Data on the long-term symptom burden in patients surviving oesophageal cancer surgery are scarce. The aim of this study was to identify the most prevalent symptoms and their interactions with ...health-related quality of life.
This was a cross-sectional cohort study of patients who underwent oesophageal cancer surgery in 20 European centres between 2010 and 2016. Patients had to be disease-free for at least 1 year. They were asked to complete a 28-symptom questionnaire at a single time point, at least 1 year after surgery. Principal component analysis was used to assess for clustering and association of symptoms. Risk factors associated with the development of severe symptoms were identified by multivariable logistic regression models.
Of 1081 invited patients, 876 (81.0 per cent) responded. Symptoms in the preceding 6 months associated with previous surgery were experienced by 586 patients (66.9 per cent). The most common severe symptoms included reduced energy or activity tolerance (30.7 per cent), feeling of early fullness after eating (30.0 per cent), tiredness (28.7 per cent), and heartburn/acid or bile regurgitation (19.6 per cent). Clustering analysis showed that symptoms clustered into six domains: lethargy, musculoskeletal pain, dumping, lower gastrointestinal symptoms, regurgitation/reflux, and swallowing/conduit problems; the latter two were the most closely associated. Surgical approach, neoadjuvant therapy, patient age, and sex were factors associated with severe symptoms.
A long-term symptom burden is common after oesophageal cancer surgery.
Between the beginning of its full-scale scientific operations in 2007 and 2012, the VERITAS Cherenkov telescope array observed more than 130 blazars; of these, 26 were detected as very-high-energy ...(VHE; E>100 GeV) {\gamma}-ray sources. In this work, we present the analysis results of a sample of 114 undetected objects. The observations constitute a total live-time of ~570 hours. The sample includes several unidentified Fermi-Large Area Telescope (LAT) sources (located at high Galactic latitude) as well as all the sources from the second Fermi-LAT catalog which are contained within the field of view of the VERITAS observations. We have also performed optical spectroscopy measurements in order to estimate the redshift of some of these blazars that do not have a spectroscopic distance estimate. We present new optical spectra from the Kast instrument on the Shane telescope at the Lick observatory for 18 blazars included in this work, which allowed for the successful measurement or constraint on the redshift of four of them. For each of the blazars included in our sample we provide the flux upper limit in the VERITAS energy band. We also study the properties of the significance distributions and we present the result of a stacked analysis of the data-set, which shows a 4 {\sigma} excess.
The aim of this clinical study was to investigate the acid resistance of enamel lesions remineralized in situ by a sugar-free chewing gum containing casein phosphopeptide-amorphous calcium phosphate ...nanocomplexes (CPP-ACP: Recaldent™). The study utilized a double-blind, randomized, crossover design with two treatments: (i) sugar-free gum containing 18.8 mg of CPP-ACP, and (ii) sugar-free gum not containing CPP-ACP as control. Subjects wore removable palatal appliances with insets of human enamel containing demineralized subsurface lesions and chewed the gum for 20 min 4 times per day for 14 days. After each treatment the enamel slabs were removed and half of each lesion challenged with acid in vitro for 8 or 16 h. The level of remineralization was determined using microradiography. The gum containing CPP-ACP produced approximately twice the level of remineralization as the control sugar-free gum. The 8- and 16-hour acid challenge of the lesions remineralized with the control gum resulted in 65.4 and 88.0% reductions, respectively, of deposited mineral, while for the CPP-ACP-remineralized lesions the corresponding reductions were 30.5 and 41.8%. The acid challenge after in situ remineralization for both control and CPP-ACP-treated lesions resulted in demineralization underneath the remineralized zone, indicating that the remineralized mineral was more resistant to subsequent acid challenge. The results show that sugar-free gum containing CPP-ACP is superior to an equivalent gum not containing CPP-ACP in remineralization of enamel subsurface lesions in situ with mineral that is more resistant to subsequent acid challenge.
Summary
Yield potential can be expressed as a product of light interception, radiation use efficiency (RUE), and the partitioning of biomass to grain yield, or harvest index (HI). Traits related to ...early or late light interception have not been shown to be associated with genetic improvement of spring wheat yield in favourable environments. It is, however, well established that yield improvement is largely a result of increased HI, although the most recent studies comparing genetic progress in HI over time in spring wheat indicate that it has not made any additional progress since the mid 1980s. These observations suggest that future genetic progress in yield will most likely be achieved by focusing on constraints to RUE. Considering the possibility that RUE may be influenced indirectly by sink limitation, it is apparent that biomass may be increased by increasing grain number, for example. Experiments with high yielding spring wheat lines containing the alien translocation 7DL.7Ag showed increased grains m‐2 (15%), yield (12%), and biomass (9%) compared with controls. The translocation was also associated with a larger investment in spike mass at anthesis (15%), more grains/spike (10%), and increased flag‐leaf photosynthetic rate during grain‐filling (20%). The data suggest that increased biomass in 7DL.7Ag lines was due to significantly increased RUE post‐anthesis, as a result of a larger kernel number (sink) that increased the demand for photosynthesis during grain‐filling. The hypothesis that increased photosynthesis and RUE may respond directly to a larger number of grains/spike was tested experimentally by imposing a light treatment during boot stage. The treatment was associated with a small increase (5%) in the proportion of biomass invested in spike mass at anthesis, reflected by on average three extra grains/spike at maturity. The treatment was associated with 25% more yield and 22% more biomass than controls, while carbon assimilation rate measured on flag‐leaves during grainfilling was 10% higher than controls. The results suggest that RUE can be increased indirectly by increasing sink strength and that the current yield limiting process in spring wheat is the determination of kernel number. Experimental data are presented on how spike fertility may be increased through breeding, for example by introgression of the multi‐ovary trait to increase grain number per spikelet. In addition, results of analysis of the physiological bases of genotype × year interaction in high yield environments are presented in the context of how such information can provide a focus for genetic studies of sink limitation.
