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1. Development and validation of an innovative administration system to facilitate controlled holmium-166 microsphere administration during TARE

Author: Meike W. M. van Wijk, Gerhard van Wolfswinkel, Mark J. Arntz, Marcel J. R. Janssen, Joey Roosen, and J. Frank W. Nijsen
Subjects: TARE, SIRT, Liver, Holmium, Image-guided, Personalisation, Medical physics. Medical radiology. Nuclear medicine, R895-920
Abstract: Abstract Background To develop and validate a novel administration device for holmium-166 transarterial radioembolisation (TARE) with the purpose of facilitating controlled fractional microsphere administration for a more flexible and image-guided TARE procedure. Methods A Controlled Administration Device (CAD) was developed using MR-conditional materials. The CAD contains a rotating syringe to keep the microspheres in suspension during administration. Different rotational speeds were tested ex vivo to optimise the homogeneity of microsphere fractions administered from the device. The technical performance, accuracy, and safety was validated in three patients in a clinical TARE setting by administering a standard clinical dose in 5 fractions (identifier: NCT05183776). MRI-based dosimetry was used to validate the homogeneity of the given fractions in vivo, and serious adverse device event ((S)A(D)E) reporting was performed to assess safety of the CAD. Results A rotational speed of 30 rpm resulted in the most homogeneous microsphere fractions with a relative mean deviation of 1.1% (range: -9.1-8.0%). The first and last fraction showed the largest deviation with a mean of -26% (std. 16%) and 7% (std. 13%). respectively. In the three patient cases the homogeneity of the microsphere fractions was confirmed given that MRI-based dosimetry showed near linear increase of mean absorbed target liver dose over the given fractions with R2 values of 0.98, 0.97 and 0.99. No (S)A(D)E’s could be contributed to the use of the CAD. Conclusions The newly developed CAD facilitates safe and accurate fractional microsphere administration during TARE, and can be used for multiple applications in the current and future workflows of TARE.
Published: 2024
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2. Accuracy of holmium-166 SPECT/CT quantification over a large range of activities

Author: Lovisa E. L. Westlund Gotby, Daphne Lobeek, Joey Roosen, Maarten de Bakker, Mark W. Konijnenberg, and J. Frank W. Nijsen
Subjects: SPECT quantification, Holmium-166, Conversion factor, Absolute quantification, Recovered activity, Medical physics. Medical radiology. Nuclear medicine, R895-920
Abstract: Abstract Background Quantitative imaging is a crucial step for dosimetry in radionuclide therapies. Traditionally, SPECT/CT imaging is quantified based on scanner-specific conversion factors or self-calibration, but recently absolute quantification methods have been introduced in commercial SPECT reconstruction software (Broad Quantification, Siemens Healthineers). In this phantom study we investigate the accuracy of three quantification methods for holmium-166 SPECT/CT imaging, and provide recommendations for clinical dosimetry. Methods One cylindrical phantom, filled with a homogeneous holmium-166-chloride activity concentration solution, was imaged at one time point to determine a scanner-specific conversion factor, and to characterize the spatial dependency of the activity concentration recovery. One Jaszczak phantom with six fillable spheres, 10:1 sphere-to-background ratio, was imaged over a large range of holmium-166 activities (61-3130 MBq). The images were reconstructed with either an ordered subset expectation maximization (OSEM, Flash3D-reconstruction; scanner-specific quantification or self-calibration quantification) or an ordered subset conjugate gradient (OSCG, xSPECT-reconstruction; Broad Quantification) algorithm. These three quantification methods were compared for the data of the Jaszczak phantom and evaluated based on whole phantom recovered activity, activity concentration recovery coefficients (ACRC), and recovery curves. Results The activity recovery in the Jaszczak phantom was 28–115% for the scanner-specific, and 57–97% for the Broad Quantification quantification methods, respectively. The self-calibration-based activity recovery is inherently always 100%. The ACRC for the largest sphere (Ø60 mm, ~ 113 mL) ranged over (depending on the activity level) 0.22–0.89, 0.76–0.86, 0.39–0.72 for scanner-specific, self-calibration and Broad Quantification, respectively. Conclusion Of the three investigated quantification methods, the self-calibration technique produces quantitative SPECT images with the highest accuracy in the investigated holmium-166 activity range.
Published: 2024
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3. Development of a model for the analysis of the biomechanical effects of Vertebral Body Tethering in a growing spine

Author: J. Frank, M. Pishnamaz, P. Trobisch, F. Hildebrand, and M. Praster
Subjects: Neurology. Diseases of the nervous system, RC346-429
Published: 2024
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4. Epigenetic signatures in antidepressant treatment response: a methylome-wide association study in the EMC trial

Author: J. Engelmann, L. Zillich, J. Frank, S. Wagner, M. Cetin, D. P. Herzog, M. B. Müller, A. Tadic, J. C. Foo, L. Sirignano, D. F. Braus, N. Dahmen, S. Sordon, M. Riemenschneider, C. Spaniol, G. Gasparoni, M. Rietschel, S. H. Witt, K. Lieb, and F. Streit
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Abstract Although the currently available antidepressants are well established in the treatment of the major depressive disorder (MDD), there is strong variability in the response of individual patients. Reliable predictors to guide treatment decisions before or in an early stage of treatment are needed. DNA-methylation has been proven a useful biomarker in different clinical conditions, but its importance for mechanisms of antidepressant response has not yet been determined. 80 MDD patients were selected out of >500 participants from the Early Medication Change (EMC) cohort with available genetic material based on their antidepressant response after four weeks and stratified into clear responders and age- and sex-matched non-responders (N = 40, each). Early improvement after two weeks was analyzed as a secondary outcome. DNA-methylation was determined using the Illumina EPIC BeadChip. Epigenome-wide association studies were performed and differentially methylated regions (DMRs) identified using the comb-p algorithm. Enrichment was tested for hallmark gene-sets and in genome-wide association studies of depression and antidepressant response. No epigenome-wide significant differentially methylated positions were found for treatment response or early improvement. Twenty DMRs were associated with response; the strongest in an enhancer region in SORBS2, which has been related to cardiovascular diseases and type II diabetes. Another DMR was located in CYP2C18, a gene previously linked to antidepressant response. Results pointed towards differential methylation in genes associated with cardiac function, neuroticism, and depression. Linking differential methylation to antidepressant treatment response is an emerging topic and represents a step towards personalized medicine, potentially facilitating the prediction of patients’ response before treatment.
Published: 2022
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5. Overview of the first Wendelstein 7-X long pulse campaign with fully water-cooled plasma facing components

Author: O. Grulke, C. Albert, J.A. Alcuson Belloso, P. Aleynikov, K. Aleynikova, A. Alonso, G. Anda, T. Andreeva, M. Arvanitou, E. Ascasibar, E. Aymerich, K. Avramidis, J.-P. Bähner, S.-G. Baek, M. Balden, J. Baldzuhn, S. Ballinger, M. Banduch, S. Bannmann, A. Bañón Navarro, L. Baylor, C.D. Beidler, M. Beurskens, C. Biedermann, G. Birkenmeier, T. Bluhm, D. Boeckenhoff, D. Boeyaert, D. Bold, M. Borchardt, D. Borodin, H.-S. Bosch, H. Bouvain, S. Bozhenkov, T. Bräuer, H. Braune, C. Brandt, S. Brezinsek, K.J. Brunner, C. Büschel, R. Bussiahn, A. Buzás, B. Buttenschoen, V. Bykov, I. Calvo, A. Cappa, F. Carovani, D. Carralero, A. Carls, B. Carvalho, D. Castaño-Bardawil, N. Chaudhary, I. Chelis, S. Chen, D. Cipciar, J.W. Coenen, G. Conway, M. Cornelissen, Y. Corre, P. Costello, K. Crombe, G. Cseh, B. Csillag, H.I. Cu Castillo, G. Czymek, H. Damm, R.J. Davies, C. Day, S. Degenkolbe, R. De Wolf, W. Dekeyser, A. Demby, P. Despontin, C.P. Dhard, A. Dinklage, F.A. d’Isa, T. Dittmar, M. Dreval, M. Drevlak, P. Drews, J. Droste, D. Dunai, C. Dyhring, P. van Eeten, E. Edlund, M. Endler, D.A. Ennis, F.J. Escoto, M.S. Espinosa, T. Estrada, D. Fehling, L. Feuerstein, J. Fellinger, Y. Feng, D.L.C. Fernando, S. Fischer, E.R. Flom, O. Ford, T. Fornal, J. Frank, H. Frerichs, G. Fuchert, G. Gantenbein, Y. Gao, K. Garcia, I. García-Cortés, J.M. García-Regaña, B. Geiger, J. Geiger, P. Geissler, M. Gerard, G. Godino-Sedano, T. Gonda, A. González, A. Goriaev, D. Gradic, M. Grahl, H. Greuner, E. Grigore, M. Gruca, J.F. Guerrero Arnaiz, V. Haak, L. van Ham, K. Hammond, B. Hamstra, X. Han, S.K. Hansen, J. Harris, D. Hartmann, D. Hathiramani, S. Hegedus, S. Heinrich, P. Helander, F. Henke, S. Henneberg, L. Henschke, M. Hirsch, U. Hoefel, K. Hoefler, S. Hoermann, K.-P. Hollfeld, A. Holtz, D. Höschen, M. Houry, J. Huang, M. Hubeny, K. Hunger, D. Hwangbo, K. Ida, Y. Igitkhanov, S. Illy, Z. Ioannidis, M. Jablczynska, S. Jablonski, B. Jabłoński, B. Jagielski, M. Jakubowski, J. Jelonnek, F. Jenko, J. Jin, A. Johansson, G. Jouniaux, S. Kajita, J.-P. Kallmeyer, U. Kamionka, W. Kasparek, C. Kawan, Ye. O. Kazakov, N. Kenmochi, W. Kernbichler, A.K. Kharwandikar, M. Khokhlov, C. Killer, A. Kirschner, R. Kleiber, C.C. Klepper, T. Klinger, J. Knauer, A. Knieps, M. Kobayashi, G. Kocsis, Y. Kolesnichenko, A. Könies, J. Kontula, P. Kornejew, S.A. Korteweg, J. Koschinsky, J. Koster, Y. Kovtun, A. Krämer-Flecken, M. Krause, T. Kremeyer, L. Krier, D.M. Kriete, M. Krychowiak, I. Ksia¸zek, M. Kubkowska, M.D. Kuczyński, D. Kulla, A. Kumar, T. Kurki-Suonio, I. Kuzmych, S. Kwak, V. Lancelotti, A. Langenberg, H. Laqua, H.P. Laqua, M.R. Larsen, S. Lazerson, C. Lechte, B. Lee, A. LeViness, M. Lewerentz, Y. Liang, L. Liao, A. Litnovsky, J. Liu, J. Loizu, R. Lopez-Cansino, L.D. Lopez Rodriguez, A. Lorenz, R. Lunsford, Y. Luo, V. Lutsenko, N. Maaziz, M. Machielsen, R. Mackenbach, D. Makowski, E. Maragkoudakis, O. Marchuk, M. Markl, S. Marsen, J. Martínez, N. Marushchenko, S. Masuzaki, D.A. Maurer, M. Mayer, K.J. McCarthy, P. McNeely, D. Medina Roque, J. Meineke, S. Meitner, S. vaz Mendes, A. Menzel-Barbara, B. van Milligen, A. Mishchenko, V. Moiseenko, A. Möller, S. Möller, D. Moseev, G. Motojima, S. Mulas, P. Mulholland, M. Nagel, D. Nagy, Y. Narbutt, D. Naujoks, P. Nelde, R. Neu, O. Neubauer, U. Neuner, D. Nicolai, S. Nielsen, C. Nührenberg, R. Ochoukov, G. Offermanns, J. Ongena, J.W. Oosterbeek, M. Otte, N. Pablant, N. Panadero Alvarez, A. Pandey, G. Partesotti, E.A. Pasch, R. Pavlichenko, E. Pawelec, T.S. Pedersen, V. Perseo, B. Peterson, F. Pisano, B. Plaum, G. Plunk, L. Podavini, N.S. Polei, P. Poloskei, S. Ponomarenko, P. Pons-Villalonga, M. Porkolab, J. Proll, M.J. Pueschel, A. Puig Sitjes, R. Ragona, K. Rahbarnia, M. Rasiński, J. Rasmussen, D. Refy, F. Reimold, M. Richou, J.S. Riemann, K. Riße, J. de la Riva Villén, G. Roberg-Clark, E. Rodriguez, V. Rohde, J. Romazanov, T. Romba, D. Rondeshagen, M. Rud, T. Ruess, T. Rummel, A. Runov, C. Ruset, N. Rust, L. Ryc, T. Rzesnicki, M. Salewski, E. Sánchez, L. Sanchis Sanchez, G. Satheeswaran, J. Schacht, E. Scharff, J. Schilling, G. Schlisio, K. Schmid, J.C. Schmitt, O. Schmitz, M. Schneider, M. Van Schoor, T. Schröder, R. Schroeder, B. Schweer, S. Sereda, B. Shanahan, G. Sias, S. Simko, L. Singh, Y. Siusko, C. Slaby, M. Śle¸czka, B.S. Smith, D.R. Smith, H. Smith, M. Spolaore, A. Spring, T. Stange, A. von Stechow, I. Stepanov, M. Stern, U. Stroth, Y. Suzuki, C. Swee, L. Syrocki, T. Szabolics, T. Szepesi, R. Takacs, H. Takahashi, N. Tamura, C. Tantos, J. Terry, S. Thiede, H. Thienpondt, H. Thomsen, M. Thumm, T. Thun, S. Togo, T. Tork, H. Trimino Mora, A. Tsikouras, Y. Turkin, L. Vano, S. Varoutis, M. Vecsei, J.L. Velasco, M. Verstraeten, M. Vervier, E. Viezzer, J. Wagner, E. Wang, F. Wang, M. Wappl, F. Warmer, T. Wegner, Y. Wei, G. Weir, N. Wendler, U. Wenzel, A. White, F. Wilms, T. Windisch, A. Winter, V. Winters, R. Wolf, G. Wurden, P. Xanthopoulos, H.M. Xiang, S. Xu, H. Yamada, J. Yang, R. Yi, M. Yokoyama, B. Zamorski, M. Zanini, M. Zarnstorff, D. Zhang, S. Zhou, J. Zhu, J. Zimmermann, A. Zocco, and S. Zoletnik
Subjects: stellarator, long-pulse operation, magnetic fusion confinement, divertor detachment, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract: After a long device enhancement phase, scientific operation resumed in 2022. The main new device components are the water cooling of all plasma facing components and the new water-cooled high heat flux divertor units. Water cooling allowed for the first long-pulse operation campaign. A maximum discharge length of 8 min was achieved with a total heating energy of 1.3 GJ. Safe divertor operation was demonstrated in attached and detached mode. Stable detachment is readily achieved in some magnetic configurations but requires impurity seeding in configurations with small magnetic pitch angle within the edge islands. Progress was made in the characterization of transport mechanisms across edge magnetic islands: Measurement of the potential distribution and flow pattern reveals that the islands are associated with a strong poloidal drift, which leads to rapid convection of energy and particles from the last closed flux surface into the scrape-off layer. Using the upgraded plasma heating systems, advanced heating scenarios were developed, which provide improved energy confinement comparable to the scenario, in which the record triple product for stellarators was achieved in the previous operation campaign. However, a magnetic configuration-dependent critical heating power limit of the electron cyclotron resonance heating was observed. Exceeding the respective power limit leads to a degradation of the confinement.
Published: 2024
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6. Suitability of administrative claims databases for bariatric surgery research – is the glass half-full or half-empty?

