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Implementation of computer-based patient records in primary care: the societal health economic effects.

OBJECTIVE: Exploration of the societal health economic effects occurring during the first year after implementation of Computerised Patient Records (CPRs) at Primary Health Care (PHC) centres. DESIGN: Comparative case studies of practice processes and their consequences one year after CPR implementation, using the constant comparison method. Application of transaction-cost analyses at a societal level on the results. SETTING: Two urban PHC centres under a managed care contract in Ostergötland county, Sweden. MAIN OUTCOME MEASURES: Central implementation issues. First-year societal direct normal costs, direct unexpected costs, and indirect costs. Societal benefits. RESULTS: The total societal effect of the CPR implementation was a cost of nearly 250,000 SEK (USD 37,000) per GP team. About 20% of the effect consisted of direct unexpected costs, accured from the reduction of practitioners' leisure time. The main issues in the implementation process were medical informatics knowledge and computer skills, adaptation of the human-computer interaction design to practice routines, and information access through the CPR. CONCLUSIONS: The societal costs exceed the benefits during the first year after CPR implementation at the observed PHC centres. Early investments in requirements engineering and staff training may increase the efficiency. Exploitation of the CPR for disease prevention and clinical quality improvement is necessary to defend the investment in societal terms. The exact calculation of societal costs requires further analysis of the affected groups' willingness to pay.

Computer Literacy↗

Single European currency and Monetary Union. Macroeconomic implications for pharmaceutical spending.

This article examines the potential implications of introducing a single currency among the Member States of the European Union for national pharmaceutical prices and spending. In doing so, it provides a brief account of the direct effects of introducing a single currency on pharmaceutical business. These are static in nature and include the elimination of exchange rate volatility and transaction costs, increased price transparency and limited potential for parallel trade. It subsequently analyses the potential medium and long term macroeconomic policy choices facing the Member States and their impact on pharmaceutical spending following the introduction of a single currency. These include policy directions in order to meet the Maastricht convergence criteria in the run-up to forming an Economic and Monetary Union (EMU) and the implications of EMU on national macroeconomic policy thereafter. This article argues that the necessity for tight fiscal policies across the EU and, in particular, in those Member States facing high budget deficits and overall debt levels, will continue to exert considerable downward pressure on pharmaceutical spending.

Costs and Cost Analysis↗

Measuring transactive memory systems in the field: scale development and validation.

This study describes the development and validity testing of a field measure of transactive memory systems. Transactive memory systems are especially important for teams designed to leverage members' expertise, but field research has lagged because there are no adequate measures of the construct. The author developed and tested a 15-item scale in a laboratory sample of 124 teams, a field sample of 64 Master of Business Administration consulting teams, and a field sample of 27 teams from technology companies. Results from the present study demonstrate that the scale is internally consistent, related to alternative measures and hypothesized causes and effects, and unrelated to theoretically distinct constructs, providing evidence of convergent, criterion-related, and discriminant validity. Suggestions for improving the scale, future validity testing, and possible boundary conditions are discussed.

Adult↗

Regulation of ATP-citrate lyase gene transcription.

It has been suggested that glucose metabolites and insulin are the most important factors inducing ATP-citrate lyase (ACL) by a high carbohydrate diet. We have used a primary culture of rat hepatocytes to confirm the role of glucose and insulin in terms of ACL gene expression. The results showed that glucose displayed a direct effect on ACL gene expression and the insulin helps the glucose effect. The nucleotide sequences from -512 to -485 of the ACL promoter are highly homologous (70%) to the sequences surrounding the carbohydrate response element (ChoRE) of the S14 gene. The gel retardation analysis using ChoRE of the S14 gene showed that the ACL promoter which contains the ChoRE-like sequence specifically inhibited the formation of the complex by the nuclear proteins isolated from rat liver. To localize the regions which are involved in the regulation of ACL gene expression, transient expression assay using ACL promoter-CAT (chloramphenicol acetyltransferase) constructs containing various lengths of a 5' flanking region of the ACL gene were carried out. The proximal promoter region -419 to -1 containing several potential Sp1 binding sites showed the strong enhancing effect, which increases the transcription of CAT genes in the various cell lines, such as the CHO (Chinese hamster ovary) cell, the HepG2 cell, and primary cultured rat hepatocytes. In response to glucose, among the ACL promoter-CAT constructs, only pNP33-CAT (-1342 to -1) showed a 2.64 fold increase in CAT activity by a high concentration of glucose. The activation of ACL gene expression by glucose seems to be regulated in a complicated manner involving interactions between the contexts of the several sequence elements and various transacting factors, which is not a simple mechanism directed only by a short sequence element.

