CA19-9 as a Potential Target for Radiolabeled Antibody-Based Positron Emission Tomography of Pancreas Cancer.

Introduction. Sensitive and specific imaging of pancreas cancer are necessary for accurate diagnosis, staging, and treatment. The vast majority of pancreas cancers express the carbohydrate tumor antigen CA19-9. The goal of this study was to determine the potential to target CA19-9 with a radiolabeled anti-CA19-9 antibody for imaging pancreas cancer. Methods. CA19-9 was quantified using flow cytometry on human pancreas cancer cell lines. An intact murine anti-CA19-9 monoclonal antibody was labeled with a positron emitting radionuclide (Iodine-124) and injected into mice harboring antigen positive and negative xenografts. MicroPET/CT were performed at successive time intervals (72 hours, 96 hours, 120 hours) after injection. Radioactivity was measured in blood and tumor to provide objective confirmation of the images. Results. Antigen expression by flow cytometry revealed approximately 1.3 × 10(6) CA19-9 antigens for the positive cell line and no expression in the negative cell line. Pancreas xenograft imaging with Iodine-124-labeled anti-CA19-9 mAb demonstrated an average tumor to blood ratio of 5 and positive to negative tumor ratio of 20. Conclusion. We show in vivo targeting of our antigen positive xenograft with a radiolabeled anti-CA19-9 antibody. These data demonstrate the potential to achieve anti-CA19-9 antibody based positron emission tomography of pancreas cancer

Tunneling magnetoresistance in devices based on epitaxial NiMnSb with uniaxial anisotropy

We demonstrate tunnel magnetoresistance (TMR) junctions based on a tri layer system consisting of an epitaxial NiMnSb, aluminum oxide and CoFe tri layer. The junctions show a tunnelling magnetoresistance of Delta R/R of 8.7% at room temperature which increases to 14.7% at 4.2K. The layers show clear separate switching and a small ferromagnetic coupling. A uniaxial in plane anisotropy in the NiMnSb layer leads to different switching characteristics depending on the direction in which the magnetic field is applied, an effect which can be used for sensor applications.Comment: 8 pages, 3 figures, submitted to Appl. Phys. Let

Workspace and Kinematic Modeling and Analysis of Semi-Robotic Laparoscopic Surgery