Author: Xiaojuan Li, Kristina H. Lewis, Katherine Callaway, J. Frank Wharam, and Sengwee Toh
Subjects: Bariatric surgery, Body mass index, Healthcare administrative claims, Predictive value of tests, Sensitivity and specificity, Validation study, Medicine (General), R5-920
Abstract: Abstract Background Claims databases are generally considered inadequate for obesity research due to suboptimal capture of body mass index (BMI) measurements. This might not be true for bariatric surgery because of reimbursement requirements and changes in coding systems. We assessed the availability and validity of claims-based weight-related diagnosis codes among bariatric surgery patients. Methods We identified three nested retrospective cohorts of adult bariatric surgery patients who underwent adjusted gastric banding, Roux-en-Y gastric bypass, or sleeve gastrectomy between January 1, 2011 and June 30, 2018 using different components of OptumLabs® Data Warehouse, which contains linked de-identified claims and electronic health records (EHRs). We measured the availability of claims-based weight-related diagnosis codes in the 6-month preoperative and 1-year postoperative periods in the main cohort identified in the claims data. We created two claims-based algorithms to classify the presence of severe obesity (a commonly used cohort selection criterion) and categorize BMI (a commonly used baseline confounder or postoperative outcome). We evaluated their performance by estimating sensitivity, specificity, positive predictive value, negative predictive value, and weighted kappa in two sub-cohorts using EHR-based BMI measurements as the reference. Results Among the 29,357 eligible patients identified using claims only, 28,828 (98.2%) had preoperative weight-related diagnosis codes, either granular indicating BMI ranges or nonspecific denoting obesity status. Among the 27,407 patients with granular preoperative codes, 12,346 (45.0%) had granular codes and 9355 (34.1%) had nonspecific codes in the 1-year postoperative period. Among the 3045 patients with both preoperative claims-based diagnosis codes and EHR-based BMI measurements, the severe obesity classification algorithm had a sensitivity 100%, specificity 71%, positive predictive value 100%, and negative predictive value 78%. The BMI categorization algorithm had good validity categorizing the last available preoperative or postoperative BMI measurements (weighted kappa [95% confidence interval]: preoperative 0.78, [0.76, 0.79]; postoperative 0.84, [0.80, 0.87]). Conclusions Claims-based weight-related diagnosis codes had excellent validity before and after bariatric surgical operation but suboptimal availability after operation. Claims databases can be used for bariatric surgery studies of non-weight-related effectiveness and safety outcomes that are well-captured.
Published: 2020
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7. Current production by non-methanotrophic bacteria enriched from an anaerobic methane-oxidizing microbial community

Author: S. Berger, D.R. Shaw, T. Berben, H.T. Ouboter, M.H. in ’t Zandt, J. Frank, J. Reimann, M.S.M. Jetten, and C.U. Welte
Subjects: Extracellular electron transfer, Microbial community, Acetate, Cytochromes, Zoogloea, ANME-2d, Biotechnology, TP248.13-248.65, Microbiology, QR1-502
Abstract: In recent years, the externalization of electrons as part of respiratory metabolic processes has been discovered in many different bacteria and some archaea. Microbial extracellular electron transfer (EET) plays an important role in many anoxic natural or engineered ecosystems. In this study, an anaerobic methane-converting microbial community was investigated with regard to its potential to perform EET. At this point, it is not well-known if or how EET confers a competitive advantage to certain species in methane-converting communities. EET was investigated in a two-chamber electrochemical system, sparged with methane and with an applied potential of +400 mV versus standard hydrogen electrode. A biofilm developed on the working electrode and stable low-density current was produced, confirming that EET indeed did occur. The appearance and presence of redox centers at −140 to −160 mV and at −230 mV in the biofilm was confirmed by cyclic voltammetry scans. Metagenomic analysis and fluorescence in situ hybridization of the biofilm showed that the anaerobic methanotroph ‘Candidatus Methanoperedens BLZ2’ was a significant member of the biofilm community, but its relative abundance did not increase compared to the inoculum. On the contrary, the relative abundance of other members of the microbial community significantly increased (up to 720-fold, 7.2% of mapped reads), placing these microorganisms among the dominant species in the bioanode community. This group included Zoogloea sp., Dechloromonas sp., two members of the Bacteroidetes phylum, and the spirochete Leptonema sp. Genes encoding proteins putatively involved in EET were identified in Zoogloea sp., Dechloromonas sp. and one member of the Bacteroidetes phylum. We suggest that instead of methane, alternative carbon sources such as acetate were the substrate for EET. Hence, EET in a methane-driven chemolithoautotrophic microbial community seems a complex process in which interactions within the microbial community are driving extracellular electron transfer to the electrode.
Published: 2021
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8. The various therapeutic applications of the medical isotope holmium-166: a narrative review

Author: Nienke J. M. Klaassen, Mark J. Arntz, Alexandra Gil Arranja, Joey Roosen, and J. Frank W. Nijsen
Subjects: Holmium-166, Holmium, Lanthanide, Radiation therapy, SIRT, Microspheres, Medical physics. Medical radiology. Nuclear medicine, R895-920, Therapeutics. Pharmacology, RM1-950
Abstract: Abstract Over the years, a broad spectrum of applications of the radionuclide holmium-166 as a medical isotope has been established. The isotope holmium-166 is attractive as it emits high-energy beta radiation which can be used for a therapeutic effect and gamma radiation which can be used for nuclear imaging purposes. Furthermore, holmium-165 can be visualized by MRI because of its paramagnetic properties and by CT because of its high density. Since holmium-165 has a natural abundance of 100%, the only by-product is metastable holmium-166 and no costly chemical purification steps are necessary for production of nuclear reactor derived holmium-166. Several compounds labelled with holmium-166 are now used in patients, such Ho166-labelled microspheres for liver malignancies, Ho166-labelled chitosan for hepatocellular carcinoma (HCC) and [166Ho]Ho DOTMP for bone metastases. The outcomes in patients are very promising, making this isotope more and more interesting for applications in interventional oncology. Both drugs as well as medical devices labelled with radioactive holmium are used for internal radiotherapy. One of the treatment possibilities is direct intratumoural treatment, in which the radioactive compound is injected with a needle directly into the tumour. Numerous other applications have been developed, like patches for treatment of skin cancer and holmium labelled antibodies and peptides. The second major application that is currently clinically applied is selective internal radiation therapy (SIRT, also called radioembolization), a novel treatment option for liver malignancies. This review discusses medical drugs and medical devices based on the therapeutic radionuclide holmium-166.
Published: 2019
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9. Provider-level rates of HEDIS-consistent HPV vaccination in a regional health plan

Author: Catherine A. Panozzo, Melissa B. Gilkey, Melanie L. Kornides, and J. Frank Wharam
Subjects: adolescent health, human papillomavirus infections/prevention & control, human papillomavirus vaccine, administrative claims, healthcare, healthcare providers, vaccination coverage, Immunologic diseases. Allergy, RC581-607, Therapeutics. Pharmacology, RM1-950
Abstract: Background. Health insurers are well-positioned to address low HPV vaccination coverage in the US through initiatives such as provider assessment and feedback. However, little is known about the feasibility of using administrative claims data to assess provider performance on vaccine delivery. Methods. We used administrative claims data from a regional health plan to estimate provider performance on the 2013–2015 Healthcare Effectiveness Data and Information Set (HEDIS) measure for HPV vaccine. This measure required that a girl receive three doses of HPV vaccine by age 13. Providers who administered ≥1 dose in a HEDIS-consistent series received credit for meeting the goal. Results. From January 2008-April 2015, 1,975 (8.5%) of 11–12 year-old girls in our sample received a HEDIS-consistent HPV vaccine series. Our sample of providers consisted of 1,236 who had ≥10 well-visits with different female patients, and 94% of these were pediatricians. A substantial minority of providers (39.4%) did not administer any HEDIS-consistent HPV vaccine doses. Only 5.5% of providers administered HPV vaccine doses that were part of a HEDIS-consistent series to at least one-quarter of their patients. These estimates did not vary by provider sex or age. Doses in a HEDIS-consistent vaccine series were often attributed to multiple providers. Conclusions. In a regional health plan, only 5.5% of providers in our sample administered doses that were part of a complete, three-dose HPV vaccine series to at least one-quarter of their 11–12 year-old female patients.
Published: 2019
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10. Opportunities to encourage mail order pharmacy delivery service use for diabetes prescriptions: a qualitative study

Author: Julie A. Schmittdiel, Cassondra J. Marshall, Deanne Wiley, Christopher V. Chau, Connie M. Trinacty, J. Frank Wharam, O. Kenrik Duru, Andrew J. Karter, and Susan D. Brown
Subjects: Diabetes, Mail order pharmacy, Barriers and facilitators, Patient preference, Acceptance of health care, Qualitative research, Public aspects of medicine, RA1-1270
Abstract: Abstract Background Medication non-adherence is a major contributor to poor outcomes in diabetes. Previous research has shown an association between use of mail order pharmacy delivery and better medication adherence, but little is known about the barriers and facilitators to mail order pharmacy use in diabetes patients. This qualitative study examined factors related to mail order pharmacy use versus traditional “brick and mortar” pharmacies to refill prescriptions. Methods We conducted four 90-min focus groups in 2016 among 28 diabetes patients in the Hawaii and Northern California regions of Kaiser Permanente, a large integrated health care delivery system. We queried participants on their preferred mode for refilling prescriptions and perceived barriers and facilitators of mail order pharmacy use. One researcher independently coded each focus group transcript, with two of these transcripts double-coded by a second researcher to promote reliability. We employed thematic analysis guided by the Capability, Opportunity, Motivation, and Behavior (COM-B) framework using NVivo 11 software. Results A total of 28 diabetes patients participated. Participants’ average age was 64.1 years; 57% were female; and racial/ethnic backgrounds included Asian/Native Hawaiian/Pacific Islander (36%), Black/African-American (21%) Hispanic/Latino (7%), and non-Hispanic White (36%). Analysis uncovered 26 themes related to the decision to use mail order pharmacy, with each theme representing a barrier or facilitator mapped to the COM-B framework. Most themes (20/26) fell into the COM-B category of ‘Opportunity.’ Opportunity barriers to mail order pharmacy use included unpredictability of medication delivery date, concerns about mail security, and difficulty coordinating refill orders for multiple prescriptions. In contrast, facilitators included greater access and convenience (e.g., no need to wait in line or arrange transportation) compared to traditional pharmacies. Motivational facilitators to mail order pharmacy use included receiving a pharmacy benefit plan incentive of a free one-month supply of prescriptions. Conclusions This study found that while patients with diabetes may benefit from mail order pharmacy use, they perceive numerous barriers to using the service. These findings will inform the design of interventions and quality improvement initiatives to increase mail order pharmacy use, which in turn may improve medication adherence and outcomes in diabetes patients, across health care systems.
Published: 2019
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11. Fanning the Flames of Passion: A Develop Mindset Predicts Strategy-Use Intentions to Cultivate Passion

Author: Patricia Chen, Yuching Lin, Don J. H. Pereira, Paul A. O’Keefe, and J. Frank Yates
Subjects: mindsets, implicit theories, passion, self-regulation, strategies, well-being, Psychology, BF1-990
Abstract: College students are encouraged to major in subjects they are passionate about but less often advised about what to do when passion is low. What self-regulatory strategies do students use to up-regulate their passion toward their subjects, and how might they be oriented toward using such effective strategies? Three studies examined how the belief that passion is developed – a “develop” mindset – relates to students’ intentions to use strategies to actively grow their passion. The more strongly students endorsed a develop mindset, the more of these “cultivation strategies” they reported using, and in turn, the larger their increase in reported passion toward their subject majors (Study 1). Instilling a develop mindset causally increased students’ intentions to use more cultivation strategies (Study 2) – with some effects lasting up to a year (Study 3). Instilling a develop mindset can potentially help students to ignite their passion when its flame burns low.
Published: 2021
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12. A Pilot Study of Cardiac MRI in Breast Cancer Survivors After Cardiotoxic Chemotherapy and Three-Dimensional Conformal Radiotherapy

Author: Carmen Bergom, Jason Rubenstein, J. Frank Wilson, Aimee Welsh, El-Sayed H. Ibrahim, Phillip Prior, Aronne M. Schottstaedt, Daniel Eastwood, Mei-Jie Zhang, Adam Currey, Lindsay Puckett, Jennifer L. Strande, Julie A. Bradley, and Julia White
Subjects: 3D conformal radiation therapy, cardiotoxicity, cardiac MRI, radiation therapy, breast cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Purpose/ObjectivesNode-positive breast cancer patients often receive chemotherapy and regional nodal irradiation. The cardiotoxic effects of these treatments, however, may offset some of the survival benefit. Cardiac magnetic resonance (CMR) is an emerging modality to assess cardiac injury. This is a pilot trial assessing cardiac damage using CMR in patients who received anthracycline-based chemotherapy and three-dimensional conformal radiotherapy (3DCRT) regional nodal irradiation using heart constraints.Materials and MethodsNode-positive breast cancer patients (2000–2008) treated with anthracycline-based chemotherapy and 3DCRT regional nodal irradiation (including the internal mammary chain nodes) with heart ventricular constraints (V25 < 10%) were invited to participate. Cardiac tissues were contoured and analyzed separately for whole heart (pericardium) and for combined ventricles and left atrium (myocardium). CMR obtained ventricular function/dimensions, late gadolinium enhancement (LGE), global longitudinal strain (GLS), and extracellular volume fraction (ECV) as measures of cardiac injury and/or early fibrosis. CMR parameters were correlated with dose-volume constraints using Spearman correlations.ResultsFifteen left-sided and five right-sided patients underwent CMR. Median diagnosis age was 50 (32–77). No patients had baseline cardiac disease before regional nodal irradiation. Median time after 3DCRT was 8.3 years (5.2–14.4). Median left-sided mean heart dose (MHD) was 4.8 Gy (1.1–11.2) and V25 was 5.7% (0–12%). Median left ventricular ejection fraction (LVEF) was 63%. No abnormal LGE was observed. No correlations were seen between whole heart doses and LVEF, LV mass, GLS, or LV dimensions. Increasing ECV did not correlate with increased heart or ventricular doses. However, correlations between higher LV mass and ventricular mean dose, V10, and V25 were seen.ConclusionAt a median follow-up of 8.3 years, this cohort of node-positive breast cancer patients who received anthracycline-based chemotherapy and regional nodal irradiation had no clinically abnormal CMR findings. However, correlations between ventricular mean dose, V10, and V25 and LV mass were seen. Larger corroborating studies that include advanced techniques for measuring regional heart mechanics are warranted.
Published: 2020
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13. Improving acceptability of nudges: Learning from attitudes towards opt-in and opt-out policies

Author: Haoyang Yan and J. Frank Yates
Subjects: nudges, opt-in, opt-out, policy, attitudes, organ donation, retirement saving, carbon emission offsetNAKeywords, Social Sciences, Psychology, BF1-990
Abstract: Policy makers should understand people’s attitudes towards opt-out nudges to smoothly promote and implement the policies. Our research compares people’s perceptions of opt-in and three improved versions of opt-out (transparency, emphasis on the low-cost opt-out option, education) in pro-social and pro-self policy domains, e.g., organ donation (N=610), carbon emission offset (N=613), and retirement saving (N=602). We found that people acknowledged more practical and societal benefits of opt-out than opt-in in organ donation and retirement saving but less so in carbon emission offset. Improved opt-out policies failed to address ethical concerns and most emotional discomfort concerns in organ donation whereas opt-out transparency and emphasis on low-cost opt-out were more successful than education at addressing concerns in retirement saving and carbon emission offset. Nonetheless, transparency and education may raise consciousness of policies’ aims. The results suggest that 1) acceptability of opt-out approaches may be more difficult to enhance in some domains than others; 2) policy makers should ensure the public understands that opt-out is a convenient choice and may consider combining all forms of improvement to increase people’s acceptance of opt-out nudges.
Published: 2019

14. Production of novel diagnostic radionuclides in small medical cyclotrons

Author: Mateusz Adam Synowiecki, Lars Rutger Perk, and J. Frank W. Nijsen
Subjects: Radionuclide production, Cyclotron, Technetium-99 m, Radioiodine, Zirconium-89, Copper-64, Medical physics. Medical radiology. Nuclear medicine, R895-920, Therapeutics. Pharmacology, RM1-950
Abstract: Abstract The global network of cyclotrons has expanded rapidly over the last decade. The bulk of its industrial potential is composed of small medical cyclotrons with a proton energy below 20 MeV for radionuclides production. This review focuses on the recent developments of novel medical radionuclides produced by cyclotrons in the energy range of 3 MeV to 20 MeV. The production of the following medical radionuclides will be described based on available literature sources: Tc-99 m, I-123, I-124, Zr-89, Cu-64, Ga-67, Ga-68, In-111, Y-86 and Sc-44. Remarkable developments in the production process have been observed in only some cases. More research is needed to make novel radionuclide cyclotron production available for the medical industry.
Published: 2018
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15. Studies on fatty liver induction by 4-aminopyrazolopyrimidine

