Behavioral Recovery and Early Decision Making in Patients with Prolonged Disturbance in Consciousness after Traumatic Brain Injury

The extent of behavioral recovery that occurs in patients with traumatic disorders of consciousness (DoC) following discharge from the acute care setting has been under-studied and increases the risk of overly pessimistic outcome prediction. The aim of this observational cohort study was to systematically track behavioral and functional recovery in patients with prolonged traumatic DoC following discharge from the acute care setting. Standardized behavioral data were acquired from 95 patients in a minimally conscious (MCS) or vegetative state (VS) recruited from 11 clinic sites and randomly assigned to the placebo arm of a previously completed prospective clinical trial. Patients were followed for 6 weeks by blinded observers to determine frequency of recovery of six target behaviors associated with functional status. The Coma Recovery Scale-Revised and Disability Rating Scale were used to track reemergence of target behaviors and assess degree of functional disability, respectively. Twenty percent (95% confidence interval [CI]: 13-30%) of participants (mean age 37.2; median 47 days post-injury; 69 men) recovered all six target behaviors within the 6 week observation period. The odds of recovering a specific target behavior were 3.2 (95% CI: 1.2-8.1) to 7.8 (95% CI: 2.7-23.0) times higher for patients in MCS than for those in VS. Patients with preserved language function ("MCS+") recovered the most behaviors (p ≤ 0.002) and had the least disability (p ≤ 0.002) at follow-up. These findings suggest that recovery of high-level behaviors underpinning functional independence is common in patients with prolonged traumatic DoC. Clinicians involved in early prognostic counseling should recognize that failure to emerge from traumatic DoC before 28 days does not necessarily portend unfavorable outcome

SBV Regularity for Genuinely Nonlinear, Strictly Hyperbolic Systems of Conservation Laws in one space dimension

We prove that if $t \mapsto u(t) \in \mathrm {BV}(\R)$ is the entropy solution to a $N \times N$ strictly hyperbolic system of conservation laws with genuinely nonlinear characteristic fields $$u_t + f(u)_x = 0,$$ then up to a countable set of times $\{t_n\}_{n \in \mathbb N}$ the function $u(t)$ is in $\mathrm {SBV}$, i.e. its distributional derivative $u_x$ is a measure with no Cantorian part. The proof is based on the decomposition of $u_x(t)$ into waves belonging to the characteristic families $$u(t) = \sum_{i=1}^N v_i(t) \tilde r_i(t), \quad v_i(t) \in \mathcal M(\R), \ \tilde r_i(t) \in \mathrm R^N,$$ and the balance of the continuous/jump part of the measures $v_i$ in regions bounded by characteristics. To this aim, a new interaction measure \mu_{i,\jump} is introduced, controlling the creation of atoms in the measure $v_i(t)$. The main argument of the proof is that for all $t$ where the Cantorian part of $v_i$ is not 0, either the Glimm functional has a downward jump, or there is a cancellation of waves or the measure $\mu_{i,\mathrm{jump}}$ is positive

Low temperature and cost-effective growth of vertically aligned carbon nanofibers using spin-coated polymer-stabilized palladium nanocatalysts

We describe a fast and cost-effective process for the growth of carbon nanofibers (CNFs) at a temperature compatible with complementary metal oxide semiconductor technology, using highly stable polymer-Pd nanohybrid colloidal solutions of palladium catalyst nanoparticles (NPs). Two polymer-Pd nanohybrids, namely poly(lauryl methacrylate)-block-poly((2-acetoacetoxy) ethyl methacrylate)/Pd (LauMA(x)-b-AEMA(y)/Pd) and polyvinylpyrrolidone/Pd were prepared in organic solvents and spin-coated onto silicon substrates. Subsequently, vertically aligned CNFs were grown on these NPs by plasma enhanced chemical vapor deposition at different temperatures. The electrical properties of the grown CNFs were evaluated using an electrochemical method, commonly used for the characterization of supercapacitors. The results show that the polymer-Pd nanohybrid solutions offer the optimum size range of palladium catalyst NPs enabling the growth of CNFs at temperatures as low as 350 degrees C. Furthermore, the CNFs grown at such a low temperature are vertically aligned similar to the CNFs grown at 550 degrees C. Finally the capacitive behavior of these CNFs was similar to that of the CNFs grown at high temperature assuring the same electrical properties thus enabling their usage in different applications such as on-chip capacitors, interconnects, thermal heat sink and energy storage solutions

Clinical and cost-effectiveness of contingency management for cannabis use in early psychosis: the CIRCLE randomised clinical trial

