As a common hydrodynamic phenomenon, multi-cavitation dynamics is widely found in many industries such as hydraulic engineering, shipping industry and chemical industry. The jet and shock wave phenomenon in the interaction of two cavitation bubbles are the basis of multi-cavitation bubbles interaction research. By respectively inducing two cavitation bubbles through laser and underwater low-voltage discharge, this paper tested the jet and shock wave resulting from the collapse of the two cavitation bubbles, and the following conclusions are obtained: (1) If the two cavitation bubbles are synchronously generated but in different size, as the distance between the two cavitation bubbles increases or the maximum radius of the smaller cavitation bubble increases, the effect of the small cavitation bubble on the larger one gradually changes from the surface wave phenomenon to jet that breaks through the larger bubble. When the two bubble center lines are parallel to the wall surface, this jet suppresses the formation of the jet to the wall surface when the large cavitation bubble collapses; if the two cavitation bubbles are generated at the same time with same size, as the initial distance of the two cavitation bubbles gradually decreases, the two bubbles are more likely to form a face-to-face collapse, and the smaller the distance between the two, the easier it is to fuse. (2) The impact of the initial moment of the cavitation bubble on the structure of the collapse shock wave is as follows: for two bubbles of different sizes formed synchronously, the shock wave propagates to the periphery in the form of a number of consecutive waves appearing in the larger bubble, while for the unsynchronized ones, shock waves appeared in both cavitation collapses, and a number of consecutive waves appear in the late-formed cavitation bubble. And multiple consecutive shock waves may overlap in some areas of the space. These conclusions have obvious implications for preventing cavitation damage and utilization of cavitation. Cavitation is a very typical hydrodynamic phenomenon that exists in many fields, such as hydraulic engineering, shipping, ultrasonic cleaning, underwater explosions and the medical industry. Since the size of the cavitation bubble is very small (millimeters) and the life cycle is very short (milliseconds or even microseconds), it is very difficult to directly observe cavitation in the engineering field. Therefore, high-speed photography is a must for observing the jet and shock waves generated by cavitation collapses, so as to explore the internal mechanism of cavitation dynamics.et al.1 concluded that when ρgRmax/P∞ > 4*10−4, the jet formed during the collapse of the cavitation bubble will pierce the far-end surface of the cavitation. Where: ρ is the liquid density, g is the gravitational acceleration, Rmax is the radius at which the cavitation bubble develops to the maximum volume, and P∞ is the hydrostatic pressure of the surrounding liquid. When the cavitation bubble shrinks and collapses, the Weber number and Reynolds number are so large that the effect of liquid viscosity and surface tension on the collapse of the cavitation bubble is negligible4. It can be seen from many current research results that the direction of jets in the late stage of cavitation collapse is strongly influenced by the surrounding boundary. For the cavitation near the free surface, the cavitation is attracted by the free surface during the expansion phase. When the jets appeared in the contraction phase, the jets deviate from the free surface8. With regard to the interaction of cavitation bubbles with rigid walls, high-speed jets of cavitation bubbles in the late stages of collapse develop towards the wall11, this jet towards the wall is an important part of the research on the cavitation erosion mechanism12.There are many reports on single cavitation bubble dynamics and the interaction between bubbles and wall surfaces. Regarding the dynamics of cavitation bubbles in the unbounded domain, Obreschkow et al.13 studied the jet flow in an air bubble induced by a nearby cavitation bubble and discovered that the speed of such a jet flow can be up to 250 m/s. Luo et al.14 used the method of high-voltage discharge technology generate a cavitation bubble to study the interaction between a cavitation bubble and an air bubble. Goh et al.15 studied the interactions between hemispheric air bubbles placed below the underwater slab and a cavitation bubble, and discovered that the ratio between oscillation time of the cavitation bubbles and the oscillation time of the air bubbles is the important parameter impacting the jet caused by cavitation bubbles collapse. The interaction between a cavitation bubble and a particle was researched by adopting a high-voltage discharge technology to induce cavitation bubble16 and low-voltage underwater discharge technology to induce a cavitation bubble17. The interaction between ice block and cavitation bubble was researched by Cui et al.18, the direction of jet and the propagation of shock waves were captured.In the real field of production, cavitation bubble often do not appear in isolation. As a result, in recent years, some new research interests on cavitation were proposed, such as studies on the interaction between cavitation bubbles and cavitation bubbles, cavitation bubbles and air bubbles, cavitation bubbles and particles, and cavitation bubbles and ice block have also been reported. Pain 21. However, in reality, each cavitation bubble in cavitation group has different properties, such as the time of inception, the size and the position at inception. Above all, in addition to these factors, the boundary around the bubble has a very important impact on the collapse characteristics of the bubbles. Bremond et al.22 experimentally studied the interaction of two hemispherical cavitation bubbles equivalent to two spherical ones and studied their interactions with rigid walls. Tomita et al.23 studied the interaction of two laser-induced cavitation bubbles near the wall surface. Blake et al.19 conducted a corresponding numerical simulation study on the conditions in the above literature. Robinson et al.24 studied the interaction of two cavitation bubbles under the free surface using a combination of experimental and numerical simulations, and found that if the distances between the two cavitation bubbles are very close, the overall collapse characteristics are greatly affected by the free surface. Chew et al.25 studied two cavitation bubbles under the circumstances that the two bubble center lines are parallel to the wall surface, and they obtained a jet prediction method under the dual influence of cavitation and wall surface.Regarding the cavitation clouds appearing in the actual project (such as the cavitation clouds inside the flood discharge tunnel in the water conservancy project), the interaction between the cavitation bubbles inside the cavitation cloud directly affects the destructive strength of the cavitation cloud collapse. Therefore, the study of the interaction mechanism between the cavitation bubbles inside the cavitation group is very important. If the two cavitation bubbles are very close at the time of inception, the surfaces of the two close to each other are flattened due to the extrusion of the expansion process, gradually approaching, and finally the two bubbles fuse together. The interaction of two cavitation bubbles is the most basic as well as the foremost part for the study of interactions of multiple bubbles. The fusion phenomenon is typical and complex, on which the researches are still incomplete so far. For two cavitation bubbles formed at the same time, the jets that appear in the late collapse of the cavitation develop toward each otheret al.22 found that the inertia of the liquid film between them had an important impact on fusion before the two cavitation bubbles were fused. Rungsiyaphornrat et al.26 proposed a mathematical model that can be used to simulate the interaction of two underwater explosive bubbles using the boundary integral method (BIM). Han et al.27 studied the dynamics of fused bubbles using numerical simulations. Although there have been some reports on fusion bubbles, the current research results are less concerned with the dynamics of fusion bubbles, especially the dynamics of cavitation bubbles to the ring stage. In recent years, with the rise of new computational methods, Smoothed Particle Hydrodynamics (SPH) has been gradually applied to the study of bubble dynamics. Zhang28 established an axisymmetric SPH numerical model for bubble dynamics, simulated the underwater explosion bubble combined with Boundary Element Method (BEM), and obtained jets and shock waves that are highly consistent with the experimental results. As the SPH computational method is gradually applied to the research field of fluid–structure interactions29, this new computational method will become a new way to solve complex bubble dynamics problems and bubble-wall interactions.In addition, there are some reports on the study of the fusion of two cavitation bubbles. Through a comprehensive comparison of theoretical and experimental studies, Bremond Based on the above-mentioned researches on two cavitation bubbles and multi-cavitation bubbles, this paper qualitatively discussed the surface wave phenomena, the development of internal jets, and the development of two bubble shock waves that occur during the interaction of two cavitation bubbles with a big difference in size. And the evolution characteristics of two cavitation