•SBRT remains controversial for operable early-stage NSCLC.•This study analyzes a cohort of >400 operable patients treated with SBRT.•Disease control outcomes for operable and inoperable SBRT ...patients are similar.•Operable SBRT patients have improved survival compared to inoperable patients.
Although stereotactic body radiation therapy (SBRT) is the standard of care for inoperable early-stage non-small cell lung carcinoma (NSCLC), its role for medically operable patients remains controversial. To address this knowledge gap, we conducted a multi-institutional study to assess post-SBRT disease control and survival outcomes in medically operable patients.
We conducted a retrospective cohort study including patients with biopsy-proven cT1-2N0M0 NSCLC treated with definitive SBRT (2006–2015). Per patient charts, inoperability referred to documentation of poor surgical candidacy with a given rationale for lack of resection. Charts of operable patients contained documentation of patients refusing surgery or choosing SBRT, without a documented rationale for inoperability. Subjects were excluded in cases of ambiguity regarding the aforementioned definitions and/or lack of clearly documented operability status. Endpoints included local failure (LF) and regional-distant failure, both evaluated with Fine and Gray competing risks regression; Kaplan-Meier methodology analyzed overall survival (OS) and progression-free survival (PFS).
Of 952 patients, 408 (42.9%) were operable, and 544 (57.1%) were inoperable. Median follow-up was 22 months. Two-year LF was 9.7% in operable patients and 8.2% in inoperable patients (p = 0.36). There was no statistical difference in regional-distant failure (p = 0.55) between cohorts. Operable patients experienced statistically higher OS (p = 0.04), but not PFS (p = 0.11). Respective 1-, 2-, and 3-year OS in operable patients were 85.4%, 66.2%, and 51.2%.
Although patients with operable NSCLC experience higher OS than their inoperable counterparts, disease-related outcomes are similar. These results may better inform shared decision-making between medically operable patients and their multidisciplinary providers.
As forests develop, changes in soil organic matter quantity and quality affect both nutrient dynamics and microbial community structure. Litter decomposition and nitrogen mineralization in ...association with soil microbial communities were compared between 45- and 135-year-old lodgepole pine (Pinus contorta var. latifolia (Englem.)) stands in southeastern Wyoming, USA. Compared with the 45-year-old stand, the 135-year-old stand was found to have greater live-tree biomass, litter decomposition rates (264 versus 135 mg·(g litter)–1·year–1), soil nitrification rates (0.38 versus 0.19 µg NO3–·(g soil)–1 after 265 days of field incubation), and total phospholipid fatty acid (PLFA) concentrations (25 versus 9.2 nmol·(g soil)–1 at 0–5 cm depth). Canonical correspondence analysis indicated that variation of PLFA profiles within the 45-year-old stand was explained by soil pH and bulk density, whereas soil process rates explained the distributions of PLFA profiles within the 135-year-old stand. The results of these studies indicate that stand age influences live-tree biomass and soil properties that can lead to changes in litter decomposition rates and soil microbial communities in lodgepole pine forests.
Celotno besedilo
Dostopno za:
BF, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
α-synuclein (aSyn) expression is implicated in neurodegenerative processes, including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). In animal models of these diseases, axon pathology ...often precedes cell death, raising the question of whether aSyn has compartment-specific toxic effects that could require early and/or independent therapeutic intervention. The relevance of axonal pathology to degeneration can only be addressed through longitudinal, in vivo monitoring of different neuronal compartments. With current imaging methods, dopaminergic neurons do not readily lend themselves to such a task in any vertebrate system. We therefore expressed human wild-type aSyn in zebrafish peripheral sensory neurons, which project elaborate superficial axons that can be continuously imaged in vivo. Axonal outgrowth was normal in these neurons but, by 2 days post-fertilization (dpf), many aSyn-expressing axons became dystrophic, with focal varicosities or diffuse beading. Approximately 20% of aSyn-expressing cells died by 3 dpf. Time-lapse imaging revealed that focal axonal swelling, but not overt fragmentation, usually preceded cell death. Co-expressing aSyn with a mitochondrial reporter revealed deficits in mitochondrial transport and morphology even when axons appeared overtly normal. The axon-protective protein Wallerian degeneration slow (WldS) delayed axon degeneration but not cell death caused by aSyn. By contrast, the transcriptional coactivator PGC-1α, which has roles in the regulation of mitochondrial biogenesis and reactive-oxygen-species detoxification, abrogated aSyn toxicity in both the axon and the cell body. The rapid onset of axonal pathology in this system, and the relatively moderate degree of cell death, provide a new model for the study of aSyn toxicity and protection. Moreover, the accessibility of peripheral sensory axons will allow effects of aSyn to be studied in different neuronal compartments and might have utility in screening for novel disease-modifying compounds.
