Heavy-duty trucks and new engine technology: impact on fuel consumption, emissions and trip cost

Road transport offers important logistic benefits at a reasonable cost for producers and consumers, hence its large market share. But, its use of diesel or gas generates large volumes of CO2, NOx and PM10 (among others). Higher emission standards and demand for greener transport call for alternatives. Literature analysis, a simulated Dutch-German road trip and a partial financial analysis are used to compare different engine-fuel combinations. Electricity from green sources removes these emissions. To stimulate full electric trucks (FET) several issues need to be addressed. First is creation of a large charging network. The Netherlands is much further with this than Germany. Affordability is another one. Operating and investment costs should at least equal those of non-FET to have comparable total cost of ownership (TCO) over the lifetime of a truck. With FET, investment costs are now much higher, which should be compensated by lower operating costs. The actual operating costs depend on many factors, but fuel costs and trip time are likely to rise if en-route recharging is needed. A more in-depth financial analysis is needed for more exact conclusions. Another issue is technical. Practice tests are needed to enhance the results of the simulation study. Hybrid diesel-electric and FET are already used in urban and regional transport. Regulation should also become tighter. Zero emission should become the norm. If these issues are successfully death with, then electric drive will become the mainstream technology. Technically, 2025 or 2030 seem feasible for large-scale production, which also lowers investment costs. With more electricity needed for transport, the supply of green electricity should grow strongly. Finally, the micro simulation is a modest example of the potential of the simulation model. Modeling of other corridors is underway, using one truck or a fleet of FET

Mode substitution induced by electric mobility hubs: Results from Amsterdam

\ua9 2024 The Author(s)Electric mobility hubs (eHUBS) are locations where multiple shared electric modes including electric cars and e-bikes are available. To assess their potential to reduce private car use, it is important to investigate to what extent people would switch to eHUBS modes after their introduction. Moreover, people may adapt their behaviour differently depending on their current travel mode. This study is based on stated preference data collected in Amsterdam. We analysed the data using mixed logit models. We found that users of different modes not only have varied general preferences for different shared modes but also have different sensitivity for attributes such as travel time and cost. Public transport users are more likely to switch to eHUBS modes than car users. People who bike and walk have strong inertia, but the percentage choosing eHUBS modes doubles when the trip distance is longer (5 or 10 km)

Eye movement desensitization and reprocessing (EMDR) for the treatment of psychosis: a systematic review

Background: Psychosis is a public health concern. There is increasing evidence suggesting trauma can play a pivotal role in the development and maintenance of psychosis. Eye Movement Desensitization and Reprocessing (EMDR) is an effective treatment for trauma and could be a vital addition to the treatment of psychosis. Objective: To explore the evidence for EMDR as a treatment for psychosis, focussing on the safety, effectiveness and acceptability of this intervention for this population. Methods: Four databases (Cochrane, EMBASE, MEDLINE PsychINFO), and the Francine Shapiro Library were systematically searched, along with grey literature and reference lists of relevant papers. No date limits were applied as this is an area of emerging evidence. Studies were screened for eligibility based on inclusion and exclusion criteria. The included studies were quality assessed and data was extracted from the individual studies, and synthesized using a narrative synthesis approach. Results: Six studies met the inclusion criteria (1 RCT, 2 Pilot studies, 2 Case series and 1 Case report). Across the studies EMDR was associated with reductions in delusional and negative symptoms, mental health service and medication use. Evidence for reductions in auditory hallucinations and paranoid thinking was mixed. No adverse events were reported, although initial increases in psychotic symptoms were observed in two studies. Average dropout rates across the studies were comparable to other trauma-focused treatments for PTSD. The acceptability of EMDR was not adequately measured or reported. Conclusion: EMDR appears a safe and feasible intervention for people with psychosis. The evidence is currently insufficient to determine the effectiveness and acceptability of the intervention for this population. Larger confirmative trials are required to form more robust conclusions

