Electrophoretic assisted fabrication of additive-free WS2 nanosheet anodes for high energy density lithium-ion batteries.

2D WS2 nanosheets (NSs) are gaining popularity in the domain of Li-ion batteries (LIBs) due to their unique structures, which can enable reversible insertion and extraction of alkali metal ions. While synthesis methods have mostly relied on the exfoliation of bulk materials or direct growth on substrates, here we report an alternative approach involving colloidal hot-injection synthesis of 2D WS2 in 2H and 1T' crystal phases followed by their electrophoretic deposition (EPD) on the current collector. The produced 2D WS2 NSs' films do not require any additional additives during deposition, which boosts the energy density of the additive-free LIBs produced. The 1T' and 2H NSs exhibit long-term stable cyclic performance at C/5 for 600 cycles. At a high cycling rate (1C), the 2H NSs outperform the 1T' NSs, delivering a 1st cycle reversible capacity of 513 mA h g-1 with capacity retention of 73% after 100 cycles (compared to 205 mA h g-1, and 84 mA h g-1 respectively for NS-1T'). Post-cycling investigation confirms that there is no leaching or cracking of the active material on the surface of anodes after 100 cycles at C/5, which enables mechanical stability, and impressive battery performance of the WS2 NS electrodes.

Inverted All-Inorganic Nanorod-Based Light-Emitting Diodes via Electrophoretic Deposition.

High performance and high stability in all-inorganic solution processed nanocrystal-based light-emitting diodes (LEDs) are highly attractive for large area devices compared to organic material-based LEDs. In this work, an inverted all-inorganic LED structure is designed to have an easy integration with thin-film transistors. Adopting robust inorganic materials such as Ni1-x O nanoparticle films as a hole transport layer (HTL) is beneficial for the performance of LED. Herein, we have optimized the HTL by introducing Mg into Ni1-x O to bridge the difference in energy offset between the nanorod emissive layer and the HTL, in addition to the advantages of low temperature solubility of Ni1-x O:Mg nanoparticles. Furthermore, CdSe/CdS-based nanorods via electrophoretic deposition (EPD) are amassed in a vertically aligned (VA-NR) fashion as an emissive layer to facilitate the carrier transportation. Fostering these approaches enabled an EQE of 1.2% of the fabricated device, establishing the viability for further development of efficient and highly stable nanocrystal-based LEDs.

Polymorph selection of pharmaceutical cocrystals via bench-top and continuous production techniques.

Polymorphism can be a valuable tool as well as an impediment in the development and approval of pharmaceuticals, providing an opportunity to tune active pharmaceutical ingredient (API) physicochemical properties. The control of polymorphism in cocrystalline systems and other multicomponent forms remains underexplored. The study herein aims to investigate the potential of several techniques, liquid-assisted grinding (LAG), solvent evaporation (SE), supercritical enhanced atomization (SEA) and electrospraying, to control the cocrystal polymorphic outcome of three cocrystals: isonicotinamide-citric acid (IsoCa), ethenzamide-saccharin (EthSac) and ethenzamide-gentisic acid (EthGa). Solvent selection employing LAG and SE showed little effect on polymorphic outcome. Electrospraying and SEA primarily produced the α form of IsoCa, with process parameter variations leading to the ß form during SEA, and a mixture of α and γ from electrospraying. Electrospraying led to the stable form I of EthSac, while SEA could produce pure form II, and a mixture. Electrospraying produced the form I of EthGa while SEA could produce form II, with an unknown polymorphic impurity. Density functional theory (DFT) computed electron density (ED) maps of cocrystal polymorph binary systems further rationalised the polymorphic predominance observed through the electrospraying. Ultimately this study provides a general road map for polymorph selection via atomization-based methodologies.

High Entropy Oxides: Mapping the Landscape from Fundamentals to Future Vistas: Focus Review.

High-entropy materials (HEMs) are typically crystalline, phase-pure and configurationally disordered materials that contain at least five elements evenly blended into a solid-solution framework. The discovery of high-entropy alloys (HEAs) and high-entropy oxides (HEOs) disrupted traditional notions in materials science, providing avenues for the exploration of new materials, property optimization, and the pursuit of advanced applications. While there has been significant research on HEAs, the creative breakthroughs in HEOs are still being revealed. This focus review aims at developing a structured framework for expressing the concept of HEM, with special emphasis on the crystal structure and functional properties of HEOs. Insights into the recent synthetic advances, that foster prospective outcomes and their current applications in electrocatalysis, and battery, are comprehensively discussed. Further, it sheds light on the existing constraints in HEOs, highlights the adoption of theoretical and experimental tools to tackle challenges, while delineates potential directions for exploration in energy application.