Author: J. Frank Henderson
Subjects: Biochemistry, QD415-436
Abstract: The effects of the adenine analogue, 4-aminopyrazolopyrimidine, on lipid metabolism in mouse liver have been studied in an attempt to ascertain the mechanism by which this drug causes fatty livers. Injection of I mg of APP caused an increase in the total liver lipid of 3- to 4-fold in 24 hr, which was almost entirely accounted for as neutral lipid. There was a small increase in the cholesterol content of treated livers, but no change in the amount of phospholipid. Treatment with APP inhibited the incorporation of acetate-C14 into lipids of liver slices in vitro, but had little effect on the oxidation of acetate-C14 and palmitate-C14 in vitro. The plasma lipid concentration was decreased by APP treatment, and this was caused by a drop in triglycerides and cholesterol, whereas phospholipids and FFA did not change. Palmitate-C14 was taken up less well by livers of mice treated with APP than by livers of control mice. Although APP caused a profound inhibition of incorporation of orotic acid-C14 into RNA, the incorporation of glycine-C14 Into liver and plasma proteins was not diminished. The hyperlipemia normally elicited by Triton WR-1339 was inhibited by APP, which strongly suggests that this compound inhibits the secretion of triglycerides from the liver.
Published: 1963
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16. Advanced Step Density Modulation Technique to Reduce Current Ripples in High-Frequency Inverter for WPT EV Charging Systems

Author: J. Franklin, R. K. Pongiannan, Roobaea Alroobaea, Ahmed Emara, and R. Narayanamoorthi
Subjects: Current ripples, delay-time, pulse density modulation, step density modulation, wireless power transfer, Electrical engineering. Electronics. Nuclear engineering, TK1-9971
Abstract: This paper analyzes Step Density Modulation (SDM) technique for high-frequency inverters in Wireless Power Transfer (WPT) systems for Electric Vehicle (EV) charging. While Pulse Density Modulation (PDM) is commonly used to control high-frequency inverters, it faces limitations in managing current ripple, leading to electromagnetic interference (EMI), reduced power transfer efficiency, and system performance degradation. Step Density Modulation is proposed as an advanced alternative to PDM, offering dynamic pulse density adjustments in discrete stages to align with inverter switching characteristics. This approach minimizes the effects of dead time, significantly reducing current ripple and total harmonic distortion (THD), thereby enhancing waveform quality and system efficiency. A comprehensive mathematical model compares current ripple magnitude, harmonic spectrum, and inverter delay time for both modulation techniques. MATLAB simulations, validated through hardware prototype implementation on a 5 kW WPT EV charger, demonstrate that SDM reduces current ripple by up to 30% and THD of 20% compared to PDM. The hardware prototype confirms smoother inverter output, improved power stability, and increased efficiency, establishing SDM as a reliable and practical solution for enhancing WPT systems in EV charging applications.
Published: 2025
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17. ClimeApp: data processing tool for monthly, global climate data from the ModE-RA palaeo-reanalysis, 1422 to 2008 CE

Author: R. Warren, N. E. Bartlome, N. Wellinger, J. Franke, R. Hand, S. Brönnimann, and H. Huhtamaa
Subjects: Environmental pollution, TD172-193.5, Environmental protection, TD169-171.8, Environmental sciences, GE1-350
Abstract: ClimeApp is a newly developed web-based processing tool for the state-of-the-art ModE-RA palaeo-climate reanalysis. It presents temperature, precipitation and pressure reconstructions with global coverage and monthly resolution for the period 1422 to 2008 CE. These can be visualized as maps or time series and are compared with historical or other climate-related information through composite, correlation and regression functions. ClimeApp allows access to three data sets: (1) ModE-RA, a reanalysis that is created by assimilating early instrumental documentary and proxy data into an ensemble of climate model simulations; (2) ModE-Sim, the native version of the underlying ensemble simulations, i.e. prior to data assimilation; and (3) ModE-RAclim, an alternative version of the reanalysis product. Together, these allow researchers to separate the effects of model simulations and observations on the reanalysis. The app is designed to allow quick data processing for climatologists and easy use for non-climatologists. Specifically, it aims to help bring climate into the humanities, where climatological data still have huge potential to advance research. This paper outlines the development, processing and applications of ClimeApp and presents an updated analysis of the calamitous Tambora volcanic eruption and the 1816 “year without a summer” in Europe, using the new ModE data sets. ClimeApp is available at https://mode-ra.unibe.ch/climeapp/ (last access: 25 October 2024).
Published: 2024
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18. Inhibition of GPX4 enhances CDK4/6 inhibitor and endocrine therapy activity in breast cancer

Author: M. T. Herrera-Abreu, J. Guan, U. Khalid, J. Ning, M. R. Costa, J. Chan, Q. Li, J-P. Fortin, W. R. Wong, P. Perampalam, A. Biton, W. Sandoval, J. Vijay, M. Hafner, R. Cutts, G. Wilson, J. Frankum, T. I. Roumeliotis, J. Alexander, O. Hickman, R. Brough, S. Haider, J. Choudhary, C. J. Lord, A. Swain, C. Metcalfe, and N. C. Turner
Subjects: Science
Abstract: Abstract CDK4/6 inhibition in combination with endocrine therapy is the standard of care for estrogen receptor (ER+) breast cancer, and although cytostasis is frequently observed, new treatment strategies that enhance efficacy are required. Here, we perform two independent genome-wide CRISPR screens to identify genetic determinants of CDK4/6 and endocrine therapy sensitivity. Genes involved in oxidative stress and ferroptosis modulate sensitivity, with GPX4 as the top sensitiser in both screens. Depletion or inhibition of GPX4 increases sensitivity to palbociclib and giredestrant, and their combination, in ER+ breast cancer models, with GPX4 null xenografts being highly sensitive to palbociclib. GPX4 perturbation additionally sensitises triple negative breast cancer (TNBC) models to palbociclib. Palbociclib and giredestrant induced oxidative stress and disordered lipid metabolism, leading to a ferroptosis-sensitive state. Lipid peroxidation is promoted by a peroxisome AGPAT3-dependent pathway in ER+ breast cancer models, rather than the classical ACSL4 pathway. Our data demonstrate that CDK4/6 and ER inhibition creates vulnerability to ferroptosis induction, that could be exploited through combination with GPX4 inhibitors, to enhance sensitivity to the current therapies in breast cancer.
Published: 2024
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19. Higher dose corticosteroids in hospitalised COVID-19 patients requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trialResearch in context

Author: O. Abani, A. Abbas, F. Abbas, J. Abbas, K. Abbas, M. Abbas, S. Abbasi, H. Abbass, A. Abbott, N. Abdallah, A. Abdelaziz, M. Abdelfattah, B. Abdelqader, A. Abdul, B. Abdul, S. Abdul, A. Abdul Rasheed, A. Abdulakeem, R. Abdul-Kadir, A. Abdullah, A. Abdulmumeen, R. Abdul-Raheem, N. Abdulshukkoor, K. Abdusamad, Y. Abed El Khaleq, M. Abedalla, A. Abeer Ul Amna, L. Abel, K. Abernethy, M. Abeywickrema, C. Abhinaya, A. Abidin, A. Aboaba, A. Aboagye-Odei, C. Aboah, H. Aboelela, H. Abo-Leyah, K. Abouelela, A. Abou-Haggar, M. Abouibrahim, A. Abousamra, M. Abouzaid, M. Abraham, T. Abraham, A. Abraheem, J. Abrams, R. Abrams, H.J. Abu, A. Abu-Arafeh, S.M. Abubacker, A. Abung, Y. Abusamra, Y. Aceampong, A. Achara, D. Acharya, F. Acheampong, P. Acheampong, S. Acheampong, J. Acheson, S. Achieng, A. Acosta, R. Acquah, C. Acton, J. Adabie-Ankrah, P. Adair, A.S. Adam, F. Adam, M. Adam, H. Adamali, M. Adamczyk, C. Adams, D. Adams, K. Adams, L. Adams, N. Adams, R. Adams, T. Adams, L. Adamu-Ikeme, K. Adatia, K. Adcock, L. Addai-Boampong, A. Addo, O. Adeagbo, A. Adebiyi, O. Adedeji, Y. Adegeye, K. Adegoke, V. Adell, S. Adenwalla, F.W. Adeoye, O.A. Adesemoye, E.O. Adewunmi, A. Adeyanju, J. Adeyemi, T. Adeyemo, B. Adhikari, S.A. Adhikari, R. Adhikary, A. Aditya, P. Adjepong, G. Adkins, A. Adnan, M. Adriaanse, J. Aeron-Thomas, D. Affleck, C. Afnan, M. Afridi, P. Afrim, F.A. Afriyie, Z.A. Aftab, A. Afum-Adjei Awuah, M. Agarwal, P.N. Agasiya, R. Agbeko, C. Agbo, S. Aggarwal, A. Aghababaie, L. Aguilar Jimenez, J.A. Agyekum, K. Agyen, E.K. Ahadome, S. Ahamed Sadiq, M.H. Ahammed Nazeer, M. Ahmad, S. Ahmad, A. Ahmed, B.A.R. Ahmed, B. Ahmed, F. Ahmed, H. Ahmed, I. Ahmed, K. Ahmed, L. Ahmed, M. Ahmed, M.C. Ahmed, M.S. Ahmed, N. Ahmed, O. Ahmed, R.A. Ahmed, R. Ahmed, S. Ahmed, S.G. Ahmed, S.H. Ahmed, R. Ahmed Ali, B. Ahmed Mohamud, S. Ahmer, A. Ahonia, C. Aidoo, C. Aiken, D. Ail, M. Ainsworth, M. Aissa, L. Aitken, B. Ajay, A. Ajibode, A. Ajmi, N. Akhtar, S. Akili, B. Akinbiyi, O. Akindolie, Y. Akinfenwa, O. Akinkugbe, I. Akinpelu, M. Akram, O. Aktinade, U. Akudi, A.S.A.R. Al Aaraj, A. Al Balushi, M. Al Dakhola, A. Al Swaifi, E. Al-Abadi, A. Alabi, N. Aladangady, M. Alafifi, A. Alam, S. Alam, A. Al-Asadi, K. Alatzoglou, P. Albert, A. Albertus, L. Albon, A. Alcala, G. Alcorn, S. Alcorn, A. Aldana, D. Alderdice, A. Aldesouki, R. Aldouri, J. Aldridge, N. Aldridge, R. Ale, R.M. Ale, A. Alegria, A. Alexander, C. Alexander, J. Alexander, P.D.G. Alexander, J. Al-fori, L. Alghazawi, O. Alhabsha, B. Al-Hakim, R. Alhameed, M. Al-Hayali, S. Al-Hity, A. Ali, F.R. Ali, J. Ali, M. Ali, M.S. Ali, N. Ali, O. Ali, R. Ali, S. Ali, E. Aliberti, J. Alin, A. Alina, A. Alipustain, B. Alisjahbana, F. Aliyuda, K. Alizadeh, M. Al-Jibury, S. Al-Juboori, M. Al-Khalil, A. Alkhudhayri, M. Alkhusheh, F. Allan, N. Allan, A. Allanson, R. Allcock, E. Allen, J. Allen, K. Allen, L. Allen, P. Allen, R. Allen, S. Allen, T. Allen, A. Alli, K. Allison, B. Allman, H.K. Allsop, L. Allsop, D. Allsup, A.F.T. Almahroos, H. Al-Moasseb, M. Al-Obaidi, L. Alomari, A. Al-Rabahi, B. Al-Ramadhani, Z. Al-Saadi, R. Al-Sammarraie, I. Alshaer, R. Al-Shahi Salman, W. Al-Shamkhani, F. Alsheikh, B. Al-Sheklly, S. Altaf, A. Alty, M. Alvarez, M. Alvarez Corral, E. Alveyn, M. Alzetani, S. Amamou, N. Amar, S. Ambalavanan, R. Ambrogetti, C. Ambrose, A. Ameen, A. Amelia Ganefianty, K. Ames, M.R. Amezaga, A. Amin, K. Amin, S. Amin, T. Amin, B. Amit, A. Amjad, N. Amjad, J. Amoah-Dankwa, A. Amoako-Adusei, V. Amosun, M. Amsal, K. Amsha, J. Amuasi, N. Amutio Martin, P. Amy, A. Anada, A. Anand, S. Anandappa, S.D. Anantapatnaikuni, N.K.N. Andari, E. Anderson, J. Anderson, L. Anderson, M. Anderson, N. Anderson, R. Anderson, S. Anderson, W. Anderson, P. Andreou, A. Andrews, J. Andrews, K. Aneke, A. Ang, W.W. Ang, T. Angel, A. Angela, P. Angelini, L. Anguvaa, O. Anichtchik, M. Anim-Somuah, K. Aniruddhan, J. Annett, L. Anning, M. Ansah, P.J. Anstey, R. Anstey, A. Anthony, A. Anthony-Pillai, P. Antill, Z. Antonina, V. Anu, M. Anwar, S. Anwar, E. Apetri, A. Apostolopoulos, S. Appleby, D. Appleyard, M.F. Aquino, B. Araba, S. Aransiola, M. Araujo, A. Archer, D. Archer, S. Archer, D. Arcoria, C. Ardley, G. Arhin-Sam, A.-M. Arias, O. Aribike, R. Arimoto, N.L.P.E. Arisanti, C. Arkley, C. Armah, I. Armata, J. Armistead, A. Armitage, C. Armstrong, M. Armstrong, S. Armstrong, W. Armstrong, P. Armtrong, H. Arndt, C. Arnison-Newgass, D. Arnold, R. Arnold, A. Arnott, D. Arora, K. Arora, P. Arora, R. Arora, A. Arter, A. Arthur, N.M. Artini, A. Arumaithurai, A. Arya, R. Arya, D. Aryal, D. Asandei, G.A. Asare, A. Asghar, M. Asghar, A. Ashab, C. Ashbrook-Raby, H. Ashby, J. Ashcroft, S. Ashcroft, G. Asher, Z. Ashfak, A. Ashfaq, H.A. Asiamah, A. Ashish, D. Ashley, S. Ashman-Flavell, S. Ashok, A.-E.-A. Ashour, M.Z. Ashraf, S. Ashraf, M.B. Ashraq, D. Ashton, S. Ashton, A. Ashworth, F.J. Ashworth, R. Ashworth, A. Aslam, I. Aslam, S. Aslam, L. Aslett, H. Asogan, A. Asrar, O. Assaf, R. Astin-Chamberlain, Y.E. Atabudzi, P. Athavale, D. Athorne, B. Atkins, C. Atkins, S. Atkins, J. Atkinson, V. Atkinson, A. Atomode, B. Atraskiewicz, A.A. Attia, E. Attubato, M. Attwood, P. Aubrey, Z. Auer, A. Aujayeb, A.T. Aung, H. Aung, H.W.W. Aung, K.K. Aung, K.T. Aung, N. Aung, Y. Aung, Z.M. Aung, E. Austin, K. Austin, A. Auwal, M. Avari, M. Avery, N. Aveyard, J. Avis, G. Aviss, C. Avram, P. Avram, A. Awadelkareem, G. Awadzi, M. Awaly, A. Awan, S. Awisi, A. Aya, E. Ayaz, J.M. Ayerh, A. Ayers, J. Azam, A. Azeem, M. Azharuddin, A. Aziz, G. Aziz, I. Aziz, N. Aziz, A. Azkoul, A. Azman Shah, G. Azzopardi, H. Azzoug, F. Babatunde, M. Babi, B. Babiker, G. Babington, M. Babirecki, M. Babores, A.O. Babs-Osibodu, T. Bac, S. Bacciarelli, R. Bachar, M.-E. Bachour, A. Bachti, G. Bacon, J. Bacon, B. Badal, A. Badat, M. Bader, G.R. Badhan, S. Badhrinarayanan, J.P. Bae, A. Baggaley, A. Baggott, G. Bagley, D. Bagmane, L. Bagshaw, K. Bahadori, Y. Bahurupi, A. Bailey, J. Bailey, K. Bailey, L. Bailey, M.A. Bailey, M. Bailey, P. Bailey, S. Bailey, H. Baillie, J.K. Baillie, J. Bain, V. Bains, D. Baird, E. Baird, K. Baird, S. Baird, T. Baird, Y. Baird, A. Bajandouh, M. Bajracharya, D.C. Baker, E. Baker, J. Baker, K. Baker, M. Baker, R. Baker, T.-A. Baker, V. Baker, H. Bakere, N. Bakerly, M. Baker-Moffatt, A. Bakhai, N. Bakhtiar, P. Bakoulas, D. Bakthavatsalam, N. Balachandran, A. Balan, P. Balasingam, T. Balaskas, M. Balasubramaniam, N. Balatoni, A. Balcombe, A. Baldwin, C. Baldwin, D. Baldwin, F. Baldwin, R. Baldwin-Jones, N. Bale, J. Balfour, M. Ball, Ro Ball, K. Ballard, I. Balluz, C. Balmforth, E. Balogh, A. Baltmr, A. Baluwala, G. Bambridge, A. Bamford, P. Bamford, A. Bamgboye, E. Bancroft, H. Bancroft, J. Banda, K. Bandaru, S. Bandi, N. Bandla, S. Bandyopadhyam, A. Banerjee, R. Banerjee, P. Bang, S. Baniya, O. Bani-Saad, H. Banks, L. Banks, P. Banks, C. Bann, H. Bannister, O. Bannister, L. Banton, D.G. Bao, T. Bao, M. Baptist, T. Baqai, A.M. Baral, S.C. Baral, D. Baramova, R. Barber, E. 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Williamson, J. Williamson, J.D. Williamson, R. Williamson, H. Williamson, E. Willis, H. Willis, J. Willis, L. Wills, L. Willsher, C. Willshire, F. Willson, J. Willson, A. Wilson, B. Wilson, D. Wilson, I. Wilson, J. Wilson, K. Wilson, K.-A. Wilson, L. Wilson, M. Wilson, S. Wilson, T. Wilson, K.L.Y. Win, M. Win, T. Win, T.T. Win, W.Y.W. Win, L. Winckworth, L. Winder, P. Winder, S. Winearl, H. Winmill, S. Winn, C. Winpenny, H. Winslow, H. Winter, J. Winter, B. Winter-Goodwin, J. Winterton, H. Winwood, J. Wischhusen, S. Wisdom, M. Wise, M. Wiselka, R. Wiseman, S. Wiseman, S. Wishart, T. WIshlade, E. Witele, N. Withers, J. Wittes, D. Wixted, T. Wodehouse, W. Wolf, N. Wolff, K. Wolffsohn, R. Wolf-Roberts, E. Wolodimeroff, A. Wolstencroft, A. Wong, C. Wong, C.-H. Wong, C.-M. Wong, E. Wong, J.S.Y. Wong, K.Y. Wong, M.Y. Wong, N. Wong, S. Wong, T. Wong, A.A. Wongkyezeng, A. Wood, C. Wood, D. Wood, F. Wood, G. Wood, H. Wood, J. Wood, L. Wood, M. Wood, S. Wood, T. Wood, K. Woodall, R. Woodfield, C. Woodford, E. Woodford, J. Woodford, L. Woodhead, T. Woodhead, P. Woodland, M. Woodman, S. Woodmansey, C. Woods, J. Woods, K. Woods, S. Woods, Z. Woodward, M. Woolcock, G. Wooldridge, R. Woolf, C. Woollard, L. Woollen, E. Woolley, J. Woolley, D. Woosey, D. Wootton, J. Wootton, D. Worley, S. Worton, J. Wraight, M. Wray, K. Wren, L. Wren, C. Wrey Brown, C. Wright, D. Wright, F. Wright, H. Wright, I. Wright, L. Wright, R. Wright, S. Wright, T. Wright, C. Wroe, H. Wroe, H. Wu, P. Wu, J. Wubetu, F. Wulandari, R. Wulandari, S. Wurie, C. Wyatt, F. Wyn-Griffiths, I. Wynter, B. Xavier, A. Xhikola, B.E. Xia, Z. Xia, E. Yacoba, S. Yadav, M. Yakubi, M. Yan, Y. Yanagisawa, F. Yang, Y. Yang, M. Yanney, W.L. Yap, N. Yaqoob, S. Yasmin, B. Yates, D. Yates, E. Yates, H. Yates, T. Yates, M. Yates, J. Ye, C. Yearwood Martin, K. Yein, F. Yelnoorkar, L. Yen, L.M. Yen, A. Yeoh, C.Y. Yeung, P. Yew, D. Yewatkar, L. Ylquimiche Melly, I. Ynter, H. Yong, J. Yorke, J. Youens, A. Younes Ibrahim, E. Young, G. Young, L. Young, A. Yousafzar, S. Youssouf, A. Yousuf, H. Yovita, C. Yu, J.S.J. Yuan, N. Yufaniaputri, B. Yung, D. Yusef, S. Yusef, I. Yusuf, A.-S. Zafar, S. Zagalo, S. Zaher, A. Zahoor, M. Zainab, T. Zak, K. Zaki, N. Zakir, K. Zalewska, A. Zamalloa, M. Zaman, S. Zaman, J. Zamikula, L. Zammit, M. Zammit-Mangion, M. Zawadzka, M. Zayed, E. Zebracki, D. Zehnder, L. Zeidan, D. Zeinali, J. Zhang, X. Zhao, D. Zheng, D. Zhu, M. Zia, O. Zibdeh, R. Zill-E-Huma, E.T. Zin, E. Zincone, G. Zindoga, E. Zinkin, V. Zinyemba, C. Zipitis, L. Zitter, A. Zmierczak, G. Zubikarai, A. Zubir, N. Zuhra, R. Zulaikha, S. Zulfikar, C. Zullo, and A. Zuriaga-Alvaro
Subjects: COVID-19, Corticosteroid, Dexamethasone, Mortality, Clinical trial, Medicine (General), R5-920
Abstract: Summary: Background: Low dose corticosteroids (e.g., 6 mg dexamethasone) have been shown to reduce mortality for hypoxic COVID-19 patients. We have previously reported that higher dose corticosteroids cause harm in patients with clinical hypoxia but not receiving ventilatory support (the combination of non-invasive mechanical ventilation, including high-flow nasal oxygen, continuous positive airway pressure and bilevel positive airway pressure ventilation, and invasive mechanical ventilation or extra-corporeal membrane oxygenation), but the balance of efficacy and safety in patients receiving ventilatory support is uncertain. Methods: This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) assessed multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients receiving ventilatory support were randomly allocated (1:1) to either usual care with higher dose corticosteroids (dexamethasone 20 mg once daily for 5 days followed by 10 mg once daily for 5 days or until discharge if sooner) or usual standard of care alone (which includes dexamethasone 6 mg once daily for 10 days or until discharge if sooner). The primary outcome was 28-day mortality; secondary outcomes were duration of hospitalisation and (among participants not on invasive mechanical ventilation at baseline) the composite of invasive mechanical ventilation or death. Recruitment closed on 31 March 2024 when funding for the trial ended. The RECOVERY trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936). Findings: Between 25 May 2021 and 9 January 2024, 477 COVID-19 patients receiving ventilatory support were randomly allocated to receive usual care plus higher dose corticosteroids vs. usual care alone (of whom 99% received corticosteroids during the follow-up period). Of those randomised, 221 (46%) were in Asia, 245 (51%) in the UK and 11 (2%) in Africa. 143 (30%) had diabetes mellitus. Overall, 86 (35%) of 246 patients allocated to higher dose corticosteroids vs. 86 (37%) of 231 patients allocated to usual care died within 28 days (rate ratio [RR] 0.87; 95% CI 0.64–1.18; p = 0.37). There was no significant difference in the proportion of patients discharged from hospital alive within 28 days (128 [52%] in the higher dose corticosteroids group vs. 120 [52%] in the usual care group; RR 1.04, 0.81–1.33]; p = 0.78). Among those not on invasive mechanical ventilation at baseline, there was no clear reduction in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (76 [37%] of 206 vs. 93 [45%] of 205; RR 0.79 [95% CI 0.63–1.00]; p = 0.05). Interpretation: In patients hospitalised for COVID-19 receiving ventilatory support, we found no evidence that higher dose corticosteroids reduced the risk of death compared to usual care, which included low dose corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute for Health Research (Grant ref: MC_PC_19056), and Wellcome Trust (Grant Ref: 222406/Z/20/Z).
Published: 2025
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20. Reproducibility of semi-quantitative assessment of aortic valve calcification and valve motion on echocardiography: a small-scale study

