Effect of neurostimulation on cognition and mood in refractory epilepsy.

Epilepsy is a common, debilitating neurological disorder characterized by recurrent seizures. Mood disorders and cognitive deficits are common comorbidities in epilepsy that, like seizures, profoundly influence quality of life and can be difficult to treat. For patients with refractory epilepsy who are not candidates for resection, neurostimulation, the electrical modulation of epileptogenic brain tissue, is an emerging treatment alternative. Several forms of neurostimulation are currently available, and therapy selection hinges on relative efficacy for seizure control and amelioration of neuropsychiatric comorbidities. Here, we review the current evidence for how invasive and noninvasive neurostimulation therapies affect mood and cognition in persons with epilepsy. Invasive therapies include vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS). Noninvasive therapies include trigeminal nerve stimulation (TNS), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS). Overall, current evidence supports stable cognition and mood with all neurostimulation therapies, although there is some evidence that cognition and mood may improve with invasive forms of neurostimulation. More research is required to optimize the effects of neurostimulation for improvements in cognition and mood

Finding diamonds in the rough: Targeted Sub-threshold Search for Strongly-lensed Gravitational-wave Events

Strong gravitational lensing of gravitational waves can produce duplicate signals separated in time with different amplitudes. We consider the case in which strong lensing produces identifiable gravitational-wave events and weaker sub-threshold signals hidden in the noise background. We present a search method for the sub-threshold signals using reduced template banks targeting specific confirmed gravitational-wave events. We apply the method to all events from Advanced LIGO's first and second observing run O1/O2. Using GW150914 as an example, we show that the method effectively reduces the noise background and raises the significance of (near-) sub-threshold triggers. In the case of GW150914, we can improve the sensitive distance by $2.0\% - 14.8\%$. Finally, we present the top $5$ possible lensed candidates for O1/O2 gravitational-wave events that passed our nominal significance threshold of False-Alarm-Rate $\leq 1/30$ days

TESLA-X: An effective method to search for sub-threshold lensed gravitational waves with a targeted population model

Strong gravitational lensing can produce copies of gravitational-wave signals from the same source with the same waveform morphologies but different amplitudes and arrival times. Some of these strongly-lensed gravitational-wave signals can be demagnified and become sub-threshold. We present TESLA-X, an enhanced approach to the original GstLAL-based TargetEd Subthreshold Lensing seArch (TESLA) method, for improving the detection efficiency of these potential sub-threshold lensed signals. TESLA-X utilizes lensed injections to generate a targeted population model and a targeted template bank. We compare the performance of a full template bank search, TESLA, and TESLA-X methods via a simulation campaign, and demonstrate the performance of TESLA-X in recovering lensed injections, particularly targeting a mock event. Our results show that the TESLA-X method achieves a maximum of $\sim 20\%$ higher search sensitivity compared to the TESLA method within the sub-threshold regime, presenting a step towards detecting the first lensed gravitational wave. TESLA-X will be employed for the LIGO-Virgo-KAGRA's collaboration-wide analysis to search for lensing signatures in the fourth observing run

Predictors of Patient Satisfaction in Spine Surgery: A Systematic Review

Background: Recently, there has been increased interest in patient satisfaction measures such as Press Ganey and Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys. In this systematic review, the spine surgery literature is analyzed to evaluate factors predictive of patient satisfaction as measured by these surveys. Methods: A thorough literature search was performed in PubMed/MEDLINE, Google Scholar, and Cochrane databases. All English-language articles from database inception to July 2020 were screened for study inclusion according to PRISMA guidelines. Results: Twenty-four of the 1899 published studies were included for qualitative analysis. There has been a statistically significant increase in the number of publications across years (P = 0.04). Overall, the studies evaluated the relationship between patient satisfaction and patient demographics (71%), preoperative and intraoperative clinical factors (21%), and postoperative factors (33%). Top positive predictors of patient satisfaction were patient and nursing/medical staff relationship (n = 4; 17%), physician–patient relationship (n = 4; 17%), managerial oversight of received care (n = 3; 13%), same sex/ethnicity between patient and physician (n = 2; 8%), and older age (n = 2; 8%). Top negative predictors of patient satisfaction were high Charlson Comorbidity Index/high disability/worse overall health functioning (n = 7; 29%), increased length of hospital stay (n = 4; 17%), high rating for pain/complications/readmissions (n = 4; 17%), and psychosocial factors (n = 3; 13%). Conclusions: There is heterogeneity in terms of different factors, both clinical and nonclinically related, that affect patient satisfaction ratings. More research is warranted to investigate the role of hospital consumer surveys in the spine surgical patient population

