Higher Detachment Rate Research Articles

Effect of water temperature and exposure duration on detachment rate of salmon lice (Lepeophtheirus salmonis); testing the relevant thermal spectrum used for delousing

Thermal delousing has become the most applied method for treatment against salmon lice. However, the temperature range used is strongly aversive for salmonids, and the method is associated with increased mortality. Treatment temperature × duration combinations should be tailored to maximise delousing efficiency and minimize welfare impacts on the host fish. We tested the detachment rate of sessile, pre-adult and adult male and female salmon lice (Lepeophtheirus salmonis) as a function of ambient temperature (11–16 °C), exposure temperature (28–36 °C), and exposure duration (0–120 s). Dead Atlantic salmon (Salmo salar) hosts were used to avoid negative fish welfare and detachment of lice due to fish behaviour. Within the range tested, higher exposure temperatures were associated with higher detachment rates among pre-adult and adult lice, while no sessile lice detached at any temperature. Moreover, no treatment combination detached 100% of lice of any stage, and at 28 °C, detachment of adult females was negligible. Most detachments occurred within the first 30 s of exposure. We conclude that for a given delousing efficiency, lower temperatures must be compensated for by considerably longer exposure durations. This may be a higher risk for the welfare of the host fish than higher temperatures and shorter exposure durations.

Sustained impact of COVID-19 on primary retinal detachment repair in atertiary eye hospital from March to December 2020.

PurposeTo review the sustained effect of COVID-19 on rhegmatogenous retinal detachment (RRD) baseline characteristics and outcomes.MethodsThis was a retrospective consecutive case series at the Birmingham and Midlands Eye Centre including patients undergoing primary RRD repair between 23 March and 31 December 2017–2019 (Group 1) and 2020 (Group 2). The deciles of indices of multiple deprivation (IMD) were determined by postcode to group patients into least deprived (IMD1-5) and most deprived (IMD6-10).ResultsIn total we reviewed 1310 patients, 1003 in Group 1 and 307 in Group 2. Relative to 2017–2019, during the first lockdown, we observed (a) a reduction in the number of patients with RRD, (b) an increase in macula-off detachments, (c) an increase in RRD primary failure, and (d) that the least deprived had proportionately higher primary failure than the most deprived (p = 0.049) with a higher detachment rate than the pre-COVID-19 period (p = 0.010) and increased presentations of macula-off detachment. During the second lockdown, these differences were not observed.ConclusionThe previously observed findings of lower presentation rates of RRD during the beginning of the first lockdown and the decreased number of macula-on RRD were not sustained over a longer period of observation or found to recur after a second national lockdown. Patients from areas with the least socioeconomic deprivation seemed to be more negatively affected by the first lockdown, with later presentation and higher rates of re-detachments compared with the most deprived during the first lockdown. Our findings offer reassurance that patient behaviour and health services had adapted to the pandemic by the second national lockdown.Supplementary InformationThe online version of this article (10.1007/s00717-022-00521-0) contains supplementary material, which is available to authorized users.

DSAEK or DMEK for failed penetrating keratoplasty: a systematic review and single-arm meta-analysis.

To review the published literature on indications and outcomes of DSAEK/DSEK and DMEK for the treatment of failed penetrating keratoplasty. This is a systematic review and single-arm meta-analysis. Literature searches were conducted in PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews. Prospective and retrospective studies reporting DSAEK/DSEK or DMEK after failed penetrating keratoplasty were included. Primary outcome measures are graft survival and detachment rates, as well as postoperative visual outcomes. A total of 25 studies with 970 patients/989 eyes were included, comprising 735 patients with 746 eyes which underwent DSAEK/DSEK surgery and 235 patients with 243 eyes which underwent DMEK surgery, all of them following a previously failed PK. There were no randomized controlled studies. In all of the DSAEK-PK studies, the graft failure rate was 18% (10%, 26%), the detachment rate was 15% (9%, 22%) and the rejection rate was 7% (3%, 12%) by the time of the last follow-up. And in all of the DMEK-PK studies, the graft failure rate was 14% (4%, 27%), the detachment rate was 42% (28%, 56%) and the rejection rate was 7% (2%, 16%). The mean visual acuity of the DSAEK-PK and DMEK-PK groups is 0.65 ± 0.18 and 0.43 ± 0.23 logMAR, respectively, at 6months postoperatively. Endothelial keratoplasty for treatment of failed penetrating keratoplasty led to improved vision and graft clarity in most recipients. Though graft survival rates and rejection rates were comparable between the two groups, the DMEK-PK group showed better visual outcomes with higher detachment rate.

