Unexpected behaviors in molecular transport through size-controlled nanochannels down to the ultra-nanoscale

Ionic transport through nanofluidic systems is a problem of fundamental interest in transport physics and has broad relevance in desalination, fuel cells, batteries, filtration, and drug delivery. When the dimension of the fluidic system approaches the size of molecules in solution, fluid properties are not homogeneous and a departure in behavior is observed with respect to continuum-based theories. Here we present a systematic study of the transport of charged and neutral small molecules in an ideal nanofluidic platform with precise channels from the sub-microscale to the ultra-nanoscale (<5 nm). Surprisingly, we find that diffusive transport of nano-confined neutral molecules matches that of charged molecules, as though the former carry an effective charge. Further, approaching the ultra-nanoscale molecular diffusivities suddenly drop by up to an order of magnitude for all molecules, irrespective of their electric charge. New theoretical investigations will be required to shed light onto these intriguing results

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Portable Medical Suction and Aspirator Devices: Are the Design and Performance Standards Relevant?

Airway clearance refers to the clearing of any airway blockage caused due to foreign objects such as mud, gravel, and biomaterials such as blood, vomit, or teeth fragments using the technology of choice, portable suction devices. Currently available devices are either too heavy and bulky to be carried, or insufficiently powered to be useful despite being in accordance with the ISO 10079-1 standards. When applied to portable suction, the design and testing standards lack clinical relevancy, which is evidenced by how available portable suction devices are sparingly used in pre-hospital situations. Lack of clinical relevancy despite being in accordance with design/manufacturing standards arise due to little if any collaboration between those developing clinical standards and the bodies that maintain design and manufacturing standards. An updated set of standards is required that accurately reflects evidence-based requirements and specifications, which should promote valid, rational, and relevant engineering designs and manufacturing standards in consideration of the unique scenarios facing prehospital casualty care. This paper aims to critically review the existing standards for portable suction devices and propose modifications based on the evidence and requirements, especially for civilian prehospital and combat casualty care situations

The Effects of Compressibility on the Performance and Modal Structures of a Sweeping Jet Emitted from Various Scales of a Fluidic Oscillator

Investigations of fluidic oscillators, or sweeping jet actuators, have primarily been conducted within the incompressible flow regime, which limits the accuracy of estimating fluidic oscillator performance for compressible flows. The objective of this study was to evaluate the effects of gas compressibility on the performance of a fluidic oscillator. A commonly used fluidic oscillator geometry (the Bray geometry) was scaled to five different sizes, 3D printed, and tested over a range of air flow rates. High-speed Schlieren images captured the sweeping jet exiting the fluidic oscillators, and custom MATLAB algorithms were used to calculate the oscillation frequencies and angles. A spectral proper orthogonal decomposition (SPOD) method was used to identify and compare the mode structures within the flow fields. All the results were compared using dimensionless parameters to observe performance trends. The results showed that the oscillation frequencies were directly proportional to the flow rate, while the oscillation angles were inversely proportional to the flow rate, regardless of scale size. The angular velocities were not proportional to the flow rate or scale size and exhibited maxima within the evaluated ranges. For all scale sizes, the mode structures were symmetric across the centerlines of the fluidic oscillators and extended further beyond the fluidic oscillators at higher flow rates. These results enable the prediction of fluidic oscillator performance, which can significantly improve the design process for an application where a fluidic oscillator may be used, such as aerospace applications, power generation, heat exchangers, or medical devices

The Effects of Compressibility on the Performance and Modal Structures of a Sweeping Jet Emitted from Various Scales of a Fluidic Oscillator