Cannabis is the most commonly used illicit substance amongst people with psychosis. Continued cannabis use following the onset of psychosis is associated with poorer functional and clinical outcomes. However, finding effective ways of intervening has been very challenging. We examined the clinical and cost-effectiveness of adjunctive contingency management (CM), which involves incentives for abstinence from cannabis use, in people with a recent diagnosis of psychosis. CIRCLE was a pragmatic multi-centre randomised controlled trial. Participants were recruited via Early Intervention in Psychosis (EIP) services across the Midlands and South East of England. They had had at least one episode of clinically diagnosed psychosis (affective or non-affective); were aged 18 to 36; reported cannabis use in at least 12 out of the previous 24 weeks; and were not currently receiving treatment for cannabis misuse, or subject to a legal requirement for cannabis testing. Participants were randomised via a secure web-based service 1:1 to either an experimental arm, involving 12 weeks of CM plus a six-session psychoeducation package, or a control arm receiving the psychoeducation package only. The total potential voucher reward in the CM intervention was £240. The primary outcome was time to acute psychiatric care, operationalised as admission to an acute mental health service (including community alternatives to admission). Primary outcome data were collected from patient records at 18 months post-consent by assessors masked to allocation. The trial was registered with the ISRCTN registry, number ISRCTN33576045. Five hundred fifty-one participants were recruited between June 2012 and April 2016. Primary outcome data were obtained for 272 (98%) in the CM (experimental) group and 259 (95%) in the control group. There was no statistically significant difference in time to acute psychiatric care (the primary outcome) (HR 1.03, 95% CI 0.76, 1.40) between groups. By 18 months, 90 (33%) of participants in the CM group, and 85 (30%) of the control groups had been admitted at least once to an acute psychiatric service. Amongst those who had experienced an acute psychiatric admission, the median time to admission was 196 days (IQR 82, 364) in the CM group and 245 days (IQR 99, 382) in the control group. Cost-effectiveness analyses suggest that there is an 81% likelihood that the intervention was cost-effective, mainly resulting from higher mean inpatient costs for the control group compared with the CM group; however, the cost difference between groups was not statistically significant. There were 58 adverse events, 27 in the CM group and 31 in the control group. Overall, these results suggest that CM is not an effective intervention for improving the time to acute psychiatric admission or reducing cannabis use in psychosis, at least at the level of voucher reward offered

Implantation of Mouse Embryonic Stem Cell-Derived Cardiac Progenitor Cells Preserves Function of Infarcted Murine Hearts

Stem cell transplantation holds great promise for the treatment of myocardial infarction injury. We recently described the embryonic stem cell-derived cardiac progenitor cells (CPCs) capable of differentiating into cardiomyocytes, vascular endothelium, and smooth muscle. In this study, we hypothesized that transplanted CPCs will preserve function of the infarcted heart by participating in both muscle replacement and neovascularization. Differentiated CPCs formed functional electromechanical junctions with cardiomyocytes in vitro and conducted action potentials over cm-scale distances. When transplanted into infarcted mouse hearts, CPCs engrafted long-term in the infarct zone and surrounding myocardium without causing teratomas or arrhythmias. The grafted cells differentiated into cross-striated cardiomyocytes forming gap junctions with the host cells, while also contributing to neovascularization. Serial echocardiography and pressure-volume catheterization demonstrated attenuated ventricular dilatation and preserved left ventricular fractional shortening, systolic and diastolic function. Our results demonstrate that CPCs can engraft, differentiate, and preserve the functional output of the infarcted heart

Inhibition of G-protein signalling in cardiac dysfunction of intellectual developmental disorder with cardiac arrhythmia (IDDCA) syndrome

BACKGROUND: Pathogenic variants of GNB5 encoding the β5 subunit of the guanine nucleotide-binding protein cause IDDCA syndrome, an autosomal recessive neurodevelopmental disorder associated with cognitive disability and cardiac arrhythmia, particularly severe bradycardia. METHODS: We used echocardiography and telemetric ECG recordings to investigate consequences of Gnb5 loss in mouse. RESULTS: We delineated a key role of Gnb5 in heart sinus conduction and showed that Gnb5-inhibitory signalling is essential for parasympathetic control of heart rate (HR) and maintenance of the sympathovagal balance. Gnb5-/- mice were smaller and had a smaller heart than Gnb5+/+ and Gnb5+/- , but exhibited better cardiac function. Lower autonomic nervous system modulation through diminished parasympathetic control and greater sympathetic regulation resulted in a higher baseline HR in Gnb5-/- mice. In contrast, Gnb5-/- mice exhibited profound bradycardia on treatment with carbachol, while sympathetic modulation of the cardiac stimulation was not altered. Concordantly, transcriptome study pinpointed altered expression of genes involved in cardiac muscle contractility in atria and ventricles of knocked-out mice. Homozygous Gnb5 loss resulted in significantly higher frequencies of sinus arrhythmias. Moreover, we described 13 affected individuals, increasing the IDDCA cohort to 44 patients. CONCLUSIONS: Our data demonstrate that loss of negative regulation of the inhibitory G-protein signalling causes HR perturbations in Gnb5-/- mice, an effect mainly driven by impaired parasympathetic activity. We anticipate that unravelling the mechanism of Gnb5 signalling in the autonomic control of the heart will pave the way for future drug screening

