Reproducible Results Research Articles

Reliability of Rehabilitative Musculoskeletal Sonography for Measuring the Visible Cross-Sectional Area of Suboccipital Muscles.

Aims The primary aim of this study is to assess the reliability of rehabilitative sonography as a non-invasive imaging technique for measuring the visible cross-sectional area (CSA) of the deep suboccipital muscles. Objectives Objectives involve determining both the intra-rater and inter-rater reliability of sonographic measurements to ensure consistent and reproducible results across different sessions and examiners. The ultimate goal is to validate rehabilitative sonography as a reliable tool for clinical and research applications in the assessment and management of musculoskeletal (MSK) conditions involving the deep suboccipital muscles. Design and setting Seventeen participants, including nine women and eight men without neck or vertebral pain, were evaluated using MSK sonography. The visible CSA of suboccipital muscles was assessed using real-time B-mode sonography in a sitting position with a linear probe (5 cm, 7.5 MHz) aligned perpendicularly to the muscle fibers of the rectus capitis posterior minor (RCPM) in one sonogram and the obliquus capitis inferior (OCI) and rectus capitis posterior major (RCPMJ) in another. Two experienced examiners performed sonography measurements, and the procedure was repeated one hour and again one day later. Results Intra-class correlation coefficient (ICC) values for Examiner 1 were 0.84 and 0.79 for RCPM, 0.84 and 0.71 for RCPMJ, and 0.86 and 0.77 for OCI at the one-hour and one-day repetitions, respectively. ICC values for Examiner 2 were 0.86 and 0.77 for RCPM, 0.77 and 0.86 for RCPMJ, and 0.61 and 0.64 for OCI at the one-hour and one-day repetitions, respectively. Inter-rater ICC values were 0.77 for RCPM, 0.82 for RCPMJ, and 0.68 for OCI. Standard error of measurement (SEM) values for Examiner 1 were 11.63 and 13.92 mm² for RCPM, 10.30 and 7.91 mm² for RCPMJ, and 22.84 and 34.61 mm² for OCI. SEM values for Examiner 2 were 11.82 and 13.40 mm² for RCPM, 11.91 and 7.04 mm² for RCPMJ, and 39.20 and 37.73 mm² for OCI. SEM values between examiners were 13.74 mm² for RCPM, 10.36 mm² for RCPMJ, and 36.03 mm² for OCI. Conclusions These findings suggest that sonography is a reliable method for measuring the CSA of the RCPM, RCPMJ, and OCI muscles, provided that the examiners are well-trained and consistent in their techniques and that the average of three measurements is used.

UK Trainee Experience with WALANT - An Audit of 102 Cases.

Background: WALANT has gained much popularity in recent years, especially with COVID-19. However, a recent survey of the American Society for Surgery of the Hand membership (i.e. attendings/consultants) showed that only 17% were exposed to WALANT during residency or fellowship training. There is much interest in WALANT from trainees, but interpretation of the type and volume to be administered is highly varied. Methods: The aims of this study were (1) to survey a group of plastic surgery trainees in the UK about their knowledge of WALANT formulas, and (2) to compare trainee logbook records of WALANT procedures (if available) with published data from the UK. Results: All trainees were familiar with the 'standard' WALANT formula (1% lidocaine, 1:100,000 adrenaline ± 8.4% NaHCO3) described by Lalonde. However, because of local formularies, rather than 1:100,000 adrenaline, all used 1:200,000 adrenaline as it comes premixed in the UK. Other formulas used by UK trainees included 0.5% bupivacaine + 1:200,000 adrenaline, and mixing 1% lidocaine + 1:200,000 adrenaline with 1% lidocaine 1:1. In comparing available trainee WALANT records with published UK data, the average volume of WALANT used was 6.6 mls in the current study versus 12.9 mls for similar procedures (wound debridement and skin closure ± local flap, digital nerve repair, fingertip reconstruction, thenar injuries, phalangeal fracture and single digit extensor repair); specifically, for single digit flexor tendon repairs, this was 10 mls versus 16.3 mls. Conclusions: While the British Society for Surgery of the Hand (BSSH) have developed official guidance for the use of WALANT in the UK, it appears there remains much variation in interpretation and hence, application. Comparison of trainee logbook records of common hand surgery procedures suggests that most can be done with much less WALANT administered than previously reported, with safe and reproducible results. Level of Evidence: Level IV (Therapeutic).

