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Grass carp (Ctenopharyngodon idella) was exposed to nanoparticles of different concentrations, i.e., copper oxide nanoparticles (CuO-NPs), silver nanoparticles (Ag-NPs), and green synthetic gold nanoparticles (Au-NPs).The administered doses of the three concentration groups were 20mg L−1, 30 mg L−1, and 40mg L−1 each for a period of 14 and 28 days, respectively. The DNA damage in the erythrocytes of grass carp was detected through a comet assay technique. The values of total comet score (TCS) were noted for the exposed concentrations with a significant increasing trend (p < 0.05) and ordered as CuO-NPs > Ag-NPs > Au-NPs. The highest TCS value of the exposed erythrocytes was recorded for CuO-NPs at 40 mg L−1 after 14 days of exposition period. Comparatively, TCS values of erythrocytes exposed to green synthetic Au-NPs at all the concentrations and exposed time were less as compared to the Ag-NPs and CuO-NPs. The study confirmed the adverse effects of nanoparticles on the genetic material of fish cells. [ABSTRACT FROM AUTHOR]

Purpose: Products formulated for intramammary (IMM) infusion are intended for the delivery of therapeutic moieties directly into the udder through the teat canal to maximize drug exposure at the targeted clinical site, the mammary gland, with little to no systemic drug exposure. Currently, to our knowledge, there has been no in-vitro matrix system available to differentiate between IMM formulations. Our goal is to develop A custom tailored in-vitro "Matrix of Chemistry, Manufacturing and Control" (MoCMC) System to be a promising future tool for identifying inequivalent IMM formulations. MoCMC can detect inter and intra batch variabilities, thereby identifying potential generics versus brand product similarities or differences with a single numeric value and a specific & distinctive fingerprint. Methods: The FDA-approved IMM formulation, SPECTRAMASTⓇ LC, was selected as the reference product for the MoCMC. Twelve in-house test formulations containing ceftiofur hydrochloride were formulated and characterized. The MoCMC was developed to include six input parameters and three output parameters. The MoCMC system was used to evaluate and compare SPECTRAMASTⓇ LC with its in-house formulations. Results: Based on the MoCMC generated parameters, the distinctive fingerprints of MoCMC for each IMM formulations, and the statistical analyses of MCI and PPI values, in-house formulations, F-01 and F-02 showed consistency while the rest of in-house formulations (F-03-F-12) were significantly different as compared to SPECTRAMASTⓇ LC. Conclusion: This research showed that the MoCMC approach can be used as a tool for intra batch variabilities, generics versus brand products comparisons, post-approval formulations changes, manufacturing changes, and formulation variabilities. [ABSTRACT FROM AUTHOR]

Emergency Resuscitative Thoracotomy (ERT) is a lifesaving procedure in selected patients. Outcome mostly in blunt trauma is believed to be poor. The primary aim of this study was to determine the predictors of postoperative mortality following ERT. We retrospectively reviewed 34 patients ≥ 18 years who underwent ERT at San Camillo—Forlanini Hospital (Rome, Italy) between January 2009 and December 2022 with traumatic arrest for blunt or penetrating injuries. Of 34 ERT, 28 (82.4%) were for blunt trauma and 6 (17.6%) were for penetrating trauma. Injury Severity Score (p-value 0.014), positive E-FAST (p-value 0.023), Systolic Blood Pressure (p-value 0.001), lactate arterial blood (p-value 0.012), pH arterial blood (p-value 0.007), and bicarbonate arterial blood (p-value < 0.001) were significantly associated with postoperative mortality in a univariate model. After adjustment, the only independent predictor of postoperative mortality was Injury Severity Score (p-value 0.048). Our experience suggests that ERT is a technique that should be utilized for patients with critical penetrating injuries and blunt trauma in patients in extremis. Our study highlights as negative prognostic factors high values of ISS and lactate arterial blood, a positive E-FAST, and low values of Systolic Blood Pressure, pH arterial blood and bicarbonate arterial blood. [ABSTRACT FROM AUTHOR]

The aim of this paper was to investigate the effects of formulation parameters on the physicochemical and pharmacokinetic (PK) behavior of amorphous printlets of lopinavir (LPV) manufactured by selective laser sintering 3D printing method (SLS). The formulation variables investigated were disintegrants (magnesium aluminum silicate at 5–10%, microcrystalline cellulose at 10–20%) and the polymer (Kollicoat® IR at 42–57%), while keeping printing parameters constant. Differential scanning calorimetry, X-ray powder diffraction, and Fourier-transform infrared analysis confirmed the transformation of the crystalline drug into an amorphous form. A direct correlation was found between the disintegrant concentration and dissolution. The dissolved drug ranged from 71.1 ± 5.7% to 99.3 ± 2.7% within 120 min. A comparative PK study in rabbits showed significant differences in the rate and extent of absorption between printlets and compressed tablets. The values for Tmax, Cmax, and AUC were 4 times faster, and 2.5 and 1.7 times higher in the printlets compared to the compressed tablets, respectively. In conclusion, the SLS printing method can be used to create an amorphous delivery system through a single continuous process. [ABSTRACT FROM AUTHOR]

Between February 2020 and January 2022, the Food and Drug Administration (FDA) recalled 281 metformin extended-release products due to the presence of N-nitrosodimethylamine (NDMA) above the acceptable daily intake (ADI, 96 ng/day). Our previous studies indicated presence of NDMA levels above ADI in both metformin immediate and extended-release products. When metformin products have NDMA impurities, it is indispensable to check for the same impurities in metformin combination products. Therefore, the objective of the present study was to evaluate in-use stability of commercial metformin combination products for NDMA. For this purpose, metformin products in combination with glyburide (GB1-GB12), glipizide (GP1-GP8), pioglitazone (P1-P3), alogliptin (A1, A2), and linagliptin (L1, L2) were repacked in pharmacy vials, stored at 30°C/75% RH for 3 months, and monitored for NDMA impurity. The NDMA level varied from 0 to 156.8 ± 32.8 ng/tablet initially and increased to 25.4 ± 5.1 to 455.0 ± 28.4 ng/tablet after 3 months of exposure to in-use condition. Initially, 18 products have NDMA level below ADI limit before exposure which decreased to 7 products (GB5, GP3, GP5, A1, A2, L1, and L2) meeting specification. In conclusion, in-use stability study provides quality and safety risk assessment of drug products where nitroso impurities are detected in the probable condition of use. [ABSTRACT FROM AUTHOR]

