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Background: Choledochal malformations comprise various congenital cystic dilatations of the extrahepatic and/or intrahepatic biliary tree. Choledochal malformation is generally considered a premalignant condition, but reliable data on the risk of malignancy and optimal surgical treatment are lacking. The objective of this systematic review was to assess the prevalence of malignancy in patients with choledochal malformation and to differentiate between subtypes. In addition, the risk of malignancy following cystic drainage versus complete cyst excision was assessed. Methods: A systematic review of PubMed and Embase databases was performed in accordance with the PRISMA statement. A meta‐analysis of the risk of malignancy following cystic drainage versus complete cyst excision was undertaken in line with MOOSE guidelines. Prevalence of malignancy was defined as the rate of biliary cancer before resection, and malignant transformation as new‐onset biliary cancer after surgery. Results: Eighteen observational studies were included, reporting a total of 2904 patients with a median age of 36 years. Of these, 312 in total developed a malignancy (10·7 per cent); the prevalence of malignancy was 7·3 per cent and the rate of malignant transformation was 3·4 per cent. Patients with types I and IV choledochal malformation had an increased risk of malignancy (P = 0·016). Patients who underwent cystic drainage had an increased risk of developing biliary malignancy compared with those who had complete cyst excision, with an odds ratio of 3·97 (95 per cent c.i. 2·40 to 6·55). Conclusion: The risk of developing malignancy among patients with choledochal malformation was almost 11 per cent. The malignancy risk following cystic drainage surgery was four times higher than that after complete cyst excision. Complete surgical resection is recommended in patients with choledochal malformation. [ABSTRACT FROM AUTHOR]

Background Experimental studies have suggested that end-ischaemic dual hypothermic oxygenated machine perfusion ( DHOPE) may restore hepatocellular energy status and reduce reperfusion injury in donation after circulatory death ( DCD) liver grafts. The aim of this prospective case-control study was to assess the safety and feasibility of DHOPE in DCD liver transplantation. Methods In consecutive DCD liver transplantations, liver grafts were treated with end-ischaemic DHOPE. Outcome was compared with that in a control group of DCD liver transplantations without DHOPE, matched for donor age, donor warm ischaemia time, and recipient Model for End-stage Liver Disease ( MELD) score. All patients were followed for 1 year. Results Ten transplantations involving liver grafts treated with DHOPE were compared with 20 control procedures. There were no technical problems. All 6-month and 1-year graft and patient survival rates were 100 per cent in the DHOPE group. Six-month graft survival and 1-year graft and patient survival rates in the control group were 80, 67 and 85 per cent respectively. During DHOPE, median (i.q.r.) hepatic adenosine 5′-triphosphate ( ATP) content increased 11-fold, from 6 (3-10) to 66 (42-87) µmol per g protein ( P = 0·005). All DHOPE-preserved livers showed excellent early function. At 1 week after transplantation peak serum alanine aminotransferase ( ALT) and bilirubin levels were twofold lower in the DHOPE group than in the control group ( ALT: median 966 versus 1858 units/l respectively, P = 0·006; bilirubin: median 1·0 (i.q.r. 0·7-1·4) versus 2·6 (0·9-5·1) mg/dl, P = 0·044). None of the ten DHOPE-preserved livers required retransplantation for non-anastomotic biliary stricture, compared with five of 20 in the control group ( P = 0·140). Conclusion This clinical study of end-ischaemic DHOPE in DCD liver transplantation suggests that the technique restores hepatic ATP, reduces reperfusion injury, and is safe and feasible. RCTs with larger numbers of patients are warranted to assess the efficacy in reducing post-transplant biliary complications. [ABSTRACT FROM AUTHOR]

In recent years, owing to advances in our understanding of hepatocarcinogenesis, rare primary liver cancers (PLCs), including combined hepatocellular-cholangiocarcinoma, fibrolamellar carcinoma, and hepatic epithelioid hemangioendothelioma have garnered increased attention. In this position paper, an international panel of experts representing oncology, hepatology, pathology, radiology, surgery, and molecular biology has summarised the available information and evidence on the pathogenesis, diagnosis, and treatment of rare PLCs. While clinical trials of systemic treatments are underway for some rare PLCs, it is evident that more research, involving national and international collaboration, is required., (Copyright © 2024. Published by Elsevier B.V.)

