Vegetative State Research Articles

A Novel Approach to Screen for Somatosensory Evoked Potentials in Critical Care.

Somatosensory evoked potentials (SSEPs) help prognostication, particularly in patients with diffuse brain injury. However, use of SSEP is limited in critical care. We propose a novel, low-cost approach allowing acquisition of screening SSEP using widely available intensive care unit (ICU) equipment, specifically a peripheral "train-of-four" stimulator and standard electroencephalograph. The median nerve was stimulated using a train-of-four stimulator, and a standard 21-channel electroencephalograph was recorded to generate the screening SSEP. Generation of the SSEP was supported by visual inspection, univariate event-related potentials statistics, and a multivariate support vector machine (SVM) decoding algorithm. This approach was validated in 15 healthy volunteers and validated against standard SSEPs in 10 ICU patients. The ability of this approach to predict poor neurological outcome, defined as death, vegetative state, or severe disability at 6months, was tested in an additional set of 39 ICU patients. In each of the healthy volunteers, both the univariate and the SVM methods reliably detected SSEP responses. In patients, when compared against the standard SSEP method, the univariate event-related potentials method matched in nine of ten patients (sensitivity = 94%, specificity = 100%), and the SVM had 100% sensitivity and specificity when compared with the standard method. For the 49 ICU patients, we performed both the univariate and the SVM methods: a bilateral absence of short latency responses (n = 8) predicted poor neurological outcome with 0% FPR (sensitivity = 21%, specificity = 100%). Somatosensory evoked potentials can reliably be recorded using the proposed approach. Given the very good but slightly lower sensitivity of absent SSEPs in the proposed screening approach, confirmation of absent SSEP responses using standard SSEP recordings is advised.

Effect of high-frequency repetitive transcranial magnetic stimulation over M1 for consciousness recovery after traumatic brain injury.

The brain area stimulated during repetitive transcranial magnetic stimulation (rTMS) treatment is important in altered states of consciousness. However, the functional contribution of the M1 region during the treatment of high-frequency rTMS remains unclear. The aim of this study was to examine the clinical [the Glasgow coma scale (GCS) and the coma recovery scale-revised (CRS-R)] and neurophysiological (EEG reactivity and SSEP) responses in vegetative state (VS) patients following traumatic brain injury (TBI) before and after a protocol of high-frequency rTMS over the M1 region. Ninety-nine patients in a VS following TBI were recruited so that their clinical and neurophysiological responses could be evaluated in this study. These patients were randomly allocated into three experimental groups: rTMS over the M1 region (test group; n=33), rTMS over the left dorsolateral prefrontal cortex (DLPFC) (control group; n=33) and placebo rTMS over the M1 region (placebo group; n=33). Each rTMS treatment lasted 20 min and was carried out once a day. The duration of this protocol was a month with 20 treatments (5 times per week) occurring with that time. We found that the clinical and neurophysiological responses improved after treatment in the test, control, and placebo groups; the improvement was highest in the test group compared to that in the control and placebo groups. Our results demonstrate an effective method of high-frequency rTMS over the M1 region for consciousness recovery after severe brain injury.

Effects of high-frequency repetitive transcranial magnetic stimulation on the nutritional status of patients in a persistent vegetative state: A pilot study.

