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The aim of this study was to identify items that healthcare providers and/or patients consider important to include in a questionnaire for clinical trials and cohort studies in shoulder instability research. This could serve as a basis to develop a core outcome set for shoulder instability research.

This study explores the news framing of A.I., China, and the U.S.A. in two mainstream news outlets: The Washington Postand The South China Morning Post. The main objective is to analyse how both, as parts of different discourse cultures, portray the competition for leadership in A.I. innovation between China and the U.S.A. The study takes a critical look at the media discourse on the ‘new arms race’ and what role the news play in localising global technology trends. The empirical part makes use of a combination of manual and automated content analyses. To this end, a dictionary approach that utilises Names Entity Recognition was applied to a large volume of news texts (N= 3.055) to identify recurring news frames. The findings show similarities in the perception of A.I.’s potentials and versatility but also clear cultural differences in how risks and conflicts are portrayed in both outlets. Although the Washington Postappears more critical about A.I., the South China Morning Postframes the technology as a driver of economic growth and global influence. The discussion offers a starting point for theorising the relationship between mediatisation, tech trends, cultural differences, and international politics.

Jerry Hendrix is not the first to disparage the Navy's and the Congress's decision to continue building and improving the large aircraft carrier. Critics have disparaged this decision all the [...]

The extreme poverty line is the most commonly used benchmark for poverty, set at US$ 1.90 by the World Bank. Another benchmark, based on the Anker living wage methodology, is the remuneration received for a standard work week necessary for a worker to meet his/her family’s basic needs in a particular place. The living wage concept has been used extensively to address incomes of plantation workers producing agricultural commodities for international markets. More recently intense discussion has emerged concerning the ‘living income’ of smallholder farmers who produce commodities for international supply chains on their own land. In this article we propose a simple method that can be used in all types of development projects to benchmark a rural ‘living income’. We launch the Living Income Methodology, as adapted from the Living Wage Methodology, to estimate the living income for rural households. In any given location this requires about one week of fieldwork. We express it per adult equivalent per day (AE/day) and data collection is focused on rural households and their immediate surroundings. Our three case studies showed that in 2017 in Lushoto District, rural Tanzania, the living income was US$ PPP 4.04/AE/day, in Isingiro District, rural Uganda, 3.82 and in Sidama Zone, rural Ethiopia, 3.60. In all cases, the extreme poverty line of US$ PPP 1.90 per capita per day is insufficient to meet the basic human rights for a decent living in low-income countries. The Living Income Methodology provides a transparent local benchmark that can be used to assess development opportunities of rural households, by employers in rural areas, including farmers hiring in labour, while respecting basic human rights on a decent living. It can be used to reflect on progress of rural households in low-income countries on their aspired path out of poverty. It further provides a meaningful benchmark to measure progress on Sustainable Development Goal 1, eliminating poverty, and 2, zero hunger and sustainable food systems, allowing for consideration of the local context.

Or is it 'all in how you raise them'? Nature vs. nurture and raising a well-adjusted dog. Dr. Ilana Reisner wanted her new Australian Shepherd puppy, Asher, to have a [...]

Sometimes something goes wrong in dogs' heads, and they become afraid of things they shouldn't be. Men with beards. Other dogs. Being alone. Sometimes their fear makes them anxious. Sometimes [...]

Basic research (cross-sectional).

To support the ongoing adaptation and implementation of an Emergency Department (ED)-based clinical decision support (CDS) tool to prevent future falls, we interviewed older adults (n= 15) during their ED stay. We elicited their feedback on the written and verbal content of the existing CDS, feelings about the automated risk-screening aspect of the CDS and asked them to identify barriers that would prevent them from following up with the Falls Clinic to which the CDS supports referral placements. Our findings suggest that the older adults interviewed saw the CDS simply as another tool that they trusted their ED physician/APP to interact with. The identified barriers to follow-up reflect common access barriers such as transportation availability and clinic distance. For CDS tools to impact real-life patient outcomes, we must consider patient’s needs and limitations and appropriately match interventions.

