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Physical review / B 106(12), 125138 (2022). doi:10.1103/PhysRevB.106.125138, We report a high-resolution angle-resolved photoemission (ARPES) study of the prototypical nearly free-electron metal sodium. The observed mass enhancement is slightly smaller than that derived in previous studies. The new results on the lifetime broadening increase the demand for theories beyond the random phase approximation. Our results do not support the proposed strong enhancement of the scattering rates of the charge carriers due to a coupling to spin fluctuations. Moreover, a comparison with earlier electron energy-loss data on sodium yields a strong reduction of the mass enhancement of dipolar electron-hole excitations compared to that of monopole hole excitations, measured by ARPES., Published by Inst., Woodbury, NY

Asbestos-related mesotheliomas belong to the group of the most frequent occupational diseases in Germany, reaching about 1,000 new cases per year. The disease has a dismal prognosis because most tumors remain asymptomatic for a long time and therefore are diagnosed as incidental findings at later stages.During the last decade the German Social Accident Insurance (DGUV) has made considerable efforts to prepone the diagnosis in order to detect the disease at earliest possible stages. These efforts resulted in new findings showing that, in a high-risk group, a combination of the biomarkers calretinin and mesothelin was able to advance the diagnosis up to 12 months.Ideally, the diagnosis of a mesothelioma at an early stage has to be accompanied by the best possible individualized therapy. Standard therapeutic strategies are surgery and chemotherapy, added by radiotherapy and psycho-oncology. In recent years, several new therapeutic avenues are being explored. This review comprehensively presents both old and new therapeutic options in mesothelioma, based on international Leitlinien and new studies.Asbestverursachte maligne Mesotheliome gehören in Deutschland mit etwa 1000 jährlichen Neuerkrankungen zu den häufigen arbeitsbedingten Krebserkrankungen. Die Prognose ist oftmals schlecht, da die Erkrankung lange symptomlos bleibt und deshalb meist erst als Zufallsbefund in bereits fortgeschrittenen Stadien diagnostiziert wird.Die deutsche gesetzliche Unfallversicherung (DGUV) hat in den letzten Jahren erhebliche Anstrengungen unternommen, eine Vorverlagerung des Diagnosezeitpunkts zu erreichen, um die Erkrankung möglichst in Frühstadien zu detektieren. Die aus diesen Bestrebungen resultierenden neuen medizinisch-wissenschaftlichen Erkenntnisse zeigen, dass die Kombination der Biomarker Calretinin und Mesothelin in einer Hochrisikogruppe die Vorverlegung der Diagnose um bis zu 12 Monaten ermöglicht.Die Diagnose eines Mesothelioms im Frühstadium wird idealerweise von der individuell bestmöglichen Therapie gefolgt. Die Standardtherapie basiert auf operativer Entfernung des Tumors und Chemotherapie, ergänzt um Strahlentherapie und Psychoonkologie. In den letzten Jahren wurden einige neue Therapieansätze entwickelt. Die Übersicht stellt den aktuellen Stand der Therapie des Mesothelioms, basierend auf den internationalen Leitlinien und neuen Studien, dar.

HistoryA 63-year-old woman with a history of left mastectomy for breast cancer and partial gastrectomy with Roux-en-Y reconstruction for nonhealing peptic ulcer presented to the emergency department and reported a 1-month history of abdominal distention, fevers, chills, and flu-like symptoms. She was initially suspected of having flu, and she completed a course of oseltamivir; however, she had continued fatigue, fever, chills, abdominal bloating, and loss of appetite. She reported no contact with a sick person or recent travel. At admission, laboratory studies revealed leukocytosis, with a white blood cell count of 15.1 × 10

HistoryA 63-year-old woman with a history of left mastectomy for breast cancer and partial gastrectomy with Roux-en-Y reconstruction for nonhealing peptic ulcer presented to the emergency department and reported a 1-month history of abdominal distention, fevers, chills, and flu-like symptoms. She was initially suspected of having flu, and she completed a course of oseltamivir; however, she had continued to experience fatigue, fever, chills, abdominal bloating, and loss of appetite. She reported no contact with a sick person or recent travel. At admission, laboratory studies revealed leukocytosis, with a white blood cell count of 15.1 × 103/μL (15.1 × 109/L) (normal range, 4.0-10.0 × 103/μL [4.0-10.0 × 109/L]), an elevated sedimentation rate of 100 mm per hour (normal range, 0-30 mm per hour), and a C-reactive protein level of 203.8 mg/L (1940.9 nmol/L) (normal range, ≤10 mg/L [≤95.2 nmol/L]). Liver enzyme levels were elevated, with an alanine aminotransferase level of 48 U/L (0.80 µkat/L) (normal range, 0-29 U/L [0-0.48 µkat/L]), an aspartate aminotransferase level of 98 U/L (1.6 µkat/L) (normal range, 10-37 U/L [0.16-0.62 µkat/L]), an alkaline phosphatase level of 682 U/L (11.4 μkat/L) (normal range, 65-195 U/L [1.1-3.3 μkat/L]), and a total bilirubin level of 1.5 mg/dL (25.7 µmol/L) (normal range, 0.3-1.0 mg/dL [5.1-17.1 μmol/L]). Abdominopelvic CT was performed.