This paper presents a preliminary study on whether repetitive transcranial magnetic stimulation (rTMS) can modulate the nutritional status of persistent vegetative state (PVS) patients (the primary endpoint) by regulating the intestinal flora and the metabolites, with the correlation between them also investigated. Seventy-six patients with PVS were selected and divided into the observation group (n = 38) and the control group (n = 38) by random numerical grouping. All subjects' stool samples were examined for metabolites and analyzed regarding the short-chain fatty acids (SCFAs) content. All subjects' serum albumin, prealbumin, and hemoglobin levels were measured before and after the treatment. Nutrition risk screening 2002 was performed on all the subjects before and after the treatment and on the 30th and 90th days of the follow-up. (1) Intestinal flora structure: the Chao index, Ace index, and Shannon index of the observation group and the control group were significantly higher (p < 0.05), while the Simpson index was significantly lower (p < 0.05) following the treatment. (2) Metabolites of the intestinal flora: the observation group had significantly higher levels of acetic acid, butyric acid, and valeric acid (p < 0.05), as well as lower levels of propionic acid (p < 0.05) following the treatment. (3) Nutritional status (the primary endpoint): following the treatment, the above serum nutritional indices were significantly higher in both groups (p < 0.05), while the indices of the observation group were significantly higher than those of the control group (p < 0.05). The rTMS method may improve the nutritional status of patients with PVS by regulating the structure of the intestinal flora and affecting the level of SCFAs through the microbiota-gut-brain axis. The possible mechanism involves how high-frequency rTMS can cause increased excitation in the frontal lobe of the right side of the brain, thus regulating the 5-hydroxytryptamine and norepinephrine levels.

Heart rate variability for the evaluation of patients with disorders of consciousness

ObjectiveClinical responsiveness of patients with a Disorder of Consciousness (DoC) correlates to sympathetic/parasympathetic homeostatic balance. Heart Rate Variability (HRV) metrics result in non-invasive proxies of modulation capabilities of visceral states. In this work, our aim was to evaluate whether HRV measures could improve the differential diagnosis between Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS) with respect to multivariate models based on standard clinical electroencephalography (EEG) labeling only in a rehabilitation setting. MethodsA prospective observational study was performed consecutively enrolling 82 DoC patients. Polygraphic recordings were performed. HRV-metrics and EEG descriptors derived from the American Clinical Neurophysiology Society's Standardized Critical Care terminology were included. Descriptors entered univariate and then multivariate logistic regressions with the target set to the UWS/MCS diagnosis. ResultsHRV measures resulted significantly different between UWS and MCS patients, with higher values being associated with better consciousness levels. Specifically, adding HRV-related metrics to ACNS EEG descriptors increased the Nagelkerke R2 from 0.350 (only EEG descriptors) to 0.565 (HRV-EEG combination) with the outcome set to the consciousness diagnosis. ConclusionsHRV changes across the lowest states of consciousness. Rapid changes in heart rate, occurring in better consciousness levels, confirm the mutual correlation between visceral state functioning patterns and consciousness alterations. SignificanceQuantitative analysis of heart rate in patients with a DoC paves the way for the implementation of low-cost pipelines supporting medical decisions within multimodal consciousness assessments.

Correction of Local Brain Temperature after Severe Brain Injury Using Hypothermia and Medical Microwave Radiometry (MWR) as Companion Diagnostics

The temperature of the brain can reflect the activity of its different regions, allowing us to evaluate the connections between them. A study involving 111 patients in a vegetative state or minimally conscious state used microwave radiometry to measure their cortical temperature. The patients were divided into a main group receiving a 10-day selective craniocerebral hypothermia (SCCH) procedure, and a control group receiving basic therapy and rehabilitation. The main group showed a significant improvement in consciousness level as measured by CRS-R assessment on day 14 compared to the control group. Temperature heterogeneity increased in patients who received SCCH, while remaining stable in the control group. The use of microwave radiometry to assess rehabilitation effectiveness and the inclusion of SCCH in rehabilitation programs appears to be a promising approach.

Clinical effect of short-term spinal cord stimulation in the treatment of patients with primary brainstem hemorrhage-induced disorders of consciousness.

