In the adult hippocampus, neuroprogenitor cells in the subgranular zone (SGZ) of the dentate gyrus give rise to newborn neuroblasts. However, only a small subset of these cells integrates into the ...hippocampal circuitry as mature neurons at the end of a 4 week period. Here, we show that the majority of the newborn cells undergo death by apoptosis in the first 1 to 4 days of their life, during the transition from amplifying neuroprogenitors to neuroblasts. These apoptotic newborn cells are rapidly cleared out through phagocytosis by unchallenged microglia present in the adult SGZ niche. Phagocytosis by the microglia is efficient and undeterred by increased age or inflammatory challenge. Our results suggest that the main critical period of newborn cell survival occurs within a few days of birth and reveal a new role for microglia in maintaining the homeostasis of the baseline neurogenic cascade.
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► Majority of SGZ newborn cells enter apoptosis during the first 1–4 days of life ► Apoptotic debris is rapidly phagocytosed by unchallenged microglia ► Microglial phagocytic efficiency is not affected by age or inflammation
This pooled analysis evaluated the outcomes of prophylactic cranial irradiation (PCI) in 739 small-cell lung cancer (SCLC patients with stable disease (SD) or better following chemotherapy ± thoracic ...radiation therapy (TRT) to examine the potential advantage of PCI in a wider spectrum of patients than generally participate in PCI trials.
Three hundred eighteen patients with extensive SCLC (ESCLC) and 421 patients with limited SCLC (LSCLC) participated in four phase II or III trials. Four hundred fifty-nine patients received PCI (30 Gy/15 or 25 Gy/10) and 280 did not. Survival and adverse events (AEs) were compared.
PCI patients survived significantly longer than non-PCI patients {hazard ratio HR = 0.61 95% confidence interval (CI): 0.52–0.72; P < 0.0001}. The 1- and 3-year survival rates were 56% and 18% for PCI patients versus 32% and 5% for non-PCI patients. PCI was still significant after adjusting for age, performance status, gender, stage, complete response, and number of metastatic sites (HR = 0.82, P = 0.04). PCI patients had significantly more grade 3+ AEs (64%) compared with non-PCI patients (50%) (P = 0.0004). AEs associated with PCI included alopecia and lethargy. Dose fractionation could be compared only for LSCLC patients and 25 Gy/10 was associated with significantly better survival compared with 30 Gy/15 (HR = 0.67, P = 0.018).
PCI was associated with a significant survival benefit for both ESCLC and LSCLC patients who had SD or a better response to chemotherapy ± TRT. Dose fractionation appears important. PCI was associated with an increase in overall and specific grade 3+ AE rates.
Safe, effective interventions to improve cancer-related fatigue (CRF) are needed because it remains a prevalent, distressing, and activity-limiting symptom. Based on pilot data, a phase III trial was ...developed to evaluate the efficacy of American ginseng on CRF.
A multisite, double-blind trial randomized fatigued cancer survivors to 2000mg of American ginseng vs a placebo for 8 weeks. The primary endpoint was the general subscale of the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) at 4 weeks. Changes from baseline at 4 and 8 weeks were evaluated between arms by a two-sided, two-sample t test. Toxicities were evaluated by self-report and the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) provider grading.
Three hundred sixty-four participants were enrolled from 40 institutions. Changes from baseline in the general subscale of the MFSI-SF were 14.4 (standard deviation SD = 27.1) in the ginseng arm vs 8.2 (SD = 24.8) in the placebo arm at 4 weeks (P = .07). A statistically significant difference was seen at 8 weeks with a change score of 20 (SD = 27) for the ginseng group and 10.3 (SD = 26.1) for the placebo group (P = .003). Greater benefit was reported in patients receiving active cancer treatment vs those who had completed treatment. Toxicities per self-report and CTCAE grading did not differ statistically significantly between arms.
Data support the benefit of American ginseng, 2000mg daily, on CRF over an 8-week period. There were no discernible toxicities associated with the treatment. Studies to increase knowledge to guide the role of ginseng to improve CRF are needed.