Cardiac tissue surrogates show promise for restoring mechanical and electrical function in infarcted left ventricular (LV) myocardium. For these cardiac surrogates to be useful in vivo, they are required to support synchronous and forceful contraction over the infarcted region. These design requirements necessitate a thickness sufficient to produce a useful contractile force, an area large enough to cover an infarcted region, and prevascularization to overcome diffusion limitations. Attempts to meet these requirements have been hampered by diffusion limits of oxygen and nutrients (100–200 µm) leading to necrotic regions. This study demonstrates a novel layer-by-layer (LbL) fabrication method used to produce tissue surrogates that meet these requirements and mimic normal myocardium in form and function. Thick (1.5–2 mm) LbL cardiac tissues created from human induced pluripotent stem cell-derived cardiomyocytes and endothelial cells were assessed, in vitro, over a 4-week period for viability (R 2 < 0.98). Functional performance assessment showed enhanced t-tubule network development, gap junction communication as well as conduction velocity (16.9 ± 2.3 cm s−1). These results demonstrate that LbL fabrication can be utilized successfully in creating complex, functional cardiac surrogates for potential therapeutic applications.

Background There is substantial interest in electrospun scaffolds as substrates for tissue regeneration and repair due to their fibrous, extracellular matrix-like composition with interconnected porosity, cost-effective production, and scalability. However, a common limitation of these scaffolds is their inherently low mechanical strength and stiffness, restricting their use in some clinical applications. In this study we developed a novel technique for 3D printing a mesh reinforcement on electrospun scaffolds to improve their mechanical properties. Methods A poly (lactic acid) (PLA) mesh was 3D-printed directly onto electrospun scaffolds composed of a 40:60 ratio of poly(ε-caprolactone) (PCL) to gelatin, respectively. PLA grids were printed onto the electrospun scaffolds with either a 6 mm or 8 mm distance between the struts. Scanning electron microscopy was utilized to determine if the 3D printing process affected the archtitecture of the electrospun scaffold. Tensile testing was used to ascertain mechanical properties (strength, modulus, failure stress, ductility) of both unmodified and reinforced electrospun scaffolds. An in vivo bone graft model was used to assess biocompatibility. Specifically, reinforced scaffolds were used as a membrane cover for bone graft particles implanted into rat calvarial defects, and implant sites were examined histologically. Results We determined that the tensile strength and elastic modulus were markedly increased, and ductility reduced, by the addition of the PLA meshes to the electrospun scaffolds. Furthermore, the scaffolds maintained their matrix-like structure after being reinforced with the 3D printed PLA. There was no indication at the graft/tissue interface that the reinforced electrospun scaffolds elicited an immune or foreign body response upon implantation into rat cranial defects. Conclusion 3D-printed mesh reinforcements offer a new tool for enhancing the mechanical strength of electrospun scaffolds while preserving the advantageous extracellular matrix-like architecture. The modification of electrospun scaffolds with 3D-printed reinforcements is expected to expand the range of clinical applications for which electrospun materials may be suitable.

BACKGROUND Variable chemotherapy exposure may cause toxicity or lack of efficacy. This study was initiated to validate pharmacokinetically (PK)-guided paclitaxel dosing in patients with advanced non-small-cell lung cancer (NSCLC) to avoid supra- or subtherapeutic exposure. PATIENTS AND METHODS Patients with newly diagnosed, advanced NSCLC were randomly assigned to receive up to 6 cycles of 3-weekly carboplatin AUC 6 or cisplatin 80 mg/m(2) either with standard paclitaxel at 200 mg/m(2) (arm A) or PK-guided dosing of paclitaxel (arm B). In arm B, initial paclitaxel dose was adjusted to body surface area, age, sex, and subsequent doses were guided by neutropenia and previous-cycle paclitaxel exposure [time above a plasma concentration of 0.05 µM (Tc>0.05)] determined from a single blood sample on day 2. The primary end point was grade 4 neutropenia; secondary end points included neuropathy, radiological response, progression-free survival (PFS) and overall survival (OS). RESULTS Among 365 patients randomly assigned, grade 4 neutropenia was similar in both arms (19% versus 16%; P = 0.10). Neuropathy grade ≥2 (38% versus 23%, P < 0.001) and grade ≥3 (9% versus 2%, P < 0.001) was significantly lower in arm B, independent of the platinum drug used. The median final paclitaxel dose was significantly lower in arm B (199 versus 150 mg/m(2), P < 0.001). Response rate was similar in arms A and B (31% versus 27%, P = 0.405), as was adjusted median PFS [5.5 versus 4.9 months, hazard ratio (HR) 1.16, 95% confidence interval (CI) 0.91-1.49, P = 0.228] and OS (10.1 versus 9.5 months, HR 1.05, 95% CI 0.81-1.37, P = 0.682). CONCLUSION PK-guided dosing of paclitaxel does not improve severe neutropenia, but reduces paclitaxel-associated neuropathy and thereby improves the benefit-risk profile in patients with advanced NSCLC. CLINICAL TRIAL INFORMATION NCT01326767 (https://clinicaltrials.gov/ct2/show/NCT01326767).

