Impacts of a word-picture training on reading in youth with mixed intellectual disabilities. A waiting-list control group comparison

Individuals with intellectual disabilities (ID) often struggle with learning how to read. Reading difficulties seem to be the most common secondary condition of ID. Only one in five children with mild or moderate ID achieves even minimal literacy skills. However, literacy education for children and adolescents with ID has been largely overlooked by researchers and educators. While there is little research on reading of children with ID, many training studies have been conducted with other populations with reading difficulties. The most common approach of acquiring literacy skills consists of sophisticated programs that train phonological skills and auditory perception. Only few studies investigated the influence of implicit learning on literacy skills. Implicit learning processes seem to be largely independent of age and IQ. Children are sensitive to the statistics of their learning environment. By frequent word reading they acquire implicit knowledge about the frequency of single letters and letter patterns in written words. Additionally, semantic connections not only improve the word understanding, but also facilitate storage of words in memory. Advances in communication technology have introduced new possibilities for remediating literacy skills. Computers can provide training material in attractive ways, for example through animations and immediate feedback .These opportunities can scaffold and support attention processes central to learning. Thus, the aim of this intervention study was to develop and implement a computer based word-picture training, which is based on statistical and semantic learning, and to examine the training effects on reading, spelling and attention in children and adolescents (9-16 years) diagnosed with mental retardation (general IQ  74). Fifty children participated in four to five weekly training sessions of 15-20 minutes over 4 weeks, and completed assessments of attention, reading, spelling, short-term memory and fluid intelligence before and after training. After a first assessment (T1), the entire sample was divided in a training group (group A) and a waiting control group (group B). After 4 weeks of training with group A, a second assessment (T2) was administered with both training groups. Afterwards, group B was trained for 4 weeks, before a last assessment (T3) was carried out in both groups. Overall, the results showed that the word-picture training led to substantial gains on word decoding and attention for both training groups. These effects were preserved six weeks later (group A). There was also a clear tendency of improvement in spelling after training for both groups, although the effect did not reach significance. These findings highlight the fact that an implicit statistical learning training in a playful way by motivating computer programs can not only promote reading development, but also attention in children with intellectual disabilities.

Can in-vitro chemoresponse assays help find new treatment regimens for malignant gliomas?

Various in-vitro chemosensitivity and resistance assays (CSRAs) have been demonstrated to be helpful decision aids for non-neurological tumors. Here, we evaluated the performance characteristics of two CSRAs for glioblastoma (GB) cells. The chemoresponse of fresh GB cells from 30 patients was studied in vitro using the ATP tumor chemoresponse assay and the chemotherapy resistance assay (CTR-Test). Both assay platforms provided comparable results. Of seven different chemotherapeutic drugs and drug combinations tested in vitro, treosulfan plus cytarabine (TARA) was the most effective, followed by nimustine (ACNU) plus teniposide (VM26) and temozolomide (TMZ). Whereas ACNU/VM26 and TMZ have proven their clinical value for malignant gliomas in large randomized studies, TARA has not been successful in newly diagnosed gliomas. This seeming discrepancy between in vitro and clinical result might be explained by the pharmacological behavior of treosulfan. Our results show reasonable agreement between two cell-based CSRAs. They appear to confirm the clinical effectiveness of drugs used in GB treatment as long as pharmacological preconditions such as overcoming the blood-brain barrier are properly considered.

Comparison of the in vitro effects of saline, hypertonic hydroxyethyl starch, hypertonic saline, and two forms of hydroxyethyl starch on whole blood coagulation and platelet function in dogs.