We have gathered optical photometry data from the literature on a large sample of Swift-era gamma-ray burst (GRB) afterglows including GRBs up to 2009 September, for a total of 76 GRBs, and present ...an additional three pre-Swift GRBs not included in an earlier sample. Furthermore, we publish 840 additional new photometry data points on a total of 42 GRB afterglows, including large data sets for GRBs 050319, 050408, 050802, 050820A, 050922C, 060418, 080413A, and 080810. We analyzed the light curves of all GRBs in the sample and derived spectral energy distributions for the sample with the best data quality, allowing us to estimate the host-galaxy extinction. We transformed the afterglow light curves into an extinction-corrected z = 1 system and compared their luminosities with a sample of pre-Swift afterglows. The results of a former study, which showed that GRB afterglows clustered and exhibited a bimodal distribution in luminosity space, are weakened by the larger sample. We found that the luminosity distribution of the two afterglow samples (Swift-era and pre-Swift) is very similar, and that a subsample for which we were not able to estimate the extinction, which is fainter than the main sample, can be explained by assuming a moderate amount of line-of-sight host extinction. We derived bolometric isotropic energies for all GRBs in our sample, and found only a tentative correlation between the prompt energy release and the optical afterglow luminosity at 1 day after the GRB in the z = 1 system. A comparative study of the optical luminosities of GRB afterglows with echelle spectra (which show a high number of foreground absorbing systems) and those without, reveals no indication that the former are statistically significantly more luminous. Furthermore, we propose the existence of an upper ceiling on afterglow luminosities and study the luminosity distribution at early times, which was not accessible before the advent of the Swift satellite. Most GRBs feature afterglows that are dominated by the forward shock from early times on. Finally, we present the first indications of a class of long GRBs, which form a bridge between the typical high-luminosity, high-redshift events and nearby low-luminosity events (which are also associated with spectroscopic supernovae) in terms of energetics and observed redshift distribution, indicating a continuous distribution overall.
Following recent advances in the analysis of centre-of-pressure (COP) recordings, we examined the structure of COP trajectories in ten children (nine in the analyses) with cerebral palsy (CP) and ...nine typically developing (TD) children while standing quietly with eyes open (EO) and eyes closed (EC) and with concurrent visual COP feedback (FB). In particular, we quantified COP trajectories in terms of both the amount and regularity of sway. We hypothesised that: (1) compared to TD children, CP children exhibit a greater amount of sway and more regular sway and (2) concurrent visual feedback (creating an external functional context for postural control, inducing a more external focus of attention) decreases both the amount of sway and sway regularity in TD and CP children alike, while closing the eyes has opposite effects. The data were largely in agreement with both hypotheses. Compared to TD children, the amount of sway tended to be larger in CP children, while sway was more regular. Furthermore, the presence of concurrent visual feedback resulted in less regular sway compared to the EO and EC conditions. This effect was less pronounced in the CP group where posturograms were most regular in the EO condition rather than in the EC condition, as in the control group. Nonetheless, we concluded that CP children might benefit from therapies involving postural tasks with an external functional context for postural control.
'Long' γ-ray bursts (GRBs) are commonly accepted to originate in the explosion of particularly massive stars, which give rise to highly relativistic jets. Inhomogeneities in the expanding flow result ...in internal shock waves that are believed to produce the γ-rays we see. As the jet travels further outward into the surrounding circumstellar medium, 'external' shocks create the afterglow emission seen in the X-ray, optical and radio bands. Here we report observations of the early phases of the X-ray emission of five GRBs. Their X-ray light curves are characterised by a surprisingly rapid fall-off for the first few hundred seconds, followed by a less rapid decline lasting several hours. This steep decline, together with detailed spectral properties of two particular bursts, shows that violent shock interactions take place in the early jet outflows.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There have been efforts around the globe to track individuals of many marine species and assess their movements and distribution, with the putative goal of supporting their conservation and ...management. Determining whether, and how, tracking data have been successfully applied to address real-world conservation issues is, however, difficult. Here, we compile a broad range of case studies from diverse marine taxa to show how tracking data have helped inform conservation policy and management, including reductions in fisheries bycatch and vessel strikes, and the design and administration of marine protected areas and important habitats. Using these examples, we highlight pathways through which the past and future investment in collecting animal tracking data might be better used to achieve tangible conservation benefits.
The value of animal tracking data to inform policy is illustrated by case studies from around the world and with a broad range of taxa.
Application of tracking data to policy and management can take various pathways, and engagement with stakeholders might often not be made by the original data collectors.
The impact of tracking data on policy and management can be improved if data collection and analyses target specific needs for management outcomes.
Early engagement among the data collectors and the stakeholders involved in policy development and implementation is important to help translate tracking data into conservation outcomes.