Laparoscopic Surgery has been revolutionized by the world of Surgical Robotics. Robot-Assisted Surgeries have been proven to have many advantages over the fundamental, traditional by-hand procedures previously conducted, and still currently being done for certain operations. Robot-assisted surgery may offer benefits to patients through the use of minimally invasive techniques, which may result in reduced blood loss, reduced blood transfusion, fewer complications, reduced postoperative pain, shorter hospital stays, and reduced recovery times (Ho et al., 2011). Studies have proven that robotic surgery may lead to patients recovering faster depending on the timeframe and the type of procedure (Tang et al., 2018). These benefits provide the highest quality care for the patient that can be provided. Robotic-assisted surgical platforms may overcome many of the shortcomings of laparoscopy while preserving the patient benefits (Boggess, 2007). Laparoscopic Surgery provides many benefits over open surgery as well and including the Robotic Surgical Assist allows for further/amplified benefits for the parties involved. The idea is to minimize the need for lengthy patient recovery time, discomfort, and complications caused by the procedure itself. The pain, discomfort, and disability, or other morbidities as a result of surgery is more frequently due to trauma involved in gaining access to the area to perform the intended procedure rather than from the procedure itself (Mack, 2001). Regulating certain areas of the procedure, such as required incision size, allows the patient a smoother recovery. With laparoscopic surgery, it limits risks and complications as a minimally invasive approach but, with robot-assisted laparoscopic surgery, it is even more as such. Currently, there seems to be a struggle in the field of medicine between how best to improve the surgical robots in comparison to how to better optimize, or create, smaller surgical devices to assist in surgeries. A factor that was found to be lacking in the field of medicine was the definition of actions done during surgical procedures. While used widely from a medical standpoint, from an operational standpoint it is not common practice to question the mathematical symbolization of the movements and actions done during surgery. The goal of this research is to determine, analyze, evaluate, and simplify the parameters that are present during Laparoscopic Surgery. These parameters will be compared between traditional surgery and robot-assisted surgery. The robot-assisted condition will be established using the Semi-Robotic Laparoscopic Surgery Support System developed by a University of Central Florida Senior Design Team finalized in the academic semester of Spring 2020. This system utilizes the aspects and features of a surgical robot while maintaining a small form factor and cheap production and purchasing price. Ultimately, this will allow for further evaluation of technologies exploiting the developed surgical robot for research in semi-autonomous control, and safety mechanisms in the context of robotic surgery. It is important to note that this technology is developed as a kinematic guide for laparoscopic surgery. This guiding assist is similar to the features incorporated in robot-assisted laparoscopic surgery which is what allows us to use this surgical assist device to represent the robot-assisted condition. This technology optimizes the condition of conventional laparoscopic surgery by introducing a braking mechanism into the standard procedure without requiring the major application of the full surgical systems. Through the utilization of this guiding system, this research has established and compared the kinematic and workspace parameters for robot-assisted laparoscopic surgery when the system is equipped vs. when it is equipped and activated; creating two different conditions of Workspace Controlled Laparoscopic Surgery and Kinematically Constrained Laparoscopic Surgery. It was deemed necessary to accomplish an understanding of both domains as well as in comparison to traditional laparoscopic surgical practices in order to engage the argument from a holistic point of view. Throughout this research, it was determined that, when evaluating traditional Laparoscopic Surgery, there are a series of parameters that are present when discussing the workspace of the human abdomen and the kinematics of the trocar, surgical tool, and camera placed into that workspace. Between these parameters, a variety of similarities was discovered using geometric rules and algebraic functional relationships within the kinematics. Upon equipping the Semi-Robotic Laparoscopic Surgery Support System to the procedure, certain parameters get zeroed out due to the fixed nature of the device from one abdominal insertion point to the next. While most parameters may maintain the same behaviors upon the installation of the technology, the majority of these same parameters get zeroed out when the technology is activated. The overall purpose and intent of this research is to define, evaluate, and compare various surgical parameters associated with the practice of laparoscopic surgery while running a comparison between the effectiveness of traditional surgery against robot-assisted surgery that can be made from a new perspective by evaluating the differences in their respective parameters. Results which will be discussed include: specific parameter definitions and labeling, how these parameters benefit the medical field, direct parameter comparison between the evaluated conditions of traditional surgery and robot-assisted surgery (represented by kinematic guiding technology and comparing when the device is applied, Workspace Controlled condition, versus when the braking system is activated, Kinematically Constrained condition), and how these different surgical techniques modify the conditions of surgery for the surgeon and the patient

Strongly reduced bias dependence in spin-tunnel junctions obtained by ultraviolet light assisted oxidation

For future implementation of ferromagnetic tunnel junctions, we need a better understanding of the influence of the insulating barrier preparation method on the junction resistance, tunnel magnetoresistance (TMR), and its voltage bias dependence. In this letter, we focus on the bias dependence of junctions (Co-Al2O3-Ni80Fe20) prepared by ultraviolet light assisted in situ oxidation in an O-2 ambient. For an initial Al thickness of 1.3 nm, the resistance times area product of the junctions is 60 k Omega mu m(2), while showing up to 20% TMR at 5 mV bias. The decrease of TMR with bias voltage up to 1 V is remarkably small leading to V-1/2, for which half of the low-bias TMR remains, well over 0.6 V. (C) 2000 American Institute of Physics. [S0003-6951(00)02908-9]

The Influence of Ethnicity on the Development of Type 2 Diabetes Mellitus in Women with Gestational Diabetes: A Prospective Study and Review of the Literature

