Prospective Evaluation of the Clinical Benefits of a Novel Tattoo-less Workflow for Nonspine Bone Stereotactic Body Radiation Therapy: Integrating Surface-Guidance With Triggered Imaging Reduces Treatment Time and Eliminates the Need for Tattoos.

PURPOSE: Oligometastatic disease has expanded the indications for nonspine bone stereotactic body radiation therapy (NSB SBRT). We investigated whether optical surface monitoring systems (OSMS) could enable tattoo-less setup and substitute for 2-dimensional/3-dimensional or cone beam computed tomography (CBCT)-based mid-imaging in NSB SBRT. METHODS AND MATERIALS: OSMS was incorporated in parallel with an existing workflow using pretreatment CBCT and 2-dimensional/3-dimensional kV/kV mid-imaging beginning November 2019. The ability of OSMS to detect out-of-tolerance (>2 mm/>2°) and commanded couch shifts was analyzed. A workflow incorporating OSMS reference captures, CBCT for pretreatment verification, and OSMS/triggered imaging (TI) for intrafraction monitoring was developed for rib/sternum SBRT beginning November 2021 and all NSB SBRT beginning February 2022. Treatment time and CBCT-related radiation dose between the OSMS and the non-OSMS intrafraction monitoring group was analyzed pre- and post-OSMS/TI workflow adoption. All fractions were analyzed through statistical process control with use of an XmR chart of treatment time per quarter from February 2019 to February 2023. Special cause rules were based on Institute for Healthcare Improvement criteria. RESULTS: From February 2019 to February 2023, 1993 NSB SBRT fractions were delivered, including 234 rib, 109 sternum, 214 ilium, and 682 multisite. Over 20 commanded shifts, OSMS could detect 2-mm shifts to within 0.4 mm 67% of the time and 0.8 mm 95% of the time. All NSB SBRT sites showed significant reductions in treatment time, including the greatest improvement in rib total treatment (21.6-13.4 minutes; P = 1.16 × 10-17) and beam time (7.9-3.2 minutes; P = 7.32 × 10-27). Significant reductions in CBCT-related radiation were also observed for several NSB sites. These process improvements were associated with OSMS adoption. CONCLUSIONS: Adoption of a novel NSB SBRT workflow incorporating OSMS/TI for bone intrafraction motion monitoring reduced treatment time and CBCT-related radiation exposure while also allowing for more continuous intrafraction motion monitoring for NSB SBRT. OSMS/TI enabled the transition to a tattoo-less workflow.

Improving data use in trachomatous trichiasis programmes: operationalisation of the TT Tracker.

Trachoma is a disease of the eye and the leading infectious cause of blindness worldwide. Years of repeated infections can cause in-turning of the lashes so that they rub against the eyeball, causing pain, discomfort and, if left untreated, blindness. This is known as trachomatous trichiasis (TT) and can be remedied by surgery. To improve oversight and reporting of TT outreach, Sightsavers developed a mobile phone application called the TT Tracker so that TT surgeons, assistants and supervisors can collect and analyse information about surgical outcomes and performance and determine when and where follow-up appointments are required. The TT Tracker is being used by seven national programmes. Examples of use and programme improvements from Nigeria, Benin and Senegal are discussed here.

Distinct variations in fluorescent DOM components along a trophic gradient in the lower Fox River-Green Bay as characterized using one-sample PARAFAC approach.