We observed GRB 190114C (redshift
z
= 0.4245), the first gamma-ray burst (GRB) ever detected at TeV energies, at optical and near-infrared wavelengths with several ground-based telescopes and the
...Hubble
Space Telescope, with the primary goal of studying its underlying supernova, SN 2019jrj. The monitoring spanned the time interval between 1.3 and 370 days after the burst, in the observer frame. We find that the afterglow emission can be modelled with a forward shock propagating in a uniform medium modified by time-variable extinction along the line of sight. A jet break could be present after 7 rest-frame days, and accordingly the maximum luminosity of the underlying supernova (SN) ranges between that of stripped-envelope core-collapse SNe of intermediate luminosity and that of the luminous GRB-associated SN 2013dx. The observed spectral absorption lines of SN 2019jrj are not as broad as in classical GRB SNe and are instead more similar to those of less-luminous core-collapse SNe. Taking the broad-lined stripped-envelope core-collapse SN 2004aw as an analogue, we tentatively derive the basic physical properties of SN 2019jrj. We discuss the possibility that a fraction of the TeV emission of this source might have had a hadronic origin and estimate the expected high-energy neutrino detection level with IceCube.
Objective
To compare the effectiveness of single, multiple, and multifactorial interventions to prevent falls and fall‐related fractures in community‐dwelling older persons.
Methods
MEDLINE, Embase, ...and Cochrane Central Register of Controlled Trials were systematically searched for randomized controlled trials (RCTs) evaluating the effectiveness of fall prevention interventions in community‐dwelling adults aged ≥65 years, from inception until February 27, 2019. Two large RCTs (published in 2020 after the search closed) were included in post hoc analyses. Pairwise meta‐analysis and network meta‐analysis (NMA) were conducted.
Results
NMA including 192 studies revealed that the following single interventions, compared with usual care, were associated with reductions in number of fallers: exercise (risk ratio RR 0.83; 95% confidence interval CI 0.77–0.89) and quality improvement strategies (e.g., patient education) (RR 0.90; 95% CI 0.83–0.98). Exercise as a single intervention was associated with a reduction in falls rate (RR 0.79; 95% CI 0.73–0.86). Common components of multiple interventions significantly associated with a reduction in number of fallers and falls rate were exercise, assistive technology, environmental assessment and modifications, quality improvement strategies, and basic falls risk assessment (e.g., medication review). Multifactorial interventions were associated with a reduction in falls rate (RR 0.87; 95% CI 0.80–0.95), but not with a reduction in number of fallers (RR 0.95; 95% CI 0.89–1.01). The following single interventions, compared with usual care, were associated with reductions in number of fall‐related fractures: basic falls risk assessment (RR 0.60; 95% CI 0.39–0.94) and exercise (RR 0.62; 95% CI 0.42–0.90).
Conclusions
In keeping with Tricco et al. (2017), several single and multiple fall prevention interventions are associated with fewer falls. In addition to Tricco, we observe a benefit at the NMA‐level of some single interventions on preventing fall‐related fractures.
This multicenter single-arm phase II study evaluated the addition of pazopanib to concurrent weekly paclitaxel following doxorubicin and cyclophosphamide as neoadjuvant therapy in human epidermal ...growth factor receptor (HER2)-negative locally advanced breast cancer (LABC). Patients with HER2-negative stage III breast cancer were treated with doxorubicin 60 mg/m
2
and cyclophosphamide 600 mg/m
2
for four cycles every 3 weeks followed by weekly paclitaxel 80 mg/m
2
on days 1, 8, and 15 every 28 days for four cycles concurrently with pazopanib 800 mg orally daily prior to surgery. Post-operatively, pazopanib was given daily for 6 months. The primary endpoint was pathologic complete response (pCR) in the breast and lymph nodes. Between July 2009 and March 2011, 101 patients with stage IIIA–C HER2-negative breast cancer were enrolled. The pCR rate in evaluable patients who initiated paclitaxel and pazopanib was 17 % (16/93). The pCR rate was 9 % (6/67) in hormone receptor-positive tumors and 38 % (10/26) in triple-negative tumors. Pre-operative pazopanib was completed in only 39 % of patients. The most frequent grade 3 and 4 adverse events during paclitaxel and pazopanib were neutropenia (27 %), diarrhea (5 %), ALT and AST elevations (each 5 %), and hypertension (5 %). Although the pCR rate of paclitaxel and pazopanib following AC chemotherapy given as neoadjuvant therapy in women with LABC met the pre-specified criteria for activity, there was substantial toxicity, which led to a high discontinuation rate of pazopanib. The combination does not appear to warrant further evaluation in the neoadjuvant setting for breast cancer.
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