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PubMed2002

Information technology and acute dialysis.

The careful application of information technology to the field of acute dialysis may result in both a better understanding of the disease as well as an improvement in patient outcomes. Often these applications increase costs and complexity with little change in understanding or quality of care. To avoid this common trap, a targeted assessment of needs and possible solutions is mandatory. Our group was assembled to provide balanced perspectives and recommendations that address how information technology should be assessed and applied to acute dialysis therapy, with the intent to increase the understanding of the current practice and to improve patient care. To achieve these goals, five areas of focus were identified: patient safety, current practice pattern assessment, practice variation, patient assessment, and dialysis machine technology. To facilitate the assessment, we formulated five specific questions and developed answers based on the available literature and group consensus.

Acute Kidney Injury↗
PubMed2006

Microarray analysis of sarcomas.

Microarrays began to be used to study gene expression profiles in the mid-1990s, but it was only after 2000 that serious attempts have been made to apply this technology to investigate sarcomas. Microarray technologies provide a comprehensive survey of active molecular pathways and potential molecular targets for diagnosis and treatment, but are challenging to use because of issues of specimen collection, cost, and complexities in experimental design and data analysis. As a discovery-based technique, microarray analyses are most valuable when framed around specific gaps in our knowledge of tumor etiology and progression, challenges in differential diagnosis, and pressing therapeutic needs. To date, microarray analyses of sarcomas support their division into molecularly defined and molecularly heterogeneous categories, and have provided useful diagnostic markers for entities such as gastrointestinal stromal tumors, synovial sarcoma, and dermatofibrosarcoma protuberans. Signatures predicting outcome and response to therapy have been published for Ewing sarcoma and osteosarcoma, and receptor tyrosine kinase expression patterns have suggested novel therapeutic approaches which may be applied to several types of sarcoma. Nevertheless, results need to be interpreted in the context of histopathology and validated by complementary technologies and/or other research groups.

Biomarkers, Tumor↗
PubMed2006

Treatment of pulmonary hypertension with selective pulmonary vasodilators.

PURPOSE OF REVIEW: Pulmonary vasodilators are important in the management of pulmonary hypertension. Although systemic vasodilators may be effective in lowering pulmonary artery pressure, systemic vasodilation is the main limitation to dose titration. This review summarizes the latest research and developments in pulmonary vasodilators in the management of acute and chronic pulmonary hypertension. RECENT FINDINGS: Nitric oxide, the prototype of selective pulmonary vasodilators, remains an effective option in the management of pulmonary hypertension; however, cost and complexity of administration have led to consideration of other pulmonary vasodilators. Animal research suggests that nitric oxide may have an important role in the prevention of pulmonary hypertension after cardiopulmonary bypass. Experience with phosphodiesterase inhibitors, as monotherapy or as part of combination therapy, suggests that these agents improve cardiopulmonary hemodynamics and can be considered as alternatives and/or adjuncts to nitric oxide. Prostacyclins are a versatile class of pulmonary vasodilator as they have been shown to improve pulmonary hemodynamics administered intravenously or via inhalation. Endothelin receptor antagonists have been shown to be effective for long-term management of pulmonary hypertension. Several gene therapy strategies are currently undergoing evaluation. SUMMARY: Selective pulmonary vasodilation can be achieved through delivery of vasodilators directly to the lungs or targeting pulmonary specific processes. Several therapeutic options are available that demonstrate selectivity for the pulmonary vasculature. These agents can facilitate optimization of cardiopulmonary hemodynamics.

Calcium Channel Blockers↗
PubMed2006

Computer-assisted total knee arthroplasty using patient-specific templating.

Current techniques used for total knee arthroplasty rely on conventional instrumentation that violates the intramedullary canals. Accuracy of the instrumentation is questionable, and assembly and disposal of the numerous pieces is time consuming. Navigation techniques are more accurate, but their broad application is limited by cost and complexity. We aimed to prove a new concept of computer-assisted preoperative planning to provide patient-specific templates that can replace conventional instruments. Computed tomography-based planning was used to design two virtual templates. Using rapid prototyping technology, virtual templates were transferred into physical templates (cutting blocks) with surfaces that matched the distal femur and proximal tibia. We performed 45 total knee arthroplasties on 16 cadaveric and 29 plastic knees, including a comparative trial against conventional instrumentations. All operations were performed using patient-specific templates with no conventional instrumentations, intramedullary perforation, tracking, or registration. The mean time for bone cutting was 9 minutes with a surgical assistant and 11 minutes without an assistant. Computer-assisted analyses of six random computed tomography scans showed mean errors for alignment and bone resection within 1.7 degrees and 0.8 mm (maximum, 2.3 degrees and 1.2 mm, respectively). Patient-specific templates are a practical alternative to conventional instrumentations, but additional clinical validation is required before clinical use.