OBJECTIVE To compare the in vitro effects of hypertonic solutions and colloids to saline on coagulation in dogs. DESIGN In vitro experimental study. SETTING Veterinary teaching hospital. ANIMALS Twenty-one adult dogs. INTERVENTIONS Blood samples were diluted with saline, 7.2% hypertonic saline solution with 6% hydroxyethylstarch with an average molecular weight of 200 kDa and a molar substitution of 0.4 (HH), 7.2% hypertonic saline (HTS), hydroxyethyl starch (HES) 130/0.4 or hydroxyethyl starch 600/0.75 at ratios of 1:22 and 1:9, and with saline and HES at a ratio of 1:3. MEASUREMENTS AND MAIN RESULTS Whole blood coagulation was analyzed using rotational thromboelastometry (extrinsic thromboelastometry-cloting time (ExTEM-CT), maximal clot firmness (MCF) and clot formation time (CFT) and fibrinogen function TEM-CT (FibTEM-CT) and MCF) and platelet function was analyzed using a platelet function analyzer (closure time, CTPFA ). All parameters measured were impaired by saline dilution. The CTPFA was prolonged by 7.2% hypertonic saline solution with 6% hydroxyethylstarch with an average molecular weight of 200 kDa and a molar substitution of 0.4 (HH) and HTS but not by HES solutions. At clinical dilutions equivalent to those generally administered for shock (saline 1:3, HES 1:9, and hypertonic solutions 1:22), CTPFA was more prolonged by HH and HTS than other solutions but more by saline than HES. No difference was found between the HES solutions or the hypertonic solutions. ExTEM-CFT and MCF were impaired by HH and HTS but only mildly by HES solutions. At clinically relevant dilutions, no difference was found in ExTEM-CFT between HTS and saline or in ExTEM-MCF between HH and saline. No consistent difference was found between the 2 HES solutions but HH impaired ExTEM-CFT and MCF more than HTS. At high dilutions, FibTEM-CT and -MCF and ExTEM-CT were impaired by HES. CONCLUSIONS Hypertonic solutions affect platelet function and whole blood coagulation to a greater extent than saline and HES. At clinically relevant dilutions, only CTPFA was markedly more affected by hypertonic solutions than by saline. At high dilutions, HES significantly affects coagulation but to no greater extent than saline at clinically relevant dilutions.

Source apportionment of elemental carbon in Beijing, China: insights from radiocarbon and organic marker measurements

Elemental carbon (EC) or black carbon (BC) in the atmosphere has a strong influence on both climate and human health. In this study, radiocarbon (14C) based source apportionment is used to distinguish between fossil fuel and biomass burning sources of EC isolated from aerosol filter samples collected in Beijing from June 2010 to May 2011. The 14C results demonstrate that EC is consistently dominated by fossil-fuel combustion throughout the whole year with a mean contribution of 79% ± 6% (ranging from 70% to 91%), though EC has a higher mean and peak concentrations in the cold season. The seasonal molecular pattern of hopanes (i.e., a class of organic markers mainly emitted during the combustion of different fossil fuels) indicates that traffic-related emissions are the most important fossil source in the warm period and coal combustion emissions are significantly increased in the cold season. By combining 14C based source apportionment results and picene (i.e., an organic marker for coal emissions) concentrations, relative contributions from coal (mainly from residential bituminous coal) and vehicle to EC in the cold period were estimated as 25 ± 4% and 50 ± 7%, respectively, whereas the coal combustion contribution was negligible or very small in the warm period.

Molecular nitrogen in comet 67P/Churyumov-Gerasimenko indicates a low formation temperature

Molecular nitrogen (N2) is thought to have been the most abundant form of nitrogen in the protosolar nebula. It is the main N-bearing molecule in the atmospheres of Pluto and Triton and probably the main nitrogen reservoir from which the giant planets formed. Yet in comets, often considered the most primitive bodies in the solar system, N2 has not been detected. Here we report the direct in situ measurement of N2 in the Jupiter family comet 67P/Churyumov-Gerasimenko, made by the Rosetta Orbiter Spectrometer for Ion and Neutral Analysis mass spectrometer aboard the Rosetta spacecraft. A N2/CO ratio of Embedded Image (2σ standard deviation of the sampled mean) corresponds to depletion by a factor of ~25.4 ± 8.9 as compared to the protosolar value. This depletion suggests that cometary grains formed at low-temperature conditions below ~30 kelvin.