Author: D. Balian, B. Koethe, S. Mohanty, Y. Daaboul, S. H. Mahrokhian, J. Frankel, J. Li, A. Kherlopian, B. C. Downey, and B. Wessler
Subjects: Echocardiography, Aortic stenosis, Semi-quantitative, Reproducibility, Inter-reader Reliability, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Background Aortic stenosis (AS) is the most common degenerative valve disease in high income countries. While hemodynamic metrics are commonly used to assess severity of stenosis, they are impacted by loading conditions and stroke volume and are often discordant. Anatomic valve assessments such as aortic valve calcification (AVC) and valve motion (VM) during transthoracic echocardiography (TTE) can offer clues to disease severity. The reliability of these semi-quantitatively assessed anatomic imaging parameters is unknown. Methods This is a retrospective study of semi-quantitative assessment of AVC and valve VM on TTE. TTEs representing a range of AS severities were identified. The degree of calcification of the aortic valve and the degree of restricted VM were assessed in standard fashion. AVC scores and valve motion were assessed by readers with varied training levels blinded to the severity of AS. Correlation and inter-reader reliability between readers were assessed. Results 420 assessments (210 each for AVC and VM) were collected for 35 TTEs. Correlation of AVC for imaging trainees (fellows and students, respectively), ranged from 0.49 (95% CI 0.18–0.70) to 0.62 (95% CI 0.36–0.79) and 0.58 (95% CI 0.30–0.76) to 0.54 (95% CI 0.25–0.74) for VM. Correlation of anatomic assessments between echocardiographer-assigned AVC grades was r = 0.76 (95% CI 0.57–0.87)). The correlation between echocardiographer-assigned assessment of VM was r = 0.73 (95% CI 0.53–0.86), p
Published: 2024
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21. Level0 to Level1B processor for MethaneAIR

Author: E. K. Conway, A. H. Souri, J. Benmergui, K. Sun, X. Liu, C. Staebell, C. Chan Miller, J. Franklin, J. Samra, J. Wilzewski, S. Roche, B. Luo, A. Chulakadabba, M. Sargent, J. Hohl, B. Daube, I. Gordon, K. Chance, and S. Wofsy
Subjects: Environmental engineering, TA170-171, Earthwork. Foundations, TA715-787
Abstract: This work presents the development of the MethaneAIR Level0–Level1B processor, which converts raw L0 data to calibrated and georeferenced L1B data. MethaneAIR is the airborne simulator for MethaneSAT, a new satellite under development by MethaneSAT LLC, a subsidiary of the Environmental Defense Fund (EDF). MethaneSAT's goals are to precisely map over 80 % of the production sources of methane from oil and gas fields across the globe to an accuracy of 2–4 ppb on a 2 km2 scale. Efficient algorithms have been developed to perform dark corrections, estimate the noise, radiometrically calibrate data, and correct stray light. A forward model integrated into the L0–L1B processor is demonstrated to retrieve wavelength shifts during flight accurately. It is also shown to characterize the instrument spectral response function (ISRF) changes occurring at each sampled spatial footprint. We demonstrate fast and accurate orthorectification of MethaneAIR data in a three-step process: (i) initial orthorectification of all observations using aircraft avionics, a simple camera model, and a medium-resolution digital elevation map; (ii) registration of oxygen (O2) channel grayscale images to reference Multispectral Instrument (MSI) band 11 imagery via Accelerated-KAZE (A-KAZE) feature extraction and linear transformation, with similar co-registration of methane (CH4) channel grayscale images to the registered O2 channel images; and finally (iii) optimization of the aircraft position and attitude to the registered imagery and calculation of viewing geometry. This co-registration technique accurately orthorectifies each channel to the referenced MSI imagery. However, in the pixel domain, radiance data for each channel are offset by almost 150–200 across-track pixels (rows) and need to be aligned for the full-physics or proxy retrievals where both channels are simultaneously used. We leveraged our orthorectification tool to identify tie points with similar geographic locations in both CH4 and O2 images in order to produce shift parameters in the across-track and along-track dimensions. These algorithms described in this article will be implemented into the MethaneSAT L0–L1B processor.
Published: 2024
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22. Developing a spatially explicit global oil and gas infrastructure database for characterizing methane emission sources at high resolution

Author: M. Omara, R. Gautam, M. A. O'Brien, A. Himmelberger, A. Franco, K. Meisenhelder, G. Hauser, D. R. Lyon, A. Chulakadabba, C. C. Miller, J. Franklin, S. C. Wofsy, and S. P. Hamburg
Subjects: Environmental sciences, GE1-350, Geology, QE1-996.5
Abstract: Reducing oil and gas methane emissions is crucially important for limiting the rate of human-induced climate warming. As the capacity of multi-scale measurements of global oil and gas methane emissions has advanced in recent years, including the emerging ecosystem of satellite and airborne remote sensing platforms, a clear need for an openly accessible and regularly updated global inventory of oil and gas infrastructure has emerged as an important tool for characterizing and tracking methane emission sources. In this study, we develop a spatially explicit database of global oil and gas infrastructure, focusing on the acquisition, curation, and integration of public-domain geospatial datasets reported by official government sources and by industry, academic research institutions, and other non-government entities. We focus on the major oil and gas facility types that are key sources of measured methane emissions, including production wells, offshore production platforms, natural gas compressor stations, processing facilities, liquefied natural gas facilities, crude oil refineries, and pipelines. The first version of this global geospatial database (Oil and Gas Infrastructure Mapping database, OGIM_v1) contains a total of ∼ 6 million features, including 2.6 million point locations of major oil and gas facility types and over 2.6×106 km of pipelines globally. For each facility record, we include key attributes – such as facility type, operational status, oil and gas production and capacity information, operator names, and installation dates – which enable detailed methane source assessment and attribution analytics. Using the OGIM database, we demonstrate facility-level source attribution for multiple airborne remote-sensing-detected methane point sources from the Permian Basin, which is the largest oil-producing basin in the United States. In addition to source attribution, we present other major applications of this oil and gas infrastructure database in relation to methane emission assessment, including the development of an improved bottom-up methane emission inventory at high resolution (1 km × 1 km). We also discuss the tracking of changes in basin-level oil and gas activity and the development of policy-relevant analytics and insights for targeted methane mitigation. This work and the OGIM database, which we anticipate updating on a regular cadence, help fulfill a crucial oil and gas geospatial data need, in support of the assessment, attribution, and mitigation of global oil and gas methane emissions at high resolution. OGIM_v1 is publicly available at https://doi.org/10.5281/zenodo.7466757 (Omara et al., 2022a).
Published: 2023
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23. Performance of a Modular Ton-Scale Pixel-Readout Liquid Argon Time Projection Chamber