Recently, short-term spinal cord stimulation (st-SCS) has been used in neurorehabilitation and consciousness recovery. However, little is known about its effects on primary brainstem hemorrhage (PBSH)-induced disorders of consciousness (DOC). In this study, we examined the therapeutic effects of st-SCS in patients with PBSH-induced DOC. Fourteen patients received a 2-week st-SCS therapy. Each patient's state of consciousness was evaluated using the Coma Recovery Scale-Revised (CRS-R). CRS-R evaluation scores were recorded at the baseline (before SCS implantation) and 14 days later. Over 70% (10/14) of the patients (CRS-R score increased to ≥2 points) responded to the SCS stimulation after 14 days of st-SCS treatment. All items included in the CRS-R exhibited a significant increase post-treatment compared with pretreatment. After 2 weeks of st-SCS treatment, seven patients showed diagnostic improvement, resulting in a 50% (7/14) overall effective rate. Approximately 75% (3/4) of patients with minimally conscious state plus (MCS+) improved to emergence from MCS (eMCS), and 50% (1/2) of patients with vegetative state or unresponsive wakefulness syndrome (VS/UWS) improved to MCS+. In PBSH-induced DOC, st-SCS is a safe and effective treatment. The clinical behavior of the patients improved significantly following the st-SCS intervention, and their CRS-R scores markedly increased. This was most effective for MCS+.

Muscular-tonic disorders in a vegetative and a minimal consciousness states

Muscular-tonic disorders (MTD) in prolonged disorders of consciousness (PDoC), including a vegetative state (VS) and a minimal consciousness state (MCS), are poorly understood.Aim. To systematize MTD in PDoC, to highlight the features of their dynamics depending on the change in consciousness.Material and methods. 87 patients in PDoC (VS — 52, MCS — 35) resulting from brain damage of diff erent etiology, lasting from 2 months up to 10 years. MTD, provoking hyperkinesis factors and consciousness were analyzed retrospectively in the dynamics and complex.Results. MTD had 98% of patients in PDoC. The ratio of occurrence of spasticity: hyperkinesis: postural spasms corresponded to 11:11:10, and hyperkinesis — dystonia: myoclonus/myokymia: athetosis: stereotypes: ballism: choreiform hyperkinesis: tremor — 17:10:6:3:2:1:1. Their clinical variants and features are noted. The total dynamics of MTD on improved consciousness was as follows. In general, regardless of the initial VS or MCS, their “change” (especially decrease) prevailed over “no changes” (p &lt; 0.001). Comparatively more often the decrease occurred in MCS “plus” (p &lt; 0.05); appearance/increase/modifi cation — in VS (p &lt; 0.05); “no changes” — in MCS “minus” (p &lt; 0.01). When considered separately, spasticity, dystonia, spasms, hemiballismus and stereotypy in MCS “plus” correlated (p &lt; 0.01) with the change of consciousness. The key provoking hyperkinesis factors in VS were pain and other sensory infl uences (p &lt; 0.01), but their role from MCS “minus” to MCS “plus” decreased, while the role both conscious emotions and movements increased (p &lt; 0.01).Conclusion. Along with academic interest, the data are promising in developing the prognosis, pathogenesis and treatment of PDoC.

A Retrospective Study of Puncture and Drainage for Primary Brainstem Hemorrhage With the Assistance of a Surgical Robot.

Whether primary brainstem hemorrhage (PBH) should be treated with a conservative treatment or with surgical intervention (such as craniotomy, puncture, and drainage) is still controversial. The aim of this study was to assess the feasibility and safety of puncture and drainage for PBH with the assistance of a surgical robot. A total of 53 patients diagnosed with PBH were included in this study. They were divided into surgical and nonsurgical groups. All patients in the surgical group underwent puncture and drainage of PBH assisted with surgical robots at Beijing Jingmei General Hospital from June 2017 to January 2021. We evaluated this technology with radiographic and clinical results. Postoperative computed tomography showed that all the drainage catheters had been pushed to the target point, which had been designated before the operation. After the operation, the hematoma was reduced by an average of 3.7 mL. None of the patients experienced serious surgery-related complications. Clinical follow-up revealed that 2 patients could not be followed-up, 8 died, and the rest were in disability or in a vegetative state. It may be safe, feasible, and effective to complete the puncture and drainage of PBH with the assistance of a surgical robot. This technique has fewer complications than the traditional puncture method and has high accuracy. It may be more suitable for patients with a hematoma volume of 5 to 10 mL in PBH. The amount of hematoma volume >10 mL may be associated with poor postoperative prognosis. However, high-quality cohorts or case-control studies are needed to verify the effect in this study.