Objective: Hypertrophic obstructive cardiomyopathy (HOCM) develops in at least 1 out of 715 young adults. Patients who are refractory to medical therapy qualify for septal myectomy. Due to anatomy, serious complications such as ventricular septal defect and heart block may occur. Establishing cardiovascular magnetic resonance (CMR)–based 3-dimensional (3D) models as part of preoperative planning and training has the potential to decrease procedure-related complications and improve results.Methods: CMR images were used to segment cardiac structures. Left ventricular wall thickness was calculated and projected on top of the in silico model. A 3D model was printed with a red layer indicating a wall thickness exceeding 15 mm and used for preoperative resection planning and patient counseling. To provide preoperative patient-specific in situ simulation, the planned resection volume was replaced with silicone in a second model. For perioperative quality control, resected silicone was compared with resected myocardial tissue. The impact of the models was evaluated descriptively through consultation of both the cardiothoracic surgeon and patients and through patient outcomes.Results: Three-dimensional in silico and 3D-printed heart models of 5 patients were established preoperatively. Since the introduction of the models in October 2020, the surgeon feels better prepared, more confident, and less difficulty with making decisions. In addition, patients feel better informed preoperatively.Conclusions: Using 3D heart models optimized preoperative planning and training, intraoperative quality control, and patient consultation. Reduction of procedure-related complications and clinical outcome should be studied in larger cohorts.

•Studies comparing RP to RT show conflicting results due to methodological flaws.•Flaws: nonrandomized, selection bias, unmeasured confounding, physician-reported outcomes.•This review appraises RCTs and summarizes ongoing trials comparing RP to RT.•10-year cancer-free and survival rates are equal for RP and RT.•RP: more urine leakage, ED. RT: more bowel issues, like blood in stools, fecal leakage.

Sacroiliac joint fusion (SIJF) is a minimally invasive treatment for sacroiliac (SI) dysfunction. It involves placing implants through the SI joint under fluoroscopic guidance, requiring precise implant positioning to avoid nerve injury. Preoperative virtual surgical planning (VSP) aids in optimal positioning, but replicating it accurately in the operating room is challenging.

Complete resection of tumor lesions in advanced stage ovarian cancer patients is of utmost importance, since the extent of residual disease after surgery strongly affects survival. Intraoperative imaging may be useful to improve surgery in these patients. Farletuzumab is a humanized IgG1 antibody that specifically recognizes the folate receptor alpha (FRα). Labeled with a radiolabel and a fluorescent dye, farletuzumab may be used for the intraoperative detection of ovarian cancer lesions. The current aim is to demonstrate the feasibility of FRα-targeted dual-modality imaging using 111In-farletuzumab-IRDye800CW in an intraperitoneal ovarian cancer model. Biodistribution studies were performed 3 days after injection of 3, 10, 30, or 100 μg of 111In-farletuzumab-IRDye800CW in mice with subcutaneous IGROV-1 tumors (5 mice per group). In mice with intraperitoneal IGROV-1 tumors the nonspecific uptake of 111In-farletuzumab-IRDye800CW was determined by coinjecting an excess of unlabeled farletuzumab. MicroSPECT/CT and fluorescence imaging were performed 3 days after injection of 10 μg of 111In-farletuzumab-IRDye800CW. FRα expression in tumors was determined immunohistochemically. Optimal tumor-to-blood-ratios (3.4–3.7) were obtained at protein doses up to 30 μg. Multiple intra-abdominal tumor lesions were clearly visualized by microSPECT/CT, while uptake in normal tissues was limited. Fluorescence imaging was used to visualize and guide resection of superficial tumors. Coinjection of an excess of unlabeled farletuzumab significantly decreased tumor uptake of 111In-farletuzumab-IRDye800CW (69.4 ± 27.6 versus 18.3 ± 2.2% ID/g, p< 0.05). Immunohistochemical analyses demonstrated that the radioactive and fluorescent signal corresponded with FRα-expressing tumor lesions. FRα-targeted SPECT/fluorescence imaging using 111In-farletuzumab-IRDye800CW can be used to detect ovarian cancer in vivoand could be a valuable tool for enhanced intraoperative tumor visualization in patients with intraperitoneal metastases of ovarian cancer.

