We developed an analytical model to describe hopping transport in organic semiconductors including both energetic disorder and polaronic contributions due to geometric relaxation. The model is based ...on a Marcus jump rate in terms of the small-polaron concept with a Gaussian energetic disorder, and it is premised upon a generalized effective medium approach yet avoids shortcomings involved in the effective transport energy or percolation concepts. It is superior to our previous treatment Phys. Rev. B 76, 045210 (2007) (http://dx.doi.org/10.1103/PhysRevB.76.045210) since it is applicable at arbitrary polaron activation energy E sub(a) with respect to the energy disorder parameter sigma. It can be adapted to describe both charge-carrier mobility and triplet exciton diffusion. The model is compared with results from Monte Carlo simulations. We show (i) that the activation energy of the thermally activated hopping transport can be decoupled into disorder and polaron contributions whose relative weight depend nonlinearly on the sigma/E sub(a) ratio, and (ii) that the choice of the density of occupied and empty states considered in configurational averaging has a profound effect on the results of calculations of the Marcus hopping transport. The sigma/E sub(a) ratio governs also the carrier-concentration dependence of the charge-carrier mobility in the large-carrier-concentration transport regime as realized in organic field-effect transistors. The carrier-concentration dependence becomes considerably weaker when the polaron energy increases relative to the disorder energy, indicating the absence of universality. This model bridges a gap between disorder and polaron hopping concepts.
In patients with severe, uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP), dupilumab 300 mg every 2 weeks can completely resolve nasal polys, sinus disease, and symptoms. In this case, ...patients ask for de-escalation. Although trials have demonstrated recurrence after stopping the biologic at 24 weeks, reducing the dose of dupilumab to once every 4 weeks did not result in deterioration of control. An extension of the treatment intervals would, however, diverge from the approval text, and is currently not recommended.
The course of 29 patients with severe CRSwNP, type‑2 inflammation-associated comorbidities, and an indication for biologic was retrospectively analyzed. After resolution of CRSwNP and symptoms under biweekly dupilumab 300 mg, the dupilumab interval had been prolonged individually, initially up to 4 weeks, thereafter up to 6 weeks, if applicable. Control was assessed via quality of life (22-item sinonasal outcome test, SNOT-22), nasal polyp score, and smell identification test (Sniffin' Sticks; Burghart Messtechnik, Holm, Germany).
All patients showed an excellent improvement within the first 3 months. The dupilumab application interval was extended to 4 weeks after 7-31 months (median 13 months) and to 6 weeks (n = 9) after 17-35 months (median 23 months). No recurrent polyps or symptoms were subsequently observed.
In case of maximal regression of polyps and discomfort, extension of dupilumab injection intervals to 4 and potentially 6 weeks is possible without clinical worsening. Further studies on de-escalation or termination of biologic treatment when CRSwNP control is achieved are essential.
The primary objective of the BATTLE (Bare Metal Stent vs. Paclitaxel Eluting Stent in the Setting of Primary Stenting of Intermediate-Length Femoropopliteal Lesions) trial is to demonstrate the ...clinical superiority of the Zilver PTX stent over the Misago stent in the treatment of femoropopliteal lesions.
No randomized studies have compared self-expanding paclitaxel-eluting stents with bare-metal stents in the treatment of femoropopliteal lesions.
BATTLE is a multicenter randomized controlled trial in patients with symptomatic (Rutherford category 2 to 5) de novo lesions of the superficial femoral or proximal popliteal artery. The primary endpoint is freedom from in-stent restenosis (ISR) at 1 year, with restenosis defined as a peak systolic velocity index >2.4 at the target lesion. The Kaplan-Meier method was used to evaluate time-to-event data for freedom from ISR over the 2-year follow-up period.
Between March 2014 and August 2016, 186 patients were enrolled; 91 were assigned to the Misago arm and 90 to the Zilver PTX arm. Kaplan-Meier 1-year estimates of freedom from ISR were 88.6% for Misago and 91% for Zilver PTX (hazard ratio HR: 1.2; 95% confidence interval CI: 0.6 to 2.4; p = 0.64). Comparing Misago with Zilver PTX, 2-year estimates were 6.4% and 1.2% (HR: 7.3; 95% CI: 0.9 to 59.3; p = 0.0632) for mortality, 74.6% and 78.8% (HR: 1.2; 95% CI: 0.6 to 2.1; p = 0.62) for patency, and 14.4% and 12.4% (HR: 1.2; 95% CI: 0.5 to 2.8; p = 0.69) for target lesion revascularization.
In the treatment of symptomatic femoropopliteal lesions, the Zilver PTX stent failed to show superiority over the Misago stent in freedom from ISR at 1 year.
