Summary
Background
Treatments for Crohn's disease (CD) and ulcerative colitis (UC) are not uniformly effective, thus necessitating dose changes, switching, and augmentation and carry adverse event ...risk, often requiring discontinuation, which reduces treatment benefits.
Aim
To assess continuity of and changes to initial CD and UC treatments, as well as costs associated with specific parameters defining suboptimal therapy.
Methods
Commercial US insurance claims (2006–2010) were retrospectively analysed. CD and UC patients receiving monotherapy with 5‐aminosalicylates (5‐ASAs), corticosteroids (CS), immunomodulators (IM) or biologics were included. Continuity of and changes to initial (index) therapy and associated costs (2011 US$) were assessed over 12 months following therapy initiation. Suboptimal therapy included discontinuation or switch (except for CS), dose escalation, augmentation, inadequate loading (biologics only), prolonged CS use (>3 months), surgery or hospitalisation.
Results
The study included 13 005 CD and 19 878 UC patients. Augmentation was a common index therapy change (~20% of 5‐ASA initiators, ~40% of CS initiators, ≥40% of IM initiators and 26–55% of biologic initiators) in both CD and UC patients. Approximately 50% of CD and UC 5‐ASA initiators discontinued/interrupted treatment. Approximately 80% of CD and UC patients had ≥1 suboptimal therapy marker. Mean all‐cause total costs per CD patient were significantly higher in those with vs. without suboptimal therapy ($18 736 vs. $10 878; P < 0.001); in UC, the disparity was smaller ($12 679 vs. $9653; P < 0.001).
Conclusions
Frequent dose and treatment changes were observed in all classes of initial UC and CD treatments. The economic impact of suboptimal therapy among UC and CD patients is substantial.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
ABSTRACT
We report the phase-connected timing ephemeris, polarization pulse profiles, Faraday rotation measurements, and Rotating-Vector-Model (RVM) fitting results of 12 millisecond pulsars (MSPs) ...discovered with the Five-hundred-meter Aperture Spherical radio Telescope (FAST) in the Commensal Radio Astronomy FAST survey (CRAFTS). The timing campaigns were carried out with FAST and Arecibo over 3 yr. 11 of the 12 pulsars are in neutron star–white dwarf binary systems, with orbital periods between 2.4 and 100 d. 10 of them have spin periods, companion masses, and orbital eccentricities that are consistent with the theoretical expectations for MSP–Helium white dwarf (He WD) systems. The last binary pulsar (PSR J1912−0952) has a significantly smaller spin frequency and a smaller companion mass, the latter could be caused by a low orbital inclination for the system. Its orbital period of 29 d is well within the range of orbital periods where some MSP–He WD systems have shown anomalous eccentricities, however, the eccentricity of PSR J1912−0952 is typical of what one finds for the remaining MSP–He WD systems.
Display omitted
•Effects of six types of biochar on anaerobic degradation of phenol was investigated.•Biochar addition triggered rapid methanogenic phenol degradation.•Electro-active Geobacter and ...Methanosaeta were enriched after biochar added.•Potential DIET was enhanced with biochar as electron transfer mediator.•Redox-active groups rather than electrical conductivity of biochar likely stimulated DIET.
In this study, six different types of biochar (based on two feedstocks and three pyrolytic temperatures) were prepared as individual additives for both syntrophic phenol degradation and methanogenesis promotion. The results showed that for phenol degradation, the addition of biochar (15 g/L) shortened the methanogenic lag time from 15.0 days to 1.1–3.2 days and accelerated the maximum CH4 production rate from 4.0 mL/d to 10.4–13.9 mL/d. Microbial community analysis revealed that the electro-active Geobacter was enriched (from 3.8–7.7% to 11.1–23.1%), depending on the type of biochar that was added. This indicates a potential shift of syntrophic phenol metabolism from a thermodynamically unfavorable pathway with H2 as the interspecies electron transfer mediator to direct interspecies electron transfer (DIET). Integrated analysis of methanogenesis dynamics and the electrochemical properties of biochar showed that compared with electrical conductivity, the electron exchange capacity of biochar was more likely to dominate the DIET process, which was due to the presence of redox-active organic functional groups in biochar. The removal of biochar from the anaerobic system generally prolonged the lag time, revealing the importance of adsorption capacity of biochar to mitigate bio-toxicity of phenol to microbial activity.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Recent developments in the instrumentation and data analysis of synchrotron small‐angle X‐ray scattering (SAXS) on biomolecules in solution have made biological SAXS (BioSAXS) a mature and popular ...tool in structural biology. This article reports on an advanced endstation developed at beamline 13A of the 3.0 GeV Taiwan Photon Source for biological small‐ and wide‐angle X‐ray scattering (SAXS–WAXS or SWAXS). The endstation features an in‐vacuum SWAXS detection system comprising two mobile area detectors (Eiger X 9M/1M) and an online size‐exclusion chromatography system incorporating several optical probes including a UV–Vis absorption spectrometer and refractometer. The instrumentation and automation allow simultaneous SAXS–WAXS data collection and data reduction for high‐throughput biomolecular conformation and composition determinations. The performance of the endstation is illustrated with the SWAXS data collected for several model proteins in solution, covering a scattering vector magnitude q across three orders of magnitude. The crystal‐model fittings to the data in the q range ∼0.005–2.0 Å−1 indicate high similarity of the solution structures of the proteins to their crystalline forms, except for some subtle hydration‐dependent local details. These results open up new horizons of SWAXS in studying correlated local and global structures of biomolecules in solution.