Purpose: Intramammary (IMM) formulations are locally acting and delivered intracisternally into the udder. No pharmacopeial in-vitro release method is available to differentiate between the IMM formulations. Our research aim is to develop in-vitro release methods that discriminate different IMM formulations (SPECTRAMAST® LC and in-house formulations). Methodology: Different in-house formulations were developed to simulate SPECTRAMAST® LC generics. SPECTRAMAST® LC and the in-house formulations were characterized for physicochemical attributes, such as particle size, rheology, drug content, sedimentation rate, and flocculation rate. The in-vitro release method was optimized by evaluating drug release using USP apparatuses 1, 2 (with and without enhancer/customized cells), and 4. Various test parameters, including medium effect (whole homogenized bovine milk versus aqueous buffer), medium volume (200–900 mL), and rotational speed (50–200 rpm) were investigated. Results: Two potential in-vitro systems can be used as discriminatory methods for IMM formulations: USP apparatus 2 with the IMM formulation loaded into two containers a) customized formulation container (83.1 cm in height and 56.4 cm in width) or b) enhancer cells with their top adapted with mesh #40 (rotation speed:125 rpm and 900 mL of whole homogenized bovine milk). The release profile of SPECTRAMAST® LC at 1 h (99.8%) was not significantly different from formulations with similar physicochemical characteristics F-01 (99.1%) and F-02 (100.5%). Formulation with different physicochemical characteristics F-03 (44.3%) and F-04 (57.2%) showed slower release (1 h) than SPECTRAMAST® LC (98.8%). Conclusion: The developed in-vitro release methods can be used as a potential tool for in-vitro comparability evaluations for IMM formulations. [ABSTRACT FROM AUTHOR]

This work investigates substrate leakage in Capacitive Micromachined Ultrasonic Transducers, (CMUTs) having thin backings. CMUTs produced with solid or rigid substrates have a high Q resonance with flat baseline. However, if the operating wavelength of CMUT becomes larger than the thickness of substrate the real part of cell impedance shows elevated baselines with more leakage at DC than at higher frequencies. When a clamped CMUT membrane is excited harmonically the vibrations produced are counterbalanced by the backing medium. Hence some of the energy is coupled to substrate as loss resulting in a lower mechanical Q of resonance. We first derive this energy coupled to the backing medium using FEA analysis considering the velocity field and associated tensile stresses in a thin backing. Substrate impedance is found numerically from isotropic damping of dispersive elastic waves in the backing. This backing impedance is introduced as a shunt mechanical loss across the transduction force in equivalent circuit model. We characterize the measured impedance of CMUT cells with both FEMs and linear circuit models. Simulations results closely agree with the measured impedance levels, frequency and bandwidth of resonance. [ABSTRACT FROM AUTHOR]

This study is focused on the design of a spectrophotometric technique for the liquid–liquid microextraction (Ss-LLME) of aluminum from water and hair samples to use a supramolecular solvent. Al (III)-curcumin complex was quantitatively isolated and preconcentrated using supramolecular solvent liquid–liquid microextraction at pH 6.0. The measured molar absorptivity for the compound was 9.28 × 104 L mol−1 cm−1 at 430 nm. Beers law was applicable in the concentration range of 0.1–12.0 µg mL−1. Extraction efficiency influencing factors like solution pH (6.0), mass of chelating agent (0.1 mg), sample volume (20 mL), type and volume of supramolecular solvent (decanol, 0.1 mL), the volume of THF (0.2 mL) and matrix effect was optimized. Parameters of merit like a limit of detection (0.056 mg L−1) and limit of quantification (0.189 mg L−1), preconcentration factors (50), enrichment factor (50), and determined relative standard deviations. The new method's precision was determined by analyzing verified reference materials TMDA-64.3 fortified water and NCS ZC81002B human hair. The procedure was applied to determination of aluminum contents of hair and water samples. [ABSTRACT FROM AUTHOR]

Water contamination is increasing globally by heavy metals, dyes, and cyanides day by day. Heavy metals are very toxic even if present in a small amount in water. Here, we have synthesized a novel type of self-healable, ultra-thin with high mechanical strength, and pH-responsive poly-(acrylic acid)@Fe/Ni (PAA@Fe/Ni) hybrid hydrogel membrane using filter paper as a substrate. Acrylic acid was polymerized on the surface and in pores of the filter paper by free radical addition polymerization reaction using NMBA as a cross-linker, iron ions as an accelerant, and persulfate radicals as initiator. The iron ions were subsequently converted to metal particles by coating with nickel particles to enhance their stability and act as an antifouling agent. The membrane was characterized by FTIR, SEM, EDX, and AFM techniques. The abundant carboxylic acid (–COOH) groups and iron ions present inside the polymer network provide self-healing ability to the membrane. The pore size of the filter paper was reduced from 2.5 to 1.04 μm and thus improving the rejection capability of the membrane. The results demonstrated that the membrane is efficient enough for the complete rejection of Cr(VI) from model water and industrial wastewater under different environmental stimuli (pH and concentration) up to 100 ppm. The self-healing behavior, ultra-thin with high mechanical stability, and responsive nature of the PAA@Fe/Ni hybrid hydrogel membrane are the significantly advanced features of the synthesized membrane. [ABSTRACT FROM AUTHOR]

The aim of this work was to design pediatric-friendly, dose-flexible orally disintegrating drug delivery systems (printlets) of the antiviral drug tenofovir disoproxil fumarate (TDF) by selective laser sintering (SLS) for potential use in hospitals along with other antiviral drugs. In order to obtain a consistent quality of printlets with desired properties, it is important to understand certain critical quality attributes for their main and interactions effect. The printlets were optimized by Box-Behnken’s design of the experiment by varying process variables while keeping the composition constant. The composition contained 16.3% TDF, 72.7% polyvinyl pyrrolidone K16-18, 8% magnesium aluminum silicate, 3% Candurin® NXT Ruby Red, and 0.3% colloidal silicon dioxide. The process variables studied were surface (X1), chamber temperatures (X2), and laser scanning speed (X3). The range of variable levels was 75–85°C for X1, 50–70°C for X2, and 200–240 mm/s for X3, respectively. The responses studied were hardness, disintegration time, dissolution, physiochemical, and pharmacokinetic characterization. X-ray powder diffraction indicated partial or complete conversion of the crystalline drug into amorphous form in the printlets. Comparative pharmacokinetics between Viread® (generic) and printlets in rats were superimposable. Pharmacokinetic parameters showed statistically insignificant differences between the two formulations in terms of Tmax, Cmax, and AUC of (p > 0.05). Printlets were bioequivalent to Viread® as per FDA bioequivalence criteria. Thus, the SLS printing method showed the fabrication of dose-flexible printlets with quality, and in vivo performance equivalent to commercial tablets. [ABSTRACT FROM AUTHOR]