Het doel van deze studie is de veiligheid en toepasbaarheid van carbonzuuranhydrase IX (CAIX)-targeted dual-modality imagingbij een heldercellig niercelcarcinoom (ccRCC) te onderzoeken. Zeven dagen voor de partiële of totale nefrectomie werden patiënten geïnjecteerd met 100MBq 111In-girentuximab-IRDye800CW (5–50 mg). Op dag vier werd een SPECT/CT-scan gemaakt. Op dag zeven was de operatie waarbij een gamma probe en een fluorescentiecamera gebruikt werden voor intraoperatieve tumordetectie. 15 patiënten werden geïncludeerd: 12 met CAIX-positieve en 3 met CAIX-negatieve tumoren. Studiegerelateerde ernstige bijwerkingen werden niet gezien. Alle ccRCC’s waren preoperatief zichtbaar op de SPECT/CT-scan en konden intraoperatief gelokaliseerd worden met de gamma probe (tumor: normale nierratio 2,5 ± 0,8), terwijl de gemiddelde tumor: normale nierratio 1,0 ± 0,1 was in CAIX-negatieve tumoren. Alle ccRCC’s waren hyperfluorescent en fluorescentie-imaging toonde één positief snijvlak. Conclusie:Tumor-targeted dual-modality imaging met 111In-girentuximab-IRDye800CW is veilig en kan worden gebruikt voor de intraoperatieve detectie van ccRCC. The aim of this study is to show the feasibility and safety of CAIX-targeted dual-modality imaging in ccRCC. Seven days before partial or radical nephrectomy, patients were injected with 100MBq 111In-girentuximab-IRDye800CW (5–50 mg). After 4 days a SPECT/CT was obtained. After 7 days surgery was performed with the use of intraoperative gamma probe detection and fluorescence imaging. Fifteen patients were included, of which three had a CAIX-negative tumor. No study-related serious adverse events were observed. All ccRCC were visualized on the SPECT/CT scan and localized by intraoperative gamma probe detection (mean T:N ratio 2.5 ± 0.8), while mean T:N ratios were 1.0 ± 0.1 in CAIX-negative tumors. All ccRCC were hyperfluorescent and in one patient fluorescence imaging revealed a positive surgical margin. Conclusion: Tumor-targeted dual-modality imaging using 111In-girentuximab-IRDye800CW is safe and can be used for intraoperative ccRCC detection.

Can a highly stressful environment during pregnancy affect how puppies turn out? Imagine this: A young dog goes stray and lives on urban streets for two months, in almost constant [...]

AimsThe Ponseti method is an effective evidence-based treatment for clubfoot. It uses gentle manipulation to adjust the position of the foot in serial treatments towards a more physiological position. Casting is used to hold the newly achieved position. At first, the foot resists the new position imposed by the plaster cast, pressing against the cast, but over time the tissues are expected to adapt to the new position and the force decreases. The aim of this study was to test this hypothesis by measuring the forces between a clubfoot and the cast during treatment with the Ponseti method.Patients and MethodsForce measurements were made during the treatment of ten idiopathic clubfeet. The mean age of the patients was seven days (2 to 30); there were nine boys and one girl. Force data were collected for several weeks at the location of the first metatarsal and the talar neck to determine the adaptation rate of the clubfoot.ResultsIn all measurements, the force decreased over time. The median (interquartile range) half-life time was determined to be at 26 minutes (20 to 53) for the first metatarsal and 22 minutes (9 to 56) for the talar neck, suggesting that the tissues of the clubfoot adapt to the new position within several hours.ConclusionThis is the first study to provide objective force data that support the hypothesis of adaptation of the idiopathic clubfoot to the new position imposed by the cast. We showed that the expected decrease in corrective force over time does indeed exist and adaptation occurs after a relatively short period of time. The rapid reduction in the forces acting on the foot during treatment with the Ponseti method may allow significant reductions in the interval between treatments compared with the generally accepted period of one week.

