Post-compression of long-wave infrared 2 picosecond sub-terawatt pulses in bulk materials.

We have experimentally demonstrated the post-compression of a long-wave infrared (9.2 µm) 150 GW peak power pulse from 2 ps to less than 500 fs using a sequence of two bulk materials with negative group velocity dispersion (GVD). The compression resulted in up to 1.6-fold increase of the peak power and up to 2.8-fold increase of the intensity in the center of a quasi-Gaussian beam. The partial decoupling of the self-phase modulation and chirp compensation stages by using two materials with significantly different ratios of nonlinear refractive index to GVD provides accurate optimization of the compression mechanism and promises a viable path to scaling peak powers to supra-terawatt levels. During the preparatory study, we measured, for the first time to our knowledge, the nonlinear refractive indices of NaCl, KCl, and BaF2 for picosecond pulses in the long-wave infrared region.

Single-shot measurement of the nonlinear refractive index of air at 9.2 µm with a picosecond terawatt CO2 laser.

We developed a simple, accurate single-shot method to determine the nonlinear refractive index of air by measuring the evolution of the spatial shape of a laser beam propagating through the atmosphere. A distinctive feature of this new method, which relies on a modified Fresnel propagation model for data analysis, is the use of a hard aperture for producing a well-defined, high-quality beam from a comparatively non-uniform quasi-flat-top beam, which is typical for high-peak-power lasers. The nonlinear refractive index of air for a very short (2 ps) long-wave infrared (LWIR) laser pulse was measured for the first time, to the best of our knowledge, yielding n2=3.0×10-23m2/W at 9.2 µm. This result is 40% lower than a corresponding measurement with longer (200 ps) LWIR pulses at a similar wavelength.

Physiological Loading of the Coonrad/Morrey, Nexel, and Discovery Elbow Systems: Evaluation by Finite Element Analysis.

PURPOSE: Wear of polyethylene bearings represents a limiting factor in the long-term success of total elbow prostheses. Bearing stress is 1 factor contributing to accelerated wear. Physiological loading of total elbow prostheses and implant design influence upon bearing stresses have not been well described. This study evaluates bearing stresses in 3 commercially available implant designs under loads associated with daily living. METHODS: Motion tracking from a healthy volunteer helped establish a musculoskeletal model to simulate flexor and extensor muscle activation at 0°, 45°, and 90° of shoulder abduction with a 2.3-kg weight in hand-forces and moments were measured at the elbow. Resulting physiological joint reaction forces and moments were applied to finite element models of 3 total elbow bearing designs (Coonrad/Morrey, Nexel, and Discovery) to evaluate contact area and polyethylene stresses. RESULTS: Increasing shoulder abduction resulted in minimal changes to the elbow joint reaction force but greater joint moments. All implants showed greater peak stresses with increasing shoulder abduction-elbow varus. Discovery and Nexel achieved greater contact area (23% vs > 100%) and demonstrated up to 39% lower peak polyethylene stresses compared with the Coonrad/Morrey design. CONCLUSIONS: Shoulder abduction results in a varus moment at the elbow. Newer bearing designs (Nexel and Discovery) provide a combination of higher contact area, improved load sharing, reduced edge loading, and lower stresses through elbow range of motion when compared with a cylindrical hinge-bearing design (Coonrad/Morrey). CLINICAL RELEVANCE: Although the Coonrad/Morrey is a clinically successful prosthesis, our physiological loading model shows that Discovery and Nexel provide greater contact area, better load sharing and lower peak stresses. This may lead to a decrease in polyethylene wear rates and the eventual risks of osteolysis and aseptic loosening. Further studies are needed to determine how these findings translate clinically.

Numerical investigation of a finite element abdominal wall model during breathing and muscular contraction.