Glow-type luminol chemiluminescence based on a supramolecular enhancer of cyclodextrin

BackgroundChemiluminescence (CL) bioassay is one of the most advanced and used detection method in clinical diagnosis and biomedical research because of the advantages of low background, easy operation, and wide-field imaging without a light source or microscope. The luminol/hydrogen peroxide/horseradish peroxidase (luminol/H2O2/HRP) system is the most popular CL system, but its application in high-throughput imaging detection is challenged due to its low luminescence efficiency and flash-type emission which is difficult in ensuring the reproducibility and consistency of detection results. ResultsWe reported a glow-type CL system of luminol@CD/H2O2/HRP by using a supramolecular enhancer of cyclodextrin (CD). This luminol@CD/H2O2/HRP system exhibited a luminescence lifetime of 41 min for sensitive and accurate imaging analysis. The long-lasting CL emission was attributed to the formation of a 1:1 host–guest complex between luminol and CD, which could stabilize the emitter and effectively reduce nonradiative relaxation. The formation of luminol@CD complex was determined through NMR experiments and theoretical analysis. Under optimum conditions, the luminol@CD/H2O2/HRP system showed higher sensitivity and much better precision than classical luminol/H2O2/HRP system for imaging detection of HRP. Especially, this glow-type luminol@CD/H2O2/HRP system realized CL imaging of microwell arrays on microfluidic chips. In addition, the luminol@CD/H2O2/HRP system was successfully applied for point-of-care detection of 17β-estradiol based on a competitive mechanism of host–guest recognition. SignificanceAn efficient CL system is crucial for obtaining reproducible and consistent results for accurate detection. Our luminol@CD/H2O2/HRP system emitted strong and persistent luminescence, resulting in reliability and efficiency at both CL macroscopic and microscopic imaging detection. We expected the luminol@CD/H2O2/HRP CL system to be applied in various detection fields.

A framework for best practices in clinical outcome assessment (COA) concept mapping: a case study.

Mapping or matching the items in a clinical outcome assessment (COA) to concepts that define a condition is a common method for evaluating a COA's concept coverage. The purpose of this research was to address the lack of formal guidance for conducting this task by developing a framework for best practices in COA concept mapping and applying it to a case study. To develop the framework, we examined the literature and created a draft set of best practices which was then reviewed by experienced researchers through focus groups before being finalized. To conduct the case study, we extracted data from a systematic review of knee osteoarthritis (KO) symptoms and impacts and used the framework to map relevant concepts to items in the SF-36v2® Health Survey (SF-36v2). The framework guides researchers in defining the purpose of and data sources for the mapping, establishing guiding principles and decision-making thresholds, and conducting the mapping exercise. The results of the case study demonstrate the usefulness of the framework in identifying 27/36 items (75%) in the SF-36v2 that addressed concepts that define KO. This case study illustrates how the framework for best practices in COA concept mapping may be used, highlighting how establishing clear concept definitions and guiding principles and following a structured process throughout can help produce consistent, reliable, and reproducible results. The results from this rigorous approach can provide valuable evidence to support decisions about the appropriateness of a COA for the intended patient population.

Facile construction of binary metal oxide heterojunction with hexagonal boron nitride nanohybrid electrocatalyst for the detection of flutamide

BackgroundFlutamide (FU) is a potential anti-androgen drug significantly prescribed to all human beings. The high solubility and poor degradability of its metabolites can adversely affect the balance of the ecosystem. Therefore, developing an efficient and reliable technique to detect this pollutant is essential. Consequently, electrochemical sensors have been widely used for the monitoring of various real-world samples. MethodsHence, nickel-zinc oxide (NZO) with hexagonal boron nitride (h-BN) nanocomposite was prepared as a proficient electrocatalyst in FU detection. Several spectroscopic measurements were carried out to characterize the prepared materials. Our NZO/h-BN nanocomposite was utilized to modify the glassy carbon electrode (GCE) and its relative catalytic activity was scrutinized with impedance and various voltammetric techniques. Significant findingsBased on the results, our NZO/h-BN/GCE sensor exhibited high conductance, appreciable linear ranges, low detection limit (0.002 μM), optimal sensitivity (2.149 µA µM−1 cm−2), and high selectivity with good repeatability, and reproducibility results. Furthermore, the practical utility of the sensor was studied by monitoring FU in human and environmental samples. Based on the outcomes, our NZO/h-BN/GCE is a promising electrochemical platform for the detection of FU.