The ongoing transition toward electric vehicles (EVs) is changing materials used for vehicle production, of which the consequences for the environmental performance of EVs are not well understood and managed. We demonstrate that electrification coupled with lightweighting of automobiles will lead to significant changes in the industry's demand not only for battery materials but also for other materials used throughout the entire vehicle. Given the automotive industry's substantial consumption of raw materials, changes in its material demands are expected to trigger volatilities in material prices, consequently impacting the material composition and attractiveness of EVs. In addition, the materials recovered during end-of-life recycling of EVs as the vehicle fleet turns over will impact recycled material supplies both positively and negatively, impacting material availabilities and the economic incentive to engage in recycling. These supply chain impacts will influence material usage and the associated environmental performance of not only the automotive sector but also other metal-heavy industries such as construction. In light of these challenges, we propose the need for new research to understand the dynamic materials impacts of the EV transition that encompasses its implications on EV adoption and fleet life cycle environmental performance. Effectively coordinating the coevolution of material supply chains is crucial for making the sustainable transition to EVs a reality.

Objective: The number of forced migrants has been rising for years. Many forced migrants suffer from post-traumatic stress disorder (PTSD), depression, and/or anxiety and need treatment. Here, we evaluate the effectiveness of psychological interventions (CBT, EMDR, expressive/art, mindfulness, mixed elements, NET and psychoeducation) in reducing symptoms of PTSD, depression, and anxiety in forced migrants., Design and Data Sources: Systematic searches in PubMed and Web of Science and searches of preprint servers and grey literature were performed (final search date: 1 September 2023). Random-effects frequentist and Bayesian meta-analyses were used for data synthesis., Results: We included 84 studies on treatment effects in adults (pooled N = 6302) and 32 on children and adolescents (pooled N = 1097). Our data show a reduction in symptoms of PTSD, depression and anxiety symptoms in both adults and child/adolescent forced migrants. Pooled pre- to post-treatment effects (effect size Cohen's d) ranged from -1.03 to -0.26 for PTSD, from -0.91 to -0.11 for depression and from -0.91 to -0.60 for anxiety, without there being differences in outcome per study design (i.e., RCT comparison vs. non-RCT comparison vs. single arm treatment study). Treatment effects remained evident over follow-up, and not a single type of treatment stood out as being superior to other treatment types. Structural differences in populations (e.g., regarding country of origin) over studies, however, could have hampered the validity of the comparisons between study characteristics such as treatment type., Conclusion: Our findings support the effectiveness of psychological treatment in adult and child/adolescent forced migrants., (© 2024 The Author(s). Clinical Psychology & Psychotherapy published by John Wiley & Sons Ltd.)