Health–economic Benefits of Treating Trauma in Psychosis

Background: Co-occurrence of posttraumatic stress disorder (PTSD) in psychosis (estimated as 12%) raises personal suffering and societal costs. Health–economic studies on PTSD treatments in patients with a diagnosis of a psychotic disorder have not yet been conducted, but are needed for guideline development and implementation. This study aims to analyse the cost-effectiveness of guideline PTSD therapies in patients with a psychotic disorder. Methods: This health–economic evaluation alongside a randomized controlled trial included 155 patients with a psychotic disorder in care as usual (CAU), with comorbid PTSD. Participants received eye movement desensitization and reprocessing (EMDR) (n = 55), prolonged exposure (PE) (n = 53) or waiting list (WL) (n = 47) with masked assessments at baseline (T0) and at the two-month (post-treatment, T2) and six-month follow-up (T6). Costs were calculated using the TiC-P interview for assessing healthcare consumption and productivity losses. Incremental cost-effectiveness ratios and economic acceptability were calculated for quality-adjusted life years (EQ-5D-3L-based QALYs) and PTSD ‘Loss of diagnosis’ (LoD, CAPS). Results: Compared to WL, costs were lower in EMDR (-€1410) and PE (-€501) per patient per six months. In addition, EMDR (robust SE 0.024, t = 2.14, p = .035) and PE (robust SE 0.024, t = 2.14, p = .035) yielded a 0.052 and 0.051 incremental QALY gain, respectively, as well as 26% greater probability for LoD following EMDR (robust SE = 0.096, z = 2.66, p = .008) and 22% following PE (robust SE 0.098, z = 2.28, p = .023). Acceptability curves indicate high probabilities of PTSD treatments being the better economic choice. Sensitivity analyses corroborated these outcomes. Conclusion: Adding PTSD treatment to CAU for individuals with psychosis and PTSD seem to yield better health and less PTSD at lower costs, which argues for implementation

A multi-site single blind clinical study to compare the effects of prolonged exposure, eye movement desensitization and reprocessing and waiting list on patients with a current diagnosis of psychosis and co morbid post traumatic stress disorder: study protocol for the randomized controlled trial Treating Trauma in Psychosis

Contains fulltext : 116518.pdf (publisher's version ) (Open Access)Background: Trauma contributes to psychosis and in psychotic disorders post-traumatic stress disorder (PTSD) is often a comorbid disorder. A problem is that PTSD is underdiagnosed and undertreated in people with psychotic disorders. This study's primary goal is to examine the efficacy and safety of prolonged exposure and eye movement desensitization and reprocessing (EMDR) for PTSD in patients with both psychotic disorders and PTSD, as compared to a waiting list. Secondly, the effects of both treatments are determined on (a) symptoms of psychosis, in particular verbal hallucinations, (b) depression and social performance, and (c) economic costs. Thirdly, goals concern links between trauma exposure and psychotic symptomatology and the prevalence of exposure to traumatic events, and of PTSD. Fourthly predictors, moderators, and mediators for treatment success will be explored. These include cognitions and experiences concerning treatment harm, credibility and burden in both participants and therapists. Methods/Design: A short PTSD-screener assesses the possible presence of PTSD in adult patients (21- to 65-years old) with psychotic disorders, while the Clinician Administered PTSD Scale interview will be used for the diagnosis of current PTSD. The M.I.N.I. Plus interview will be used for diagnosing lifetime psychotic disorders and mood disorders with psychotic features. The purpose is to include consenting participants (N = 240) in a multi-site single blind randomized clinical trial. Patients will be allocated to one of three treatment conditions (N = 80 each): prolonged exposure or EMDR (both consisting of eight weekly sessions of 90 minutes each) or a six-month waiting list. All participants are subjected to blind assessments at pre-treatment, twomonths post treatment, and six monthspost treatment. In addition, participants in the experimental conditions will have assessments at mid treatment and at 12 months follow-up. Discussion: The results from the post treatment measurement can be considered strong empirical indicators of the safety and effectiveness of prolonged exposure and EMDR. The six-month and twelve-month follow-up data have the potential of reliably providing documentation of the long-term effects of both treatments on the various outcome variables. Data from pre-treatment and midtreatment can be used to reveal possible pathways of change.19 p

Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer

<p>Aims: DDX3 is an RNA helicase that has antiapoptotic properties, and promotes proliferation and transformation. In addition, DDX3 was shown to be a direct downstream target of HIF-1α (the master regulatory of the hypoxia response) in breast cancer cell lines. However, the relation between DDX3 and hypoxia has not been addressed in human tumors. In this paper, we studied the relation between DDX3 and the hypoxic responsive proteins in human breast cancer.</p> <p>Methods and Results: DDX3 expression was investigated by immunohistochemistry in breast cancer in comparison with hypoxia related proteins HIF-1α, GLUT1, CAIX, EGFR, HER2, Akt1, FOXO4, p53, ERα, COMMD1, FER kinase, PIN1, E-cadherin, p21, p27, Transferrin receptor, FOXO3A, c-Met and Notch1. DDX3 was overexpressed in 127 of 366 breast cancer patients, and was correlated with overexpression of HIF-1α and its downstream genes CAIX and GLUT1. Moreover, DDX3 expression correlated with hypoxia-related proteins EGFR, HER2, FOXO4, ERα and c-Met in a HIF-1α dependent fashion, and with COMMD1, FER kinase, Akt1, E-cadherin, TfR and FOXO3A independent of HIF-1α.</p> <p>Conclusions: In invasive breast cancer, expression of DDX3 was correlated with overexpression of HIF-1α and many other hypoxia related proteins, pointing to a distinct role for DDX3 under hypoxic conditions and supporting the oncogenic role of DDX3 which could have clinical implication for current development of DDX3 inhibitors.</p&gt