Historically, patients with chronic mesenteric ischemia (CMI) are underweight with a low body mass index (BMI). However, with the recent obesity epidemic many of these patients now are overweight with a high BMI. We evaluated the impact of BMI on outcomes after mesenteric revascularization for CMI.

This research was conducted to find out whether demographics such as age, gender and working within different departments have an influence on the motivational factors of workers in the luxury hospitality industry. Questionnaires were filled out by 39 employees from the luxury five-star XYZ Hotel situated in an Italian city. In this questionnaire all the participants had to rank the motivational factors on a Likert scale. This study found, by using the ANOVA statistical test, that there was only a relation between age, the opportunity for advancement and sympathetic personal help. This study also found that appreciation for a job well done was the most important motivational factor, whereas the opportunity for advancement was ranked as least important. Moreover, each age group, gender and department is motivated by different factors. It was notable that previous research showed similarities with the current research. However, there were also various differences noticed. XYZ Hotel can use this research to get a better insight into the motivational factors from its workers, and better motivation strategies can be developed. Moreover, this research can be duplicated within other segments of the hospitality industry.

Novel approach on treatment and imaging of a potential limb-threatening vascular overuse shoulder injury in elite volleyball.We report on a 34-yr-old male elite volleyball player with symptomatic emboli in the spiking hand from a partially thrombosed aneurysm of the posterior circumflex humeral artery (PCHA) in his dominant shoulder. At initial diagnosis and follow-up, a combination of time-resolved and high-resolution steady state contrast-enhanced magnetic resonance angiography (CE-MRA) enabled detailed visualization of: (1) emboli that were not detectable by vascular ultrasound; and (2) the PCHA aneurysm, including compression during abduction and external rotation (ABER provocation). At 15-month follow-up, including forced cessation of volleyball activities over the preceding 9 months, the PCHA aneurysm remained unchanged. Central filling defects in the palmar arch and digital arteries resolved over time and affected arterial vessel segments showed postthrombotic changes. Digital blood pressure values improved substantially and almost normalized during follow-up. In conclusion, this case report is the first to show promising results of nonoperative management for a vascular shoulder overuse injury in a professional volleyball player as an alternative to invasive therapeutic options.

In a case of first impression, a tribunal at the International Centre for Settlement of Investment Disputes (ICSID) rejected Claimants' novel legal argument that the Most Favoured Nation (MFN) clause in Article II of the World Trade Organisation's General Agreement on Trade in Services (GATS) enabled Menzies Middle East and Africa S.A. (MMEA) to access the offers to arbitrate under the Senegal–Netherlands and the Senegal–United Kingdom bilateral investment treaties (BITs).

The article focuses on the Financial Accounting Standards Board's (FASB) pronouncement on foreign exchange translation and its effects on corporate finance in the United States. FASB Statement 8 is criticized due to the opinion of many professionals that it distorts the value of their operations and leads investors to believe highly risky ventures are being undertaken, even if they are conservative. To remedy the situation, the board needs to consider how best to describe the more specific aspects of an international company's financial situation.

Sonographers performing venous duplex ultrasound (VDUS) of patients with coronavirus disease 2019 (COVID-19) have an increased risk of exposure owing to their close contact with these patients for an extended period. The objective of the present study was to evaluate the efficacy of a modified COVID-19 VDUS protocol to reduce sonographer exposure to COVID-19 patients.

Prostate-specific membrane antigen positron emission tomography (PSMA PET) has been approved by the Food and Drug Administration (FDA) to identify prostate cancer in the setting of biochemical recurrence but can also identify other malignancies. 18F-PSMA PET has not been studied as a potential tool for hepatocellular carcinoma (HCC). We describe the case of a 76-year-old male with a rising prostate-specific antigen (PSA) after definitive prostate cancer treatment and no prior liver pathology who was incidentally found to have HCC on 18F-PSMA PET.

