278 research outputs found
Analytical Techniques to Support Hospital Case Mix Planning
This article introduces analytical techniques and a decision support tool to
support capacity assessment and case mix planning (CMP) approaches previously
created for hospitals. First, an optimization model is proposed to analyse the
impact of making a change to an existing case mix. This model identifies how
other patient types should be altered proportionately to the changing levels of
hospital resource availability. Then we propose multi-objective decision-making
techniques to compare and critique competing case mix solutions obtained. The
proposed techniques are embedded seamlessly within an Excel Visual Basic for
Applications (VBA) personal decision support tool (PDST), for performing
informative quantitative assessments of hospital capacity. The PDST reports
informative metrics of difference and reports the impact of case mix
modifications on the other types of patient present. The techniques developed
in this article provide a bridge between theory and practice that is currently
missing and provides further situational awareness around hospital capacity.Comment: 20 pages, 11 tables, 6 figure
Developing A Personal Decision Support Tool for Hospital Capacity Assessment and Querying
This article showcases a personal decision support tool (PDST) called
HOPLITE, for performing insightful and actionable quantitative assessments of
hospital capacity, to support hospital planners and health care managers. The
tool is user-friendly and intuitive, automates tasks, provides instant
reporting, and is extensible. It has been developed as an Excel Visual Basic
for Applications (VBA) due to its perceived ease of deployment, ease of use,
Office's vast installed userbase, and extensive legacy in business. The
methodology developed in this article bridges the gap between mathematical
theory and practice, which our inference suggests, has restricted the uptake
and or development of advanced hospital planning tools and software. To the
best of our knowledge, no personal decision support tool (PDST) has yet been
created and installed within any existing hospital IT systems, to perform the
aforementioned tasks. This article demonstrates that the development of a PDST
for hospitals is viable and that optimization methods can be embedded quite
simply at no cost. The results of extensive development and testing indicate
that HOPLITE can automate many nuanced tasks. Furthermore, there are few
limitations and only minor scalability issues with the application of free to
use optimization software. The functionality that HOPLITE provides may make it
easier to calibrate hospitals strategically and/or tactically to demands. It
may give hospitals more control over their case-mix and their resources,
helping them to operate more proactively and more efficiently.Comment: 33 pages, 11 tables, 17 figure
Biological Channeling of a Reactive Intermediate in the Bifunctional Enzyme DmpFG
It has been hypothesized that the bifunctional enzyme DmpFG channels its intermediate, acetaldehyde, from one active site to the next using a buried intermolecular channel identified in the crystal structure. This channel appears to switch between an open and a closed conformation depending on whether the coenzyme NAD(+) is present or absent. Here, we applied molecular dynamics and metadynamics to investigate channeling within DmpFG in both the presence and absence of NAD(+). We found that substrate channeling within this enzyme is energetically feasible in the presence of NAD(+) but was less likely in its absence. Tyr-291, a proposed control point at the channel's entry, does not appear to function as a molecular gate. Instead, it is thought to orientate the substrate 4-hydroxy-2-ketovalerate in DmpG before reaction occurs, and may function as a proton shuttle for the DmpG reaction. Three hydrophobic residues at the channel's exit appear to have an important role in controlling the entry of acetaldehyde into the DmpF active site
Biological Channeling of a Reactive Intermediate in the Bifunctional Enzyme DmpFG
AbstractIt has been hypothesized that the bifunctional enzyme DmpFG channels its intermediate, acetaldehyde, from one active site to the next using a buried intermolecular channel identified in the crystal structure. This channel appears to switch between an open and a closed conformation depending on whether the coenzyme NAD+ is present or absent. Here, we applied molecular dynamics and metadynamics to investigate channeling within DmpFG in both the presence and absence of NAD+. We found that substrate channeling within this enzyme is energetically feasible in the presence of NAD+ but was less likely in its absence. Tyr-291, a proposed control point at the channel's entry, does not appear to function as a molecular gate. Instead, it is thought to orientate the substrate 4-hydroxy-2-ketovalerate in DmpG before reaction occurs, and may function as a proton shuttle for the DmpG reaction. Three hydrophobic residues at the channel's exit appear to have an important role in controlling the entry of acetaldehyde into the DmpF active site
The Efficacy of Utility Functions for Multicriteria Hospital Case-Mix Planning
A new approach to perform hospital case-mix planning (CMP) is introduced in
this article. Our multi-criteria approach utilises utility functions (UF) to
articulate the preferences and standpoint of independent decision makers
regarding outputs. The primary aim of this article is to test whether a utility
functions method (UFM) based upon the scalarization of aforesaid UF is an
appropriate quantitative technique to, i) distribute hospital resources to
different operating units, and ii) provide a better capacity allocation and
case mix. Our approach is motivated by the need to provide a method able to
evaluate the trade-off between different stakeholders and objectives of
hospitals. To the best of our knowledge, no such approach has been considered
before in the literature. As we will later show, this idea addresses various
technical limitations, weaknesses, and flaws in current CMP. The efficacy of
the aforesaid approach is tested on a case study of a large tertiary hospital.