BACKGROUND AND OBJECTIVE: Ventral hernia repair is faced with high recurrence rates. The personalization of the diagnosis, the surgical approach and the choice of the prosthetic implant seem relevant axes to improve the current results. Numerical models have the potential to allow this patient-specific approach, yet currently existing models lack validation. This work extensively investigated a realistic finite element abdominal wall model including the implementation of muscle activation. METHODS: A parametric 3D finite element model composed of bone, muscle and aponeurotic structures was introduced. Hyperelastic anisotropic materials were implemented. Two loading scenarios were simulated: passive inflation of the abdominal cavity to represent, e.g., breathing, and passive inflation followed by muscular activation to simulate other daily activities such as cough. The impact of the inter-individual variability (e.g., BMI, tissue thickness, material properties, intra-abdominal pressure (IAP) and muscle contractility) on the model outputs was studied through a sensitivity analysis. RESULTS: The overall model predictions were in good agreement with the experimental data in terms of shape variation, muscles displacements, strains and midline forces. A total of 34 and 41 runs were computed for the passive and active sensitivity analysis respectively. The regression model fits rendered high R-squared in both passive (84.0 ± 6.7 %) and active conditions (82.0 ± 8.3 %). IAP and muscle thickness were the most influential factors for the selected outputs during passive (breathing) activities. Maximum isometric stress, muscle thickness and pre-activation IAP were found to drive the response of the simulations involving muscular contraction. The material properties of the connective tissue were essential contributors to the behaviour of the medial part of the abdominal wall. CONCLUSIONS: This work extensively investigated a realistic abdominal wall model and evaluated its robustness using experimental data from literature. Such a model could improve patient-specific simulation for ventral hernia surgical planning, prevention, and repair or implant evaluation. Further investigations will be conducted to evaluate the impact of the surgical technique and the mechanical characteristic of prosthetic meshes on the model outputs.

Sensory training system for use at home by people with complex regional pain syndrome in England: protocol for a proof-of-concept study.

INTRODUCTION: Complex regional pain syndrome (CRPS) is a disabling and distressing chronic pain condition characterised by a range of sensory, motor, autonomic and trophic symptoms. UK guidelines recommend therapy interventions to help normalise touch perception through self-administered tactile and thermal desensitisation activities. Interventions have been developed, aiming to help individuals broaden their sensory experience, thereby relieving chronic pain. However, therapy-led interventions often experience practical constraints and poor adherence. In response, a sensory training system (STS) device has been designed for unsupervised independent home-use. METHODS: This proof-of-concept study aims to explore whether people with CRPS use the device at home for 30 minutes a day for 30 days. Secondary aims are to determine whether the STS device will change tactile acuity and perceived levels of pain intensity, pain interference, sensitivity or feelings towards the affected limb. We will seek to recruit 20 eligible participants. Participants will be asked to measure tactile acuity using a two-point discrimination assessment, complete an online questionnaire before and after use of the device and complete a daily diary. On completion of the 30-day use, participants will be invited to take part in a semi-structured interview to explore their experiences of using the device. ANALYSIS: Pain intensity and pain interference will be scored using the online Assessment Center Scoring Service or using the look-up table in the PROMIS scoring manual. The remaining questionnaire data, including tactile acuity results, and device-use data, including frequency and duration of use, will be analysed using descriptive statistics. Qualitative data will be thematically analysed. ETHICS AND DISSEMINATION: London-Stanmore Research Ethics Committee provided a favourable opinion on 19 April 2021 (ref 21/LO/0200). The NHS Health Research Authority, UK, approved this study on 7 June 2021. Dissemination will include peer-reviewed publications, presentations at conferences, social media and reports to the funder and patient charities. TRIAL REGISTRATION NUMBER: ISRCTN89099843.

Toward A Regulatory Pathway for the Use of in Silico Trials in the CE Marking of Medical Devices.

In Silico Trials methodologies will play a growing and fundamental role in the development and de-risking of new medical devices in the future. While the regulatory pathway for Digital Patient and Personal Health Forecasting solutions is clear, it is more complex for In Silico Trials solutions, and therefore deserves a deeper analysis. In this position paper, we investigate the current state of the art towards the regulatory system for in silico trials applied to medical devices while exploring the European regulatory system toward this topic. We suggest that the European regulatory system should start a process of innovation: in principle to limit distorted quality by different internal processes within notified bodies, hence avoiding that the more innovative and competitive companies focus their attention on the needs of other large markets, like the USA, where the use of such radical innovations is already rapidly developing.

Lateral transmission of force is impaired in skeletal muscles of dystrophic mice and very old rats.