Author: A. Abed Abud, B. Abi, R. Acciarri, M. A. Acero, M. R. Adames, G. Adamov, M. Adamowski, D. Adams, M. Adinolfi, C. Adriano, A. Aduszkiewicz, J. Aguilar, B. Aimard, F. Akbar, K. Allison, S. Alonso Monsalve, M. Alrashed, A. Alton, R. Alvarez, T. Alves, H. Amar, P. Amedo, J. Anderson, D. A. Andrade, C. Andreopoulos, M. Andreotti, M. P. Andrews, F. Andrianala, S. Andringa, N. Anfimov, A. Ankowski, M. Antoniassi, M. Antonova, A. Antoshkin, A. Aranda-Fernandez, L. Arellano, E. Arrieta Diaz, M. A. Arroyave, J. Asaadi, A. Ashkenazi, D. Asner, L. Asquith, E. Atkin, D. Auguste, A. Aurisano, V. Aushev, D. Autiero, F. Azfar, A. Back, H. Back, J. J. Back, I. Bagaturia, L. Bagby, N. Balashov, S. Balasubramanian, P. Baldi, W. Baldini, J. Baldonedo, B. Baller, B. Bambah, R. Banerjee, F. Barao, G. Barenboim, P. B̃arham Alzás, G. J. Barker, W. Barkhouse, G. Barr, J. Barranco Monarca, A. Barros, N. Barros, D. Barrow, J. L. Barrow, A. Basharina-Freshville, A. Bashyal, V. Basque, C. Batchelor, L. Bathe-Peters, J. B. R. Battat, F. Battisti, F. Bay, M. C. Q. Bazetto, J. L. L. Bazo Alba, J. F. Beacom, E. Bechetoille, B. Behera, E. Belchior, G. Bell, L. Bellantoni, G. Bellettini, V. Bellini, O. Beltramello, N. Benekos, C. Benitez Montiel, D. Benjamin, F. Bento Neves, J. Berger, S. Berkman, J. Bernal, P. Bernardini, A. Bersani, S. Bertolucci, M. Betancourt, A. Betancur Rodríguez, A. Bevan, Y. Bezawada, A. T. Bezerra, T. J. Bezerra, A. Bhat, V. Bhatnagar, J. Bhatt, M. Bhattacharjee, M. Bhattacharya, S. Bhuller, B. Bhuyan, S. Biagi, J. Bian, K. Biery, B. Bilki, M. Bishai, A. Bitadze, A. Blake, F. D. Blaszczyk, G. C. Blazey, E. Blucher, J. Bogenschuetz, J. Boissevain, S. Bolognesi, T. Bolton, L. Bomben, M. Bonesini, C. Bonilla-Diaz, F. Bonini, A. Booth, F. Boran, S. Bordoni, R. Borges Merlo, A. Borkum, N. Bostan, J. Bracinik, D. Braga, B. Brahma, D. Brailsford, F. Bramati, A. Branca, A. Brandt, J. Bremer, C. Brew, S. J. Brice, V. Brio, C. Brizzolari, C. Bromberg, J. Brooke, A. Bross, G. Brunetti, M. Brunetti, N. Buchanan, H. Budd, J. Buergi, D. Burgardt, S. Butchart, G. Caceres V., I. Cagnoli, T. Cai, R. Calabrese, J. Calcutt, M. Calin, L. Calivers, E. Calvo, A. Caminata, A. F. Camino, W. Campanelli, A. Campani, A. Campos Benitez, N. Canci, J. Capó, I. Caracas, D. Caratelli, D. Carber, J. M. Carceller, G. Carini, B. Carlus, M. F. Carneiro, P. Carniti, I. Caro Terrazas, H. Carranza, N. Carrara, L. Carroll, T. Carroll, A. Carter, E. Casarejos, D. Casazza, J. F. Castaño Forero, F. A. Castaño, A. Castillo, C. Castromonte, E. Catano-Mur, C. Cattadori, F. Cavalier, F. Cavanna, S. Centro, G. Cerati, C. Cerna, A. Cervelli, A. Cervera Villanueva, K. Chakraborty, S. Chakraborty, M. Chalifour, A. Chappell, N. Charitonidis, A. Chatterjee, H. Chen, M. Chen, W. C. Chen, Y. Chen, Z. Chen-Wishart, D. Cherdack, C. Chi, R. Chirco, N. Chitirasreemadam, K. Cho, S. Choate, D. Chokheli, P. S. Chong, B. Chowdhury, D. Christian, A. Chukanov, M. Chung, E. Church, M. F. Cicala, M. Cicerchia, V. Cicero, R. Ciolini, P. Clarke, G. Cline, T. E. Coan, A. G. Cocco, J. A. B. Coelho, A. Cohen, J. Collazo, J. Collot, E. Conley, J. M. Conrad, M. Convery, S. Copello, P. Cova, C. Cox, L. Cremaldi, L. Cremonesi, J. I. Crespo-Anadón, M. Crisler, E. Cristaldo, J. Crnkovic, G. Crone, R. Cross, A. Cudd, C. Cuesta, Y. Cui, F. Curciarello, D. Cussans, J. Dai, O. Dalager, R. Dallavalle, W. Dallaway, H. da Motta, Z. A. Dar, R. Darby, L. Da Silva Peres, Q. David, G. S. Davies, S. Davini, J. Dawson, R. De Aguiar, P. De Almeida, P. Debbins, I. De Bonis, M. P. Decowski, A. de Gouvêa, P. C. De Holanda, I. L. De Icaza Astiz, P. De Jong, P. Del Amo Sanchez, A. De la Torre, G. De Lauretis, A. Delbart, D. Delepine, M. Delgado, A. Dell’Acqua, G. Delle Monache, N. Delmonte, P. De Lurgio, R. Demario, G. De Matteis, J. R. T. de Mello Neto, D. M. DeMuth, S. Dennis, C. Densham, P. Denton, G. W. Deptuch, A. De Roeck, V. De Romeri, J. P. Detje, J. Devine, R. Dharmapalan, M. Dias, A. Diaz, J. S. Díaz, F. Díaz, F. Di Capua, A. Di Domenico, S. Di Domizio, S. Di Falco, L. Di Giulio, P. Ding, L. Di Noto, E. Diociaiuti, C. Distefano, R. Diurba, M. Diwan, Z. Djurcic, D. Doering, S. Dolan, F. Dolek, M. J. Dolinski, D. Domenici, L. Domine, S. Donati, Y. Donon, S. Doran, D. Douglas, T. A. Doyle, A. Dragone, F. Drielsma, L. Duarte, D. Duchesneau, K. Duffy, K. Dugas, P. Dunne, B. Dutta, H. Duyang, D. A. Dwyer, A. S. Dyshkant, S. Dytman, M. Eads, A. Earle, S. Edayath, D. Edmunds, J. Eisch, P. Englezos, A. Ereditato, T. Erjavec, C. O. Escobar, J. J. Evans, E. Ewart, A. C. Ezeribe, K. Fahey, L. Fajt, A. Falcone, M. Fani’, C. Farnese, S. Farrell, Y. Farzan, D. Fedoseev, J. Felix, Y. Feng, E. Fernandez-Martinez, G. Ferry, L. Fields, P. Filip, A. Filkins, F. Filthaut, R. Fine, G. Fiorillo, M. Fiorini, S. Fogarty, W. Foreman, J. Fowler, J. Franc, K. Francis, D. Franco, J. Franklin, J. Freeman, J. Fried, A. Friedland, S. Fuess, I. K. Furic, K. Furman, A. P. Furmanski, R. Gaba, A. Gabrielli, A. M. Gago, F. Galizzi, H. Gallagher, A. Gallas, N. Gallice, V. Galymov, E. Gamberini, T. Gamble, F. Ganacim, R. Gandhi, S. Ganguly, F. Gao, S. Gao, D. Garcia-Gamez, M. Á. García-Peris, F. Gardim, S. Gardiner, D. Gastler, A. Gauch, J. Gauvreau, P. Gauzzi, S. Gazzana, G. Ge, N. Geffroy, B. Gelli, S. Gent, L. Gerlach, Z. Ghorbani-Moghaddam, T. Giammaria, D. Gibin, I. Gil-Botella, S. Gilligan, A. Gioiosa, S. Giovannella, C. Girerd, A. K. Giri, C. Giugliano, V. Giusti, D. Gnani, O. Gogota, S. Gollapinni, K. Gollwitzer, R. A. Gomes, L. V. Gomez Bermeo, L. S. Gomez Fajardo, F. Gonnella, D. Gonzalez-Diaz, M. Gonzalez-Lopez, M. C. Goodman, S. Goswami, C. Gotti, J. Goudeau, E. Goudzovski, C. Grace, E. Gramellini, R. Gran, E. Granados, P. Granger, C. Grant, D. R. Gratieri, G. Grauso, P. Green, S. Greenberg, J. Greer, W. C. Griffith, F. T. Groetschla, K. Grzelak, L. Gu, W. Gu, V. Guarino, M. Guarise, R. Guenette, E. Guerard, M. Guerzoni, D. Guffanti, A. Guglielmi, B. Guo, Y. Guo, A. Gupta, V. Gupta, G. Gurung, D. Gutierrez, P. Guzowski, M. M. Guzzo, S. Gwon, A. Habig, H. Hadavand, L. Haegel, R. Haenni, L. Hagaman, A. Hahn, J. Haiston, J. Hakenmueller, T. Hamernik, P. Hamilton, J. Hancock, F. Happacher, D. A. Harris, J. Hartnell, T. Hartnett, J. Harton, T. Hasegawa, C. Hasnip, R. Hatcher, K. Hayrapetyan, J. Hays, E. Hazen, M. He, A. Heavey, K. M. Heeger, J. Heise, S. Henry, M. A. Hernandez Morquecho, K. Herner, V. Hewes, A. Higuera, C. Hilgenberg, S. J. Hillier, A. Himmel, E. Hinkle, L. R. Hirsch, J. Ho, J. Hoff, A. Holin, T. Holvey, E. Hoppe, S. Horiuchi, G. A. Horton-Smith, M. Hostert, T. Houdy, B. Howard, R. Howell, I. Hristova, M. S. Hronek, J. Huang, R. G. Huang, Z. Hulcher, M. Ibrahim, G. Iles, N. Ilic, A. M. Iliescu, R. Illingworth, G. Ingratta, A. Ioannisian, B. Irwin, L. Isenhower, M. Ismerio Oliveira, R. Itay, C. M. Jackson, V. Jain, E. James, W. Jang, B. Jargowsky, D. Jena, I. Jentz, X. Ji, C. Jiang, J. Jiang, L. Jiang, A. Jipa, F. R. Joaquim, W. Johnson, C. Jollet, B. Jones, R. Jones, D. José Fernández, N. Jovancevic, M. Judah, C. K. Jung, T. Junk, Y. Jwa, M. Kabirnezhad, A. C. Kaboth, I. Kadenko, I. Kakorin, A. Kalitkina, D. Kalra, M. Kandemir, D. M. Kaplan, G. Karagiorgi, G. Karaman, A. Karcher, Y. Karyotakis, S. Kasai, S. P. Kasetti, L. Kashur, I. Katsioulas, A. Kauther, N. Kazaryan, L. Ke, E. Kearns, P. T. Keener, K. J. Kelly, E. Kemp, O. Kemularia, Y. Kermaidic, W. Ketchum, S. H. Kettell, M. Khabibullin, N. Khan, A. Khvedelidze, D. Kim, J. Kim, M. Kim, B. King, B. Kirby, M. Kirby, A. Kish, J. Klein, J. Kleykamp, A. Klustova, T. Kobilarcik, L. Koch, K. Koehler, L. W. Koerner, D. H. Koh, L. Kolupaeva, D. Korablev, M. Kordosky, T. Kosc, U. Kose, V. A. Kostelecký, K. Kothekar, I. Kotler, M. Kovalcuk, V. Kozhukalov, W. Krah, R. Kralik, M. Kramer, L. Kreczko, F. Krennrich, I. Kreslo, T. Kroupova, S. Kubota, M. Kubu, Y. Kudenko, V. A. Kudryavtsev, G. Kufatty, S. Kuhlmann, J. Kumar, P. Kumar, S. Kumaran, P. Kunze, J. Kunzmann, R. Kuravi, N. Kurita, C. Kuruppu, V. Kus, T. Kutter, J. Kvasnicka, T. Labree, T. Lackey, A. Lambert, B. J. Land, C. E. Lane, N. Lane, K. Lang, T. Langford, M. Langstaff, F. Lanni, O. Lantwin, J. Larkin, P. Lasorak, D. Last, A. Laudrain, A. Laundrie, G. Laurenti, E. Lavaut, A. Lawrence, P. Laycock, I. Lazanu, M. Lazzaroni, T. Le, S. Leardini, J. Learned, T. LeCompte, C. Lee, V. Legin, G. Lehmann Miotto, R. Lehnert, M. A. Leigui de Oliveira, M. Leitner, D. Leon Silverio, L. M. Lepin, J.-Y. Li, S. W. Li, Y. Li, H. Liao, C. S. Lin, D. Lindebaum, S. Linden, R. A. Lineros, J. Ling, A. Lister, B. R. Littlejohn, H. Liu, J. Liu, Y. Liu, S. Lockwitz, M. Lokajicek, I. Lomidze, K. Long, T. V. Lopes, J. Lopez, I. López de Rego, N. López-March, T. Lord, J. M. LoSecco, W. C. Louis, A. Lozano Sanchez, X.-G. Lu, K. B. Luk, B. Lunday, X. Luo, E. Luppi, J. Maalmi, D. MacFarlane, A. A. Machado, P. Machado, C. T. Macias, J. R. Macier, M. MacMahon, A. Maddalena, A. Madera, P. Madigan, S. Magill, C. Magueur, K. Mahn, A. Maio, A. Major, K. Majumdar, M. Man, R. C. Mandujano, J. Maneira, S. Manly, A. Mann, K. Manolopoulos, M. Manrique Plata, S. Manthey Corchado, V. N. Manyam, M. Marchan, A. Marchionni, W. Marciano, D. Marfatia, C. Mariani, J. Maricic, F. Marinho, A. D. Marino, T. Markiewicz, F. Das Chagas Marques, C. Marquet, D. Marsden, M. Marshak, C. M. Marshall, J. Marshall, L. Martina, J. Martín-Albo, N. Martinez, D. A. Martinez Caicedo, F. Martínez López, P. Martínez Miravé, S. Martynenko, V. Mascagna, C. Massari, A. Mastbaum, F. Matichard, S. Matsuno, G. Matteucci, J. Matthews, C. Mauger, N. Mauri, K. Mavrokoridis, I. Mawby, R. Mazza, A. Mazzacane, T. McAskill, N. McConkey, K. S. McFarland, C. McGrew, A. McNab, L. Meazza, V. C. N. Meddage, B. Mehta, P. Mehta, P. Melas, O. Mena, H. Mendez, P. Mendez, D. P. Méndez, A. Menegolli, G. Meng, A. C. E. A. Mercuri, A. Meregaglia, M. D. Messier, S. Metallo, J. Metcalf, W. Metcalf, M. Mewes, H. Meyer, T. Miao, A. Miccoli, G. Michna, V. Mikola, R. Milincic, F. Miller, G. Miller, W. Miller, O. Mineev, A. Minotti, L. Miralles, O. G. Miranda, C. Mironov, S. Miryala, S. Miscetti, C. S. Mishra, S. R. Mishra, A. Mislivec, M. Mitchell, D. Mladenov, I. Mocioiu, A. Mogan, N. Moggi, R. Mohanta, T. A. Mohayai, N. Mokhov, J. Molina, L. Molina Bueno, E. Montagna, A. Montanari, C. Montanari, D. Montanari, D. Montanino, L. M. Montaño Zetina, M. Mooney, A. F. Moor, Z. Moore, D. Moreno, O. Moreno-Palacios, L. Morescalchi, D. Moretti, R. Moretti, C. Morris, C. Mossey, M. Mote, C. A. Moura, G. Mouster, W. Mu, L. Mualem, J. Mueller, M. Muether, F. Muheim, A. Muir, M. Mulhearn, D. Munford, L. J. Munteanu, H. Muramatsu, J. Muraz, M. Murphy, T. Murphy, J. Muse, A. Mytilinaki, J. Nachtman, Y. Nagai, S. Nagu, R. Nandakumar, D. Naples, S. Narita, A. Nath, A. Navrer-Agasson, N. Nayak, M. Nebot-Guinot, A. Nehm, J. K. Nelson, O. Neogi, J. Nesbit, M. Nessi, D. Newbold, M. Newcomer, R. Nichol, F. Nicolas-Arnaldos, A. Nikolica, J. Nikolov, E. Niner, K. Nishimura, A. Norman, A. Norrick, P. Novella, J. A. Nowak, M. Oberling, J. P. Ochoa-Ricoux, S. Oh, S. B. Oh, A. Olivier, A. Olshevskiy, T. Olson, Y. Onel, Y. Onishchuk, A. Oranday, M. Osbiston, J. A. Osorio Vélez, L. Otiniano Ormachea, J. Ott, L. Pagani, G. Palacio, O. Palamara, S. Palestini, J. M. Paley, M. Pallavicini, C. Palomares, S. Pan, P. Panda, W. Panduro Vazquez, E. Pantic, V. Paolone, V. Papadimitriou, R. Papaleo, A. Papanestis, D. Papoulias, S. Paramesvaran, A. Paris, S. Parke, E. Parozzi, S. Parsa, Z. Parsa, S. Parveen, M. Parvu, D. Pasciuto, S. Pascoli, L. Pasqualini, J. Pasternak, C. Patrick, L. Patrizii, R. B. Patterson, T. Patzak, A. Paudel, L. Paulucci, Z. Pavlovic, G. Pawloski, D. Payne, V. Pec, E. Pedreschi, S. J. M. Peeters, W. Pellico, A. Pena Perez, E. Pennacchio, A. Penzo, O. L. G. Peres, Y. F. Perez Gonzalez, L. Pérez-Molina, C. Pernas, J. Perry, D. Pershey, G. Pessina, G. Petrillo, C. Petta, R. Petti, M. Pfaff, V. Pia, L. Pickering, F. Pietropaolo, V. L. Pimentel, G. Pinaroli, J. Pinchault, K. Pitts, K. Plows, R. Plunkett, C. Pollack, T. Pollman, D. Polo-Toledo, F. Pompa, X. Pons, N. Poonthottathil, V. Popov, F. Poppi, J. Porter, M. Potekhin, R. Potenza, J. Pozimski, M. Pozzato, T. Prakash, C. Pratt, M. Prest, F. Psihas, D. Pugnere, X. Qian, J. L. Raaf, V. Radeka, J. Rademacker, B. Radics, A. Rafique, E. Raguzin, M. Rai, S. Rajagopalan, M. Rajaoalisoa, I. Rakhno, L. Rakotondravohitra, L. Ralte, M. A. Ramirez Delgado, B. Ramson, A. Rappoldi, G. Raselli, P. Ratoff, R. Ray, H. Razafinime, E. M. Rea, J. S. Real, B. Rebel, R. Rechenmacher, M. Reggiani-Guzzo, J. Reichenbacher, S. D. Reitzner, H. Rejeb Sfar, E. Renner, A. Renshaw, S. Rescia, F. Resnati, D. Restrepo, C. Reynolds, M. Ribas, S. Riboldi, C. Riccio, G. Riccobene, J. S. Ricol, M. Rigan, E. V. Rincón, A. Ritchie-Yates, S. Ritter, D. Rivera, R. Rivera, A. Robert, J. L. Rocabado Rocha, L. Rochester, M. Roda, P. Rodrigues, M. J. Rodriguez Alonso, J. Rodriguez Rondon, S. Rosauro-Alcaraz, P. Rosier, D. Ross, M. Rossella, M. Rossi, M. Ross-Lonergan, N. Roy, P. Roy, C. Rubbia, A. Ruggeri, G. Ruiz Ferreira, B. Russell, D. Ruterbories, A. Rybnikov, A. Saa-Hernandez, R. Saakyan, S. Sacerdoti, S. K. Sahoo, N. Sahu, P. Sala, N. Samios, O. Samoylov, M. C. Sanchez, A. Sánchez Bravo, P. Sanchez-Lucas, V. Sandberg, D. A. Sanders, S. Sanfilippo, D. Sankey, D. Santoro, N. Saoulidou, P. Sapienza, C. Sarasty, I. Sarcevic, I. Sarra, G. Savage, V. Savinov, G. Scanavini, A. Scaramelli, A. Scarff, T. Schefke, H. Schellman, S. Schifano, P. Schlabach, D. Schmitz, A. W. Schneider, K. Scholberg, A. Schukraft, B. Schuld, A. Segade, E. Segreto, A. Selyunin, C. R. Senise, J. Sensenig, M. H. Shaevitz, P. Shanahan, P. Sharma, R. Kumar, K. Shaw, T. Shaw, K. Shchablo, J. Shen, C. Shepherd-Themistocleous, A. Sheshukov, W. Shi, S. Shin, S. Shivakoti, I. Shoemaker, D. Shooltz, R. Shrock, B. Siddi, M. Siden, J. Silber, L. Simard, J. Sinclair, G. Sinev, Jaydip Singh, J. Singh, L. Singh, P. Singh, V. Singh, S. Singh Chauhan, R. Sipos, C. Sironneau, G. Sirri, K. Siyeon, K. Skarpaas, J. Smedley, E. Smith, J. Smith, P. Smith, J. Smolik, M. Smy, M. Snape, E. L. Snider, P. Snopok, D. Snowden-Ifft, M. Soares Nunes, H. Sobel, M. Soderberg, S. Sokolov, C. J. Solano Salinas, S. Söldner-Rembold, S. R. Soleti, N. Solomey, V. Solovov, W. E. Sondheim, M. Sorel, A. Sotnikov, J. Soto-Oton, A. Sousa, K. Soustruznik, F. Spinella, J. Spitz, N. J. C. Spooner, K. Spurgeon, D. Stalder, M. Stancari, L. Stanco, J. Steenis, R. Stein, H. M. Steiner, A. F. Steklain Lisbôa, A. Stepanova, J. Stewart, B. Stillwell, J. Stock, F. Stocker, T. Stokes, M. Strait, T. Strauss, L. Strigari, A. Stuart, J. G. Suarez, J. Subash, A. Surdo, L. Suter, C. M. Sutera, K. Sutton, Y. Suvorov, R. Svoboda, S. K. Swain, B. Szczerbinska, A. M. Szelc, A. Sztuc, A. Taffara, N. Talukdar, J. Tamara, H. A. Tanaka, S. Tang, N. Taniuchi, A. M. Tapia Casanova, B. Tapia Oregui, A. Tapper, S. Tariq, E. Tarpara, E. Tatar, R. Tayloe, D. Tedeschi, A. M. Teklu, J. Tena Vidal, P. Tennessen, M. Tenti, K. Terao, F. Terranova, G. Testera, T. Thakore, A. Thea, A. Thiebault, S. Thomas, A. Thompson, C. Thorn, S. C. Timm, E. Tiras, V. Tishchenko, N. Todorović, L. Tomassetti, A. Tonazzo, D. Torbunov, M. Torti, M. Tortola, F. Tortorici, N. Tosi, D. Totani, M. Toups, C. Touramanis, D. Tran, R. Travaglini, J. Trevor, E. Triller, S. Trilov, J. Truchon, D. Truncali, W. H. Trzaska, Y. Tsai, Y.-T. Tsai, Z. Tsamalaidze, K. V. Tsang, N. Tsverava, S. Z. Tu, S. Tufanli, C. Tunnell, J. Turner, M. Tuzi, J. Tyler, E. Tyley, M. Tzanov, M. A. Uchida, J. Ureña González, J. Urheim, T. Usher, H. Utaegbulam, S. Uzunyan, M. R. Vagins, P. Vahle, S. Valder, G. A. Valdiviesso, E. Valencia, R. Valentim, Z. Vallari, E. Vallazza, J. W. F. Valle, R. Van Berg, R. G. Van de Water, D. V. Forero, A. Vannozzi, M. Van Nuland-Troost, F. Varanini, D. Vargas Oliva, S. Vasina, N. Vaughan, K. Vaziri, A. Vázquez-Ramos, J. Vega, S. Ventura, A. Verdugo, S. Vergani, M. Verzocchi, K. Vetter, M. Vicenzi, H. Vieira de Souza, C. Vignoli, C. Vilela, E. Villa, S. Viola, B. Viren, A. Vizcaya-Hernandez, T. Vrba, Q. Vuong, A. V. Waldron, M. Wallbank, J. Walsh, T. Walton, H. Wang, J. Wang, L. Wang, M. H. L. S. Wang, X. Wang, Y. Wang, K. Warburton, D. Warner, L. Warsame, M. O. Wascko, D. Waters, A. Watson, K. Wawrowska, A. Weber, C. M. Weber, M. Weber, H. Wei, A. Weinstein, H. Wenzel, S. Westerdale, M. Wetstein, K. Whalen, J. Whilhelmi, A. White, L. H. Whitehead, D. Whittington, M. J. Wilking, A. Wilkinson, C. Wilkinson, F. Wilson, R. J. Wilson, P. Winter, W. Wisniewski, J. Wolcott, J. Wolfs, T. Wongjirad, A. Wood, K. Wood, E. Worcester, M. Worcester, M. Wospakrik, K. Wresilo, C. Wret, S. Wu, W. Wu, M. Wurm, J. Wyenberg, Y. Xiao, I. Xiotidis, B. Yaeggy, N. Yahlali, E. Yandel, K. Yang, T. Yang, A. Yankelevich, N. Yershov, K. Yonehara, T. Young, B. Yu, H. Yu, J. Yu, Y. Yu, W. Yuan, R. Zaki, J. Zalesak, L. Zambelli, B. Zamorano, A. Zani, O. Zapata, L. Zazueta, G. P. Zeller, J. Zennamo, K. Zeug, C. Zhang, S. Zhang, M. Zhao, E. Zhivun, E. D. Zimmerman, S. Zucchelli, J. Zuklin, V. Zutshi, R. Zwaska, and on behalf of the DUNE Collaboration
Subjects: neutrino, near detector, Deep Underground Neutrino Experiment, DUNE, Physics, QC1-999, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract: The Module-0 Demonstrator is a single-phase 600 kg liquid argon time projection chamber operated as a prototype for the DUNE liquid argon near detector. Based on the ArgonCube design concept, Module-0 features a novel 80k-channel pixelated charge readout and advanced high-coverage photon detection system. In this paper, we present an analysis of an eight-day data set consisting of 25 million cosmic ray events collected in the spring of 2021. We use this sample to demonstrate the imaging performance of the charge and light readout systems as well as the signal correlations between the two. We also report argon purity and detector uniformity measurements and provide comparisons to detector simulations.
Published: 2024
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24. Any differences between patients in a global cohort of patients with degenerative lumbar disease who undergo additional spine surgeries following minimally invasive lumbar interbody fusion?