We present a 142 ks Chandra observation of the enigmatic combination supernova remnant G310.6-1.6 consisting of a bright pulsar-wind nebula driven by an energetic pulsar, surrounded by a highly ...circular, very faint shell with a featureless, probably synchrotron, spectrum. Comparison with an observation 6 yr earlier shows no measurable expansion of the shell, though some features in the pulsar-wind nebula have moved. We find an expansion age of at least 2500 yr, implying a current shock velocity less than about 1000 km s−1. We place severe upper limits on thermal emission from the shell; if the shell locates the blast wave, a Sedov interpretation would require the remnant to be very young, about 1000 yr, and to have resulted from a dramatically sub-energetic supernova, ejecting <0.02M with energy E 3 × 1047 erg. Even a merger-induced collapse of a white dwarf to a neutron star, with a low-energy explosion, is unlikely to produce such an event. Other explanations seem equally unlikely.
Regulatory factor binding to genomic DNA protects the underlying sequence from cleavage by DNase I, leaving nucleotide-resolution footprints. Using genomic DNase I footprinting across 41 diverse cell ...and tissue types, we detected 45 million transcription factor occupancy events within regulatory regions, representing differential binding to 8.4 million distinct short sequence elements. Here we show that this small genomic sequence compartment, roughly twice the size of the exome, encodes an expansive repertoire of conserved recognition sequences for DNA-binding proteins that nearly doubles the size of the human cis-regulatory lexicon. We find that genetic variants affecting allelic chromatin states are concentrated in footprints, and that these elements are preferentially sheltered from DNA methylation. High-resolution DNase I cleavage patterns mirror nucleotide-level evolutionary conservation and track the crystallographic topography of protein-DNA interfaces, indicating that transcription factor structure has been evolutionarily imprinted on the human genome sequence. We identify a stereotyped 50-base-pair footprint that precisely defines the site of transcript origination within thousands of human promoters. Finally, we describe a large collection of novel regulatory factor recognition motifs that are highly conserved in both sequence and function, and exhibit cell-selective occupancy patterns that closely parallel major regulators of development, differentiation and pluripotency.
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A pharmaceutical compound was used to study the effect of batch wet granulation process parameters in combination with the residual moisture content remaining after drying on granule ...and tablet quality attributes. The effect of three batch wet granulation process parameters was evaluated using a multivariate experimental design, with a novel constrained design space. Batches were characterised for moisture content, granule density, crushing strength, porosity, disintegration time and dissolution.
Mechanisms of the effect of the process parameters on the granule and tablet quality attributes are proposed. Water quantity added during granulation showed a significant effect on granule density and tablet dissolution rate. Mixing time showed a significant effect on tablet crushing strength, and mixing speed showed a significant effect on the distribution of tablet crushing strengths obtained. The residual moisture content remaining after granule drying showed a significant effect on tablet crushing strength. The effect of moisture on tablet tensile strength has been reported before, but not in combination with granulation parameters and granule properties, and the impact on tablet dissolution was not assessed. Correlations between the energy input during granulation, the density of granules produced, and the quality attributes of the final tablets were also identified. Understanding the impact of the granulation and drying process parameters on granule and tablet properties provides a basis for process optimisation and scaling.
Summary
Background
In asthma, the airway inflammatory phenotype influences clinical characteristics and treatment response. Although induced sputum is the gold standard test for phenotyping asthma, a ...more accessible method is needed for clinical practice.
Objective
To investigate whether white blood cell counts and/or their derived ratios can predict sputum eosinophils or neutrophils in uncontrolled asthma.
Methods
This cross‐sectional study evaluated 164 treated but uncontrolled asthmatic patients with sputum induction and blood collection. Receiver‐operating characteristic (ROC) curves were used to assess the relationship between blood and sputum parameters.