Fibrous PVDF membranes modified by anchored g-C3N4@GO composite with enhanced photocatalytic activity

Recently, the development of fibrous membranes for pollutant filtration from air or water has been a topic of great interest. However, these filters’ high and rapid fouling has limited their use. In response, we have prepared photocatalytic active membranes that harness the synergic effect between graphene oxide (GO) and graphitic carbon nitride (g-C3N4). Theresultingcomposite demonstrated the highest photocatalytic activity (kobs = 88 × 10−3 min−1). This g-C3N4@GO composite was then carefully deposited on/in an electrospun polyvinyl difluoride (PVDF) fibrous membrane. The reproducible results of the chemical bonding ofthecomposite to the PVDF matrix were evident during photocatalytic experiments after ten Rhodamine B (Rh B) photocatalytic degradation cycles. Importantly, the fiber structure analysis post-reaction did not reveal any fiber cracks or void formation defects, indicating the excellent chemical stability of the PVDF fibrous matrix. This research offers a promising, sustainable, eco-friendly, and efficient solution for removing pollutants from different environments, inspiring further exploration and development in this field.

Nasal Tip Deprojection in Rhinoplasty.

Rhinoplasty is one of the most commonly performed facial surgeries in the USA. There exist many major and minor nasal tip support structures that impact tip projection. Overprojection may result from anatomic factors or may occur iatrogenically during primary rhinoplasty. Achieving reliable, reproducible, and stable results is the aim of nasal tip deprojection rhinoplasty. This technique is designed to decrease nasal tip deprojection in patients with an overly projected nasal tip. A retrospective chart review of 2,003 rhinoplasty cases in the senior author's practice was conducted between July 2014 and June 2022. The inclusion criteria were cosmetic or functional rhinoplasty cases with nasal tip deprojection, with a minimum of 12 months of follow-up. Outcomes of interest included the rate of operative revisions and the rate of postoperative infection. 447 patients met the inclusion criteria. The mean age of our study group was 32.1 years old, with 409 females. 291 cases were primary rhinoplasties. Mean follow-up period was 22.4 months. Eight patients (1.8%) required empiric antibiotics postoperatively, with 17 patients (3.8%) requiring operative revision. Our case series demonstrates that combining resection of the medial crura with lateral crural steal and a columellar strut graft allows us to achieve considerable nasal tip deprojection. The comprehensive patient follow-up with a mean of 22.4 months further supports the reliability of our technique.

The Predictive Accuracy of Anogenital Distance and Genital Tubercle Angle for First-Trimester Fetal Sex Determination.

Early identification of fetal gender is crucial for managing gender-linked genetic disorders. This study aimed to evaluate the predictive performance of anogenital distance (AGD) and genital tubercle angle (GTA) for fetal sex determination during the first trimester. A multicenter retrospective cohort study was conducted on 312 fetal cases between 11 and 13 + 6 weeks of gestation from two tertiary hospitals. AGD and GTA measurements were taken from midsagittal plane images using ultrasound, with intra- and inter-reader reproducibility assessed. Binomial logistic regression and ROC curve analysis were employed to determine the diagnostic performance and optimal cutoff points. AGD had a mean of 7.16 mm in male fetuses and 4.42 mm in female fetuses, with a sensitivity of 88.8%, specificity of 94.4%, and an area under the ROC curve (AUC) of 0.931 (95% CI: 0.899-0.962) using 5.74 mm as a cutoff point. For GTA, the mean was 35.90 degrees in males and 21.57 degrees in females, with a sensitivity of 92%, specificity of 84.7%, and an AUC of 0.932 (95% CI: 0.904-0.961) using 28.32 degrees as a cutoff point. The reproducibility results were excellent for AGD (intra-operator ICC = 0.938, inter-operator ICC = 0.871) and moderate for GTA (intra-operator ICC = 0.895, inter-operator ICC = 0.695). The findings suggest that AGD and GTA are reliable markers for early fetal sex determination, with AGD showing higher reproducibility. The findings highlight the feasibility and accuracy of these non-invasive sonographic markers and their potential usefulness in guiding timely interventions and enhancing the management of gender-linked genetic conditions.

Performance of three multiplex real-time PCR assays for simultaneous detection of 12 infectious pathogens in mice affected with respiratory and digestive diseases.