Spatial characteristics of soil microbial community structure and selected soil chemical factors were analyzed in soil surrounding
Agropyron smithii (Western wheatgrass) and
Artemisia tridentata ...(Wyoming big sagebrush) plants in sites reclaimed after surface mining and adjacent undisturbed sites in Wyoming. Microbial biomass C (MBC) and fatty acid methyl ester (FAME) biomarkers for total biomass, bacteria, and fungi were used as indicators of soil microbial community abundance and structure. In soil 20 years after reclamation FAME total microbial biomass, bacterial and fungal biomarkers, MBC and soil organic matter (SOM) averaged only 20, 16, 28, 44 and 36% of values found in undisturbed soils. In contrast to undisturbed soils, FAME biomarkers and MBC of reclaimed soils exhibited spatial correlation up to 42
cm. Reclaimed soils also exhibited localized enrichment of bacterial, fungal, and total microbial biomass, as well as depletion of inorganic N concentrations, around plant bases (<10
cm), suggesting relatively poor soil exploration by roots and microorganisms compared to the undisturbed ecosystem. Strong spatial stratification of undisturbed SOM and soil NH
4
+ pools was found with highest concentrations on the leeward side of shrubs, likely due to localized changes in microclimate and plant litter deposition. This indicates that shrub cover plays a central role in the establishment of site heterogeneity and regulation of ecological processes, such as C and N mineralization and immobilization, which has important implications for reclamation.
The UV photoproduction of a hydrophilic TiO2(110)(1×1) surface has been investigated in a pressurized ultrahigh vacuum apparatus under controlled conditions of hydrocarbon concentration in oxygen gas ...at 1 atm pressure. Water droplet contact angles have been measured continuously as the droplet is exposed to UV irradiation, yielding the first observations of a sudden wetting process during irradiation. Using hexane as a model hydrocarbon, it is found that when low partial pressures of hexane are present, the sudden onset of surface wetting occurs during UV irradiation after an induction period under photooxidation conditions. The induction period to reach the critical condition for sudden wetting increases when the partial pressure (and equilibrium surface coverage) of hexane is increased. These results indicate that the removal of adsorbed hydrocarbons by photooxidation is the critical factor leading to the UV-induced hydrophilicity phenomenon on TiO2. The phenomenon does not occur in the absence of O2 gas. A concept concerned with kinetic screening of the TiO2−H2O interface from O2 by water droplets is presented to explain the observation of sudden wetting in our experiments, compared to gradual wetting which is observed following UV irradiation in all other experiments reported in the literature. Complementary infrared spectroscopy measurements of the effect of UV irradiation in an O2 atmosphere on adsorbed Ti−OH groups and on adsorbed H2O on the surface of a high-area TiO2 powder show that no spectroscopic changes occur. This indicates that UV-induced changes in the −OH coverage or the nature of −OH bonding to TiO2, as suggested by others, cannot be used to explain the photoinduced hydrophilicity effect.