Accessible high-capacity weighing scales are scarce in healthcare facilities, in part due to high device cost and weight. This shortage impairs weight monitoring and health maintenance for people with disabilities and/or morbid obesity. We conducted this study to design and validate a lighter, lower cost, high-capacity accessible weighing device. A prototype featuring 360 kg (800 lbs) of weight capacity, a wheelchair-accessible ramp, and wireless data transmission was fabricated. Forty-five participants (20 standing, 20 manual wheelchair users, and five power wheelchair users) were weighed using the prototype and a calibrated scale. Participants were surveyed to assess perception of each weighing device and the weighing procedure. Weight measurements between devices demonstrated a strong linear correlation (R2 = 0.997) with absolute differences of 1.4 ± 2.0% (mean±SD). Participant preference ratings showed no difference between devices. The prototype weighed 11 kg (38%) less than the next lightest high-capacity commercial device found by author survey. The prototype’s estimated commercial price range, $500–$600, is approximately half the price of the least expensive commercial device found by author survey. Such low cost weighing devices may improve access to weighing instrumentation, which may in turn help eliminate current health disparities. Future work is needed to determine the feasibility of market transition.

One approach to encourage and facilitate exercise is through interaction with virtual environments. The present study assessed the utility of Microsoft Kinect as an interface for choosing between multiple routes within a virtual environment through body gestures and voice commands. The approach was successfully tested on 12 individuals post-stroke and 15 individuals with cerebral palsy (CP). Participants rated their perception of difficulty in completing each gesture using a 5-point Likert scale questionnaire. The "most viable" gestures were defined as those with average success rates of 90% or higher and perception of difficulty ranging between easy and very easy. For those with CP, hand raises, hand extensions, and head nod gestures were found most viable. For those post-stroke, the most viable gestures were torso twists, head nods, as well as hand raises and hand extensions using the less impaired hand. Voice commands containing two syllables were viable (85% successful) for those post-stroke; however, participants with CP were unable to complete any voice commands with a high success rate. This study demonstrated that Kinect may be useful for persons with mobility impairments to interface with virtual exercise environments, but the effectiveness of the various gestures depends upon the disability of the user.

Cardiac tamponade is a life-threatening compression of the heart due to accumulation of fluid surrounding the heart. It occurs in two out of 10 000 people annually and is universally fatal if the fluid is not timely drained.1 The more rapidly accumulation occurs, the quicker the patient develops symptoms, including dyspnoea, fatigue and chest pain.2 Vital sign changes include tachycardia, tachypnoea and hypotension with a narrow pulse pressure. Pericardiocentesis is the required treatment to drain this fluid improving cardiac output.3 Simulation is an adjunct education tool to practise rare but crucial procedures.1 Current manikins do not have the capabilities to practise pericardiocentesis. Only torso task trainers are available.4 5 Our objective was to develop a pericardiocentesis trainer model that could both reliably recreate the procedure and be placed in a manikin, with no fluid leakage. ### Model assembly and design The Department of Biomedical Engineering collaborated with the Department of Pediatrics to build an inexpensive pericardiocentesis model with the following constraints: 1. Fit existing child simulators without significant chest wall distortion. 2. Have components to protect simulator both structurally and electronically from fluid spills using self-sealing technology. 3. Provide realistic fluid removal. 4. Have easily refillable fluid compartment that does not require direct access to task trainer. 5. Costs less than $500 budget. The final design encompasses a two-piece tray system, a top and bottom tray, attached by a peg …