The dystrophin­glycoprotein complex (DGC) provides an essential link from the muscle fibre cytoskeleton to the extracellular matrix. In dystrophic humans and mdx mice, mutations in the dystrophin gene disrupt the structure of the DGC causing severe damage to muscle fibres. In frog muscles, transmission of force laterally from an activated fibre to the muscle surface occurs without attenuation, but lateral transmission of force has not been demonstrated in mammalian muscles. A unique 'yoke' apparatus was developed that attached to the epimysium of muscles midway between the tendons and enabled the measurement of lateral force. We now report that in muscles of young wild-type (WT) mice and rats, compared over a wide range of longitudinal forces, forces transmitted laterally showed little or no decrement. In contrast, for muscles of mdx mice and very old rats, forces transmitted laterally were impaired severely. Muscles of both mdx mice and very old rats showed major reductions in the expression of dystrophin. We conclude that during contractions, forces developed by skeletal muscles of young WT mice and rats are transmitted laterally from fibre to fibre through the DGC without decrement. In contrast, in muscles of dystrophic or very old animals, disruptions in DGC structure and function impair lateral transmission of force causing instability and increased susceptibility of fibres to contraction-induced injury.

Non-uniform distribution of strain during stretch of relaxed skeletal muscle fibers from rat soleus muscle.

Tension and regional average sarcomere length (L(s)) behavior were examined during repeated stretches of single, permeabilized, relaxed muscle fibers isolated from the soleus muscles of rats. We tested the hypothesis that during stretches of single permeabilized fibers, the global fiber strain is distributed non-uniformly along the length of a relaxed fiber in a repeatable pattern. Each fiber was subjected to eight constant-velocity stretch and release cycles with a strain of 32% and strain rate of 54% s(-1). Stretch-release cycles were separated by a 4.5 min interval. Throughout each stretch-release cycle, sarcomere lengths were measured using a laser diffraction technique in which 20 contiguous sectors along the entire length of a fiber segment were scanned within 2 ms. The results revealed that: (1) the imposed length change was not distributed uniformly along the fiber, (2) the first stretch-release cycle differed from subsequent cycles in passive tension and in the distribution of global fiber strain, and (3) a characteristic "signature" for the L(s) response emerged after cycle 3. The findings support the conclusions that longitudinal heterogeneity exists in the passive stiffness of individual muscle fibers and that preconditioning of fibers with stretch-release cycles produces a stable pattern of sarcomere strains.

Persistent institutional breaches: Technology use in healthcare work.

Various mobile phone applications (hereafter apps) challenge instituted ways of working in healthcare. This study explores the institutional breaches arising from the use of apps in doctor-patient interactions. This paper argues that institutional breaches, however small, are important occasions for observing the contextual intersections between healthcare, regulation and technology in a hospital setting. Based on healthcare professionals' normative judgements, the paper offers an empirically grounded understanding of institutional legitimacy-claiming; safeguarding responses deployed by the instituted regime, and the case-building responses deployed by the instituting persuaders. Institutional breach persistence arises from the moral dimension of legitimacy and is grounded in asymmetrical dynamics between two virtuous healthcare narratives. The paper concludes with a discussion of the contextual intersections between healthcare, regulation and technology, paying particular attention to institutional breaches as experimentation, the contestation of normativity and patterns of technology indulgency in healthcare work.

The impact of myocardial compressibility on organ-level simulations of the normal and infarcted heart.

Myocardial infarction (MI) rapidly impairs cardiac contractile function and instigates maladaptive remodeling leading to heart failure. Patient-specific models are a maturing technology for developing and determining therapeutic modalities for MI that require accurate descriptions of myocardial mechanics. While substantial tissue volume reductions of 15-20% during systole have been reported, myocardium is commonly modeled as incompressible. We developed a myocardial model to simulate experimentally-observed systolic volume reductions in an ovine model of MI. Sheep-specific simulations of the cardiac cycle were performed using both incompressible and compressible tissue material models, and with synchronous or measurement-guided contraction. The compressible tissue model with measurement-guided contraction gave best agreement with experimentally measured reductions in tissue volume at peak systole, ventricular kinematics, and wall thickness changes. The incompressible model predicted myofiber peak contractile stresses approximately double the compressible model (182.8 kPa, 107.4 kPa respectively). Compensatory changes in remaining normal myocardium with MI present required less increase of contractile stress in the compressible model than the incompressible model (32.1%, 53.5%, respectively). The compressible model therefore provided more accurate representation of ventricular kinematics and potentially more realistic computed active contraction levels in the simulated infarcted heart. Our findings suggest that myocardial compressibility should be incorporated into future cardiac models for improved accuracy.

