Whole-body uptake classification and prostate cancer staging in 68Ga-PSMA-11 PET/CT using dual-tracer learning

Purpose In PSMA-ligand PET/CT imaging, standardized evaluation frameworks and image-derived parameters are increasingly used to support prostate cancer staging. Clinical applicability remains challenging wherever manual measurements of numerous suspected lesions are required. Deep learning methods are promising for automated image analysis, typically requiring extensive expert-annotated image datasets to reach sufficient accuracy. We developed a deep learning method to support image-based staging, investigating the use of training information from two radiotracers. Methods In 173 subjects imaged with 68Ga-PSMA-11 PET/CT, divided into development (121) and test (52) sets, we trained and evaluated a convolutional neural network to both classify sites of elevated tracer uptake as nonsuspicious or suspicious for cancer and assign them an anatomical location. We evaluated training strategies to leverage information from a larger dataset of 18F-FDG PET/CT images and expert annotations, including transfer learning and combined training encoding the tracer type as input to the network. We assessed the agreement between the N and M stage assigned based on the network annotations and expert annotations, according to the PROMISE miTNM framework. Results In the development set, including 18F-FDG training data improved classification performance in four-fold cross validation. In the test set, compared to expert assessment, training with 18F-FDG data and the development set yielded 80.4% average precision [confidence interval (CI): 71.1–87.8] for identification of suspicious uptake sites, 77% (CI: 70.0–83.4) accuracy for anatomical location classification of suspicious findings, 81% agreement for identification of regional lymph node involvement, and 77% agreement for identification of metastatic stage. Conclusion The evaluated algorithm showed good agreement with expert assessment for identification and anatomical location classification of suspicious uptake sites in whole-body 68Ga-PSMA-11 PET/CT. With restricted PSMA-ligand data available, the use of training examples from a different radiotracer improved performance. The investigated methods are promising for enabling efficient assessment of cancer stage and tumor burden.

FORCOAST - Earth Observation services for Wild Fisheries, Oystergrounds Restoration and Bivalve Mariculture along European Coasts*

<p>The European Blue Growth perspective suggests a larger share in global economic production<br>and food security appointed to the marine and coastal zone and an increase of marine and coastal<br>infrastructures   and   operations.   However,   this   growth   must   be   aligned   with   increasing<br>environmental constraints as well as complying and restoring regulations and frameworks. The<br>compliance of growth and sustainability requires the adoption of economically and ecologically<br>efficient behaviours, based on a wider incorporation of available information and knowledge from<br>the industry and citizens alike. Marine and coastal managers must make decisions to maintain<br>the social, economic, and ecological health of marine and coastal areas while operating, planning<br>and managing their activities at sea.<br>The European funded FORCOAST project represents a step forward in this direction by bringing<br>the coastal water quality and met-ocean information closer to the target sectors: wild fisheries,<br>oyster   grounds   restoration,   and   bivalve   mariculture.   FORCOAST   will   develop,   test   and<br>demonstrate, in operational mode, novel Copernicus-based downstream information services that<br>will  incorporate  and  combine  Copernicus  Marine  Environment  Monitoring  Service  (CMEMS),<br>Copernicus Land  Monitoring Service (CLMS) and  Climate Change Monitoring Service  (CMS),<br>local monitoring data and advanced modelling in the service.<br>FORCOAST will provide consistent high-resolution data products for coastal applications, based<br>on a standardized data processing scheme. The services of FORCOAST will provide managerial<br>tools (e.g decision support, user warnings, on-demand case study) built upon those products and<br>implemented through cloud-processing infrastructures.<br>FORCOAST will develop and provide those services in eight pilot service uptake sites covering<br>five  different  regional  waters  (North  Sea,  Baltic  Sea,  Mediterranean  Sea,  Black  Sea and  the<br>coastal Atlantic Ocean). Each of those pilots gathers marine information producers (eg. models),<br>providers (dissemination) and user (operating SMEs), to ensure inter-sectoral consistency.<br>The outcome of FORCOAST is a novel commercial service that will provide Copernicus-based<br>downstream  information  coastal  services  to  a  variety  of  stakeholders,  which  will  result  in  an<br>operation, planning and management improvement of different marine activities in the sectors of<br>wild fisheries and aquaculture, having an economic and societal positive effect on the involved<br>parties.</p><p><br>*This  project  has  received  funding  from  the  European  Union’s  Horizon  2020  research  and  innovation<br>programme under grant agreement No 870465</p>