Heavy metal-based pollutants are one of the most alarming health hazards causing multiple diseases including cancer, hepatotoxicity, brain hemorrhage, kidney and heart failures, etc. In this study, we report an ecofriendly, low cost, and simple synthesis of silver nanoparticles (AgNPs) mediated by Nannorrhops ritchiana leaf-based biomolecular extract as a key biosensor for the mercury(II) heavy metal. The formation of AgNPs was confirmed by using different characterization techniques including UV–visible spectroscopy, energy-dispersive X-ray analysis, Fourier transform infrared spectroscopy, and scanning electron microscopy. The synthesized AgNPs are yellowish-brown and exhibit the surface plasmon resonance around 435 nm. The various functional groups responsible for reduction of Ag+ to Ag0 and capping agents present in the leaf extract were confirmed by infrared spectroscopy. Energy-dispersive X-ray and scanning electron microscopic analysis were used to confirm the presence of silver and surface morphology of the nanoparticles, respectively. X-ray diffraction data suggested crystalline nature of the prepared nanoparticles. The AgNPs were successfully applied as a sensitive and selective platform for sensing of mercury(II) ions. Various parameters including nanoparticles loading, concentration of Hg+2, pH, and reaction time were optimized. The platform demonstrates a low limit of detection (4.8 × 10–7 M) and limit of quantification (4.8 × 10–7 M) with an R2 value of 0.999. The SS-DNA interaction with the AgNPs, studied by UV–Vis spectroscopy revealed intercalative mode of binding with a binding constant of 1.04 × 104 units. Importantly, this AgNPs platform also demonstrated good antibacterial efficacy against Proteus mirabilis, Shigella flexneria, Escherichia coli, and Staphylococcus aureus. [ABSTRACT FROM AUTHOR]

Hydrogen peroxide (H2O2) is a by-product of oxidase-catalyzed reactions that serves as a signaling molecule and can cause DNA and protein damage. This leads to an increase in our susceptibility toward various kinds of diseases including diabetes mellitus and hypertension, The novelty of this work lies in the synergistic effect of all three components of the Ag-Fe2O3-IL composite for the colorimetric detection of H2O2. Silver-doped iron oxide nanostructures (Ag-Fe2O3 NS) were synthesized and then coated with ionic liquid (IL) having peculiar characteristics of aromaticity and conductivity to enhance their properties. The prepared Ag-Fe2O3 nanoparticles were characterized through spectroscopic techniques namely FTIR, XRD, SEM and EDX. The characterized Ag-Fe2O3 NS and 3, 3', 5, 5' Tetramethylbenzidine (TMB) solutions were employed for the colorimetric sensing of H2O2. To optimize the proposed sensor different reaction conditions including (a) amount of Ag-Fe2O3NS/IL (b) TMB, (c) pH, (d) H2O2 concentration and (e) incubation time were optimized. At optimum conditions, the desired sensor showed a wide linear range 1 × 10−9–3.2 × 10−7 M, a lower limit of quantification 3.20 × 10−7 M, and a limit of detection 1.07 × 10−8 M with a 0.9996 R2 value. The selectivity of the proposed sensor was compared with the potential interfering species and the incubation time was just 5 min. Additionally, the sensor was effectively applied for detecting hydrogen peroxide in the urine samples of diabetes mellitus patients. [ABSTRACT FROM AUTHOR]

Background: Radiology trainees were uncomfortable going to the CT scanner to review trauma panscans and interacting with trauma surgeons. Objective: This study aims to determine if radiology residents can be trained to accurately identify injuries requiring immediate surgical attention at the CT scanner. Methods: A high-fidelity simulation model was created to provide an immersive training experience. Between February 2015 and April 2017, 62 class 1 trauma panscans were read at the CT scanner by 11 PGY-3 radiology residents. Findings made at the scanner were compared to resident preliminary and attending radiology reports and correlated with clinical outcomes. Timestamps were recorded and analyzed. Surveys were administered to assess the impact of training on radiology residents' self-confidence and to assess trauma surgeons' preference for radiology at the scanner. Significance level was set at p < 0.05. Results: The mean time to provide results at the CT scanner was 11.1 min. Mean time for the preliminary report for CT head and cervical spine was 24.4 ± 9.8 min, and for the CT chest, abdomen, and pelvis was 16.3 ± 6.9 min. 53 traumatic findings on 62 panscans were identified at the scanner and confirmed at preliminary and final reports, for a concordance rate of 85%, compared to 72% for the control group. Radiology residents agreed or strongly agreed the training prepared them for trauma panscan reporting. Trauma surgeons shifted in favor of radiology presence at the scanner. Conclusion: Radiology residents can be trained to accurately and rapidly identify injuries requiring immediate surgical attention at the CT scanner. Clinical impact: These findings support the value-added of an in-person radiologist at the CT scanner for whole-body trauma panscans to facilitate timely detection of life-threatening injuries and improve professional relations between radiologists and trauma surgeons. [ABSTRACT FROM AUTHOR]

Many nitrosamines have been recognized to be carcinogenic for many decades. Despite the fact that several nitrosamine precursors are frequently used in the manufacturing of pharmaceutical products, their potential presence in pharmaceutical products has previously been overlooked due to a lack of understanding on how they form during the manufacturing process. From the risk assessment, it is clear that nitrosamines or their precursors may be present in any component of the finished dosage form. As a risk mitigation strategy, components with a high potential to form nitrosamine should be avoided. In the absence of suitable alternatives, sufficient measures to maintain nitrosamines below acceptable intake levels must be applied. Excipient manufacturing pathways must be extensively studied in order to identify probable excipient components that may contribute to nitrosamine formation. The manufacturers must not solely rely on pharmacopeial specifications for APIs and excipients, rather, they should also develop and implement additional strategies to control nitrosamine impurities. The formulation can be supplemented with nitrosating inhibitors, such as vitamin C, to stop the generation of nitrosamine. The purpose of this review is to identify key risk factors with regard to nitrosamine formation in pharmaceutical dosage forms and provide an effective control strategy to contain them below acceptable daily intake limits. [ABSTRACT FROM AUTHOR]