Targeting cancer addiction for SALL4 by shifting its transcriptome with a pharmacologic peptide

Sal-like 4 (SALL4) is a nuclear factor central to the maintenance of stem cell pluripotency and is a key component in hepatocellular carcinoma, a malignancy with no effective treatment. In cancer cells, SALL4 associates with nucleosome remodeling deacetylase (NuRD) to silence tumor-suppressor genes, such as PTEN. Here, we determined the crystal structure of an amino-terminal peptide of SALL4(1-12) complexed to RBBp4, the chaperone subunit of NuRD, at 2.7 Å, and subsequent design of a potent therapeutic SALL4 peptide (FFW) capable of antagonizing the SALL4-NURD interaction using systematic truncation and amino acid substitution studies. FFW peptide disruption of the SALL4-NuRD complex resulted in unidirectional up-regulation of transcripts, turning SALL4 from a dual transcription repressor-activator mode to singular transcription activator mode. We demonstrate that FFW has a target affinity of 23 nM, and displays significant antitumor effects, inhibiting tumor growth by 85% in xenograft mouse models. Using transcriptome and survival analysis, we discovered that the peptide inhibits the transcription-repressor function of SALL4 and causes massive up-regulation of transcripts that are beneficial to patient survival. This study supports the SALL4-NuRD complex as a drug target and FFW as a viable drug candidate, showcasing an effective strategy to accurately target oncogenes previously considered undruggable

An Early-warning System for Electromagnetic Follow-up of Gravitational-wave Events

Binary neutron stars (BNSs) will spend ≃10–15 minutes in the band of Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO) and Virgo detectors at design sensitivity. Matched-filtering of gravitational-wave (GW) data could in principle accumulate enough signal-to-noise ratio (S/N) to identify a forthcoming event tens of seconds before the companions collide and merge. Here we report on the design and testing of an early-warning GW detection pipeline. Early-warning alerts can be produced for sources that are at low enough redshift so that a large enough S/N accumulates ~10–60 s before merger. We find that about 7% (49%) of the total detectable BNS mergers will be detected 60 s (10 s) before the merger. About 2% of the total detectable BNS mergers will be detected before merger and localized to within 100 deg² (90% credible interval). Coordinated observing by several wide-field telescopes could capture the event seconds before or after the merger. LIGO–Virgo detectors at design sensitivity could facilitate observing at least one event at the onset of merger

An early warning system for electromagnetic follow-up of gravitational-wave events

Binary neutron stars (BNSs) will spend $\simeq 10$ -- 15 minutes in the band of Advanced LIGO and Virgo detectors at design sensitivity. Matched-filtering of gravitational-wave (GW) data could in principle accumulate enough signal-to-noise ratio (SNR) to identify a forthcoming event tens of seconds before the companions collide and merge. Here we report on the design and testing of an early warning gravitational-wave detection pipeline. Early warning alerts can be produced for sources that are at low enough redshift so that a large enough SNR accumulates $\sim 10 - 60\,\rm s$ before merger. We find that about 7% (respectively, 49%) of the total detectable BNS mergers will be detected $60\, \rm s$ ($10\, \rm s$) before the merger. About 2% of the total detectable BNS mergers will be detected before merger and localized to within $100\, \rm \text{deg}^2$ (90% credible interval). Coordinated observing by several wide-field telescopes could capture the event seconds before or after the merger. LIGO-Virgo detectors at design sensitivity could facilitate observing at least one event at the onset of merger.Comment: small update in numbers caused by using a more updated local BNS rate estimat