Binder-Free Anodes for Potassium-ion Batteries Comprising Antimony Nanoparticles on Carbon Nanotubes Obtained Using Electrophoretic Deposition.

Antimony has a high theoretical capacity and suitable alloying/dealloying potentials to make it a future anode for potassium-ion batteries (PIBs); however, substantial volumetric changes, severe pulverization, and active mass delamination from the Cu foil during potassiation/depotassiation need to be overcome. Herein, we present the use of electrophoretic deposition (EPD) to fabricate binder-free electrodes consisting of Sb nanoparticles (NPs) embedded in interconnected multiwalled carbon nanotubes (MWCNTs). The anode architecture allows volume changes to be accommodated and prevents Sb delamination within the binder-free electrodes. The Sb mass ratio of the Sb/CNT nanocomposites was varied, with the optimized Sb/CNT nanocomposite delivering a high reversible capacity of 341.30 mA h g-1 (∼90% of the initial charge capacity) after 300 cycles at C/5 and 185.69 mA h g-1 after 300 cycles at 1C. Postcycling investigations reveal that the stable performance is due to the unique Sb/CNT nanocomposite structure, which can be retained over extended cycling, protecting Sb NPs from volume changes and retaining the integrity of the electrode. Our findings not only suggest a facile fabrication method for high-performance alloy-based anodes in PIBs but also encourage the development of alloying-based anodes for next-generation PIBs.

Screening, Synthesis, and Characterization of a More Rapidly Dissolving Celecoxib Crystal Form.

The prevalence of poor solubility in active pharmaceutical ingredients (APIs) such as celecoxib (CEL) is a major bottleneck in the pharmaceutical industry, leading to a low concentration gradient, poor passive diffusion, and in vivo failure. This study presents the synthesis and characterization of a new cocrystal of the API CEL. CEL is a nonsteroidal anti-inflammatory drug used for the treatment of osteoarthritis and rheumatoid arthritis. Computational screening was completed for CEL against a large library of generally recognized as safe (GRAS) coformers, based on molecular complementarity and hydrogen bond propensity (HBP). The generated list of 17 coformers with a likelihood for cocrystallization with CEL were experimentally screened using four techniques: liquid-assisted grinding (LAG), solvent evaporation (SE), gas antisolvent crystallization (GAS), and supercritical enhanced atomization (SEA). One new crystalline form was isolated, employing the liquid coformer N-ethylacetamide (NEA). This novel form, celecoxib-di-N-ethylacetamide (CEL·2NEA), was characterized by a variety of different techniques. The crystal structure was determined through single-crystal X-ray diffraction. Both NEA molecules are evolved from the crystal structure at a desolvation temperature of approximately 65 °C. The CEL·2NEA cocrystal exhibited a dissolution rate, with more than a twofold improvement in comparison to as-received CEL after only 15 min.

Marine waste derived carbon materials for use as sulfur hosts for Lithium-Sulfur batteries.

Lithium-sulfur batteries are a promising alternative to lithium-ion batteries as they can potentially offer significantly increased capacities and energy densities. The ever-increasing global battery market demonstrates that there will be an ongoing demand for cost effective battery electrode materials. Materials derived from waste products can simultaneously address two of the greatest challenges of today, i.e., waste management and the requirement to develop sustainable materials. In this study, we detail the carbonisation of gelatin from blue shark and chitin from prawns, both of which are currently considered as waste biproducts of the seafood industry. The chemical and physical properties of the resulting carbons are compared through a correlation of results from structural characterisation techniques, including electron imaging, X-ray diffraction, Raman spectroscopy and nitrogen gas adsorption. We investigated the application of the resulting carbons as sulfur-hosting electrode materials for use in lithium-sulfur batteries. Through comprehensive electrochemical characterisation, we demonstrate that value added porous carbons, derived from marine waste are promising electrode materials for lithium-sulfur batteries. Both samples demonstrated impressive capacity retention when galvanostatically cycled at a rate of C/5 for 500 cycles. This study highlights the importance of looking towards waste products as sustainable feeds for battery material production.