Purpose: Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) represents a minimally invasive technique of aortic occlusion (AO). It has been demonstrated to be safe and effective with appropriate training in traumatic hemorrhage with hemodynamic instability; however, its indications are still debated. The aim of this systematic review and meta-analysis is to assess the impact of REBOA on mortality in torso trauma patient with severe non-compressible hemorrhage compared to other temporizing hemostatic techniques. Study design: The primary outcome is represented by 24-h, and in-hospital mortality. Secondary outcomes are post-procedural hemodynamic improvement (systolic blood pressure—SBP), mean injury severity score (ISS) differences, treatment-related morbidity, transfusional requirements and identification of prognostic factors. Results: A significant survival benefit at 24 h (RR 0.46; 95% CI 0.27–0.79; I2: 55%; p = 0.005) was highlighted in patients undergoing REBOA. Regarding in-hospital mortality (RR 0.99; 95% CI 0.75–1.32; I2: 73%; p = 0.98) no differences in risk of death were noticed. A hemodynamic improvement—although not significant—was highlighted, with 55.8 mmHg post-AO SBP mean difference between REBOA and control groups. A significantly lower mean number of packed Red Blood Cells (pRBCs) was noticed for REBOA patients (mean difference: − 3.02; 95% CI − 5.79 to − 0.25; p = 0.033). Nevertheless, an increased risk of post-procedural complications (RR 1.66; 95% CI 0.39–7.14; p = 0.496) was noticed in the REBOA group. Conclusions: REBOA may represent a valid tool in the initial treatment of multiple sites subdiaphragmatic hemorrhage with refractory hemodynamic instability. However, due to several important limitations of the present study, our findings should be interpreted with caution. Level of evidence: Level III according to ELIS (SR/MA with up to two negative criteria). [ABSTRACT FROM AUTHOR]

Antimony (Sb) is highly hazardous to human health even in minute concentration. Therefore, its accurate and precise determination in the real environmental samples is of immense importance. In this work for the first time, UV–Vis spectrophotometric method was developed for the quantification of Sb(III) from water samples using supramolecular solvent (undecanol-tetrahydrofuran)–based extraction. The maximum absorption wavelength for antomony-diathizone complex was found to be 590 nm having molar absorptivity of 3.1 × 104 L.mol.cm−1. Factors affecting extraction efficiency like solution sample volume, amount of chelating agent, pH, matrix effect, and type and volume of supramolecular solvent were determined and optimized. Analytical parameters like limit of detection (0.19 µg L−1), limit of quantification (0.62 µg L−1), pre-concentration factor (15), enhancement factor (15), and relative standard deviation for 8 successive analysis (0.8%) were calculated under optimized experimental conditions. The method was applied to real water samples like tap water of laboratory, waste water from Kohat hospitals, and dam water (Tanda dam Kohat) with quantitative addition recovery (94–100%). [ABSTRACT FROM AUTHOR]

Airborne capacitive micromachined ultrasonic transducers (CMUTs) have predominantly large input capacitive reactance with small series radiation resistance. To maximize the acoustic power radiation at resonance we employ low cost LC matching networks between the low output impedance driving source and CMUT transducer. Conventional LC networks, including pi and T-network topologies are employed to provide a high-Q match. An important free parameter that controls the bandwidth of match in pi and T-networks is the center impedance. Since a simple pi-network can be formed from two basic L-sections, the center impedance of two L-sections provides control over the bandwidth of match. Hence these are tunable-Q matching networks. We use the lumped circuit model of CMUT to derive the input impedance of CMUT at resonance. At resonance the lumped equivalent circuit of transducer can be reduced to a series RC circuit consisting of radiation resistance and transducer's equivalent capacitance only. From the input impedance of CMUT we determine the lumped inductance and capacitances of various LC matching networks. The aim of these matching networks is to cancel the large input capacitive reactance of CMUT cell and to match the cell's radiation resistance to source resistance at resonance. We report significant improvement in the radiated power when CMUT is driven at resonance using the proposed matching schemes. [ABSTRACT FROM AUTHOR]

Motion estimation (ME) process is the most computational complex part of a video encoder. It exploits temporal redundancy present in a video sequence to achieve compression. To make the video encoding process in real time, alleviating the computational burden of motion estimation is mandatory. In this work, an efficient hierarchical diamond search (EHDS) ME algorithm is being presented. This algorithm consists of multiresolution hierarchies, modified diamond search and modified early jump-out mechanism. Multiresolution hierarchies and the modified diamond search algorithm help either locate the global minima or some location nearby it, as best match by first finding starting point of search near the global minima which improves quality and reduces complexity, while the modified early jump-out mechanism further reduces complexity. Results have shown that the proposed algorithm has less complexity and power consumption than the conventional diamond search (DS) and other existing DS algorithms, while the quality is comparable to full search (FS) ME algorithm. [ABSTRACT FROM AUTHOR]

This work presents a novel frequency reconfigurable patch antenna design for Internet of Things (IoT) applications. The proposed antenna structure has hexagonal patch element. Frequency reconfiguration is realized by employing a varactor diode in the microstrip feedline. The miniaturization in the proposed antenna design is obtained by incorporating defected ground structure (DGS) in the ground plane along with reactive loading employing varactor diode. These miniaturization techniques result in size reduction with an overall antenna size of 40 × 40 mm2. The results achieved show that the presented antenna produces frequency reconfigurable feature with continuous tunability from 1.4 to 2.9 GHz, thus covering several wireless communication technologies like WiFi, Bluetooth, ZigBee, GPS, and other 2G/3G/4G cellular standards. The proposed antenna has stable gain patterns with maximum measured gain of 2.4 dBi. To prove the concept, proposed antenna is fabricated and measured. The simulations and measurements exhibit good agreement. The antenna design is compact, simple, planar and low-profile making it suitable for wireless handheld applications including IoT. [ABSTRACT FROM AUTHOR]

