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The NHS English National Service framework for older people: opportunities and risks.

The English National Service Framework (NSF) for Older People conforms to the emerging pattern of NSFs as hybrids of policy and evidence, drafted and edited within the Department of Health, albeit with external advisory input. Physicians welcome its much-needed focus on the needs of older people, but its dynamic differs from that underlying the evolution of comprehensive services to date, raising concerns that its declared objectives may be unrealised or perversely interpreted. This applies to the first three (of eight) 'standards' currently being applied: rooting out ageism, the single assessment process and intermediate care. With each, there are problems of concept, operational feasibility, expertise and accountability for standards. Conversely, the standards for subspecialty service models (stroke, falls, mental health) are more significantly underpinned by evidence and operational experience. Success overall will depend on more clearly defined resource flow and accountability, career recruitment, research direction and engagement with specialist physicians than are immediately apparent in the document.

Aged↗

Sequence of C region of L chains from Xenopus laevis Ig.

A cDNA expression library, prepared from Xenopus laevis splenocytes, was screened with antibodies to Xenopus Ig. One clone, lambda XIg23, reacted with antibodies to IgY and to IgM; the insert hybridized to approximately 1.3-kb RNA from spleen, the approximate size expected for L chain mRNA. An additional clone, lambda XIg31, was identified by cross-hybridization. The inserts of lambda XIg23 and lambda XIg31 begin in the third framework region of the V region and extend through the C region to the poly(A) tail. Except for a single nucleotide difference, the two C region sequences are identical. The amino acid sequence of the C region was compared with the sequences of a variety of C kappa and C lambda, as well as to C region sequences of L chains from Rana catesbeiana and from two species of shark. The Xenopus C region resembles mouse and human C kappa slightly more than C lambda. The similarity of the Xenopus and Rana C regions to each other is approximately the same as that of either amphibian sequence to mammalian CL. The data are discussed in terms of the evolution of kappa and lambda C regions.

Amino Acid Sequence↗

Classical polarization in hybrid QM/MM methods.

We have presented a method for modeling polarization in hybrid QM/MM calculations. The method, which expresses the induced dipoles as a set of "induced" charges, is based on the induced dipole approach and methodology for calculating potential-derived point charges from distributed multipole series. The method has the advantage that the same methodology can be used to determine the induced charges and the potential derived charges and so both sets of charges are rigorously defined within the same framework. This underlying link with the wave function makes the method particularly suitable for use in hybrid QM/MM calculations. Here we assess the importance of explicit polarization in the classical part of a QM/MM system with regard to improving the classical description and the consequent effects on the quantum description. The main advantages of the induced charge approach are that the method is readily interfaced with quantum mechanical methods and that induced charges are more readily interpreted than induced dipoles. The ease of interpretation is illustrated by analysis of the charges involved in dimeric and trimeric hydrogen bonded systems. The method for treating the MM polarization has been validated by a regression analysis of the charges induced in both the QM and MM systems against those derived from full quantum mechanical calculations. The method has also been validated using two energy decomposition approaches, which show that MM polarization makes a significant and reliable contribution to the QM - MM interaction energy in a hybrid system. The distance dependency of the induced charges is investigated in calculations on methylsuccinyl-Ala-Ala-Pro-Ala chlormethyl ketone interacting with human neutrophil elastase and propranolol interacting with asparagine residues in a model of the beta(2)-adrenergic receptor.

Algorithms↗

Universal DNA tag systems: a combinatorial design scheme.

Custom-designed DNA arrays offer the possibility of simultaneously monitoring thousands of hybridization reactions. These arrays show great potential for many medical and scientific applications, such as polymorphism analysis and genotyping. Relatively high costs are associated with the need to specifically design and synthesize problem-specific arrays. Recently, an alternative approach was suggested that utilizes fixed, universal arrays. This approach presents an interesting design problem-the arrays should contain as many probes as possible, while minimizing experimental errors caused by cross-hybridization. We use a simple thermodynamic model to cast this design problem in a formal mathematical framework. Employing new combinatorial ideas, we derive an efficient construction for the design problem and prove that our construction is near-optimal.

Base Sequence↗

Optimal erasure protection for scalably compressed video streams with limited retransmission.