There exists a need for educational processes in which students gain experience with design and commercialization of medical devices. This manuscript describes the implementation of, and assessment results from, the first year offering of a project course sequence in Master of Engineering (MEng) in Design and Commercialization at our institution. The three-semester course sequence focused on developing and applying hands-on skills that contribute to product development to address medical device needs found within our university hospital and local community. The first semester integrated computer-aided drawing (CAD) as preparation for manufacturing of device-related components (hand machining, computer numeric control (CNC), three-dimensional (3D) printing, and plastics molding), followed by an introduction to microcontrollers (MCUs) and printed circuit boards (PCBs) for associated electronics and control systems. In the second semester, the students applied these skills on a unified project, working together to construct and test multiple weighing scales for wheelchair users. In the final semester, the students applied industrial design concepts to four distinct device designs, including user and context reassessment, human factors (functional and aesthetic) design refinement, and advanced visualization for commercialization. The assessment results are described, along with lessons learned and plans for enhancement of the course sequence.

Background Guidelines for metastatic non-small cell lung cancer recommend stratified treatment by biomarker test results. We used CRISP to evaluate treatment and outcome of patients (pts) in whom neither targetable molecular alterations nor any PD-L1 expression were detected. Methods Currently 163 sites in Germany have recruited >3700 pts at start of 1st-line who will be followed until death or end of project. Data from 2204 pts recruited by 133 sites from 12/2015 to 06/2018 was analyzed. These pts started treatment prior approval of immune checkpoint inhibitors (ICI) for this group of pts. Progression-free survival (PFS) was determined in pts ≥1 year under observation (recruited until 06/2017 (n = 906), outcome sample (ous)). Results 6% of pts with non-squamous (nsq) and 35% with squamous (sq) tumors received no type of biomarker testing prior to start of 1st-line, and in 49% and 36% no targetable alterations or any PD-L1 expression were detected. Thus, 55% and 71% of pts (nsq/sq) were eligible for chemotherapy (ctx) but no type of targeted therapy at start of 1st-line. Median age at start of 1st-line was 66 and 68 years (nsq/sq). 29%/23% had ECOG=0 and 82%/90% ≤1 comorbidity. 10%/6% were never-smokers. In 1st-line, pts received carboplatin- (55%) or cisplatin-based ctx (24%), 13% targeted therapy (e.g. ICI in trial, switch to TKI but test result not yet documented). At database cut, 33% of all pts had started 2nd-line, 24% had died prior to a 2nd-line and remaining pts were still in 1st-line. In the ous, median PFS was 5.0 months (66% events, 95%-CI 4.5-5.5 months, n = 457) for nsq tumors and 4.5 months (66% events, 95%-CI 3.4-5.3 months, n = 154) for sq tumors. In total 55% of pts with nsq and 53% of pts with sq tumors had died. Conclusions CRISP presents current real life data from Germany. Despite break-throughs with targeted therapies and high test rates in routine care, the majority of pts do not qualify for targeted therapy because no targetable alterations are found. First outcome results indicate that prognosis is poor in these pts. Outcome will hopefully improve in the cohort now treated with ctx-ICI combination. Clinical trial identification NCT02622581. Legal entity responsible for the study AIO-Studien-gGmbH. Funding AstraZeneca GmbH, Boehringer Ingelheim Pharma GmbH & Co. KG, Bristol-Myers Squibb GmbH & Co. KGaA, Celgene GmbH, MSD Sharp & Dohme GmbH, Lilly Deutschland GmbH, Novartis Pharma GmbH, Pfizer Pharma GmbH, Roche Pharma AG, and Takeda Pharma Vertriebs GmbH & Co. KG. Disclosure F. Griesinger: Honoraria (self), Advisory / Consultancy: Ariad; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myer-Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Celgene; Honoraria (self), Advisory / Consultancy: Clovis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck-Sharp-Dome; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche. N.W. Marschner: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Research grant / Funding (institution): MSD Sharp & Dohme ; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Leadership role, Shareholder / Stockholder / Stock options, Officer / Board of Directors: iOMEDICO. M. Janicke: Leadership role, Full / Part-time employment: iOMEDICO. A. Fleitz: Full / Part-time employment: iOMEDICO. L. Spring: Full / Part-time employment: iOMEDICO. J. Sahlmann: Leadership role, Full / Part-time employment: iOMEDICO. A. Karatas: Research grant / Funding (institution): AstraZeneca ; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): MSD Sharp & Dohme; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Takeda. A. Hipper: Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): MSD Sharp & Dohme; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): AstraZeneca. M. Sebastian: Advisory / Consultancy: Bristol-Myers Squibb ; Advisory / Consultancy: MSD Sharp & Dohme ; Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim Pharma; Advisory / Consultancy: Celgene; Advisory / Consultancy: Lilly; Advisory / Consultancy: Pfizer. M. Thomas: Advisory / Consultancy, Travel / Accommodation / Expenses: MSD Sharp & Dohme ; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb ; Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca ; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis. All other authors have declared no conflicts of interest.