bubbles induced by the two systems were compared.30 was adopted, the principle of which is shown in Fig. Studying interactions of two cavitation bubbles from the mesoscopic level requires a multi-cavitation-inducing system. The jet and shock wave phenomena appearing in the interaction between the cavitation bubbles need to be observed by means of a high-speed dynamic acquisition and analysis system. In this paper, the method of laser-induced cavitation is mainly used for the jet phenomenon in the two cavitation bubbles interactions. The principle is shown in Fig. The method of using laser underwater focusing to induce cavitation bubble is shown in Fig. The method of inducing cavitation bubbles through low-voltage underwater discharge is shown in Fig. The evolution cycle of the cavitation bubbles is very short. In order to observe the cavitation dynamics process, a high-speed dynamic acquisition and analysis system must be adopted. The system consists of a high-speed camera, a macro lens, and a light source. Among them, the experiment used Fastcam SA-Z high-speed camera . Due to the small size of the cavitation bubbles, the experiment used a macro lens  for the high-speed camera. In order to obtain a clear bubble profile, the evolution and migration of the cavitation bubbles, as well as the development of jets, a cold light source (power: 150 W) must be used as a background supplemental light source. For the evolution of shock waves during cavitation bubble collapse, we used a white light (power: 3 W) with parallel light source as a background light. The shock waves can change the density of the water before and after the wave. The intensity of the parallel light that is projected into the lens after the water with the density variations will change, so we can observe the shock wave on the image.Rmax is used as the characteristic parameter of the cavitation bubble when it expands to the maximum volume, t represents the time during which the bubbles developed, wherein the subscripts represent different bubble numbers; the distance of two bubbles in the interaction process is represented as L. The distance between the bubble and the wall is expressed by the dimensionless parameter γ, and its physical meaning is the ratio of the minimum distance from the position of the bubble at the moment of inception to the wall surface h and the characteristic parameter of the cavitation bubble Rmax. v represents the velocity of jet, and Vw represents the velocity of shock wave.In the study of this paper, the radius t = 0 μs), and the current evolution time of the cavitation bubble is marked in each picture. In Fig. Figure t = 0 μs, the focused spot penetrates the water and emits a dazzling white light. As the pulse of the laser energy ends, the bubble gradually expands outward. When t = 75 μs, the Bubble_1 develops to its maximum volume with the maximum radius of 0.26 mm. During the period of 0 μs < t < 75 μs, since the distance between the two bubbles is very close, they interact with each other during the expansion. But the energy of Bubble_1 is very small, so that ripples appeared on the surface of the Bubble_2 (on the side close to the surface of the Bubble_1). And as the Bubble_1 expands to its maximum volume, the ripples on the surface of the Bubble_2 gradually advancing toward its far-end surface. During the period of 75 μs < t < 137.5 μs, the Bubble_1 enters the contraction phase, while the Bubble_2 continues to expand until it reaches a maximum radius of 1.28 mm. At the same time, the Bubble_1 is gradually swallowed by the Bubble_2 (not completely fused), and the ripples on the surface of the Bubble_2 are gradually weakened. During the period of 137.5 μs < t < 237.5 μs, both the Bubble_1 and Bubble_2 contract, and the Bubble_2 shrinks to its minimum volume at t = 237.5 μs. It is obvious from Fig. a20 that the minimum volume of Bubble_2 is slightly larger than the one of Bubble_1. During the period of 237.5 μs < t < 337.5 μs, both bubbles enter the rebound regeneration stage. It can be clearly seen from the rebound regeneration stage of the two cavitation bubbles that the Bubble_2 shows a pronounced jet under the influence of the Bubble_1 (in the direction away from the Bubble_1), while the Bubble_2 does not show a jet and re-expands only at the original inception position. According to the studies of Obreschkow et al.1, when ρgRmax/P∞ is less than 4*10−4, the cavitation bubbles do not form a jet that pierces the far-end surface. Under the experimental conditions of this paper, ρgRmax/P∞ = 1.26*10−4, which less than 4*10−4. However, the Bubble_2 forms a jet that develops away from the Bubble_1 under the influence of Bubble_1. It can be seen that in the free field, a single cavitation bubble is slightly disturbed by the surroundings, which will change the collapse characteristics in its free field.In Fig. t = 0 μs. When the laser pulse energy is over, the bubble gradually expands until t = 60 μs when Bubble_1 develops to its maximum volume with a maximum radius of 0.47 mm. And within the period of 0 μs < t < 60 μs, the minimum distance of the surfaces of the two bubbles is gradually reduced from 1.11 mm to 0.11 mm. Besides, the surface of the Bubble_1 (the side close to the Bubble_2) takes on a flat bottom form. The Bubble_2 is in an expansion stage at this time, and its surface flat bottom form is not as obvious as Bubble_1. During the period of 60 μs < t < 110 μs, the Bubble_1 continues to shrink, while the Bubble_2 continues to expand to the maximum volume, and the distance between the Bubble_1 and the Bubble_2 is further reduced to 0.06 mm, and the adjacent surfaces of the two bubbles exhibit a flat bottom form. In this process, the far-end surface of the Bubble_1 (the surface away from Bubble_2) shrinks faster than the surface near the Bubble_2, which is an asymmetric contraction form. With the strong asymmetric contraction of the Bubble_1, finally Bubble_1 formed a jet that pierced Bubble_2. Since the jet develops inside the cavitation bubble, it moves very fast, the velocity of the jet is about 326.50 m/s obtained by image measurement. When piercing the far-end surface of the bubble, the velocity of the jet decreases sharply to 85.4 m/s due to the retardation of the water. When t = 140 μs, the velocity of the jet drops to 55.80 m/s. Within 140 μs < t < 175 μs, the Bubble_2 begins to enter the contraction phase. As Bubble_2 gradually shrinks, the jet of the Bubble_1 to it is further developed. It can be seen from Fig. b16 that when the jet piercing the far-end surface of the Bubble_2, not only the velocity gradually decreases, but also the forms changes, bifurcation occurs at the tip of the jet, and finally the jet breaks. During the period of 175 μs < t < 260 μs, the two bubbles gradually fuse into one and enter the rebound regeneration stage.By adjusting the transmittance of the half-transmitting mirror in the laser-induced cavitation bubble system and the angle of the corresponding focusing mirror to change the relative position and relative size of the two cavitation bubbles. Figure a10 and b14 in Fig. Figures 31 and Rui32 studied the interactions of two cavitation bubbles of different sizes through low-voltage discharging method. The two cavitation bubbles described herein are induced by the contactless laser, so there are the following differences: (1) the relative sizes and relative distances of the two bubbles obtained in this paper are far less than the range studied in the literature ; (2) under the condition of no external interference, we found that when two cavitation bubbles generated at the same time have a big difference in size and the distance between the two bubbles is very close, the small bubble only forms a surface wave towards the big one while the big bubble forms a jet that is far away from the collapse of the small bubble. It should be noted that due to the limitations of the experimental technique, we have not been able to obtain the critical value at which point that the extremely small bubble exerts no influence on the big one.ChewIt can be seen from Figs t = 0 μs), and the current evolution time of the cavitation bubble is marked in each picture. In Fig. Figure t < 112.5 μs, the two cavitation bubbles expand synchronously to the maximum volume, and during the expansion, the respective central positions remain substantially unchanged, while the adjacent side surfaces gradually becoming planar, and the liquid in the middle of the two bubbles is gradually squeezed by the expansion of them. When expanded to the maximum volume, the middle layer becomes a very thin liquid film, but as can be seen from the image, the two bubbles did not fuse. During the period of 112.5 μs < t < 200 μs, the two bubbles gradually shrink. During the shrinking process, the adjacent surfaces of the bubbles still appear planar, while the surfaces away from each other violently shrink toward the center of the respective bubbles. And during the shrinking process, there was no obvious fusion between the two, as well as no jets. During the period of 200 μs < t < 312.5 μs, the bubble enters the rebound phase. At this stage, the surface of the bubble appears to be non-smooth. During this rebound expansion and contraction, the two bubbles are finally integrated into one.In Fig. t < 112.5 μs, the two bubbles expand synchronously to their maximum volume with the maximum radii of 0.83 mm and 0.84 mm, respectively. During the process, the two bubbles are not interfered by each other, and no obvious deformation forms appear on the adjacent sides. During