This paper investigates the design of a Class-E amplifier to be used to drive a CMUT element. An important parameter of amplifier design is the load which determines the overall noise performance, bandwidth of CMUT operation and its transmit efficiency. Airborne CMUTs unlike PZTs have a large capacitive reactance at resonance along with the radiation resistance. We employ a simple LC section between the amplifier output and CMUT input to cancel the capacitive reactance and transform its radiation resistance to any desired amplifier load. Class-E amplifier can then be designed for the given transformed load. In this work we show that higher transformed CMUT loads have lower radiated power with increased 3-dB bandwidth and improved overall noise performance of amplifier and CMUT system. We use lumped equivalent circuit model of CMUT in air to determine the input impedance of CMUT at resonance and then transform its impedance to various design load values. Harmonic balance circuit simulations results show that CMUT 3-dB bandwidth increases from 14 kHz to 44 kHz with fractional loss of amplifier reducing from 6.8 % to 0.14 % when designed with a 500 Ω transformed load instead of 10 Ω . However the radiated power decreases from 4.92 μ W to 0.14 μ W at the same frequency. [ABSTRACT FROM AUTHOR]

The focus of the present investigation was to develop amorphous glassy solutions (AGSs) of BCS Class II and IV drugs using sucrose acetate isobutyrate (SAIB). The drugs studied were rifaximin (RFX), dasatinib (DST), aripiprazole (APZ), dolutegravir (DLT), cyclosporine (CYS), itraconazole (ITZ), tacrolimus (TAC), sirolimus (SRL), aprepitant (APT), and carbamazepine (CBZ). AGSs were prepared by dissolving known quantity of the drug in the SAIB at 120 (TAC and APZ), 140 (CYS) or 150 oC (RFX, DST, DLT, ITZ, SRL, APT, and CBZ). They were characterized visually and by NIR, NIR hyperspectroscopy (NIR-H), and XRPD. Stability were determined by exposing open vials to 40 oC/75% RH for a week. AGSs behave like a glassy solid at room temperature and liquified above 60 oC. The solubility of APT, DLT, SRL, APZ, RFX, CBZ, TAC and CYS in SAIB was 0.4±0.0, 1.7±0.4, 1.9±0.0, 21.6±2.6, 36.4±0.9, 76.5±4.0, 115.1±2.3, and 239.0±12.6 mg/g, respectively. NIR, NIR-H, and XRPD data indicated the amorphous nature of the AGSs. Furthermore, AGSs were stable against devitrification on exposure to high temperature and humidity. In summary, SAIB can be employed to develop stable AGSs of poorly soluble drugs to increase dissolution, and oral bioavailability with the addition of hydrophilic excipients. [ABSTRACT FROM AUTHOR]

Technique, indications and outcomes of laparoscopic splenectomy in stable trauma patients have not been well described yet. All hemodynamically non-compromised abdominal trauma patients who underwent splenectomy from 1/2013 to 12/2017 at our Level 1 trauma center were included. Demographic and clinical data were collected and analysed with per-protocol and an intention-to-treat comparison between open vs laparoscopic groups. 49 splenectomies were performed (16 laparoscopic, 33 open). Among the laparoscopic group, 81% were successfully completed laparoscopically. Laparoscopy was associated with a higher incidence of concomitant surgical procedures (p 0.016), longer operative times, but a significantly faster return of bowel function and oral diet without reoperations. No significant differences were demonstrated in morbidity, mortality, length of stay, or long-term complications, although laparoscopic had lower surgical site infection (0 vs 21%).The isolated splenic injury sub-analysis included 25 splenectomies,76% (19) open and 24% (6) laparoscopic and confirmed reduction in post-operative morbidity (40 vs 57%), blood transfusion (0 vs 48%), ICU admission (20 vs 57%) and overall LOS (7 vs 9 days) in the laparoscopic group. Laparoscopic splenectomy is a safe and effective technique for hemodynamically stable patients with splenic trauma and may represent an advantageous alternative to open splenectomy in terms of post-operative recovery and morbidity. [ABSTRACT FROM AUTHOR]

The objective of current research was to develop the models of dissolution prediction of tablets coated with cellulose acetate (CA 320S or CA 398-10) and cellulose acetate phthalate (C-A-P) blends. Independent variables selected were coating percent (X1) and percent of CA 320S or CA 398-10 (X2) in the blend. Dependent variables selected were dissolution in 1 (Y1), 8 (Y2), and 24 h (Y3). Diclofenac sodium core tablets were coated with blend of either CA 320S and C-A-P or CA 398-10 and C-A-P at approximately 5, 7.5, and 10% weight gain. CA 320S and CA 398-10 content in the corresponding blends varied from 33.3-66.7% and 25.0-50.0% relative to C-A-P, respectively. Dissolution was performed in phosphate buffer 6.8 using USP apparatus 2. Coated tablets were also characterized for surface morphology and coating uniformity by near infrared hyperspectroscopy. Y1, Y2, and Y3 were statistically (p < 0.05) affected by X2 in CA 320S/C-A-P and CA 398-10/C-A-P blends coated tablets. On the other hand, X1 had statistically significant (p < 0.05) effect only on the Y3 in CA 320S/C-A-P while Y1 was statistically (p < 0.05) affected by X2 in CA 398-10/C-A-P. Analysis of variance also indicated statistically significant (p < 0.05) effect of the studied variables on the dependent variables for both the blends. The models were verified by independent experiment. Model predicted and empirical values of Y1, Y2, and Y3 were close with maximum residual of 7.0%. In conclusion, dissolution can be modulated by varying composition of blend, polymer type, and coating weight. [ABSTRACT FROM AUTHOR]

The focus of the study was to develop discriminatory dissolution methods for portioned snus and moist snuff sub-categories of smokeless tobacco products (STPs) using USP basket and paddle apparatuses. Skoal Classic Wintergreen (SCW) and CORESTA CRP1.1 pouches were used as test products. The dissolution was performed at 10, 20, 30, 40, and 50 rpm basket or paddle speed in 500 ml artificial saliva pH 6.8. The products were also characterized for assay, pH, particle size, and loss on drying. The dissolution profiles were evaluated for amount/% of nicotine dissolved, time to reach plateau, and profiles comparison by f2 and f1 factors. The nicotine assay was 13.3 ± 0.2 and 7.6 ± 0.1 mg/pouch for SCW and CRP1.1, respectively. The nicotine dissolved in 30 min from SCW and CRP1.1 were 38.4–81.8 and 37.6–88.1, and 50.5–64.9 and 72.3–92.1% by paddle and basket methods, respectively. The f2 and f1 values were ≤ 39.2 and ≥ 42.1 and ≤ 43.2 and ≥ 34.1 for basket methods and paddle methods. RSD were less than 20% at all points of dissolution profiles, and dissolution plateau were achieved in 30 min at some of the tested conditions. In summary, dissolution methods based on basket and paddle can be used as a performance test for STPs. [ABSTRACT FROM AUTHOR]