A Batch Experiment of Cesium Uptake Using Illitic Clays with Different Degrees of Crystallinity

Radiocesium released by the severe nuclear accident and nuclear weapon test is a hazardous material. Illitic clays play a key role in the spatial distribution of radiocesium in groundwater environments due to selective uptake sites at the illite mineral, such as frayed edge sites. However, the cesium uptake capabilities of illitic clays are diverse, which could be associated with the illite crystallinity. This study was performed to determine the cesium uptake of illitic clays and evaluate the crystallinity effects on cesium uptake using statistical approaches. A total of 10 illitic clays showed various crystallinity, which was parameterized by the full width at half maximum (FWHM) at 10 Å XRD peak ranging from 0.15 to 0.64. The uptake behavior of illitic clays was well fitted with the Freundlich model (i.e., r2 > 0.946). The uptake efficiency of illitic clays increased with the decrease in dissolved cesium concentrations. The cesium uptake was significantly correlated with the FWHM and cation exchange capacity, suggesting that the uptake becomes higher with decreasing crystallinity through expansion of the edge site and/or formation of ion-exchangeable sites.

A description of the influenza vaccination program for health care workers in Vietnam

Background In 2017, the Vietnam Ministry of Health conducted a demonstration project to introduce seasonal influenza vaccination to health care workers (HCWs). A total of 11,000 doses of influenza vaccine, single-dose prefilled syringes, were provided free to HCWs at 29 selected hospitals, clinics, and research institutes in four provinces: Hanoi, Khanh Hoa, Dak Lak and Ho Chi Minh City. Methods Before the campaign, a workshop was organized to discuss an implementation plan including technical requirements, cold chain, uptake reporting, and surveillance for adverse events following immunization (AEFIs). All sites distributed communication materials and encouraged their staff to register for vaccination. Following immunization sessions, sites sent reports on uptake and AEFI cases. Left-over vaccine was transferred to other sites to maximize vaccine use. Results The average uptake was 57% for all HCWs, with 11 sites achieving 90% and above. These 11 sites were small with less than 500 staff, including 5 primary hospitals, 3 preventive medicine units, and 2 referral hospitals. Among the six biggest sites with over 1,000 staff, four sites had the lowest uptake (14%-47%). Most of the high-uptake sites were from the central to the south; only one site, a referral hospital, was from the north. After redistribution of left-over vaccine, only 130 vaccine doses (1.2%) were not used and destroyed. Based on factors that affected uptake, including registration levels, differing communication strategies, availability of vaccination, and commitment by health facility leaders, we recommended ways to increase HCW coverage; recommendations to improve AEFI reporting also were made. Conclusions The project demonstrated that it was feasible to conduct influenza vaccination campaigns among HCWs in Vietnam. Improvements in promotion of registration, more intense pre-planning, especially at larger facilities, and wider, more consistent availability of communication materials will result in increased efficiency and coverage in this program’s future expansion.

Distinct functions of megalin and cubilin receptors in recovery of normal and nephrotic levels of filtered albumin

Proximal tubule (PT) cells express a single saturable albumin-binding site whose affinity matches the estimated tubular concentration of albumin; however, albumin uptake capacity is greatly increased under nephrotic conditions. Deciphering the individual contributions of megalin and cubilin to the uptake of normal and nephrotic levels of albumin is impossible in vivo, as knockout of megalin in mice globally disrupts PT endocytic uptake. We quantified concentration-dependent albumin uptake in an optimized opossum kidney cell culture model and fit the kinetic profiles to identify albumin-binding affinities and uptake capacities. Mathematical deconvolution fit best to a three-component model that included saturable high- and low-affinity uptake sites for albumin and underlying nonsaturable uptake consistent with passive uptake of albumin in the fluid phase. Knockdown of cubilin or its chaperone amnionless selectively reduced the binding capacity of the high-affinity site, whereas knockdown of megalin impacted the low-affinity site. Knockdown of disabled-2 decreased the capacities of both binding sites. Additionally, knockdown of megalin or disabled-2 profoundly inhibited the uptake of a fluid phase marker, with cubilin knockdown having a more modest effect. We propose a novel model for albumin retrieval along the PT in which cubilin and megalin receptors have different functions in recovering filtered albumin in proximal tubule cells. Cubilin binding to albumin is tuned to capture normally filtered levels of the protein. In contrast, megalin binding to albumin is of lower affinity, and its expression is also essential for enabling the recovery of high concentrations of albumin in the fluid phase.