This paper shows how the priority encoding transmission (PET) framework may be leveraged to exploit both unequal error protection and limited retransmission for RD-optimized delivery of streaming media. Previous work on scalable media protection with PET has largely ignored the possibility of retransmission. Conversely, the PET framework has not been harnessed by the substantial body of previous work on RD optimized hybrid forward error correction/automatic repeat request schemes. We limit our attention to sources which can be modeled as independently compressed frames (e.g., video frames), where each element in the scalable representation of each frame can be transmitted in one or both of two transmission slots. An optimization algorithm determines the level of protection which should be assigned to each element in each slot, subject to transmission bandwidth constraints. To balance the protection assigned to elements which are being transmitted for the first time with those which are being retransmitted, the proposed algorithm formulates a collection of hypotheses concerning its own behavior in future transmission slots. We show how the PET framework allows for a decoupled optimization algorithm with only modest complexity. Experimental results obtained with Motion JPEG2000 compressed video demonstrate that substantial performance benefits can be obtained using the proposed framework.

Algorithms↗

Regional resolving power of combined MEG/EEG.

Different modeling frameworks (such as error analyses for dipole localization [Fuchs, 1998] [Huizenga, 2001]; crosstalk and point spread analyses for linear estimators [Liu, 2002]; etc.) have demonstrated improved three-dimensional (3D) resolution for combined MEG/EEG (or EMEG) source estimation. Complementary to these, an empirical analysis of 2D surface data suggested that MEG and EEG information content could be superadditive [Pflieger, 2000]. Taking a hybrid approach in the present study, we made simulations within a regional activity estimation (REGAE, [Pflieger, 2001]) framework, which quantifies the ability of EMEG to discriminate brain activity originating within a 3D region of interest (ROI) from simultaneous non-ROI activity. Two metrics were employed: Kullback-Leibler divergence (KLD) and area under the receiver operator characteristic curve (AUROC). High-density sensor configurations (248 magnetometers, 256 electrodes) were combined with a gray matter source space model (7931 dipole triples, maximum entropy activities), assuming magnetic 3-shell sphere and electric BEM head models. Superadditive KLD was observed frequently across 89 representative brain ROIs and 3 ROI sizes (5, 10, and 15 mm radii), especially for regions already fairly visible to each modality. We also report an observed functional relationship between AUROC and KLD.

Computer Simulation↗

A system control framework for the self-fertilization and selection process of breeding.

The self-fertilization and selection process is the main method for speeding up the purifying course of a hybrid population in breeding. This is a complex combinatorial random process with large time delay. To raise the control effectiveness and efficiency of the process, we try, in this paper, to construct a mathematical model of the process by means of effective factors. Then, a control framework for the process is presented which can be used as a guide by breeders for helping them in selecting appropriate control actions.

Fertilization↗

A genetic map in the Mimulus guttatus species complex reveals transmission ratio distortion due to heterospecific interactions.

As part of a study of the genetics of floral adaptation and speciation in the Mimulus guttatus species complex, we constructed a genetic linkage map of an interspecific cross between M. guttatus and M. nasutus. We genotyped an F(2) mapping population (N = 526) at 255 AFLP, microsatellite, and gene-based markers and derived a framework map through repeated rounds of ordering and marker elimination. The final framework map consists of 174 marker loci on 14 linkage groups with a total map length of 1780 cM Kosambi. Genome length estimates (2011-2096 cM) indicate that this map provides thorough coverage of the hybrid genome, an important consideration for QTL mapping. Nearly half of the markers in the full data set (49%) and on the framework map (48%) exhibited significant transmission ratio distortion (alpha = 0.05). We localized a minimum of 11 transmission ratio distorting loci (TRDLs) throughout the genome, 9 of which generate an excess of M. guttatus alleles and a deficit of M. nasutus alleles. This pattern indicates that the transmission ratio distortion results from particular interactions between the heterospecific genomes and suggests that substantial genetic divergence has occurred between these Mimulus species. We discuss possible causes of the unequal representation of parental genomes in the F(2) generation.

Alleles↗

A diffusion-reaction model for DNA microarray assays.

DNA microarrays are extensively used for the quantification of the degree of differential mRNA expression. The assay involves hybridization of mobile DNA strands with immobilized complementary DNA strands to form duplexes. The overall duplex formation rate depends on the rate of transport of strands in solution to the corresponding spot on the surface, and the rate of the hybridization reaction. We present a theoretical model that incorporates both kinetics of the reversible hybridization reaction and diffusional transport of the labeled strands, and analyze DNA microarray hybridization using this model. Simulations are carried out in a geometrically realistic domain for labeled DNA concentrations corresponding to rare and abundant transcripts for typical assay conditions. The rate of strand diffusion in solution is shown to strongly affect the overall hybridization rate. We compute the minimum inter-spot spacing for replicate spots to enhance sensitivity. We also determine the hybridization time for which reliable estimates of the relative mRNA abundance of two species can be obtained using total fluorescence intensities. An analytical solution for the concentration distribution of mobile strands at intermediate hybridization times provides a convenient tool to calculate the mobile strand concentration profiles. This model provides a framework for the process analysis of all microarray assays currently used for genomic transcriptional analysis.