Abstract P412: The Effect of Targeted Therapeutic Management in ST-Elevation Myocardial Infarction Cardiac Arrest

Introduction: ST-elevation myocardial infarction (STEMI) is a known cause of cardiac arrest (CA). Little is known about the impact of targeted therapeutic management in CA patients with STEMI (SCA). Our aim was to investigate the effect of TTM on SCA. Methods: This was a retrospective cohort study using the 2019 Nationwide Inpatient Sample database to identify admissions in adults with diagnoses of CA and STEMI. Regression models were adjusted for demographic variables. Primary outcome was mortality, and secondary outcomes were length of stay (LOS) and total charge in USD. Results: Out of 13895 admissions with SCA, 440 underwent TTM. Compared to Non-TTM-SCA cohort, TTM-SCA cohort had fewer females (18.18% vs 31.03,p&lt;0.05), more males (81.82% vs 68.97,p&lt;0.05), lower mean age (62.17 vs 64.57,p&lt;0.05), more Native American (2.27% vs 0.63%,p&lt;0.05), less South region hospitals (25.00% vs 39.95%,p&lt;0.05), less acute respiratory failure with hypercapnia (0.47% vs 8.53%,p&lt;0.05), acute respiratory failure with hypoxia (1.94% vs 38.90%,p&lt;0.001), history of cardiac arrest (0.11% vs 0.61%,p&lt;0.01), ventricular fibrillation (2.27% vs 50.59%,p&lt;0.001), cerebral infarction (0.29% vs 4.28%,p&lt;0.05), more alcohol abuse (12.50% vs 4.72%,p&lt;0.001), and more persistent vegetative state (1.14% vs 0.15%,p&lt;0.05). Compared to Non-TTM-SCA, TTM-SCA group had similar mortality rates (38.64% vs 42.96%,p=0.3940), mortality OR 1.04 (95%CI 0.66-1.62,p=0.869), higher mean LOS 10.69 vs 6.25 days (95%CI 2.39-6.17,p&lt;0.001), and higher mean total hospitalization charge $238960.90 vs $179880.10 (95%CI 18772.87-98404.78,p&lt;0.01). Conclusion: In SCA patients, TTM presence had no difference in mortality rate, odds of mortality, but had higher mean LOS and total hospitalization charge. TTM was associated with fewer females, more males, lower mean age, more Native Americans, less acute respiratory failure, history of cardiac arrest, ventricular fibrillation, cerebral infarction, and more alcohol abuse and persistent vegetative state.

Czy można uśmiercić pacjenta z powodu niskiej jakości życia? Uwagi na tle orzecznictwa Europejskiego Trybunału Praw Człowieka

The subject of the article is the issue of legal protection of the life of patients in a state of minimal consciousness, in a vegetative state or other form of serious health condition. The analyses the problem from the point of view of three high-profile court cases involving the termination of treatment of Vincent Lambert, Charlie Gard and Alfie Evans.

EEG lexicality effect predicts clinical outcome in disorders of consciousness.

This study aimed at probing covert language processing in patients with disorders of consciousness. An auditory paradigm contrasting words to pronounceable pseudowords was designed, while recording bedside electroencephalogram and computing the two main correlates of lexicality: N400 and late positive component (LPC). Healthy volunteers and 19 patients, 10 in a minimally conscious state and 9 in a vegetative state (also coined unresponsive wakefulness syndrome), were recorded. N400 was present in all groups, whereas LPC was only present in the healthy volunteers and minimally conscious state groups. At the individual level, an unprecedented detection rate of N400 and LPC was reached, and LPC predicted overt cognitive improvement at 6 months. ANN NEUROL 2023;93:762-767.

Cerebrospinal Fluid and Blood Biomarkers in Patients with Post-Traumatic Disorders of Consciousness: A Scoping Review.