Aripiprazole (APZ) has poor physicochemical properties and bitter taste. The current study aimed to prepare salts of APZ with polycarboxylic acids (citric, malic, and tartaric acids) to improve physicochemical properties and impart sour taste to the drug. The salts were prepared by solubilization-crystallization method, and characterized by electron microscopic, spectroscopic, diffractometry, and thermal methods. The salts were assessed for pH solubility, pH-stability, dissolution, and solid-state stability. Fourier transformed infrared, X-ray powder diffraction, and differential scanning calorimetry data indicated formation of new solid phases. APZ and the salts exhibited pH-dependent solubility. The pH solubility curve shape was inverted “V,” inverted “W,” and inverted “U” for APZ, APZ-Citrate, and APZ-Malate and APZ-Tartrate, respectively. Compared to APZ, the solubility of salts at pH 4, 5, and 6 was 3.6–7.1, 23.9–31.5, and 143.4–373.3 folds of APZ. Increase in solubility in water by citrate, malate, and tartrate salts was 5562.8, 21,284.7, and 22,846.7 folds of APZ. The salt formation also leads to an increase in rate and extent of dissolution. The dissolution extent was 3.5 ± 0.5, 71.3 ± 1.2, 80.1 ± 6.2, and 86.1 ± 1.1% for APZ, APZ-Citrate, APZ-Malate, and APZ-Tartrate, respectively. Liquid and solid-state stabilities of the salts were comparable to APZ. In conclusion, salts of APZ with polycarboxylic acids improved solubility, and dissolution, and impart sour taste, which may improve palatability of the drug. [ABSTRACT FROM AUTHOR]

Purpose: There is much debate regarding the use of anticoagulation following vascular trauma. The aim of this meta-analysis was to compare the outcome of trauma following administration of anticoagulation medication. Methods: The literature search was carried out using Ovid MEDLINE and PubMed databases to search for keywords and MeSH terms including "Anticoagulation", "Vascular Surgery", "Vascular Trauma", "Vascular Repair", "Repair" and "Wounds and Injuries". Results: Use of anticoagulation was associated with a better prognosis for overall vascular trauma outcomes (weighted OR 0.46; 95% CI 0.34–0.64; P < 0.00001), as well as reduced risk of amputation for both lower and upper limb vascular trauma (weighted OR 0.42; 95% CI 0.22–0.78; P = 0.007), and reduced occurrence of reoperation events and amputations in isolated lower limb vascular trauma (weighted OR 0.27; 95% CI 0.14–0.52; P < 0.0001). Conclusion: There was a statistically significant correlation between the use of anticoagulation and vascular trauma outcome. A major limitation with many of the studies includes a lack of prospective analysis and therefore we recommend prospective studies to properly elucidate prognostic outcomes following use of these anticoagulants. Further studies need to be conducted to assess the effects of timing of anticoagulant delivery, dosages and severity of traumatic injury. Thus, this would prove to be very useful in the formation of guidelines. [ABSTRACT FROM AUTHOR]

In this work we present least squares (LS) approach to design linear phase Finite Impulse Response (FIR) filter. Since the design of FIR digital filters is non-analytic, we aim at ideal zero-phase magnitude response and minimize the weighted error in passband and stopbands. The problem of least squares can then be solved non-iteratively by solving system of linear equations. Solution of which yields impulse response that is both real and symmetric. Frequency response of the proposed LS FIR filter shows a flat passband, and higher stop-band attenuation than traditional window based FIR design and comparable attenuation with Parks–McClellan method of the same order. In addition we have implemented LS FIR filter on FPGA based VLSI architectures. Performance evaluation of proposed LS FIR design on VLSI architecture shows comparable throughput, area and power consumption compared to classical filter design approaches. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate rheology and rheological models to elucidate the structural characteristics of graphene oxide doped poly(2-acryloamido-2-methyl propyl sulfonic acid) [GO@p(AMPS)] composite hydrogel. The graphene oxide (GO) was synthesized via modified Hammers method and characterized by X-ray diffraction. This GO-hydrogels were synthesized in GO dispersed medium by adding AMPS as a monomer via free radical addition polymerization. The material was characterized by SEM, FT-IR spectroscopy and Rheometry. The flow curve and flow sweep study of the GO@p(AMPS) hydrogel indicates that the material has pseudo-plastic thixotropic behavior. The finding from the study of storage (G′) and loss (G″) moduli shows that the GO@p(AMPS) behave elastically, semisolid and pseudo-plastic in their nature. The yield stress data indicate that the materials need an external force (activation energy) to break the internal network of the gel. Creep-recovery tests were applied which show that the gels have the ability to recover the network after removal of the external stress. The flow characteristics of the gel were studied by various rheological models, the data were best fitted in the Bingham modified model. Further the damping factor (tan δ) is near to 0.3, which shows the improvement of the damping of the materials due to the interlocking and penetration of GO particles within the gel. Thus, the rheological analysis show that these materials can be applied for complex cosmetics, controlled drug loading and release due to the presence of GO as a drugs binding effector in GO@p(AMPS) composites. [ABSTRACT FROM AUTHOR]

The focus of the present work was to investigate compatibility between commonly used diluents and the drug (salt and acid form of the phenytoin). Lactose monohydrate (LMH), lactitol hydrate (LCT), and mannitol (MNT) were selected based on commercial products information of phenytoin sodium (PS) and phenytoin acid (PHT). Binary mixtures of the drug-diluent were stored at 60°C and 40°C/75% RH. Similarly, two commercial products, namely Product-A and Product-B, were also investigated in in-use stability. Color of PS-LMH changed from white to yellowish-brown and pH dropped by 3.4 units after 4 weeks exposure. FTIR, XRPD, and NIR chemical images indicated disproportionation in PS-LMH and PS-LCT mixtures stored at 40°C/75% RH. Furthermore, PS-LMH also indicated chemical interactions as indicated by distortion of LMH peaks. PHT-diluent mixture did not exhibit any physical and chemical modifications. Product-A changed color, increased weight, dropped pH value, and exhibited disproportionation and chemical reactions. The dissolution of Product-A decreased from 83.3 ± 1.4 to 7.1 ± 4.4% on 8 weeks exposure to 30°C/75% RH. On the other hand, Product-B did not change; however, dissolution decreased by 15%. In conclusion, PS showed disproportionation and chemical reactions with LMH. Therefore, LMH should be avoided in PS formulations. [ABSTRACT FROM AUTHOR]