Mixing of a mAb Formulation in a New Magnetically Coupled Single-Use Mixing System: Key Learnings of Preliminary Experimental and Computational Evaluation.

MilliporeSigma recently introduced a new magnetically coupled single-use mixing system (Mobius® Power MIX) for more efficient mixing of buffers and media in biopharmaceutical applications. Experimental and computational fluid dynamics (CFD) assessments were performed on the Power MIX 100 system to understand product quality impact, shear, and mixing efficiency. It was interesting to note slightly higher submicron (0.4-1 µm) and subvisible (1-54 µm) particle formation at the lower mixing speed (50 RPM) compared to higher mixing speeds (100/200 RPM). Mixing speed and time showed negligible impact on the other product quality attributes tested, including protein concentration, turbidity, general appearance, purity, and soluble aggregates. The CFD simulations provided useful information with respect to the impact of batch size (20-100 L), viscosity (2-50 cP), and impeller speed (100-300 RPM) on mixing time (mixing time ranged from 10 to 365 s) and shear (maximum shear rate was found to be localized around the impeller and it was about 30,260 s-1, whereas the average shear rate ranged from 4 to 36 s-1). Statistical analysis of the CFD results showed that natural-log transformation and quadratic fitting were found to be suitable statistical models to predict mixing time and shear within the design space of the parameters assessed in the present study.

Syringe Filling of a High-Concentration mAb Formulation: Experimental, Theoretical, and Computational Evaluation of Filling Process Parameters That Influence the Propensity for Filling Needle Clogging.

This article summarizes experimental, theoretical, and computational assessments performed to understand the effect of filling and suck-back cycle factors on fluid behaviors that increase the propensity for filling needle clogging. Product drying under ambient conditions decreased considerably when the liquid front was altered from a droplet or meniscus at the needle tip to a point approximately 5 mm inside the needle. Minimizing the variation in size of product droplet formed after the fill cycle is critical to achieve a uniform meniscus height after the suck-back cycle. Several factors were found to contribute to droplet size variability, including filling and suck-back pump speed, suck-back volume, and product temperature. Filling trials and the computational fluid dynamics simulations showed that product meniscus stability during the suck-back cycle can be improved by reducing the suck-back flow rate. The computational fluid dynamics simulations also showed that a decrease in contact angle had the greatest effect in reducing meniscus stability. As the number of filling line stoppages increases, the product buildup at the needle increases. The interaction between stoppages and the number of dispenses between stoppages was established to minimize product buildup at the filling needle. Improved suck-back control was shown to improve process capability of large-scale batches.

Magnitude of sarcomere extension correlates with initial sarcomere length during lengthening of activated single fibers from soleus muscle of rats.

A laser-diffraction technique was developed that rapidly reports the lengths of sarcomeres (L(s)) in serially connected sectors of permeabilized single fibers. The apparatus translates a laser beam along the entire length of a fiber segment within 2 ms, with brief stops at each of 20 contiguous sectors. We tested the hypothesis that during lengthening contractions, when maximally activated fibers are stretched, sectors that contain the longer sarcomeres undergo greater increases in L(s) than those containing shorter sarcomeres. Fibers (n = 16) were obtained from the soleus muscles of adult male rats and the middle portions (length = 1.05 +/- 0.11 mm; mean +/- SD) were investigated. Single stretches of strain 27% and a strain rate of 54% s(-1) were initiated at maximum isometric stress and resulted in a 19 +/- 9% loss in isometric stress. The data on L(s) revealed that 1), the stretch was not distributed uniformly among the sectors, and 2), during the stretch, sectors at long L(s) before the stretch elongated more than those at short lengths. The findings support the hypothesis that during stretches of maximally activated skeletal muscles, sarcomeres at longer lengths are more susceptible to damage by excessive strain.

Testing the robustness of management decisions to uncertainty: Everglades restoration scenarios.

