•A novel method for measuring fluctuations in subthalamic LFP power in Parkinson’s disease using a baseline of power.•Modeling physiological brain activity using a simulated 1/f spectrum.•Burst ...durations depend on choice of bandwidth and center frequency.•Burst durations progressively shorten during increasing intensities of neurostimulation.•Comparison of event detection methods in the distribution of burst durations with increasing intensities of neurostimulation.
Pathologically prolonged bursts of neural activity in the 8−30 Hz frequency range in Parkinson’s disease have been measured using high power event detector thresholds.
This study introduces a novel method for determining beta bursts using a power baseline based on spectral activity that overlapped a simulated 1/f spectrum. We used resting state local field potentials from people with Parkinson’s disease and a simulated 1/f signal to measure beta burst durations, to demonstrate how tuning parameters (i.e., bandwidth and center frequency) affect burst durations, to compare burst duration distributions with high power threshold methods, and to study the effect of increasing neurostimulation intensities on burst duration.
The baseline method captured a broad distribution of resting state beta band burst durations. Mean beta band burst durations were significantly shorter on compared to off neurostimulation (p = 0.0046), and their distribution shifted towards that of the 1/f spectrum during increasing intensities of stimulation.
High power event detection methods, measure duration of higher power bursts and omit portions of the neural signal. The baseline method captured the broadest distribution of burst durations and was more sensitive than high power detection methods in demonstrating the effect of neurostimulation on beta burst duration.
The baseline method captured a broad range of fluctuations in beta band neural activity and demonstrated that subthalamic neurostimulation shortened burst durations in a dose (intensity) dependent manner, suggesting that beta burst duration is a useful control variable for closed loop algorithms.
Benznidazole is recommended for treatment of Chagas infection. Effects of combination therapy with benznidazole and posaconazole have not been tested in Trypanosoma cruzi carriers.
The purpose of ...this study was to determine whether posaconazole alone or combined with benznidazole were superior to benznidazole monotherapy in eliminating T. cruzi parasites measured by real time polymerase chain reaction (RT-PCR) in asymptomatic Chagas carriers.
A prospective, multicenter randomized placebo-controlled study was conducted in 120 subjects from Latin America and Spain who were randomized to 4 groups: posaconazole 400 mg twice a day (b.i.d.); benznidazole 200 mg + placebo b.i.d.; benznidazole 200 mg b.i.d. + posaconazole 400 mg b.i.d.; or placebo 10 mg b.i.d. T. cruzi deoxyribonucleic acid was detected by RT-PCR at 30, 60, 90, 120, 150, 180, and 360 days. The primary efficacy outcome is the proportion of subjects with persistent negative RT-PCR by day 180; the secondary outcome was negative RT-PCR at 360 days.
Only 13.3% of those receiving posaconazole and 10% receiving placebo achieved the primary outcome, compared with 80% receiving benznidazole + posaconazole and 86.7% receiving benznidazole monotherapy (p < 0.0001 vs. posaconazole/placebo). Posaconazole monotherapy or posaconazole combined with benznidazole achieved high RT-PCR conversion rates during treatment (30 days; 93.3% and 88.9% and 60 days; 90%, and 92.3%) that were similar to benznidazole (89.7% and 89.3%); all were superior to placebo or posaconazole (10% and 16.7%, p < 0.0001). This was not observed at 360 days; benznidazole + posaconazole and benznidazole monotherapy (both 96%) versus placebo (17%) and posaconazole (16%, p < 0.0001). Serious adverse events were rare (6 patients) and were observed in the benznidazole-treated patients. Permanent discontinuation was reported in 19 patients (31.7%) receiving either benznidazole monotherapy or combined with posaconazole.
Posaconazole demonstrated trypanostatic activity during treatment, but it is ineffective long-term in asymptomatic T. cruzi carriers. Benznidazole monotherapy is superior to posaconazole, with high RT-PCR conversion rates sustained at 1 year. Side effects lead to therapy discontinuation in 32%. No advantages were observed with combined therapy versus benznidazole monotherapy. (A Study of the Use of Oral Posaconazole POS in the Treatment of Asymptomatic Chronic Chagas Disease P05267 STOP CHAGAS: NCT01377480).
The angular size of the broad line region (BLR) of the nearby active galactic nucleus NGC 3783 has been spatially resolved by recent observations with VLTI/GRAVITY. A reverberation mapping (RM) ...campaign has also recently obtained high quality light curves and measured the linear size of the BLR in a way that is complementary to the GRAVITY measurement. The size and kinematics of the BLR can be better constrained by a joint analysis that combines both GRAVITY and RM data. This, in turn, allows us to obtain the mass of the supermassive black hole in NGC 3783 with an accuracy that is about a factor of two better than that inferred from GRAVITY data alone. We derive
M
BH
= 2.54
−0.72
+0.90
× 10
7
M
⊙
. Finally, and perhaps most notably, we are able to measure a geometric distance to NGC 3783 of 39.9
−11.9
+14.5
Mpc. We are able to test the robustness of the BLR-based geometric distance with measurements based on the Tully–Fisher relation and other indirect methods. We find the geometric distance is consistent with other methods within their scatter. We explore the potential of BLR-based geometric distances to directly constrain the Hubble constant,
H
0
, and identify differential phase uncertainties as the current dominant limitation to the
H
0
measurement precision for individual sources.