the period of 112.5 μs < t < 187.5 μs, the two bubbles enter the contraction phase. During this phase, the adjacent surfaces exhibit a slight mutual attraction effect, and the bubbles take on an ellipsoidal shape, as shown in Fig. b14 and b15. And during the synchronous shrinkage process, the surface contraction speed away from each other is faster than the adjacent sides, and finally the jet emerges when the bubble shrinks to the minimum distance, as shown in Fig. b16. During the period of 187.5 μs < t < 337.5 μs, the two bubbles entered the rebound phase. During this phase, both bubbles shoot jets to each other as shown in Fig. b17, and two bubbles are fused at t = 212.5 μs. After the fusion, the two bubbles move more vigorously on the upper and lower surfaces, and finally become tabular as in Fig. In Fig. et al.32 studied the fusion mechanism of two cavitation bubbles near the wall with the low-voltage underwater discharge test method. The influence of the wall on the two-bubble collapse was not covered in this study, but the research case in this paper was similar to the “weak” affected area in the literature. By comparing the experiments in this paper and numerical results in the literature, we can find that although the experimental methods and the sizes of the bubbles are different, the form of the fusion of the two bubbles in this paper is basically consistent with the simulated pattern in the literature. Especially, in the late stage of cavitation bubble collapse, the surface forms of the upper and lower cavitation bubbles are basically symmetrical . It can be seen that for two cavitation bubbles of the same size that are generated at the same time, in the case where the distance between the two bubbles is very small, the collapsed form is similar to that of a single cavitation bubble in the boundless domain. Due to the limitations of experimental technique, this paper only qualitatively analyzed the fusion process of two bubbles of the same size. The collapse strength after the fusion of the two cavitation bubbles is often the most concerned issue in practical engineering, which requires more in-depth quantitative researches.Rui see Fig. a8 ~ a17It can be concluded from the analysis of Figs There are two typical bubble dynamics are presented during the collapse process of cavitation bubbles, namely jets and shock waves. In the previous section, we focused on the jet phenomenon exhibited by the interactions of two laser-induced cavitation bubbles. In this part, underwater low-voltage discharge technology is used to induce two cavitation bubbles, so as to study the differences between shock waves resulting from collapse of two cavitation bubbles and the ones from single cavitation bubble. The differences between the jets resulting from collapse of spark-induced two cavitation bubbles and the ones from laser-induced two cavitation bubbles are also analyzed and compared. Figure t < 2411 μs. During this phase, the two bubbles expand synchronously, but since the energy obtained by the Bubble_1 in the initial stage is smaller than that of the Bubble_2, the Bubble_1 expands to the maximum radius first than the Bubble_2, as shown in Fig. a11. The Bubble_2 reached the maximum volume 578 μs later than Bubble_1, as shown in Fig. a15. During the expansion of the Bubble_1, the surface near Bubble_2 is flat. Subsequently, the two bubbles are in the stage of contraction and collapse. In this stage, due to the small volume of the Bubble_1, the surface away from Bubble_2 shrinks faster. Finally, when Bubble_1 shrinks to its minimum volume, a jet that penetrates the Bubble_2 is formed as shown in Fig. a21. Rui32 studied the characteristics of the micro-jets formed when the two cavitation bubbles collapse with the same test method as this paper. Therefore, this paper mainly discusses the shock waves from the collapse of two cavitation bubbles. To capture the shock wave, the exposure time must be reduced to 0.25 μs. Therefore, the development of the jet inside Bubble_2 is not observed in the image, but it is apparent from Fig. a21 the jet is developing very fast and has penetrated the far-end surface of the Bubble_2. For a24, a25 and a26 in Fig. a25 and a26.Figure b8 ~ b13. During the phase of b9 ~ b21, Bubble_1 continues to expand, while the Bubble_2 enters the contraction phase. At the time of b21, the Bubble_1 has developed to the maximum volume, and the Bubble_2 has not contracted to the minimum volume. At the time of b23, the Bubble_2 shrinks to the minimum volume. It can be seen from the image that the two bubbles are not fusing. The Bubble_2 exhibits a hemispherical-shape contraction, and the surface on the side far from the Bubble_1 contracts faster. Finally, at the time of b23, the Bubble_2 has a collapse shock wave, and the shock wave does not affect the shape of the Bubble_1 during the outward development. After that, the Bubble_1 continues to shrink and shrinks as shown in Fig. b30. And a significant shock wave appears, and the development of which does not have a significant effect on the Bubble_2 in the rebound phase.Figure Figure b3, c is a shock wave resulting from the collapse of two cavitation bubbles generated at different time, in which Fig. c1 ~ c4 is the earlier cavitation collapse shock wave, and Fig. c5 ~ c8 is the later cavitation collapse shock wave. The collapse shock wave of the earlier cavitation bubbles in Fig. c8.Figure It can be clearly seen from Figs For the jet and shock wave phenomena that occur in multiple bubble collapses, the above analysis is carried out by using different experimental systems. However, for the utilization and prevention of multi-cavitation interactions, it is necessary to consider the influence of boundary conditions around multi-cavitation bubbles. This section only studies the collapse modes of the two bubble center lines parallel to the wall. Figure a18. This is mainly because the cavitation bubble is far away from the wall surface at the time of inception, and its characteristic parameter γ = 1.90. During the second expansion and collapse of the cavitation bubble, the cavitation bubble moves toward the wall surface quickly. For Fig. Rmax = 0.86 mm, which is basically the same as the size of Fig. a15 and b16. (3) In the rebound regeneration stage, under the small cavitation bubble disturbance, the cavitation bubble does not form a jet directly impacting the wall surface, but the whole body moves rapidly toward the wall surface.It can be clearly seen from Fig. et al.25 and Rui et al.32 studied the interaction of two cavitation bubbles near the wall by the underwater low-voltage discharge method, in which Chew et al.25 studied the state of the two bubble center line parallel to the wall and Rui et al.32 studied the state of the two bubble center line perpendicular to the wall. Chew et al.25 obtained a method of predicting the micro-jets of the two bubbles near the wall by judging the migration direction of the cavitation bubble. In the study of this paper, the details of the internal jet of the small cavitation bubble on the large one and those of the small cavitation bubble suppressing the formation of the micro-jet by the large one to the wall surface can be clearly seen. The literature32 divided the interactions of the two bubbles near the wall into three parts according to the bubble-wall distance, and Bubble_1 and Bubble_2 in Fig. Chew If the two cavitation bubbles are synchronously generated but in different size, as the distance between the two cavitation bubbles increases or the maximum radius of the smaller cavitation bubble increases, the effect of the small cavitation bubble on the large one gradually changes from the surface wave phenomenon to jet that breaks through the large bubble. If the two cavitation bubbles are generated at the same time with same size, as the initial distance of the two cavitation bubbles gradually decreases, the two bubbles are more likely to form a face to face collapses, and the smaller the distance between the two, the easier it is to fuse. When the two bubble center lines are parallel to the wall surface, the above-mentioned jet will suppress the formation of the jet to the wall surface when the large cavitation collapses.The initial moment of the cavitation bubble also has a significant effect on the structure of the collapse shock wave. The collapse shock wave is different from the spherical shock wave of the single cavitation bubble collapse in the free field. Specific manifestation is as follows: for two cavitation bubbles of different sizes formed synchronously, the development of the shock wave in the collapse is dominated by the larger one. For cavitation bubbles generated at different time, they have shock waves successively in the collapses. In both cases, the shock waves are not released once, but a continuous number of waves in a short time. Due to different speeds, these waves may overlap in some areas of the space.By respectively inducing two cavitation bubbles through laser and underwater low-voltage discharge, this paper tested the jet and shock wave during the collapse of the two cavitation bubbles with different time of inception, and the following conclusions are obtained:The conclusions obtained from the two cavitation bubble interactions  induced with the interference-free method and the shock wave test during the two cavitation bubble collapse induced with the underwater low-voltage discharge method have potential value for the anti-corrosion design and the corrosion resistance of hydraulic mechanical blades in hydraulic engineering.