Aged↗
PubMed2005

Does the presence of an upper extremity injury affect outcomes after major trauma?

BACKGROUND: There is a paucity of information about the impact of upper extremity (UE) injuries on patient outcomes, particularly after major trauma. METHODS: Data were obtained from a statewide trauma registry. Cases were defined as major trauma cases (Injury Severity Score > 15) with (UE group) and without (no-UE group) an associated upper extremity injury. Multivariate analysis was performed to identify independent predictors of outcome. RESULTS: Major trauma patients with UE injury were 1.5 times (p = 0.011) more likely than the no-UE group to have a length of stay greater than 7 days. After adjusting for age, mechanism of injury, and Injury Severity Score, UE injury was not an independent predictor of discharge destination. CONCLUSION: In major trauma patients, the presence of an upper extremity injury is a significant predictor of length of stay, indicating a greater complexity and cost of care associated with this group of major trauma patients.

Accidental Falls↗
PubMed2026

SurvGRN: a multi-feature fusion framework for bladder cancer survival prediction.

Bladder cancer survival outcomes exhibit significant heterogeneity, influenced by multifaceted factors. While digital pathology-based survival models leveraging artificial intelligence show promise, they often overlook complementary data sources. Conversely, imaging lacks cellular detail, and genomics/proteomics entail complexity and cost. To integrate multidimensional data for enhanced survival prediction, we propose SurvGRN, a multi-feature fusion framework. SurvGRN synergistically combines clinical variables, transcriptomics, and digital pathology slides using a gated residual network architecture. Pathological features are extracted via multiple instance learning, while clinical and transcriptomic data are processed as static inputs. These features are dynamically fused using a long short-term memory (LSTM) network for comprehensive survival risk assessment. Evaluated on 400 bladder cancer patients, SurvGRN significantly outperformed existing methods: improving the C-index by 12.6% over DeepMISL; 20.6% and 7.1% over graph-based models (DeepGraphConv and Patch-GCN); and 5.4% and 4.0% over attention-based approaches (Surformer and HVTSurv). Ablation studies confirmed the contributions of pathology features (extracted via ResNet-50 pre-trained on bladder tissue), clinical/transcriptomic data, and the LSTM fusion. SurvGRN also enabled significant stratification of patients into distinct risk cohorts. This work demonstrates that holistic integration of multi-source data through tailored fusion architectures substantially improves bladder cancer survival prediction.

bladder cancer↗
PubMed2007

Adaptation of the ultrasensitive HIV-1 p24 antigen assay to dried blood spot testing.

Implementation of molecular tests for the assessment of pediatric HIV-1 infection in resource-limited countries is difficult because of technical complexity and costs. Alternatives like the ultrasensitive HIV-1 p24 antigen enzyme-linked immunosorbent assay have therefore been proposed. We have now adapted this test to dried blood spot (DBS) plasma p24 antigen (p24). High background activity was recognized as originating from endogenous peroxidase and eliminated by H2O2 quenching. The assay was evaluated with 72 pediatric specimens from Tanzania and with 210 pediatric or adult specimens from Switzerland. A real-time polymerase chain reaction assay for DBS DNA and/or plasma RNA identified HIV-1 infection in 38 Tanzanian children. HIV-1 subtypes included 18 C, 9 A1, 8 D, 1 AC, 1 J-like, and 1 unidentified. The detection rates for the different assays were as follows: DBS-p24, 32 (84%) of 38 samples; DBS DNA, 30 (79%) of 38 samples; plasma-p24, 23 (85%) of 27 samples; and plasma RNA, 30 (100%) of 30 samples. False-negative DBS-p24 was associated with subtype D (P < 0.01). DBS-p24 detection for non-D subtypes was 93% (95% confidence interval: 81% to 99%), and for subtype C, it was 94% (95% confidence interval: 76% to 99%). Specificity among 193 HIV-negative DBS samples was 100%. Correlation of DBS-p24 and plasma-p24 concentrations was excellent (R = 0.83, P < 0.0001). DBS-p24 is thus a promising alternative to molecular tests for HIV-1 in subtype C regions. It should now be evaluated in large studies of children for accurate assessment of diagnostic sensitivity.