Ziel: Ziel war es zu zeigen, dass der bei der MR-Myelografie durch die starke T2-Gewichtung auftretende Nachteil der fehlenden anatomischen Zuordnung, durch eine Bildfusion sowie durch in koronarer Phasenkodierrichtung generierte Quellbilder behoben werden kann, wodurch eine dem Goldstandard – dem postmyelografischen CT – vergleichbare Bildinformation erzielt werden kann. Material und Methoden: Untersucht wurden insgesamt 110 Patienten mit extraduralen Pathologien der HWS und der LWS. Alle Patienten erhielten eine 3D-MR-Myelografie und ein postmyelografisches CT. Anschliesend wurden die MRT-Datensatze durch Bildfusion und Rekonstruktionen nachverarbeitet und mit den entsprechenden Schnittbildern des postmyelografischen CT verglichen. Ergebnisse: Die in der Arbeit verwendete Visualisierungstechnik (3D-MR-Myelografie) ist hierbei in der Lage intradurale Substrukturen hochauflosend und artefaktfrei darzustellen. Die erreichbaren Visualisierungsergebnisse sind mit dem aktuellen Goldstandard (postmyelografisches CT) vergleichbar. Eine anatomische Zuordnung ist durch Verwendung uberlagerter MRT-Sequenzen im Rahmen einer Bildfusion moglich. Die hierzu notwendigen Arbeitsschritte lassen sich rasch umsetzen und sind auf kommerziellen Workstations verfugbar. Schlussfolgerung: Durch die Fusion von unterschiedlichen MRT-Sequenzen entstehen neue Qualitaten bei der Visualisierung komplexer 3D-Datensatze. Insbesondere konnen der konventionellen Myelografie einschlieslich der postmyelografischen CT vergleichbare Visualisierungsergebnisse in Form der sogenannten 3D-MR-Myelografie realisiert werden. Der durch die starke T2-Gewichtung verlorene Bezug zu anatomischen Leitstrukturen kann durch Fusion mit einem weiteren MRT-Datensatz ausgeglichen werden.

There is a global shift in the teaching methodology of science and engineering toward multidisciplinary, team-based processes. To meet the demands of an evolving technical industry and lead the way in engineering education, innovative curricula are essential. This paper describes the development of multidisciplinary, team-based learning environments in undergraduate and graduate engineering curricula focused on medical device design. In these programs, students actively collaborate with clinicians, professional engineers, business professionals, and their peers to develop innovative solutions to real-world problems. In the undergraduate senior capstone courses, teams of biomedical engineering (BME) and business students have produced and delivered numerous functional prototypes to satisfied clients. Pursuit of commercialization of devices has led to intellectual property (IP) disclosures and patents. Assessments have indicated high levels of success in attainment of student learning outcomes and student satisfaction with their undergraduate design experience. To advance these projects toward commercialization and further promote innovative team-based learning, a Master of Engineering (MEng) in Design and Commercialization was recently launched. The MEng facilitates teams of graduate students in engineering, life sciences, and business who engage in innovation-commercialization (IC) projects and coursework that take innovative ideas through research and development (R&D) to create marketable devices. The activities are structured with students working together as a “virtual company,” with targeted outcomes of commercialization (license agreements and new start-ups), competitive job placement, and/or career advancement.

Segmental bone loss remains a challenging clinical problem. A frequent mitigating factor is inadequate blood supply. Small molecules that activate the hypoxia-inducible factor pathway can be used to stimulate angiogenesis. We investigated an approach to promote healing using angiogenic and osteogenic compounds in combination with a biodegradable, weightbearing scaffold.Adult rats underwent removal of a 5-mm segment of femur stabilized by a cylindrical biodegradable implant and intramedullary fixation. Treatment groups included 1) saline (negative control); 2) desferrioxamine (DFO, a hypoxia-inducible factor activator; 3) low-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) (5 μg); 4) DFO and low-dose rhBMP-2 (5 μg); or 5) rh-BMP-2 (10 μg). Angiography was used to evaluate vascularity. Bone healing was assessed by radiographs, microcomputed tomography, histology, and biomechanical testing.Increased vascularity was seen at 6 weeks in the DFO treatment group. There appeared to be increased bone bridging as assessed by radiographic scores and microcomputed tomography in the BMP groups, although the quantification of bone volume did not show statistically significant differences. Biomechanical testing revealed improved stiffness in the treatment groups.DFO improved angiogenesis and stiffness of bone healing in segmental defects. BMP improved radiographic scores and stiffness. Use of angiogenic compounds in segmental bone loss is promising.Activation of the hypoxia-inducible factor pathway may prove useful for bone defects, particularly where impaired blood supply exists.The low-cost approach could be useful in segmental bone defects clinically.

