Thermal dosimetry for bladder hyperthermia treatment. An overview.

The urinary bladder is a fluid-filled organ. This makes, on the one hand, the internal surface of the bladder wall relatively easy to heat and ensures in most cases a relatively homogeneous temperature distribution; on the other hand the variable volume, organ motion, and moving fluid cause artefacts for most non-invasive thermometry methods, and require additional efforts in planning accurate thermal treatment of bladder cancer. We give an overview of the thermometry methods currently used and investigated for hyperthermia treatments of bladder cancer, and discuss their advantages and disadvantages within the context of the specific disease (muscle-invasive or non-muscle-invasive bladder cancer) and the heating technique used. The role of treatment simulation to determine the thermal dose delivered is also discussed. Generally speaking, invasive measurement methods are more accurate than non-invasive methods, but provide more limited spatial information; therefore, a combination of both is desirable, preferably supplemented by simulations. Current efforts at research and clinical centres continue to improve non-invasive thermometry methods and the reliability of treatment planning and control software. Due to the challenges in measuring temperature across the non-stationary bladder wall and surrounding tissues, more research is needed to increase our knowledge about the penetration depth and typical heating pattern of the various hyperthermia devices, in order to further improve treatments. The ability to better determine the delivered thermal dose will enable clinicians to investigate the optimal treatment parameters, and consequentially, to give better controlled, thus even more reliable and effective, thermal treatments

Effect of voluntary waiting period on metabolism of dairy cows during different phases of the lactation.

An extended calving interval (CInt) by extending the voluntary waiting period (VWP) could be associated with altered metabolism in dairy cows. The aim of this study was first to evaluate the effects of VWP on metabolism and body condition during the first 305 days after the first calving in the experiment (calving 1), around the end of the VWP, and during pregnancy (280 d before calving 2). Second, the effects of the VWP on metabolism were determined from 2 wk before until 6 wk after calving 2. Third, individual cow characteristics were used to predict milk production and body condition of cows after different VWP. Holstein-Friesian cows (N=154, 41 primiparous (PP), 113 multiparous (MP)) were blocked for parity, milk production, and lactation persistency, randomly assigned to a VWP of 50, 125, or 200 days (VWP50, VWP125, or VWP200) and followed from calving 1 until 6 wk after calving 2. In the first 6 wk after calving 1 and from 2 wk before until 6 wk after calving 2, weekly plasma samples were analyzed for non-esterified fatty acids (NEFA), β-hydroxybutyrate, glucose, insulin, and insulin-like growth factor 1 (IGF-1). From wk 7 after calving 1 until 2 wk before calving 2, insulin and IGF-1 were analyzed every 2 wk. Fat- and protein-corrected milk (FPCM) and body weight (BW) gain were measured weekly. Cows were divided in two parity classes based on calving 1 (PP and MP) and remained in these classes after calving 2. During pregnancy, MP cows in VWP200 had greater plasma insulin and IGF-1 concentration and lower FPCM compared with MP cows in VWP125 (insulin: 18.5 vs 13.9 µU/mL, CI 13.0 - 19.7, P<0.01; IGF-1: 198.5 vs 175.3 ng/mL ± 5.3, P=0.04; FPCM: 22.6 vs 30.0 kg/d ± 0.8, P<0.01) or VWP50 (insulin: 15.8 µU/mL, P<0.01; IGF-1: 178.2 ng/mL, P<0.01; FPCM: 26.6 kg/d, P<0.01) and had a greater daily BW gain compared with cows in VWP50 (3.6 vs 2.5 kg/d ± 0.2; P<0.01). After calving 2, MP cows in VWP200 had greater plasma NEFA concentration (0.41 mmol/L) compared with MP cows in VWP125 (0.30 mmol/L, P=0.04) or VWP50 (0.26 mmol/L, P<0.01). For PP cows, the VWP did not affect FPCM or body condition during the first lactation in the experiment, or metabolism after calving 2. Independent of the VWP, higher milk production and lower body condition before insemination were associated with higher milk production and lower body condition at the end of the lactation. Variation in these characteristics among cows could call for an individual approach for an extended VWP

Temperature and thermal dose during radiotherapy and hyperthermia for recurrent breast cancer are related to clinical outcome and thermal toxicity: a systematic review