(1) Background: Cerebrospinal fluid (CSF) and blood biomarkers are emerging tools used to obtain information on secondary brain damage and to improve diagnostic and prognostic accuracy for patients with prolonged post-traumatic disorders of consciousness (DoC). We synthesized available data from studies evaluating CSF and blood biomarkers in these patients. (2) Methods: A scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist to identify and synthesize data from relevant studies. Studies were identified by PubMed and manual searches. Those involving patients with unresponsive wakefulness syndrome or in a minimally conscious state for >28 days, evaluating CSF or blood biomarkers, and conducted on patients with traumatic brain injuries older than 16 years were included in the review. (3) Results: In total, 17 studies were included. Findings on neurofilament light chain, proteins, metabolites, lipids, amyloid-β, tau, melatonin, thyroid hormones, microtubule-associated protein 2, neuron-specific enolase, and brain-derived neurotrophic factor were included in the qualitative synthesis. (4) Conclusions: The most promising applications for CSF and blood biomarkers are the monitoring of secondary neurodegeneration, support of DoC diagnoses, and refinement of prognoses, although current evidence remains too scarce to recommend such uses of these biomarkers in clinical practice.

Repetitive transcranial magnetic stimulation over the posterior parietal cortex improves functional recovery in nonresponsive patients: A crossover, randomized, double-blind, sham-controlled study.

Recent studies have shown that patients with disorders of consciousness (DoC) can benefit from repetitive transcranial magnetic stimulation (rTMS) therapy. The posterior parietal cortex (PPC) is becoming increasingly important in neuroscience research and clinical treatment for DoC as it plays a crucial role in the formation of human consciousness. However, the effect of rTMS on the PPC in improving consciousness recovery remains to be studied. We conducted a crossover, randomized, double-blind, sham-controlled clinical study to assess the efficacy and safety of 10 Hz rTMS over the left PPC in unresponsive patients. Twenty patients with unresponsive wakefulness syndrome were recruited. The participants were randomly divided into two groups: one group received active rTMS treatment for 10 consecutive days (n = 10) and the other group received sham treatment for the same period (n = 10). After a 10-day washout period, the groups crossed over and received the opposite treatment. The rTMS protocol involved the delivery of 2000 pulses/day at a frequency of 10 Hz, targeting the left PPC (P3 electrode sites) at 90% of the resting motor threshold. The primary outcome measure was the JFK Coma Recovery Scele-Revised (CRS-R), and evaluations were conducted blindly. EEG power spectrum assessments were also conducted simultaneously before and after each stage of the intervention. rTMS-active treatment resulted in a significant improvement in the CRS-R total score (F = 8.443, p = 0.009) and the relative alpha power (F = 11.166, p = 0.004) compared to sham treatment. Furthermore, 8 out of 20 patients classified as rTMS responders showed improvement and evolved to a minimally conscious state (MCS) as a result of active rTMS. The relative alpha power also significantly improved in responders (F = 26.372, p = 0.002) but not in non-responders (F = 0.704, p = 0.421). No adverse effects related to rTMS were reported in the study. This study suggests that 10 Hz rTMS over the left PPC can significantly improve functional recovery in unresponsive patients with DoC, with no reported side effects. www.ClinicalTrials.gov, identifier: NCT05187000.

Decompressive Craniectomy in Pediatric Traumatic Brain Injury: A Retrospective Cohort Study