Crisis resolution teams for people experiencing mental health crises: the CORE mixed-methods research programme including two RCTs

Background Crisis resolution teams (CRTs) seek to avert hospital admissions by providing intensive home treatment for people experiencing a mental health crisis. The CRT model has not been highly specified. CRT care is often experienced as ending abruptly and relapse rates following CRT discharge are high. Aims The aims of CORE (Crisis resolution team Optimisation and RElapse prevention) workstream 1 were to specify a model of best practice for CRTs, develop a measure to assess adherence to this model and evaluate service improvement resources to help CRTs implement the model with high fidelity. The aim of CORE workstream 2 was to evaluate a peer-provided self-management programme aimed at reducing relapse following CRT support. Methods Workstream 1 was based on a systematic review, national CRT manager survey and stakeholder qualitative interviews to develop a CRT fidelity scale through a concept mapping process with stakeholders (n = 68). This was piloted in CRTs nationwide (n = 75). A CRT service improvement programme (SIP) was then developed and evaluated in a cluster randomised trial: 15 CRTs received the SIP over 1 year; 10 teams acted as controls. The primary outcome was service user satisfaction. Secondary outcomes included CRT model fidelity, catchment area inpatient admission rates and staff well-being. Workstream 2 was a peer-provided self-management programme that was developed through an iterative process of systematic literature reviewing, stakeholder consultation and preliminary testing. This intervention was evaluated in a randomised controlled trial: 221 participants recruited from CRTs received the intervention and 220 did not. The primary outcome was re-admission to acute care at 1 year of follow-up. Secondary outcomes included time to re-admission and number of days in acute care over 1 year of follow-up and symptoms and personal recovery measured at 4 and 18 months’ follow-up. Results Workstream 1 – a 39-item CRT fidelity scale demonstrated acceptability, face validity and promising inter-rater reliability. CRT implementation in England was highly variable. The SIP trial did not produce a positive result for patient satisfaction [median Client Satisfaction Questionnaire score of 28 in both groups at follow-up; coefficient 0.97, 95% confidence interval (CI) –1.02 to 2.97]. The programme achieved modest increases in model fidelity. Intervention teams achieved lower inpatient admission rates and less inpatient bed use. Qualitative evaluation suggested that the programme was generally well received. Workstream 2 – the trial yielded a statistically significant result for the primary outcome, in which rates of re-admission to acute care over 1 year of follow-up were lower in the intervention group than in the control group (odds ratio 0.66, 95% CI 0.43 to 0.99; p = 0.044). Time to re-admission was lower and satisfaction with care was greater in the intervention group at 4 months’ follow-up. There were no other significant differences between groups in the secondary outcomes. Limitations Limitations in workstream 1 included uncertainty regarding the representativeness of the sample for the primary outcome and lack of blinding for assessment. In workstream 2, the limitations included the complexity of the intervention, preventing clarity about which were effective elements. Conclusions The CRT SIP did not achieve all its aims but showed potential promise as a means to increase CRT model fidelity and reduce inpatient service use. The peer-provided self-management intervention is an effective means to reduce relapse rates for people leaving CRT care. Study registration The randomised controlled trials were registered as Current Controlled Trials ISRCTN47185233 and ISRCTN01027104. The systematic reviews were registered as PROSPERO CRD42013006415 and CRD42017043048. Funding The National Institute for Health Research Programme Grants for Applied Research programme

Residual stress in laser cladded rail

To improve the fatigue life of components subject to loads with high surface strain gradients, it is possible to coat them with an alloy of higher durability. The present study focuses on the effect of cladding high value track components, made of a standard rail steel UIC 900A/grade 260, with a layer of a premium martensitic stainless steel to reduce wear and fatigue. The laser cladding process inevitably generates residual stresses in the clad and parent metal, which could be detrimental to the integrity of the component. Therefore, measurements to determine the residual stress state of cladded rail were performed using semi-destructive centre-hole and deep hole drilling and non-destructive neutron diffraction techniques. Subsequently, the effects of cycling loading and wear, representative of typical service loads, on the redistribution of the residual stress field were investigated. It was observed that laser cladding causes a triaxial compressive residual stress field in the clad and near the interface and a tensile stress field in the parent material. The stress field is shown to change when the first cycle of load is applied but reaches a steady state after only 10 cycles: After the 10th cycle there is no evidence that the clad continues accumulating strain which could indicate that there is low risk of ratcheting. Wear effect on residual stress redistribution was found to be local on the surface of the specimen only