The enigma that is the nucleus pulposus cell: the search goes on

The development of an effective treatment for degenerative disc disease has been hampered for many years by what seems a fundamental problem; what exactly defines a nucleus pulposus (NP) cell? The paper by Gilson and colleagues elegantly re-opens the debate concerning the lineage and identity of NP cells that are alike yet different from chondrocytes. As we pursue novel investigations and treatment strategies for degenerative disc disease, how do we isolate these unique cells and what is the role of the primordial notochordal cell that may well linger within the NP far longer and perhaps in a different phenotypic appearance than previously thought? The paper by Gilson and colleagues that is the subject of the present editorial presents compelling data concerning the heterogeneity of the cells of the NP, and their origin, development, maturation and function

A framework for health care planning and control

Rising expenditures spur health care organizations to organize their processes more efficiently and effectively. Unfortunately, health care planning and control lags far behind manufacturing planning and control. Successful manufacturing planning and control concepts can not be directly copied, because of the unique nature of health care delivery. We analyze existing planning and control concepts or frameworks for health care operations management, and find that they do not properly address various important planning and control problems. We conclude that they only focus on hospitals, and are too narrow, focusing on a single managerial area, such as resource capacity planning, or ignoring hierarchical levels. We propose a modern framework for health care planning and control. Our framework integrates all managerial areas involved in health care delivery operations and all hierarchical levels of control, to ensure completeness and coherence of responsibilities for every managerial area. The framework can be used to structure the various planning and control functions, and their interaction. It is applicable broadly, to an individual department, an entire health care organization, and to a complete supply chain of cure and care providers. The framework can be used to identify and position various types of managerial problems, to demarcate the scope of organization interventions, and to facilitate a dialogue between clinical staff and managers. We illustrate the application of the framework with examples

Electronic Structure of Superconducting Ba6c60

We report the results of first-principles electronic-structure calculations for superconducting Ba6C60. Unlike the A3C60 superconductors, this new compound shows strong Ba-C hybridization in the valence and conduction regions, mixed covalent/ionic bonding character, partial charge transfer, and insulating zero-gap band structure.Comment: 11 pages + 4 figures (1 appended, others on request), LaTeX with REVTE

Improve OR-schedule to reduce number of required beds

After surgery most of the surgical patients have to be admitted in a ward in the hospital. Due to financial reasons and an decreasing number of available nurses in the Netherlands over the years, it is important to reduce the bed usage as much as possible. One possible way to achieve this is to create an operating room (OR) schedule that spreads the usage of beds nicely over time, and thereby minimizes the number of required beds. An OR-schedule is given by an assignment of OR-blocks to specific days in the planning horizon and has to fulfill several resource constraints. Due to the stochastic nature of the length of stay of patients, the analytic calculation of the number of required beds for a given OR-schedule is a complex task involving the convolution of discrete distributions. In this paper, two approaches to deal with this complexity are presented. First, a heuristic approach based on local search is given, which takes into account the detailed formulation of the objective. A second approach reduces the complexity by simplifying the objective function. This allows modeling and solving the resulting problem as an ILP. Both approaches are tested on data provided by Hagaziekenhuis in the Netherlands. Furthermore, several what-if scenarios are evaluated. The computational results show that the approach that uses the simplified objective function provides better solutions to the original problem. By using this approach, the number of required beds for the considered instance of HagaZiekenhuis can be reduced by almost 20%

An analytical comparison of the patient-to-doctor policy and the doctor-to-patient policy in the outpatient clinic

Outpatient clinics traditionally organize processes such that the doctor remains in a consultation room, while patients visit for consultation, we call this the Patient-to-Doctor policy. A different approach is the Doctor-to-Patient policy, whereby the doctor travels between multiple consultation rooms, in which patients prepare for their consultation. In the latter approach, the doctor saves time by consulting fully prepared patients. We compare the two policies via a queueing theoretic and a discrete-event simulation approach. We analytically show that the Doctor-to-Patient policy is superior to the Patient-to-Doctor policy under the condition that the doctor’s travel time between rooms is lower than the patient’s preparation time. Simulation results indicate that the same applies when the average travel time is lower than the average preparation time. In addition, to calculate the required number of consultation rooms in the Doctor-to-Patient policy, we provide an expression for the fraction of consultations that are in immediate succession; or, in other words, the fraction of time the next patient is prepared and ready, immediately after a doctor finishes a consultation.We apply our methods for a range of distributions and parameters and to a case study in a medium-sized general hospital that inspired this research