AbstractDecompressive craniectomy (DC) in children with traumatic brain injury (TBI) and refractory raised intracranial pressure (ICP) remains controversial. We aimed to describe the clinical and operative characteristics of children with moderate to severe TBI who underwent DC, and compare outcomes with those who had medical therapy. We performed a retrospective observational cohort study on children &lt; 16 years of age with moderate to severe TBI (Glasgow coma scale [GCS] ≤13) who underwent DC in two pediatric centers in Singapore and China between 2014 and 2017, and compared their outcomes with children who underwent medical treatment, among participating centers of the Pediatric Acute and Critical Care Medicine Asian Network. We defined poor functional outcomes as moderate, severe disability, vegetative or comatose state, or mortality, using the Pediatric Cerebral Performance Category scale. We performed multivariable logistic regression to identify predictors for poor functional outcomes. We analyzed 18 children who underwent DC with 214 who had medical therapy. A greater proportion of children with DC (14, 77.8%) experienced poor functional outcomes, compared with those with medical therapy (87, 41.2%, p = 0.003). Children who underwent DC had fewer median 14-day intensive care unit (ICU)-free days (2.5 days, interquartile range [IQR]: 0.0–5.8 vs. 8.0 days, IQR: 0.0–11.0, p = 0.033), median 28-day hospital-free days (0 day, IQR: 0.0–3.5 vs. 11.0 days, IQR: 0.0–21.0, p = 0.002) and 14-day mechanical ventilation-free days (6.5 days, IQR: 0.0–12.3 vs. 11.0 days, IQR: 3.0–14.0, p = 0.011). After accounting for age, sex, GCS, cerebral edema, uncal herniation, nonaccidental injury, and need for intubation, there was no significant association between DC and poor functional outcomes (adjusted odds ratio: 1.59, 95% confidence interval: 0.35–7.24, p = 0.548). Children with DC had severe injuries, and prolonged hospital and ICU stays. Future studies are needed to understand the effectiveness of DC on children with TBI.

Physicians' attitudes towards ethical issues and end-of-life decision-making for pediatric patients with unresponsive wakefulness syndrome: An international survey.

We examined physicians' perspectives on the mental capabilities of pediatric patients with unresponsive wakefulness syndrome (UWS) and their attitudes towards limiting life-sustaining treatment (LST) in an international context. A questionnaire survey was conducted among 267 neuropediatricians, practicing in 65 countries. Comparisons were made according to the Human Development Index (HDI) of the countries. The Idler Index of Religiosity was applied to determine religiosity. Participants from countries with a very high HDI were generally more favorable to limiting LST (p < 0.001), specifically cardiopulmonary resuscitation (p=0.021), intubation/ventilation (p=0.014), hemodialysis/hemofiltration (p < 0.001), and antibiotic therapy (p < 0.001). Treatment costs that were too high had a weaker influence on their decisions (p < 0.001). Participants who found it never ethically justifiable to limit LST had a higher mean Idler Index of private (p=0.001) and general (p=0.020) religiosity and were less satisfied with treatment decisions (p < 0.001) and the communication during the process (p=0.016). The perspectives towards limiting LST for pediatric patients with UWS are markedly different between physicians from countries with very high and lower HDIs.

Overcoming Conflicting Definitions of “Euthanasia,” and of “Assisted Suicide,” Through a Value-Neutral Taxonomy of “End-Of-Life Practices”

The term “euthanasia” is used in conflicting ways in the bioethical literature, as is the term “assisted suicide,” resulting in definitional confusion, ambiguities, and biases which are counterproductive to ethical and legal discourse. I aim to rectify this problem in two parts. Firstly, I explore a range of conflicting definitions and identify six disputed definitional factors, based on distinctions between (1) killing versus letting die, (2) fully intended versus partially intended versus merely foreseen deaths, (3) voluntary versus nonvoluntary versus involuntary decisions, (4) terminally ill versus non-terminally ill patients, (5) patients who are fully conscious versus those in permanent comas or persistent vegetative states, and (6) patients who are suffering versus those who are not. Secondly, I distil these factors into six “building blocks” and combine them to develop an unambiguous, value-neutral taxonomy of “end-of-life practices.” I hope that this taxonomy provides much-needed clarification and a solid foundation for future ethical and legal discourse.

