Multimodal interventional molecular imaging of tumor margins and distant metastases by targeting αvβ3 integrin

α(v)β(3) integrin is involved in (tumor-induced) angiogenesis and is a promising candidate for the specific visualization of both primary tumors and of their distant metastases. Combination of radioactive and fluorescent imaging labels in a single multimodal, or rather hybrid, RGD-based imaging agent enables integration of pre-, intra-, and postoperative angiogenesis imaging. A hybrid imaging agent targeting the α(v)β(3) integrin--(111)In-MSAP-RGD (MSAP = multifunctional single-attachment-point reagent), which contains a targeting moiety, a pentetic acid (DTPA) chelate, and a cyanine dye--was evaluated for its potential value in combined lesion detection and interventional molecular imaging in a 4T1 mouse breast cancer model. SPECT/CT and fluorescence imaging were used to visualize the tumor in vivo. Tracer distribution was evaluated ex vivo down to the microscopic level. The properties of (111)In-MSAP-RGD were compared with those of (111)In-DTPA-RGD. Biodistribution studies revealed a prolonged retention and increased tumor accumulation of (111)In-MSAP-RGD relative to (111)In-DTPA-RGD. With (111)In-MSAP-RGD, identical features could be visualized preoperatively (SPECT/CT) and intraoperatively (fluorescence imaging). As well as the primary tumor, (111)In-MSAP-RGD also enabled detection and accurate excision of distant metastases in the head and neck region of the mice. Therefore, the hybrid RGD derivative (111)In-MSAP-RGD shows potential in preoperative planning and fluorescence-based surgical intervention.     

A magnetofluorescent nanoparticle for ex-vivo cell labeling by covalently linking the drugs protamine and Feraheme

We synthesized a nanoparticle (NP) for ex-vivo cell labeling and MRI tracking by covalently coupling the C-terminus of a rhodamine-labeled protamine (ProRho) to Feraheme (FH) in order to yield the nanoparticle denoted ProRho-FH. Since protamine can adsorb to certain charged surfaces, we confirmed a covalent interaction between ProRho and FH by heparin affinity chromatography. ProRho-FH lacks a net charge (zeta potential approximately 0) due to the combination of negative FH and positive ProRho charges. ProRho-FH was readily internalized by U87 cells and mouse mesenchymal stem cells as determined by FACS and MR relaxometry. Finally, some 4,000 stem cells were implanted in a mouse brain and imaged by MRI. Due to its lack of net surface charge, ProRho-FH relies on the internalizing properties of the surface guanidinium groups present in the arginine-rich protamine to induce NP uptake. ProRho-FH is a unique cell-labeling agent due to its synthesis using two approved drugs, magnetofluorescence, site-specific covalent attachment chemistry, and lack of surface charge.     

Learning capabilities in organizational networks: case studies of six construction projects

Organizational learning is a key mechanism for adapting to changes in the organization's environment, sharing know‐how and experiences, and for providing innovative solutions. Practices of organization learning are examined in six Swedish construction projects. In the Swedish construction industry, organization learning practices are in many cases underdeveloped and therefore mechanisms for sharing know‐how, information, and experiences remain an organizational capability not fully exploited. Findings suggest that construction projects are primarily relying on informal and personal contacts rather than more formal reporting and computer‐based management control systems. The implications for management in the industry are that new arenas wherein various professional groups can share knowledge and information would be beneficial for construction projects in terms of enabling for joint learning and a better use of the intellectual resources employed the project.     

ST segment elevation induced by class IC antiarrhythmic agents: underlying electrophysiologic mechanisms and insights into drug-induced proarrhythmia

Large-scale analyses of causes of neonatal deaths are usually based on death-certificate information. A new computer-based method has been introduced to define the cause of stillbirths and neonatal deaths in large amounts of material and to classify them according to two different models [Wigglesworth and Neonatal and Intrauterine death Classification according to (a)Etiology (NICE)]. The method is based on a combination of detailed information from health care registries and the death-certificate information. The present study aimed to compare these two classification models with a previously published method based solely on death certificate information [International Collaborative Effort (ICE)]. The study population comprised 2378 neonatal deaths in Sweden between 1987 and 1992. Cross-tabulation was made between the ICE classification and the other two classification models. In addition, case examples are presented in detail, exemplifying how classification errors arose. The ICE classification gives a rather low precision, notably for two important causes of death: asphyxia and immaturity. Among 328 infants dying from asphyxia according to computerized Wigglesworth classification, ICE classified 59% as asphyxia and 22% were labelled immaturity. When ICE classified the deaths as due to asphyxia, this was verified in only 50%. Among 792 infants dying from immaturity according to computerized Wigglesworth classification, 64% were classified as such by ICE. The findings cast doubts on the results of studies based exclusively on death-certificate information. Whenever possible in the analysis of neonatal deaths, death-certificate information should be supplemented with more detailed data. The computer-based method introduced here makes such analyses possible for large databases.     