To effectively manage large natural reserves, resource managers must prepare for future contingencies while balancing the often conflicting priorities of different stakeholders. To deal with these issues, managers routinely employ models to project the response of ecosystems to different scenarios that represent alternative management plans or environmental forecasts. Scenario analysis is often used to rank such alternatives to aid the decision making process. However, model projections are subject to uncertainty in assumptions about model structure, parameter values, environmental inputs, and subcomponent interactions. We introduce an approach for testing the robustness of model-based management decisions to the uncertainty inherent in complex ecological models and their inputs. We use relative assessment to quantify the relative impacts of uncertainty on scenario ranking. To illustrate our approach we consider uncertainty in parameter values and uncertainty in input data, with specific examples drawn from the Florida Everglades restoration project. Our examples focus on two alternative 30-year hydrologic management plans that were ranked according to their overall impacts on wildlife habitat potential. We tested the assumption that varying the parameter settings and inputs of habitat index models does not change the rank order of the hydrologic plans. We compared the average projected index of habitat potential for four endemic species and two wading-bird guilds to rank the plans, accounting for variations in parameter settings and water level inputs associated with hypothetical future climates. Indices of habitat potential were based on projections from spatially explicit models that are closely tied to hydrology. For the American alligator, the rank order of the hydrologic plans was unaffected by substantial variation in model parameters. By contrast, simulated major shifts in water levels led to reversals in the ranks of the hydrologic plans in 24.1-30.6% of the projections for the wading bird guilds and several individual species. By exposing the differential effects of uncertainty, relative assessment can help resource managers assess the robustness of scenario choice in model-based policy decisions.

Experimental observations of dry powder inhaler dose fluidisation.

Dry powder inhalers (DPIs) are widely used to deliver respiratory medication as a fine powder. This study investigates the physical mechanism of DPI operation, assessing the effects of geometry, inhalation and powder type on dose fluidisation. Patient inhalation through an idealised DPI was simulated as a linearly increasing pressure drop across three powder dose reservoir geometries permitting an analysis of shear and normal forces on dose evacuation. Pressure drop gradients of 3.3, 10 and 30 kPa s(-1)were applied to four powder types (glass, aluminium, and lactose 6 and 16% fines) and high speed video of each powder dose fluidisation was recorded and quantitatively analysed. Two distinct mechanisms are identified, labelled 'fracture' and 'erosion'. 'Fracture' mode occurs when the initial evacuation occurs in several large agglomerates whilst 'erosion' mode occurs gradually, with successive layers being evacuated by the high speed gas flow at the bed/gas interface. The mechanism depends on the powder type, and is independent of the reservoir geometries or pressure drop gradients tested. Both lactose powders exhibit fracture characteristics, while aluminium and glass powders fluidise as an erosion. Further analysis of the four powder types by an annular shear cell showed that the fluidisation mechanism cannot be predicted using bulk powder properties.

Fat reduction using phosphatidylcholine/sodium deoxycholate injections: standard of practice.

The practice of injecting phosphatidylcholine/sodium deoxycholate compounds into subcutaneous fat is growing rapidly. As with any new procedure, a standard of practice should be developed so that practitioners maintain patient safety as the primary goal. Efficacy and predictability of outcome are another priority. As injection lipolysis, also known as "lipodissolve," becomes more accepted, many standards are being set, such as indications, contraindications, acceptable postinjection sequelae, best regions to treat, regions to avoid, and expected outcomes. This article establishes a basis of practice for the practitioner interested in adding this procedure to his or her repertoire.

Evaluation of pyrethrin aerial ultra-low volume applications for adult Culex tarsalis control in the desert environments of the Coachella Valley, Riverside County, California.

Eliminating infected female mosquitoes by aerial applications of ultra-low volume adulticides is the intervention strategy currently recommended to interrupt the epidemic transmission of encephalitis viruses, including West Nile. The current research optimized pyrethrin formulations and evaluated their efficacy in the desert environment of the Coachella Valley, Riverside County, California. After seven trials during 2004, a 1:2 by volume mixture of Pyrenone 25-5 in BVA oil optimized particle size, droplet descent to ground level, and kill of sentinel mosquitoes. Three subsequent experiments used 3 aerial applications of the 1:2 Pyrenone 25-5:BVA oil mixture on alternate nights to suppress Culex tarsalis Coquillett host-seeking abundance over a 1-square-mile target area. Mortality patterns among caged sentinel mosquitoes varied among sites and replicate sprays, indicating variable particle dispersion at ground level within the target area. In addition, mortality was observed for sentinels up to 1 mile downwind from the target area, indicating considerable particle drift. Geometric mean abundance of host-seeking Cx. tarsalis females collected at dry ice-baited traps within each of 3 sprayed and 2 unsprayed negative control strata varied similarly over time, indicating that our sprays minimally impacted the target population or that drift combined with other factors led to widespread area control. Experiments during March and June when recruitment rates were minimal showed general area-wide suppression of abundance following spray, whereas an experiment during September when recruitment rates were high from newly flooded marshes failed to prevent an area-wide increase in abundance. Clearly additional research is needed to standardize the efficacy of aerial applications of pyrethrins in hot dry desert environments.