Variations in molecular weight distributions of dissolved organic matter (DOM) and PARAFAC-derived fluorescent components were investigated along a transect in the seasonally hypereutrophic lower Fox River-Green Bay using the one-sample PARAFAC approach coupling flow field-flow fractionation for size-separation with fluorescence excitation-emission matrix (EEM) and PARAFAC analysis. Concentrations of dissolved organic carbon and nitrogen, chromophoric-DOM, specific UV absorbance at 254 nm, and humification index all decreased monotonically from river to open bay, showing a strong river-dominated DOM source and a dynamic change in DOM quality along the river-lake transect. The relative abundance of colloidal DOM (>1 kDa) derived from ultrafiltration exhibited minimal variation, averaging 71 ± 4 % of the bulk DOM, across the entire estuarine transect although the colloidal concentration decreased in general. Using the one-sample EEM-PARAFAC approach, the identified major fluorescent components were distinct between stations along the river-estuary-open bay continuum, with four components in river/upper-estuary but three components in open bay waters. Among the four common fluorescent components (C475, C410, C320 and C290), the most abundant and refractory humic-like component, C475, behaved conservatively and its relative abundance (%ΣFmax) remained fairly constant (50 ± 4 %) along the transect, while the semi-labile humic-like component, C410, consistently decreased from river to estuary and eventually vanished in open Green Bay. In contrast, the two autochthonous protein-like components (C320 and C290) increased from river to open bay along the trophic gradient. The new results presented here provide an improved understanding of the diverse and fluctuating characteristics in DOM composition, lability, and estuarine mixing behavior across the river-lake interface and demonstrate the efficacy of the one-sample PARAFAC approach.

The future of data management for pediatric cataract.

Cataract is a leading cause of blindness in children worldwide. Blindness can be treated with effective surgery, but in low-resource settings this treatment can be difficult to access. In addition, positive outcomes of the surgery are heavily dependent on comprehensive postoperative care. To date in Nigeria and many other low-resource countries, robust electronic data-management systems that help facility teams to manage their patient data, especially when it comes to tracking children for follow-up visits after surgery, have either yet to be put into place or are in place but have yet to be refined to respond to the specific needs of eye care programs. Sightsavers has worked with multiple state ministries in Nigeria to set up and test a system that responds to those needs.

Calculating the carbon footprint of a Geriatric Medicine clinic before and after COVID-19.

BACKGROUND: climate change is a health emergency. Central to addressing this is understanding the carbon footprint of our daily life and work, in order to reduce it effectively. The coronavirus disease of 2019 (COVID-19) pandemic has brought about rapid change to clinical practice, most notably in use of virtual clinics and personal protective equipment (PPE). AIM: to estimate the carbon footprint of a Geriatric Medicine clinic, including the effect of virtual consultation and PPE, in order to inform design of a service that addresses both the health of our patients and our environment. METHOD: data from the Greenhouse Gas Protocol, NHS Carbon Footprint Plus and UK Government were used to estimate the carbon emissions per consultation. Values were calculated for virtual and face-to-face contact and applied to actual clinics both before and during the COVID-19 pandemic. RESULTS: the carbon footprint of a face-to-face clinic consultation is 4.82 kgCO2e, most of which is patient travel, followed by staff travel and use of PPE. The footprint of a virtual consultation is 0.99 kgCO2e, most of which is staff travel, followed by data use.Using our hybrid model for a single session clinic reduced our annual carbon footprint by an estimated 200 kgCO2e, roughly equivalent to a surgical operation. DISCUSSION: the COVID-19 pandemic has made us deliver services differently. The environmental benefits seen of moving to a partially virtual clinic highlight the importance of thinking beyond reverting to 'business as usual'-instead deliberately retaining changes, which benefit the current and future health of our community.

Fractional CO2 laser treatment as adjunctive therapy to topical steroids for managing vulvar lichen sclerosus.