Outcomes of Descemet Membrane Endothelial Keratoplasty in Aphakic and Aniridic Patients.

To evaluate the outcomes of Descemet membrane endothelial keratoplasty (DMEK) in aphakic and aniridic eyes. A retrospective chart review of either aphakic or aniridic patients who underwent DMEK at Toronto Western Hospital, Canada, between 2015 and 2019 was performed. Demographic characteristics, intraoperative and postoperative complications, and best corrected visual acuity (BCVA) were analyzed. Nine eyes of 9 patients, aged 51.0 ± 8.6 years, were included (3 aniridic, 5 aphakic, and 1 combined). The average follow-up was 15.7 ± 12.7 months. The best corrected visual acuities before surgery and 3 and 6 months after surgery were 1.28 ± 0.47, 1.33 ± 0.98, and 1.03 ± 0.56 LogMAR, respectively. Six eyes (67%) had graft detachment, with 3 of them larger than 30% of the graft area. One eye (11%) developed hyphema. The overall failure rate was 88% (8 of 9 eyes), meaning only one was viable at the last follow-up. Primary graft failure was seen in 4 eyes (44%) after detachment (n = 3) and intraoperative hyphema (n = 1). Secondary failure occurred in 4 eyes (44%) at 7, 12, 15, and 36 months. The secondary failure at 36 months was after rejection. Failures were managed with penetrating keratoplasty (n = 2), repeat DMEK (n = 3), Descemet stripping automated endothelial keratoplasty (n = 1), and observation because of poor vision potential (n = 2). Cumulative graft survival probabilities at 12 and 24 months were 44% and 17%, respectively. Aniridic and aphakic patients experienced unacceptably high detachment and failure rates after DMEK. Before performing DMEK, the risks and benefits should be carefully weighed and perhaps other keratoplasty techniques should be used.

Enhanced Dynamic Adhesion in Nematic Liquid Crystal Elastomers.

Smart adhesives that undergo reversible detachment in response to external stimuli enable a wide range of applications in household products, medical devices, or manufacturing. Here, a new model system for the design of smart soft adhesives that dynamically respond to their environment is presented. By exploiting the effect of dynamic soft elasticity in nematic liquid crystal elastomers (LCE), the temperature-dependent control of adhesion to a solid glass surface is demonstrated. The adhesion strength of LCE is more than double in the nematic phase, in comparison to the isotropic phase, further increasing at higher detachment rates. The static work of adhesion, related to the interfacial energy of adhesive contact, is shown to change very little within the explored temperature range. Accordingly, the observed enhanced adhesion in the nematic phase is primarily attributable to the increased internal energy dissipation during the detachment process. This adhesion effect is correlated with the inherent bulk dynamic-mechanical response in the nematic LCE. The reported enhanced dynamic adhesion can lead to the development of a new class of stimuli-responsive adhesives.

Transition mechanism of negative DC corona modes in atmospheric air: from Trichel pulses to pulseless glow

Corona discharge in high voltage power transmission lines can generate audible noise and radio inference, causing environmental problems in daily life. There are three different discharge modes of negative corona depending on DC voltage amplitude, namely, Trichel pulses, stable glow and negative streamers. A 2D fluid model, incorporating three species (electrons, positive oxygen ions and negative oxygen ions), was successfully built to simulate the formation of repetitive Trichel pulses in air. However, this simplified model cannot correctly predict the transition to pulseless glow. The calculated transition voltage is higher than experimental results. In this work the gas dynamics and a detachment reaction are taken into account in the model. Gas heating due to the deposited discharge energy will influence the chemical reaction rates and reduce the gas density. Besides the mobility of charged particles, the ionization and attachment coefficients are determined by the reduced electric field. The calculation results of the gas density from the gas dynamics model are coupled back to the discharge model. The corona discharge in a needle-cylinder electrode configuration is simulated and the results show that the mode transitions at a lower voltage, which agrees well with the experimental data. The ionization rate is greatly enhanced around the needle because of the gas density reduction. Therefore, the reduced electric field will not easily be decreased by the generation and accumulation of negative ions. A higher detachment rate also causes the Trichel pulses to disappear. The simulation results suggest that gas heating is more important for the mode transition of negative coronas from Trichel pulses to pulseless glow than was previously expected.