The objective of the present investigation was to understand the effect of sucrose acetate isobutyrate (SAIB) on abuse-deterrent properties (ADPs) of abuse-deterrent formulations (ADFs) based on Polyox™. SAIB would enhance ADPs of Polyox™-based formulations due to its glassy liquid and hydrophobic properties. Formulations were prepared by granulation followed by compression and heat curing at 90°C. The formulations were evaluated for surface morphology, hardness, manipulation in coffee grinder, particle size distribution, drug (pseudoephedrine hydrochloride) extraction in water, alcohol, 0.1 N HCl, 0.1 N NaOH at room temperature and elevated temperature using microwave and oven, syringeability and injectability, and dissolution. The heat curing of formulations significantly increased the hardness (> 490 N). Addition of SAIB imparted elasticity to formulations and decreased brittleness as indicated by lower values of work done and gradient compared to control formulations. After grinding, about 7.7–25.6% of the powder remained on the sieve (1 mm pore opening), D90 was 53.1–136.7 μm more, and Q (fraction < 500 μm) was 17.8–40.7% less in SAIB-based formulations compared to control formulations. Drug extraction between control and test intact formulations was similar. However, drug extraction was 23.9–42.5% (water), 20.6–26.1% (0.1 N HCl), and 37.4–50.6% (0.1 N NaOH) less in SAIB-based powder cured and uncured formulations compared to control formulations. Dissolution varied from 65.6 ± 4.2 to 97.6 ± 4.0% in 9 h from the formulations. In conclusion, addition of SAIB to Polyox™-based ADFs has synergistic effect on ADPs. This would further decrease potential of drug abuse/misuse by various routes. [ABSTRACT FROM AUTHOR]

The original article can be found online at https://doi.org/10.1007/s10140-022-02109-2. Correction to: In-person radiologist to review the trauma panscan: a high-fidelity simulation training program for radiology trainees at an academic level 1 trauma center B Correction to: Emergency Radiology (2022) b https://doi.org/10.1007/s10140-022-02109-2 The above article was published with error in author name. [Extracted from the article]

Study objective was to assess skin-to-skin drug transfer potential that may occur due to drug retention in human epidermis (DRE) pretreated with application of estradiol transdermal drug delivery systems (TDDS) and other estradiol transdermal dosage forms (gels and sprays). TDDS (products- A, B, and C) with varying formulation design and composition, and other estradiol transdermal products (gel and spray) were applied to heat separated human epidermis (HSE) and subjected to in vitro drug permeation study. Amounts of DRE were quantified after 24 h. The DRE with product- B was significantly ( P < 0.001) higher than that with product- C, product- A, gel, and spray. However, products- A and C, gel, and spray showed almost the same ( P > 0.05) amounts of DRE. A separate in vitro permeation study was carried out to determine amounts of drug transferred from drug-retaining epidermis to untreated HSE. The amounts of drug transferred, due to DRE after 8 h, with product- C were significantly ( P < 0.001) higher than those with products- A and B, gel, and spray. The in vitro study results indicate a high potential of skin-to-skin drug transfer due to the DRE after labeled period of using estradiol TDDS, though the clinical relevance of these findings is yet to be determined. [ABSTRACT FROM AUTHOR]

The term 'patient centered,' 'patient centric,' or 'patient centricity' is increasingly used in the scientific literature in a wide variety of contexts. Generally, patient centric medicines are recognized as an essential contributor to healthy aging and the overall patient's quality of life and life expectancy. Besides the selection of the appropriate type of drug substance and strength for a particular indication in a particular patient, due attention must be paid that the pharmaceutical drug product design is also adequately addressing the particular patient's needs, i.e., assuring adequate patient adherence and the anticipate drug safety and effectiveness. Relevant pharmaceutical design aspects may e.g., involve the selection of the route of administration, the tablet size and shape, the ease of opening the package, the ability to read the user instruction, or the ability to follow the recommended (in-use) storage conditions. Currently, a harmonized definition on patient centric drug development/design has not yet been established. To stimulate scientific research and discussions and the consistent interpretation of test results, it is essential that such a definition is established. We have developed a first draft definition through various rounds of discussions within an interdisciplinary AAPS focus group of experts. This publication summarizes the outcomes and is intended to stimulate further discussions with all stakeholders towards a common definition of patient centric pharmaceutical drug product design that is useable across all disciplines involved. [ABSTRACT FROM AUTHOR]

Consistent high-quality and defect-free production is the demand of the day. The product recall not only increases engineering and manufacturing cost but also affects the quality and the reliability of the product in the eye of users. The monitoring and improvement of a manufacturing process are the strength of statistical process control. In this article we propose a process monitoring memory-based scheme for continuous data under the assumption of normality to detect small non-random shift patterns in any manufacturing or service process. The control limits for the proposed scheme are constructed. The in-control and out-of-control average run length (AVL) expressions have been derived for the performance evaluation of the proposed scheme. Robustness to non-normality has been tested after simulation study of the run length distribution of the proposed scheme, and the comparisons with Shewhart and exponentially weighted moving average (EWMA) schemes are presented for various gamma and t-distributions. The proposed scheme is effective and attractive as it has one design parameter which differentiates it from the traditional schemes. Finally, some suggestions and recommendations are made for the future work. [ABSTRACT FROM AUTHOR]

Phosphorus-containing polymer grafted 4-aminoantipyrine has been synthesized and used for solid phase extraction of U(VI) prior to its UV-Visible spectrophotometric determination by using arsenazo(III). The adsorbent was characterized by using FT-IR and SEM analysis. The influence of parameters including pH, adsorbent dose, amount of complexing reagent, sample volume and matrix effect have been optimized. The detection limit was determined as 1.4 µg L with preconcentration factor of 30 and RSD of 1.4 %. The accuracy was checked by the analysis of GBW07424 soil and TMDA-64.2 environmental water certified reference materials. The method was applied to natural water and soil samples. [ABSTRACT FROM AUTHOR]

