A new column-generation-based algorithm for VMAT treatment plan optimization

We study the treatment plan optimization problem for volumetric modulated arc therapy (VMAT). We propose a new column-generation-based algorithm that takes into account bounds on the gantry speed and dose rate, as well as an upper bound on the rate of change of the gantry speed, in addition to MLC constraints. The algorithm iteratively adds one aperture at each control point along the treatment arc. In each iteration, a restricted problem optimizing intensities at previously selected apertures is solved, and its solution is used to formulate a pricing problem, which selects an aperture at another control point that is compatible with previously selected apertures and leads to the largest rate of improvement in the objective function value of the restricted problem. Once a complete set of apertures is obtained, their intensities are optimized and the gantry speeds and dose rates are adjusted to minimize treatment time while satisfying all machine restrictions. Comparisons of treatment plans obtained by our algorithm to idealized IMRT plans of 177 beams on five clinical prostate cancer cases demonstrate high quality with respect to clinical dose–volume criteria. For all cases, our algorithm yields treatment plans that can be delivered in around 2 min. Implementation on a graphic processing unit enables us to finish the optimization of a VMAT plan in 25–55 s.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98593/1/0031-9155_57_14_4569.pd

Sensitivity analysis for lexicographic ordering in radiation therapy treatment planning

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134937/1/mp0218.pd

A DVH‐guided IMRT optimization algorithm for automatic treatment planning and adaptive radiotherapy replanning

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135098/1/mp5700.pd

Ultrafast treatment plan optimization for volumetric modulated arc therapy (VMAT)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134981/1/mp1675.pd

The Counterpart Principle of Analogical Support by Structural Similarity

We propose and investigate an Analogy Principle in the context of Unary Inductive Logic based on a notion of support by structural similarity which is often employed to motivate scientific conjectures

Atomic force microscopy measurements of anionic liposomes reveal the effect of liposomal rigidity on antigen-specific regulatory T cell responses

Regulatory T cells (Tregs) are vital for maintaining a balanced immune response and their dysfunction is oftenassociated with auto-immune disorders. We have previously shown that antigen-loaded anionic liposomescomposed of phosphatidylcholine (PC) and phosphatidylglycerol (PG) and cholesterol can induce strong antigenspecificTreg responses. We hypothesized that altering the rigidity of these liposomes while maintaining theirsize and surface charge would affect their capability of inducing Treg responses. The rigidity of liposomes isaffected in part by the length and saturation of carbon chains of the phospholipids in the bilayer, and in part bythe presence of cholesterol. We used atomic force microscopy (AFM) to measure the rigidity of anionic OVA323-containing liposomes composed of different types of PC and PG, with or without cholesterol, in a molar ratio of4:1(:2) distearoyl (DS)PC:DSPG (Young's modulus (YM) 3611 ± 1271 kPa), DSPC:DSPG:CHOL(1498 ± 531 kPa), DSPC:dipalmitoyl (DP)PG:CHOL (1208 ± 538), DPPC:DPPG:CHOL (1195 ± 348 kPa),DSPC:dioleoyl (DO)PG:CHOL (825 ± 307 kPa), DOPC:DOPG:CHOL (911 ± 447 kPa), and DOPC:DOPG(494 ± 365 kPa). Next, we assessed if rigidity affects the association of liposomes to bone marrow-deriveddendritic cells (BMDCs) in vitro. Aside from DOPC:DOPG liposomes, we observed a positive correlation betweenliposomal rigidity and cellular association. Finally, we show that rigidity positively correlates with Treg responsesin vitro in murine DCs and in vivo in mice. Our findings underline the suitability of AFM to measureliposome rigidity and the importance of this parameter when designing liposomes as a vaccine delivery system

Atomic force microscopy measurements of anionic liposomes reveal the effect of liposomal rigidity on antigen-specific regulatory T cell responses

Regulatory T cells (Tregs) are vital for maintaining a balanced immune response and their dysfunction is oftenassociated with auto-immune disorders. We have previously shown that antigen-loaded anionic liposomescomposed of phosphatidylcholine (PC) and phosphatidylglycerol (PG) and cholesterol can induce strong antigenspecificTreg responses. We hypothesized that altering the rigidity of these liposomes while maintaining theirsize and surface charge would affect their capability of inducing Treg responses. The rigidity of liposomes isaffected in part by the length and saturation of carbon chains of the phospholipids in the bilayer, and in part bythe presence of cholesterol. We used atomic force microscopy (AFM) to measure the rigidity of anionic OVA323-containing liposomes composed of different types of PC and PG, with or without cholesterol, in a molar ratio of4:1(:2) distearoyl (DS)PC:DSPG (Young's modulus (YM) 3611 ± 1271 kPa), DSPC:DSPG:CHOL(1498 ± 531 kPa), DSPC:dipalmitoyl (DP)PG:CHOL (1208 ± 538), DPPC:DPPG:CHOL (1195 ± 348 kPa),DSPC:dioleoyl (DO)PG:CHOL (825 ± 307 kPa), DOPC:DOPG:CHOL (911 ± 447 kPa), and DOPC:DOPG(494 ± 365 kPa). Next, we assessed if rigidity affects the association of liposomes to bone marrow-deriveddendritic cells (BMDCs) in vitro. Aside from DOPC:DOPG liposomes, we observed a positive correlation betweenliposomal rigidity and cellular association. Finally, we show that rigidity positively correlates with Treg responsesin vitro in murine DCs and in vivo in mice. Our findings underline the suitability of AFM to measureliposome rigidity and the importance of this parameter when designing liposomes as a vaccine delivery system