Selenium Interactions with Algae: Chemical Processes at Biological Uptake Sites, Bioaccumulation, and Intracellular Metabolism

Selenium (Se) uptake by primary producers is the most variable and important step in determining Se concentrations at higher trophic levels in aquatic food webs. We gathered data available about the Se bioaccumulation at the base of aquatic food webs and analyzed its relationship with Se concentrations in water. This important dataset was separated into lotic and lentic systems to provide a reliable model to estimate Se in primary producers from aqueous exposure. We observed that lentic systems had higher organic selenium and selenite concentrations than in lotic systems and selenate concentrations were higher in lotic environments. Selenium uptake by algae is mostly driven by Se concentrations, speciation and competition with other anions, and is as well influenced by pH. Based on Se species uptake by algae in the laboratory, we proposed an accurate mechanistic model of competition between sulfate and inorganic Se species at algal uptake sites. Intracellular Se transformations and incorporation into selenoproteins as well as the mechanisms through which Se can induce toxicity in algae has also been reviewed. We provided a new tool for risk assessment strategies to better predict accumulation in primary consumers and consequently to higher trophic levels, and we identified some research needs that could fill knowledge gaps.

Earth Observation services for Wild Fisheries, Oystergrounds Restoration and Bivalve Mariculture along European Coasts*

<p>Sea related activities are set to increase and the growth in food production from sea enhancing global food security is already a reality. However, this growth must be aligned with increasing environmental constraints as well as complying and restoring regulations and frameworks. This requires the adoption of improved and efficient behaviors based on wider incorporation of available information and knowledge from the industry and citizens alike. Marine and coastal managers must make decisions to maintain the social, economic, and ecological health of marine and coastal areas in coastal and nearshore areas and to operate, plan and manage their activities at sea. The European funded FORCAST project represents a step forward in this direction by bringing the coastal water quality and met-ocean information closer to the target sectors: wild fisheries, oystergrounds restoration, and bivalve mariculture. FORCOAST will develop, test and demonstrate, in operational mode, novel Copernicus-based downstream information services that will incorporate and combine Copernicus Marine Environment Monitoring Service (CMEMS), Copernicus Land Monitoring Service (CLMS) and Climate Change Monitoring Service (CMS), local monitoring data and advanced modelling in the service. FORCOAST will provide consistent high resolution data products for coastal applications, based on a standardized data processing scheme. Furthermore, FORCOAST will make use DIAS which will help to develop the data access and cloud processing service. FORCOAST will provide those services in eight pilot service uptake sites covering five different regional waters (North Sea, Baltic Sea, Mediterranean Sea, Black Sea and the coastal Atlantic Ocean). The outcome of FORCAST is a novel commercial service that will provide Copernicus-based downstream information coastal services to a variety of stakeholders, which will result in an operation, planning and management improvement of different marine activities in the sectors of wild fisheries and aquaculture, having an economic and societal positive effect on the involved parties.</p><p>*This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 870465</p>

Creating and disseminating a home-based cardiac rehabilitation program: experience from the Veterans Health Administration

Background Cardiac rehabilitation (CR) programs provide significant benefit for people with cardiovascular disease. Despite these benefits, such services are not universally available. We designed and evaluated a national home-based CR (HBCR) program in the Veterans Health Administration (VHA). The primary aim of the study was to examine barriers and facilitators associated with site-level implementation of HBCR. Methods This study used a convergent parallel mixed-methods design with qualitative data to analyze the process of implementation, quantitative data to determine low and high uptake of the HBCR program, and the integration of the two to determine which facilitators and barriers were associated with adoption. Data were drawn from 16 VHA facilities, and included semi-structured interviews with multiple stakeholders, document analysis, and quantitative analysis of CR program attendance codes. Qualitative data were analyzed using the Consolidated Framework for Implementation Research codes including three years of document analysis and 22 interviews. Results Comparing high and low uptake programs, readiness for implementation (leadership engagement, available resources, and access to knowledge and information), planning, and engaging champions and opinion leaders were key to success. High uptake sites were more likely to seek information from the external facilitator, compared to low uptake sites. There were few adaptations to the design of the program at individual sites. Conclusion Consistent and supportive leadership, both clinical and administrative, are critical elements to getting HBCR programs up and running and sustaining programs over time. All sites in this study had external funding to develop their program, but high adopters both made better use of those resources and were able to leverage existing resources in the setting. These data will inform broader policy regarding use of HBCR services.