The cement-bone interface plays an important role in load transfer between cemented implant systems and adjacent bone, but little is known about the micromechanical behavior of this interface following in vivo service. Small samples of postmortem-retrieved cement-bone specimens from cemented total hip replacements were prepared and mechanically loaded to determine the response to tensile and compressive loading. The morphology of the cement-bone interface was quantified using a CT-based stereology approach. Laboratory-prepared specimens were used to represent immediate postoperative conditions for comparison. The stiffness and strength of the cement-bone interface from postmortem retrievals was much lower than that measured from laboratory-prepared specimens. The cement-bone interfaces from postmortem retrievals were very compliant (under tension and compression) and had a very low tensile strength (0.21 +/- 0.32 MPa). A linear regression model, including interface contact fraction and intersection fraction between cement and bone, could explain 71% (p < 0.0001) of the variability in experimental response. Bony remodeling following an arthroplasty procedure may contribute to reduced contact between cement and bone, resulting in weaker, more compliant interfaces.

The use of highly cross-linked ultra-high molecular weight polyethylene in total hip arthroplasty has become a popular alternative to the use of conventional polyethylene. Evaluations with use of hip simulator tests1-4 and clinical evaluations of total hip replacements5-10 have independently shown that polyethylene materials processed with gamma irradiation followed by melting or annealing have extremely low wear rates. However, it also has been demonstrated that such cross-linking processes may reduce the fracture toughness and resistance to fatigue crack propagation of polyethylene11-16. Bradford et al.14 found that retrieved cross-linked polyethylene acetabular liners exhibited surface cracking that had not been predicted by in vitro hip simulator studies. Tower et al.17 observed fatigue failure at the superior aspect of the rim of four retrieved highly cross-linked acetabular bearings. They concluded that the factors contributing to these failures included thin polyethylene at the cup rim, a relatively vertical cup alignment, and compromised material properties of the cross-linked polyethylene in comparison with conventional polyethylene. In the current case report, we describe the failure of a highly cross-linked polyethylene acetabular liner less than three years after implantation. We believe that the mechanisms of failure were fracture of the cross-linked polyethylene where it was thin along the locking groove and abnormal loading of the cup because of improper seating of the liner in the shell at the time of the original procedure. This study was conducted with institutional review board approval and in compliance with HIPAA (Health Insurance Portability and Accountability Act) requirements at our institution. A seventy-four-year-old woman underwent a primary right total hip replacement through a posterior minimally invasive approach. The femoral component was a VerSys Advocate cemented stem (Zimmer, Warsaw, Indiana) with a satin surface finish, a 34-mm neck length, and a …

Summary: Purpose: In some patients with temporal lobe epilepsy, histopathological evaluation of resected brain tissue after surgical treatment may reveal several features indicative of discrete cortical malformations. We sought to determine whether these histopathological features were accompanied by hippocampal changes detectable preoperatively by proton magnetic resonance (MR) spectroscopy and to evaluate their relationship with postoperative outcome. Methods: In 25 consecutive temporal lobe epilepsy patients who were scheduled for surgical treatment, MR spectroscopy was performed, and resected brain tissue was analyzed histopathologically for the presence of discrete cortical malformations (e.g., microdysgenesis). Outcome was assessed in all patients with an average postoperative period of 26 months. Results: In 13 patients, we found subtle, histopathologically detectable signs of cortical malformation: 6 of them with concomitant hippocampal sclerosis (dual pathology) and 7 without. The latter subgroup had a worse surgical outcome and showed enhanced bilateral and/or contralateral pathological changes in the hippocampal formation when investigated by MR spectroscopy. Conclusions: These data suggest that by showing contralaterally or bilaterally abnormal spectra, MR spectroscopy might be able to indicate pathological changes in subtle developmental disorders that are possibly more widespread over the brain. This observation may improve noninvasive diagnosis in presurgical evaluation and the neurobiological understanding of cortical malformations in pharmacoresistant temporal lobe epilepsy.

Long fiber thermoplastic (LFT) composite/metal laminate (LML) is a hybrid composite consisting of alternate layers of metals such as aluminum and an LFT composite, which combines advantages from both the constituents. The LFT/Al laminates (LMLs) were processed by compression molding and were characterized for their Young’s modulus, mechanical strength, and low-velocity impact (LVI) properties. The average values of specific elastic modulus and specific tensile strength were approximately 20 GPa/(gcm−3) and 108.5 MPa/(gcm−3), respectively. Failure mechanisms included delamination between LFT composite and Al, fiber fracture and pullout in LFT composite, and shear fracture of aluminum and LFT composite layers. Rule-of-mixtures (ROM) predictions of laminate properties in tension compared well with the experimental values. Specific perforation energy of the laminates determined by LVI tests was 7.58 J/(kgm−2), which is significantly greater than that of the LFT composite alone, 1.72 J/(kgm−2). Overall, the LML showed significant improvement in the properties as compared to the LFT composite.