Differential distribution of ivacaftor and its metabolites in plasma and human airway epithelia.

Ivacaftor is the first clinically approved monotherapy potentiator to treat CFTR channel dysfunction in people with cystic fibrosis. Ivacaftor (Iva) is a critical component for all current modulator therapies, including highly effective modulator therapies. Clinical studies show that CF patients on ivacaftor-containing therapies present various clinical responses, off-target effects, and adverse reactions, which could be related to metabolites of the compound. In this study, we reported the concentrations of Iva and two of its major metabolites (M1-Iva and M6-Iva) in capillary plasma and estimated M1-Iva and M6-Iva metabolic activity via the metabolite parent ratio in capillary plasma over 12 h. We also used the ratio of capillary plasma versus human nasal epithelial cell concentrations to evaluate entry into epithelial cells in vivo. M6-Iva was rarely detected by LC-MS/MS in epithelial cells from participants taking ivacaftor, although it was detected in plasma. To further explore this discrepancy, we performed in vitro studies, which showed that M1-Iva, but not M6-Iva, readily crossed 16HBE cell membranes. Our studies also suggest that metabolism of these compounds is unlikely to occur in airway epithelia despite evidence of expression of metabolism enzymes. Overall, our data provide evidence that there are differences between capillary and cellular concentrations of these compounds that may inform future studies of clinical response and off-target effects.

Structure-Property Correlations in CZTSe Domains within Semiconductor Nanocrystals as Photovoltaic Absorbers.

Semiconductor nanocrystals (NCs) are promising materials for various applications. Two of four recently identified CuαZnßSnγSeδ (CZTSe) domains demonstrate metallic character, while the other two exhibit semiconductor character. The presence of both metallic and semiconductor domains in one NC can hugely benefit future applications. In contrast to traditional band gap studies in the NC community, this study emphasizes that NC domain interfaces also affect the electronic properties. Specifically, the measured band gap of a tetrapod-shaped CZTSe NC is demonstrated to originate from two specific domains (tetragonal I 4 ¯ $\bar 4$ and monoclinic P1c1 Cu2ZnSnSe4). The heterojunction between these two semiconductor domains exhibits a staggered type-II band alignment, facilitating the separation of photogenerated electron-hole pairs. Interestingly, tetrapod NCs have the potential to be efficient absorber materials with higher capacitance in photovoltaic applications due to the presence of both semiconductor/semiconductor interfaces and metal/semiconductor "Schottky"-junctions. For the two photo-absorbing domains, the calculated absorption spectra yield maximum photon-absorption coefficients of about 105 cm-1 in the visible and UV regions and a theoretical solar power conversion efficiency up to 20.8%. These insights into the structure-property relationships in CZTSe NCs will guide the design of more efficient advanced optical CZTSe materials for various applications.

Improved Compatibility of α-NaMnO2 Cathodes at the Interface with Ionic Liquid Electrolytes.

The behaviour and compatibility of monoclinic sodium manganite, α-NaMnO2, cathodes at the interface with electrolytes based on the 1-ethyl-3-methylimidazolium bis(fluorosulfonyl)imide (EMIFSI) and N-trimethyl-N-butylammonium bis(fluorosulfonyl)imide (N1114FSI) ionic liquids is presented and discussed. The Na+ insertion process was analysed through cyclic voltammetry tests combined with impedance spectroscopy measurements and the cell performance was tested by charge-discharge cycles. XPS and FIB-SEM measurements allowed analysis of the surface composition and the morphology of post-mortem cathodes. Overall, the α-NaMnO2 cathode showed high reversibility in N1114FSI-based electrolyte, delivering 60 % of the initial capacity after 1200 cycles in conjunction with a Coulombic efficiency above 99 %. To our knowledge, these very promising results are the best result obtained till now for monolithic α-NaMnO2 cathodes, are ascribable to the formation of a stable passive layer onto the electrode surface, as confirmed by spectroscopic analysis.

Pharmacokinetic variability of CFTR modulators from standard and alternative regimens.