Objective: Hyperthermia therapy (HT), heating tumors to 40–45 °C, is a known radiotherapy (RT) and chemotherapy sensitizer. The additional benefit of HT to RT for recurrent breast cancer has been proven in multiple randomized trials. However, published outcome after RT + HT varies widely. We performed a systematic review to investigate whether there is a relationship between achieved HT dose and clinical outcome and thermal toxicity for patients with recurrent breast cancer treated with RT + HT. Method: Four databases, EMBASE, PubMed, Cochrane library and clinicaltrials.gov, were searched with the terms breast, radiotherapy, hyperthermia therapy and their synonyms. Final search was performed on 3 April 2019. Twenty-two articles were included in the systematic review, reporting on 2330 patients with breast cancer treated with RT + HT. Results: Thirty-two HT parameters were tested for a relationship with clinical outcome. In studies reporting a relationship, the relationship was significant for complete response in 10/15 studies, in 10/13 studies for duration of local control, in 2/2 studies for overall survival and in 7/11 studies for thermal toxicity. Patients who received high thermal dose had on average 34% (range 27%–53%) more complete responses than patients who received low thermal dose. Patients who achieved higher HT parameters had increased odds/probability on improved clinical outcome and on thermal toxicity. Conclusion: Temperature and thermal dose during HT had significant influence on complete response, duration of local control, overall survival and thermal toxicity of patients with recurrent breast cancer treated with RT + HT. Higher temperature and thermal dose improved outcome, while higher maximum temperature increased incidence of thermal toxicity

Udder health of dairy cows with an extended voluntary waiting period from calving until the first insemination

This study aimed to evaluate the effect of an extended voluntary waiting period (VWP) on SCC, SCC elevations and clinical mastitis incidence during the complete lactation and the first 6 weeks of the next lactation. Holstein-Friesian dairy cows ( N = 154) were blocked for parity, expected milk yield, calving season and breeding value for persistency and were randomly distributed across 3 VWP (50, 125, or 200 d: VWP-50, VWP-125, VWP-200). Cows were monitored from calving until 6 weeks into the next lactation, or until culling. An elevation of SCC in milk was defined as SCC in milk ≥200 000 cells/ml after two previous weeks with SCC < 200 000 cells/ml. Over the complete lactation, extending the VWP did not affect SCC elevations and the occurrence of clinical mastitis per lactation or per cow per year. There was no clear effect of VWP length on SCC in the complete lactation, except that multiparous cows in VWP-125 had a higher SCC compared with multiparous cows in VWP-50. Dry-off antibiotic usage per cow per year was lower in VWP-200 compared with VWP-50 for multiparous cows. In the first 6 weeks of the next lactation, cows in VWP-200 had a higher SCC compared with cows in VWP-50, with no effect of VWP on the number of elevations of SCC or the occurrence of clinical mastitis. Extending the VWP may therefore be used to reduce the frequency of transition periods and the associated use of dry-cow antibiotics, with limited impact on udder health, and a similar occurrence of SCC elevations and clinical mastitis per year

Effect of voluntary waiting period on metabolism of dairy cows during different phases of the lactation

An extended calving interval (CInt) by extending the voluntary waiting period (VWP) could be associated with altered metabolism in dairy cows. The aim of this study was first to evaluate the effects of VWP on metabolism and body condition during the first 305 d after the first calving in the experiment (calving 1), around the end of the VWP, and during pregnancy (280 d before calving 2). Second, the effects of the VWP on metabolism were determined from 2 wk before until 6 wk after calving 2. Third, individual cow characteristics were used to predict milk production and body condition of cows after different VWP. Holstein-Friesian cows (N = 154, 41 primiparous [PP], 113 multiparous [MP]) were blocked for parity, milk production, and lactation persistency, randomly assigned to a VWP of 50, 125, or 200 d (VWP50, VWP125, or VWP200) and followed from calving 1 until 6 wk after calving 2. In the first 6 wk after calving 1 and from 2 wk before until 6 wk after calving 2, weekly plasma samples were analyzed for nonesterified fatty acids (NEFA), β-hydroxybutyrate, glucose, insulin, and insulin-like growth factor 1 (IGF-1). From wk 7 after calving 1 until 2 wk before calving 2, insulin and IGF-1 were analyzed every 2 wk. Fat- and protein-corrected milk (FPCM) and body weight (BW) gain were measured weekly. Cows were divided in two parity classes based on calving 1 (PP and MP) and remained in these classes after calving 2. During pregnancy, MP cows in VWP200 had greater plasma insulin and IGF-1 concentration and lower FPCM compared with MP cows in VWP125 (insulin: 18.5 vs. 13.9 µU/mL, CI 13.0-19.7, P < 0.01; IGF-1: 198.5 vs. 175.3 ng/mL ± 5.3, P = 0.04; FPCM: 22.6 vs. 30.0 kg/d ± 0.8, P < 0.01) or VWP50 (insulin: 15.8 µU/mL, P < 0.01; IGF-1: 178.2 ng/mL, P < 0.01; FPCM: 26.6 kg/d, P < 0.01) and had a greater daily BW gain compared with cows in VWP50 (3.6 vs. 2.5 kg/d ± 0.2; P < 0.01). After calving 2, MP cows in VWP200 had greater plasma NEFA concentration (0.41 mmol/liter) compared with MP cows in VWP125 (0.30 mmol/liter, P = 0.04) or VWP50 (0.26 mmol/liter, P < 0.01). For PP cows, the VWP did not affect FPCM or body condition during the first lactation in the experiment, or metabolism after calving 2. Independent of the VWP, higher milk production and lower body condition before insemination were associated with higher milk production and lower body condition at the end of the lactation. Variation in these characteristics among cows could call for an individual approach for an extended VWP