Author: W. Senker, E. Vialle, P. de la Dehesa, Y. Park, S.W. Park, V. Arzoglou, Y.P. Charles, J. Franke, G. Bordon, S. He, Y. Song, D. Vanhauwaert, and P. Pereira
Subjects: Neurology. Diseases of the nervous system, RC346-429
Published: 2024
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25. Wound drainage decreases early revision rate in posterior spinal fusion surgery - A prospective randomized multicenter study

Author: D. Rappert, A. Hammer, O. Cheremina, M. Pumberger, T. Khakzad, J. Franke, L. Klapproth, T. Kluba, and K.J. Schnake
Subjects: Neurology. Diseases of the nervous system, RC346-429
Published: 2024
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26. Climate change detection and attribution using observed and simulated tree-ring width

Author: J. Franke, M. N. Evans, A. Schurer, and G. C. Hegerl
Subjects: Environmental pollution, TD172-193.5, Environmental protection, TD169-171.8, Environmental sciences, GE1-350
Abstract: The detection and attribution (D&A) of paleoclimatic change to external radiative forcing relies on regression of statistical reconstructions on simulations. However, this procedure may be biased by assumptions of stationarity and univariate linear response of the underlying paleoclimatic observations. Here we perform a D&A study, modeling paleoclimate data observations as a function of paleoclimatic data simulations. Specifically, we detect and attribute tree-ring width (TRW) observations as a linear function of TRW simulations, which are themselves a nonlinear and multivariate TRW simulation driven with singly forced and cumulatively forced climate simulations for the period 1401–2000 CE. Temperature- and moisture-sensitive TRW simulations detect distinct patterns in time and space. Temperature-sensitive TRW observations and simulations are significantly correlated for Northern Hemisphere averages, and their variation is attributed to volcanic forcing. In decadally smoothed temporal fingerprints, we find the observed responses to be significantly larger and/or more persistent than the simulated responses. The pattern of simulated TRW of moisture-limited trees is consistent with the observed anomalies in the 2 years following major volcanic eruptions. We can for the first time attribute this spatiotemporal fingerprint in moisture-limited tree-ring records to volcanic forcing. These results suggest that the use of nonlinear and multivariate proxy system models in paleoclimatic detection and attribution studies may permit more realistic, spatially resolved and multivariate fingerprint detection studies and evaluation of the climate sensitivity to external radiative forcing than has previously been possible.
Published: 2022
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27. Revealing four decades of snow cover dynamics in the Hindu Kush Himalaya

Author: K. Naegeli, J. Franke, C. Neuhaus, N. Rietze, M. Stengel, X. Wu, and S. Wunderle
Subjects: Medicine, Science
Abstract: Abstract Knowledge about the distribution and dynamics of seasonal snow cover (SSC) is of high importance for climate studies, hydrology or hazards assessment. SSC varies considerably across the Hindu Kush Himalaya both in space and time. Previous studies focused on regional investigations or the influence of snow melt on the local hydrological system. Here, we present a systematic assessment of metrics to evaluate SSC dynamics for the entire HKH at regional and basin scale based on AVHRR GAC data at a 0.05° spatial and daily temporal resolution. Our findings are based on a unique four-decade satellite-based time series of snow cover information. We reveal strong variability of SSC at all time scales. We find significantly decreasing SSC trends in individual summer and winter months and a declining tendency from mid-spring to mid-fall, indicating a shift in seasonality. Thanks to this uniquely spatio-temporally resolved long-term data basis, we can particularly highlight the unique temporally variable character of seasonal snow cover and its cross-disciplinary importance for mountain ecosystems and downstream regions.
Published: 2022
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28. Statistical determinants of visuomotor adaptation along different dimensions during naturalistic 3D reaches

Author: E. Ferrea, J. Franke, P. Morel, and A. Gail
Subjects: Medicine, Science
Abstract: Abstract Neurorehabilitation in patients suffering from motor deficits relies on relearning or re-adapting motor skills. Yet our understanding of motor learning is based mostly on results from one or two-dimensional experimental paradigms with highly confined movements. Since everyday movements are conducted in three-dimensional space, it is important to further our understanding about the effect that gravitational forces or perceptual anisotropy might or might not have on motor learning along all different dimensions relative to the body. Here we test how well existing concepts of motor learning generalize to movements in 3D. We ask how a subject’s variability in movement planning and sensory perception influences motor adaptation along three different body axes. To extract variability and relate it to adaptation rate, we employed a novel hierarchical two-state space model using Bayesian modeling via Hamiltonian Monte Carlo procedures. Our results show that differences in adaptation rate occur between the coronal, sagittal and horizontal planes and can be explained by the Kalman gain, i.e., a statistically optimal solution integrating planning and sensory information weighted by the inverse of their variability. This indicates that optimal integration theory for error correction holds for 3D movements and explains adaptation rate variation between movements in different planes.
Published: 2022
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29. Influence of warming and atmospheric circulation changes on multidecadal European flood variability