Research quality can be improved with reliable and reproducible experimental results when animal experiments are conducted using laboratory animals with guaranteed microbiological and genetic quality through health monitoring. Therefore, health monitoring requires the rapid and accurate diagnosis of infectious diseases in laboratory animals. This study presents a performance evaluation of a commercially available multiplex real-time PCR (mRT-PCR) assay for the rapid detection of 12 infectious pathogens (Set 1: Sendai virus [SeV, formally murine respirovirus], Mycoplasma spp., Rodentibacter pneumotropicus, and Rodentibacter heylii; Set 2: Helicobacter spp., Murine norovirus [MNV], Murine hepatitis virus [MHV], and Salmonella spp.; Set 3: Staphylococcus aureus, Streptobacillus moniliformis, Corynebacterium kutscheri, and Pseudomonas aeruginosa). To evaluate the efficacy of the mRT-PCR assay, 102 clinical samples encompassing fecal and cecal specimens were analyzed. The resulting data were then compared with the findings from sequence analysis for validation. The assay's detection limit ranged from 1 to 100 copies per reaction. Specificity testing involving various viruses and bacteria indicated no cross-reactivity between strains. Additionally, the assay exhibited good reproducibility, with mean coefficients of variation for inter- and intra assay variation below 3%. The overall positive rate was 52.9% (n = 54), with the mRT-PCR assay findings matching sequence analysis results (κ = 1). MHV (n = 29, 28.4%) was the most prevalent pathogen, followed by Helicobacter spp. (n = 28, 27.5%), R. heylii (n = 18, 17.6%), Mycoplasma spp. (n = 14, 13.7%), MNV (n = 12, 11.8%), S. aureus (n = 9, 8.8%), P. aeruginosa (n = 4, 3.9%), and R. pneumotropicus (n = 1, 0.9%). This assay offers a rapid turnaround time of 100 min, including 30 min for DNA preparation and 70 min for target DNA/RNA amplification. It ensures accuracy, minimizing false positives or negatives, making it a convenient tool for the simultaneous detection of infectious diseases in many samples. Overall, the propose‑d assay holds promise for the effective detection of the most important pathogens in laboratory animal health monitoring.

Automated Optimization of the Synthesis of Alkyl Arenesulfonates in an Undivided Electrochemical Flow Cell

AbstractThe necessary separation of anodic and cathodic compartments in the electrochemical multicomponent synthesis of alkyl arenesulfonates in batch was overcome by the transfer of this reaction in an undivided electrochemical flow cell. The yield was increased from an initial 23 % to 67 % by optimization using Design of Experiments (DoE). The experiments were carried out using an automated experimental flow electrolysis setup controlled by the automation software LABS (Laboratory Automation and Batch Scheduling), an open‐source software that allows to plan and conduct experiments with an arbitrary, freely selectable experimental setup. The automated experimental setup turned out to be stable and provides reproducible results. In total, 6 examples are demonstrated with isolated yields up to 81 %. In addition, the robust scalability of the electrochemical reaction was demonstrated in a 10‐fold scale‐up.

Separation of microplastics from deep-sea sediment using an affordable, simple to use, and easily accessible density separation device

Microplastics accumulate in the environment but methods to extract particles from sediment for quantification and identification often lack accuracy and reproducibility. Existing methods vary greatly and many do not achieve adequate microplastic separation. During method development for extraction procedures, spike-recovery experiments (positive controls) are essential to ensure accurate and reproducible results from each sample matrix. Furthermore, the large variability in grain size and organic matter can affect the extraction of microplastics from the matrix. Scientists have used density separation to separate microplastics from matrices for decades, but apparatuses are often made of plastic, need to be custom made, and require multiple sample transfers from one apparatus to another. This study presents an affordable, easily accessible, and simple to use Density Separation Device (DSD) to remove plastics from deep-sea sediments. Eight polymers were spiked into replicates of environmental sediment, including six fragments: high density polyethylene (HDPE), polypropylene (PP), polyvinyl chloride (PVC), polystyrene (PS), nylon (PA6), and crumb rubber (CR) and two fibers: cellulose acetate (CA) and polyester (PEST). Two size classes of polymers were used: 100 μm to 300 μm and > 300 μm. Using a sodium polytungstate solution at a density of 1.9 g/mL and reflectance FTIR microscopy for particle identification, mean recoveries of all fragments exceeded 78% (CR: 92.7% ± 30.8%, PP: 78.4% ± 34.0%, HDPE: 93.8% ± 13.5%, PS: 86.9% ± 25.7%, PA6: 98.4% ± 63.2%, PVC: 100.0% ± 12.4%). Fiber recovery was much lower (PEST: 28.1% ± 28.1% and CA: 25.9% ± 17.3%) because they aggregated, passed through sieves vertically, or were obscured under other particles. The fragment recovery success, accessibility (available online, all parts under $200) and ease of use of this DSD should facilitate widespread use, thus helping to standardize sample preparation methods for microplastic metrology.