Dosing schedules for oral levodopa in advanced stages of Parkinson’s disease (PD) require careful tailoring to fit the needs of each patient. This study proposes a dosing algorithm for oral administration of levodopa and evaluates its integration into a sensor-based dosing system (SBDS).In collaboration with two movement disorder experts a knowledge-driven, simulation based algorithm was designed and integrated into a SBDS. The SBDS uses data from wearable sensors to fit individual patient models, which are then used as input to the dosing algorithm. To access the feasibility of using the SBDS in clinical practice its performance was evaluated during a clinical experiment where dosing optimization of oral levodopa was explored. The supervising neurologist made dosing adjustments based on data from the Parkinson’s KinetiGraph™ (PKG) that the patients wore for a week in a free living setting. The dosing suggestions of the SBDS were compared with the PKG-guided adjustments.t test indicated no statistical differences between the algorithmic suggestions and the clinician’s adjustments.The SBDS maintenance and morning dosing suggestions had a Pearson’s correlation of 0.80 and 0.95 (with mean relative errors of 21% and 12.5%), to the PKG-guided dosing adjustments. Paired This study shows that it is possible to use algorithmic sensor-based dosing adjustments to optimize treatment with oral medication for PD patients. Parkinson’s disease (PD) is a movement disorder that is characterized by the cardinal symptoms: bradykinesia, tremor, rigidity and postural instability . There iThe process of titrating the dosing schedule for PD patients can be vaguely categorized into three stages, along with disease progression. In the first stage, physicians prescribe oral administration of levodopa using a generic dosing schedule but as the disease progresses the patients start experiencing shortening of medication effect, wearing-off fluctuations, and sometimes dyskinesia (manifestation of involuntary movements—attributed to overmedication) , 3. In tIndividualizing the dosing routines, however, presents difficulties. Patient diaries  and limi®), which are specifically designed for optimization of levodopa dosage [Before that becomes necessary, the best option for patients that can be managed with oral medication , would be to further adjust the dosing routines to minimize the periods of sub-optimal treatment. This requires well-informed dosing adjustments. To that end, sensor-based systems that allow for objective measurements of the patients’ motor status have been developed and become increasingly popular. Over the past years studies about symptom monitoring through wearable sensors have been published , 9 and ca dosage , in stepIn Thomas et al.  a dosingThe aim of the process is to find the combination of morning and maintenance dose that minimizes the period of “off” and “dyskinesia”  for each dosing frequency. The simulations are run on the treatment response scale (TRS), which ranges from − 3 to + 3, with negative values indicating to “off”, positive values to dyskinesia, and values close to 0 to the optimal status . This scBefore initiating the above simulation process the dosing frequencies to be examined are selected together with the target state  for each patient. Setting a positive value close to 0 as target is usually preferred to avoid fluctuation between two does. To avoid overmedication and keep the dose at acceptable levels, a target range is set around the target value which ensures that there is some reduction in effect before the next dose is taken, thus balancing the dose to a value that is sufficiently large but also low enough. For every dosing frequency a combination of maintenance doses and morning doses are simulated, the dose–effect curve values are stored for each combination, and the best one is selected. The best combination of morning and maintenance doses is defined as the one that minimizes the time the simulated dose–effect curve is outside the target-range Fig. . FurtherA graphical illustration of a dose optimization example can be seen in Fig. As mentioned earlier, the input to the dosing algorithm are individual patient models. In Thomas at al . a methoThe parameter description of the PKPD model is given in Table The individual models were fitted by altering a subset of the parameter values of the population PKPD model, using the dosing information and fitting patient-specific dose–effect curve to a series of clinical observations, through least squares optimization . The parAs the model-fitting process requires individual ratings, the use of wearable sensors to extract the necessary information was explored. This was done to investigate whether this algorithm could be embedded into a sensor-based system. It is also possible to use this algorithm with clinical ratings as input. However, these are not usually available in real time and their acquisition requires the presence of an expert neurologist. Embedding the algorithm into a SBDS presents the opportunity of making dosing suggestions directly from patient-derived sensor data without the need for interpretation by a clinician.In Thomas et al. , the useThe extracted objective ratings on TRS  were useThe feasibility of using the dosing algorithm as part of the SBDS was evaluated during a clinical observational study. In Johansson et al. , a cliniDuring the first visit the patients’ old dosing schedules were converted to the microtablet equivalent  and the Of the 28 (there were 3 screening failures) patients that completed the first visit, 25 completed the first two visits and 24 completed all three visits. In Table The SBDS was applied during the patients’ second visit to the clinic. At that time the patients put on the Shimmer3 sensors and performed pronation-supination tests at a pre-determined time schedule as in . The tesThe individual models (the estimated patient-specific parameters of the PKPD dose–effect model) were used as input to the dosing algorithm which had two settings for the target-range on the test day, depending on the maximum TRS the patients demonstrated. If it was higher than 0, the target-range would be set as a percentage value of their maximum TRS. For the patients where the maximum TRS was lower than 0.05, or negative, the target-range was set in absolute terms, since the percentage approach calculation was not suitable in those two cases. In the first case a percentage value of a score close to 0 would also be 0, thus not allowing for any wear off in effect (leading to overmedication). In the second case, a percentage value of negative scores would only allow for the fluctuations to get larger for the lower effect values. This adjustment to the design was necessary since the sensor-based TRS ratings would not produce positive values for some patients. The fluctuation criterion value was set as 0.5 points of the TRS.The dosing frequencies examined by the SBDS were per 90 min  to per 240 min (as 4 h was the maximum dosing frequency according to inclusion criteria) and there was a 10 min increment between every simulation. The algorithm performed the simulations for each dosing frequency, starting from a minimum dose of 0 mg of levodopa (no dose) to a maximum dose that was patient-specific, depending on the dose they received during the test day (the maximum was 300 mg of levodopa for maintenance doses and 400 mg for morning dose). This procedure was performed for all dosing frequencies and the algorithm would only suggest one dosing combination (morning and maintenance dose) for each, the one with the minimum area outside the target-range that satisfied the fluctuation criterion. For a 90–240 min dosing frequency selection with 10 min increments there would be 16 dosing frequencies investigated and for each of them there would be a single combination of morning and maintenance dose derived. In this example, 16 different dosing schedules for each patient would be derived and about 120,000 (301 × 401) dosing combinations would be simulated for every dosing schedule.The suggestions of the SBDS were compared to the PKG-aided dosing adjustments of the second visit, for the same dosing frequency. For example, if a schedule that required dosing every 100 min was selected by FB based on the PKG recordings, those dosing adjustments would be compared to the dosing adjustments suggestions of the SBDS for the 100 min frequency .In total, sensor readings for all 25 patients were obtained, but appropriate individual models could only be fitted for 19 patients. One patient could not perform the hand rotation task, one patient had limited response to levodopa during the test day, and for four patients the algorithm predictions misrepresented the dose–effect behavior at the day of the trial. For those four patients, the series of sensor index scores did not represent a “normal” dose–response curve, i.e the values did not go from baseline to a peak effect and then back to baseline. Results from the remaining 19 patients are presented here, for nine of which one test occasion was removed as outlier in the model fitting process and for one patient two test occasions were removed as outliers. Outliers were identified as scores that had either a sudden drop in value after the onset of effect, or displayed a sudden spike in effect after wearing off started to demonstrate. Sudden motor fluctuations do happen, but cannot be accommodated by the current PKPD models. That is why these values were selected as outliers, even though they might not be in clinical practice. The outliers were removed based on a visual inspection of the TRS scores.The Pearson’s correlation of the maintenance dosing suggestions with the PKG-guided prescriptions, for the same frequency, was 0.80, and the mean relative error of the predictions was 21%. For the morning dose the Pearson’s correlation was higher (0.95) with a lower mean relative error, 12.5%. The results for the maintenance dose are influenced by three values that have high relative error. In Fig. t test was performed to check if there were significant statistical differences. The test was conducted with the null hypothesis that the dosing values were not significantly different (mean difference is 0). The results of the t test had a p value of 0.61 for the morning dose and 0.79 for the maintenance dose, meaning that the null hypothesis could not be rejected in any case. Based on these results, there was no evidence in the data that the algorithmic dosing suggestions were different from PKG-guided adjustments. These dosing adjustments improved the patients’ motor functions [To test the similarity of the algorithmic suggestions to the PKG-guided choices, a paired sample unctions . Since tThe necessity of a SBDS emerges from a continuous discussion raised also by Espay et al.  and TitoThe algorithm can be described as one that follows a dose-fractionation principle, allowing about 5–15 doses per day  and is dThis algorithm mimics well-informed clinical decision-making. Such a design was chosen as a first attempt to investigate the feasibility of algorithmic dosing suggestions, and different designs, such as pattern recognition algorithms or mathematical optimization algorithms, could and actually should be explored in the future. The feasibility of using the method was tested during a clinical study where it was found that the suggestions of the method had high correlation to the supervising physician’s prescriptions, which were not subjective but PKG-guided. At the next stages, the algorithm could be integrated into an interactive platform such as the one in , so thatHowever, there were limitations, mainly the need to manually remove outliers before the model fitting process. At least one sensor rating was removed for ten patients, out of 19 reported in this study. It should also be pointed out that FB had input on the design of the algorithm (setting targets and ranges) as well as the patients’ dosing adjustments and the generalizability of the results might, therefore, be somewhat limited. This is why it is important to consider that the PKG readings were the basis of the adjustment decisions and FB was merely the facilitator between patient and PKG-recording. Since the algorithm was designed to mimic dosing optimization as it is performed in clinical practice, the similarity of the algorithm output and the clinician’s dose suggestions is a positive outcome.It can be concluded that given a high enough dose to produce a dose–effect and the ability of the patients to perform motor tasks the SBDS is quite robust when producing dosing suggestions. There were certainly occasions where individual models would fail to provide useful information. In these cases, however, the limitation of the method is also attributed to the inability to make accurate predictions with the SVM model , therefoThe future work will focus on addressing the limitations of the current version of the SBDS and automate the model fitting process including algorithmic exclusion of outliers. The current comparison with clinical decisions was made to provide proof of concept, but future development should have the broader aim of optimizing patient outcome instead.