Data collected around $\sqrt{s}=91$ GeV by the OPAL experiment at the LEP e super(+)e super(-) collider are used to study the mechanism of baryon formation. As the signature, the fraction of super(-) ...hyperons whose baryon number is compensated by the production of a $\overline{\Sigma,\overline{\Lambda}$ or $\overline{\Xi$ antihyperon is determined. The method relies entirely on quantum number correlations of the baryons, and not rapidity correlations, making it more model independent than previous studies. Within the context of the JETSET implementation of the string hadronization model, the diquark baryon production model without the popcorn mechanism is strongly disfavored with a significance of 3.8 standard deviations including systematic uncertainties. It is shown that previous studies of the popcorn mechanism with $\Lambda \overline{\Lambda}$ and $\mathrm{p}\pi \overline{\mathrm{p}}$ correlations are not conclusive, if parameter uncertainties are considered.
Replicated international studies have underscored the human and societal costs associated with major depressive disorder. Despite the proven efficacy of monoamine-based antidepressants in major ...depression, the majority of treated individuals fail to achieve full syndromal and functional recovery with the index and subsequent pharmacological treatments. Ketamine and esketamine represent pharmacologically novel treatment avenues for adults with treatment-resistant depression. In addition to providing hope to affected persons, these agents represent the first non-monoaminergic agents with proven rapid-onset efficacy in major depressive disorder. Nevertheless, concerns remain about the safety and tolerability of ketamine and esketamine in mood disorders. Moreover, there is uncertainty about the appropriate position of these agents in treatment algorithms, their comparative effectiveness, and the appropriate setting, infrastructure, and personnel required for their competent and safe implementation. In this article, an international group of mood disorder experts provides a synthesis of the literature with respect to the efficacy, safety, and tolerability of ketamine and esketamine in adults with treatment-resistant depression. The authors also provide guidance for the implementation of these agents in clinical practice, with particular attention to practice parameters at point of care. Areas of consensus and future research vistas are discussed.
Real-life clinical outcomes of patients treated with anti-VEGF drugs for neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), or macular edema secondary to branch ...retinal vein occlusion (BRVO) are often inferior to results from randomized clinical trials. This observational cohort study investigates treatment adherence and real-life clinical outcomes within the first year of treatment.
A total of 708 treatment-naïve patients (466 nAMD, 134 DME, and 108 BRVO) were included. Patients were followed with a PRN treatment protocol with three intravitreal injections (IVIs) and a series of 3 monthly injections in case of persistent or recurrent disease activity, as determined by monthly follow-up exams including optical coherence tomographies. Occurrence of gaps of >56 days between treatments or follow-up (nonadherence NA) and the reasons for NA (patient- or center-associated) as well as disease activity within the first 12 months of treatment were analyzed. Visual acuity (VA) as well as numbers and dates of optical coherence tomography and IVI were extracted from medical records.
NA occurred significantly more often in patients with DME (44%) than nAMD (32%) or BRVO (25%,
<0.01 between groups). NA was mainly patient-associated (nAMD: 80.0%, DME: 83.1%, BRVO: 70.4%,
=0.38 between groups). Patients with nAMD and DME and appropriate treatment/follow-up adherence had a better chance of significantly gaining or maintaining VA, respectively (19.9% vs 12.0% with 3-line-gain in nAMD and 1.3% vs 15.3% 3-line loss in DME; each
<0.05). NA did not correlate with VA outcomes in BRVO (3-line gain 30.9% vs 48.1% and 3-line loss 8.6% vs 7.4%;
>0.05).
NA to treatment and follow-up regimens is a common problem in the management of patients with AMD and DME and limits clinical treatment outcomes under real-life conditions. Patients with DME have the highest risk of patient-associated NA, associated with a higher risk for significant VA loss.
This paper critiques state-led strategies for land consolidation in Central and Eastern Europe. The critique builds on empirical research about the dynamics of land fragmentation and its presumable ...effects on cropland abandonment in Albania. Research results indicate that cropland abandonment was driven by a massive turn to non-farm opportunities, especially migration. Land fragmentation was not a rigid constraint on production but resulted from producers’ strategic risk spreading. The negotiated nature of land tenure questions the emphasis on state initiatives and administrative procedures in post-socialist land consolidation. Central and Eastern European states instead need to support desirable adaptations initiated by local communities.
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