More milking days with lower yields : sustainability impacts of short or no dry periods in dairy cows

Farmers traditionally stop milking a cow 6 to 8 weeks before next calving. This ‘dry period’ (DP) maximises milk production in the next lactation. The resulting high milk production in early lactation, however, results in a negative energy balance and is associated with reduced health and fertility. Shortening or omitting the DP improves the energy balance in early lactation at the cost of milk production. This project aimed to evaluate and integrate sustainability impacts of shortening or omitting the DP, with a focus on cow welfare, cash flows at farm level, and greenhouse gas (GHG) emissions per unit milk. Welfare was addressed by monitoring lying and feeding behaviour of 81 cows with no DP or a 30-day DP in weeks -4 and 4 relative to calving. On average, cows with no DP had a 1 hour per day shorter lying time in week -4 than cows with a DP, but the absolute daily lying time (12.6 h) and relatively constant feeding rate suggest that welfare of cows with no DP was not impaired by milking in late gestation. Moreover, cows with no DP had a 1 hour longer lying time and a greater feed intake in week 4 of lactation, suggesting a better adaptation to the start of the next lactation. The number of meals, feed intake, and lying time of dairy cows were associated with physiological indicators of high metabolic load during this period. To compare milk yield between cows with different DP lengths, accounting for extra milk before calving and possible changes in calving interval, the ‘effective lactation yield’ measure was developed. The impact of DP length on effective lactation yields of second and greater parity cows was assessed over multiple lactations. The reduction in effective lactation yield compared with a standard DP was larger for no DP than for a short DP, and did not differ between the first and a subsequent shortening or omission of the DP, although the timing of milk yield changed. The overall impact of DP length on milk production, cash flows and GHG emissions were modelled based on production data of dairy farms that voluntarily managed cows for a short or no DP. First, introduction of no DP resulted in a dip in milk production of the herd in the second year the strategy was applied. On average over 5 years, applying a short DP reduced milk yield of the herd by 3.1%, and applying no DP reduced milk yield of the herd by 3.5%. Moreover, short and no DP reduced partial cash flows by €12 and €16 per cow per year, and increased GHG emissions per unit milk by 0.8% and 0.5%, respectively. These relatively small negative impacts of short and no DP on cash flows and GHG emissions can be offset by improved cow health and lifespan, which could result from the improved energy balance in early lactation (more pronounced for no DP than for a short DP) when these strategies are adopted. In conclusion, both shortening and omitting the DP can improve cow welfare with a small negative impact on cash flows and GHG emissions, which may be offset by improved cow health.</p

Modelling curved contact flexible microstrip applicators for patient-specific superficial hyperthermia treatment planning

This paper describes a method to reconstruct bendable superficial hyperthermia applicators for routine clinical patient-specific treatment planning. The reconstruction uses a CT scan with a flexible silicone dummy applicator positioned on the patient. The curvature was approximated by two second-degree polynomial functions. A realistic treatment series was mimicked using a standard Alderson radiation therapy phantom and a treatment planning model was reconstructed from a CT scan. The variation among treatment curvatures was compared to the modelled curvature. The mathematical approximation of the applicator curvature was validated for this phantom experiment, as well as for clinical treatments. The average maximum variation among the successive mimicked sessions was 3.67 ± 0.69 mm (range 2.98–4.60mm). The maximum deviation between the treatment curvature and the modelled curvature was 4.35 mm. Comparing the treatment and approximated curvature yielded a maximum deviation between 2.98 mm and 4.12 mm. For clinical treatments the maximum deviation of the treatment and approximated curvature varied between 0.48 mm and 1.98 mm. These results allow adequate reconstruction of bendable hyperthermia applicators for treatment planning, which can further improve treatment quality, for example by optimizing the water bolus temperature for patient-specific tumor depths. Predictive parameters for hyperthermia treatment outcome can easily be evaluated and compared for various input parameters