OBJECTIVES: Uncontrolled vulvar lichen sclerosus (VLS) is often associated with distressful symptoms of genital itch, irritation, and pain and can lead to a pathological process including anatomical changes, scarring, and an elevated risk of cancer in the genital area. First-line topical corticosteroid as monotherapy is frequently not adequate to fully suppress disease activity and control symptoms. This study evaluated the efficacy of fractional CO2 laser treatments as adjunctive therapy where recalcitrant VLS had been improved, but not adequately controlled, with topical corticosteroid treatment. Outcomes were evaluated up to 12 months after a series of CO2 laser treatments delivered via a fractional handpiece. MATERIALS AND METHODS: Women with a diagnosis of VLS supported by histologic findings on biopsy and/or clinical signs on physical examination received up to five monthly laser treatments. Subjects maintained existing topical corticosteroid and any exogenous hormone treatment during the study. Investigators assessed severity (0 = not present, 1 = mild, 2 = moderate, or 3 = severe) of clinical signs and architectural changes present before adjunctive study interventions and at follow-up visits. Subjects reported the presence of clinical symptoms and impact on quality of life on 4- or 5-point Likert scales. The validated Female Sexual Function Index (FSFI) was used to assess changes in sexual function. Four subjects were biopsied before adjunctive laser treatment and at follow-up. RESULTS: Twelve females, 11 postmenopausal, with a mean age of 57 ± 10 years received three to five monthly CO2 laser treatments. Significant improvement in all prominent clinical signs and architectural changes were reported at the 3- and 6-month follow-ups after the treatment series. Significant improvement was maintained at the 12-month follow-up, with 89% of subjects showing at least one-point improvement in elasticity compared to baseline; 86% in lichenification; 88% in sclerosis; and 80% in whitening and parchment-like skin. Labial fusion and the extent of disease improved in 50% of patients. Ulcerations present in three subjects at baseline resolved after treatment. Subjects reported 86% improvement in dyspareunia and 83% in skin tearing. Quality of life improved significantly after treatment (p < 0.01). The 6-month follow-up FSFI showed significant improvement in sexual function compared to baseline (p < 0.05), with a mean point improvement of 4.5. Histology findings after treatment showed some positive improvement, as a decrease in dermal hyalinized zone thickness. There were no treatment complications or adverse events related to the treatment. CONCLUSIONS: Fractional CO2 laser treatment outcomes showed improvement in predominant clinical signs and architectural changes in VLS recalcitrant to topical corticosteroid treatment. Adjunctive laser treatment relieved symptoms and improved quality of life as well as sexual function. Fractional CO2 laser treatment may provide an advanced treatment modality for the management of recalcitrant VLS with improved patient care and sustainable outcomes. Further study in a larger population and with CO2 laser treatment to both vulvar tissue and the vaginal canal should be explored.

Improving data use for decision making by neglected tropical disease program teams: eight use cases.

Background: The achievement of neglected tropical diseases (NTDs) program goals depends on numerous factors, including the ability of national programs to use high-quality, timely data to inform their decision-making and program delivery. This paper presents a use case analysis of the routine data used by national NTD programs targeting lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiasis, and trachoma. Methods: The use cases were developed through a combination of secondary and primary research focused on both global trends and deep dives into Burkina Faso, Ethiopia, and Tanzania. Results were refined through a stakeholder convening and the final eight use cases were determined through iteration and prioritization with stakeholders. Results: Eight use cases were developed: improve treatment register data quality, strengthen supervision of drug distributors during mass drug administration (MDA), generate accurate community-level population data for MDAs, create and manage an accurate inventory of drugs, meet district coverage targets during MDA campaigns, feedback and performance to sub-district teams, feedback on performance to sub-national teams, and national-level program use of data for evaluation and decision making. Each use case identifies key actors and their data-related needs and critical challenges, defines the current and desired state, and articulates the profile of a solution (digital and non-digital) needed to complete the use case. Conclusion: The systematic strengthening of data use for decision-making in NTD programs is key for reaching the 2030 Roadmap goals. Integrated together, the presented use cases, when translated into action using appropriate and innovative solutions, can help to ensure that accurate and timely data are present at every step of a program and empower countries to use these data to make program decisions.

A bi-institutional multi-disciplinary failure mode and effects analysis (FMEA) for a Co-60 based total body irradiation technique.