SBRT with extreme hypo‐fractionation in treating tumors including prostate where ablative dose is delivered in smaller number of fractions, rectum remains a dose‐limiting organ and at the risk of rectal toxicity or secondary cancer. The same limitation of rectal toxicity exists for high‐dose rate (HDR) treatments of cervical, endometrial, or prostate cancer when creating even a short distance between the anterior rectal wall and field of radiation is ideal in delivering ablative dose to the target. An effective solution to such problem is to physically displace rectum as the organ at risk. This research presents an organ retractor device that is designed to displace the rectum away from the path of radiation beam employing a Nitinol shape memory alloy that is designed for displacing the rectum upon actuation. A control system regulates the motion in a reproducible and safe manner by creating the desirable shape in moving the anterior rectal wall. The study finds the novel organ retractor device to be a promising tool that can be applied in a clinical setting for minimizing dose to the rectum during treatment of pelvic tumors, and creating the potential to deliver an ablative dose to tumor volume or to escalate the dose when needed.An effective radiotherapy treatment entails maximizing radiation dose to the tumor while sparing the surrounding and normal tissues. With the advent of  For instance, one technique is used to fixate the prostate gland during the course of radiation treatment via a rectal balloon to reduce the prostate motion and to make sure the dose delivered to the target volume is efficient.® hydrogel for patients with larger prostate glands tend to be more challenging to make sure it is injected properly and in a symmetrical fashion. The procedure takes anywhere from 10 to 30 min and sometimes under anesthesia. These lead to higher costs for the treatment procedure. It should also be noted that some patients have reported declines in bowel QOL or urinary QOL as well as gastrointestinal (GI) toxicity when the bioabsorbable gel is used. Uhl et al. in a study® hydrogel insertion as reported elsewhere.On the other hand, there is another clinically utilized technique in some clinics to spare the rectal dose via using materials such as hydrogel, hyaluronic acid gels, and collagen.This work aims to better understand the current trend in treatment of the tumors in pelvic cavity and present a novel organ repositioning device that was originally suggested by Parsai et al. and presented at AAPM annual conferences,In the presented methodology, a Nitinol actuator is incorporated in a rectal balloon immobilizer that has been clinically approved and used for prostate radiation therapy (RT) to reduce prostate motion. The Nitinol alloy offers multiple advantages such as biocompatibility and biomimetic actuation .Nitinol alloy has two crystalline structures: austenite and martensite, which allows for its unique and reversible shape memory effect. In the rectal retractor, before the insertion, the Nitinol is soft and flexible . The device will be inserted into the rectum so that the marking on the device is pointed toward the posterior rectal wall. Barium is then injected into the rectal retractor to determine the position of the device inside the pelvic cavity. Once localized, the balloon is inflated and the Nitinol will be actuated via joule heating. The heating is controlled by adjusting the current through a controller. When heated, the Nitinol element transforms to the austenitic phase, changes its shape, and as a result creates the desired motion. The retractor device pushes the posterior rectum wall, which will in turn move the anterior rectal wall as well away from the radiation field. Upon completion of the treatment, the actuator will trigger the positioner so it returns to its original shape  so the device can be removed with patient's comfort. Due to the high fatigue resistance of the NiTi alloy, the core component can be used many times, which in turn reduces the cost of the procedure. Fatigue studies for such biomedical wires with various geometries are extensively studied elsewhere.The rectal retractor device also offers an open distal end to allow the integration of the marker with a barium delivery system for onboard imaging application which allows the device to serve a dual function of both providing a desirable geometry for a positioner device and facilitating the localization when imaging the area.2The COMSOL Multiphysics software allowed for the simulation of the SMA wire's actuation and it's interfacing with the human body with accurate physiological and material properties. Heat transfer and the displacement of the rectal re‐positioner were simulated using the Joules Heating, Bio Heat Transfer, and Structural Dynamics modules.The device was designed for easy insertion, based on anatomical constraint, and the NiTi shape memory alloy's features were exploited through cooling and heating the core alloy also known as shape setting for programming the memory effects.Finally, the temperature of the actuator was precisely monitored for patients’ safety using the Micro‐Epsilon TIM camera and the prototype's actuation and displacement was tested with an experimental design that utilized an Agilent Power Supply E3631A, DS1104 R&D Controller Board, Micro‐Epsilon optoNCDT, Control Desk, and MATLAB programming Software.In addition to the evaluation of the performance of the device, we have performed a preliminary cadaveric experiment to ensure that the suggested rectal retractor is able to displace the rectal tissue. A full and detailed cadaveric test will be published in a separate paper.33.AAfter the prototype was modeled and tested in COMSOL, the results were captured and are depicted in Fig. These values were then compared to the experimental data that were obtained in the Dynamic and Smart Systems Lab at University of Toledo School of engineering.As seen in Fig. Next, the heat dissipation and respective temperature profile of the device's components were studied; these experiments served to research whether the surface of the device that interfaced with the rectum would introduce hyperthermia and the associated heat shock response. In Fig. Upon operating the device for 30 s, this region of the wire was found to have a temperature of 30.3°C, which is a negligible difference from the simulated 30.0°C. Furthermore, the temperature of the flexible cylinder (covering the Nitinol wire) after it was operated for 70 s was approximately 30.0°C in contrary to the simulated 32.5°C; however, for the clinical application of this device, less than 60 s of operating time is preferred before the patient is ready for imaging.In the second series of prototype testing, the device's displacement between the rectum and prostate was studied. Specifically, the experiment was to obtain the qualitative relationship that would correlate the resistance of the Nitinol wire to the magnitude of the device's displacement. The results revealed that the maximum displacement is obtained around 30 s of operation with a 5 A current supply. This mathematical design will allow for safe and controlled actuation within the rectum. It is worth noting that the displacement test was done while there is no external load on the actuator. Another set of experiments were done to verify the actuator is able to apply up to 7N loads while actuating. In the case of existence of a 7N external load, the maximum displacement of the device was reported as 1 cm.3.BIn order to ensure the feasibility of the rectal displacement, we have tested the proposed rectal retractor on a fresh cadaver. Figure The retractor used for this study was an earlier version of the rectal retractor device and as shown in the CT scan, upon actuation moved the rectal tissue on one side of the coccyx bone, but it still moved the majority of the rectum away from the prostate. The newer prototypes have been designed for even more effective displacement of the rectum. A treatment plan generated using the cadaver CT scan for with and without the applicator in place indicates a significant sparing of rectal tissue by comparing the DVH diagram shown in Fig. 4With most pelvic tumors benefiting from radiation, especially in younger patients with longer life expectancy, the success of treatment and the absence of late term radiation induced complications is a direct function of how the surrounding and normal tissue are spared during the course of radiotherapy. Ample literature in recent years indicates that radiation‐induced chronic morbidities in critical structures located in vicinity of or in the path of radiation fields are common and RT‐induced second malignancies will likely increaseThe authors suggest a retracting device whereby the rectal wall can be shifted away from the source of radiation, or from vicinity of the radiation field. This will result in lower dose to this dose‐limiting structure, hence creating potentials to deliver ablative dose to tumor volume, or escalate dose when needed. Moving the rectum away even a short distance from the plane of radiation could dramatically relax the prescription dose limitation, particularly in HDR brachytherapy treatments and also in SBRT treatments of the pelvic tumors.The COMSOL simulation and the prototype testing data are strongly suggestive of the device not inducing patients risks such as hyperthermia, which allows for patient safety and comfort during operation. Specifically, the temperature of the prototype device at the hottest portion will not surpass 30.0°C in experimentation.The displacement testing allowed for a correlation between the displacement of the rectum and the Nitinol wire's resistance; a design equation details when the rectum has been displaced 1.0 cm so that the current supply may be terminated. Data suggest that the device displaces the rectum 1.0 cm after it has been activated for less than 30 s, which is appropriate during prostate cancer radiotherapy for an efficient dose sparing to the rectum. The prototype device is able to apply as high as 7N loads while creating a displacement of 1 cm. For any other cases with lower level of resistance , the required displacement  will occur before 30 s and can be controlled using the controller unit.None to report.