Workplace factors and care seeking for low-back pain among female nursing personnel. MUSIC-Norrt?lje Study Group

Primary biliary cirrhosis (PBC) is a liver disease of unknown etiology characterized by chronic nonsuppurative destructive cholangitis (CNSDC) of intrahepatic septal and interlobular bile ducts. It is generally defined as an autoimmune disease. Characteristically, patients with PBC have a cholestatic serum hepatic profile and circulating antimitochondrial antibodies (AMA). PBC is progressive and ultimately leads to biliary cirrhosis and liver failure. It occurs at least three times more often in women than in men and it is the most common indication for liver transplantation in women around the world. There is no known cure for PBC. Despite the remarkable progress elucidating the genetics of breast cancer, and the effort placed on breast cancer education and screening methods, the mortality of breast cancer remains unacceptably high. In this essay, we describe the similarities between breast cancer and PBC and how their pathogenesis may be related. The hypothesis stated herein has evolved from reports from the early 1980s that linked an increased risk for breast cancer with PBC, and from the author's clinical experience with patients who suffer from both diseases. The association between these two diseases in the USA merits further investigation. If it is confirmed, risk factors involved in their pathogenesis will be identified.     

Vacuum Web Coating - State of the Art and Potential for Electronics

Going flexible seems to be a major trend for a variety of electronic applications such as displays, printed circuit boards, solar cells, and solid-state lighting. Driving forces, which may often include the function of "flexibility," are the potential to build units with less thickness and with less weight or the ability for very-large-area applications. Last but not least, there is the need for a remarkable reduction of production costs, which can be fulfilled by changing the production process from sheet processing to roll to roll. The first vacuum web coater was built 70 years ago, and vacuum web coating is currently used for a wide variety of applications. In the packaging industry, aluminum coating is primarily used for barrier improvement of plastic substrates. Such coatings are deposited with an evaporation process in machines of up to 4-m coating widths on rolls up to 60 000-m length and at coating speeds of more than 16 m/s. For capacitor production, thin webs with thicknesses down to the submicrometer range are vacuum-coated with aluminum, silver, or zinc layers, and uncoated stripes or patterns are also needed. Vacuum-coated web-shaped substrates can also be used for antireflective, antistatic function in the front of monitors, as window films for cars and architectural applications or as front electrodes for touch panels as a few examples. Different coating tools such as evaporation, sputtering, plasma-enhanced chemical-vapor deposition (PECVD), as well as pretreatment tools and inline layer measurement systems are available. Many of the currently available tools and processes existing in the web coating industry may become useful for upcoming electronic applications, but special demands for these new applications, such as exact area tracking, zero defects, roll-to-roll masking, and reduced substrate temperature during coating, require further development of machine design and process technology. This paper will summarize the state of the art of vacuum w     

Hybrid pharmacologic and ablative therapy: a novel and effective approach for the management of atrial fibrillation

PURPOSE: This paper presents a critical review of the literature on neurosensory disturbances associated with implant surgery. MATERIALS AND METHODS: The reviewed literature includes mainly retrospective implant studies and patients' surveys, as well as a few prospective psychophysical studies on sensory disorders following maxillofacial surgeries. RESULTS: The available data suggest that injury to the peripheral branches of the trigeminal nerve and subsequent sensory disturbances are potential complications following implant surgery. Cross-sectional studies suggest that gross tactile sensation was regained in the vast majority of patients. However, data on the spatial and temporal patterns of recovery of this and other somatic sensation such as fine touch, nociception, and temperature sense after implant surgery is still lacking. The prevalence of sensory disturbances depends on several factors: the site of implant placement, the type of surgical procedures adopted, the design of the studies, the sensitivity of the testing methods, the choice of the outcome measures, and the terminology used to describe sensory disturbances. Extreme variation in the reported prevalence of neurosensory disturbances (0% to 100%) suggest that these problems have not been adequately evaluated. CONCLUSION: Although sensory disturbances are transient in the majority of implant patients, their profound impact on the quality of life of the subjects affected and the possibility that they may persist clearly indicate that they should be identified and evaluated through prospective studies, using validated testing protocols and outcome measures.