Adolescent↗
PubMed2003

Ultrastructure meets reproductive success: performance of a sphecid wasp is correlated with the fine structure of the flight-muscle mitochondria.

Organisms show a remarkable inter-individual variation in reproductive success. The proximate causes of this variation are not well understood. We hypothesized that the ultrastructure of costly or complex tissues or organelles might affect reproductive performance. We tested this hypothesis in females of a sphecid wasp, the European beewolf, Philanthus triangulum (Hymenoptera, Sphecidae), that show considerable variation in reproductive success. The most critical component of reproduction in beewolf females is flying with paralysed honeybees, which more than double their weight. Because of the high energetic requirements for flight, we predicted that the ultrastructure of the flight-muscle mitochondria might influence female success. We determined the density of mitochondria and the density of the inner mitochondrial membranes (DIMM) of the flight muscles as well as age, body size and fat content. Only DIMM had a significant influence on female reproductive success, which might be mediated by an elevated adenosine triphosphate (ATP) supply. The variation in DIMM might result from differences in larval provisions or from an accumulation of mutations in the mitochondrial genome. Our results support the hypothesis that the organization of complex structures contributes to inter-individual variation in reproductive success.

Adenosine Triphosphate↗
PubMed2026

Architectural logic of the 3D genome: mechanisms of dysregulation and emerging cancer therapeutics.

The three-dimensional (3D) genome provides an essential layer of organization that shapes genome function in space and time. Chromatin compartments and topologically associating domains (TADs) arise from the interplay between intrinsic properties of chromatin and architectural factors, including cohesin and CTCF. Despite substantial progress in defining these structural features, whether 3D genome architecture plays a causal role in regulating processes such as transcription, DNA replication, and DNA repair, or instead reflects underlying regulatory activity, remains unresolved. Here, we use the distinction between chromatin-intrinsic features and architectural factors as a framework to evaluate evidence for causality in genome structure-function relationships. We extend this framework to cancer, where both intrinsic alterations (including noncoding mutations, structural variants, and changes in chromatin state) and architectural factor perturbations (such as mutations in architectural proteins and dysregulation of transcriptional machinery) disrupt genome organization and contribute to disease progression. These findings suggest that alterations in genome structure can, in some contexts, actively reshape oncogenic programs. A major limitation in applying 3D genome insights to cancer biology is the cost and complexity of omics assays. Recent advances in artificial intelligence (AI) and machine learning (ML) enable inference and prediction of 3D genome organization from sequence and epigenomic features, providing insight into the extent to which genome folding is encoded intrinsically versus dynamically regulated in architectural factors. This perspective provides a unified view of how genome structure is established, how it relates to function, and how its disruption contributes to tumorigenesis.

3D genome↗
PubMed1998

An automated hydrodynamic process for controlled, unbiased DNA shearing.

An automated, inexpensive, easy-to-use, and reproducible technique for controlled, random DNA fragmentation has been developed. The technique is based on point-sink hydrodynamics that result when a DNA sample is forced through a small hole by a syringe pump. Commercially available components are used to reduce the cost and complexity of the instrument. The design is optimized to reduce the volume of sample required and to speed processing time. Shearing of the samples can be completely automated by computer control. Ninety percent of sheared DNA fragments fall within a twofold size distribution that is highly reproducible. Three parameters are critical: the flow geometry, the flow rate, and a minimum number of iterations. Shearing is reproducible over a wide range of temperatures, DNA concentrations, and initial DNA size. The cloning efficiency of the sheared DNA is very good even without end repair, the distribution of assembled sequences is random, and there is no sequence bias at the ends of sheared fragments that have been cloned. The instrument, called the Point-sink Shearer (PtS), has already been exported successfully to many other laboratories.

Automation↗
PubMed2001

Novel final focus design for future linear colliders.

The length, complexity, and cost of the present final focus designs for linear colliders grow very quickly with the beam energy. In this Letter, a novel final focus system is presented and compared with the one proposed for the Next Linear Collider (NLC Zeroth-Order Design Report, edited by T. O. Raubenheimer, SLAC Report No. 474, 1996). This new design has fewer optical elements and is much shorter, nonetheless achieving better chromatic properties. Moreover, the new system is more suitable for operation over a larger energy range.

Journal Article↗
PubMed2003

Overview and new developments in softer X-ray (2A < lambda < 5A) protein crystallography.