The hypoxia-inducible factor-1α (HIF-1α) pathway is the central regulator of adaptive responses to low oxygen availability and is required for normal skeletal development. Here, we demonstrate that the HIF-1α pathway is activated during bone repair and can be manipulated genetically and pharmacologically to improve skeletal healing. Mice lacking pVHL in osteoblasts with constitutive HIF-1α activation in osteoblasts had markedly increased vascularity and produced more bone in response to distraction osteogenesis, whereas mice lacking HIF-1 α in osteoblasts had impaired angiogenesis and bone healing. The increased vascularity and bone regeneration in the pVHL mutants were VEGF dependent and eliminated by concomitant administration of VEGF receptor antibodies. Small-molecule inhibitors of HIF prolyl hydroxylation stabilized HIF/VEGF production and increased angiogenesis in vitro . One of these molecules (DFO) administered in vivo into the distraction gap increased angiogenesis and markedly improved bone regeneration. These results identify the HIF-1α pathway as a critical mediator of neoangiogenesis required for skeletal regeneration and suggest the application of HIF activators as therapies to improve bone healing.

Background Some loss of joint prostheses has been attributed to osteolytic phenomena leading to loosening and associated with debris from wear of polyethylene articulating against metal alloys. Reduced polyethylene wear has been reported with ceramics serving as an alternative counterface.

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines of treatment in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on locally advanced disease.

We report on fabrication of nanoimprint stamps for fabrication of two dimensional photonic crystals in visible range of spectra. Nanoimprint stamps made of silicon and/or nickel were successfully fabricated using electron beam lithography and advanced dry etching techniques. The quality of the stamps was evaluated using scanning electron microscopy. The fabricated stamps were also evaluated by imprinting them into suitable polymer materials.

Although mortality of lung cancer in men among the countries of the European Union is steadily decreasing, there is still an increasing mortality among women, and as a consequence the overall rate of lung cancer-related deaths has not been declining in Europe [1, 2]. Thus, the development of optimized treatment approaches in lung cancer patients remains an urgent issue. Today, non-small-cell lung cancer (NSCLC) histopathologies represent the vast majority, representing >85% of all lung cancer patients [3]. Stage III NSCLC, the locally advanced tumor stage, has offered the best chances for possible therapeutic innovations and improvements by the introduction of interdisciplinary, combined modality treatment strategies [4, 5]. With systemic relapses being a major problem in this patient subgroup, combination chemotherapy has emerged as an integral part of the overall treatment management [6, 7]. Combinations of radiotherapy and platinum-based chemotherapy have consequently been proposed as standard of care for the vast majority of these patients in stage III [5, 7, 8]. Surgery plays a generally accepted role in only a small group of patients with minimal or operable (‘surgical’) stage III disease [6, 8–10]. In 2000, we reviewed the literature for a comprehensive overview on combined modality treatment of NSCLC [11]. In the following paper, we will give a short update on important new developments since the year 2000 in multidisciplinary treatment approaches, including both combination chemotherapy and radiotherapy. Special focus has been on newer drug combinations in this setting, innovations in radiotherapy application and concurrent treatment protocols. New findings dealing with the overall role of surgery in this setting will be critically discussed.

The pervasive impact of historical land use is often underappreciated in the management and restoration of conservation areas and natural resources. We used historical and ecological approaches to determine the relative influences of past land use, fire, and site conditions on woodland vegetation patterns in Cape Cod National Seashore (CACO), the largest protected coastal landscape and area of sand-plain vegetation in New England. Coastal sand plains are the focus of intense conservation activity because they support uncommon plant and animal assemblages that are dynamic as a result of past disturbance and ongoing human impacts. CACO was predominantly wooded prior to extensive land clearance for historical ag- riculture. Historical maps and modern soil profiles indicate that by the mid-19th century, -44% of the area supporting sand-plain woodlands in CACO was plowed for crops or pasture, 42% was logged repeatedly but never cleared, and 14% was open and subjected to diverse uses. Relationships between modern vegetation and 19th-century land use are striking and largely independent of site conditions. Continuously wooded areas support pine-oak woodlands with abundant ericaceous shrubs, whereas previously plowed sites have less canopy oak, more pine, few ericaceous shrubs, and a distinct understory including the grass Deschampsia flexuosa and the shade-intolerant shrub Arctostaphylos uva-ursi. Current composition and historical sources suggest that past agriculture generated extensive heathland and grassland habitats, much of which has subsequently reforested. In contrast to many interpretations and management guidelines, the persistent influence of fire is prin- cipally on the canopy composition and structure of former woodlots. The results highlight a need (1) to integrate an understanding of past land use into ecological models underlying the management of biological reserves; and (2) to consider the use of management ap- proaches that mimic past agricultural practices in order to maintain and restore important sand-plain habitats.