Straw mulch as a sustainable solution to decrease runoff and erosion in glyphosate-treated clementine plantations in Eastern Spain. An assessment using rainfall simulation experiments

In many Mediterranean areas, citrus orchards exhibit high soil loss rates because of the expansion of drip irrigation that allows cultivation on sloping terrain and the widespread use of glyphosate. To mitigate these non-sustainable soil losses, straw mulch could be applied as an efficient solution but this has been poorly studied. Therefore, the main goal of this paper was to assess the use of straw mulch as a tool to reduce soil losses in clementine plantations, which can be considered representative of a typical Mediterranean citrus orchard. A total of 40 rainfall simulation experiments were carried out on 20 pairs of neighbouring bare and mulched plots. Each experiment involved applying 38.8 mm of rain at a constant rate over 1 h to a circular plot of 0.28 m2 circular plots. The results showed that a cover of 50% of straw (60 g m−2) was able to delay the time to ponding from 32 to 52 s and the time to runoff initiation from 57 to 129 s. Also, the mulching reduced the runoff coefficient from 65.6 to 50.5%. The effect on sediment transport was even more pronounced, as the straw mulch reduced the sediment concentration from 16.7 g l−1 to 3.6 g l−1 and the soil erosion rates from 439 g to 73 g. Our results indicated that mulching can be used as a useful management practice to control soil erosion rates due to the immediate effect on high soil detachment rate and runoff initiation reduction in conventional clementine orchards on sloping land, by slowing down runoff initiation and by reducing runoff generation and, especially, sediment losses. We indirectly concluded that straw mulch is also a sustainable solution in glyphosate-treated citrus plantations.

Molecular mechanisms of the interhead coordination by interhead tension in cytoplasmic dyneins

Cytoplasmic dyneins play a major role in retrograde cellular transport by moving vesicles and organelles along microtubule filaments. Dyneins are multidomain motor proteins with two heads that coordinate their motion via their interhead tension. Compared with the leading head, the trailing head has a higher detachment rate from microtubules, facilitating the movement. However, the molecular mechanism of such coordination is unknown. To elucidate this mechanism, we performed molecular dynamics simulations on a cytoplasmic dynein with a structure-based coarse-grained model that probes the effect of the interhead tension on the structure. The tension creates a torque that influences the head rotating about its stalk. The conformation of the stalk switches from the α registry to the β registry during the rotation, weakening the binding affinity to microtubules. The directions of the tension and the torque of the leading head are opposite to those of the trailing head, breaking the structural symmetry between the heads. The leading head transitions less often to the β registry than the trailing head. The former thus has a greater binding affinity to the microtubule than the latter. We measured the moment arm of the torque from a dynein structure in the simulations to develop a phenomenological model that captures the influence of the head rotating about its stalk on the differential detachment rates of the two heads. Our study provides a consistent molecular picture for interhead coordination via interhead tension.

Mechanosensing in Myosin Filament Solves a 60 Years Old Conflict in Skeletal Muscle Modeling between High Power Output and Slow Rise in Tension.

Almost 60 years ago Andrew Huxley with his seminal paper (Huxley, 1957) laid the foundation of modern muscle modeling, linking chemical to mechanical events. He described mechanics and energetics of muscle contraction through the cyclical attachment and detachment of myosin motors to the actin filament with ad-hoc assumptions on the dependence of the rate constants on the strain of the myosin motors. That relatively simple hypothesis is still present in recent models, even though with several modifications to adapt the model to the different experimental constraints which became subsequently available. However, already in that paper, one controversial aspect of the model became clear. Relatively high attachment and detachment rates of myosin to the actin filament were needed to simulate the high power output at intermediate velocity of shortening. However, these rates were incompatible with the relatively slow rise in tension upon activation, despite the rise should be generated by the same rate functions. This discrepancy has not been fully solved till today, despite several hypotheses have been forwarded to reconcile the two aspects. Here, using a conventional muscle model, we show that the recently revealed mechanosensing mechanism of recruitment of myosin motors (Linari et al., 2015) can solve this long standing problem without any further ad-hoc hypotheses.