Aurora B phosphorylates spatially distinct targets to differentially regulate the kinetochore-microtubule interface

Accurate chromosome segregation requires carefully regulated interactions between kinetochores and microtubules, but how plasticity is achieved to correct diverse attachment defects remains unclear. Here we demonstrate that Aurora B kinase phosphorylates three spatially distinct targets within the conserved outer kinetochore KNL1/Mis12 complex/Ndc80 complex (KMN) network, the key player in kinetochore-microtubule attachments. The combinatorial phosphorylation of the KMN network generates graded levels of microtubule-binding activity, with full phosphorylation severely compromising microtubule binding. Altering the phosphorylation state of each protein causes corresponding chromosome segregation defects. Importantly, the spatial distribution of these targets along the kinetochore axis leads to their differential phosphorylation in response to changes in tension and attachment state. In total, rather than generating exclusively binary changes in microtubule binding, our results suggest a mechanism for the tension-dependent fine-tuning of kinetochore-microtubule interactions.Smith Family FoundationMassachusetts Life Sciences CenterKinship Foundation. Searle Scholars ProgramNational Institute of General Medical Sciences (U.S.) (Grant number GM088313

Effects of Pharmacogenetic Screening for CYP2D6 Among Elderly Starting Therapy With Nortriptyline or Venlafaxine:A Pragmatic Randomized Controlled Trial (CYSCE Trial)

PURPOSE/BACKGROUND: The duration of untreated depression is a predictor for poor future prognosis, making rapid dose finding essential. Genetic variation of the CYP2D6 isoenzyme can influence the optimal dosage needed for individual patients. The aim of this study was to determine the effectiveness of CYP2D6 pharmacogenetic screening to accelerate drug dosing in older patients with depression initiating nortriptyline or venlafaxine. METHODS/PROCEDURES: In this randomized controlled trial, patients were randomly allocated to one of the study arms. In the intervention arm (DG-I), the specific genotype accompanied by a standardized dosing recommendation based on the patients' genotype and the prescribed drug was directly communicated to the physician of the participant. In both the deviating genotype control arm (DG-C) and the nonrandomized control arm, the physician of the participants was not informed about the genotype and the associated dosing advise. The primary outcome was the time needed to reach adequate drug levels: (1) blood levels within the therapeutic range and (2) no dose adjustments within the previous 3 weeks. FINDINGS/RESULTS: No significant difference was observed in mean time to reach adequate dose or time to adequate dose between DG-I and DG-C. Compared with the nonrandomized control arm group, adequate drug levels were reached significantly faster in the DG-I group (log-rank test; P = 0.004), and there was a similar nonsignificant trend for the DG-C group (log-rank test; P = 0.087). IMPLICATIONS/CONCLUSIONS: The results of this study do not support pharmacogenetic CYP2D6 screening to accelerate dose adjustment for nortriptyline and venlafaxine in older patients with depression

Quality of Life in Male Breast Cancer:Prospective Study of the International Male Breast Cancer Program (EORTC10085/TBCRC029/BIG2-07/NABCG)

INTRODUCTION: Prospective data about quality of life (QoL) in men with breast cancer (BC) are lacking. A prospective registry (EORTC10085) of men with all BC stages, including a QoL correlative study, was performed as part of the International Male Breast Cancer Program.METHODS: Questionnaires at BC diagnosis included the EORTC QLQ-C30 and BR23 (BC specific module), adapted for men. High functioning and global health/QoL scores indicate high functioning levels/high QoL; high symptom-focused measures scores indicate high symptoms/problems levels. EORTC reference data for healthy men and women with BC were used for comparisons.RESULTS: Of 422 men consenting to participate, 363 were evaluable. Median age was 67 years, and median time between diagnosis and survey was 1.1 months. A total of 114 men (45%) had node-positive early disease, and 28 (8%) had advanced disease. Baseline mean global health status score was 73 (SD: 21), better than in female BC reference data (62, SD: 25). Common symptoms in male BC were fatigue (22, SD: 24), insomnia (21, SD: 28), and pain (16, SD: 23), for which women's mean scores indicated more burdensome symptoms at 33 (SD: 26), 30 (SD: 32), and 29 (SD: 29). Men's mean sexual activity score was 31 (SD: 26), with less sexual activity in older patients or advanced disease.CONCLUSIONS: QoL and symptom burden in male BC patients appears no worse (and possibly better) than that in female patients. Future analyses on impact of treatment on symptoms and QoL over time, may support tailoring of male BC management.</p