This study aimed to evaluate the effectiveness of different treatments for hepatic artery thrombosis (HAT) and hepatic artery stenosis (HAS) after pediatric liver transplantation. We systematically reviewed studies published since 2000 that investigated the management of HAT and/or HAS after pediatric liver transplantation. Studies with a minimum of 5 patients in one of the treatment methods were included. The primary outcomes were technical success rate and graft and patient survival. The secondary outcomes were hepatic artery patency, complications, and incidence of HAT and HAS. Of 3570 studies, we included 19 studies with 328 patients. The incidence was 6.2% for HAT and 4.1% for HAS. Patients with an early HAT treated with surgical revascularization had a median graft survival of 45.7% (interquartile range, 30.7%-60%) and a patient survival of 61.3% (interquartile range, 58.7%-66.9%) compared with the other treatments (conservative, endovascular revascularization, or retransplantation). As for HAS, endovascular and surgical revascularization groups had a patient survival of 85.7% and 100% (interquartile range, 85%-100%), respectively. Despite various treatment methods, HAT after pediatric liver transplantation remains a significant issue that has profound effects on the patient and graft survival. Current evidence is insufficient to determine the most effective treatment for preventing graft failure., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Introduction: In 2017, the Southampton guideline stated that minimally invasive liver resections (MILR) should considered standard practice for minor liver resections. This study aimed to assess recent implementation rates of minor MILR, factors associated with performing MILR, hospital variation, and outcomes in patients with colorectal liver metastases (CRLM)., Methods: This population-based study included all patients who underwent minor liver resection for CRLM in the Netherlands between 2014 and 2021. Factors associated with MILR and nationwide hospital variation were assessed using multilevel multivariable logistic regression. Propensity-score matching (PSM) was applied to compare outcomes between minor MILR and minor open liver resections. Overall survival (OS) was assessed with Kaplan-Meier analysis on patients operated until 2018., Results: Of 4,488 patients included, 1,695 (37.8%) underwent MILR. PSM resulted in 1,338 patients in each group. Implementation of MILR increased to 51.2% in 2021. Factors associated with not performing MILR included treatment with preoperative chemotherapy (aOR 0.61 CI:0.50-0.75, p < 0.001), treatment in a tertiary referral hospital (aOR 0.57 CI:0.50-0.67, p < 0.001), and larger diameter and number of CRLM. Significant hospital variation was observed in use of MILR (7.5% to 93.0%). After case-mix correction, six hospitals performed fewer, and six hospitals performed more MILRs than expected. In the PSM cohort, MILR was associated with a decrease in blood loss (aOR 0.99 CI:0.99-0.99, p < 0.01), cardiac complications (aOR 0.29, CI:0.10-0.70, p = 0.009), IC admissions (aOR 0.66, CI:0.50-0.89, p = 0.005), and shorter hospital stay (aOR CI:0.94-0.99, p < 0.01). Five-year OS rates for MILR and OLR were 53.7% versus 48.6%, p = 0.21., Conclusion: Although uptake of MILR is increasing in the Netherlands, significant hospital variation remains. MILR benefits short-term outcomes, while overall survival is comparable to open liver surgery., (© 2023. The Author(s).)

Acute liver failure (ALF) is rare but life-threatening. Common causes include intoxications, infections, and metabolic disorders. Indeterminate etiology is still frequent. No systematic data on incidence, causes, and outcome of ALF across Europe are available. Via an online survey we reached out to European Reference Network Centers on rare liver diseases. Numbers and etiology of ALF cases during 2020 were retrieved and diagnostic and treatment availabilities assessed. In total, 455 cases (306 adult, 149 pediatric) were reported from 36 centers from 20 countries. Intoxication was the most common cause in adult and pediatric care. The number of cases with indeterminate etiology is low. Diagnostic tools and specific treatment options are broadly available within this network. This is the first approach to report on etiology and outcome of ALF in the pediatric and adult population in Europe. High diagnostic yield and standard of care reflects the expert status of involved centers., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Anxiety-related disorders are characterized by high levels of avoidance, but experimental research into avoidance learning in patients is scarce. To fill this gap, we compared healthy controls (HC, n = 47) with patients with obsessive-compulsive disorder (OCD, n = 33), panic disorder with agoraphobia (PDA, n = 40), and post-traumatic stress disorder (PTSD, n = 66) in a computer-based avoidance learning task, in order to examine (1) differences in rates of avoidance responses, (2) differences in action-safety learning during avoidance, and (3) differences in subjective relief following successful avoidance. The task comprised aversive negative pictures (unconditional stimulus, US) that followed pictures of two colored lamps (conditional stimuli, CS+), but not a third colored lamp (safety stimulus, CS-), and could be avoided by pressing a button during one CS+ (CS+ avoidable) but not the other (CS+ unavoidable). Participants rated their US-expectancy and level of relief on a trial-by-trial basis. Compared to the HC group, patient groups displayed higher levels of avoidance to the safety stimulus, and higher levels of US-expectancy and relief following the safety and avoidable danger stimulus. We propose that patients with anxiety disorders have low confidence in the safety consequences of avoidance actions, which induces increased relief during US omissions that reinforce the avoidance action., Competing Interests: Conflict of interest All authors declare to have no conflict of interest related to the presented work., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The COVID-19 pandemic has accelerated the growth of e-commerce and automated warehouses, vehicles, and robots and has created new options for grocery supply chains. We report and compare the greenhouse gas (GHG) emissions for a 36-item grocery basket transported along 72 unique paths from a centralized warehouse to the customer, including impacts of micro-fulfillment centers, refrigeration, vehicle automation, and last-mile transportation. Our base case is in-store shopping with last-mile transportation using an internal combustion engine (ICE) SUV (6.0 kg CO 2 e). The results indicate that emissions reductions could be achieved by e-commerce with micro-fulfillment centers (16-54%), customer vehicle electrification (18-42%), or grocery delivery (22-65%) compared to the base case. In-store shopping with an ICE pick-up truck has the highest emissions of all paths investigated (6.9 kg CO 2 e) while delivery using a sidewalk automated robot has the least (1.0 kg CO 2 e). Shopping frequency is an important factor for households to consider, e.g. halving shopping frequency can reduce GHG emissions by 44%. Trip chaining also offers an opportunity to reduce emissions with approximately 50% savings compared to the base case. Opportunities for grocers and households to reduce grocery supply chain carbon footprints are identified and discussed.