Author: S. Brönnimann, P. Stucki, J. Franke, V. Valler, Y. Brugnara, R. Hand, L. C. Slivinski, G. P. Compo, P. D. Sardeshmukh, M. Lang, and B. Schaefli
Subjects: Environmental pollution, TD172-193.5, Environmental protection, TD169-171.8, Environmental sciences, GE1-350
Abstract: European flood frequency and intensity change on a multidecadal scale. Floods were more frequent in the 19th (central Europe) and early 20th century (western Europe) than during the mid-20th century and again more frequent since the 1970s. The causes of this variability are not well understood and the relation to climate change is unclear. Palaeoclimate studies from the northern Alps suggest that past flood-rich periods coincided with cold periods. In contrast, some studies suggest that more floods might occur in a future, warming world. Here we address the contribution of atmospheric circulation and of warming to multidecadal flood variability. For this, we use long series of annual peak streamflow, daily weather data, reanalyses, and reconstructions. We show that both changes in atmospheric circulation and moisture content affected multidecadal changes of annual peak streamflow in central and western Europe over the past two centuries. We find that during the 19th and early 20th century, atmospheric circulation changes led to high peak values of moisture flux convergence. The circulation was more conducive to strong and long-lasting precipitation events than in the mid-20th century. These changes are also partly reflected in the seasonal mean circulation and reproduced in atmospheric model simulations, pointing to a possible role of oceanic variability. For the period after 1980, increasing moisture content in a warming atmosphere led to extremely high moisture flux convergence. Thus, the main atmospheric driver of flood variability changed from atmospheric circulation variability to water vapour increase.
Published: 2022
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30. Spectral calibration of the MethaneAIR instrument

Author: C. Staebell, K. Sun, J. Samra, J. Franklin, C. Chan Miller, X. Liu, E. Conway, K. Chance, S. Milligan, and S. Wofsy
Subjects: Environmental engineering, TA170-171, Earthwork. Foundations, TA715-787
Abstract: MethaneAIR is the airborne simulator of MethaneSAT, an area-mapping satellite currently under development with the goal of locating and quantifying large anthropogenic CH4 point sources as well as diffuse emissions at the spatial scale of an oil and gas basin. Built to closely replicate the forthcoming satellite, MethaneAIR consists of two imaging spectrometers. One detects CH4 and CO2 absorption around 1.65 and 1.61 µm, respectively, while the other constrains the optical path in the atmosphere by detecting O2 absorption near 1.27 µm. The high spectral resolution and stringent retrieval accuracy requirements of greenhouse gas remote sensing in this spectral range necessitate a reliable spectral calibration. To this end, on-ground laboratory measurements were used to derive the spectral calibration of MethaneAIR, serving as a pathfinder for the future calibration of MethaneSAT. Stray light was characterized and corrected for through fast-Fourier-transform-based Van Cittert deconvolution. Wavelength registration was examined and found to be best described by a linear relationship for both bands with a precision of ∼ 0.02 spectral pixel. The instrument spectral spread function (ISSF), measured with fine wavelength steps of 0.005 nm near a series of central wavelengths across each band, was oversampled to construct the instrument spectral response function (ISRF) at each central wavelength and spatial pixel. The ISRFs were smoothed with a Savitzky–Golay filter for use in a lookup table in the retrieval algorithm. The MethaneAIR spectral calibration was evaluated through application to radiance spectra from an instrument flight over the Colorado Front Range.
Published: 2021
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31. Assimilating monthly precipitation data in a paleoclimate data assimilation framework

Author: V. Valler, Y. Brugnara, J. Franke, and S. Brönnimann
Subjects: Environmental pollution, TD172-193.5, Environmental protection, TD169-171.8, Environmental sciences, GE1-350
Abstract: Data assimilation approaches such as the ensemble Kalman filter method have become an important technique for paleoclimatological reconstructions and reanalysis. Different sources of information, from proxy records and documentary data to instrumental measurements, were assimilated in previous studies to reconstruct past climate fields. However, precipitation reconstructions are often based on indirect sources (e.g., proxy records). Assimilating precipitation measurements is a challenging task because they have high uncertainties, often represent only a small region, and generally do not follow a Gaussian distribution. In this paper, experiments are conducted to test the possibility of using information about precipitation in climate reconstruction with monthly resolution by assimilating monthly instrumental precipitation amounts or the number of wet days per month, solely or in addition to other climate variables such as temperature and sea-level pressure, into an ensemble of climate model simulations. The skill of all variables (temperature, precipitation, sea-level pressure) improved over the pure model simulations when only monthly precipitation amounts were assimilated. Assimilating the number of wet days resulted in similar or better skill compared to assimilating the precipitation amount. The experiments with different types of instrumental observations being assimilated indicate that precipitation data can be useful, particularly if no other variable is available from a given region. Overall the experiments show promising results because with the assimilation of precipitation information a new data source can be exploited for climate reconstructions. The wet day records can become an especially important data source in future climate reconstructions because many existing records date several centuries back in time and are not limited by the availability of meteorological instruments.
Published: 2020
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32. The importance of input data quality and quantity in climate field reconstructions – results from the assimilation of various tree-ring collections

Author: J. Franke, V. Valler, S. Brönnimann, R. Neukom, and F. Jaume-Santero
Subjects: Environmental pollution, TD172-193.5, Environmental protection, TD169-171.8, Environmental sciences, GE1-350
Abstract: Differences between paleoclimatic reconstructions are caused by two factors: the method and the input data. While many studies compare methods, we will focus in this study on the consequences of the input data choice in a state-of-the-art Kalman-filter paleoclimate data assimilation approach. We evaluate reconstruction quality in the 20th century based on three collections of tree-ring records: (1) 54 of the best temperature-sensitive tree-ring chronologies chosen by experts; (2) 415 temperature-sensitive tree-ring records chosen less strictly by regional working groups and statistical screening; (3) 2287 tree-ring series that are not screened for climate sensitivity. The three data sets cover the range from small sample size, small spatial coverage and strict screening for temperature sensitivity to large sample size and spatial coverage but no screening. Additionally, we explore a combination of these data sets plus screening methods to improve the reconstruction quality. A large, unscreened collection generally leads to a poor reconstruction skill. A small expert selection of extratropical Northern Hemisphere records allows for a skillful high-latitude temperature reconstruction but cannot be expected to provide information for other regions and other variables. We achieve the best reconstruction skill across all variables and regions by combining all available input data but rejecting records with insignificant climatic information (p value of regression model >0.05) and removing duplicate records. It is important to use a tree-ring proxy system model that includes both major growth limitations, temperature and moisture.
Published: 2020
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33. Evaluation of bacterial glycerol dialkyl glycerol tetraether and 2H–18O biomarker proxies along a central European topsoil transect

Author: J. Hepp, I. K. Schäfer, V. Lanny, J. Franke, M. Bliedtner, K. Rozanski, B. Glaser, M. Zech, T. I. Eglinton, and R. Zech
Subjects: Ecology, QH540-549.5, Life, QH501-531, Geology, QE1-996.5
Abstract: Molecular fossils, like bacterial branched glycerol dialkyl glycerol tetraethers (brGDGTs), and the stable isotopic composition of biomarkers, such as δ2H of leaf wax-derived n-alkanes (δ2Hn-alkane) or δ18O of hemicellulose-derived sugars (δ18Osugar), are increasingly used for the reconstruction of past climate and environmental conditions. Plant-derived δ2Hn-alkane and δ18Osugar values record the isotopic composition of plant source water (δ2Hsource-water and δ18Osource-water), which usually reflects mean annual precipitation (δ2Hprecipiation and δ18Oprecipiation), modulated by evapotranspirative leaf water enrichment and biosynthetic fractionation (εbio). Accuracy and precision of respective proxies should be ideally evaluated at a regional scale. For this study, we analysed topsoils below coniferous and deciduous forests as well as grassland soils along a central European transect in order to investigate the variability and robustness of various proxies and to identify effects related to vegetation. Soil pH values derived from brGDGTs correlate reasonably well with measured soil pH values but are systematically overestimated (ΔpH = 0.6±0.6). The branched vs. isoprenoid tetraether index (BIT) can give some indication whether the pH reconstruction is reliable. Temperatures derived from brGDGTs overestimate mean annual air temperatures slightly (ΔTMA=0.5 ∘C ± 2.4). Apparent isotopic fractionation (εn-alkane/precipitation and εsugar∕precipitation) is lower for grassland sites than for forest sites due to signal damping; i.e. grass biomarkers do not record the full evapotranspirative leaf water enrichment. Coupling δ2Hn-alkane with δ18Osugar allows us to reconstruct the stable isotopic composition of the source water more accurately than without the coupled approach (Δδ2H = ∼-21 ‰ ± 22 ‰ and Δδ18O = ∼-2.9 ‰ ± 2.8 ‰). Similarly, relative humidity during daytime and the vegetation period (RHMDV) can be reconstructed using the coupled isotope approach (ΔRHMDV=∼-17±12). Especially for coniferous sites, reconstructed RHMDV values as well as source water isotope composition underestimate the measured values. This can likely be explained by understorey grass vegetation at the coniferous sites contributing significantly to the n-alkane pool but only marginally to the sugar pool in the topsoils. Vegetation-dependent variable signal damping and εbio (regarding 2H between n-alkanes and leaf water) along our European transect are difficult to quantify but likely contribute to the observed underestimation in the source water isotope composition and RH reconstructions. Microclimate variability could cause the rather large uncertainties. Vegetation-related effects do, by contrast, not affect the brGDGT-derived reconstructions. Overall, GDGTs and the coupled δ2Hn-alkane–δ18Osugar approach have great potential for more quantitative paleoclimate reconstructions.
Published: 2020
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34. Two types of North American droughts related to different atmospheric circulation patterns

Author: A.-M. Burgdorf, S. Brönnimann, and J. Franke
Subjects: Environmental pollution, TD172-193.5, Environmental protection, TD169-171.8, Environmental sciences, GE1-350
Abstract: Proxy-based studies suggest that the southwestern USA is affected by two types of summer drought, often termed Dust Bowl-type droughts and 1950s-type droughts. The spatial drought patterns of the two types are distinct. It has been suggested that they are related to different circulation characteristics, but a lack of observation-based data has precluded further studies. In this paper, we analyze multi-annual summer droughts in North America back to 1600 in tree-ring-based drought reconstructions and in a global, monthly three-dimensional reconstruction of the atmosphere. Using cluster analysis of drought indices, we confirm the two main drought types and find a similar catalog of events as previous studies. These two main types of droughts are then analyzed with respect to 2 m temperatures (T2m), sea-level pressure (SLP), and 500 hPa geopotential height (GPH) in boreal summer. 1950s-type droughts are related to a stronger wave train over the Pacific–North American sector than Dust Bowl-type droughts, whereas the latter show the imprint of a poleward-shifted jet and establishment of a Great Plains ridge. The 500 hPa GPH patterns of the two types differ significantly not only over the contiguous United States and Canada but also over the extratropical North Atlantic and the Pacific. Dust Bowl-type droughts are associated with positive GPH anomalies, while 1950s-type droughts exhibit strong negative GPH anomalies. In comparison with 1950s-type droughts, the Dust Bowl-type droughts are characterized by higher sea-surface temperatures (SSTs) in the northern North Atlantic. Results suggest that atmospheric circulation and SST characteristics not only over the Pacific but also over the extratropical North Atlantic affect the spatial pattern of North American droughts.
Published: 2019
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35. Impact of different estimations of the background-error covariance matrix on climate reconstructions based on data assimilation

Author: V. Valler, J. Franke, and S. Brönnimann
Subjects: Environmental pollution, TD172-193.5, Environmental protection, TD169-171.8, Environmental sciences, GE1-350
Abstract: Data assimilation has been adapted in paleoclimatology to reconstruct past climate states. A key component of some assimilation systems is the background-error covariance matrix, which controls how the information from observations spreads into the model space. In ensemble-based approaches, the background-error covariance matrix can be estimated from the ensemble. Due to the usually limited ensemble size, the background-error covariance matrix is subject to the so-called sampling error. We test different methods to reduce the effect of sampling error in a published paleoclimate data assimilation setup. For this purpose, we conduct a set of experiments, where we assimilate early instrumental data and proxy records stored in trees, to investigate the effect of (1) the applied localization function and localization length scale; (2) multiplicative and additive inflation techniques; (3) temporal localization of monthly data, which applies if several time steps are estimated together in the same assimilation window. We find that the estimation of the background-error covariance matrix can be improved by additive inflation where the background-error covariance matrix is not only calculated from the sample covariance but blended with a climatological covariance matrix. Implementing a temporal localization for monthly resolved data also led to a better reconstruction.
Published: 2019
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36. The longest homogeneous series of grape harvest dates, Beaune 1354–2018, and its significance for the understanding of past and present climate

Author: T. Labbé, C. Pfister, S. Brönnimann, D. Rousseau, J. Franke, and B. Bois
Subjects: Environmental pollution, TD172-193.5, Environmental protection, TD169-171.8, Environmental sciences, GE1-350
Abstract: Records of grape harvest dates (GHDs) are the oldest and the longest continuous phenological data in Europe. However, many available series, including the well-known (Dijon) Burgundy series, are error prone because scholars so far have uncritically drawn the data from 19th century publications instead of going back to the archives. The GHDs from the famous vine region of Beaune (Burgundy) were entirely drawn from the archives and critically cross-checked with narrative evidence. In order to reconstruct temperature, the series was calibrated against the long Paris temperature series comprising the 360 years from 1659 to 2018. The 664-year-long Beaune series from 1354 to 2018 is also significantly correlated with tree-ring and documentary proxy evidence as well as with the central European temperature series (from 1500). The series is clearly subdivided into two parts. From 1354 to 1987 grapes were on average picked from 28 September on, whereby during the last 31-year-long period of rapid warming from 1988 to 2018 harvests began 13 d earlier. Early harvest dates are shown to be accompanied by high pressure over western–central Europe and atmospheric blocking over Denmark. The 33 extremely early harvests comprising the fifth percentile bracket of GHDs are unevenly distributed over time; 21 of them occurred between 1393 and 1719, while this is the case for just 5 years between 1720 and 2002. Since the hot summer of 2003, 8 out of 16 spring–summer periods were outstanding according to the statistics of the last 664 years, no less than 5 among them within the last 8 years. In the Paris temperature measurements since 1659, April-to-July temperature reached the highest value ever in 2018. In sum, the 664-year-long Beaune GHD series demonstrates that outstanding hot and dry years in the past were outliers, while they have become the norm since the transition to rapid warming in 1988.
Published: 2019
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37. Causes of increased flood frequency in central Europe in the 19th century

Author: S. Brönnimann, L. Frigerio, M. Schwander, M. Rohrer, P. Stucki, and J. Franke
Subjects: Environmental pollution, TD172-193.5, Environmental protection, TD169-171.8, Environmental sciences, GE1-350
Abstract: Historians and historical climatologists have long pointed to an increased flood frequency in central Europe in the mid- and late 19th century. However, the causes have remained unclear. Here, we investigate the changes in flood frequency in Switzerland based on long time series of discharge and lake levels, precipitation, and weather types and based on climate model simulations, focusing on the warm season. Annual series of peak discharge or maximum lake level, in agreement with previous studies, display increased frequency of floods in the mid-19th century and decreased frequency after the Second World War. Annual series of warm-season mean precipitation and high percentiles of 3 d precipitation totals (partly) reflect these changes. A daily weather type classification since 1763 is used to construct flood probability indices for the catchments of the Rhine in Basel and the outflow of Lake Lugano, Ponte Tresa. The indices indicate an increased frequency of flood-prone weather types in the mid-19th century and a decreased frequency in the post-war period, consistent with a climate reconstruction that shows increased (decreased) cyclonic flow over western Europe in the former (latter) period. To assess the driving factors of the detected circulation changes, we analyze weather types and precipitation in a large ensemble of atmospheric model simulations driven with observed sea-surface temperatures. In the simulations, we do not find an increase in flood-prone weather types in the Rhine catchment in the 19th century but a decrease in the post-war period that could have been related to sea-surface temperature anomalies.
Published: 2019
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38. Author Correction: Statistical determinants of visuomotor adaptation along different dimensions during naturalistic 3D reaches

Author: E. Ferrea, J. Franke, P. Morel, and A. Gail
Subjects: Medicine, Science
Published: 2022
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39. Treatment on active surveillance of small renal masses: Progression versus anxiety

Author: D. Cheung, J. Frankel, P. Tut, M. Komisarenko, L. Martin, M.A.S. Jewett, and A. Finelli
Subjects: Diseases of the genitourinary system. Urology, RC870-923, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Published: 2020
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40. Job satisfaction and stressors for working in out-of-hours care – a pilot study with general practitioners in a rural area of Germany