Coupling of Bond Breaking With State Transition Leads to High Apparent Detachment Rates of a Single Myosin

Quantifying interactions between motors and filaments is important for the understanding of intriguing emergent behaviors of motor–filament systems, which play critical roles in various biological processes. Recently, unusually high detachment rates of a myosin from actin were obtained with a force spectroscopy technique of an unprecedented spatial–temporal resolution. Here, we suggest that these high apparent detachment rates may be due to the inherent coupling between bond breaking and state transition, which can be common in protein–protein interactions. Based on a kinetic model for the chemomechanical cycle of single myosin, rates of bond breaking between myosin and actin at different nucleotide states are systematically calculated. These quantitative results indicate that myosins may adopt much higher transition rates than bond breaking rates at different nucleotide states under physiological conditions when applied forces are relatively low. This work also indicates that accurate biophysical models considering both protein unbinding dynamics and protein state transitions are required in order to properly interpret the experimental data when the ultrafast force-clamp spectroscopy technique is employed to study, for example, the DNA–protein interactions.

Influence of In Situ Oxide Dissolution on the Bottom Morphologies of Detached TiO2 Nanotube Films

Free‐standing TiO2 nanotube (NT) films with through holes (i.e., open bottoms) are useful for various applications. In this paper, we report the significant influence of in situ chemical etching during the detachment process on the morphological variation of TiO2 NT bottoms. Under a high temperature detachment anodization, we noted a high detachment rate with controllable bottom morphologies. Influenced by anodization durations, the bottom opening size could be controlled with morphology transition changing from closed to partially open and then to fully open bottoms. The underlying formation mechanism of variable bottom conditions has been examined through the consideration of field‐assisted chemical dissolution of both the barrier layer and the sides of the tubes at the bottom. The production of well‐defined through‐hole tube membranes in a reliable and controllable way is essential for their practical applications.

Modelling clogging and biofilm detachment in sponge carrier media

Sponge carrier media provide a large surface area for biofilm support; however, little information is known about how to model their dual nature as a moving bed and as porous media. To investigate the interaction of mass transfer and detachment with bio-clogging, a novel biofilm model framework was built based on individual-based modelling, and hydrodynamics were modelled using the lattice Boltzmann method. The combined model structure enabled the simulation of oxygen and biomass distribution inside the porous network as well as inside the biofilm. In order to apply the model to moving bed biofilm reactors (MBBR), biofilm detachment due to abrasion (carrier collisions) was modelled to be dependent on intracarrier distance. In the initial growth stage, biofilm grew homogeneously on the internal skeleton after which a more discontinuous growth developed which significantly increased permeability. Low detachment rates caused clogging in the outer pores which limited growth of biofilm to the surface region of the sponge. High detachment rates on the surface enabled deeper oxygen penetration with higher internal biomass activity. The degree of clogging was also sensitive to the presence of extracellular polymeric substances because of its large spatial occupancy.

Perchlorate reduction from a highly contaminated groundwater in the presence of sulfate‐reducing bacteria in a hydrogen‐fed biofilm

We used a hydrogen (H2 )-based biofilm to treat a groundwater contaminated with perchlorate (ClO(4)(-) ) at ~10 mg/L, an unusually high concentration. To enhance ClO(4)(-) removal, we either increased the H2 pressure or decreased the electron-acceptor surface loading. The ClO(4)(-) removal increased from 94% to 98% when the H2 pressure was increased from 1.3 to 1.7 atm when the total acceptor surface loading was 0.49 g H2 /m(2) day. We then decreased the acceptor surface loading stepwise from 0.49 to 0.07 g H2 /m(2) day, and the ClO(4)(-) removal improved to 99.6%, giving an effluent ClO(4)(-) concentration of 41 µg/L. However, the tradeoff was that sulfate (SO(4)(2-) ) reduction occurred, reaching 85% conversion at the lowest acceptor surface loading (0.07 g H(2) /m(2) day). In two steady states with the highest ClO(4)(-) reduction, we assayed for the presence of perchlorate-reducing bacteria (PRB), denitrifying bacteria (DB), and sulfate-reducing bacteria (SRB) by quantitative polymerase chain reaction (qPCR) targeting characteristic reductases. The qPCR results documented competition between PRB and SRB for space within the biofilm. A simple model analysis for a steady-state biofilm suggests that competition from SRB pushed the PRB to locations having a higher detachment rate, which prevented them from driving the ClO(4)(-) concentration below 41 µg/L.