Tuning Ceramic Surface to Minimize the Ionic Resistance at the Interface between PEO- and LATP-Based Ceramic Electrolyte.

New battery technologies are currently under development, and among them, all-solid-state batteries should deliver better electrochemical performance and enhanced safety. Composite solid electrolytes, combining a solid polymer electrolyte (SPE) and a ceramic electrolyte (CE), should then provide high ionic conductivity coupled to high mechanical stability. To date, this synergy has not yet been reached due to the complexity of the Li-ion transport within the hybrid solid electrolyte, especially at the SPE/CE interface currently considered the limiting step. Yet, there is no proper kinetic model to elucidate the parameters influencing this interfacial barrier. The limited understanding of the SPE/CE interface can be partly explained by scattered SPE/CE interface resistances reported in the literature as well as the lack of systematic studies. Herein, we propose a systematic study of the effect on the SPE/CE interfacial resistance of chemical and thermal treatments of a model LATP-based ceramic based on a methodology relying on electrochemical impedance spectroscopy (EIS) and X-ray photoemission spectroscopy (XPS). The results provide different levers for the optimization of this interface and valuable insights into experimental precautions needed to obtain more reproducible results.

Compositional Analysis of Cutin in Maize Leaves.

The cuticle is a lipid barrier that covers the air-exposed surfaces of plants. It consists of waxes and cutin, a cell wall-attached lipid polyester of oxygenated fatty acids and glycerol. Unlike waxes, cutin is insoluble in organic solvents, and its composition is typically studied by chemical depolymerization followed by monomer analysis by gas chromatography (GC). Here, we describe a method for the chemical depolymerization of cutin in maize leaves and subsequent compositional analysis of the constituent lipid monomers. The method has been adapted from protocols for cutin analysis developed for Arabidopsis, by both optimizing the amount of leaf tissue used and including a data analysis process specific to the monomers present in maize cutin. The approach uses base-catalyzed transmethylation, which produces fatty acid methyl esters, and silylation, which gives trimethylsilyl ether derivatives of hydroxyl groups for gas chromatographic analysis. For monomer identification, a few representative samples are first analyzed by GC-mass spectrometry (GC-MS). This is then followed by analysis of all replicates by gas chromatography coupled to a flame ionization detector (GC-FID) for monomer quantification, because the flame ionization detector provides a linear response over a wide mass range, is relatively simple to operate, and is more cost-effective to maintain compared to mass spectrometry detectors. Although the protocol bypasses time-consuming cuticle isolation steps by using whole-leaf samples, this means that a fraction of the compounds in the chromatographic profiles do not derive from cutin. Accordingly, we discuss some considerations for the interpretation of the resulting depolymerization products. Our protocol offers specific guidance on preparing maize leaf samples, ensuring reproducible results, and enabling the detection of subtle variations in cutin monomer composition among plant genotypes or developmental stages.

Precision medicine-based platform to guide the treatment of EML4-ALK driven lung cancers and other NSCLC in real time.

215 Background: Lung cancer (LC) is the top cause of cancer-associated mortality worldwide, with a 10-year overall survival rate of 5%. Although most LCs are smoking related, in the US, 25% of non-small cell LC (NSCLC) are diagnosed in persons with little or no smoking history. Fusions involving anaplastic lymphoma kinase (ALK) are the oncogenic driver in ~3–7% of NSCLC. While inhibitors targeting the kinase domain of ALK (TKIs) have proven extremely effective, inevitably, resistance develops with limited treatment options beyond second line TKIs. Additionally, NSCLCs without identified molecular alterations have even more limited tumor specific treatment options. Methods: We developed a precision medicine-based platform (PMP) to screen patient-derived, minimally cultured, organoid material (PDM) directly from resections with curated panels of drugs. PDM collected during clinically indicated procedures is plated in 3D-culture to generate patient-derived organoids (PDOs) and screened with drugs tailored to each tumor type. PDOs are screened at therapeutically relevant doses, drawing from pharmacokinetic data for each drug. We have optimized an assay to rapidly screen for EML4-ALK fusions and can perform next-generation sequencing in real time (~7 days) to integrate with drug screening results. Our organoid cultures retain the full spectrum of tumor microenvironment present in the original sample. Results: To date, we have analyzed 83 cases, including 8 EML4-ALK NSCLC. We have demonstrated the ability to produce high quality data from low input samples (biopsies). In one EML4-ALK NSCLC we were able to collect PDM from two distinct anatomic spaces (pleural effusion and peritoneal fluid) and screen with the same panel of drugs, with nearly identical results, highlighting the reproducibility and consistency of our assay. Screening of EML4-ALK tumors which have progressed to second or higher line TKIs, demonstrate sensitivity to earlier generation ALK TKIs, a known phenomenon. Characterization of tumors with unknown clinical drivers identifies that ~1/3 tumors which have no actionable or hypothetically prioritized variants, and they exhibit particularly poor response to chemotherapies. Our results recapitulate known resistance/progression in samples previously exposed to therapy, demonstrating a strong negative predictive value. Longitudinal assessment is being tracked to robustly assess positive predictive value (PPV). Conclusions: Our PMP captures robust and reproducible results that are consistent with known clinical pathogenesis. Moving forward, we are collecting longitudinal data from enrolled patients in parallel with clinical trials to demonstrate the PPV of our PMP. We additionally strive to demonstrate reproducibility to obtain Clinical Laboratory Improvement Amendments approval and to deliver results to patients and physicians to help guide clinical care.