As the worldwide prevalence of type 2 diabetes continues to rise at an alarming rate, the search for susceptible populations likely to benefit from preventative measures becomes more important. One such population is women with a previous history of gestational diabetes mellitus (GDM). In this prospective study of 101 women who had GDM in Australia, ethnicity was a major risk factor for the development of diabetes following a diagnosis of GDM. With a mean followup of 5.5 years after GDM, South Asian women had a significantly higher risk of developing abnormal glucose tolerance (AGT) (69%) than women of all other ethnicities (P < 0.05). The prevalence of diabetes and impaired glucose tolerance was also very high amongst other groups: South East and East Asian (11/27, 41%), Middle-Eastern (8/18, 44%), South European backgrounds (5/12, 42%), and Australian-born women 39% (11/28). A review of the literature supports the role of ethnicity in the development of diabetes amongst these women. These findings have implications for South Asian countries and countries such as Australia where there is a population from diverse ethnic backgrounds and where the implementation of targeted measures to stem the growing tide of diabetes is needed

Acceptability and effectiveness of opportunistic referral of smokers to telephone cessation advice from a nurse: a randomised trial in Australian general practice

<p>Abstract</p> <p>Background</p> <p>GPs often lack time to provide intensive cessation advice for patients who smoke. This study aimed to determine the effectiveness of opportunistic referral of smokers by their GP for telephone cessation counselling by a trained nurse.</p> <p>Methods</p> <p>Adult smokers (n = 318) attending 30 GPs in South Western Sydney, Australia were randomly allocated to usual care or referral to a telephone-based program comprising assessment and stage-based behavioural advice, written information and follow-up delivered by a nurse. Self-reported point prevalence abstinence at six and 12 months was compared between groups. Characteristics of patients who accepted and completed the intervention were investigated.</p> <p>Results</p> <p>Of 169 smokers randomised to the intervention, 76 (45%) consented to referral. Compared with smokers in 'pre-contemplation', those further along the stage-of-change continuum were significantly more likely to consent (p = 0.003). Those further along the continuum also were significantly more likely to complete all four calls of the intervention (OR 2.6, 95% CI: 0.8–8.1 and OR 8.6, 95% CI: 1.7–44.4 for 'contemplation' and 'preparation' respectively). At six months, there was no significant difference between groups in point prevalence abstinence (intention to treat) (9% versus 8%, p = 0.7). There was no evidence of differential intervention effectiveness by baseline stage-of-change (p = 0.6) or patient sex (p = 0.5). At 12 months, point prevalence abstinence in the intervention and control groups was 8% and 6% respectively (p = 0.6).</p> <p>Conclusion</p> <p>Acceptance of opportunistic referral for nurse delivered telephone cessation advice was low. This trial did not demonstrate improved quit rates following the intervention. Future research efforts might better focus support for those patients who are motivated to quit.</p> <p>Australian Clinical Trials Registry number</p> <p>ACTRN012607000091404</p

Targeting CEA in Pancreas Cancer Xenografts with a Mutated scFv-Fc Antibody Fragment

BackgroundSensitive antibody-based tumor targeting has the potential not only to image metastatic and micrometastatic disease, but also to be the basis of targeted therapy. The vast majority of pancreas cancers express carcinoembryonic antigen (CEA). Thus, we sought to evaluate the potential of CEA as a pancreatic cancer target utilizing a rapidly clearing engineered anti-CEA scFv-Fc antibody fragment with a mutation in the Fc region [anti-CEA scFv-Fc H310A].MethodsImmunohistochemistry (IHC) with the antibody fragment was used to confirm expression of CEA on human pancreas cancer specimens. In vivo tumor targeting was evaluated by tail vein injection of I124-labeled anti-CEA scFv-Fc(H310A) into mice harboring CEA-positive and -negative xenografts. MicroPET/CT imaging was performed at successive time intervals. Radioactivity in blood and tumor was measured after the last time point. Additionally, unlabeled anti-CEA scFv-Fc(H310A) was injected into CEA-positive tumor bearing mice and ex vivo IHC was performed to identify the presence of the antibody to define the microscopic intratumoral pattern of targeting.ResultsModerate to strong staining by IHC was noted on 84% of our human pancreatic cancer specimens and was comparable to staining of our xenografts. Pancreas xenograft imaging with the radiolabeled anti-CEA scFv-Fc(H310A) antibody demonstrated average tumor/blood ratios of 4.0. Immunolocalization demonstrated peripheral antibody fragment penetration of one to five cell diameters (0.75 to 1.5 μm).ConclusionsWe characterized a preclinical xenograft model with respect to CEA expression that was comparable to human cases. We demonstrated that the anti-CEA scFv-Fc(H310A) antibody exhibited antigen-specific tumor targeting and shows promise as an imaging and potentially therapeutic agent