A new endstation for biological small‐ and wide‐angle X‐ray scattering is detailed, which provides development opportunities for studying correlated local and global structures of biomolecules in solution.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
By designing a structured gas density profile between the dual-stage gas jets to manipulate electron seeding and energy chirp reversal for compressing the energy spread, we have experimentally ...produced high-brightness high-energy electron beams from a cascaded laser wakefield accelerator with peak energies in the range of 200-600 MeV, 0.4%-1.2% rms energy spread, 10-80 pC charge, and ∼0.2 mrad rms divergence. The maximum six-dimensional brightness B_{6D,n} is estimated as ∼6.5×10^{15} A/m^{2}/0.1%, which is very close to the typical brightness of e beams from state-of-the-art linac drivers. These high-brightness high-energy e beams may lead to the realization of compact monoenergetic gamma-ray and intense coherent x-ray radiation sources.
Full text
Available for:
CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Cholinergic projections to cerebral cortical and subcortical regions are decreased in Parkinson disease (PD), but not evaluated in the parkinsonian syndromes of multiple system atrophy (MSA-P) and ...progressive supranuclear palsy (PSP). We studied cholinergic innervation in these disorders as compared to age-appropriate normal control subjects.
We used PET with (11)CPMP to measure acetylcholinesterase (AChE) activity in multiple cerebral cortical and subcortical regions. We studied 22 normal controls, 12 patients with PD, 13 patients with MSA-P, and 4 patients with PSP.
We found significantly decreased AChE activity in most cerebral cortical regions in PD and MSA-P, and a similar but nonsignificant decrease in PSP. No differences were found between PD and MSA-P. Significantly decreased AChE activity was found in PD in striatum, cerebellum, and thalamus, with a marginally significant decrease in mesencephalon and no change in pons. Significantly greater declines in AChE activity in all subcortical regions were seen in MSA-P and PSP vs in PD. Decreased AChE activity in brainstem and cerebellum of all 3 disorders correlated with disturbances of balance and gait.
Cerebral cortical cholinergic activity is decreased to a similar level in Parkinson disease (PD), parkinsonian syndromes of multiple system atrophy (MSA-P), and progressive supranuclear palsy (PSP) as compared to normal controls. Subcortical cholinergic activity is significantly more decreased in MSA-P and PSP than in PD. The more substantial decrease reflects greater impairment in the pontine cholinergic group, which is important in motor activity, particularly gait. These differences may account for the greater gait disturbances in the early stages of MSA-P and PSP than in PD.
Functional failure of tau contributes to age-dependent, iron-mediated neurotoxicity, and as iron accumulates in ischemic stroke tissue, we hypothesized that tau failure may exaggerate ...ischemia-reperfusion-related toxicity. Indeed, unilateral, transient middle cerebral artery occlusion (MCAO) suppressed hemispheric tau and increased iron levels in young (3-month-old) mice and rats. Wild-type mice were protected by iron-targeted interventions: ceruloplasmin and amyloid precursor protein ectodomain, as well as ferroptosis inhibitors. At this age, tau-knockout mice did not express elevated brain iron and were protected against hemispheric reperfusion injury following MCAO, indicating that tau suppression may prevent ferroptosis. However, the accelerated age-dependent brain iron accumulation that occurs in tau-knockout mice at 12 months of age negated the protective benefit of tau suppression against MCAO-induced focal cerebral ischemia-reperfusion injury. The protective benefit of tau knockout was revived in older mice by iron-targeting interventions. These findings introduce tau-iron interaction as a pleiotropic modulator of ferroptosis and ischemic stroke outcome.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
PDF