Abstract WP121: Can The Extended Glasgow Outcome Scale (e-gos) Augment The Interpretation Of Results From Clinical Trials Of Minimally Invasive Surgery Of Spontaneous Intracerebral Hemorrhage Using The Modified Rankin Scale (mrs): A Secondary Analysis Of The Clear-iii And Mistie-iii Trials

Introduction: Currently, the modified Rankin scale (mRS) is most commonly used to assess functional outcome in clinical trials of interventions for spontaneous intracerebral hemorrhage (ICH). Extended Glasgow Outcome Score (eGOS) is often used to assess global disability/recovery after traumatic brain injury and provides additional discrimination of vegetative state (VS) from lower severe disability (LSD). We compared primary outcomes from 2 clinical trials of minimally invasive surgery for intracerebral and intraventricular hemorrhage (ICH/IVH) at different thresholds of eGOS. Methods: Post-hoc analysis of primary outcomes (PO) from the CLEAR-III trial (intraventricular alteplase [IVtPA] vs. saline for obstructive IVH; N=500; PO: mRS 0-3 at day 180), and MISTIE-III trial (stereotactic thrombolysis [MIS+tPA] vs. conservative management; N=499; PO: mRS 0-3 at day 365). eGOS was derived from functional outcome scales obtained during the trials. Outcomes on eGOS were categorized into 5 subgroups: good outcomes: 7-8 (A), 5-6 (B), 4 (C), and poor outcomes: 3 (D), and 1-2 (E). Generalized, ordered logistic regression analysis was performed, adjusting for age, ICH location, stability ICH and IVH volumes, and randomization GCS. Results: eGOS scales were available in 481 (96%) patients at day 180 in CLEAR-III and 478 (96%) patients at day 365 in MISTIE-III. In CLEAR-III, odds of being in eGOS category D (LSD) or E (death or VS) vs. the others, were approximately 40% lower for IVtPA group compared to saline group (aOR = 0.59; 95% CI, 0.38-0.90; p=0.016), and odds of being in category E (vs. the others) were almost 50% lower (aOR = 0.51; 95% CI, 0.33-0.80; p=0.004). VS occurred in 2.49% of IVtPA and 2.07% of saline group patients. In MISTIE-III, odds of being in eGOS category D or E (vs. the others) were not significantly different for MIS+tPA vs. conservative treatment: aOR = 0.84; 95% CI, 0.55-1.28; p=0.41), as were odds for being in eGOS category E (vs. the others), aOR = 0.77; 95% CI, 0.48-1.24; p=0.29). Conclusions: The 5-category dichotomized eGOS (4-8 vs. 1-3) defines a functional outcome improvement in CLEAR-III at day 180, which was not observed using the PO with mRS. Use of eGOS did not result in a different interpretation of the MISTIE-III trial.

Data-driven approximation for extracting the transition dynamics of a genetic regulatory network with non-Gaussian Lévy noise

In the study of biological systems, several methods based on statistical physics or machine learning have been developed for inference or prediction in the presence of complicated nonlinear interactions and random noise perturbations. However, there have been few studies dealing with the stochastic non-Gaussian perturbation case, which is more natural and universal than Gaussian white noise. In this manuscript, for a two-dimensional biological model (the MeKS network) perturbed by non-Gaussian stable Lévy noise, we use a data-driven approach with theoretical probabilistic foundation to extract the rare transition dynamics representing gene expression. This involves theories of non-local Kramers–Moyal formulas and the non-local Fokker–Planck equation, as well as the corresponding numerical algorithms, aimed at extracting the maximum likelihood transition path. The feasibility and accuracy of the method are checked. Furthermore, several dynamical behaviors and indicators are investigated. In detail, the investigation shows a bistable transition probability state of the ComK protein concentration and bifurcations in the learned transition paths from vegetative state to competence state. Analysis of the tipping time illustrates the difficulty of the gene expression. This method will serve as an example in the study of stochastic systems with non-Gaussian perturbations from biological data, and provides some insights into the extraction of other dynamical indicators, such as the mean first exit time and the first escape probability with respect to their own biological interpretations.