The effectiveness of antibacterial therapeutic clothing compared with non-antibacterial therapeutic clothing in patients with moderate-to-severe atopic dermatitis: A randomized controlled, observer-blind pragmatic trial (ABC trial)

BACKGROUND Increased Staphylococcus aureus (SA) colonization is considered an important factor in the pathogenesis of atopic dermatitis (AD). Antibacterial therapeutic clothing aims to reduce SA colonization and AD inflammation, however its role in the management of AD remains poorly understood. OBJECTIVE To investigate the effectiveness of antibacterial therapeutic clothing plus standard topical treatment in patients with moderate-to-severe AD, compared to standard therapeutic clothing plus standard topical treatment. If effectiveness is demonstrated, the cost-effectiveness will be evaluated. METHODS A pragmatic, double-blinded, multicenter, randomized, controlled, trial (NCT04297215) was conducted in patients of all ages with moderate-to-severe AD. Patients were centrally randomized 1:1:1 to receive standard therapeutic clothing, antibacterial clothing based on chitosan or silver. The primary outcome was the between-group difference in Eczema Area and Severity Index (EASI) measured over 52 weeks. Secondary outcomes included patient-reported outcomes, topical corticosteroid use, SA colonization, safety, and cost-effectiveness. Outcomes were assessed by means of (generalized) linear mixed model analyses. RESULTS Between March 16, 2020, and December 20, 2021, 171 patients were enrolled. In the analyses 159 patients were included (n=54 in the standard therapeutic clothing group, n=50 in the chitosan group and n=55 in the silver group). Adherence was high (median: 7 nights/week, IQR: 3-7). Median EASI scores at baseline, 4, 12, 26 and 52 weeks were in the standard therapeutic clothing group 11.8, 4.3, 4.6, 4.2, 3.6 compared to 11.3, 5.0, 3.0, 3.0, 4.4 in the chitosan and 11.6, 5.0, 5.4, 4.6 and 5.8 in the silver group. No differences in EASI over 52 weeks between the standard therapeutic clothing, chitosan (-0.1, 95%CI: -0.3 to 0.2, p=0.53), and silver group (-0.1, 95%CI: -0.3 to 0.2, p=0.58) were found. However, a small significant (P=0.035) group-by-time interaction effect between the standard and silver group was found, in which the silver group performed worse after 26 weeks. No differences between groups were found in patient-reported outcomes, topical corticosteroid use, SA skin colonization, and healthcare utilization. No severe adverse events or silver absorption were observed. CONCLUSIONS The results of this study suggest no additional benefits of antibacterial agents in therapeutic clothing in patients with moderate-to-severe AD

Chronic hand eczema in Europe:Patient experiences and perspectives (CHEPEP) in qualitative interviews

Background: Chronic hand eczema (CHE) is a very common skin disease among the European population. It causes itch and pain and, in more severe cases, seriously impairs hand functioning at work and in private life. Objectives: To explore perspectives of people with lived experience on CHE-related problems, wishes and goals. Methods: Following a qualitative approach, we conducted topic-guided interviews in five European countries and applied template analysis to identify recurrent themes among patients with CHE. Results: We interviewed 60 patients in seven outpatient dermatological and occupational medicine clinics in Croatia, Denmark, Germany, the Netherlands and Spain. Five main themes were identified: (1) knowledge about the disease and its course, (2) preventive behaviour, (3) hand eczema therapy, (4) impact on everyday life and (5) attitudes towards CHE and healthcare. Participants did not feel well informed about CHE, especially about causes, triggers and treatment options. Preventive measures were experienced as more or less effective but also cumbersome. Experiences with therapy were diverse. Treatment satisfaction depended on the results and on the perceived support from the treatment teams. Participants found it important to be taken seriously, to receive practical advice, to try out additional treatments or examinations, find new hope and have occupational perspectives. They wished that others could better understand the physical and emotional burden of CHE. Patient support groups were not mentioned. Participants found it important to learn to take care of themselves and accept life with CHE. Conclusions: Due to its annoying symptoms, high visibility and impaired functioning at work and in private life, CHE has a high emotional and social impact. Some people may require support to learn coping with CHE and its prevention. Patients wish for information about causes and triggers. They value physicians who listen to them and keep looking for solutions.</p