The photodissociation of Au3 is studied by time-resolved photoelectron spectroscopy using femtosecond laser pulses. The spectra show the time evolution of the electronic structure after photoabsorption. Absorption of a "pump" photon results in the formation of a metastable activated complex (Au3)*, which decays by dissociation into AuT + Au2 and, less favorably, into Au2 + Au 1. Photoelectron spectra recorded with the "probe" laser pulse at increasing delay time first show the spectrum of the intact Au3, then that of the activated complex (Au3)* and, finally, the spectra of the two charged dissociation products AuT and Au2. The lifetime of (Au~)* decreases dramatically with increasing energy of the "pump" photon. © 1998 Elsevier Science B.V.

The use of linear and second order stress extrapolation to obtain K I and K II in two-dimensional finite element models of a thick plate containing an edge crack was examined. Three loading cases were studied, including classical Mode I and Mode II problems and a problem of tribological contact. Linear extrapolation was observed to yield accurate predictions of K I in cases of dominant Mode I loading. In Mode II situations, notably where the crack faces experienced compressive normal stresses, second order extrapolation was observed to improve estimates of K II .

To evaluate properties of bone quantity/quality using young non-obese Type 1 (T1D)-diabetic (NOD) prone and syngenic non-diabetic (NOD.scid) mice.Quantitative bone assessment of tibia was conducted using dual-energy X-ray absorptiometry (DXA) for the evaluation of body mass, bone mineral content, body fat mass and lean mass. Qualitative assessment was accomplished by three-point breakage for assessment of force to failure and micro-computed tomography for evaluation of trabecular and cortical properties of bone. In addition, fasting blood was evaluated prior to sacrifice at week eleven and fifteen to evaluate and compare glucose homeostasis between the strains of mice.Our findings support a perturbation in the relationship between bone quantity, quality, and subsequently, the association between structure and strength. There were no differences in DXA-assessed body composition (body fat, % fat mass and lean mass) and bone composition (bone mineral content and bone mineral density) between strains. However, relative to NOD.scid, NOD mice had lower trabecular bone volume, relative trabecular bone volume, trabecular number and trabecular total material density (P0.05). Conversely, NOD mice had greater cortical total mean volume (P0.05). General linear models analysis adjusted for body weight revealed a significant contribution of T1D to bone health as early as 5 wk.It is well-established that diabetes is a significant risk factor for increased fractures, although the underlying mechanisms are not fully understood. Investigation of bone parameters encompassing strength and structure early in the life course will facilitate the elucidation of the pathogenesis of impaired bone integrity.

The effects of different surface treatments, including ex-situ H2 and H2+O2 plasma exposure, chromic acid treatment and in-situ vacuum annealing at elevated temperatures, on the electronic properties, particularly the electron affinity of microwave plasma-grown polycrystalline diamond films, were investigated using UV photo-electron spectroscopy (UPS) and X-ray photo-electron spectroscopy (XPS). H2 and H2 + O2 plasma exposure results in a negative electron affinity (NEA) for all diamond films, independent of morphology, thickness or phase purity. An additional peak in the region of low kinetic energies of the UPS spectra correlates with plasma-generated defects that are removed by in-situ vacuum annealing for several minutes at 700 °C. NEA is not affected by this annealing procedure. Oxidation of the diamond surface by hot chromic acid results in a positive electron affinity (PEA) that correlates with a pronounced increase in film surface resistivity and complete suppression of electron emission. NEA alone is not sufficient to ensure good electron emission properties.

It has been kindly notified to us by Giovanni De Ninno (Sincrotrone Trieste, Italy) that our statement in the abstract (‘‘Currently, this setup is the only source worldwide producing coherent fs-light pulses with variable polarization in the vacuum ultraviolet.’’) is incorrect. The Elettra storage ring free-electron laser has achieved coherent harmonic generation (CHG) in circular polarization at 133 nm [1]. CHG at 87 nm has later also been obtained [2]. The main conclusion from our article is valid in the sense that this is, to date, the shortest published wavelength of helical coherent radiation, here achieved by CHG utilizing an APPLE II undulator in helical mode (66 nm, the 4th harmonic of a 263 nm seed laser).