High-frequency stimulation of the globus pallidus internus (GPi) is a highly effective therapy in primary dystonia. Recent reports have also demonstrated almost immediate improvement of motor ...symptoms in patients with tardive dystonia after pallidal deep brain stimulation (DBS). Here, we show the long-term effect of continuous bilateral GPi DBS in tardive dystonia on motor function, quality of life (QoL), and mood.
Nine consecutive patients undergoing DBS for tardive dystonia were assessed during continuous DBS at 3 time points: 1 week, 3 to 6 months, and last follow-up at the mean of 41 (range 18-80) months after surgery using established and validated movement disorder and neuropsychological scales. Clinical assessment was performed by a neurologist not blinded to the stimulation settings.
One week and 3 to 6 months after pallidal DBS, Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor scores were ameliorated by 56.4 +/- 26.7% and 74.1 +/- 15.8%, BFMDRS disability scores by 62.5 +/- 21.0% and 88.9 +/- 10.3%, and Abnormal Involuntary Movement Scale (AIMS) scores by 52.3 +/- 24.1% and 69.5 +/- 27.6%, respectively. At last follow-up, this improvement compared with the presurgical assessment was maintained as reflected by a reduction of BFMDRS motor scores by 83.0 +/- 12.2%, BFMDRS disability scores by 67.7 +/- 28.0%, and AIMS scores by 78.7 +/- 19.9%. QoL improved significantly in physical components, and there was a significant improvement in affective state. Furthermore, cognitive functions remained unchanged compared with presurgical status in the long-term follow-up. No permanent adverse effects were observed.
Pallidal deep brain stimulation is a safe and effective long-term treatment in patients with medically refractory tardive dystonia.
There is a long history of human–riverine interactions throughout the period of agriculture that in some regions of the world started several thousand years ago. These interactions have altered ...rivers to human dominated systems with often negative impacts on fluvial environments. To achieve a good ecological and chemical status of rivers, as intended in the European Water Framework Directive (WFD), a better understanding of the natural status of rivers and an improved quantification of human–riverine interactions is necessary. Over the last decade the PAGES-LUCIFS (Land Use and Climate Impact on Fluvial Systems) program has been investigating both contemporary and long-term (centuries to millennia) river responses to global change with the principal aims of: 1) quantifying land use and climate change impacts of river-borne fluxes of water, sediment, C, N and P; 2) identification of key controls on these fluxes at the catchment scale; and 3) identification of the feedback on both human society and biogeochemical cycles of long-term changes in the fluxes of these materials. Here, we review recent progress on identifying fluvial system baselines and quantifying the response of long-term sediment budgets, biogeochemical fluxes and flood magnitude and frequency to Holocene global change. Based on this review, we outline the future LUCIFS research agenda within the scope of the PAGES-PHAROS (Past Human-Climate-Ecological Interactions) research program. Key research strategies should be focused on: 1) synthesising the data available from existing case studies; 2) targeting research in data-poor regions; 3) integrating sediment, C, N and P fluxes; 4) quantifying the relative roles of allogenic and autogenic forcing on fluvial regimes, extreme events and sediment fluxes; 5) improving long-term river basin modelling; and 6) integration of LUCIFS with other research communities within PHAROS, namely HITE (land cover) and LIMPACS (water quality and biodiversity).
Introduction
Hydrocephalus is still a not well-understood diagnostic and a therapeutic dilemma because of the lack of sufficient and comprehensive model of cerebrospinal fluid circulation and ...pathological alterations.
Conclusions
Based on current studies, reviews, and knowledge of cerebrospinal fluid dynamics, brain water dynamics, intracranial pressure, and cerebral perfusion physiology, a new concept is deducted that can describe normal and pathological changes of cerebrospinal fluid circulation and pathophysiology of idiopathic intracranial hypertension.
Background and Objectives
Severe periodontitis affects about 10% of the world population. In addition, associations between periodontitis and systemic diseases exist. Therefore, the diagnosis should ...be made quickly and at an early stage. Matrix metalloproteinase‐8 (MMP‐8) is the most prominent collagenase found in inflamed periodontal tissues. Its active form (aMMP‐8) is increasingly used as a diagnostic biomarker. Aim of the present study is to evaluate the diagnostic accuracy of a novel aMMP‐8 point‐of‐care (POC) test in comparison to the standard laboratory test to diagnose the disease rapidly and reliably.
Material and Methods
In a prospective, mono‐center, double‐blinded, case–control study, participants with healthy gums (n = 35), gingivitis (n = 60) and periodontitis (n = 35) were investigated before and after therapy. Beside clinical variables for plaque and inflammation, aMMP‐8 concentrations were determined in oral rinsing specimens by the enzyme‐linked immunosorbent assay (ELISA) and by POC. Positive and negative percent agreements with their exact one‐sided lower 95% confidence limits were calculated.