Expanded use of novel oil extraction technologies has increased the variability of petroleum resources and diversified the carbon footprint of the global oil supply 1 . Past life-cycle assessment (LCA) studies overlooked upstream emission heterogeneity by assuming that a decline in oil demand will displace average crude oil 2 . We explore the life-cycle greenhouse gas emissions impacts of marginal crude sources, identifying the upstream carbon intensity (CI) of the producers most sensitive to an oil demand decline (for example, due to a shift to alternative vehicles). We link econometric models of production profitability of 1,933 oilfields (~90% of the 2015 world supply) with their production CI. Then, we examine their response to a decline in demand under three oil market structures. According to our estimates, small demand shocks have different upstream CI implications than large shocks. Irrespective of the market structure, small shocks (-2.5% demand) displace mostly heavy crudes with ~25-54% higher CI than that of the global average. However, this imbalance diminishes as the shocks become bigger and if producers with market power coordinate their response to a demand decline. The carbon emissions benefits of reduction in oil demand are systematically dependent on the magnitude of demand drop and the global oil market structure., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Recently, the first randomized trials comparing minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) for non-malignant and malignant disease showed a 2-day reduction in time to functional recovery after MIDP. However, for pancreatic ductal adenocarcinoma (PDAC), concerns have been raised regarding the oncologic safety (i.e., radical resection, lymph node retrieval, and survival) of MIDP, as compared to ODP. Therefore, a randomized controlled trial comparing MIDP and ODP in PDAC regarding oncological safety is warranted. We hypothesize that the microscopically radical resection (R0) rate is non-inferior for MIDP, as compared to ODP., Methods/design: DIPLOMA is an international randomized controlled, patient- and pathologist-blinded, non-inferiority trial performed in 38 pancreatic centers in Europe and the USA. A total of 258 patients with an indication for elective distal pancreatectomy with splenectomy because of proven or highly suspected PDAC of the pancreatic body or tail will be randomly allocated to MIDP (laparoscopic or robot-assisted) or ODP in a 1:1 ratio. The primary outcome is the microscopically radical resection margin (R0, distance tumor to pancreatic transection and posterior margin ≥ 1 mm), which is assessed using a standardized histopathology assessment protocol. The sample size is calculated with the following assumptions: 5% one-sided significance level (α), 80% power (1-β), expected R0 rate in the open group of 58%, expected R0 resection rate in the minimally invasive group of 67%, and a non-inferiority margin of 7%. Secondary outcomes include time to functional recovery, operative outcomes (e.g., blood loss, operative time, and conversion to open surgery), other histopathology findings (e.g., lymph node retrieval, perineural- and lymphovascular invasion), postoperative outcomes (e.g., clinically relevant complications, hospital stay, and administration of adjuvant treatment), time and site of disease recurrence, survival, quality of life, and costs. Follow-up will be performed at the outpatient clinic after 6, 12, 18, 24, and 36 months postoperatively., Discussion: The DIPLOMA trial is designed to investigate the non-inferiority of MIDP versus ODP regarding the microscopically radical resection rate of PDAC in an international setting., Trial Registration: ISRCTN registry ISRCTN44897265 . Prospectively registered on 16 April 2018., (© 2021. The Author(s).)