On the Use of Pad Mechanical Properties as a Proxy for Conditioning Response

A proliferation of pad materials in recent years, coupled with the increasing complexity of process integration and limited resources available for process development, has highlighted the need for a more in depth understanding of conditioning interactions and better predictive tools for process and consumable design. We have previously noted a range of conditioning response as illustrated in Figure 1. As the figure illustrates, on some materials the surface height distribution imparted by the pad conditioner is shifted to the left relative to the exponential signature of the pad native porosity which is used as a reference. Denoted regime 1, these surfaces are characterized by the prevalence of “eyelid” features which obscure the line-of-sight path to the bottoms of the pores. In regime 2, the surface height distribution is more balanced, with a smooth transition between the exponential porosity signature and the conditioning signature. In regime 3, there is an abrupt disconnect between the exponential porosity signature and the conditioner signature. Such surfaces are characterized by deep gouges.We are investigating pad material tensile properties as a proxy to help understand and predict these conditioning responses. Figure 2 illustrates the range of typical tensile behavior for polymers. While Figure 2 invokes temperature as the variable that drives these behaviors, note that strain rate can also drive tensile behavior across this range with high temperature being analogous to low strain rate and vice versa.Figure 3 and Table 1 summarize some results from our testing of IC1000, VP5000, VP6000, IK4250H and IK4350L. We have determined that grooved pad materials at their nominal dimensions are adequate for testing according to ASTM D638: Standard Test Method for Tensile Properties of Plastics. Typical delivered pad thickness is within the specifications for sample thickness, and as long as the grooves are oriented to be substantially parallel with the strain axis (pulling direction) reproducible results can be obtained. A range of properties spanning at least about 2x is observed in these pads.Figure 4 gives one example of how this information can be directly applied. The figure illustrates a manifestation of the threshold behavior that is typically observed when conditioning with a pad conditioner with uniform tip height, where all the cutting points are controlled within a height range of about 10 µm. As opposed to a conventional conditioning platform, where there is a much wider range of tip heights, the uniform height-controlled conditioner exhibits a threshold behavior where no measurable cutting occurs below a limiting condition down-force (cdf). Figure 4 illustrates the disconnect between a high down-force, accelerated cutting test, using 14 lbs cdf and designed to return the “CR” value for a conditioner, and typical process cdf levels, in the range of 5 lbs cdf. Note that CR values are generally about an order of magnitude higher than comparable polishing tool level pad wear rates. Whereas conventional platforms yield a linear response between CR and tool level pad wear rates, the uniform height design exhibits an offset, such that at low CR levels, low pad wear rates are observed. The position of this threshold is a function of pad type. These data suggest that this threshold can be correlated with the mechanical strength of the pad material, as determined by the tensile test results.We have also explored the effect of strain rate on tensile response. Strain rates in a typical CMP process may be as high as 105 s-1, and as shown in Figure 2, strain rate can have a significant effect on material behavior. Figure 5 illustrates typical results, illustrating the extremes of response for this group of pads, and Figure 6 shows the normalized response of offset yield and tensile strength as a function of strain rate. Of these materials, only IK4350L exhibits a divergent response, and as shown in Figure 7, IK4350L typically exhibits the most abrupt transition between the exponential porosity signature and the conditioner cutting signature, indicating a tendency towards the gross over-conditioning behavior characteristic of regime 3.Over the range of strain rates explored here, all of these materials can be characterized as “rubbery”. This rubbery behavior can be understood in the context of reported property measurements of CMP pads, which indicate distinct glass transitions related to the soft and hard phases of the polyurethane from which the pad is made. This analysis suggests that pad behavior is dominated by the “rubbery plateau” of the soft segment of the polymer, with the glass transition of the hard segment occurring above typical polishing temperatures. Figure 1