Computer-Aided Design↗

Comparison of latent and nominal rabbit Ig VHa1 allotype cDNA sequences.

The genetic basis for the expression of a latent VH allotype in the rabbit was investigated. VH region cDNA libraries were produced from spleen mRNA derived from a homozygous a2a2 rabbit expressing an induced latent VHa1 allotype and, for comparison, from a normal homozygus a1a1 rabbit expressing nominal VHa1 allotype. The deduced amino acid sequences of the nominal VHa1 cDNA were concordant with previously published VHa1 protein sequences. A comparison of two complete VH-DH-JH and six partial VHa1 sequences reveals highly conserved sequence within VH framework regions (FR) and considerable diversity in complementarity-determining regions and D region sequences. Two functional JH genes or alleles are evident. Amino acid sequencing of the N-terminal 15 residues of pooled affinity-purified latent VHa1 H chain showed complete sequence identity with the nominal VHa1 sequences. Possible latent VHa1-encoding cDNA clones, derived from the a2a2 rabbit, were selected by hybridization with oligonucleotide probes corresponding to the VHa1 allotype-associated segments of the first and third framework regions (FR1 and FR3). cDNA sequence analysis reveals that the 5' untranslated regions of nominal and latent VHa1 cDNA were virtually identical to each other and to previously reported sequences associated with VHa2 and VHa-negative genes. Moreover, some latent VHa1 genes encode FR1 segments that are essentially homologous to the corresponding segment of a nominal VHa1 allotype. In contrast, other putative latent genes display blocks of VHa1 sequence in either FR1 or FR3 that are flanked by blocks of sequence identical to other rabbit VH genes (i.e., VHa2 or VHa-negative). These composite sequences may be directly encoded by composite germ-line VH genes or may be the products of somatically generated recombination or gene conversion between genes encoding latent and nominal allotypes. The data do not support the hypothesis that latent genes are the result of extensive modification by somatic point mutation.

Amino Acid Sequence↗

Development of hydroxyapatite bone scaffold for controlled drug release via poly(epsilon-caprolactone) and hydroxyapatite hybrid coatings.

A scaffold-coating design, the hydroxyapatite (HA) porous bone scaffold coated with poly(epsilon-)caprolactone (PCL) and HA powder hybrids, was developed for use as tissue-regeneration and controlled-release system. An antibiotic drug, tetracycline hydrochloride (TCH), was encapsulated within the hybrid coating layer through a dip-coating and solvent-casting method. Coating cycle and drug loading amount differed to control the level of drug-release rate. The HA scaffold framework, obtained by a polymeric foam reticulate method, exhibited a highly porous structure, with porosity and pore size of approximately 87% and 180 microm, respectively. The hybrid layer, consisting of PCL sheet and HA fine powders, was uniformly coated on the scaffold surface. The coating layer exhibited only PCL and HA phases and structures, revealing no chemical interaction among the coating components, as observed by X-ray diffraction (XRD) and Fourier-transform infrared (FTIR) analyses. The coated-HA scaffolds showed an effective stress distribution behavior in response to an applied load, as confirmed by the compressive stress-strain curve. The mechanical properties of the coated scaffolds were improved highly with coatings; the compressive strength and elastic modulus of the cyclic coated scaffolds were approximately 3-4 times, and the energy absorption were approximately 8 times, higher than those without coating. These improvements were attributed mainly to the shielding of framework flaws by a flexible coating layer and partially to the thicker stems (porosity reduction). The dissolution of the coated scaffolds in a phosphate-buffered saline (PBS) solution increased with incubation time. The drug was released sharply within the initial several hours ( approximately 2 h), but the rate decreased further, showing a sustained release. The release amount was well controlled via coating-cycle and initial drug loading amount, suggesting the effectiveness of the coating-scaffold design as a drug-delivery system.

Bone and Bones↗

Latent a1 VH germline genes in an a2a2 rabbit. Evidence for gene conversion at both the germline and somatic levels.