Elite overhead athletes are at risk of vascular injury due to repetitive abduction and external rotation of the dominant arm. The posterior circumflex humeral artery (PCHA) is prone to degeneration, aneurysm formation, and thrombosis in elite volleyball players and baseball pitchers. The prevalence of PCHA‐related thromboembolic complications is unknown in this population. However, the prevalence of symptoms associated with digital ischemia is 31% in elite volleyball players. A standardized noninvasive imaging tool will aid in early detection of PCHA injury, prevention of thromboembolic complications, and measurement reproducibility. A standardized vascular sonographic protocol for assessment of the proximal PCHA (SPI‐US protocol [Shoulder PCHA Pathology and Digital Ischemia–Ultrasound protocol]) is presented.

The article discusses the results of several studies involving undergraduate students that examined the effects of gender, race and changing the status quo among finalists for a job position on their chances of being hired, and measured unconscious racism and sexism in the participants.

In the article, the authors discuss issues in efforts to promote diversity in business, particularly whether women and nonwhite executives are adversely affected if they assist other women and minorities, as well as their study showing that executives promoting diversity are rated worse by bosses.

Percutaneous needle insertion procedures are commonly used for diagnostic and therapeutic purposes. Although current technology allows accurate localization of lesions, they cannot yet be precisely targeted. Lung cancer is the most common cause of cancer-related death, and early detection reduces the mortality rate. Therefore, suspicious lesions are tested for diagnosis by performing needle biopsy. In this paper, we have presented a novel computed tomography (CT)-compatible needle insertion device (NID). The NID is used to steer a flexible needle ($${\phi }0.55\,\hbox {mm}$$ ϕ0.55mm ) with a bevel at the tip in biological tissue. CT images and an electromagnetic (EM) tracking system are used in two separate scenarios to track the needle tip in three-dimensional space during the procedure. Our system uses a control algorithm to steer the needle through a combination of insertion and minimal number of rotations. Noise analysis of CT images has demonstrated the compatibility of the device. The results for three experimental cases (case 1: open-loop control, case 2: closed-loop control using EM tracking system and case 3: closed-loop control using CT images) are presented. Each experimental case is performed five times, and average targeting errors are $$2.86\pm 1.14$$ 2.86±1.14 , $$1.11\pm 0.14$$ 1.11±0.14 and $$1.94\pm 0.63\,\hbox {mm}$$ 1.94±0.63mm for case 1, case 2 and case 3, respectively. The achieved results show that our device is CT-compatible and it is able to steer a bevel-tipped needle toward a target. We are able to use intermittent CT images and EM tracking data to control the needle path in a closed-loop manner. These results are promising and suggest that it is possible to accurately target the lesions in real clinical procedures in the future.

The Jan. 31 issue of the San Diego Business Journal contains an article in which Paul Nieto, a developer and the vice chairman of the San Diego County Regional Airport [...]

This paper presents the stress–strain response and general lifetime damage modelling of glass fibre reinforced epoxy (GRE) composite pipes subjected to multi-ratios stress loadings at room temperature (RT). This particular modelling work was developed to predict the non-linear stress–strain response caused by the fatigue static and cyclic loading in the multiaxial ultimate elastic wall stress (UEWS) tests by considering the effects of matrix cracking within the laminates. Although the UEWS procedure is not a standard protocol used for qualification of GRE pipes, it appears to offer an option to existing procedures delineated in ASTM D2992. The ply properties initially expressed as a function of crack density was computed as a function of increasing stress and strain using shear lag approximation. In general lifetime damage model, the effects of stress developed in each ply from ultimate elastic wall stress (UEWS) test were expressed in a single quadratic term of axial and hoop stress. The term then solved to produce limits with respect to axial and hoop stress, which represented in a graphical form of failure envelope. The predictions from both models are found to be in good agreement with the data from the multiaxial UEWS tests of ±55° filament wound GRE pipes. These models thus enable for the long term performance prediction of the pipes under combined loadings.