Elexacaftor, tezacaftor, ivacaftor (ETI) is a CFTR modulator combination approved for use in ∼90 % of people with cystic fibrosis (pwCF) over 2 years old. While most pwCF tolerate this therapy well, some are intolerant to standard dosing, and others show little response. Clinical providers may adjust ETI dosing to combat these issues, but these adjustments are not well guided by pharmacokinetic evidence. Our post-approval study aimed to describe pharmacokinetic variability of ETI plasma concentrations in 15 participants who were administered a standard or reduced dose. ETI were quantified by LC-MS/MS in plasma samples taken prior to the morning dose. Results showed non-significant differences for each compound regardless of dosing regimen and after dose equivalence normalization. The majority of participants in both dosing groups had concentrations expected to elicit clinical response to ETI therapy. These findings indicate that dose reduction may be a viable strategy to maintain clinical benefit while managing intolerance.

Real-Time TEM Observation of the Role of Defects on Nickel Silicide Propagation in Silicon Nanowires.

Metal silicides have received significant attention due to their high process compatibility, low resistivity, and structural stability. In nanowire (NW) form, they have been widely prepared using metal diffusion into preformed Si NWs, enabling compositionally controlled high-quality metal silicide nanostructures. However, unlocking the full potential of metal silicide NWs for next-generation nanodevices requires an increased level of mechanistic understanding of this diffusion-driven transformation. Herein, using in situ transmission electron microscopy (TEM), we investigated the defect-controlled silicide formation dynamics in one-dimensional NWs. A solution-based synthetic route was developed to form Si NWs anchored to Ni NW stems as an optimal platform for in situ TEM studies of metal silicide formation. Multiple in situ annealing experiments led to Ni diffusion from the Ni NW stem into the Si NW, forming a nickel silicide. We observed the dynamics of Ni propagation in straight and kinked Si NWs, with some regions of the NWs acting as Ni sinks. In NWs with high defect distribution, we obtained direct evidence of nonuniform Ni diffusion and silicide retardation. The findings of this study provide insights into metal diffusion and silicide formation in complex NW structures, which are crucial from fundamental and application perspectives.

Highly Efficient Inverted Light-Emitting Diodes Based on Vertically Aligned CdSe/CdS Nanorod Layers Fabricated by Electrophoretic Deposition.

Inverted colloidal-nanocrystal-based LEDs (NC-LEDs) are highly interesting and invaluable for large-scale display technology and flexible electronics. Semiconductor nanorods (NRs), in addition to the tunable wavelengths of the emitted light (achieved, for example, by the variation of the NR diameter or the diameter of core in a core-shell configuration), also exhibit linearly polarized emission, a larger Stokes shift, faster radiative decay, and slower bleaching kinetics than quantum dots (QDs). Despite these advantages, it is difficult to achieve void-free active NR layers using simple spin-coating techniques. Herein, we employ electrophoretic deposition (EPD) to make closely packed, vertically aligned CdSe/CdS core/shell nanorods (NRs) as the emissive layer. Following an inverted architecture, the device fabricated yields an external quantum efficiency (EQE) of 6.3% and a maximum luminance of 4320 cd/m2 at 11 V. This good performance can be attributed to the vertically aligned NR layer, enhancing the charge transport by reducing the resistance of carrier passage, which is supported by our finite element simulations. To the best of our knowledge, this is the first time vertically aligned NR layers made by EPD have been reported for the fabrication of NC-LEDs and the device performance is one of the best for inverted red NR-LEDs. The findings presented in this work bring forth a simple and effective technique for making vertically aligned NRs, and the mechanism behind the NR-LED device with enhanced performance using these NRs is illustrated. This technique may prove useful to the development of a vast class of nanocrystal-based optoelectronics, including solar cells and laser devices.

Resolving Multielement Semiconductor Nanocrystals at the Atomic Level: Complete Deciphering of Domains and Order in Complex CuαZnßSnγSeδ (CZTSe) Tetrapods.

Semiconductor nanocrystals (NCs) with high elemental and structural complexity can be engineered to tailor for electronic, photovoltaic, thermoelectric, and battery applications etc. However, this greater complexity causes ambiguity in the atomic structure understanding. This in turn hinders the mechanistic studies of nucleation and growth, the theoretical calculations of functional properties, and the capability to extend functional design across complementary semiconductor nanocrystals. Herein, we successfully deciphered the atomic arrangements of 4 different nanocrystal domains in CuαZnßSnγSeδ (CZTSe) nanocrystals using crucial zone axis analysis on multiple crystals in different orientations. The results show that the essence of crystallographic progression from binary to multielemental semiconductors is actually the change of theoretical periodicity. This transition is caused by decreased symmetry in the crystal instead of previously assumed crystal deformation. We further reveal that these highly complex crystalline entities have highly ordered element arrangements as opposed to the previous understanding that their elemental orderings are random.