New methodologies with synchrotron radiation and X-ray free electron lasers (XFELs) in structural biology are being developed. Recent trends in harnessing softer X-rays in protein crystallography for phase determination are described. These include reference to a data-collection test at 2.6 A wavelength with a lysozyme crystal on SRS station 7.2 (Helliwell, 1983) and also use of softer X-rays (2 A wavelength) to optimise f " at the xenon L1 absorption edge in the Single Isomorphous Replacement Optimised Anomalous Scattering ('SIROAS') structure determination of apocrustacyanin A1 with four, partially occupied, xenon atoms (Cianci et al., 2001; Chayen et al., 2000). The hand of the protein was determined using the f " enhanced sulphur anomalous signal from six disulphides in the protein dimer of 40 kDa. In a follow-up study the single wavelength xenon L1-edge f " optimised data set alone was used for phase determination and phase improvement by solvent flattening etc. (CCP4 DM) (Olczak et al., 2003). Auto-tracing of the protein was feasible but required additional diffraction data at higher resolution. This latter could be avoided in future by using improved tilted detector settings during use of softer X-rays, i.e. towards back-scattering recording (Helliwell, 2002). The Olczak et al. study has already led to optimisation of the new SRS beamline MPW MAD 10 (see www.nwsgc.ac.uk) firstly involving the thinning of the beryllium windows as much as possible and planning for a MAR Research tilted detector 'desk top beamline' geometry. Thus the use of softer, i.e. 2 to 3 A wavelength range, X-rays will allow optimisation of xenon and iodine L-edge f " and enhancing of sulphur f " signals for higher throughput protein crystallography. Softer X-rays utilisation in protein crystallography includes work done on SRS bending-magnet station 7.2 in the early 1980s by the author as station scientist (Helliwell, 1984). In the future development of XFELs these softer X-ray wavelengths could also be harnessed and relax the demands to some extent on the complexity and cost of an XFEL. Thus, by use of say 4 A XFEL radiation and use of a back-scattering geometry area detector the single molecule molecular transform could be sampled to a spatial resolution of 2 A, sufficient, in principle, for protein model refinement (Miao et al., 1999). Meanwhile, Miao et al. (2003) report the first experimental recording of the diffraction pattern from intact Escherichia coli bacteria using coherent X-rays, with a wavelength of 2 A, at a resolution of 30 nm and a real-space image constructed. The new single-particle X-ray diffraction-imaging era has commenced.

Crystallography, X-Ray↗
PubMed2002

Using geographical information systems for management of back-pain data.

In the medical world, statistical visualisation has largely been confined to the realm of relatively simple geographical applications. This remains the case, even though hospitals have been collecting spatial data relating to patients. In particular, hospitals have a wealth of back pain information, which includes pain drawings, usually detailing the spatial distribution and type of pain suffered by back-pain patients. Proposes several technological solutions, which permit data within back-pain datasets to be digitally linked to the pain drawings in order to provide methods of computer-based data management and analysis. In particular, proposes the use of geographical information systems (GIS), up till now a tool used mainly in the geographic and cartographic domains, to provide novel and powerful ways of visualising and managing back-pain data. A comparative evaluation of the proposed solutions shows that, although adding complexity and cost, the GIS-based solution is the one most appropriate for visualisation and analysis of back-pain datasets.

Back Pain↗
PubMed2000

Method of reduction of the number of driving system channels for phased-array transducers using isolation transformers.

Phased-array technology offers an incredible advantage to therapeutic ultrasound due to the ability to electronically steer foci, create multiple foci, or to create an enlarged focal region by using phase cancellation. However, to take advantage of this flexibility, the phased-arrays generally consist of many elements. Each of these elements requires its own radio-frequency generator with independent amplitude and phase control, resulting in a large, complex, and expensive driving system. A method is presented here where in certain cases the number of amplifier channels can be reduced to a fraction of the number of transducer elements, thereby simplifying the driving system and reducing the overall system complexity and cost, by using isolation transformers to produce 180 degrees phase shifts.

Electric Impedance↗
PubMedDate not supplied

The Allient dialysis system.

The Allient is a dialysis system that combines various technologies to allow dialysis to be performed at sites outside of dialysis units (intensive care unit [ICU] or home) with ease and safety. A sorbent column regenerates dialysate, removing toxins and providing ultrapure dialysate from only 6 liters of tap water. The use of the sorbent column eliminates the need for costly and complex water purification systems. The Pulsar Blood Movement System provides blood flow at constant negative or positive pressure through single-lumen or dual-lumen accesses, maximizing blood flow rate while eliminating bothersome pressure alarms. Ultrasonic flow monitors control the operation of the pump and ensure adequate blood flow during each dialysis treatment. A completely disposable blood tubing and dialysate circuit eliminates the need for sterilization of the machine. The Allient should make dialysis in the ICU or home setting much more practical, reducing training requirements and increasing safety.