BACKGROUND: We aim to assess the risks associated with total body irradiation (TBI) delivered using a commercial dedicated Co-60 irradiator, and to evaluate inter-institutional and inter-professional variations in the estimation of these risks. METHODS: A failure mode and effects analysis (FMEA) was generated using guidance from the AAPM TG-100 report for quantitative estimation of prospective risk metrics. Thirteen radiation oncology professionals from two institutions rated possible failure modes (FMs) for occurrence (O), severity (S), and detectability (D) indices to generate a risk priority number (RPN). The FMs were ranked by descending RPN value. Absolute gross differences (AGD) in resulting RPN values and Jaccard Index (JI; for the top 20 FMs) were calculated. The results were compared between professions and institutions. RESULTS: A total of 87 potential FMs (57, 15, 10, 3, and 2 for treatment, quality assurance, planning, simulation, and logistics respectively) were identified and ranked, with individual RPN ranging between 1-420 and mean RPN values ranging between 6 and 74. The two institutions shared 6 of their respective top 20 FMs. For various institutional and professional comparison pairs, the number of common FMs in the top 20 FMs ranged from 6 to 13, with JI values of 18-48%. For the top 20 FMs, the trend in inter-professional variability was institution-specific. The mean AGD values ranged between 12.5 and 74.5 for various comparison pairs. AGD values differed the most for medical physicists (MPs) in comparison to other specialties i.e. radiation oncologists (ROs) and radiation therapists (RTs) [MPs-vs-ROs: 36.3 (standard deviation SD = 34.1); MPs-vs-RTs: 41.2 (SD = 37.9); ROs-vs-RTs: 12.5 (SD = 10.8)]. Trends in inter-professional AGD values were similar for both institutions. CONCLUSION: This inter-institutional comparison provides prospective risk analysis for a new treatment delivery unit and illustrates the institution-specific nature of FM prioritization, primarily due to operational differences. Despite being subjective in nature, the FMEA is a valuable tool to ensure the identification of the most significant risks, particularly when implementing a novel treatment modality. The creation of a bi-institutional, multidisciplinary FMEA for this unique TBI technique has not only helped identify potential risks but also served as an opportunity to evaluate clinical and safety practices from the perspective of both multiple professional roles and different institutions.

Partitioning and transformation of organic and inorganic phosphorus among dissolved, colloidal and particulate phases in a hypereutrophic freshwater estuary.

Phosphorus (P) loadings to the Great Lakes have been regulated for decades, but re-eutrophication and seasonal hypoxia have recently been increasingly reported. It is of paramount importance to better understand the fate, transformation, and biogeochemical cycling processes of different P species across the river-lake interface. We report here results on chemical speciation of P in the seasonally hypoxic Fox River-Green Bay system and variations in sources and partitioning of P species along the aquatic continuum. During midsummer when productivity is generally high, phosphate and dissolved organic P (DOP) were the major species in river water while particulate-organic-P predominated in open bay waters, showing a dynamic change in the chemical speciation of P along the river-bay transect with active transformations between inorganic and organic P and between colloidal and particulate phases. Colloidal organic P (COP, >1 kDa) comprised 33‒65% of the bulk DOP, while colloidal inorganic P was generally insignificant and undetectable especially in open bay water. Sources of COP changed from mainly allochthonous in the Fox River, having mostly smaller sized colloids (1-3 kDa) and a lower organic carbon to phosphorus (C/P) ratio, to predominantly autochthonous in open bay waters with larger sized colloids (>10 kDa) and a higher organic C/P ratio. The observed high apparent distribution coefficients (Kd) of P between dissolved and particulate phases and high-abundant autochthonous colloidal and particulate organic P in the hypereutrophic environment suggest that, in addition to phosphate, colloidal/particulate organic P may play a critical role in the biogeochemical cycling of P and the development of seasonal hypoxia.

Treating the SARS-CoV-2-positive patient with cancer: A proposal for a pragmatic and transparent ethical process.

The treatment of patients with cancer who test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses unique challenges. In this commentary, the authors describe the ethical rationale and implementation details for the creation of a novel, multidisciplinary treatment prioritization committee, including physicians, frontline staff, an ethicist, and an infectious disease expert. Organizational obligations to health care workers also are discussed. The treatment prioritization committee sets a threshold of acceptable harm to patients from decreased cancer control that is justified to reduce risk to staff. The creation of an ethical, consistent, and transparent decision-making process involving such frontline stakeholders is essential as departments across the country are faced with decisions regarding the treatment of SARS-CoV-2-positive patients with cancer.