Improved VMAT planning for head and neck tumors with an advanced optimization algorithm

OBJECTIVE In this study, the "Progressive Resolution Optimizer PRO3" (Varian Medical Systems) is compared to the previous version "PRO2" with respect to its potential to improve dose sparing to the organs at risk (OAR) and dose coverage of the PTV for head and neck cancer patients. MATERIALS AND METHODS For eight head and neck cancer patients, volumetric modulated arc therapy (VMAT) treatment plans were generated in this study. All cases have 2-3 phases and the total prescribed dose (PD) was 60-72Gy in the PTV. The study is mainly focused on the phase 1 plans, which all have an identical PD of 54Gy, and complex PTV structures with an overlap to the parotids. Optimization was performed based on planning objectives for the PTV according to ICRU83, and with minimal dose to spinal cord, and parotids outside PTV. In order to assess the quality of the optimization algorithms, an identical set of constraints was used for both, PRO2 and PRO3. The resulting treatment plans were investigated with respect to dose distribution based on the analysis of the dose volume histograms. RESULTS For the phase 1 plans (PD=54Gy) the near maximum dose D2% of the spinal cord, could be minimized to 22±5 Gy with PRO3, as compared to 32±12Gy with PRO2, averaged for all patients. The mean dose to the parotids was also lower in PRO3 plans compared to PRO2, but the differences were less pronounced. A PTV coverage of V95%=97±1% could be reached with PRO3, as compared to 86±5% with PRO2. In clinical routine, these PRO2 plans would require modifications to obtain better PTV coverage at the cost of higher OAR doses. CONCLUSION A comparison between PRO3 and PRO2 optimization algorithms was performed for eight head and neck cancer patients. In general, the quality of VMAT plans for head and neck patients are improved with PRO3 as compared to PRO2. The dose to OARs can be reduced significantly, especially for the spinal cord. These reductions are achieved with better PTV coverage as compared to PRO2. The improved spinal cord sparing offers new opportunities for all types of paraspinal tumors and for re-irradiation of recurrent tumors or second malignancies.

Anatomic characteristics and clinical implications of angiographic coronary thrombus: insights from a patient-level pooled analysis of SYNTAX, RESOLUTE, and LEADERS Trials.

BACKGROUND The distribution of thrombus-containing lesions (TCLs) in an all-comer population admitted with a heterogeneous clinical presentation (stable, ustable angina, or an acute coronary syndrome) and treated with percutaneous coronary intervention is yet unclear, and the long-term prognostic implications are still disputed. This study sought to assess the distribution and prognostic implications of coronary thrombus, detected by coronary angiography, in a population recruited in all-comer percutaneous coronary intervention trials. METHODS AND RESULTS Patient-level data from 3 contemporary coronary stent trials were pooled by an independent academic research organization (Cardialysis, Rotterdam, the Netherlands). Clinical outcomes in terms of major adverse cardiac events (major adverse cardiac events, a composite of death, myocardial infarction, and repeat revascularization), death, myocardial infarction, and repeated revascularization were compared between patients with and without angiographic TCL. Preprocedural TCL was present in 257 patients (5.8%) and absent in 4193 (94.2%) patients. At 3-year follow-up, there was no difference for major adverse cardiac events (25.3 versus 25.4%; P=0.683); all-cause death (7.4 versus 6.8%; P=0.683); myocardial infarction (5.8 versus 6.0%; P=0.962), and any revascularizations (17.5 versus 17.7%; P=0.822) between patients with and without TCL. The comparison of outcomes in groups weighing the jeopardized myocardial by TCL also did not show a significant difference. TCL were seen more often in the first 2 segments of the right (43.6%) and left anterior descending (36.8%) coronary arteries. The association of TCL and bifurcation lesions was present in 40.1% of the prespecified segments. CONCLUSIONS TCL involved mainly the proximal coronary segments and did not have any effect on clinical outcomes. A more detailed thrombus burden quantification is required to investigate its prognostic implications. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00114972, NCT01443104, NCT00617084.