Background
We assessed the clinical effectiveness of cefiderocol (CFDC) in comparison with colistin (COL) for the treatment of carbapenem-resistant
Acinetobacter baumannii
(CRAB) bloodstream ...infections (BSI).
Materials/methods
Retrospective cohort study including adults with CRAB-BSI. Outcomes were mortality, clinical cure and adverse events during therapy. The average treatment effect of CFDC compared to COL was weighted with the inverse-probability treatment weight (IPTW).
Results
Overall, 104 patients were included (50 CFDC, 54 COL), median age 66.5 years, median Charlson Comorbidity Index 5, septic shock in 33.6% of patients. Primary BSI accounted for 43.3% of cases, followed by ventilator-associated pneumonia (VAP) (26%), catheter-related BSI (20.2%) and hospital-acquired pneumonia (HAP) (9.6%). Although not significantly, mortality at all time points was lower for CFDC than COL, while clinical cure was higher in CFDC than COL (66% vs. 44.4%,
p
= 0.027). Adverse events were more frequent in COL than CFDC-group (38.8% vs. 10%,
p
< 0.0001), primarily attributed to acute kidney injury (AKI) in the COL group. Patients with bacteremic HAP/VAP treated with CFDC had a significant lower 30-d mortality and higher clinical cure than COL (
p
= 0.008 and
p
= 0.0008, respectively). Increment of CCI (
p
= 0.005), ICU (
p
= 0.025), SARS-CoV2 (
p
= 0.006) and ECMO (
p
< 0.0001) were independently associated with 30-d mortality, while receiving CFDC was not associated with survival.
Conclusions
CFDC could represent an effective and safe treatment option for CRAB BSI, especially in patients with bacteremic HAP/VAP and frail patients where the risk of acute renal failure during therapy should be avoided.
Key summary points
Increasing real-life data support the clinical effectiveness and safety of cefiderocol (CFDC) for carbapenem resistant
Acinetobacter baumannii
(CRAB) infections.
We investigated CFDC in comparison with colistin (COL) for the treatment of CRAB bloodstream infections (BSI).
Clinical cure was higher in CFDC than COL group.
Patients with hospital acquired/ventilator-associated pneumonia treated with CFDC had a statistically significant lower 30-d mortality and higher clinical cure than those treated with COL.
Adverse events were more frequent in COL than in CFDC-group.
CFDC could be an effective and safe treatment option for CRAB BSI, especially in patients with HAP/VAP and frail patients where the risk of acute renal failure during therapy should be avoided.
Cyclo-oxygenase-2 (COX-2) and cancer associated fibroblasts (CAFs) play an important role in the development and progression of tumor malignancy in humans and animals, showing that both can influence ...the tumor microenvironment. However, the impact of these two markers in feline mammary carcinogenesis has not yet been addressed.
In the present study, the clinicopathological significance of COX-2 immunoexpression and alpha-smooth muscle actin (α-SMA)-positive cancer-associated fibroblasts (CAFs) was determined and correlated with disease-free and overall survival of 50 felines with malignant mammary tumors.
COX-2 overexpression was positively associated with mitotic index (p=0.031), degree of malignancy (p≤0.001), lymph node metastasis (p≤0.001), vascular invasion (p=0.002), disease recurrence (p=0.019) and distant metastasis (p=0.036). α-SMA-positive CAFs were associated with mitotic index (p=0.004), lymph node metastasis (p=0.027), vascular invasion (p=0.05), disease recurrence (p≤0.001) and distant metastasis (p≤0.001). Additionally, both markers were correlated with disease-free and overall survival, emerging as predictors of poor prognosis.
Our results indicate for the first time that the presence of two markers, COX-2 and α-SMA, is associated with carcinogenesis and worse prognosis in feline mammary cancer and that α-SMA-positive CAFs have a role in feline mammary tumorigenesis, cancer development, and clinical outcome.
In the Mediterranean environment, floods pose a significant threat to people, in spite of the noteworthy improvements in forecasting, emergency management, and defensive works. This paper examines ...flood mortality in the Mediterranean environment based on a 36‐year long database (1980–2015) that was built in five study areas using documentary sources. Information on fatal accidents was disaggregated in database fields describing victim's profile and the circumstances of the accidents. Data show an increasing trend of flood fatalities during the study period. Accidents mainly occurred outdoor: the majority of the 458 fatalities were males, mainly aged between 30 and 49 years, and residents in the area of the accident. In the majority of cases, people were dragged by water/mud when travelling by car. Some cases of hazardous behaviours, such as fording rivers or trying to save belongings, were also detected. The cause of death was drowning in the majority of cases, and heart attack in a few cases it was. The results of the research can be proficiently used in information campaigns aiming to increase people safety during future floods.
We report on a comprehensive analysis of simultaneous X-ray polarimetric and spectral data of the bright atoll source GX 9+9 with the Imaging X-ray Polarimetry Explorer (IXPE) and
NuSTAR
. The source ...is significantly polarized in the 4–8 keV band, with a degree of 2.2% ± 0.5% (uncertainty at the 68% confidence level). The
NuSTAR
broad-band spectrum clearly shows an iron line, and is well described by a model including thermal disc emission, a Comptonized component, and reflection. From a spectro-polarimetric fit, we obtain an upper limit to the polarization degree of the disc of 4% (at the 99% confidence level), while the contribution of Comptonized and reflected radiation cannot be conclusively separated. However, the polarization is consistent with resulting from a combination of Comptonization in a boundary or spreading layer, plus reflection off the disc, which significantly contributes in any realistic scenario.
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