Increased E-commerce and demand for contactless delivery during the COVID-19 pandemic have fueled interest in robotic package delivery. We evaluate life cycle greenhouse gas (GHG) emissions for automated suburban ground delivery systems consisting of a vehicle (last-mile) and a robot (final-50-feet). Small and large cargo vans (125 and 350 cubic feet; V125 and V350) with an internal combustion engine (ICEV) and battery electric (BEV) powertrains were assessed for three delivery scenarios: (i) conventional , human-driven vehicle with human delivery; (ii) partially automated , human-driven vehicle with robot delivery; and (iii) fully automated , connected automated vehicle (CAV) with robot delivery. The robot's contribution to life cycle GHG emissions is small (2-6%). Compared to the conventional scenario, full automation results in similar GHG emissions for the V350-ICEV but 10% higher for the V125-BEV. Conventional delivery with a V125-BEV provides the lowest GHG emissions, 167 g CO 2 e/package, while partially automated delivery with a V350-ICEV generates the most at 486 g CO 2 e/package. Fuel economy and delivery density are key parameters, and electrification of the vehicle and carbon intensity of the electricity have a large impact. CAV power requirements and efficiency benefits largely offset each other, and automation has a moderate impact on life cycle GHG emissions.

Much about the aetiology, pathophysiology, natural course and optimal treatment of choledochal malformation remains under debate. Surgeons continuously strive to optimize their roles in the management of choledochal malformation. Nowadays the standard treatment is complete cyst excision followed by Roux-en-Y hepaticojejunostomy, be it via a laparotomy, laparoscopy or robot-assisted procedure. Whatever surgical endeavor is undertaken, it will be a major operation, with significant morbidity. It is important to realize that especially in asymptomatic cases, this is considered prophylactic surgery, aimed at preventing symptoms but even more important the development of malignancy later in life. A clear overview of long-term outcomes is therefore necessary. This paper aims to review the long-term outcomes after surgery for choledochal malformation. We will focus on biliary complications such as cholangitis, the development of malignancy and quality of life. We will try and identify factors related to a worse outcome. Finally, we make a plea for a large scale study into quality and course of life after resection of a choledochal malformation, to help patients, parents and their treating physicians to come to a well-balanced decision regarding the treatment of a choledochal malformation., (Copyright © 2020. Published by Elsevier Inc.)

Background: Many patients with post-traumatic stress disorder (PTSD) experience dissociative symptoms. The question of whether these dissociative symptoms negatively influence the effectiveness of psychotherapy for PTSD is unresolved., Aims: To determine the influence of dissociative symptoms on psychotherapy outcome in PTSD., Method: We conducted a systematic search in Cochrane, Embase, PILOTS, PsycINFO, PubMed and Web of Science for relevant clinical trials. A random-effects meta-analysis examined the impact of dissociation on psychotherapy outcome in PTSD (pre-registered at Prospero CRD42018086575)., Results: Twenty-one trials (of which nine were randomised controlled trials) with 1714 patients were included. Pre-treatment dissociation was not related to treatment effectiveness in patients with PTSD (Pearson's correlation coefficient 0.04, 95% CI -0.04 to 0.13). Between-study heterogeneity was high but was not explained by moderators such as trauma focus of the psychotherapy or risk of bias score. There was no indication for publication bias., Conclusions: We found no evidence that dissociation moderates the effectiveness of psychotherapy for PTSD. The quality of some of the included studies was relatively low, emphasising the need for high-quality clinical trials in patients with PTSD. The results suggest that pre-treatment dissociation does not determine psychotherapy outcome in PTSD.

Background: Prior research indicates that the factors that trigger suicidal ideation may differ from those that maintain it, but studies into the maintenance of suicidal ideation remain scarce. Our aim was to assess the longitudinal course of suicidal ideation, and to identify predictors of persistent suicidal ideation., Methods: We used data from the Netherlands Study of Depression and Anxiety (NESDA). We performed a linear mixed-effects growth model analysis (n = 230 with current suicidal ideation at baseline) to assess the course of suicidal ideation over time (baseline through 2-, 4-, 6- and 9-year follow-up). We used logistic regression analysis (n = 195) to test whether factors previously associated with the incidence of suicidal ideation in the literature (insomnia, hopelessness, loneliness, borderline personality traits, childhood trauma, negative life events) also predict persistence of suicidal ideation (i.e., reporting ideation at two consecutive assessment points, 6- and 9-years). We controlled for socio-demographics, clinical diagnosis and severity, medication use, and suicide attempt history., Results: Suicidal ideation decreased over time, and this decrease became slower with increasing time, with the majority of symptom reductions occurring in the first two years of follow-up. More severe insomnia and hopelessness were associated with increased odds of persistent suicidal ideation, and hopelessness was a significant mediator of the relationship between insomnia and persistent suicidal ideation., Limitations: Findings may not generalize to those with more severe suicidal ideation due to dropout of those with the worst clinical profile., Conclusions: Targeting insomnia and hopelessness in treatment may be particularly important to prevent the persistence of suicidal ideation., (Copyright © 2019. Published by Elsevier B.V.)