Results
There was a significant positive relationship between blood eosinophil parameters and the percentage of sputum eosinophil count. A weak but significant correlation was found between sputum neutrophil percentage and blood neutrophil percentage (r = 0.219, P = 0.005). ROC curve analysis identified that blood eosinophil percentage count was the best predictor for eosinophilic asthma, with an area under the curve (AUC) of 0.907 (P < 0.001). The optimum cut‐point for blood eosinophil percentage was 2.7%, and this yielded a sensitivity of 92.2% and a specificity of 75.8%. The absolute blood eosinophil count was also highly predictive with an AUC of 0.898 (P < 0.0001) at a blood eosinophil cut‐off of 0.26 × 109/L. The blood eosinophil/lymphocyte ratio (ELR) and eosinophil/neutrophil ratio (ENR) were increased in eosinophilic asthma, and the neutrophil/lymphocyte ratio (NLR) was increased in neutrophilic asthma. Neutrophilic asthma could also be detected by blood neutrophil percentages and NLR, but with less accuracy.
Conclusions and Clinical Relevance
Blood eosinophil counts and derived ratios (ELR and ENR) can accurately predict eosinophilic asthma in patients with persistent uncontrolled asthma despite treatment. Blood neutrophil parameters are poor surrogates for the proportion of sputum neutrophils. Blood counts may be a useful aid in the monitoring of uncontrolled asthma.
Targeting interhemispheric inhibition using brain stimulation has shown potential for enhancing stroke recovery. Following stroke, increased inhibition originating from the contralesional hemisphere ...impairs motor activation in ipsilesional areas. We have previously reported that low-intensity electrical theta burst stimulation (TBS) applied to an implanted electrode in the contralesional rat motor cortex reduces interhemispheric inhibition, and improves functional recovery when commenced three days after cortical injury. Here we apply this approach at more clinically relevant later time points and measure recovery from photothrombotic stroke, following three weeks of low-intensity intermittent TBS (iTBS), continuous TBS (cTBS) or sham stimulation applied to the contralesional motor cortex. Interhemispheric inhibition and cellular excitability were measured in the same rats from single pyramidal neurons in the peri-infarct area, using in vivo intracellular recording. A minimal dose of iTBS did not enhance motor function when applied beginning one month after stroke. However both a high and a low dose of iTBS improved recovery to a similar degree when applied 10 days after stroke, with the degree of recovery positively correlated with ipsilesional excitability. The final level of interhemispheric inhibition was negatively correlated with excitability, but did not independently correlate with functional recovery. In contrast, contralesional cTBS left recovery unaltered, but decreased ipsilesional excitability. These data support focal contralesional iTBS and not cTBS as an intervention for enhancing stroke recovery and suggest that there is a complex relationship between functional recovery and interhemispheric inhibition, with both independently associated with ipsilesional excitability.
•Three weeks of contralesional electrical intermittent theta-burst stimulation from 10 days post stroke enhances recovery in rats.•Functional recovery following contralesional stimulation positively correlates with excitability of the ipsilesional cortex.•Interhemispheric inhibition negatively correlates with ipsilesional excitability, but not with functional recovery.
Elderly patients with major depression are at high risk for recurrence, increased mortality, and chronic disability.
To determine the efficacy of maintenance nortriptyline hydrochloride and ...interpersonal psychotherapy (IPT) in preventing recurrence of major depressive episodes in patients older than 59 years.
A 2 x 2 randomized, double-blind, placebo-controlled clinical trial, stratified by therapist.
University-based psychiatric research clinic.
Of a total of 187 patients with recurrent nonpsychotic unipolar major depression (average age, 67 years; one third aged > or =70 years) recruited through clinical referral and media announcements, 107 were fully recovered after open acute and treatment continuation with nortriptyline and IPT. These patients were randomly assigned to 1 of 4 maintenance therapy conditions.
Monthly medication clinic with nortriptyline hydrochloride (80-120 ng/mL steady-state levels) (n = 24); medication clinic with placebo (n = 29); monthly maintenance IPT with placebo (n = 21); and monthly maintenance IPT with nortriptyline (n = 22).
Recurrence of major depressive episode.
The time to recurrence of a major depressive episode for all 3 active treatments was significantly better than for placebo. Recurrence rates over 3 years were as follows: nortriptyline and IPT, 20% (95% confidence interval CI, 4%-36%); nortriptyline and medication clinic visits, 43 % (95% CI, 25%-61%); IPT and placebo, 64% (95% CI, 45%-83%); and placebo and medication clinic visits, 90% (95% CI, 79%-100%). Combined treatment with nortriptyline and IPT was superior to IPT and placebo and showed a trend to superior efficacy over nortriptyline monotherapy (Wald chi2 = 3.56; P = .06). Subjects aged 70 years and older had a higher and more rapid rate of recurrence than those aged 60 to 69 years.
In geriatric patients with recurrent major depression, maintenance treatment with nortriptyline or IPT is superior to placebo in preventing or delaying recurrence. Combined treatment using both appears to be the optimal clinical strategy in preserving recovery.
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