Bringing GDE Half-Cell and MEA Single Cell Testing Closer Together

In the context of the energy transition, the fuel cell represents a key technology. On the way to higher performance and efficiency, the development and testing of catalysts for the oxygen reduction reaction (ORR) is crucial [1]. Over the past years, the gas diffusion electrode (GDE) half-cell setup has been introduced as a bridging tool between RDE half-cell testing and MEA single cell testing for catalyst characterization [2,3]. Compared to the MEA testing, the GDE proved to be pronounced faster and cheaper, while still reaching relevant current densities (3 A cm-2) other than RDE setups. In recent studies the potential and reliability of this technique has been proven. It was shown, that the GDE can correctly predict trends of catalytic activity in the MEA until the mass transport limitation in the MEA appears. Furthermore, the mass transport influence of ionic liquid modifications of the catalyst layer could also be deduced in the GDE half-cell, without the tedious ink development needed for MEA preparation [4]. Proton transport is not limited in the GDE half-cell, if the catalyst layer is directly immersed within the liquid electrolyte. Depending on if the intrinsic activity of the catalyst or the proton resistance wants to be studied this is an advantage or disadvantage. This opens the question, whether proton mass transport resistance can also be studied in the GDE setup, when separating the catalyst layer from the liquid electrolyte through a membrane. Adding a membrane will change the mass transport of the system by two aspects: First, the protons must be transported through the membrane to reach the catalyst layer and second, the formed water during the reaction can no longer be flushed away from the liquid electrolyte but must leave through the gas diffusion layer (GDL). Developing such a manufacturing procedure and measurement protocol to gain valid, reproducible, and reliable results is scope of this study.In the first step the membrane (Nafion™ NR211) was spray coated via an ultra-sonic spray coater with a commercial Pt/C catalyst (HiSPEC®3000, 20 wt% Pt). Afterwards the catalyst coated membrane (CCM) was hot-pressed to the GDL (Toray™ TP-090-T5). Different pressing times and pressures were examined. The resulting electrode was characterized using a commercial GDE half-cell (Flexcell® PTFE, Gaskatel GmbH) and the measurement protocol according to Schmitt et al. [5].On the way towards the final manufacturing procedure many challenges have been overcome. The biggest was how to deal with membrane swelling and detachment when measuring at high current densities where large quantities of water are produced. To cope this issue a GDL without a microporous layer was chosen to support the water transport. Furthermore, the application of a membrane in a GDE half-cell brings up - yet unsolved – challenges, when using impedance spectroscopy for iR-correction.With our final manufacturing procedure and measurement protocol additional mass transport resistances and limitations can be captured in the ohmic region and at high current densities in the GDE half-cell-setup.In summary we showed a working proof of concept for the membrane application in GDE half-cell setups, which give comparable results to actual MEA measurements and remaining the advantages of GDE testing.Literature:[1] Banhamet al. ACS Energy Lett. 2017, 2, 629. [2] Ehelebe et al. ACS Energy Lett. 2022, 7, 816. [3] Schmitt et al. Journal of Power Sources 2022, 539, 231530. [4] Schmitt et al. Energy Adv. 2023, 2, 854. [5] Schmitt et al. Electrochemistry Communications 2022, 141, 107362.

Swift and precise detection of unlabeled pathogens using a nanogap electrode impedimetric sensor facilitated by electrokinetics

For the protection of human health and environment, there is a growing demand for high-performance, user-friendly biosensors for the prompt detection of pathogenic bacteria in samples containing various substances. We present a nanogap electrode-based purely electrical impedimetric sensor that utilizes the dielectrophoresis (DEP) mechanism. Our nanogap sensor can directly and sensitively detect pathogens present at concentrations as low as 1–10 cells/assay in buffers and drinking milk without the need for separation, purification, or specific ligand binding. This is achieved by minimizing the electrical double-layer effect and electrode polarization in nanogap impedance sensors, reducing signal loss. In addition, even at low DEP voltages, nanogap sensors can quickly establish strong DEP forces between the nanogap electrodes to control the spatial concentration of pathogens around the electrodes. This activates and stabilizes inter-electrode signal transmission along the nanogap-aligned pathogens, increasing sensitivity and reducing errors during repeated measurements. The DEP-enabled nanogap impedance sensor developed in this study is valuable for a variety of pathogen detection and monitoring systems including point-of-care testing (POCT) as it can detect pathogens in diverse samples containing multiple substances quickly and with high sensitivity, is compatible with complex solutions such as food and beverages, and provides highly reproducible results without the need for separate binding and separation processes.