Substituting conventional materials with lightweight materials is an effective way to reduce the life cycle greenhouse gas (GHG) emissions from light-duty vehicles. However, estimated GHG emission reductions of lightweighting depend on multiple factors including the vehicle powertrain technology and efficiency, lightweight material employed, and end-of-life material recovery. We developed a fleet-based life cycle model to estimate the GHG emission changes due to lightweighting the U.S. light-duty fleet from 2016 to 2050, using either high strength steel or aluminum as the lightweight material. Our model estimates that implementation of an aggressive lightweighting scenario using aluminum reduces 2016 through 2050 cumulative life cycle GHG emissions from the fleet by 2.9 Gt CO 2 eq (5.6%), and annual emissions in 2050 by 11%. Lightweighting has the greatest GHG emission reduction potential when implemented in the near-term, with two times more reduction per kilometer traveled if implemented in 2016 rather than in 2030. Delaying implementation by 15 years sacrifices 72% (2.1 Gt CO 2 eq) of the cumulative GHG emission mitigation potential through 2050. Lightweighting is an effective solution that could provide important near-term GHG emission reductions especially during the next 10-20 years when the fleet is dominated by conventional powertrain vehicles.

Objective: This trial followed a structured nationwide training program in minimally invasive distal pancreatectomy (MIDP), according to the IDEAL framework for surgical innovation, and aimed to compare time to functional recovery after minimally invasive and open distal pancreatectomy (ODP)., Background: MIDP is increasingly used and may enhance postoperative recovery as compared with ODP, but randomized studies are lacking., Methods: A multicenter patient-blinded randomized controlled superiority trial was performed in 14 centers between April 2015 and March 2017. Adult patients with left-sided pancreatic tumors confined to the pancreas without vascular involvement were randomly assigned (1:1) to undergo MIDP or ODP. Patients were blinded for type of surgery using a large abdominal dressing. The primary endpoint was time to functional recovery. Analysis was by intention to treat. This trial was registered with the Netherlands Trial Register (NTR5689)., Results: Time to functional recovery was 4 days [interquartile range (IQR) 3-6) in 51 patients after MIDP versus 6 days (IQR 5-8) in 57 patients after ODP (P < 0.001). The conversion rate of MIDP was 8%. Operative blood loss was less after MIDP (150 vs 400 mL; P < 0.001), whereas operative time was longer (217 vs 179 minutes; P = 0.005). The Clavien-Dindo grade ≥III complication rate was 25% versus 38% (P = 0.21). Delayed gastric emptying grade B/C was seen less often after MIDP (6% vs 20%; P = 0.04). Postoperative pancreatic fistulas grade B/C were seen in 39% after MIDP versus 23% after ODP (P = 0.07), without difference in percutaneous catheter drainage (22% vs 20%; P = 0.77). Quality of life (day 3-30) was better after MIDP as compared with ODP, and overall costs were non-significantly less after MIDP. No 90-day mortality was seen after MIDP versus 2% (n = 1) after ODP., Conclusions: In patients with left-sided pancreatic tumors confined to the pancreas, MIDP reduces time to functional recovery compared with ODP. Although the overall rate of complications was not reduced, MIDP was associated with less delayed gastric emptying and better quality of life without increasing costs.