ATP Citrate (pro-S)-Lyase↗

Rape perpetration by young, rural South African men: Prevalence, patterns and risk factors.

Sexual violence is a well-recognised global health problem, but there has been remarkably little research on men as perpetrators. The objectives of this paper are to describe the prevalence, patterns and factors associated with rape of an intimate partner and a woman who was not a partner with men aged 15-26 years in rural South Africa. The analysis presented here is of data collected during a baseline survey of participants in a cluster randomised controlled trial of an HIV behavioural intervention. A total of 1370 male volunteers were recruited from 70 rural South African villages. They completed a questionnaire asking about background, sexual practices and perpetration of rape and intimate partner violence. Among these men 16.3% had raped a non-partner, or participated in a form of gang rape; 8.4% had been sexually violent towards an intimate partner; and 79.1% had done neither. The mean age of first rape was 17 years. There was overlap between rape of a non-partner and partner, in that 44.3% of men who raped an intimate partner had also raped a non-partner, but overall the great majority of men who raped did not disclose both types of rape. The factors associated with rape of an intimate partner and non-partner had similarities and differences. After adjusting for the other variables, both forms of rape were strongly associated with ever having been physically violent to a partner, having had transactional sex with a casual partner and more sexual partners. Non-partner rape was also associated with peer-related variables, including gang membership and peer pressure to have sex, and also drug use. Non-partner rape was more common among wealthier and relatively more socially advantaged men. Both types of rape were associated with having more adverse childhood experiences. There was considerable overlap between rape-associated factors and known HIV risk factors, suggesting a need for further research on the interface of rape and HIV, and integrated prevention programming.

Adolescent↗

A hedging point strategy--balancing effluent quality, economy and robustness in the control of wastewater treatment plants.

An operational space map is an efficient tool to compare a large number of operational strategies to find an optimal choice of setpoints based on a multicriterion. Typically, such a multicriterion includes a weighted sum of cost of operation and effluent quality. Due to the relative high cost of aeration such a definition of optimality result in a relatively high fraction of the effluent total nitrogen in the form of ammonium. Such a strategy may however introduce a risk into operation because a low degree of ammonium removal leads to a low amount of nitrifiers. This in turn leads to a reduced ability to reject event disturbances, such as large variations in the ammonium load, drop in temperature, the presence of toxic/inhibitory compounds in the influent etc. Hedging is a risk minimisation tool, with the aim to "reduce one's risk of loss on a bet or speculation by compensating transactions on the other side" (The Concise Oxford Dictionary (1995)). In wastewater treatment plant operation hedging can be applied by choosing a higher level of ammonium removal to increase the amount of nitrifiers. This is a sensible way to introduce disturbance rejection ability into the multi criterion. In practice, this is done by deciding upon an internal effluent ammonium criterion. In some countries such as Germany, a separate criterion already applies to the level of ammonium in the effluent. However, in most countries the effluent criterion applies to total nitrogen only. In these cases, an internal effluent ammonium criterion should be selected in order to secure proper disturbance rejection ability.

Automation↗

Characterization and genetic analysis of functional corticotropin-releasing hormone receptors in primary cerebellar cultures.

We demonstrate that granular cerebellar neurons express functional corticotropin-releasing hormone (CRH) receptors. Activation of these receptors with CRH receptor agonists leads to a dose-dependent increase in cyclic AMP (cAMP) levels with an apparent EC50 close to 10(-9) M. Using the c-fos protooncogene as a system to evaluate genomic effects of CRH, we show that activation of CRH receptors regulates gene expression at the transcriptional level. CRH rapidly induced c-fos mRNA accumulation. Genetic studies, using chimera genes containing human c-fos promoter sequences coupled to a chloramphenicol acetyltransferase (CAT) reporter gene, confirmed and extended this observation. When protein kinase A (PKA) was specifically inactivated by gene transfer of a mutated regulatory subunit of PKA lacking cAMP binding sites, CRH-stimulated c-fos transcription was suppressed but the increase in cAMP level was not affected, indicating a key role of PKA in mediating CRH-stimulated transcription. As CRH clearly modulates gene expression via the cAMP pathway, we analyzed the genomic effect of this neurohormone on a deleted c-fos-CAT construct containing only the cAMP-responsive element (CRE) and on a heterologous promoter construct bearing the minimal palindromic consensus CRE (core sequence TGACGTCA). These minimal cAMP-responsive genes are induced by CRH. These inductions are dependent on functional PKA. Taken together, our results demonstrate the presence of functional CRH receptors in primary cerebellar cultures. Activation of these receptors stimulates gene expression via the cAMP/PKA pathway and the transacting factor CREB (cAMP-responsive element binding protein).