Results
Of 130 participants, 111 finished the study. Overall, positive percent agreements were 75.8% (57.7–88.9) before treatment and 73.7% (56.9–86.6) after treatment. Negative percent agreements were 92.8% (85.7–97.0) before and 93.3% (85.1–97.8) after treatment. Positive test results (POC and ELISA) ranged from 5.7% to 8.6% in healthy patients, 25.0–29.8% in patients with gingivitis and 40.0–48.1% in patients with periodontitis. Patients who had positive aMMP‐8 test results (POC) showed higher scores for plaque and inflammation.
Conclusions
The novel POC test to detect aMMP‐8 has proved to agree strongly with the standard method, ELISA. The test can be recommended to screen patients at risk for periodontitis in dental offices, at the general practitioner and at specialists for associated diseases.
Purpose
Progressive supranuclear palsy (PSP) is primary 4-repeat tauopathy. Evidence spanning from imaging studies indicate aberrant connectivity in PSPs. Our goal was to assess functional ...connectivity network alterations in PSP patients and the potential link between regional tau-burden and network-level functional connectivity using the next-generation tau PET tracer
18
FPI-2620 and resting-state functional MRI (fMRI).
Material and methods
Twenty-four probable PSP patients (70.9 ± 6.9 years, 13 female), including 14 Richardson syndrome (RS) and 10 non-RS phenotypes, underwent
18
FPI-2620 PET/MRI imaging. Distribution volume ratios (DVRs) were estimated using non-invasive pharmacokinetic modeling. Resting-state fMRI was also acquired in these patients as well as in thirteen older non-AD MCI reference group (64 ± 9 years, 4 female). The functional network was constructed using 141 by 141 region-to-region functional connectivity metrics (RRC) and network-based statistic was carried out (connection threshold
p
< 0.001, cluster threshold pFDR < 0.05).
Results
In total, 9870 functional connections were analyzed. PSPs compared to aged non-AD MCI reference group expressed aberrant connectivity evidenced by the significant NBS network consisting of 89 ROIs and 118 connections among them (NBS mass 4226, pFDR < 0.05). Tau load in the right globus pallidus externus (GPe) and left dentate nucleus (DN) showed significant effects on functional network connectivity. The network linked with increased tau load in the right GPe was associated with hyperconnectivity of low-range intra-opercular connections (NBS mass 356, pFDR < 0.05), while the network linked with increased tau load in the left cerebellar DN was associated with cerebellar hyperconnectivity and cortico-cerebellar hypoconnectivity (NBS mass 517, pFDR < 0.05).
Conclusions
PSP patients show altered functional connectivity. Network incorporating deep gray matter structures demonstrate hypoconnectivity, cerebellum hyperconnectivity, while cortico-cortical connections show variable changes. Tau load in the right GPe and left DN is associated with functional networks which strengthen low-scale intra-opercular and intra-cerebellar connections and weaken opercular-cerebellar connections. These findings support the concept of tau load-dependent functional network changes in PSP, by that providing evidence for downstream effects of neuropathology on brain functionality in this primary tauopathy.
Introduction
In unresectable intrahepatic cholangiocarcinoma (ICC), systemic chemotherapy often is viewed as the only option, although efficacy is limited. Radioembolization (RE) using yttrium-90 (
...90
Y) microspheres is an accepted therapy for patients with hepatocellular-carcinoma or metastatic liver tumors. However, there are limited data on the value of RE in patients with ICC and few data on factors influencing prognosis. The purpose of our retrospective analysis was to establish which factors influenced time-to-progression (TTP) and overall survival (OS).
Methods
Patients with unresectable ICC were treated with
90
Y resin-microspheres and assessed at 3-monthly intervals. Radiologic response was evaluated by using Response Criteria in Solid Tumors (RECIST). Baseline characteristics, biochemical/clinical toxicities, and response were examined for impact on TTP and OS.
Results
Thirty-four treatments were administered to 33 patients without major complications. By RECIST, 12 patients had a partial response, 17 had stable disease, and 5 had progressive disease after 3 months. The median OS was 22 months posttreatment and 43.7 months postdiagnosis. Median TTP was 9.8 months. Survival and TTP were significantly prolonged in patients with ECOG 0 (vs. ECOG 1 or 2; median OS: 29.4, 10, and 5.1 months; TTP: 17.5, 6.9, and 2.4 months), tumor burden ≤25% (OS: 26.7 vs. 6 months; TTP: 17.5 vs. 2.3 months), or tumor response (PR or SD vs. PD; OS: 35.5, 17.7 vs. 5.7 months; TTP: 31.9, 9.8 vs. 2.5 months), respectively (
P
< 0.001).
Conclusions
Radioembolization is an effective and safe option for patients with unresectable ICC. Predictors for prolonged survival are performance status, tumor burden, and RECIST response.
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