The literature analyzing the fuel saving, life cycle greenhouse gas (GHG) emission, and ownership cost impacts of lightweighting vehicles with different powertrains is reviewed. Vehicles with lower powertrain efficiencies have higher fuel consumption. Thus, fuel savings from lightweighting internal combustion engine vehicles can be higher than those of hybrid electric and battery electric vehicles. However, the impact of fuel savings on life cycle costs and GHG emissions depends on fuel prices, fuel carbon intensities and fuel storage requirements. Battery electric vehicle fuel savings enable reduction of battery size without sacrificing driving range. This reduces the battery production cost and mass, the latter results in further fuel savings. The carbon intensity of electricity varies widely and is a major source of uncertainty when evaluating the benefits of fuel savings. Hybrid electric vehicles use gasoline more efficiently than internal combustion engine vehicles and do not require large plug-in batteries. Therefore, the benefits of lightweighting depend on the vehicle powertrain. We discuss the value proposition of the use of lightweight materials and alternative powertrains. Future assessments of the benefits of vehicle lightweighting should capture the unique characteristics of emerging vehicle powertrains.

Background: Despite robust empirical support for the efficacy of trauma-focused treatments, the dissemination proves difficult, especially in relation to patients with comorbid psychosis. Many therapists endorse negative beliefs about the credibility, burden, and harm of such treatment., Objective: This feasibility study explores the impact of specialized training on therapists' beliefs about trauma-focused treatment within a randomized controlled trial., Method: Therapist-rated (n=16) credibility, expected burden, and harm expectancies of trauma-focused treatment were assessed at baseline, post-theoretical training, post-technical training, post-supervised practical training, and at 2-year follow-up. Credibility and burden beliefs of therapists concerning the treatment of every specific patient in the trial were also assessed., Results: Over time, therapist-rated credibility of trauma-focused treatment showed a significant increase, whereas therapists' expected burden and harm expectancies decreased significantly. In treating posttraumatic stress disorder (PTSD) in patients with psychotic disorders (n=79), pre-treatment symptom severity was not associated with therapist-rated credibility or expected burden of that specific treatment. Treatment outcome had no influence on patient-specific credibility or burden expectancies of therapists., Conclusions: These findings support the notion that specialized training, including practical training with supervision, has long-term positive effects on therapists' credibility, burden, and harm beliefs concerning trauma-focused treatment.

The need to study molecular and functional parameters of Alzheimer's disease progression in animal models has led to the development of disease-specific fluorescent markers. However, curved optical interfaces and a highly heterogeneous internal structure make quantitative fluorescence imaging of the murine brain a particularly challenging tomographic problem. We investigated the integration of X-ray computed tomography (CT) information into a state-of-the-art fluorescence molecular tomography (FMT) scheme and establish that the dual-modality approach is essential for high fidelity reconstructions of distributed fluorescence within the murine brain, as compared to conventional fluorescence tomography. We employ this method in vivo using a fluorescent oxazine dye to quantify amyloid-beta plaque burden in transgenic APP23 mice modeling Alzheimer's disease. Multi-modal imaging allows for accurate signal localization and correlation of in vivo findings to ex vivo studies. The results point to FMT-CT as an essential tool for in vivo study of neurodegenerative disease in animal models and potentially humans.

The ability to visualize molecular processes and cellular regulators of complex pulmonary diseases such as asthma, chronic obstructive pulmonary disease (COPD), or adult respiratory distress syndrome (ARDS), would aid in the diagnosis, differentiation, therapy assessment and in small animal-based drug-discovery processes. Herein we report the application of normalized transillumination and fluorescence molecular tomography (FMT) for the noninvasive quantitative imaging of the mouse lung in vivo. We demonstrate the ability to visualize and quantitate pulmonary response in a murine model of LPS-induced airway inflammation. Twenty-four hours prior to imaging, BALB/c female mice were injected via tail vein with 2 nmol of a cathepsin-sensitive activatable fluorescent probe (excitation: 750 nm; emission: 780 nm) and 2 nmol of accompanying intravascular agent (excitation: 674 nm; emission: 694 nm). Six hours later, the mice were anesthetized with isoflurane and administered intranasal LPS in sterile 0.9% saline in 25 microl aliquots (one per nostril). Fluorescence molecular imaging revealed the in vivo profile of cysteine protease activation and vascular distribution within the lung typifying the inflammatory response to LPS insult. Results were correlated with standard in vitro laboratory tests (Western blot, bronchoalveolar lavage or BAL analysis, immunohistochemistry) and revealed good correlation with the underlying activity. We demonstrated the capacity of fluorescence tomography to noninvasively and longitudinally characterize physiological, cellular, and subcellular processes associated with inflammatory disease burden in the lung. The data presented herein serve to further evince fluorescence molecular imaging as a technology highly appropriate for the biomedical laboratory.