Trigeminal neuralgia and trigeminal neuropathic pain.

It is very important that the dental team are aware of the varied presentations of pain in the mouth, face and other parts of the trigeminal region which are not directly caused by teeth or oral structures. Our understanding of underlying causes in this complex area is evolving. Ultimately, patients who present with what may at first seem to be oral or dental problems will require specialist input in secondary care with potential for use of systemic medications. This article reviews the common non-dental pains encountered in the orofacial region related to dysfunction of the trigeminal nerve.

Binder-free germanium nanoparticle decorated multi-wall carbon nanotube anodes prepared via two-step electrophoretic deposition for high capacity Li-ion batteries.

Germanium (Ge) has a high theoretical specific capacity (1384 mA h g-1) and fast lithium-ion diffusivity, which makes it an attractive anode material for lithium-ion batteries (LIBs). However, large volume changes during lithiation can lead to poor capacity retention and rate capability. Here, electrophoretic deposition (EPD) is used as a facile strategy to prepare Ge nanoparticle carbon-nanotube (Ge/CNT) electrodes. The Ge and CNT mass ratio in the Ge/CNT nanocomposites can be controlled by varying the deposition time, voltage, and concentration of the Ge NP dispersion in the EPD process. The optimized Ge/CNT nanocomposite exhibited long-term cyclic stability, with a capacity of 819 mA h g-1 after 1000 cycles at C/5 and a reversible capacity of 686 mA h g-1 after 350 cycles (with a minuscule capacity loss of 0.07% per cycle) at 1C. The Ge/CNT nanocomposite electrodes delivered dramatically improved cycling stability compared to control Ge nanoparticles. This can be attributed to the synergistic effects of implanting Ge into a 3D interconnected CNT network which acts as a buffer layer to accommodate the volume expansion of Ge NPs during lithiation/delithiation, limiting cracking and/or crumbling, to retain the integrity of the Ge/CNT nanocomposite electrodes.

Revealing Seed-Mediated Structural Evolution of Copper-Silicide Nanostructures: Generating Structured Current Collectors for Rechargeable Batteries.

Metal silicide thin films and nanostructures typically employed in electronics have recently gained significant attention in battery technology, where they are used as active or inactive materials. However, unlike thin films, the science behind the evolution of silicide nanostructures, especially 1D nanowires (NWs), is a key missing aspect. CuxSiy nanostructures synthesized by solvent vapor growth technique are studied as a model system to gain insights into metal silicide formation. The temperature-dependent phase evolution of CuxSiy structures proceeds from Cu>Cu0.83Si0.17>Cu5Si>Cu15Si4. The role of Cu diffusion kinetics on the morphological progression of Cu silicides is studied, revealing that the growth of 1D metal silicide NWs proceeds through an in situ formed, Cu seed-mediated, self-catalytic process. The different CuxSiy morphologies synthesized are utilized as structured current collectors for K-ion battery anodes. Sb deposited by thermal evaporation upon Cu15Si4 tripod NWs and cube architectures exhibit reversible alloying capacities of 477.3 and 477.6 mAh g-1 at a C/5 rate. Furthermore, Sb deposited Cu15Si4 tripod NWs anode tested in Li-ion and Na-ion batteries demonstrate reversible capacities of ≈518 and 495 mAh g-1.

Strategies to decrease inequalities in cancer therapeutics, care and prevention: Proceedings on a conference organized by the Pontifical Academy of Sciences and the European Academy of Cancer Sciences, Vatican City, February 23-24, 2023.

