show that the high-dimensional cellular state scape can predict heterogenous infections, and cells move through the cellular state landscape according to infection progression. Spatial information reveals that infection changes the cellular state of both infected cells and of their neighbors. The multiplexed imaging of HSV-1-induced cellular modifications links infection progression to changes in signaling responses, transcriptional activity, and processing bodies. Our data show that multiplexed quantification of responses at the single-cell level, across thousands of cells helps predict infections and identify new targets for antivirals.
Background
Knowing that your parent or caregiver will be there for you in times of emotional need and distress is a core aspect of the human experience of feeling loved and being securely attached. ...In contrast, an insecure attachment pattern is found in many antisocial youth and is related to less sensitive caregiving. Such youth are often distrustful of adults and authority figures, and are at high risk of poor outcomes. As they become adults, they require extensive health, social and economic support, costing society ten times more than their well‐adjusted peers. However, it is not known whether insecure attachment itself is associated with higher costs in at‐risk youth, independently of potential confounders, nor whether cost differences are already beginning to emerge early in adolescence.
Methods
Sample: A total of 174 young people followed up aged 9–17 years (mean 12.1, SD 1.8): 85 recruited with moderate antisocial behaviour (80th percentile) from a school screen aged 4–6 years; 89 clinically referred with very high antisocial behaviour (98th percentile) aged 3–7 years. Measures: Costs by detailed health economic and service‐use interview; attachment security to mother and father from interview; diagnostic interviews for oppositional and conduct problems; self‐reported delinquent behaviour.
Results
Costs were greater for youth insecurely attached to their mothers (secure £6,743, insecure £10,199, p = .001) and more so to fathers (secure £1,353, insecure £13,978, p < .001). These differences remained significant (mother p = .019, father p < .001) after adjusting for confounders, notably family income and education, intelligence and antisocial behaviour severity.
Conclusions
Attachment insecurity is a significant predictor of public cost in at‐risk youth, even after accounting for covariates. Since adolescent attachment security is influenced by caregiving quality earlier in childhood, these findings add support to the public health case for early parenting interventions to improve child outcomes and reduce the financial burden on society.
Read the Commentary on this article at doi: 10.1111/jcpp.13111
Summary
The mobility of goethite (OMCG) colloids coated with organic matter was studied in goethite‐coated quartz sand and in undisturbed subsoil rich in natural coatings of iron oxide. Classic ...Derjaguin–Landau–Verwey–Overbeek (DLVO) interactions and DLVO extended by Lewis acid–base parameters (XDLVO) were estimated between colloids and goethite‐coated sand from zeta potentials and sessile drop contact angles. The OMCG colloids were retained completely in goethite‐coated sand, whereas preconditioning of the solid matrix with dissolved organic matter (DOM) enabled subsequent colloid transport. Zeta potential values showed that goethite‐coated sand was modified strongly by DOM preconditioning. The DLVO and XDLVO interactions were estimated for the pairs of OMCG colloids and for (i) quartz, (ii) goethite and (iii) organic matter‐coated goethite. Both DLVO approaches were able to predict general trends of colloid breakthrough. An exception was the XDLVO interaction for combination (iii), which showed short‐distance (<1.3 nm) repulsive interactions that were inconsistent with breakthrough behaviour. Analogous to OMCG colloid transport in the sand, DOM preconditioning was also the prerequisite for OMCG colloid transport in undisturbed subsoil. Total colloid breakthrough in the soil was less than in the sand, probably because of straining in pore throats and retention at air–water interfaces. We concluded that the DLVO and XDLVO approaches were in general capable of predicting trends of OMCG colloid mobility in goethite‐coated sand. We concluded further that the basic principles of OMCG colloid transport were transferrable from the simplified model system to the more complex natural system despite considerable differences in surface properties, pore structure and water content.
Highlights
How will organic matter (OM) coatings on the solid matrix affect mobility of iron oxide colloids?
Effect of OM on mobility was assessed in simple model soil systems and in undisturbed soil.
OM coatings modify properties of the solid matrix surface and are a prerequisite for colloid transport.
Balances between OM transport, coating formation and decomposition control colloid mobility.
Large amounts of total organic carbon are temporarily stored in soils, which makes soil respiration one of the major sources of terrestrial CO2 fluxes within the global carbon cycle. More than half ...of global soil organic carbon (SOC) is stored in subsoils (below 30 cm), which represent a significant carbon (C) pool. Although several studies and models have investigated soil respiration, little is known about the quantitative contribution of subsoils to total soil respiration or about the sources of CO2 production in subsoils. In a 2-year field study in a European beech forest in northern Germany, vertical CO2 concentration profiles were continuously measured at three locations, and CO2 production was quantified in the topsoil and the subsoil. To determine the contribution of fresh litter-derived C to CO2 production in the three soil profiles, an isotopic labelling experiment, using 13C-enriched leaf litter, was performed. Additionally, radiocarbon measurements of CO2 in the soil atmosphere were used to obtain information about the age of the C source in the CO2 production. At the study site, it was found that 90 % of total soil respiration was produced in the first 30 cm of the soil profile, where 53 % of the SOC stock is stored. Freshly labelled litter inputs in the form of dissolved organic matter were only a minor source for CO2 production below a depth of 10 cm. In the first 2 months after litter application, fresh litter-derived C contributed, on average, 1 % at 10 cm depth and 0.1 % at 150 cm depth to CO2 in the soil profile. Thereafter, its contribution was less than 0.3 % and 0.05 % at 10 and 150 cm depths, respectively. Furthermore CO2 in the soil profile had the same modern radiocarbon signature at all depths, indicating that CO2 in the subsoil originated from young C sources despite a radiocarbon age bulk SOC in the subsoil. This suggests that fresh C inputs in subsoils, in the form of roots and root exudates, are rapidly respired, and that other subsoil SOC seems to be relatively stable. The field labelling experiment also revealed a downward diffusion of 13CO2 in the soil profile against the total CO2 gradient. This isotopic dependency should be taken into account when using labelled 13C and 14C isotope data as an age proxy for CO2 sources in the soil.
Despite our growing knowledge about the pathomechanisms of cancer cachexia, a whole clinical picture of the cachectic patient is still missing. Our objective was to evaluate the clinical ...characteristics in cancer patients with and without cachexia to get the whole picture of a cachectic patient.
Cancer patients of the University Clinic "Klinikum rechts der Isar" with gastrointestinal, gynecological, hematopoietic, lung and some other tumors were offered the possibility to take part in the treatment concept including a nutrition intervention and an individual training program according to their capability. We now report on the first 503 patients at the time of inclusion in the program between March 2011 and October 2015. We described clinical characteristics such as physical activity, quality of life, clinical dates and food intake.
Of 503 patients with cancer, 131 patients (26.0%) were identified as cachectic, 369 (73.4%) as non-cachectic. The change in cachexia were 23% reduced capacity performance (108 Watt for non-cachectic-patients and 83 Watt for cachectic patients) and 12% reduced relative performance (1.53 Watt/kg for non-cachectic and 1.34 Watt/kg for cachectic patients) in ergometry test. 75.6% of non-cachectic and 54.3% of cachectic patients still received curative treatment.
Cancer cachectic patients have multiple symptoms such as anemia, impaired kidney function and impaired liver function with elements of mild cholestasis, lower performance and a poorer quality of life in the EORTC questionnaire. Our study reveals biochemical and clinical specific features of cancer cachectic patients.
PDF