The Microscope and Beyond: Current Trends in the Characterization of Kidney Allograft Rejection From Tissue Samples.

The Banff classification is regularly updated to integrate recent advances in the characterization of kidney allograft rejection, gathering novel diagnostic, prognostic, and theragnostic data into a diagnostic and pathogenesis-based framework. Despite ongoing research on noninvasive biomarkers of kidney rejection, the Banff classification remains, to date, biopsy-centered, primarily relying on a semiquantitative histological scoring system that overall lacks reproducibility and granularity. Besides, the ability of histopathological injuries and transcriptomics analyses from bulk tissue to accurately infer the pathogenesis of rejection is questioned. This review discusses findings from past, current, and emerging innovative tools that have the potential to enhance the characterization of allograft rejection from tissue samples. First, the digitalization of pathological workflows and the rise of deep learning should yield more reproducible and quantitative results from routine slides. Additionally, novel histomorphometric features of kidney rejection could be discovered with an overall genuine clinical implementation perspective. Second, multiplex immunohistochemistry enables in-depth in situ phenotyping of cells from formalin-fixed samples, which can decipher the heterogeneity of the immune infiltrate during kidney allograft rejection. Third, transcriptomics from bulk tissue is gradually integrated into the Banff classification, and its specific context of use is currently under extensive consideration. Finally, single-cell transcriptomics and spatial transcriptomics from formalin-fixed and paraffin-embedded samples are emerging techniques capable of producing up to genome-wide data with unprecedented precision levels. Combining all these approaches gives us hope for novel advances that will address the current blind spots of the Banff system.

Psychometric properties of the French Infant-Toddler Working Alliance Inventory Short version (IT-WAI-S)

Objective Therapeutic alliance has been little investigated in infant and toddler therapy, with no tools specifically adapted to this population. However, we have developed the Infant-Toddler Working Alliance Inventory-Short form (IT-WAI-S) which is based on the Working Alliance Inventory. The aim of this study was to assess the psychometric properties of this original French tool, in its two versions: for parent (IT-WAI-SP) and for therapist (IT-WAI-STh). Method This study included 227 families consulting with their 18–48-month-old child for emotional or behavioral disorders. The scales were filled in at the first three therapy sessions. The IT-WAI-S acceptability, internal validity, reliability and predictive validity (association with child and mother’s outcomes) were evaluated. Results Confirmatory then exploratory factor analyses revealed a three-factor structure for the both scales: Negative Experience of Care Relationship, Positive Alliance and Alliance with the Child. Acceptability, reproducibility and construct validity were satisfactory for both versions. The two versions predicted the child's outcome. The IT-WAI-SP predicted also the mother’s outcome. The IT-WAI-STh gave more reproducible results, whereas the IT-WAI-SP was a better predictor of the child's progress. Conclusion The two IT-WAI-S versions showed good psychometric properties and could be used to study the therapeutic alliance in young children.

A Highly Standardized Pre-Clinical Porcine Wound Healing Model Powered by Semi-Automated Histological Analysis.

The wound-healing process is a physiological response that begins after a disruption to the integrity of tissues present in the skin. To understand the intricacies involved in this process, many groups have tried to develop different in vitro models; however, the lack of a systemic response has, until this day, been the major barrier to the establishment of these models as the main study platform. Therefore, in vivo models are still the most common system for studying healing responses following different treatments, especially porcine models, which share several morphological similarities to the human skin. In this work, we developed a porcine excisional wound model and used semi-automated software as a strategy to generate quantitative morphometric results of healing responses by specific tissues and compartments. Our aim was to extract the most information from the model while producing reliable, reproducible, and standardized results. In order to achieve this, we established a 7-day treatment using a bacterial cellulose dressing as our standard for all the analyzed wounds. The thickness of the residual dermis under the wound (DUtW) bed was shown to influence the healing outcome, especially for the regeneration of epidermal tissue, including the wound closure rate. The analysis of the DUtW throughout the entire dorsal region of the animals opened up the possibility of establishing a map that will facilitate the experimental design of future works, increasing their standardization and reproducibility and ultimately reducing the number of animals needed. Thus, the developed model, together with the automated morphometric analysis approach used, offers the possibility to generate robust quantitative results with a rapid turnaround time while allowing the study of multiple extra morphometric parameters, creating a more holistic analysis.