Luciferases are widely used to monitor biological processes. Here we describe the naturally secreted Gaussia princeps luciferase (Gluc) as a highly sensitive reporter for quantitative assessment of cells in vivo by measuring its concentration in blood. The Gluc blood assay complements in vivo bioluminescence imaging, which has the ability to localize the signal and provides a multifaceted assessment of cell viability, proliferation and location in experimental disease and therapy models.

Fluctuating high fluid pressures have been reported in pseudojoints after total hip arthroplasty, and may be present throughout the effective joint space. When the pressure extends locally to the bone implant interface, we hypothesized that it might have led to bone resorption. We developed an experimental implant model to study whether oscillating fluid pressure, applied during 2 hours a day, can lead to osteolysis at the bone implant interface. 12 mature rabbits received a titanium implant, which was allowed to osseointegrate. Thereafter, fluid pressure was applied to a specific area of the titanium bone interface at the periosteal side of the cortex in 6 of the rabbits. The pressure, applied during 2 hours a day for 14 days, oscillated between 70 and 150 mm Hg, with a frequency of 0.1 Hz. Bone resorption was not found in any of the control animals, but it occurred under 4 implants exposed to fluid pressure (p = 0.03; Fisher's exact test). Localized osteolytic lesions had developed, with evidence of osteocyte death in the surrounding cortical bone. In 1 of the 2 specimens without osteolysis, there was evidence of fluid leakage into the soft tissues. In 4 specimens (3 with and 1 without osteolysis), bone formation was observed at the endosteal side opposite to the pressure zone. This did not occur in the controls. No signs of infection were observed. Our findings indicate that oscillating fluid pressure, even when present only during short periods, can lead to osteolysis and may be a cause of prosthetic loosening. Endosteal bone apposition may be a result of the interstitial flow that was created, giving false signals of mechanical load to the osteocytes.

The aim of this study was to investigate performance of preserved arterial allografts under the protection of a high-dose and a low-dose immunosuppressive regimen, with cyclosporine (CsA). Dog carotid arteries were harvested and stored for 14 days at 4 degrees C in University of Wisconsin organ preservation solution. Segments (6 cm) of carotid artery were orthotopically and bilaterally implanted in mongrel dogs (n = 18). CsA was given in two dosage regimens: 25 mg/kg/day (group I, n = 7) and 10 mg/kg/day (group II, n = 7). The control group received no CsA (group III, n=4). After 3 months of implantation, patency was assessed by angiography. The grafts were excised for investigation of vessel wall and endothelial function and morphology. For assessment of function in vitro, slices of arterial segments were connected as ring preparations to an isometric force transducer and immersed in a 5 ml organ bath (37 degrees C) containing Tyrode's solution. The contractile response was examined by adding 40 mM KCl and phenylephrine (100 microM) to the organ bath; endothelium-dependent relaxation was examined by adding methacholine (100 microM). Morphology was assessed semiquantitatively. The functional responses to KCl, phenylephrine (Phe) and methacho- line (Met) after 14 days of storage in UW, were 30.2 +/- 1.2 mN, 26.9 +/- 1.0 and 45 +/- 1.2% (means +/- SEM, n=9), respectively. Patency after three months of implantation for group I was 100% (14/14), for group II 50% (7/14), and for group III 75% (6/8). In vitro functional responses of preserved arteries, after 3 months of implantation in group I were 58.5 +/- 10.6 mN (KCl), 36.5 +/- 5.8 mN (Phe), and 57.4 +/- 9.7% (Met), respectively. Functions in group II were 1.2 +/- 0.1 mN (KCl, 0.0 mN (Phe), and 0.0% (Met). Grafts in group III showed no function. Measurement of medial thickness showed significant thinning (P <0.05) in groups II and III. Patency and function of arterial allografts under a therapeutic dose of CsA were superior to grafts implanted under low-dose CsA or no immunosuppressive treatment.