Analysis of banded microstructures in multiphase steels assisted by transformation-induced plasticity

The influence of the spatial distribution of the austenitic phase on the effective mechanical properties of a multiphase steel assisted by transformation-induced plasticity is analyzed using a numerical homogenization scheme. Representative three-dimensional volume elements with distinct microstructures are created applying a newly-developed algorithm based on the generation of a multilevel Voronoi tessellation; this approach allows for straightforwardly incorporating grains with complex, non-convex shapes in the microstructure. The effective macroscopic response of the samples is computed under the formulation of a set of non-redundant, periodic boundary conditions, which warrants a consistent transition between the microscopic and macroscopic scales. A sample in which austenitic grains are clustered within a ferritic matrix by means of a band-like region is compared to a sample with austenitic grains being randomly dispersed within the ferritic matrix. It is found that the banded microstructure may be detrimental in comparison to the dispersed microstructure, since it allows substantial plastic localization to occur in the ferritic matrix, which in turn diminishes the strengthening effect provided by the austenitic phase

Technical and Clinical Evaluation of the ALBA-4D 70MHz Loco-Regional Hyperthermia System

Hyperthermia, increasing tumor temperatures to 39-43°C for 1 h, enhances the effectiveness of radiotherapy and chemotherapy. Deep seated pelvic tumors are usually heated by arrays of radiofrequency or microwave antennas placed around the patient, capable of focussing power onto the tumor. The AMC developed the AMC 4 loco-regional hyperthermia system with 4 rectangular 70 MHz waveguide antennas for heating deep-seated pelvic tumors. This system has been commercialized as the ALBA4D utilizing the same geometric layout and the same waveguides. Goal of this study was to evaluate the performance of the ALBA4D system. We compared electric field (E-field) distributions in a patient-mimicking phantom and confirmed that phase control of the focal point is similar to the AMC 4, thus ensuring similar clinical performance

Exploring synchrony of lying on commercial dairy farms in relation to management

Synchronous lying may be an indicator of positive welfare in dairy cows. However, little is known about whether farms differ in the level of lying synchrony and how consistent this is within a farm. Moreover, the level of synchrony may vary within the day. Accelerometers used for estrus detection of cows enable continuous monitoring of synchronous lying of herds. We studied the level, timing and duration of synchronous lying in 8 Holstein Friesian or Holstein dairy herds across 1 year, in relation to grazing and milking management (robotic milking, 2x and 3x daily milking). In ‘winter’ months (November-March), herds were housed; in ‘summer’ months (May-September), 6 of 8 herds had access to pasture for 5–8 h per day, the other 2 herds were full-time housed. April and October were excluded because of variable management. Herds had 0.9–1.4 cubicles available per cow. After cleaning individual accelerometer data, herd average lying time was computed per 15-min (900 s) interval. An interval was defined as synchronous lying when the herd average lying time > 540 or > 630 s (i.e. assuming 60% or 70% of the herd was lying). Daily synchronous lying time was defined as the number of synchronous intervals × 15 min. A general linear model was used to assess effects of farm, season, and their interaction on synchronous lying time per day; with Tukey-adjusted pairwise comparisons. Correlations were made per farm per season to assess the association between total daily lying time and synchronous lying time. Across all herds and calendar days, the highest level of synchrony reached was on average 78%. Most synchronous lying occurred between 2AM and 6AM, though this was not true for all farms. Synchronous lying occurred least between 4 and 8 PM. Across farms, average synchronous (60% threshold) lying time per day was 5.9 h in summer (range: 2.7 – 7.9 h) and 5.5 h in winter (range: 1.6 – 9.1 h). In 3 out of 6 farms with grazing, synchronous lying time was higher in summer due to occurrence of synchronous lying during periods with pasture access. On 2 farms, synchronous lying time was higher in winter than summer due to increased synchronous lying at night. Across farms, average daily lying time and synchronous lying time generally showed moderate correlations. Monitoring synchronous lying in dairy herds using accelerometers was feasible, and 24-h synchrony patterns seemed consistent within farms. Its validity as a positive or negative welfare indicator requires further study