A norm utilisation for scarce hospital resources: Evidence from operating rooms in a Dutch university hospital

Background:\ud Utilisation of operating rooms is high on the agenda of hospital managers and researchers. Many efforts in the area of maximising the utilisation have been focussed on finding the holy grail of 100% utilisation. The utilisation that can be realised, however, depends on the patient mix and the willingness to accept the risk of working in overtime.\ud \ud Materials and methods:\ud This is a mathematical modelling study that investigates the association between the utilisation and the patient mix that is served and the risk of working in overtime. Prospectively, consecutively, and routinely collected data of an operating room department in a Dutch university hospital are used. Basic statistical principles are used to establish the relation between realistic utilisation rates, patient mixes, and accepted risk of overtime.\ud \ud Results:\ud Accepting a low risk of overtime combined with a complex patient mix results a low utilisation rate. If the accepted risk of overtime is higher and the patient mix is less complex, the utilisation rate that can be reached is closer to 100%.\ud \ud Conclusion:\ud Because of the inherent variability of health-care processes, the holy grail of 100% utilisation is unlikely to be found. The method proposed in this paper calculates a realistic benchmark utilisation that incorporates the patient mix characteristics and the willingness to accept risk of overtime

Notochordal cells protect nucleus pulposus cells from degradation and apoptosis: implications for the mechanisms of intervertebral disc degeneration

Abstract Introduction The relative resistance of non-chondrodystrophic (NCD) canines to degenerative disc disease (DDD) may be due to a combination of anabolic and anti-catabolic factors secreted by notochordal cells within the intervertebral disc (IVD) nucleus pulposus (NP). Factors known to induce DDD include interleukin-1 beta (IL-1ß) and/or Fas-Ligand (Fas-L). Therefore we evaluated the ability of notochordal cell conditioned medium (NCCM) to protect NP cells from IL-1ß and IL-1ß +FasL-mediated cell death and degeneration. Methods We cultured bovine NP cells with IL-1ß or IL-1ß+FasL under hypoxic serum-free conditions (3.5% O2) and treated the cells with either serum-free NCCM or basal medium (Advanced DMEM/F-12). We used flow cytometry to evaluate cell death and real-time (RT-)PCR to determine the gene expression of aggrecan, collagen 2, and link protein, mediators of matrix degradation ADAMTS-4 and MMP3, the matrix protection molecule TIMP1, the cluster of differentiation (CD)44 receptor, the inflammatory cytokine IL-6 and Ank. We then determined the expression of specific apoptotic pathways in bovine NP cells by characterizing the expression of activated caspases-3, -8 and -9 in the presence of IL-1ß+FasL when cultured with NCCM, conditioned medium obtained using bovine NP cells (BCCM), and basal medium all supplemented with 2% FBS. Results NCCM inhibits bovine NP cell death and apoptosis via suppression of activated caspase-9 and caspase-3/7. Furthermore, NCCM protects NP cells from the degradative effects of IL-1ß and IL-1ß+Fas-L by up-regulating the expression of anabolic/matrix protective genes (aggrecan, collagen type 2, CD44, link protein and TIMP-1) and down-regulating matrix degrading genes such as MMP-3. Expression of ADAMTS-4, which encodes a protein for aggrecan remodeling, is increased. NCCM also protects against IL-1+FasL-mediated down-regulation of Ank expression. Furthermore, NP cells treated with NCCM in the presence of IL-1ß+Fas-L down-regulate the expression of IL-6 by almost 50%. BCCM does not mediate cell death/apoptosis in target bovine NP cells. Conclusions Notochordal cell-secreted factors suppress NP cell death by inhibition of activated caspase-9 and -3/7 activity and by up-regulating genes contributing anabolic activity and matrix protection of the IVD NP. Harnessing the restorative powers of the notochordal cell could lead to novel cellular and molecular strategies in the treatment of DDD