European Dermatology Forum Guidelines on topical photodynamic therapy

Topical photodynamic therapy (PDT) is a widely approved therapy for actinic keratoses, squamous cell carcinoma in-situ, superficial and certain thin basal cell carcinomas. Recurrence rates are typically equivalent to existing therapies, although inferior to surgery for nodular basal cell carcinoma. PDT can be used both as a lesional or as a field therapy and has the potential to delay/reduce the development of new lesions. PDT has also been studied for its place in the treatment of, as well as its potential to prevent, superficial skin cancers in immune-suppressed patients, although sustained clearance rates are lower than for immunocompetent individuals. Many additional indications have been evaluated, including photo-rejuvenation and inflammatory and infective dermatoses. This S2 guideline considers all current and emerging indications for the use of topical photodynamic therapy in Dermatology, prepared by the PDT subgroup of the European Dermatology Forum guidelines committee. It presents consensual expert recommendations reflecting current published evidence. An unabridged version of this guideline is available online at: http://www.euroderm.org/edf/index.php/edf-guidelines.

Hypercoagulation and hyperkinetic blood pressure indicative of physiological loss-of-control despite behavioural control in Africans: The SABPA study.

OBJECTIVES A dissociation between behavioural (in-control) and physiological parameters (indicating loss-of-control) is associated with cardiovascular risk in defensive coping (DefS) Africans. We evaluated relationships between DefS, sub-clinical atherosclerosis, low-grade inflammation and hypercoagulation in a bi-ethnic sex cohort. METHODS Black (Africans) and white Africans (Caucasians) (n = 375; aged 44.6 ± 9.7 years) were included. Ambulatory BP, vascular structure (left carotid cross-sectional wall area (L-CSWA) and plaque counts), and markers of coagulation and inflammation were quantified. Ethnicity/coping style interaction was revealed only in DefS participants. RESULTS A hypertensive state, less plaque, low-grade inflammation, and hypercoagulation were more prevalent in DefS Africans (27-84%) than DefS Caucasians (18-41%). Regression analyses demonstrated associations between L-CSWA and 24 hour systolic BP (R(2) = 0.38; β = 0.78; p < 0.05) in DefS African men but not in DefS African women or Caucasians. No associations between L-CSWA and coagulation markers were evident. CONCLUSION Novel findings revealed hypercoagulation, low-grade inflammation and hyperkinetic BP (physiological loss-of-control responses) in DefS African men. Coupled to a self-reported in-control DefS behavioural profile, this reflects dissociation between behaviour and physiology. It may explain changes in vascular structure, increasing cerebrovascular disease risk in a state of hyper-vigilant coping.

Bevacizumab continuation versus no continuation after first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a randomized phase III non-inferiority trial (SAKK 41/06)

BACKGROUND Chemotherapy plus bevacizumab is a standard option for first-line treatment in metastatic colorectal cancer (mCRC) patients. We assessed whether no continuation is non-inferior to continuation of bevacizumab after completing first-line chemotherapy. PATIENTS AND METHODS In an open-label, phase III multicentre trial, patients with mCRC without disease progression after 4-6 months of standard first-line chemotherapy plus bevacizumab were randomly assigned to continuing bevacizumab at a standard dose or no treatment. CT scans were done every 6 weeks until disease progression. The primary end point was time to progression (TTP). A non-inferiority limit for hazard ratio (HR) of 0.727 was chosen to detect a difference in TTP of 6 weeks or less, with a one-sided significance level of 10% and a statistical power of 85%. RESULTS The intention-to-treat population comprised 262 patients: median follow-up was 36.7 months. The median TTP was 4.1 [95% confidence interval (CI) 3.1-5.4] months for bevacizumab continuation versus 2.9 (95% CI 2.8-3.8) months for no continuation; HR 0.74 (95% CI 0.58-0.96). Non-inferiority could not be demonstrated. The median overall survival was 25.4 months for bevacizumab continuation versus 23.8 months (HR 0.83; 95% CI 0.63-1.1; P = 0.2) for no continuation. Severe adverse events were uncommon in the bevacizumab continuation arm. Costs for bevacizumab continuation were estimated to be ∼30,000 USD per patient. CONCLUSIONS Non-inferiority could not be demonstrated for treatment holidays versus continuing bevacizumab monotheray, after 4-6 months of standard first-line chemotherapy plus bevacizumab. Based on no impact on overall survival and increased treatment costs, bevacizumab as a single agent is of no meaningful therapeutic value. More efficient treatment approaches are needed to maintain control of stabilized disease following induction therapy. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, number NCT00544700.