Although bottom water hypoxia (O < 2 mg L) is presently widespread in the Baltic Sea coastal zone, there is a lack of insight into past changes in bottom water oxygen in these areas on timescales of millennia, and the possible driving factors. Here, we present a sediment-based environmental reconstruction of surface water productivity, salinity and bottom water oxygen for the past 5400 years at Gåsfjärden, a coastal site in SE Sweden. As proxies, we use dinoflagellate cysts, benthic foraminifera, organic carbon (C), biogenic silica (BSi), C/N, C/P, Ti/Al, K/Al and grain size distribution. The chronology of the sediment sequence is well constrained, based on Pb, Cs and AMS C dates. Between 3400 and 2100 BCE, isostatic conditions favored enhanced deep water exchange between Gåsfjärden and the open Baltic Sea. At that time, Gåsfjärden was characterized by relatively high productivity and salinity, as well as frequently occurring hypoxic-anoxic bottom water, despite the relatively large connection with the Baltic Sea. The most severe interval of oxygen depletion is recorded between 2400 and 2100 BCE, and appears to coincide with a similar hypoxic event in the Gotland Basin in the open Baltic Sea. As regional climate became wetter and colder between 2100 BCE and 700 BCE, salinity declined and bottom water oxygen conditions improved. Throughout the record, grain size, Ti/Al and K/Al data indicate an evolution towards a more enclosed coastal system, as suggested by reconstructions of the post-glacial shoreline regression. Gåsfjärden shifted to close to modern conditions after 700 BCE, and was characterized by less hypoxia and lower salinity compared with 3400-700 BCE. The timing of the shift corresponds with the Sub-Boreal/Sub-Atlantic transition in Europe. Human-induced erosion in the catchment is observed as early as 600 CE, and is particularly prominent since regional copper mining activity increased around 1700 CE. A sharp increase in sediment C concentration is recorded since the 1950s, indicating significant anthropogenic impact on biogeochemical cycles in the coastal zone, as observed elsewhere in the Baltic Sea. [ABSTRACT FROM AUTHOR]

Purpose: Liposomes are robust drug delivery systems that have been developed into FDA-approved drug products for several pharmaceutical indications. Direct control in producing liposomes of a particular particle size and particle size distribution is extremely important since liposome size may impact cellular uptake and biodistribution. Methods: A device consisting of an injection-port was fabricated to form a coaxial turbulent jet in co-flow that produces liposomes via the ethanol injection method. By altering the injection-port dimensions and flow rates, a fluid flow profile ( i.e., flow velocity ratio vs. Reynolds number) was plotted and associated with the polydispersity index of liposomes. Results: Certain flow conditions produced unilamellar, monodispersed liposomes and the mean particle size was controllable from 25 up to >465 nm. The mean liposome size is highly dependent on the Reynolds number of the mixed ethanol/aqueous phase and independent of the flow velocity ratio. Conclusions: The significance of this work is that the Reynolds number is predictive of the liposome particle size, independent of the injection-port dimensions. In addition, a new model describing liposome formation is outlined. The significance of the model is that it relates fluid dynamic properties and lipid-molecule physical properties to the final liposome size. [ABSTRACT FROM AUTHOR]

The focus of the present investigation was to explore the use of solid-state nuclear magnetic resonance (C ssNMR) and X-ray powder diffraction (XRPD) for quantification of nimodipine polymorphs (form I and form II) crystallized in a cosolvent formulation. The cosolvent formulation composed of polyethylene glycol 400, glycerin, water, and 2.5% drug, and was stored at 5°C for the drug crystallization. The C ssNMR and XRPD data of the sample matrices containing varying percentages of nimodipine form I and form II were collected. Univariate and multivariate models were developed using the data. Least square method was used for the univariate model generation. Partial least square and principle component regressions were used for the multivariate models development. The univariate models of the C ssNMR were better than the XRPD as indicated by statistical parameters such as correlation coefficient, R, root mean square error, and standard error. On the other hand, the XRPD multivariate models were better than the C ssNMR as indicated by precision and accuracy parameters. Similar values were predicted by the univariate and multivariate models for independent samples. In conclusion, the univariate and multivariate models of C ssNMR and XRPD can be used to quantitate nimodipine polymorphs. [ABSTRACT FROM AUTHOR]

Compared to small molecule process analytical technology (PAT) applications, biotechnology product PAT applications have certain unique challenges and opportunities. Understanding process dynamics of bioreactor cell culture process is essential to establish an appropriate process control strategy for biotechnology product PAT applications. Inline spectroscopic techniques for real time monitoring of bioreactor cell culture process have the distinct potential to develop PAT approaches in manufacturing biotechnology drug products. However, the use of inline Fourier transform infrared (FTIR) spectroscopic techniques for bioreactor cell culture process monitoring has not been reported. In this work, real time inline FTIR Spectroscopy was applied to a lab scale bioreactor mAb IgG3 cell culture fluid biomolecular dynamic model. The technical feasibility of using FTIR Spectroscopy for real time tracking and monitoring four key cell culture metabolites (including glucose, glutamine, lactate, and ammonia) and protein yield at increasing levels of complexity (simple binary system, fully formulated media, actual bioreactor cell culture process) was evaluated via a stepwise approach. The FTIR fingerprints of the key metabolites were identified. The multivariate partial least squares (PLS) calibration models were established to correlate the process FTIR spectra with the concentrations of key metabolites and protein yield of in-process samples, either individually for each metabolite and protein or globally for all four metabolites simultaneously. Applying the 2nd derivative pre-processing algorithm to the FTIR spectra helps to reduce the number of PLS latent variables needed significantly and thus simplify the interpretation of the PLS models. The validated PLS models show promise in predicting the concentration profiles of glucose, glutamine, lactate, and ammonia and protein yield over the course of the bioreactor cell culture process. Therefore, this work demonstrated the technical feasibility of real time monitoring of the bioreactor cell culture process via FTIR spectroscopy. Its implications for enabling cell culture PAT were discussed. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

On September 16 and 17, 2014, the Food and Drug Administration (FDA) and Product Quality Research Institute (PQRI) inaugurated their Conference on Evolving Product Quality. The Conference is conceived as an annual forum in which scientists from regulatory agencies, industry, and academia may exchange viewpoints and work together to advance pharmaceutical quality. This Conference Summary Report highlights key topics of this conference, including (1) risk-based approaches to pharmaceutical development, manufacturing, regulatory assessment, and post-approval changes; (2) FDA-proposed quality metrics for products, facilities, and quality management systems; (3) performance-based quality assessment and clinically relevant specifications; (4) recent developments and implementation of continuous manufacturing processes, question-based review, and European Medicines Agency (EMA)-FDA pilot for Quality-by-Design (QbD) applications; and (5) breakthrough therapies, biosimilars, and international harmonization, focusing on ICH M7 and Q3D guidelines. The second FDA/PQRI conference on advancing product quality is planned for October 5-7, 2015. [ABSTRACT FROM AUTHOR]