The scarcity of water can result in a direct conflict between the protection of aquatic resources and water use. For many agencies, environmental flow (EF) methods are essential in environmental impact assessments and in the protection of important fisheries resources. The objective of this paper is to compare selected hydrological and hydraulic methods and determine the scientifically acceptable and cost-effective way to environmental flow within a section of a mountain river with high naturalness, on the example of the Wisłoka. In this paper, environmental flow was calculated using conventional hydrological methods: Tennant’s, Tessman’s, flow duration curve and hydraulic methods, wetted perimeter method (WPM) and method based directly on ichthyofauna habitat requirements (spawn and migration). The novelty is the combined use of the hydraulic and hydrological methods which relates to flow hydraulics based directly on ichthyofauna habitat conditions. The hydraulic methods provide lower values of environmental flow in comparison with the hydrological methods. The key issue in the use of the hydraulic methods is the choice of criteria. The development of the required set of parameters while taking into account their seasonal nature shifts the method toward habitat modeling methods. However, the scope of habitat requirements of ecosystems must be defined, including the set of aquatic organisms and watercourse type before a hydraulic method may be widely used. Being generally low-cost and simple, the methods presented in this paper can be applied in the water management legislative process. According to the ecosystem services concept, what man benefits from natural environment is defined as a set of the products and functions of the ecosystem which is used by the community, namely provision, regulation, support, and cultural services , water demand management forecasts in drought periods, and water management strategies.Q) and what is termed instream flow (Qn). The instream flow is defined as the amount of water which should be kept in the river at its cross-sectional minimum for biological and communal needs . It is defined as the part of natural flows which should be left in a watercourse and in flooded areas in order to keep high natural values of water ecosystems and water-dependent ecosystems Tharme . It is cMore than 200 methods to determine environmental flow have been developed. According to Tharme , methodsHydrological methods are regarded as the simplest and most easily used ones to calculate EF. They comprise some 30% of all those used. In the hydrological methods, the value of EF depends on the given characteristic flow  are ones that use quantitative and qualitative relationships between habitats for fish species and flows. The hydraulic methods analyze the effect of increasing flows on the habitats of important fish species in vital phases of their lives, including migration, reproduction, and feeding. Practically, every one out of hundreds of available hydraulic parameters may be used in the methods. The hydraulic parameters which are used for determining EF often include wetted perimeter or maximum depth, usually measured cross-sectionally at such points as are typical of vertical systems. Above all, the hydraulic methods are recommended for use in catchments where hydrometric observations are not carried out, or for controlled cross sections , which indirectly assumes habitat conditions for invertebrates. The novelty is the combined use of the hydraulic and hydrological methods which relates to flow hydraulics based directly on ichthyofauna habitat conditions. It may be a simple way to apply specified ecosystem requirements in detailed scale when decisions of water use have to be made. This method does not require great investments in time and resources. Hughes et al.  emphasizThe choice of these two types of methods is not incidental—the cost of their use is the lowest, which is not a negligible criterion in developing new solutions; the only challenge is to make sure the solution is useful for many purposes.2. It starts in the Beskid Niski mountain range in the Małopolska province .The research section of the Wisłoka is located in the vicinity of the Site of Community Importance, the Lower Wisłoka with tributaries PLH180053. According to the classification of surface water bodies, the research section of the river is located within the natural surface water body RW200019218771 “Wisłoka from the Chotowski Stream to the Rzeka river”, with good chemical and ecological status. The environmental objective of a surface water body is to maintain its good chemical and environmental status and to make the watercourse passable to the aquatic organisms. There is no threat to the attainment of the environmental objectives.−1. The intensity of the process was lower after the year 1990 . As in a number of Carpathian rivers in the years 1950–1990, the sand-and-gravel bottom of the Wisłoka dropped at an average rate of 5–9 cm year90 Wyżga .Hydrological methods are some of the most widely used techniques of the assessment of environmental flow. They are based on the assumption that ecological requirements are reflected by hydrological conditions. Determination of environmental flows by hydrological methods is based on hydrological regime indices, such as mean flow MAF, low mean flows MLF, and values resulting from flow duration curves. It is worth noting that, for the respective methods, the values of environmental flows vary significantly  to mean annual flow  by pb factor specified for the river type. The basis for determining the pb coefficient was a habitat model MesoHabsim (Parasiewicz pbparameters of the method for gauged and ungauged catchments (-),LAFqb3 s−1 km−2)unit low annual flow in bioperiod (mA2).catchment area , II—feeding (July–September), III—autumn spawning (October–December), and IV—winterizing (January–February).S statistics for a time series is determined from the following equation —variance S, defined by the equation:Based on normalized α = 0.05 in this paper), then the analyzed trend is regarded as statistically significant.The probability connected with the normalized Z test statistics was calculated. A trend is regarded as increasing if the Z statistics is positive and is regarded as decreasing if the Z statistics is negative. If the calculated p test probability value is lower than the adopted significance level   are office methods, based on relationships between the hydraulic parameters P, e.g., wetted perimeter or depth, and the value of flow in the river. The relationship can be described by the function (Q) Fig. . The rea(Q) Fig. .Fig. 3ReThe wetted perimeter method (WPM) is the most popular of all hydraulic methods. It is based on the relationship between the wetted perimeter for a given cross section of the river and the value of flow with reference to biological requirements. The method is based on the assumption that food availability to fish species is the decisive factor of their existence and condition. Aquatic invertebrates, which breed mainly on riffles, are the essential food for ichthyofauna Gopal . RifflesSalmo trutta fario), which is one of the indicator species in good quality water in gravel-bottomed rivers, was selected as the reference. Habitat conditions define the values of depth and flow velocity which are required in the ichthyofauna spawning and migration seasons. The habitat suitability criteria for brown trout during spawning were applied on the base of MesoHabsim model of Wisłoka river  exist, first riffle may not be the most critical. So cross sections in three consecutive riffles within the research section of the Wisłoka river were selected. The cross section is located at the highest points of the riffle. In these locations, fish passage is likely to be limited. Maintenance of flow in these critical cross sections provide river longitudinal connectivity. The measurements included the following parameters: flow (ADCP acoustic Doppler current profiler), water slope, and profile shape. Measurements for the profile shape comprised the exact measurements of bottom configuration and were made using an ADCP probe in the part of the cross section where the depth was > 0.20 m and GPS RTK in the other parts.The necessary hydraulic relationships were found based on conventional hydraulic calculations. They were then used to find mean velocity and flow for various fillings so as to establish the relationship between the wetted perimeter and flow.C—velocity coefficient Rh—hydraulic radius, Rh = F/Oz, Oz—wetted perimeter, F—cross-sectional area, n—Manning’s roughness coefficient obtained from rating curve calibration, Se—energy line gradient (replaced by the water table difference in steady motion conditions). The calculations based on the Chezy formula comprise cross-sectional values of flow and mean depths, whereas the flow hydraulics requirements for habitats relate to local values of flows and depths which are true for the entire habitat area. A riffle is a morphological unit having a uniform bottom with a wide and shallow flow; therefore, it can be assumed that velocities and depths are the same throughout the cross section. This implies that the mean values of hydraulic calculations may be regarded as local for the riffle area.The hydraulic parameters of water flow were calculated using Chezy formula:α = 0.05.Table p, as found for the Mann-Kendall normalized Z statistics, which is higher than the assumed significance level. Hence, it is concluded that, in the multi-annual period of interest, there has been no factor significantly affecting the hydrological regime of the river.Based on the results in Table The results are consistent with those concerning flow trend significance MF for other rivers in the upper Vistula region. In studies reported by Młyński et al. , no statBasic indices describing the hydrological regime of the river in the multi-annual period 1985–2015 were found, and changes in the dynamics of fluctuations in daily flows in the Wisłoka river have been analyzed. The results of these calculations are shown in Table Cs. This is accounted for, first of all, by the alternation of extremely dry and extremely wet years over the entire multi-annual period. The 1980s were a relatively dry decade: the underground water table dropped in the whole territory of Poland, resulting in lower flows in rivers. In contrast, 1997, 1998, and 2010 were extremely wet years with precipitation levels leading to disastrous floods. The obtained value of skewness indicates a right-hand asymmetry of the empirical distribution of daily flows (above zero). Therefore, a majority of hydrometric observations are higher than the value of MAF. On the other hand, the value of kurtosis indicates a leptokurtic empirical distribution of daily flows .Based on the results of these calculations, it was found that daily flow fluctuations in the Wisłoka river were very high in the multi-annual period 1985–2015, as indicated by the value of the coefficient of variation 3 s−1 and the highest was 61.5 m3 s−1 for flushing