We have previously reported the sequences of putative latent a1 cDNA derived from an alpha 2 alpha 2 rabbit. Significant similarity to nominal a1 cDNA sequences was noted, but none of the latent sequences were completely a1-like. We have now probed a genomic library, produced from the same alpha 2 alpha 2 rabbit, for evidence of germline latent a1 VH genes. Four hundred ninety-four VH+ clones were screened with oligonucleotides specific for a1 diagnostic regions of framework region 1 (FR1) and FR3. Twenty-two percent of the VH+ clones hybridized with an a1FR3 oligonucleotide probe. Two a1 FR1 probes yielded weak signals with 6% to 13% of the VH+ clones. Twenty VH genes from clones positive for one or more of the a1-specific oligonucleotide probes were sequenced, revealing 14 unique germline VH genes. All but one of these genes were 85% to 92% identical to the VH1-a1 nominal gene prototype, with sequence identity extending into the leader intron. Most genes displayed extended regions of similarity to a1 in FR1, FR3, or both and expressed 13 to 17 of the 21 allotype-associated residues, consistent with the nominal a1 sequence. The a1-like sequences were variously interspersed with short non-a1 segments, suggestive of germline gene conversion. Although none of the germline a1-like VH genes we have isolated from the alpha 2 alpha 2 rabbits are identical to the known a1 genes or protein sequences from alpha 1 alpha 1 rabbits and 8 of 14 are pseudogenes, most could make significant contributions to the synthesis of a complete nominal a1 sequence by serving as a pool of sequence donors during somatic gene conversion.

Amino Acid Sequence↗

A new class of hybrid materials via salt inclusion: novel copper(II) arsenates Na(5)ACu(4)(AsO(4))(4)Cl(2) (A = Rb, Cs) composed of alternating covalent and ionic lattices.

Two novel copper(II) arsenates Na5ACu4(AsO4)4Cl2 (A = Rb, Cs) were synthesized by conventional solid-state methods using reactive molten salt media. These compounds are isostructural and crystallize in an orthorhombic lattice (Fmmm, No. 69; Z = 8). The cell constants are a = 14.632(3) A, b = 18.872(2) A, c = 14.445(3) A, V = 3989(1) A3, for A = Rb; a = 14.638(3) A, b = 18.990(4) A, c = 14.418(3) A, V = 4008(1) A3, for A = Cs. Single-crystal structure studies reveal a new composite framework consisting of alternating covalent and ionic lattices. The covalent lattice contains highly oriented oligomeric mu-oxo [Cu4O12]16- tetrameric units with a cyclo-S8-like Cu4O4 magnetic core that resembles the building block of layered cuprates. The ionic slab consists of a novel framework of mixed alkali metal chloride lattice and rarely seen Na6O8 clusters. Similar to organic-inorganic hybrid materials, the title compounds present a new class of host-guest chemistry via salt inclusion reactions.

Journal Article↗

Comparative mapping between humans and pigs: localization of 58 anchorage markers (TOASTs) by use of porcine somatic cell and radiation hybrid panels.

To increase the number of Type I markers that are directly informative for comparative mapping, 58 anchorage markers, TOASTs (Traced Orthologous Amplified Sequence Tags), were mapped in pig. With specific consensus primers, 76 TOASTs were tested in pig: 50 were regionally localized in pig on a somatic cell hybrid panel (SCHP), and 51 were mapped on the whole genome, INRA/University of Minnesota porcine Radiation Hybrid panel (IMpRH). Comparison of marker positions on RH and cytogenetic maps indicated general concordance except for two chromosomal regions. For RH mapping, all markers, apart from one, were significantly linked (LOD > 4.8) to a marker of the first-generation radiation hybrid map. Localization of new markers on the initial map is necessary for drawing a framework map as shown for Chromosome Sscr 14. The addition of four TOASTs has enabled us to propose an improved map, using a threshold likelihood ratio of 1000/1. At the whole-genome level, this work significantly increased (by 50%) the number of precisely mapped genes on the porcine RH map and confirmed that the IMpRH panel is a valuable tool for high-resolution gene mapping in pig. Porcine PCR products were sequenced and compared with human sequences to verify their identity. Most of the localizations made it possible to either confirm or refine the previous comparative data between humans and pigs obtained through heterologous chromosomal painting or gene mapping. Moreover, the use of TOASTs in mapping studies appears to be a complement to other strategies using CATS, human ESTs, or heterologous FISH with BACs which had already been applied to improve the gene density of comparative genomic maps for mammals.

Animals↗

An ordered mesoporous organosilica hybrid material with a crystal-like wall structure.