Animals↗

Administrative reports for monitoring pharmacy purchasing.

The use of administrative reports in a hospital pharmacy department to monitor communication regarding drug supply problems and to assist pharmacy administration in assessing the performance of its purchasing area is described. The weekly drug supply problems report was developed as a method to communicate problems in the storeroom to other pharmacy areas. The weekly borrow and loan report, which accounts for all borrow and loan transactions, helps determine the proper reorder quantities of drug products borrowed frequently and monitors repayment for loaned items. The inventory assessment report is prepared annually; in this report, drug expenditures for a "market-basket" list of drug products are compared for the current and previous years. To assess the use of nonformulary drugs, a quarterly report of expenditures for nonformulary drugs is compiled. The purchasing pharmacist, who is responsible for inventory control, prepares these reports. When considered in relation to the budget and workload statistics, the reports can be used to assess the performance of the purchasing area. Increased accountability and more orderly operation of the purchasing area has accompanied the use of these reports.

Chicago↗

Regulation of caulimovirus gene expression and the involvement of cis-acting elements on both viral transcripts.

In a further analysis of gene regulation of figwort mosaic virus (FMV), a caulimovirus, we studied transient gene expression with modified viral genomes in Nicotiana edwardsonii cell suspension protoplasts. The results demonstrated that the presence of the promoter for the full-length RNA interferes with expression from the separate downstream promoter for gene VI. In addition, expression of gene VI was inhibited by cis-acting sequences within gene VI itself. Both inhibitory effects could be partially relieved by coelectroporation with a plasmid that produces gene VI protein, demonstrating that expression of gene VI is transactivated by its own product. Subsequent expression studies with partially redundant FMV plasmids containing a reporter gene in frame with gene IV showed that efficient transactivation of CAT expression relies on a cis-acting element inside the downstream gene VI. Insertions of a transcriptional terminator upstream of the cis-acting element for premature termination of transcription showed that the cis-acting region is not a DNA element but is active only as a feature of the RNA transcript. We conclude that the cis-acting element, together with the transacting gene VI product, enhances expression of all major genes, including gene VI, from the polycistronic mRNA and the separate mRNA for gene VI.

Enhancer Elements, Genetic↗

SUV39H1 interacts with HTLV-1 Tax and abrogates Tax transactivation of HTLV-1 LTR.

BACKGROUND: Tax is the oncoprotein of HTLV-1 which deregulates signal transduction pathways, transcription of genes and cell cycle regulation of host cells. Transacting function of Tax is mainly mediated by its protein-protein interactions with host cellular factors. As to Tax-mediated regulation of gene expression of HTLV-1 and cellular genes, Tax was shown to regulate histone acetylation through its physical interaction with histone acetylases and deacetylases. However, functional interaction of Tax with histone methyltransferases (HMTase) has not been studied. Here we examined the ability of Tax to interact with a histone methyltransferase SUV39H1 that methylates histone H3 lysine 9 (H3K9) and represses transcription of genes, and studied the functional effects of the interaction on HTLV-1 gene expression. RESULTS: Tax was shown to interact with SUV39H1 in vitro, and the interaction is largely dependent on the C-terminal half of SUV39H1 containing the SET domain. Tax does not affect the methyltransferase activity of SUV39H1 but tethers SUV39H1 to a Tax containing complex in the nuclei. In reporter gene assays, co-expression of SUV39H1 represses Tax transactivation of HTLV-1 LTR promoter activity, which was dependent on the methyltransferase activity of SUV39H1. Furthermore, SUV39H1 expression is induced along with Tax in JPX9 cells. Chromatin immunoprecipitation (ChIP) analysis shows localization of SUV39H1 on the LTR after Tax induction, but not in the absence of Tax induction, in JPX9 transformants retaining HTLV-1-Luc plasmid. Immunoblotting shows higher levels of SUV39H1 expression in HTLV-1 transformed and latently infected cell lines. CONCLUSION: Our study revealed for the first time the interaction between Tax and SUV39H1 and apparent tethering of SUV39H1 by Tax to the HTLV-1 LTR. It is speculated that Tax-mediated tethering of SUV39H1 to the LTR and induction of the repressive histone modification on the chromatin through H3 K9 methylation may be the basis for the dose-dependent repression of Tax transactivation of LTR by SUV39H1. Tax-induced SUV39H1 expression, Tax-SUV39H1 interaction and tethering to the LTR may provide a support for an idea that the above sequence of events may form a negative feedback loop that self-limits HTLV-1 viral gene expression in infected cells.