A Modified Huxley-Type Model that Simulates Activation-Dependent Rates of Tension Recovery

Many laboratories now estimate how quickly cross-bridges cycle in chemically permeabilized muscle preparations by measuring how quickly tension recovers to its steady-state after a rapid-shortening/re-stretch perturbation. Brenner, who developed this technique (PNAS, 85:3265-3269, 1988), showed that the rate of force development (ktr) increased with the level of Ca2+ activation. K.B. Campbell (no relation to the present author) developed an analytical model (Biophys J, 72:254-262, 1997) that attributed the activation-dependence of the rate constant to cooperative effects. The current work extends this approach by modifying a strain-dependent Huxley-type model (Prog Biophys Biophys Chem, 7:255-318, 1957) so that the proportion of binding sites that are available for cross-bridges to attach to (pon) depends on the prevailing Ca2+ concentration and the muscle's history of movement. Specifically, dpon/dt = (kon[Ca2+] + ψpon)(1-pon) - koff(pon-pbound), where kon and koff are rate constants, ψ is a scaling factor, and pbound is the proportion of binding sites that have myosin heads attached. During a rapid shortening/re-stretch maneuver, myosin heads are forcibly detached as they are pulled into configurations with high detachment rates. This increases the (pon-pbound) term above and the pon population thus declines. At high Ca2+ concentrations, this effect is short-lived and pon quickly returns to its steady-state value. ktr under these conditions is thus limited by the f and g rate functions. At low Ca2+ concentrations, dpon/dt is suppressed and ktr is dictated by how quickly binding sites become available for myosin heads to attach to. Initial calculations have shown that when this model is driven by a realistic length perturbation, the simulated force records accurately reproduce those measured in real experiments using rat myocardial preparations.

Ag transport in CrN–Ag nanocomposite coatings

2-μm-thick CrN–Ag composite coatings containing 22at.% Ag were deposited on Si(001) by reactive co-sputtering at Ts=300, 400, and 500°C. Subsequent vacuum annealing at Ta=425, 525, and 625°C causes Ag transport to the surface. Auger electron spectroscopy and plan-view microscopy are used to quantify the Ag transport to the surface, which increases strongly with increasing ΔT=Ta−Ts. Compositional depth profiles and cross-sectional microscopy show that annealing causes a negligible Ag gradient through the composite layer, suggesting that the Ag transport is detachment-limited as opposed to diffusion-limited. Statistical analyses of Ag aggregate size-distributions within the matrix show that large aggregates (≥50nm) are unaffected by annealing, while the Ag in a large fraction of small aggregates (<50nm) moves to the surface, leaving behind 10–50nm wide voids in the annealed composite. This indicates that the Ag from the smaller grains, with a higher chemical potential and thus a higher detachment rate, is transferred to the large grains on the surface which are 200–1000nm wide.

Descemet-stripping automated endothelial keratoplasty: a successful alternative to repeat penetrating keratoplasty

Although Descemet-stripping automated endothelial keratoplasty has replaced penetrating keratoplasty for primary treatment of endothelial disorders, many patients have already undergone penetrating keratoplasty. It is unclear when repeat penetrating keratoplasty is necessary or when endothelial keratoplasty may restore clarity to a failed graft. Retrospective case series of patients undergoing Descemet-stripping automated endothelial keratoplasty after penetrating keratoplasty by three surgeons at an academic tertiary care centre. Eight patients with Descemet-stripping automated endothelial keratoplasty after penetrating keratoplasty from 2006 to 2009. Microkeratome-prepared Descemet-stripping automated endothelial keratoplasty donor tissue was used. In seven cases, the penetrating keratoplasty bed was neither stripped nor scraped, and in one, scraping only was performed. Preoperative and 6-month postoperative best-corrected visual acuities in logMAR (logarithm of the minimum angle of resolution). The average pre-Descemet-stripping automated endothelial keratoplasty best-corrected visual acuity was 1.375, and the average best-corrected visual acuity 6months postoperatively was logMAR 1.0, a 2.5-fold improvement in the minimum angle of resolution (P=0.22). Seven of the eight patients showed an improvement in best-corrected visual acuity, and one patient had failure of Descemet-stripping automated endothelial keratoplasty and required penetrating keratoplasty. Five had a postoperative event: one had a gap that resolved spontaneously, three required rebubblings (injections of air only without otherwise repositioning the graft), and one experienced graft failure. Descemet-stripping automated endothelial keratoplasty can successfully rescue a prior penetrating keratoplasty, even with a fairly high detachment rate. Given these favourable visual outcomes, further study of this promising strategy is justified.