This paper presents the modelling of a general lifetime performance for glass fibre reinforced epoxy (GRE) composite pipes similar to the well-known Tsai-Hill interactive failure criterion. Tsai Hill criterion is based on the Von Misses distortional energy criterion which was modified to satisfy the orthotropic nature of GRE composite pipes. The effects of stress developed in each ply from ultimate elastic wall stress (UEWS) test were expressed in a single quadratic term of axial and hoop stress through laminate theory. The term then solved to produce limits with respect to axial and hoop stress, which represented in a graphical form of failure envelope. The modelled envelop shows a good agreement with experimental data from the multiaxial UEWS test of ±55° GRE composite pipes. This indicates that such model can be used to predict the long-term performance of GRE pipes under combine loadings.

This paper presents an experimental investigation into the influence of winding angles in multiaxial ultimate elastic wall stress (UEWS) tests of glass-fibre reinforced epoxy (GRE) composite pipes. Currently, UEWS test is one of the alternative methods used to the 1000-hour test procedure detailed in ASTM D2992 for the detection of manufacturing changes and reconfirmation of the design basis of composite pipes. A stress-strain response was obtained for each winding angle and the results then compared with those computed through conventional laminate theory. Experimental data showed that the UEWS point varies for each winding angle, and the difference becomes even more pronounced, especially when the angles deviated from the ideal ±55°. It is also concluded that the UEWS stresses, which represent the onset of non-linearity were very much dependent on the transverse and shear stress responses, and these values were found to be consistent with the predicted values from the commonly used Tsai Wu failure criterion.

The article presents steps in completing a merger while maintaining physician autonomy in an age of consolidation in the U.S. It states that surgeons still desire the autonomy of private practice despite the promises on healthcare reform and reimbursement changes. It further suggests to make critical investments, improve business management and to identify potential business partners.

Procedures for qualifying fibreglass pipes are discussed here in relation to industry needs. The ultimate elastic wall stress (UEWS) test appears to provide an efficient means of rating pressure pipe, and indeed vessels, for the case where weepage failure occurs resulting from the accumulation of matrix cracks. The principle behind the UEWS test is to identify, from the pressure–strain response, a pressure level below which damage growth is either negligible or at least sufficiently low to avoid failure within the design life. The version of the UEWS test most often used involves the application of groups of 10 one‐minute pressure cycles at increasing pressure values, recording the hoop or axial strain. The onset of non‐linearity in the pressure–strain relationship can be accurately determined and enables a safe long term pressure level to be identified. The UEWS test appears to provide a desirable alternative to the currently used procedure laid down in ISO 14692, which involves an expensive series of long term constant pressure tests, as described in ASTM 2992, running for a period in excess of 10 000 h. It is shown here that the UEWS test reflects the cyclic fatigue behaviour of fibreglass pipe, but further work on the relationship between cyclic and static behaviour would be desirable. It has been shown that a Miner's law approach is effective in modelling damage due to combined static and cyclic effects, and that damage can be directly related to matrix crack growth. This approach could form the basis of a future procedure for describing lifetime behaviour of glass reinforced epoxy pipes under any required combination of static, fatigue, hydrostatic and non‐hydrostatic (multiaxial) loading.

The human immunological mechanisms defining the clinical outcome of SARS-CoV-2 infection remain elusive. This knowledge gap is mostly driven by the lack of appropriate experimental platforms recapitulating human immune responses in a controlled human lung environment. Here, we report a mouse model (i.e., HNFL mice) co-engrafted with human fetal lung xenografts (fLX) and a myeloid-enhanced human immune system to identify cellular and molecular correlates of lung protection during SARS-CoV-2 infection. Unlike mice solely engrafted with human fLX, HNFL mice are protected against infection, severe inflammation, and histopathological phenotypes. Lung tissue protection from infection and severe histopathology associates with macrophage infiltration and differentiation and the upregulation of a macrophage-enriched signature composed of 11 specific genes mainly associated with the type I interferon signaling pathway. Our work highlights the HNFL model as a transformative platform to investigate, in controlled experimental settings, human myeloid immune mechanisms governing lung tissue protection during SARS-CoV-2 infection.