Base Sequence↗

Expression of heat shock protein 70 and c-myc protein in human breast cancer: an immunohistochemical study.

The major heat shock protein, HSP70, protects cells from a variety of stressful stimuli, while c-myc protein allegedly stimulates the expression of HSP70 by transacting on the HSP70 promotor. The present study was aimed at correlating the expression of HSP70 with that of c-myc protein in benign and malignant breast lesions. Indirect immunoperoxidase and immunoblotting techniques using monoclonal antibodies were employed. Fresh frozen sections were prepared from five fibroadenomas and 59 breast carcinomas. Immunohistochemically, both substances were localized in the nuclei and/or cytoplasm of normal and neoplastic epithelial cells. The stromal cells were positive for c-myc protein but negative for HSP70. The expressions of HSP70 and c-myc protein were comparable to each other in the malignant cells from 37 (63%) carcinomas. In 17 (29%) carcinomas, c-myc protein expression predominated over that of HSP70, whereas in five (8%) carcinomas, HSP70 was predominant. Carcinomas with high-grade nuclear atypia often showed negative HSP70 staining, whereas tumors with nuclear HSP70 localization tended to accompany lower-grade nuclear atypia. A similar relation was also observed between c-myc protein expression and nuclear atypia of the tumor. All five fibroadenomas and most of the non-neoplastic epithelial cells adjacent to cancer showed strong reactivities with both substances. Immunoblot analysis for HSP70 revealed a clear, single band in the extract of tumors with strong HSP70 staining, but no, or only faint, bands were seen in the extract of immunohistochemically HSP70-negative carcinomas. The discrepancy between the expressions of each substance in a certain percentage of breast carcinomas may suggest the presence of HSP70 production mechanisms other than the c-myc protein-triggered promotor pathway.

Adenofibroma↗

Teaching a functional leisure skill cluster to rehabilitation clients: the art of macrame.

Disabled people often do not use leisure time productively. Past research has focused on teaching specific recreational activities isolated from related skills that would provide subjects a functional independent living repertoire. In the present study disabled subjects were taught the art of macrame. Additionally, they role-played related shopping skills such as buying materials, engaging in appropriate social-interpersonal skills, making monetary transactions, and securing their own transportation to and from the store. Subjects were taught six basic macrame knots using an instructional manual, series of error-correction procedures, and social reinforcement. After mastering those basic knots they independently used the instructional materials to make three complete macrame projects without direct instruction on the projects themselves. Subjects also demonstrated skill maintenance and generalization by making a novel project after independently engaging in all relevant shopping behavior. Two varieties of the multiple baseline design were employed. The importance of teaching a leisure skill cluster and adapting instructional materials were emphasized.

Activities of Daily Living↗

Effect of DNA supercoiling on the geometry of holliday junctions.