Lacrimal Sac Malignant Melanoma in 15 Japanese Patients: Case Report and Literature Review

Background. Primary malignant melanoma of the lacrimal sac is rare. A patient with lacrimal sac melanoma was presented, and 14 Japanese patients with lacrimal sac melanoma in the literature were reviewed. Case Presentation. A 78-year-old Japanese man was presented with painless swelling of the lacrimal sac on the left side. Dacryocystectomy revealed diffuse infiltration with large epithelioid cells, sometimes with pigments, which were positive for cocktail mix of antibodies to tyrosinase, melan A (MART-1), and HMB45, leading to pathological diagnosis of melanoma. One month later, positron emission tomography (PET) revealed 2 high-uptake sites (SUVmax = 10.29 and 15.38) at the levels of medial canthus and nasolacrimal duct, but no abnormal uptake in the other site of the body. The lesion had the BRAF V600E mutation. He began to take daily oral dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor), leading to no abnormal uptake on PET in half a year. He had stable disease in good physical status with small and weak uptake sites of lymph nodes on PET 1 year later. Results. In the review of 15 Japanese patients, including this patient, local recurrence was noted in 4 patients, regional lymph node metastasis only in 3, distant metastasis in 6, and no metastasis in 6. Five patients died within 2 years and the others were alive in short follow-up periods. Conclusions. Chemotherapy was the standard for local recurrence or metastasis. Emerging molecular target drugs, as shown in the present patient, would change the strategy for management of lacrimal sac melanoma.

Mixed-Methods Evaluation of the Phased Implementation of a National Telehealth Weight Management Program for Veterans (Preprint)

BACKGROUND The burden of obesity is high among U.S. veterans yet many face barriers to engaging in in-person, facility-based treatment programs. To improve access to weight-management services, the Veterans Health Administration (VHA) developed TeleMOVE®, a home-based 82-day curriculum that utilizes in-home messaging devices to promote weight loss in VHA patients facing barriers to accessing facility-based services. OBJECTIVE Our primary aims were to establish preliminary evidence for the program to engage the priority population based on the number of patients enrolled per site as well as the program’s clinical effectiveness as demonstrated by average weight lost per patient. A secondary aim was to understand factors influencing implementation variability across demonstration sites to develop recommendations to inform the national TeleMOVE dissemination. METHODS We employed a formative mixed-methods design to evaluate the phased implementation of TeleMOVE programming at nine demonstration sites and to compare patient- and site-level measures of program uptake. Data was collected between October 1, 2009 and September 30, 2012. Twenty-eight stakeholders were recruited to provide contextual details while patient-level program outcomes were extracted from VHA patient care databases. Program stakeholders were recruited to participate in two rounds of semi-structured interviews about aspects of implementation processes, site-level contextual factors, and daily program delivery. Administrative data was used to evaluate program enrollment rates and clinical outcomes. To assess preliminary clinical effectiveness, weight loss outcomes for veterans who enrolled in TeleMOVE were compared to outcomes for participants enrolled in standard MOVE! at each demonstration site as well as to national averages during the first two years of program implementation. RESULTS Program uptake was high at two sites, delayed-high at one site, low at three sites, and three late-adopting sites declined interviews. At six months post-enrollment, mean weight loss was comparable for TeleMOVE (n=417) and MOVE! (n=1543) participants at -5.2 lb (SD=14.4) and -5.1 lb (SD=12.2), respectively (p=.91). All sites reported high program complexity because TeleMOVE required more staff time per participant than MOVE! due to logistical and technical assistance issues related to the devices. High-uptake sites overcame implementation challenges by leveraging strong communication networks with stakeholders, adapting the program to patient needs whenever possible, setting programmatic goals and monitoring feedback of results, and taking time to reflect and evaluate on delivery to foster incremental delivery improvements whereas, low-uptake sites reported less leadership support and effective communication among stakeholders. CONCLUSIONS This evaluation of the phased implementation of a new clinical telehealth program demonstrates the value of partnership-based research in which researchers not only provide operational leaders with rapid and responsive feedback regarding the effectiveness of a new clinical program but also relevant feedback into contextual factors related to implementation to enable adaptations for national rollout of the program.