Lakes at Risk of Chloride Contamination.

Lakes in the Midwest and Northeast United States are at risk of anthropogenic chloride contamination, but there is little knowledge of the prevalence and spatial distribution of freshwater salinization. Here, we use a quantile regression forest (QRF) to leverage information from 2773 lakes to predict the chloride concentration of all 49 432 lakes greater than 4 ha in a 17-state area. The QRF incorporated 22 predictor variables, which included lake morphometry characteristics, watershed land use, and distance to the nearest road and interstate. Model predictions had an r2 of 0.94 for all chloride observations, and an r2 of 0.86 for predictions of the median chloride concentration observed at each lake. The four predictors with the largest influence on lake chloride concentrations were low and medium intensity development in the watershed, crop density in the watershed, and distance to the nearest interstate. Almost 2000 lakes are predicted to have chloride concentrations above 50 mg L-1 and should be monitored. We encourage management and governing agencies to use lake-specific model predictions to assess salt contamination risk as well as to augment their monitoring strategies to more comprehensively protect freshwater ecosystems from salinization.

Automated Subdaily Sampling of Cyanobacterial Toxins on a Buoy Reveals New Temporal Patterns in Toxin Dynamics.

Temporal variability of toxins produced by cyanobacteria in lakes is relatively unknown at time scales relevant to public health (i.e., hourly). In this study, a water quality monitoring buoy was outfitted with an automated water sampler taking preserved samples every 6 h for 68.75 days over a drinking water intake. A total of 251 samples were analyzed by tandem mass spectrometry for 21 cyanotoxin congeners in 5 classes producing 5020 data points. Microcystins (MCs) were the most abundant toxins measured (mean ± sd = 3.9 ± 3.3 µg/L) followed by cyanopeptolins (CPs) (1.1 ± 1.5 µg/L), anabaenopeptins (APs) (1.0 ± 0.6 µg/L), anatoxin-a (AT-A) (0.03 ± 0.06 µg/L), and microginin-690 (MG-690) (0.002 ± 0.01 µg/L). Advanced time series analyses uncovered patterns in cyanotoxin production. The velocity of cyanotoxin concentration varied from -0.7 to 0.9 µg/L/h with a maximum positive velocity just prior to peak toxin concentration during nonbloom periods. A backward-looking moving window of variance analysis detected major increases in cyanotoxin concentration and predicted the two greatest increases in MC. A wavelet analysis identified a significant ( p < 0.01) 2.8-4.2 day periodicity in toxin concentration over a ∼25 day period during peak toxin production, which is partially explained by easterly wind velocity ( R = -0.2, p < 0.05). Diversity in congener profiles was explored with principle component analysis showing that cyanotoxin dynamics followed a seasonal trajectory where toxin profiles were significantly clustered (ANOSIM R = 0.7, p < 0.05) on a daily basis. Variability in toxin profiles was strongly correlated with time ( R = -0.8, p < 0.001) as well as the C:N ratio of the toxin pool ( R = 0.17, p < 0.05). The methods employed here should be useful for uncovering patterns in cyanotoxin dynamics in other systems.

Site-Specific Immuno-PET Tracer to Image PD-L1.