Unusual DNA conformations including cruciforms play an important role in gene regulation and various DNA transactions. Cruciforms are also the models for Holliday junctions, the transient DNA conformations critically involved in DNA homologous and site-specific recombination, repair, and replication. Although the conformations of immobile Holliday junctions in linear DNA molecules have been analyzed with the use of various techniques, the role of DNA supercoiling has not been studied systematically. We utilized atomic force microscopy (AFM) to visualize cruciform geometry in plasmid DNA with different superhelical densities at various ionic conditions. Both folded and unfolded conformations of the cruciform were identified, and the data showed that DNA supercoiling shifts the equilibrium between folded and unfolded conformations of the cruciform toward the folded one. In topoisomers with low superhelical density, the population of the folded conformation is 50-80%, depending upon the ionic strength of the buffer and a type of cation added, whereas in the sample with high superhelical density, this population is as high as 98-100%. The time-lapse studies in aqueous solutions allowed us to observe the conformational transition of the cruciform directly. The time-dependent dynamics of the cruciform correlates with the structural changes revealed by the ensemble-averaged analysis of dry samples. Altogether, the data obtained show directly that DNA supercoiling is the major factor determining the Holliday junction conformation.

DNA↗

Comparative genomics of the T4-Like Escherichia coli phage JS98: implications for the evolution of T4 phages.

About 130 kb of sequence information was obtained from the coliphage JS98 isolated from the stool of a pediatric diarrhea patient in Bangladesh. The DNA shared up to 81% base pair identity with phage T4. The most conserved regions between JS98 and T4 were the structural genes, but their degree of conservation was not uniform. The head genes showed the highest sequence conservation, followed by the tail, baseplate, and tail fiber genes. Many tail fiber genes shared only protein sequence identity. Except for the insertion of endonuclease genes in T4 and gene 24 duplication in JS98, the structural gene maps of the two phages were colinear. The receptor-recognizing tail fiber proteins gp37 and gp38 were only distantly related to T4, but shared up to 83% amino acid identity to other T6-like phages, suggesting lateral gene transfer. A greater degree of variability was seen between JS98 and T4 over DNA replication and DNA transaction genes. While most of these genes came in the same order and shared up to 76% protein sequence identity, a few rearrangements, insertions, and replacements of genes were observed. Many putative gene insertions in the DNA replication module of T4 were flanked by intron-related endonuclease genes, suggesting mobile DNA elements. A hotspot of genome diversification was located downstream of the DNA polymerase gene 43 and the DNA binding gene 32. Comparative genomics of 100-kb genome sequence revealed that T4-like phages diversify more by the accumulation of point mutations and occasional gene duplication events than by modular exchanges.

Bacteriophage T4↗

Transformational and transactional leadership: a meta-analytic test of their relative validity.

This study provided a comprehensive examination of the full range of transformational, transactional, and laissez-faire leadership. Results (based on 626 correlations from 87 sources) revealed an overall validity of .44 for transformational leadership, and this validity generalized over longitudinal and multisource designs. Contingent reward (.39) and laissez-faire (-.37) leadership had the next highest overall relations; management by exception (active and passive) was inconsistently related to the criteria. Surprisingly, there were several criteria for which contingent reward leadership had stronger relations than did transformational leadership. Furthermore, transformational leadership was strongly correlated with contingent reward (.80) and laissez-faire (-.65) leadership. Transformational and contingent reward leadership generally predicted criteria controlling for the other leadership dimensions, although transformational leadership failed to predict leader job performance.

Humans↗

Quantum Threats to Bitcoin, Cryptocurrency and Blockchain.