Metabolism is recognized as an important driver of cancer progression and other complex diseases, but global metabolite profiling remains a challenge. Protein expression profiling is often a poor proxy since existing pathway enrichment models provide an incomplete mapping between the proteome and metabolism. To overcome these gaps, we introduce multiomic metabolic enrichment network analysis (MOMENTA), an integrative multiomic data analysis framework for more accurately deducing metabolic pathway changes from proteomics data alone in a gene set analysis context by leveraging protein interaction networks to extend annotated metabolic models. We apply MOMENTA to proteomic data from diverse cancer cell lines and human tumors to demonstrate its utility at revealing variation in metabolic pathway activity across cancer types, which we verify using independent metabolomics measurements. The novel metabolic networks we uncover in breast cancer and other tumors are linked to clinical outcomes, underscoring the pathophysiological relevance of the findings.

Modelling and simulation are important analysis and presynthesis tools in engineering. Flat end milling processes are accurately modelled using Artificial Neural Networks (ANNs) and real experimentation. ANNs are expensive techniques, as they require enormous experiments over ranges of input parameters. This is crucial to any realistic modelling. Orthogonal Arrays (OAs) and Design of Experiments (DOEs) are used to remedy the modelling expense using Neural Networks (NNs). The high cost of ANNs is offset by combining DOEs with ANNs to model part of the domain instead of the full domain. The process variables include depth of cut (a), spindle speed (n), feed rate (f) and tool diameter (d). Our interest is in measuring the dynamic variations of the cutting forces and their time behaviour. Several experimental models are developed, including two-level, three-level, four-level and five-level OA-based models. The result is a valid neural model for flat end milling over realistic domains of process parameters. [Submitted 21 February 2008; Revised 07 May 2008; Accepted 23 June 2008]

The serine/threonine kinase C-Raf is a key mediator in cellular signaling. Translocation of Raf to membranes has been proposed to be facilitated by Ras proteins in their GTP-bound state. In this study we provide evidence that both purified B- and C-Raf kinases possess lipophilic properties and associate with phospholipid membranes. In the presence of phosphatidylserine and lipid second messengers such as phosphatidic acid and ceramides these associations were very specific with affinity constants (KD) in the range of 0.5–50 nm. Raf association with liposomes was accompanied by displacement of 14-3-3 proteins and inhibition of Raf kinase activities. Interactions of Raf with cholesterol are of particular interest, since cholesterol has been shown to be involved, together with sphingomyelin and glycerophospholipids in the formation of specialized lipid microdomains called rafts. We demonstrate here that purified Raf proteins have moderate binding affinity for cholesterol. However, under conditions of lipid raft formation, Raf association with cholesterol (or rafts) increased dramatically. Since ceramides also support formation of rafts and interact with Raf we propose that Raf may be present at the plasma membrane in two distinct microdomains: in raft regions via association with cholesterol and ceramides and in non-raft regions due to interaction with phosphatidylserine and phosphatidic acid. At either location Raf kinase activity was inhibited by lipid binding in the absence or presence of Ras. Ras-Raf interactions with full-length C-Raf were studied both in solution and in phospholipid environment. Ras association with Raf was GTP dependent as previously demonstrated for C-Raf-RBD fragments. In the presence of liposomes the recruitment of C-Raf by reconstituted Ras-farnesyl was only marginal, since almost 70% of added C-Raf was bound by the lipids alone. Thus Ras-Raf binding in response to activation of Ras-coupled receptors may utilize Raf protein that is already present at the membrane.

Stiction can be a major detriment to the performance of machines that move at low velocities or attempt to position with high accuracy. The control of machines with stiction is further complicated if the machine has flexible dynamics that lead to vibration and transient deflection. Command generation schemes have recently been shown to eliminate many of the problems associated with flexible dynamics. This paper investigates the use of command generation techniques for reducing the effects of stiction, as well as vibration. It is shown that command generation allows the positioning feedback gains to be increased, thereby reducing the positioning error associated with stiction, without increasing vibration.

The treatment of posttransplant lymphoproliferative disorder (PTLD) remains empirical. We review our treatment of seven cases of PTLD consisting of five interventions 1) reduction of immunosuppression; 2) antiviral drugs; 3) interferon-; 4) gamma-globulins; and 5) anti-CD19 monoclonal antibodies.