Healthy lifestyles are associated with better vitamin D status in community-dwelling older men: The Health In Men Study (HIMS)

Objective: Older people are more prone to vitamin D deficiency than younger populations. Individual lifestyle factors have been associated with vitamin D status. We examined the influence of a combination of lifestyle factors on vitamin D status in older men. Participants and Measurements: In a population-based cohort study of older men (age ≥65 years), a lifestyle score was calculated from eight prudent health-related behaviours (smoking, exercise, alcohol, fish and meat consumption, adding salt, milk choices and obesity) collected via questionnaire at baseline. Blood samples were collected 5 years afterwards to measure plasma 25-hydroxyvitamin D (25OHD) levels. Associations between lifestyles and the likelihood of having plasma 25OHD levels of ≥75 versus <75 nmol/L and ≥50 versus <50 nmol/L were tested using logistic regression models. Results: Of the 2717 men analysed, mean plasma 25OHD was 69.0 ± 23.5 nmol/L, with 20.7% having plasma 25OHD <50 nmol/L. Men engaging in ≥4 healthy lifestyle behaviours had 20% higher odds of plasma 25OHD ≥75 nmol/L (adjusted OR = 1.20, 95% CI: 1.01−1.45) compared to those with <4 healthy behaviours. No association was found for 25OHD ≥50 nmol/L. Higher physical activity was the only individual component significantly associated with vitamin D sufficiency (highest vs. lowest quintiles of physical activity, adjusted OR = 2.01, 95% CI: 1.47−2.74 for 25OHD ≥50 nmol/L, adjusted OR = 2.35, 95% CI: 1.81−3.06 for 25OHD ≥75 nmol/L). Conclusion: Multiple healthy lifestyle behaviours are associated with better vitamin D status in older men. Further work is needed to determine the effects of promoting healthy lifestyle behaviours, including physical activity, on vitamin D sufficiency

Re-engage: A novel nurse-led program for survivors of childhood cancer who are disengaged from cancer-related care

Background: Survivors of childhood cancer often experience treatmentrelated chronic health conditions. Survivorship care improves survivors' physical and mental health, yet many are disengaged from care. Innovative models of care are necessary to overcome patient-reported barriers to accessing survivorship care and to maximize survivors' health. Methods:We piloted a novel survivorship program, called "Reengage,"a distance-delivered, nurse-led intervention aiming to engage, educate, and empower survivors not receiving any cancerrelated care. Re-engage involves a nurse-led consultation delivered via telephone/online to establish survivors' medical history and needs. Participants completed questionnaires at baseline, 1 month postintervention, and 6-month follow-up. Results: A total of 27 survivors who had not accessed survivorship care in the last 2 years participated (median age, 31 years; interquartile range [IQR], 27-39 years); of which, 82% were at high-risk for treatment-related complications. Participation in Re-engage was high (75%) and there was no attrition once survivors enrolled. At 1 month postintervention, 92% of survivors reported that Re-engage was "beneficial,"which all survivors reported at 6-month follow-up. Survivors' overall satisfaction with their care increased from 52% before Re-engage to 84% at 1 month postintervention. Survivors' mean self-efficacy scores remained similar from baseline to 1 month postintervention (b520.33, 95% CI, 21.31 to 0.65), but increased significantly from baseline to 6-month follow-up (b 5 1.64, 95% CI, 0.28-3.00). At 6-month follow-up, 73% of survivors showed an increase in health-related self-efficacy compared with baseline. Conclusions: Re-engage is a highly acceptable and feasible intervention and promotes health-related self-efficacy, which is integral to survivors being advocates for their own health. Further empirical work is needed to evaluate the long-term efficacy of Re-engage. Trial registration: ACTRN12618000194268