OBJECTIVE: The authors evaluated how quantum computing threatens the cryptographic primitives used in Bitcoin and other blockchain systems. These findings were translated into a standards-aligned post-quantum migration profile for healthcare ledgers, including consent, identity, provenance, audit, and encrypted off-chain data exchange. METHODOLOGY: Narrative analysis, theoretical security analysis, and healthcare-oriented deployment mapping of classical public-key and hash primitives used in blockchain protocols were paired with an implementation-oriented migration profile based on finalized National Institute of Standards and Technology (NIST) post-quantum standards. We summarize the mathematical assumptions underlying RSA, Elliptic Curve Cryptography/Elliptic Curve Digital Signature Algorithm (ECC/ECDSA), and Secure Hash Algorithm (SHA-2/SHA-3-family) hash functions; analyze their susceptibility to Shor's and Grover's quantum algorithms; compare Federal Information Processing Standards (FIPS) 203 Module-Lattice-Based Key-Encapsulation Mechanism Standard (ML-KEM), FIPS 204 Module-Lattice-Based Digital Signature Standard (ML-DSA), and FIPS 205 Stateless Hash-Based Digital Signature Standard (SLH-DSA); and map their distinct roles to healthcare-ledger authorization, auditability, identity, and encrypted off-chain exchange. The term Advanced Hybrid Module-LWE & Code-Based (AHMC) is used only as shorthand for a standards-aligned hybrid post-quantum cryptography (PQC) migration profile and does not denote a proprietary product, a novel algorithm, or a new cryptographic primitive. Proposed adoption of hybrid, quantum-resistant cryptographic primitives for cryptocurrency wallets, transaction signatures, and ledger security during an interim migration period (hybrid classical + PQC, followed by PQC-only). Qualitative and implementation-oriented assessment of (1) break feasibility of RSA/ECC under Shor's algorithm, (2) effective security reduction for hash functions under Grover's algorithm, (3) security assumptions and composition requirements of a standards-aligned hybrid migration profile, (4) transaction-size and verification-cost impact, and (5) healthcare-specific implications for long-retention consent, identity, provenance, and audit records. RESULTS: Shor's algorithm reduces integer factorization and discrete logarithms to polynomial time, directly compromising Rivest-Shamir-Adleman (RSA) and ECC/ECDSA once fault-tolerant, large-scale quantum computers exist. Grover's algorithm yields a quadratic speedup for brute-force search, effectively halving the security margin of symmetric keys and hash functions at fixed output sizes. The AHMC-L1/L3/L5 profiles use ML-KEM-512/768/1024 for key establishment and ML-DSA-44/65/87 for transaction authentication, with SLH-DSA as a hash-based fallback. During a hybrid ECDSA+PQC migration, verification requires one classical and one PQC verification per authorization; transaction-size overhead is dominated by PQC signatures, approximately 2.4 KB for ML-DSA-44, 3.3 KB for ML-DSA-65, and 4.6 KB for ML-DSA-87 before script and encoding overhead. For healthcare ledgers, these findings support selective use of post-quantum signatures for:high-value state transitions,one-time public-key registration where possible, andcontinued off-chain storage of protected health information.Deployment suitability remains contingent on workflow-specific latency, storage, availability, key lifecycle, and side-channel testing. CONCLUSIONS: Quantum risk to blockchain signatures has direct implications for healthcare systems that depend on long-lived consent, identity, provenance, and audit records. A staged, standards-aligned migration profile can preserve authorization and ledger verifiability while keeping protected health information off-chain. The AHMC label refers only to this migration profile, not to a new cryptographic primitive; healthcare adoption requires open implementations, empirical benchmarking, crypto-agile key governance, and side-channel-resistant engineering.

ML-DSA↗

Experimental comparisons of data entry by automated speech recognition, keyboard, and mouse.

In a series of experiments isolated-word automated speech recognition (ASR) was compared with keyboard and mouse interfaces for three data entry tasks: textual phrase entry, selection from a list, and numerical data entry. To effect fair comparisons, the tasks were designed to minimize the transaction cycle for each input mode and data type, and the main comparisons used times from only correct data entries. With the hardware and software employed the results indicate that for inputting short phrases, ASR competes only if the typist's speed is below 45 words per minute. For selecting an item from a list, ASR offers an advantage only if the list length exceeds 15 items. For entering numerical data, ASR offers no advantage over keypad or mouse. An extrapolation to latency-free ASR suggests that even as hardware and software become faster, human factors will dominate and the results would shift only slightly in favor of ASR.

Computer Peripherals↗

Coping style, health beliefs, and breast self-examination.

The purpose of this study was to determine the role of coping style in women's practice of breast self-examination (BSE). The framework was adapted from the Cognitive Transactional Model of Stress and Coping and the Health Belief Model. The convenience sample consisted of 269 women recruited from an employee list of a medical center and a membership list of a professional nurses' group. Survey booklets were distributed via interdepartmental or U.S. mail and contained measures of trait anxiety and defensiveness and questions related to health beliefs, BSE practice, and demographics. The sample was categorized by coping style (i.e., repressive, true high anxious, defensive high anxious, or true low anxious), and data were analyzed via MANOVAs, ANOVAs, and hierarchical regression. Results indicated that coping style predicted BSE practice (i.e., proficiency, frequency) and health beliefs of barriers, confidence, seriousness, and susceptibility. The findings provide nurses with information for developing interventions to foster BSE.

Adaptation, Psychological↗