flow. When using Tessman’s method, environmental flows were found versus mean monthly flows. However, the magnitude between the respective months is not high over the hydrological year: the difference between the minimum and the maximum value is lower than 2%. It is worth noting that the values of environmental flow, as found by Tessman’s method, correspond to the following conditions in Tennant’s method: good for April–September and outstanding for October–March. On the other hand, environmental flow, established as a guaranteed flow at 90%, was 6.025 m3 s−1 in that multi-annual period; this is comparable to the flow condition good in Tennant’s method. For NWMA method, the lowest value was 1.73 m3 s−1 (autumn spawning period) and the highest was 16.4 m3 s−1 (spring spawning period).Because the Mann-Kendall test did not detect any statistically significant trend, in the next step, the hydrometric data (mean daily flows from 1985 to 2015 years) were used for determination of environmental flows for the Wisłoka river. The results of the calculations are shown in Fig. The calculations were followed by an analysis of environmental flows, as found by hydrological methods, versus flow exceedance time curves for the two periods: October to March and April to September. The results are shown in Fig. An analysis of the possibility of using the Wisłoka river as available water resources indicates that, in the economic aspect, the least desirable solution is to maintain environmental flow at the flushing flow level. It enables water intake for 9.8% time during the year (9.8% 365 day = 36 days per year), on average. The most desirable value in the economic aspect is an environmental flow at the fair and poor level in the winter and poor in the summer. The guaranteed flow for these values is 98%, both in the winter and in the summer. For NWMA (PWMI in fig) method, the guaranteed flow is equal to 89% for autumn spawning and 52% for spring spawning period. From January to July, the flow according to NWMA method was near excellent condition and for the rest of period was—poor to fair conditions—Fig. Q1(crit) and minimum flow for spawning Qspaw/min, of less than 1 m3 s−1. Taking into account the flow width in channel, these values cover between 24 and 31% of the cross-sectional width, relative to the MAF flow width. Surveyed channel provides at least three points of inflection on the curve at each cross section. Higher flow values Q2(opt/crit) have been obtained based on the second inflection point previously defined as the beginning of the WMP-based range of optimum habitat conditions: from 3.02 m3 s−1 for riffle 3 to 3.90 m3 s−1 for riffle 2; these flows cover a cross section of a width ranging from 43 to 80% of the MAF flow width. The average optimum flow value is about 75% MLF. The third inflection point indicates flow optimum value Q3(opt) 11.39 m3 s−1 and it is in excellent range according to Tennant. The WPM method providing different flow values depends on morphology scale in dispute. The lowest inflection point seems to be disqualified as a breakpoint. In that case, second and third flow values would be defined as critical and optimal respectively, and WPM breakpoint and Tennant’s poor value are similar values  but inside of the spawning limitations (Q = 18.71 m3 s−1) meeting habitat requirements. In this way, EF will be limited by both hydrological, hydraulic and habitat requirements methods.Figure The study by Filipek et al.  indicate3 s−1) is comparable to the minimum flow as found by Tessman’s methods and is higher than 50% MAF. According to Karakoyun et al. .In WPM without hydrologic characteristic values of the river, it may be difficult to find out the proper morphology scale to concern.The habitat requirement method provides width scale of acceptable EF flows based on one species, limited spawning period, and relatively unrestricted timely open migration criteria.This paper presents the principal groups of methods for determination of environmental flows, including hydrological and hydraulic methods with the aim of finding the EF value in the cost-effective way. The practical result of the study is proposed as an approach where first step is to calculate EF range using Tennant, limit the WPM inflection points to only those in the range of Tennant flows finding between the rest the final EF. In this way, resulting EF would be supported by the morphological conditions of the river.The essential advantages of the hydraulic method include its low cost, fast and easy use, easy adaptability—this makes it applicable for highly biodiversified river sections. It is also important to take into account the fact that requirements tend to change in the course of the year and to vary with river categories and types. Also in hydraulic methods, a greater number of parameters (discriminants) may be used, and then the scientific discipline of flow hydraulics in open channels becomes a useful tool for their analysis.


The increasing prevalence of type 2 diabetes in the UK creates an additional, potentially preventable burden on health care and service providers. The Healthier You: NHS Diabetes Prevention Programme aims to reduce the incidence of type 2 diabetes through the identification of people at risk and the provision of intensive lifestyle change support. The provision of this care can be monitored through quality measurement at both the general practice and specialist service level.To develop quality measures through piloting to assess the validity, credibility, acceptability, reliability, and feasibility of any proposed measures.The non-experimental mixed design piloting study consists of consensus testing and exploratory research with GPs, commissioners, and patients from Herefordshire, England.A mixed-method approach will be used to develop and validate measures for diabetes prevention care and evaluate their performance over a 6-month pilot period consisting of consensus testing using a modified RAND approach with GPs and commissioners; four focus groups with 8–10 participants discussing experiences of non-diabetic hyperglycaemia (NDH), perceived ability to access care and prevent diabetes, and views on potential quality measures; and piloting final measures with at least five general practices for baseline and 6-month data.The findings will inform the implementation of the diabetes prevention quality measures on a national scale while addressing any issue with validity, credibility, feasibility, and cost-effectiveness.Healthcare professionals and patients have the opportunity to evaluate the reliability, acceptability, and validity of measures. Relevant National Institute for Health and Social Care Excellence (NICE) guidelines and wider literature have identified potential measures to prevent patients identified with NDH progressing to diabetes or to help manage their condition. The application of these measures will be piloted with clinicians, to identify their suitability. 1 Type 2 diabetes is a preventable chronic disease, and lifestyle change can help reduce risk.2The growing incidence and management of type 2 diabetes presents a significant cost to the NHS in England.3 Intensive lifestyle modification programmes or interventions can target people with NDH in order to delay or prevent the onset of type 2 diabetes and associated morbidity.4 The efficacy of lifestyle interventions requires further investigation, alongside evaluation of diabetes incidence and risk reduction in health outcomes.8Patients with NDH have raised levels of Hb1Ac or fasting glucose but these are not high enough to be diagnosed with type 2 diabetes.Five Year Forward View, the NHS and Public Health England has announced the development and implementation of a diabetes prevention programme to support people managing their own health.9 As part of this programme, interest has been expressed in developing quality measures suitable for use at the general practice and clinical commissioning group (CCG) level for those at risk of developing diabetes. The National Collaborating Centre for Indicator Development (NCCID) works on behalf of the NICE to develop and evaluate quality measures of primary care. Within primary care they have also been used to incentivise certain aspects of care through the Quality and Outcomes Framework (QOF).10As part of the 11 Piloting measures can help identify any concerns prior to use in assessment frameworks, thus giving time to adapt indicator wording or measurement protocols to address issues such as tunnel vision, gaming, misinterpretation, and measure fixation.12Evaluation has been part of the NCCID protocol since 2009 and is a recommended step by the National Committee for Quality Assurance.17 , process (related activities), and outcome ,The aim of this unique work is to develop and evaluate a set of quality measures for the identification and management of people with NDH that are suitable for use in England at the general practice and CCG levels, as well as research questions that are relevant to clinical practice. The findings from the focus groups will provide clinicians with insight into patients' perspectives on and experiences of communication and management of NDH. The specific objectives are:to develop a comprehensive set of quality measures based on relevant NICE guidance and the evidence of reviews underpinning NHS England’s Diabetes Prevention Programme;to undertake preliminary evaluation of the validity and feasibility of these measures through the use of a RAND consensus methodology;to explore patients’ experiences of being identified with NDH and views on quality outcome measures;to develop and test data extraction specifications to support these measures at general practices including IT system compatibility; andto evaluate the resulting measures in a 6-month pilot.19 Recommendations from these will be developed into quality measure statements initially with an 'IF, THEN, BECAUSE' approach to ensure clarity in terms of population of interest; the care activity to be undertaken; the circumstances under which this activity should be performed, for example duration; and the rationale , outcomes , and risk adjustment .21A comprehensive set of quality measures will be developed to address the multifaceted nature of quality and the different organisational structures involved in the provision of this care, incorporating statements about structure, process, or outcomes to generate review criteria and standards that help measure quality.20 Benefits include the opportunity to discuss issues and maintain all potential information, as no indicators are dropped between meetings, as well as the use of scientific literature. The RAND panel will be a convenience sample of GPs. Recruitment to the RAND panels will be open to GPs from diverse backgrounds; for example, those with recent qualifications versus long-standing registered GPs, salaried versus partnered GPs. However, panels can be small, patients are rarely involved, and there is potential for dominant personalities to carry more influence.20The RAND appropriateness method uses a group judgment