Surfactant-mediated synthesis strategies are widely used to fabricate ordered mesoporous solids in the form of metal oxides, metals, carbon and hybrid organosilicas. These materials have amorphous pore walls, which could limit their practical utility. In the case of mesoporous metal oxides, efforts to crystallize the framework structure by thermal and hydrothermal treatments have resulted in crystallization of only a fraction of the pore walls. Here we report the surfactant-mediated synthesis of an ordered benzene-silica hybrid material; this material has an hexagonal array of mesopores with a lattice constant of 52.5 A, and crystal-like pore walls that exhibit structural periodicity with a spacing of 7.6 A along the channel direction. The periodic pore surface structure results from alternating hydrophilic and hydrophobic layers, composed of silica and benzene, respectively. We believe that this material is formed as a result of structure-directing interactions between the benzene-silica precursor molecules, and between the precursor molecules and the surfactants. We expect that other organosilicas and organo-metal oxides can be produced in a similar fashion, to yield a range of hierarchically ordered mesoporous solids with molecular-scale pore surface periodicity.

Journal Article↗

A novel matrix protein participating in the nacre framework formation of pearl oyster, Pinctada fucata.

Understanding the molecular composition is of great interest for both nacre formation mechanism and biomineralization in mollusk shell. A cDNA clone encoding an MSI31 relative, termed MSI7 because of its estimated molecular mass of 7.3 kDa, was isolated from the pearl oyster, Pinctada fucata. This novel protein shares similarity with MSI31, a prismatic framework protein of P. fucata. It is peculiar that MSI7 is much shorter in size, harboring only the Gly-rich sequence that has been proposed to be critical for Ca(2+) binding. In situ hybridization result showed that MSI7 mRNA was expressed specifically at the folds and outer epithelia of the mantle, indicating that MSI7 participates in the framework formation of both the nacreous layer and prismatic layer. In vitro experiment on the function of MSI7 suggested that it accelerates the nucleation and precipitation of CaCO(3). Taken together, we have identified a novel matrix protein of the pearl oyster, which may play an important role in determining the texture of nacre.

Amino Acid Sequence↗

Hydrated metal complexes of N-(6-amino-3,4-dihydro-3-methyl-5-nitroso-4-oxopyrimidin-2-yl)glycinate: interplay of molecular, molecular-electronic and supramolecular structures.

The title anion, (C(7)H(8)N(5)O(4))(-), L(-), forms hydrated metal complexes with a range of metal ions M(+) and M(2+). Lithium and manganese(II) form finite molecular aggregates [Li(L)(H(2)O)(3)] (1) and [Mn(L)(2)(H(2)O)(4)].6H(2)O (4) in which the molecular aggregates are linked into three-dimensional frameworks by extensive hydrogen bonding. The sodium and potassium derivatives, [Na(2)(L)(2)(H(2)O)(3)] (2) and [K(L)(H(2)O)] (3) both form organic-inorganic hybrid sheets in which metal-oxygen ribbons are linked by strips containing only organic ligands: these sheets are linked by hydrogen bonds into three-dimensional frameworks. In (2) the metal-oxygen ribbon is built from pairs of edge-shared trigonal bipyramids linked by water molecules, while in (3) it consists of a continuous chain of vertex-sharing octahedra. The nitroso group in the anion acts as an eta(1) ligand towards Na(+) and as an eta(2) ligand towards K(+). In all cases the anion L(-) shows the same unusual pattern of interatomic distances as the neutral parent LH.

Journal Article↗

Improving insurance deduction identification: a hybrid artificial intelligence model using machine learning and expert systems.

PURPOSE: Financial challenges in healthcare systems worldwide, especially in low- and middle-income countries like Iran, have increased hospitals' reliance on insurance reimbursements. Unrecognized insurance deductions often cause severe financial shortages, making efficient deduction management crucial. This study aimed to design a hybrid intelligent system for identifying and predicting insurance deductions by combining machine learning and expert system frameworks. DESIGN/METHODOLOGY/APPROACH: A mixed-methods design was applied in four stages. First, a scoping review identified the causes and patterns of insurance deductions. Second, interviews with 15 insurance experts produced a validated checklist and a dataset from inpatient billing records. Third, using the CRISP-DM methodology, machine learning algorithms were developed and tested in SPSS Modeler alongside a fuzzy expert system developed in MATLAB. Finally, the model was validated using the holdout method. FINDINGS: Four categories of deduction drivers were identified: service provision, registration errors, document submission issues, and revenue conversion processes. The CHAID decision tree outperformed other algorithms with a 99% precision rate and the lowest Mean Absolute Error (9.43). A brief assessment of potential overfitting was conducted to ensure that the CHAID model's high accuracy was interpreted cautiously and supported by the validation results. The fuzzy expert system with validated rules was adaptable for deduction classification, especially for cases unsuitable for quantitative modeling. ORIGINALITY/VALUE: The hybrid model improves detection and prevention of deductions, offering actionable insights for hospital administrators, insurers, and policymakers. Its implementation can enhance hospital information systems, streamline claims processing, and optimize revenue management amid financial constraints.

Machine Learning↗