Equipment Design↗
PubMed1979

Enzyme linked immunosorbent assay (ELISA) for IgG and IgE antibodies to protein and polysaccharide antigens of Aspergillus fumigatus.

ELISA has emerged as a useful alternative to other more costly and complex tests. Polystyrene microhaemagglutination plates have been used as solid phase to absorb Aspergillus fumigatus protein and polysaccharide components for detection of specific antibodies in patients with various forms of pulmonary aspergillosis. IgG and IgE antibodies to the polysaccharide as well as the protein allergens have been found. For the IgE test a double antibody technique has been developed, which is more sensitive than the conventional indirect ELISA.

Antigens, Fungal↗
PubMed1995

Future challenges to coronary angioplasty: perspectives on intracoronary imaging and physiology.

Several intravascular techniques have been developed with the purpose of achieving optimal guidance for treatment during coronary angioplasty (PTCA). Although the coronary angiographic technique is well established, there are still some inherent limitations. Due to intimal rupture, tears, dissection and thrombus following PTCA treatment, angiography does not allow exact delineation of the true borders of the vessel. Coronary angioscopy is currently the most sensitive method to detect coronary thrombus and can also be used to classify atheromatous plaques. Furthermore, coronary dissection can be detected with more accuracy than with angiography. One limitation associated with angioscopy is the need to occlude the vessel during imaging, which may create myocardial ischaemia. Furthermore, there is presently no method for quantifying angioscopic findings. Intravascular ultrasound produces a cross-sectional image of the vessel, which permits analysis of the layers of the vascular wall. Characterization and classification of various types of plaque can be made because thrombus, lipid, fibrous tissue and calcium have different ultrasonic echogenicity. Flow velocity measurement with the Doppler technique is an interesting approach to the physiological assessment of coronary stenoses. Coronary flow reserve can be estimated with this method and monitoring of the flow signal following angioplasty will aid in the diagnosis of flow-limiting complications. The trans-stenotic pressure gradient is a valuable measure of the haemodynamic importance of a coronary lesion. Trans-stenotic gradients during maximal hyperaemia obtained with a miniaturized pressure transducer yield reliable information regarding the severity of the stenosis, and the pressure values may be used to calculate the relative coronary flow reserve. In conclusion, all of these intracoronary diagnostic techniques will to some extent play a role in the future of coronary angioplasty. Safety, cost and complexity are some of the factors which will determine the growth potential of each method.

Angioplasty, Balloon, Coronary↗
PubMed2005

Genomics and systems biology--how relevant are the developments to veterinary pharmacology, toxicology and therapeutics?

This review discusses some of the recent developments in genomics and its current and future relevance for veterinary pharmacology and toxicology. With the rapid progress made in this field several new approaches in pharmacological and toxicological research have developed and drug discovery and drug development strategies have changed dramatically. In this review, the term genomics is used to encompass the three sub-disciplines transcriptomics, proteomics and metabolomics (or metabonomics) to describe the formation and fate of mRNA, proteins and metabolites, respectively. The current status and methods of the technology and some applications are briefly described. Although the DNA sequencing programmes are receiving considerable attention, the real value of genomics for pharmacology and toxicology is brought by the parallel developments in bio-informatics, bio-statistics and the integration of biology with mathematics and information technology. The ultimate level of integration is now mostly called systems biology, where mRNA, proteins and metabolites are being analysed in parallel, using a complete arsenal of analytical techniques (DNA-array, LC-MS/MS, GC-MS/MS, NMR, etc.). The information thus collected is analysed, integrated, linked to database information and translated to pathways and systems. This approach offers an enormous potential to study disease mechanisms and find new drug targets. Thus far, genomics and systems biology have not been introduced significantly in typical veterinary pharmacological and toxicological research programmes. The high costs and complexity connected to these large projects often form major obstacles for research groups with limited budgets. In other veterinary areas and disciplines, including infectious diseases, animal production and food-safety more examples of application are available. Genomics and bio-informatics provide outstanding opportunities to study pharmacology and toxicology in a more holistic way, taking into account the complexity of biological systems and based on the basic principles of physiology and the concept of homeostasis. Knowledge of biology, in vivo and in vitro models, and comparative pharmacology/toxicology is essential here, creating excellent opportunities for the veterinary trained scientist.

Animals↗