Investigations of fluidic oscillators, or sweeping jet actuators, have primarily been conducted within the incompressible flow regime, which limits the accuracy of estimating fluidic oscillator performance for compressible flows. The objective of this study was to evaluate the effects of gas compressibility on the performance of a fluidic oscillator. A commonly used fluidic oscillator geometry (the Bray geometry) was scaled to five different sizes, 3D printed, and tested over a range of air flow rates. High-speed Schlieren images captured the sweeping jet exiting the fluidic oscillators, and custom MATLAB algorithms were used to calculate the oscillation frequencies and angles. A spectral proper orthogonal decomposition (SPOD) method was used to identify and compare the mode structures within the flow fields. All the results were compared using dimensionless parameters to observe performance trends. The results showed that the oscillation frequencies were directly proportional to the flow rate, while the oscillation angles were inversely proportional to the flow rate, regardless of scale size. The angular velocities were not proportional to the flow rate or scale size and exhibited maxima within the evaluated ranges. For all scale sizes, the mode structures were symmetric across the centerlines of the fluidic oscillators and extended further beyond the fluidic oscillators at higher flow rates. These results enable the prediction of fluidic oscillator performance, which can significantly improve the design process for an application where a fluidic oscillator may be used, such as aerospace applications, power generation, heat exchangers, or medical devices

Characterizing Thermal Augmentation of Convection-Enhanced Drug Delivery with the Fiberoptic Microneedle Device

Convection-enhanced delivery (CED) is a promising technique leveraging pressure-driven flow to increase penetration of infused drugs into interstitial spaces. We have developed a fiberoptic microneedle device for inducing local sub-lethal hyperthermia to further improve CED drug distribution volumes, and this study seeks to quantitatively characterize this approach in agarose tissue phantoms. Infusions of dye were conducted in 0.6% (w/w) agarose tissue phantoms with isothermal conditions at 15 °C, 20 °C, 25 °C, and 30 °C. Infusion metrics were quantified using a custom shadowgraphy setup and image-processing algorithm. These data were used to build an empirical predictive temporal model of distribution volume as a function of phantom temperature. A second set of proof-of-concept experiments was conducted to evaluate a novel fiberoptic device capable of generating local photothermal heating during fluid infusion. The isothermal infusions showed a positive correlation between temperature and distribution volume, with the volume at 30 °C showing a 7-fold increase at 100 min over the 15 °C isothermal case. Infusions during photothermal heating (1064 nm at 500 mW) showed a similar effect with a 3.5-fold increase at 4 h over the control (0 mW). These results and analyses serve to provide insight into and characterization of heat-mediated enhancement of volumetric dispersal

Sustained Administration of Hormones Exploiting Nanoconfined Diffusion through Nanochannel Membranes

Implantable devices may provide a superior means for hormone delivery through maintaining serum levels within target therapeutic windows. Zero-order administration has been shown to reach an equilibrium with metabolic clearance, resulting in a constant serum concentration and bioavailability of released hormones. By exploiting surface-to-molecule interaction within nanochannel membranes, it is possible to achieve a long-term, constant diffusive release of agents from implantable reservoirs. In this study, we sought to demonstrate the controlled release of model hormones from a novel nanochannel system. We investigated the delivery of hormones through our nanochannel membrane over a period of 40 days. Levothyroxine, osteocalcin and testosterone were selected as representative hormones based on their different molecular properties and structures. The release mechanisms and transport behaviors of these hormones within 3, 5 and 40 nm channels were characterized. Results further supported the suitability of the nanochannels for sustained administration from implantable platforms

Characterizing and Tuning Perfusion Parameters Within an Innovative, Versatile Oxygenating Perfusion System

The advantages of oxygenated perfusion are continuing to be demonstrated by many groups focused on improving the efficacy of tissue preservation for transplant, bioreactors for studies of basic tissue physiology, and closed-loop resuscitation. This work presents a novel and portable device that supplies oxygenated and pulsatile perfusion, both of which are regulated by a single pump-oxygenator component comprised of silicone tubes that are cyclically inflated/deflated with compressed oxygen. In this study, pump variables (oxygen supply pressure and length of a silicone tube) were evaluated against hydraulic elements that mimicked the vascular resistance of kidneys, livers, and hearts. The perfusion pressures, flow rates, and oxygenation rates produced by the device were characterized for all configurations of pump variables, and the pulse rates were tuned to improve performance. The device supplied perfusion pressures ranging from 3.5 to 109 mmHg, flow rates ranging from 1.4 to 71.8 mL min−1, and oxygenation rates up to 316.6 µmol min−1. From those results, it was determined that the device was capable of achieving perfusion parameters used in previous kidney, liver, and heart preservation studies. Ultimately, this research demonstrated the efficacy of a novel device that is designed to supply oxygenated perfusion across a range of applications