process to systematically and quantitatively incorporate expert opinion with scientific evidence, whereby panellists rate, discuss, and re-rate quality measures.et al, a consensus method was used in all 35 included studies, 15 of which used a modified RAND method to limit stakeholder influence and incorporate expert opinion.22 The use of RAND in UK quality measurement has been outlined in research for conditions such as angina and non-insulin dependent diabetes in general practice settings.23In a systematic review by Kotter 24The research panels will be undertaken with GPs and CCG commissioners which could result in missing out patient experiences, but there is a risk in combining patient and professional views as patients may be dominated by professionals.25 It has been widely used to develop quality measures in the UK and internationally.26The clarity, validity, and feasibility of identified measures will be evaluated using a modified RAND consensus methodology with groups of GPs and CCG level commissioners within Herefordshire CCG. A modified RAND methodology offers a unique systematic approach to synthesising the evidence base underpinning the quality measures, using existing literature as well as professional opinions.Each RAND panel will consist of two rounds of quality measure ranking .Figure 1Qualitative research with patients lends itself to the enhancement of the validity and clarity of measures, not only for providers but also patients who face the consequences of being identified with the condition and of being part of the healthcare system.27 The COM-B model provides three factors — capability, opportunity and motivation — to develop behavioural targets as a basis for intervention design.28 The model encompasses a variety of psychosocial factors that can determine initiation and maintenance of behavioural change.29 The model has been applied successfully in a number of contexts to understand behaviour change.28 By investigating patient views and behaviours in relation to health management, researchers can identify potential barriers to or facilitators for changing behaviour once an identification of chronic disease risk has been made.There is a diverse range of behaviour change theories that can help develop an understanding of constructs regarding people’s behaviour.22Although patient involvement in measure development has been carried out, there is a limited number of works in this field, especially regarding details of involvement and representativeness.28 Data collection will be an iterative process where focus group recordings will be transcribed and analysed to monitor data saturation and provide additional topics for subsequent focus groups.30 Incorporating patient views will further strengthen understanding of quality measure suitability. Furthermore, the use of the COM-B model of behaviour change to guide data collection, analysis, and interpretation will provide findings that can be understood from different healthcare perspectives, for example, for health interventions considering patient views on preventative care.29Patient views will be explored through a minimum of four focus groups, each consisting of 8–10 participants. Braun and Clarke suggest 3–6 focus groups can provide sufficient data for a medium sized project.Patients will be identified through direct recruitment from GP practices or through local support networks as eligible for the focus groups if they:have been recorded as having NDH or their latest HbA1c was between 42–47 mmol/mol in the last 6 months ; andare aged ≥18 yearsThe practice will be asked to send patients information sheets about the study and an invitation to participate. No personal information will leave the practice/CCG. Patients will be contacted if they are at risk and inclusion will not be limited to patients taking part in the diabetes prevention programme.The focus group will begin with an initial discussion of people’s experiences of diabetes prevention care and then each potential measure will be presented to the group with the reason for its development.29 , motivation, and opportunity 29 .31 Participants will therefore be encouraged to make suggestions not only to improve clarity and acceptability of the potential measures for diabetes prevention, but also to shed light on their experiences and perception of having an elevated blood sugar level and their capability, motivation, and opportunities in relation to it. Analysis of participants’ comments will be an iterative process and run concurrently through data collection.Participants' experience of risk assessment can parallel the experience of illness and associated social implications.A convenience sample of five GP practices will be recruited in NHS Herefordshire CCG to a maximum of 24 .Practices which agree to take part will be expected to:Work with the quality measure for the 6 months of the pilot.electronic data will be extracted for participating practices using EMIS web queries at the beginning and end of the pilot period in order to assess how performance against the measure changed over time. Demographic data will be extracted to explore potential differences as a result of age, sex, and ethnicity.Complete baseline and end of pilot computerised data extraction of quality measure achievement;these consist of completing a spreadsheet that monitors how much time was spent on each quality measure.Complete a workload diary for 1 month of the pilot;Complete an end of pilot interview.The lead GP at each practice and any other staff, including diabetic nurses who were actively involved in piloting, will be interviewed at the end of the pilot.32All interviews will be audiorecorded and transcribed verbatim. Data will be analysed thematically.33 In summary, the method applies the following calculation to an indicator:For any QOF indicators developed from the agreed measures, their cost-effectiveness will be determined using a net (monetised) benefit approach.Net benefit =  – QOF payment.QOF payments are an incentive paid to GP practices when certain quality thresholds relating to the indicators are achieved.The costs and benefits for each indicator are estimated through a rapid review of the available economic evidence. Evidence of delivery costs and benefits, expressed as quality-adjusted life years (QALYs), is sought. The opinions of those involved in delivering the indicators at pilot GP sites are also sought.The costs associated with an indicator include service delivery costs; for example, the costs of additional GP or nurse consultations to monitor a patient’s health status over a period of time, the initial cost of implementing the intervention, and, if relevant, secondary care service usage. Unit costs will either be extracted from the literature review or derived from published sources such as NHS Reference Costs.The benefits refer to health benefits which might be gained by a patient as a result of the introduction of the indicator. Effectiveness will be derived from the literature in the form of utility values, which can be converted to QALYs. The monetised health benefit of the indicator refers to the value of the health improvements associated with achieving the predicted benefits of the indicator. These benefits are presented in terms of the changes in QALYs as a result of introducing the new indicator compared to standard practice without the new indicator.Sensitivity analysis is performed through simple scenario analysis rather than probabilistic sensitivity analysis.34The focus groups will be conducted with two members of the research team and all focus group interviews will be analysed and verified among the team to limit research subjectivity or bias of one researcher.Participants are free to withdraw from the research at any time without giving any reason. There is no intervention, manipulation or deception taking place.The study undertakes the piloting of quality measure validity, credibility, and feasibility as part of the diabetes prevention programme.The strengths of this study include: a practical design; patient evaluation, which is rarely carried out and will contribute to a wider understanding of identification of NDH and consequences (if any) on quality of life; a theoretical framework to inform data collection in the focus group; exploration of patient experiences to provide insight into identification of NDH and measure appropriateness; and piloting, which will allow the evaluation of quality measures before they are implemented as part of a longitudinal national project. Insight into patient experiences and perspectives on quality measures will help care providers and health services to understand the effects of identification and its consequences for patients’ lifestyle, engagement with care services, and overall wellbeing.Nonetheless, there are challenges with recruiting and retaining participants across a multi-stage piloting process. GP practices within the overall Herefordshire health economy will be approached and potentially recruited to participate in the study. The identification by the GP of patients meeting the inclusion criteria and the inviting of participants to take part in the research may be limited to participants who are actively aware of their risk and not apprehensive about discussing it.Managing practices to collect baseline and final measurements from patients may create potential difficulties. This will require a considerable amount of resources to meet the recruitment targets and involve collaboration with NHS Herefordshire. Any issues with non-responsive patients will be discussed with the practice manager.The RAND methodology is also limited in its ability to incorporate patient views, but this study aims to address this by carrying out a number of focus group sessions to gather data on patients' experiences of being identified as having NDH and their views on quality measures. Although RAND panels may be limited in group size and the piloting focus is restricted to one geographical area (Hereford) that is not representative of England, the research will not only gauge expert opinion, but will also incorporate patient views on these measures and any implications which identification of pre-diabetes has for their emotional wellbeing.Herefordshire CCG is a first wave implementation site of the diabetes prevention programme. The population provides the opportunity to sample individuals from a lower rural socioeconomic status. However, Herefordshire is a relatively homogenous area in terms of ethnicity and this could limit generalisability of the focus groups. Focus groups should be replicated in more diverse areas.The focus of the current pilot is not on outcome-driven quality measures in diabetes prevention care, as they are not normally rewarded. The findings may suggest alternative measures need to be implemented to support process and risk adjustment factors.The pilot will contribute to the evidence base about quality measure piloting and implementation, but also inform the Diabetes Prevention Programme about barriers and facilitators to the management of care for people with NDH.