Author: R. Leutgeb, J. Frankenhauser-Mannuß, M. Scheuer, J. Szecsenyi, and Katja Goetz
Subjects: Effort-reward imbalance, General practitioner, Health services research, Out-of-hours care, Job satisfaction, Medicine (General), R5-920
Abstract: Abstract Background Challenging work environment, high workload, and increasing physician shortages characterize current rural general practice in Germany and in most European Countries. These factors extend into Out-Of-Hours Care (OOHC). However, little research about potential stressors for general practitioners (GPs) in OOHC settings is available. This pilot study aimed to evaluate workload, different elements of job satisfaction and stressors for GPs in OOHC and to analyze whether these aspects are associated with overall job satisfaction. Methods Cross-sectional survey with a sample of 320 GPs who are working in OOHC was used to measure workload in OOHC, job satisfaction (using the Warr-Cook-Wall scale) and stressors with the effort-reward imbalance questionnaire. In order to assess associations between workload, job satisfaction and stressors at work we performed descriptive analyses as well as multivariable regression analyses. Results The response rate was 40.9%. Over 80% agreed that OOHC was perceived as a stressor and 79% agreed that less OOHC improved job satisfaction. Only 42% of our sample were satisfied with their overall job satisfaction. The regression analysis showed that the modification of current OOHC organization was significantly associated with overall job satisfaction. Conclusions Our results suggest that OOHC in the current form is a relevant stressor in daily work of rural GPs in Germany and one of the reasons for a decreasing overall job satisfaction. Strategic changes such as the implementation of structural reforms e.g. reducing frequency of OOHC duties for each GP and improving continuing professional development options related to OOHC are needed to address current workload challenges experienced by GPs providing OOHC in Germany.
Published: 2018
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41. ALLOGENEIC BONE GRAFTING MATERIALS – UPDATE OF THE CURRENT SCIENTIFIC STATUS

Author: R. Schnettler, J. Franke, D. Rimashevskiy, N. Zagorodniy, N. Batpenov, R. E. Unger, S. Wenisch, and M. Barbeck
Subjects: allogeneic bone substitute, bone grafting, bone tissue regeneration, Orthopedic surgery, RD701-811
Abstract: Worldwide population aging and associated with it epidemics of osteoporosis, widespread of bone and joint reconstructive surgery and first of all joint replacement lead to explosive growth of interest in bone grafting.Although autografts are still the golden standard in bone regeneration, allogeneic bone substitutes have reached a state that allows for their application with satisfying clinical results. However, it has repeatedly been supposed that the different allogeneic materials underwent different purification processes, which modifies bone regeneration properties of these materials and also for different safety conditions. In the present publication, the treatment of the precursor tissue, the safety conditions, and the regenerative possibilities of C+TBA bone blocks based in preclinical and clinical data are described. Thus, it is described how the risks of infections and also immunological reactions becomes completely eliminated, while the special purification process allows for preservation of the native structure of the bone block. Both the in vitro studies and the clinical trials including histological follow-ups showed the optimal regeneration properties of these bone blocks. It has been shown that the allogeneic bone grafts have been integrated without causing inflammatory anomalies at the implantation site. Altogether, the allogeneic bone substitute material serves as an excellent basis for the formation of new bone. Finally, the combination of the allogeneic C+TBA bone blocks with different antibiotics is described. Interestingly, it is possible to combine the allogeneic bone substitute ether with antibiotics in the sense of prophylaxis and/or with bone marrow aspirate in order to accelerate bone remodeling.
Published: 2017
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42. Leaf waxes in litter and topsoils along a European transect

Author: I. K. Schäfer, V. Lanny, J. Franke, T. I. Eglinton, M. Zech, B. Vysloužilová, and R. Zech
Subjects: Environmental sciences, GE1-350, Geology, QE1-996.5
Abstract: Lipid biomarkers are increasingly used to reconstruct past environmental and climate conditions. Leaf-wax-derived long-chain n-alkanes and n-alkanoic acids may have great potential for reconstructing past changes in vegetation, but the factors that affect the leaf wax distribution in fresh plant material, as well as in soils and sediments, are not yet fully understood and need further research. We systematically investigated the influence of vegetation and soil depth on leaf waxes in litter and topsoils along a European transect. The deciduous forest sites are often dominated by the n-C27 alkane and n-C28 alkanoic acid. Conifers produce few n-alkanes but show high abundances of the C24 n-alkanoic acid. Grasslands are characterized by relatively high amounts of C31 and C33 n-alkanes and C32 and C34 n-alkanoic acids. Chain length ratios thus may allow for distinguishing between different vegetation types, but caution must be exercised given the large species-specific variability in chain length patterns. An updated endmember model with the new n-alkane ratio (n-C31 + n-C33) / (n-C27 + n-C31 + n-C33) is provided to illustrate, and tentatively account for, degradation effects on n-alkanes.
Published: 2016
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43. Fall and Rise of Polish Shipbuilding Industry

Author: Krzysztof Wrobel and J. Frankowski
Subjects: Shipbuilding Industry, Shipyard, Polish Shipbuilding Industry, Economic Crisis, History, Canals and inland navigation. Waterways, TC601-791, Transportation and communications, HE1-9990
Abstract: The hereby paper describes a brief history of fall and rise of Polish shipbuilding industry in the 21st century and confronts stereotypes about it using data available from variety of statistical sources as well as impressions regarding its current and future condition presented by different authors, including industry representatives. The main goal of the article is the confrontation of political statement with the statistical data and current sectoral trends within the shipbuilding industry in Poland. Firstly, we introduce a historical background in a scope of economic transition in Poland. Then, socio-political issues are addressed together with economic condition using statistical data. Lastly, the newest trends and perspectives are analyzed. Eventually, we come to conclusion that despite encountering great difficulties and arguments about its collapse from political actors, shipbuilding sector did manage to retain its strong position in Polish economy.
Published: 2016
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44. Everything is Data – Overview of Modular System of Sensors for Museum Environment

Author: J. Valach, K. Juliš, P. Štefcová, M. Pech, B. Wolf, M. Kotyk, and J. Frankl
Subjects: Technology, Engineering (General). Civil engineering (General), TA1-2040, Applied optics. Photonics, TA1501-1820
Abstract: The main aim of project nearing completion was to develop a modular and scalable system of sensors for monitoring of internal environment of museum exhibitions and depositories. The sensors vary according to parameters being monitored and at the same time also according to required energy autonomy, processing capability and bandwidth requirements. Sensors developed can be divided into three groups: environmental sensors, biosensors and sensors of vibrations. Data acquired by the sensors are archived and stored in open format. Metadata stored alongside true numerical data from measurement, represent assurance of future computer readability in data mining application. Long continuous series of data can provide sufficient data for acquisition of dose-response function.
Published: 2015
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45. Uncontrolled Hypertension amongst People Living with HIV on Antiretroviral Therapy at an Urban HIV Clinic in Swaziland

Author: O. Jimoh, A.B. Gachuhi, S. Simelane, M. Rabkin, H. Nuwagaba-Biribonwoha, P. Bongomin, A. Palma, M. McNairy, J. Franks, R. Bitchong, V. Okello, and W.M. El-Sadr
Subjects: Infectious and parasitic diseases, RC109-216, Public aspects of medicine, RA1-1270
Published: 2017
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46. A global historical ozone data set and prominent features of stratospheric variability prior to 1979

Author: S. Brönnimann, J. Bhend, J. Franke, S. Flückiger, A. M. Fischer, R. Bleisch, G. Bodeker, B. Hassler, E. Rozanov, and M. Schraner
Subjects: Physics, QC1-999, Chemistry, QD1-999
Abstract: We present a vertically resolved zonal mean monthly mean global ozone data set spanning the period 1901 to 2007, called HISTOZ.1.0. It is based on a new approach that combines information from an ensemble of chemistry climate model (CCM) simulations with historical total column ozone information. The CCM simulations incorporate important external drivers of stratospheric chemistry and dynamics (in particular solar and volcanic effects, greenhouse gases and ozone depleting substances, sea surface temperatures, and the quasi-biennial oscillation). The historical total column ozone observations include ground-based measurements from the 1920s onward and satellite observations from 1970 to 1976. An off-line data assimilation approach is used to combine model simulations, observations, and information on the observation error. The period starting in 1979 was used for validation with existing ozone data sets and therefore only ground-based measurements were assimilated. Results demonstrate considerable skill from the CCM simulations alone. Assimilating observations provides additional skill for total column ozone. With respect to the vertical ozone distribution, assimilating observations increases on average the correlation with a reference data set, but does not decrease the mean squared error. Analyses of HISTOZ.1.0 with respect to the effects of El Niño–Southern Oscillation (ENSO) and of the 11 yr solar cycle on stratospheric ozone from 1934 to 1979 qualitatively confirm previous studies that focussed on the post-1979 period. The ENSO signature exhibits a much clearer imprint of a change in strength of the Brewer–Dobson circulation compared to the post-1979 period. The imprint of the 11 yr solar cycle is slightly weaker in the earlier period. Furthermore, the total column ozone increase from the 1950s to around 1970 at northern mid-latitudes is briefly discussed. Indications for contributions of a tropospheric ozone increase, greenhouse gases, and changes in atmospheric circulation are found. Finally, the paper points at several possible future improvements of HISTOZ.1.0.
Published: 2013
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47. Circulation pattern based parameterization of a multiplicative random cascade for disaggregation of observed and projected daily rainfall time series

Author: D. Lisniak, J. Franke, and C. Bernhofer
Subjects: Technology, Environmental technology. Sanitary engineering, TD1-1066, Geography. Anthropology. Recreation, Environmental sciences, GE1-350
Abstract: The use of multiplicative random cascades (MRCs) for temporal rainfall disaggregation has been extensively studied in the past. MRCs are appealing for rainfall disaggregation due to their formal simplicity and the possibility to extract the model parameters directly from observed high resolution rainfall data. These parameters, however, represent the rainfall characteristics of the observation period. Since rainfall characteristics of different time slices are changing due to climate variability, we propose a parameterization approach for MRCs to adjust the parameters according to past (observed) or future (projected) time series. This is done on the basis of circulation patterns (CPs) by extracting a distinct MRC parameterization from high resolution rainfall data, as observed on days governed by each individual CP. The parameterization approach is tested by comparing the statistical properties of disaggregated rainfall time series of two time slices, 1969–1979 and 1989–1999, to the results obtained by two other disaggregation methods (a conceptually similar MRC without CP-based parameterization and a recombination approach) and to the statistical properties of observed hourly rainfall data. In this context, all three approaches use rainfall data of the time slice 1989–1999 for parameterization. We found that the inclusion of CPs into the parameterization of a MRC yields hourly time series that better reproduce the properties of observed rainfall in time slice 1989–1999, as compared to the simple MRC. Despite similar results of both MRCs in the validation period of 1969–1979, we can conclude that the CP-based parameterization approach is applicable for temporal rainfall disaggregation in time slices distinct from the parameterization period. This approach accounts for changes in rainfall characteristics due to changes in the frequency of occurrence of the CPs and allows generating hourly rainfall from daily data, as often provided by a statistical downscaling of global climate change.
Published: 2013
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48. An ensemble-based approach to climate reconstructions

Author: J. Bhend, J. Franke, D. Folini, M. Wild, and S. Brönnimann
Subjects: Environmental pollution, TD172-193.5, Environmental protection, TD169-171.8, Environmental sciences, GE1-350
Abstract: Data assimilation is a promising approach to obtain climate reconstructions that are both consistent with observations of the past and with our understanding of the physics of the climate system as represented in the climate model used. Here, we investigate the use of ensemble square root filtering (EnSRF) – a technique used in weather forecasting – for climate reconstructions. We constrain an ensemble of 29 simulations from an atmosphere-only general circulation model (GCM) with 37 pseudo-proxy temperature time series. Assimilating spatially sparse information with low temporal resolution (semi-annual) improves the representation of not only temperature, but also other surface properties, such as precipitation and even upper air features such as the intensity of the northern stratospheric polar vortex or the strength of the northern subtropical jet. Given the sparsity of the assimilated information and the limited size of the ensemble used, a localisation procedure is crucial to reduce "overcorrection" of climate variables far away from the assimilated information.
Published: 2012
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49. Phase II study of novel CXCR2 agonist and Plerixafor for rapid stem cell mobilization in patients with multiple myeloma

Author: Surbhi Sidana, Andriyana K. Bankova, Hitomi Hosoya, Shaji K. Kumar, Tyson H. Holmes, John Tamaresis, Anne Le, Lori S. Muffly, Sofia Maysel-Auslender, Laura Johnston, Sally Arai, Robert Lowsky, Everett Meyer, Andrew Rezvani, Wen-Kai Weng, Matthew J. Frank, Parveen Shiraz, Holden T. Maecker, Ying Lu, David B. Miklos, and Judith A. Shizuru
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract MGTA-145 or GROβT, a CXCR2 agonist, has shown promising activity for hematopoietic stem cell (HSC) mobilization with plerixafor in pre-clinical studies and healthy volunteers. Twenty-five patients with multiple myeloma enrolled in a phase 2 trial evaluating MGTA-145 and plerixafor for HSC mobilization (NCT04552743). Plerixafor was given subcutaneously followed 2 h later by MGTA-145 (0.03 mg/kg) intravenously with same day apheresis. Mobilization/apheresis could be repeated for a second day in patients who collected
Published: 2024
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50. CEFLES2: the remote sensing component to quantify photosynthetic efficiency from the leaf to the region by measuring sun-induced fluorescence in the oxygen absorption bands

Author: S. van der Linden, A. Zaldei, P. Toscano, T. Udelhoven, G. Toci, M. Stellmes, J. A. Sobrino, A. Schickling, V. Raimondi, L. Palombi, A. Ounis, A. Okujeni, I. Moya, B. Neininger, J. Moreno, F. Miglietta, A. Moersch, M. Meroni, D. Lognoli, M. Kosvancova, P. Hostert, M. Jiménez, K. Hamdi, Ó. Gutiérrez-de-la-Cámara, Y. Goulas, L. Guanter, J. A. Gómez, B. Gioli, C. Gerbig, J. Franke, B. Franch, G. Fernandez, F. Daumard, E. de Miguel, A. Damm, R. Colombo, S. Champagne, G. Cecchi, L. Alonso, G. Agati, and U. Rascher
Subjects: Ecology, QH540-549.5, Life, QH501-531, Geology, QE1-996.5
Abstract: The CEFLES2 campaign during the Carbo Europe Regional Experiment Strategy was designed to provide simultaneous airborne measurements of solar induced fluorescence and CO2 fluxes. It was combined with extensive ground-based quantification of leaf- and canopy-level processes in support of ESA's Candidate Earth Explorer Mission of the "Fluorescence Explorer" (FLEX). The aim of this campaign was to test if fluorescence signal detected from an airborne platform can be used to improve estimates of plant mediated exchange on the mesoscale. Canopy fluorescence was quantified from four airborne platforms using a combination of novel sensors: (i) the prototype airborne sensor AirFLEX quantified fluorescence in the oxygen A and B bands, (ii) a hyperspectral spectrometer (ASD) measured reflectance along transects during 12 day courses, (iii) spatially high resolution georeferenced hyperspectral data cubes containing the whole optical spectrum and the thermal region were gathered with an AHS sensor, and (iv) the first employment of the high performance imaging spectrometer HYPER delivered spatially explicit and multi-temporal transects across the whole region. During three measurement periods in April, June and September 2007 structural, functional and radiometric characteristics of more than 20 different vegetation types in the Les Landes region, Southwest France, were extensively characterized on the ground. The campaign concept focussed especially on quantifying plant mediated exchange processes (photosynthetic electron transport, CO2 uptake, evapotranspiration) and fluorescence emission. The comparison between passive sun-induced fluorescence and active laser-induced fluorescence was performed on a corn canopy in the daily cycle and under desiccation stress. Both techniques show good agreement in detecting stress induced fluorescence change at the 760 nm band. On the large scale, airborne and ground-level measurements of fluorescence were compared on several vegetation types supporting the scaling of this novel remote sensing signal. The multi-scale design of the four airborne radiometric measurements along with extensive ground activities fosters a nested approach to quantify photosynthetic efficiency and gross primary productivity (GPP) from passive fluorescence.
Published: 2009

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