The rapid ascension of immune checkpoint blockade treatments has placed an emphasis on the need for viable, robust, and noninvasive imaging methods for immune checkpoint proteins, which could be of diagnostic value. Immunoconjugate-based positron emission tomography (immuno-PET) allows for sensitive and quantitative imaging of target levels and has promising potential for the noninvasive evaluation of immune checkpoint proteins. However, the advancement of immuno-PET is currently limited by available imaging tools, which heavily rely on full-length IgGs with Fc-mediated effects and are heterogeneous mixtures upon random conjugation with chelators for imaging. Herein, we have developed a site-specific αPD-L1 Fab conjugate with the chelator 1,4,7-triazacyclononane- N, N', N″-triacetic acid (NOTA), enabling radiolabeling for PET imaging, using the amber suppression-mediated genetic incorporation of unnatural amino acid (UAA), p-azidophenylalanine. This Fab conjugate is homogeneous and demonstrated tight binding toward the PD-L1 antigen in vitro. The radiolabeled version, 64Cu-NOTA-αPD-L1, has been employed in PET imaging to allow for effective visualization and mapping of the biodistribution of PD-L1 in two normal mouse models, including the capturing of different PD-L1 expression levels in the spleens of the different mouse types. Follow-up in vivo blocking studies and ex vivo fluorescent staining further validated specific tissue uptakes of the imaging agent. This approach illustrates the utility of UAA-based site-specific Fab conjugation as a general strategy for making sensitive PET imaging probes, which could facilitate the elucidation of the roles of a wide variety of immune checkpoint proteins in immunotherapy.

Elimination through collaboration: success factors in a global consortium.

The Global Trachoma Mapping Project (GTMP) is the largest infectious disease survey ever undertaken. With 60 partners, 2.6 million people were examined across 29 countries for the blinding neglected tropical disease (NTD) trachoma, establishing the prevalence of the disease globally. Such an achievement was only made possible by building a diverse worldwide consortium. This article examines that public-private consortium and attempts to highlight key factors in the success of its development and operation. Two critical factors in the project's success were the establishment of an evidence-based common approach and urgency around a shared goal. The common approach (the GTMP methodologies, tools and training approach) and the goal (GET2020 through the SAFE strategy) are thoroughly detailed in this article. Transparency at all levels; clear roles for committees, partners, agencies and ministries of health and shared funding played important roles and are explored here. It is hoped that by examining and sharing the positive factors leading to the establishment and work of this specific consortium, other similar initiatives-for NTDs, for health more broadly and for other development areas-will be able to adopt such an approach for effective collaboration.

Analysis of cyanobacterial metabolites in surface and raw drinking waters reveals more than microcystin.

Freshwater cyanobacterial blooms are becoming increasingly problematic in regions that rely on surface waters for drinking water production. Microcystins (MCs) are toxic peptides produced by multiple cyanobacterial genera with a global occurrence. Cyanobacteria also produce a variety of other toxic and/or otherwise bioactive peptides (TBPs) that have gained less attention including cyanopeptolins (Cpts), anabaenopeptins (Apts), and microginins (Mgn). In this study, we compared temporal and spatial trends of four MCs (MCLR, MCRR, MCYR, MCLA), three Cpts (Cpt1020, Cpt1041, Cpt1007), two Apts (AptF, AptB), and Mgn690 in raw drinking water and at six surface water locations above these drinking water intakes in a eutrophic lake. All four MC congeners and five of six TBPs were detected in lake and raw drinking water. Across all samples, MCLR was the most frequently detected metabolite (100% of samples) followed by MCRR (97%) > Cpt1007 (74%) > MCYR (69%) > AptF (67%) > MCLA (61%) > AptB (54%) > Mgn690 (29%) and Cpt1041 (15%). Mean concentrations of MCs, Apts, and Cpts into two drinking water intakes were 3.9 ±â€¯4.7, 0.14 ±â€¯0.21, and 0.38 ±â€¯0.92, respectively. Mean concentrations in surface water were significantly higher (p < 0.05) than in drinking water intakes for MCs but not for Cpts and Apts. Temporal trends in MCs, Cpts, and Apts in the two raw drinking water intakes were significantly correlated (p < 0.05) with measures of cell abundance (chlorophyll-a, Microcystis cell density), UV absorbance, and turbidity in surface water. This study expands current information about cyanobacterial TBPs that occur in lakes and that enter drinking water treatment plants and underscores the need to determine the fate of less studied cyanobacterial metabolites during drinking water treatment that may exacerbate toxicity of more well-known cyanobacterial toxins.