The treatment of recurrent aortic prosthetic detachment with modified Bentall procedure: Results of two cases

Recurrent prosthetic valve detachment after aortic valve replacement (AVR) for aortic regurgitation is a most serious complication. Endocarditis, aortitis, or other factors are the common causes. AVR or repair of the detachment are usually difficult to manage and still have a high detachment rate. We report 2 cases of successful surgical management with the translocated Bentall procedure for recurrent aortic valve detachment resulting from indefinite causes.

Transport of Coliphage in the Presence and Absence of Manure Suspension

Mechanisms of coliphage transport and fate in the presence and absence of manure suspension were studied in saturated column experiments. In the presence of manure suspension, little inactivation of indigenous somatic coliphage occurred and the transport was controlled by deposition. The deposition followed a power law distribution with depth, and the magnitude increased with decreasing sand size. Comparison of the cumulative size distribution of manure components in the suspension initially and after passage through sand, suggested that particles retained by mechanical filtration and/or straining decreased the effective pore size and potentially induced straining of the somatic coliphage. A 2-site kinetic deposition model was used to estimate the magnitudes of attachment and straining in the presence of manure suspension, and provided a good description of the data. Modeling results indicated that straining accounted for 16 to 42% of the deposited somatic coliphage, and that both straining and attachment increased with decreasing sand size due to smaller pores and higher surface area, respectively. In the absence of manure suspension, phiX174 (a representative somatic coliphage) and MS2 (a male-specific RNA coliphage) transport was controlled by inactivation induced by the solid phase. This conclusion was based on comparison of coliphage transport behavior at 5 and 20 degrees C, mass balance information, and numerical modeling. Comparison of somatic coliphage transport data in the presence and absence of manure suspension revealed much higher effluent concentrations in the presence of manure. This difference was attributed to lower inactivation and higher detachment rates. The observed coliphage transport behavior suggests that survival of viruses may be extended in the presence of manure suspensions, and that transport studies conducted in the absence of manure suspension may not accurately characterize the transport potential of viruses in manure-contaminated environments.

Detachment of multi species biofilm in circulating fluidized bed bioreactor

In this study, the detachment rates of various microbial species from the aerobic and anoxic biofilms in a circulating fluidized bed bioreactor (CFBB) with two entirely separate aerobic and anoxic beds were investigated. Overall detachment rate coefficients for biomass, determined on the basis of volatile suspended solids (VSS), glucose and protein as well as for specific microbial groups, i.e., for nitrifiers, denitrifiers, and phosphorous accumulating organisms (PAOs), were established. Biomass detachment rates were found to increase with biomass attachment on carrier media in both beds. The detachment rate coefficients based on VSS were significantly affected by shear stress, whereas for protein, glucose and specific microbial groups, no significant effect of shear stress was observed. High detachment rates were observed for the more porous biofilm structure. The presence of nitrifiers in the anoxic biofilm and denitrifiers in the aerobic biofilm was established by the specific activity measurements. Detachment rates of PAOs in aerobic and anoxic biofilms were evaluated.

The Mode of Drug Particle Detachment from Carrier Crystals in an Air Classifier-Based Inhaler

To investigate the mode of drug particle detachment from carrier crystals in an air classifier as a function of the carrier size fraction, payload, and the circulation time in the classifier. Laser diffraction analysis of the aerosol cloud from the classifier has been performed at 10, 20, 30, and 60 l/min, using a special adapter, for different adhesive mixture compositions. A significant part of the drug particles is detached from carrier crystals during inhalation as small agglomerates. Such agglomerates originate from the starting material or are newly formed on the carrier surface during mixing. The degree of agglomeration during mixing depends on the carrier size, payload, and surface rugosity. The size of the agglomerates that are formed during mixing, increases with the size of the carrier particles. Predominantly the largest drug particles and agglomerates are detached within the first 0.5 s of inhalation. After 0.5 s, smaller primary particles are dislodged. A high ratio of removal forces to adhesive forces causes a high drug detachment rate from carrier crystals in a classifier within the first 0.5 s of inhalation. The high ratio can be explained by dislodgment of agglomerates and the largest primary particles in the early phases of inhalation. At higher flow rates, detached agglomerates may be further disintegrated into primary particles before they are discharged from the classifier. Agglomeration of drug particles on the carrier surface is the result of the same forces that are responsible for pressing these particles firmly to the carrier crystals during mixing.