Phenotypic plasticity is a negative, though weak, predictor of the commonness of 105 grassland species

Aim The usual hypothesis about the relationship between niche breadth and range size posits that species with the capacity to use a wider range of resources or to tolerate a greater range of environmental conditions should be more widespread. In plants, broader niches are often hypothesized to be due to pronounced phenotypic plasticity, and more plastic species are therefore predicted to be more common. We examined the relationship between the magnitude of phenotypic plasticity in five functional traits, mainly related to leaves, and several measures of abundance in 105 Central European grassland species. We further tested whether mean values of traits, rather than their plasticity, better explain the commonness of species, possibly because they are pre-adapted to exploiting the most common resources. Location Central Europe. Methods In a multispecies experiment with 105 species we measured leaf thickness, leaf greenness, specific leaf area, leaf dry matter content and plant height, and the plasticity of these traits in response to fertilization, waterlogging and shading. For the same species we also obtained five measures of commonness, ranging from plot-level abundance to range size in Europe. We then examined whether these measures of commonness were associated with the magnitude of phenotypic plasticity, expressed as composite plasticity of all traits across the experimental treatments. We further estimated the relative importance of trait plasticity and trait means for abundance and geographical range size. Results More abundant species were less plastic. This negative relationship was fairly consistent across several spatial scales of commonness, but it was weak. Indeed, compared with trait means, plasticity was relatively unimportant for explaining differences in species commonness. Main conclusions Our results do not indicate that larger phenotypic plasticity of leaf morphological traits enhances species abundance. Furthermore, possession of a particular trait value, rather than of trait plasticity, is a more important determinant of species commonness.

Local Interstellar Medium: Six Years of Direct Sampling by IBEX

The Interstellar Boundary Explorer (IBEX) has been directly observing neutral atoms from the local interstellar medium for the last six years (2009–2014). This paper ties together the 14 studies in this Astrophysical Journal Supplement Series Special Issue, which collectively describe the IBEX interstellar neutral results from this epoch and provide a number of other relevant theoretical and observational results. Interstellar neutrals interact with each other and with the ionized portion of the interstellar population in the “pristine” interstellar medium ahead of the heliosphere. Then, in the heliosphereʼs close vicinity, the interstellar medium begins to interact with escaping heliospheric neutrals. In this study, we compare the results from two major analysis approaches led by IBEX groups in New Hampshire and Warsaw. We also directly address the question of the distance upstream to the pristine interstellar medium and adjust both sets of results to a common distance of ~1000 AU. The two analysis approaches are quite different, but yield fully consistent measurements of the interstellar He flow properties, further validating our findings. While detailed error bars are given for both approaches, we recommend that for most purposes, the community use “working values” of ~25.4 km s⁻¹, ~75°7 ecliptic inflow longitude, ~−5°1 ecliptic inflow latitude, and ~7500 K temperature at ~1000 AU upstream. Finally, we briefly address future opportunities for even better interstellar neutral observations to be provided by the Interstellar Mapping and Acceleration Probe mission, which was recommended as the next major Heliophysics mission by the NRCʼs 2013 Decadal Survey.