Evaluation of pyrethrin and permethrin ground ultra-low volume applications for adult Culex control in rural and urban environments of the Coachella Valley of California.

Six experimental ground ultra-low volume (ULV) applications of Pyrenone 25-5 (0.0025 lb/acre) and Aqua-Reslin (0.007 lb/acre) were made by truck-mounted Pro-Mist or London Fog equipment over 1-mi2 study areas in rural and residential environments of the Coachella Valley, Riverside County, California. Efficacy of replicate applications was evaluated by measuring mortality among caged sentinel mosquitoes, by evaluating changes in host-seeking abundance at replicated dry ice-baited traps positioned along intersecting east-west and north-south transects, and by differential recapture patterns of marked females released near traps in the sprayed central core and unsprayed control areas. Sentinel mortality agreed well with estimates of droplet density measured by "slide spinners" and was affected by 1) distance of cages from the truck route; 2) landscape features, such as tree lines that created wind shadows; 3) irregular landscape that disrupted the particle cloud; 4) low wind speed that failed to carry the droplet cloud through the environment; and 5) failure of the droplets to penetrate dead airspace within stands of vegetation. Despite variable sentinel mortality, Culex tarsalis relative abundance in rural landscapes within and around our study areas always declined after ULV applications. Concurrent decreases in abundance at traps within sprayed and adjoining unsprayed areas confounded our estimates of percentage of control using Mulla's formula, which compares abundance in sprayed and unsprayed areas pre- and postspray. ULV applications significantly affected recapture patterns, in that recapture rates within the spray zone usually were significantly less than in the unsprayed zone. Collectively, our data indicated that ground ULV applications measurably reduced Cx. tarsalis abundance in rural areas of the Coachella Valley but that further evaluations may be necessary to validate efficacy on Culex quinquefasciatus populations in residential communities.

In silico assessment of biomedical products: The conundrum of rare but not so rare events in two case studies.

In silico clinical trials, defined as "The use of individualized computer simulation in the development or regulatory evaluation of a medicinal product, medical device, or medical intervention," have been proposed as a possible strategy to reduce the regulatory costs of innovation and the time to market for biomedical products. We review some of the the literature on this topic, focusing in particular on those applications where the current practice is recognized as inadequate, as for example, the detection of unexpected severe adverse events too rare to be detected in a clinical trial, but still likely enough to be of concern. We then describe with more details two case studies, two successful applications of in silico clinical trial approaches, one relative to the University of Virginia/Padova simulator that the Food and Drug Administration has accepted as possible replacement for animal testing in the preclinical assessment of artificial pancreas technologies, and the second, an investigation of the probability of cardiac lead fracture, where a Bayesian network was used to combine in vivo and in silico observations, suggesting a whole new strategy of in silico-augmented clinical trials, to be used to increase the numerosity where recruitment is impossible, or to explore patients' phenotypes that are unlikely to appear in the trial cohort, but are still frequent enough to be of concern.

Syringe Filling of High-Concentration mAb Formulation: Slow Suck-Back Pump Speed Prevented Filling Needle Clogging.

Partial and complete clogging of filling needles occurred during syringe filling of a high-concentration mAb formulation. This caused nonvertical liquid flow, which eventually led to the termination of filling. Overcoming this phenomenon was essential to ensure minimal fill weight variation, product waste, and manufacturing downtime. The liquid behavior inside the filling needle was studied using glass and stainless steel needles and demonstrated that effective suck-back control was critical for preventing needle clogging. A key finding of our work is that the suck-back pump speed was a critical factor to achieve an effective suck back. More specifically, a slow suck-back pump speed (<10 rpm; liquid flow rate, <5 mL/min) was essential to improve suck-back control inside the conventional stainless steel filling needles. In contrast, higher suck-back pump speeds (>10 rpm; liquid flow rate, >5 mL/min) resulted in downward product migration within the filling needle leading to formation of a liquid plug at the needle tip, which was prone to rapid drying. Slowing the suck-back pump speed in conjunction with modifying the suck-back volume was effective at consistently withdrawing product into the stainless steel filling needles and prevented needle clogging.