Currently UF are not used by hospital managers, and real functions are
unavailable, hence, 14 rational options are tested. Our exploratory analysis
has provided important guidelines for the application of these UF. It indicates
that these UF provide a valuable starting point for planners, managers, and
executives of hospitals to impose their goals and aspirations. In conclusion,
our approach may be better at identifying case mix that users want to treat and
seems more capable of modelling the varying importance of different levels of
output. Apart from finding desirable case mixes to consider, the approach can
provide important insights via a sensitivity analysis of the parameters of each
UF.Comment: 35 pages, 6 tables, 29 figure
Multicriteria Optimization Techniques for Understanding the Case Mix Landscape of a Hospital
Various medical and surgical units operate in a typical hospital and to treat
their patients these units compete for infrastructure like operating rooms (OR)
and ward beds. How that competition is regulated affects the capacity and
output of a hospital. This article considers the impact of treating different
patient case mix (PCM) in a hospital. As each case mix has an economic
consequence and a unique profile of hospital resource usage, this consideration
is important. To better understand the case mix landscape and to identify those
which are optimal from a capacity utilisation perspective, an improved
multicriteria optimization (MCO) approach is proposed. As there are many
patient types in a typical hospital, the task of generating an archive of
non-dominated (i.e., Pareto optimal) case mix is computationally challenging.
To generate a better archive, an improved parallelised epsilon constraint
method (ECM) is introduced. Our parallel random corrective approach is
significantly faster than prior methods and is not restricted to evaluating
points on a structured uniform mesh. As such we can generate more solutions.
The application of KD-Trees is another new contribution. We use them to perform
proximity testing and to store the high dimensional Pareto frontier (PF). For
generating, viewing, navigating, and querying an archive, the development of a
suitable decision support tool (DST) is proposed and demonstrated.Comment: 38 pages, 17 figures, 11 table
An improved open-channel structure of MscL determined from FRET confocal microscopy and simulation
Mechanosensitive channels act as molecular transducers of mechanical force exerted on the membrane of living cells by opening in response to membrane bilayer deformations occurring in physiological processes such as touch, hearing, blood pressure regulation, and osmoregulation. Here, we determine the likely structure of the open state of the mechanosensitive channel of large conductance using a combination of patch clamp, fluorescence resonance energy transfer (FRET) spectroscopy, data from previous electron paramagnetic resonance experiments, and molecular and Brownian dynamics simulations. We show that structural rearrangements of the protein can be measured in similar conditions as patch clamp recordings while controlling the state of the pore in its natural lipid environment by modifying the lateral pressure distribution via the lipid bilayer. Transition to the open state is less dramatic than previously proposed, while the N terminus remains anchored at the surface of the membrane where it can either guide the tilt of or directly translate membrane tension to the conformation of the pore-lining helix. Combining FRET data obtained in physiological conditions with simulations is likely to be of great value for studying conformational changes in a range of multimeric membrane proteins
Model Channel Ion Currents in NaCl - SPC/E Solution with Applied-Field Molecular Dynamics
Using periodic boundary conditions and a constant applied field, we have
simulated current flow through an 8.125 Angstrom internal diameter, rigid,
atomistic channel with polar walls in a rigid membrane using explicit ions and
SPC/E water. Channel and bath currents were computed from ten 10-ns
trajectories for each of 10 different conditions of concentration and applied
voltage. An electric field was applied uniformly throughout the system to all
mobile atoms. On average, the resultant net electric field falls primarily
across the membrane channel, as expected for two conductive baths separated by
a membrane capacitance. The channel is rarely occupied by more than one ion.
Current-voltage relations are concentration-dependent and superlinear at high
concentrations.Comment: Accepted for publication in Biophysical Journa
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