Analyses of inequalities related to prevention and cancer therapeutics/care show disparities between countries with different economic standing, and within countries with high Gross Domestic Product. The development of basic technological and biological research provides clinical and prevention opportunities that make their implementation into healthcare systems more complex, mainly due to the growth of Personalized/Precision Cancer Medicine (PCM). Initiatives like the USA-Cancer Moonshot and the EU-Mission on Cancer and Europe's Beating Cancer Plan are initiated to boost cancer prevention and therapeutics/care innovation and to mitigate present inequalities. The conference organized by the Pontifical Academy of Sciences in collaboration with the European Academy of Cancer Sciences discussed the inequality problem, dependent on the economic status of a country, the increasing demands for infrastructure supportive of innovative research and its implementation in healthcare and prevention programs. Establishing translational research defined as a coherent cancer research continuum is still a challenge. Research has to cover the entire continuum from basic to outcomes research for clinical and prevention modalities. Comprehensive Cancer Centres (CCCs) are of critical importance for integrating research innovations to preclinical and clinical research, as for ensuring state-of-the-art patient care within healthcare systems. International collaborative networks between CCCs are necessary to reach the critical mass of infrastructures and patients for PCM research, and for introducing prevention modalities and new treatments effectively. Outcomes and health economics research are required to assess the cost-effectiveness of new interventions, currently a missing element in the research portfolio. Data sharing and critical mass are essential for innovative research to develop PCM. Despite advances in cancer research, cancer incidence and prevalence is growing. Making cancer research infrastructures accessible for all patients, considering the increasing inequalities, requires science policy actions incentivizing research aimed at prevention and cancer therapeutics/care with an increased focus on patients' needs and cost-effective healthcare.

Widespread chemical dilution of streams continues as long-term effects of acidic deposition slowly reverse.

Studies of recovery from acidic deposition have focused on reversal of acidification and its associated effects, but as recovery proceeds slowly, chemical dilution of surface waters is emerging as a key factor in the recovery process that has significant chemical and biological implications. This investigation uses long-term chemical records from 130 streams in the Adirondack region of New York, USA, to evaluate the role of ongoing decreases in conductance, an index of dilution, in the recovery of these streams. Stream chemistry data spanning up to 40 years (1980s-2022) showed that acid-neutralizing capacity has increased in 92% of randomly selected streams, but that harmful levels of acidification still occur in 37% of these streams. Conductance and Ca2+ concentrations decreased in 79% of streams, and SO42- concentrations in streams continued to show strong decreases but remained several times higher than concentrations in precipitation. These changes were ongoing through 2022 even though acidic deposition levels were approaching those estimated for pre-industrialization. Further dilution is continuing through ongoing decreases in stream SO42-. Nevertheless, Ca2+ continued to be leached from soils by SO42-, organic acids and NO3-, limiting the replenishment of available soil Ca2+, a prerequisite to stem further dilution of stream water.

Type 1 VWD classification revisited: novel insights from combined analysis of the LoVIC and WiN studies.

ABSTRACT: There is significant ongoing debate regarding type 1 von Willebrand disease (VWD) defintion. Previous guidelines recommended patients with von Willebrand factor (VWF) levels <30 IU/dL be diagnosed type 1 VWD, whereas patients with significant bleeding and VWF levels from 30 to 50 IU/dL be diagnosed with low VWF. To elucidate the relationship between type 1 VWD and low VWF in the context of age-induced increases in VWF levels, we combined data sets from 2 national cohort studies: 162 patients with low VWF from the Low VWF in Ireland Cohort (LoVIC) and 403 patients with type 1 VWD from the Willebrand in The Netherlands (WiN) studies. In 47% of type 1 VWD participants, VWF levels remained <30 IU/dL despite increasing age. Conversely, VWF levels increased to the low VWF range (30-50 IU/dL) in 30% and normalized (>50 IU/dL) in 23% of type 1 VWD cases. Crucially, absolute VWF antigen (VWF:Ag) levels and increase of VWF:Ag per year overlapped between low VWF and normalized type 1 VWD participants. Moreover, multiple regression analysis demonstrated that VWF:Ag levels in low VWF and normalized type 1 VWD patients would not have been different had they been diagnosed at the same age (ß = 0.00; 95% confidence interval, -0.03 to 0.04). Consistently, no difference was found in the prevalence of VWF sequence variants; factor VIII activity/VWF:Ag or VWF propeptide/VWF:Ag ratios; or desmopressin responses between low VWF and normalized type 1 VWD patients. In conclusion, our findings demonstrate that low VWF does not constitute a discrete clinical or pathological entity. Rather, it is part of an age-dependent type 1 VWD evolving phenotype. Collectively, these data have important implications for future VWD classification criteria.