Intrathecal Morphine for Laparoscopic Segmental Colonic Resection as Part of an Enhanced Recovery Protocol: A Randomized Controlled Trial

Background and Objectives: Management of postoperative pain after laparoscopic segmental colonic resections remains controversial. We compared 2 methods of analgesia within an Enhanced Recovery After Surgery (ERAS) program. The goal of the study was to investigate whether admin

Consolidation of Geologic Studies of Geopressured Geothermal Resources in Texas

The objective of the current studies at the Pleasant Bayou geopressured geothermal reservoir in Brazoria County, Texas, was to evaluate the resource base and long-term performance. The approach was to develop an integrated understanding of the hydrogeology of the reservoir and the hydrochemistry of the produced brine. Such an understanding would allow determination of the extent of lateral and vertical hydrologic continuity of the target zone and to identify the sources of brine being produced from the geopressured reservoir. The current phase of long-term production testing of the Frio C-zone at Pleasant Bayou Well No. 2 began in May 1988. During the past 16 months of production, nearly 6.8 million barrels of brine and 162.2 million cubic feet of gas have been produced, and a relatively small (less than 300 psi) drop in bottom-hole pressure has been observed at sustained producing rates of between 15,000 and 20,000 barrels per day. Earlier geologic studies have estimated the effective pore volume of the C-zone in the neighborhood of 6.2 to 6.6 billion barrels. Analysis of pressure and production data from current testing indicates that the limits of the geopressured reservoir at Pleasant Bayou have not been reached; that is, either the size of the reservoir could be larger than anticipated, or there could be a continuous influx of waters from other geopressured sources that sustains the reservoir energy at Pleasant Bayou. Geochemical testing has proved inconclusive in identifying other sources of water partly because of the variability of chemical composition within the produced zone. Evaluation of reservoir performance at active oil and gas fields in the immediate vicinity of the Pleasant Bayou fault block has not provided evidence of direct hydrologic communication between the geopressured aquifer and the overlying hydrocarbon reservoirs. The pattern of depletion in these oil and gas fields reflects some characteristic features that may become evident in Pleasant Bayou over a long period of production. Moreover, additional refinement of the integrated hydrogeologic-hydrochemical model is possible either through prolonged testing at Pleasant Bayou No. 2 well or through drilling and testing of additional wells in the Pleasant Bayou fault block. Determining the nature of bounding faults around the test well will require additional seismic data as well as multiwell testing of the reservoir.Bureau of Economic Geolog

Patch-Seq Protocol to Analyze the Electrophysiology, Morphology and Transcriptome of Whole Single Neurons Derived From Human Pluripotent Stem Cells

The human brain is composed of a complex assembly of about 171 billion heterogeneous cellular units (86 billion neurons and 85 billion non-neuronal glia cells). A comprehensive description of brain cells is necessary to understand the nervous system in health and disease. Recently, advances in genomics have permitted the accurate analysis of the full transcriptome of single cells (scRNA-seq). We have built upon such technical progress to combine scRNA-seq with patch-clamping electrophysiological recording and morphological analysis of single human neurons in vitro. This new powerful method, referred to as Patch-seq, enables a thorough, multimodal profiling of neurons and permits us to expose the links between functional properties, morphology, and gene expression. Here, we present a detailed Patch-seq protocol for isolating single neurons from in vitro neuronal cultures. We have validated the Patch-seq whole-transcriptome profiling method with human neurons generated from embryonic and induced pluripotent stem cells (ESCs/iPSCs) derived from healthy subjects, but the procedure may be applied to any kind of cell type in vitro. Patch-seq may be used on neurons in vitro to profile cell types and states in depth to unravel the human molecular basis of neuronal diversity and investigate the cellular mechanisms underlying brain disorders