Phylogenetic relationships and systematics of the bamboo‐specialist Amaurospiza blue seedeaters

The Amaurospiza ‘seedeaters’ are bamboo‐specialized mixed strategists, most often found in bamboos in vegetative state, feeding on buds, shoots, petioles and insects. As bamboos die after flowering, birds may wander in search of live vegetative bamboo. The three currently recognized species of Amaurospiza are allopatrically distributed: the Blackish‐blue Seedeater Amaurospiza moesta in the Atlantic Forest of Argentina, Brazil and Paraguay, and in forest enclaves in the Cerrado; the recently described Carrizal Seedeater Amaurospiza carrizalensis known from a few localities in southeastern Venezuela; and the Blue Seedeater Amaurospiza concolor distributed patchily from Mexico to Peru. Three subspecies are recognized within A. concolor: relicta in southwest Mexico, concolor from southern Mexico to Panama and aequatorialis from southwest Colombia to northwest Peru. Full species status has been advocated for relicta and aequatorialis but evidence supporting their recognition is weak, while relicta was described in the monospecific genus Amaurospizopsis. Here we (1) test the monophyly of Amaurospiza, (2) reconstruct the phylogenetic relationships of all its constituent taxa using mitochondrial and nuclear markers, (3) re‐assess species limits in Amaurospiza with the aid of vocalizations and genetic and plumage data, and (4) discuss the link between bamboo life history, biogeographical patterns and extent of genetic differentiation. Amaurospiza was found to be monophyletic in both the ND2 and multilocus analyses. In the ND2 tree A. moesta and A. carrizalensis were sister to each other, A. concolor was found to be paraphyletic because aequatorialis was placed as sister to moesta–carrizalensis, and a clade including nominate concolor and relicta was sister to all the other taxa. The multilocus tree showed the same relationships, but lacked nuclear samples of relicta. Mean ND2 pairwise distance between concolor and aequatorialis (8.3%) was greater than that between moesta and carrizalensis (5.7%), while relicta diverged on average 1.0% from nominate concolor. The South American clade has more slender bills and white underwing coverts, while the Central American clade has thicker bills and bluish underwing coverts. All taxa exhibited typical Amaurospiza songs with quickly delivered, warbled, pure and fairly high‐pitched musical notes. Number of inflections/second exhibited a stepped pattern, with concolor and relicta on the lower end and carrizalensis, aequatorialis and moesta on the upper end. Similarly, moesta, carrizalensis and aequatorialis had overall more inflections per note than concolor and relicta. Linear discriminant analysis using nine acoustic variables correctly assigned all 62 songs to the correct taxon. Morphology, plumage, vocalizations and phylogenetic data indicate that aequatorialis should be afforded full species status as the Ecuadorian Seedeater (A. aequatorialis), suggest keeping relicta as a subspecies of A. concolor and support continued recognition of A. carrizalensis. Our data support merging Amaurospizopsis into Amaurospiza.

Characterization of a sex-determining locus and development of early molecular assays in Telfairia occidentalisHook. F., a dioecious cucurbit

Although there exist over 7000 crop species, only a few are commercially valuable and grown on a large scale in monocultures worldwide. However, underutilised crops (also called orphan crops) have significant potential for food security and Telfairia occidentalis Hook. F. (Cucurbitaceae) is one such orphan crop grown in West Africa for its nutritious leaves, oil and protein-rich seeds. In this dioecious crop, farmers like to eliminate male plants and keep mostly females to increase their yield. However, they face the challenge of determining sex due to limited morphological differences between females and males before flowering. This study used double digested restriction site-associated DNA sequencing data (ddRADseq) to examine the genetic diversity within and among landraces of T. occidentalis, identify common sex-determining loci, and establish reliable assays to characterize the sex of immature plants in the vegetative state. To differentiate males from females of T. occidentalis, two molecular assays were thereupon developed based on polymerase chain reaction (PCR) to genotype sex-specific sequence variation either through restriction by Mfe1 or the direct use of sex-specific primers. Both assays require standard laboratory conditions to reach a certainty of 94.3% for females and 95.7% for males from the studied samples. With the inclusion of additional landraces, medium to largescale farms growing T. occidentalis as a crop can readily benefit from an early determination of the sex of plants.