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Biomedical subjects

J C Robinson

Publications and source records attributed to J C Robinson.

At least 19 recordsLinked to original sources

A silicon-based, sequential coat-and-etch process to fabricate nearly perfect substrate surfaces.

For many thin-film applications substrate imperfections such as particles, pits, scratches, and general roughness, can nucleate film defects which can severely detract from the coating's performance. Previously we developed a coat-and-etch process, termed the ion beam thin film planarization process, to planarize substrate particles up to approximately 70 nm in diameter. The process relied on normal incidence etching; however, such a process induces defects nucleated by substrate pits to grow much larger. We have since developed a coat-and-etch process to planarize approximately 70 nm deep by 70 nm wide substrate pits; it relies on etching at an off-normal incidence angle, i.e., an angle of approximately 470 degrees from the substrate normal. However, a disadvantage of this pit smoothing process is that it induces defects nucleated by substrate particles to grow larger. Combining elements from both processes we have been able to develop a silicon-based, coat-and-etch process to successfully planarize approximately 70 nm substrate particles and pits simultaneously to at or below 1 nm in height; this value is important for applications such as extreme ultraviolet lithography (EUVL) masks. The coat-and-etch process has an added ability to significantly reduce high-spatial frequency roughness, rendering a nearly perfect substrate surface.

Electrochemistry↗

Photofragment translation spectroscopy of ClN3 at 248 nm: determination of the primary and secondary dissociation pathways.

Photofragmentation translational spectroscopy was used to identify the primary and secondary reaction pathways in the KrF laser (248 nm) photodissociation of chlorine azide (ClN(3)) under collision-free conditions. Both the molecular channel producing NCl (X (3)Sigma,a (1)Delta) + N(2) and the radical channel producing Cl ((2)P(J)) + N(3) were analyzed in detail. Consistent with previously reported velocity map ion imaging experiments [N. Hansen and A. M. Wodtke, J. Phys. Chem. A 107, 10608 (2003)] a bimodal translational energy distribution is seen when Cl atoms are monitored at mz = 35(Cl(+)). Momentum-matched N(3) counterfragments can be seen at mz = 42(N(3) (+)). The characteristics of the observed radical-channel data reflect the formation of linear azide radical and another high-energy form of N(3) (HEF-N(3)) that exhibits many of the characteristics one would expect from cyclic N(3). HEF-N(3) can be directly detected by electron-impact ionization more than 100 mus after its formation. Products of the unimolecular dissociation of HEF-N(3) are observed in the mz = 14(N(+)) and mz = 28(N(2) (+)) data. Anisotropy parameters were determined for the primary channels to be beta = -0.3 for the NCl forming channel and beta = 1.7 and beta = 0.4 for the linear N(3) and HEF-N(3) forming channels, respectively. There is additional evidence for secondary photodissociation of N(3) and of NCl.

Journal Article↗

Efficacy of topical aciclovir for the treatment of feline herpetic keratitis: results of a prospective clinical trial and data from in vitro investigations.

This study aimed to evaluate the efficacy of topical ophthalmic aciclovir applied five times daily as a treatment for feline herpesvirus type 1 (FHV-1) keratitis in a group of cats in a first-opinion practice setting. Cats with ocular signs indicative of FHV-1 or Chlamydophila species infection, predominantly conjunctivitis and keratitis, were tested for FHV-1 antigen using an immunofluorescent technique on air-dried conjunctival swabs. They were first treated with topical chlortetracycline with efficacy against Chlamydophila species and then, in cases positive for FHV-1, with topical aciclovir. The time to recovery was determined and illustrated using a Kaplan-Meier plot. Three cats were infected with Chlamydophila species and showed a median time to recovery of 14 days (95 per cent confidence interval [CI] 10 to 18 days), while 30 cats infected with FHV-1 showed a median time to recovery of 12 days (95 per cent CI 10 to 14 days). The drug dose at which 50 per cent plaque reduction (ED50) occurred in a standard plaque reduction assay was determined in an in vitro study. This showed a mean (SD) ED50 of aciclovir of 25 (3.5) mg/ml compared with 0.4 (0.05) mg/ml for trifluorothymidine, a drug known to be efficacious against FHV-1. The study shows that even though aciclovir is generally considered to lack efficacy against ocular FHV-1 infection, when used frequently it can have a beneficial effect in FHV-1 conjunctivitis and keratitis.

Acyclovir↗

Evaluation of French Guiana traditional antimalarial remedies.

In order to evaluate the antimalarial potential of traditional remedies used in French Guiana, 35 remedies were prepared in their traditional form and screened for blood schizonticidal activity in vitro on Plasmodium falciparum chloroquine re4sistant strain (W2). Some of these extracts were screened in vivo against Plasmodium yoelii rodent malaria. Ferriprotoporphyrin inhibition test was also performed. Four remedies, widely used among the population as preventives, were able to inhibit more than 50% of the parasite growth in vivo at around 100 mg/kg: Irlbachia alata (Gentiananceae), Picrolemma pseudocoffea (Simaroubaceae), Quassia amara (Simaroubaceae), Tinospora crispa (Menispermaceae) and Zanthoxylum rhoifolium (Rutaceae). Five remedies displayed an IC50 in vitro < 10 microg/ml: Picrolemma pseudocoffea, Pseudoxandra cuspidata (Annonaceae) and Quassia amara leaves and stem, together with a multi-ingredient recipe. Two remedies were more active than a Cinchona preparation on the ferriprotoporphyrin inhibition test: Picrolemma pseudocoffea and Quassia amara. We also showed that a traditional preventive remedy, made from Geissospermum argenteum bark macerated in rum, was able to impair the intrahepatic cycle of the parasite. For the first time, traditional remedies from French Guiana have been directly tested on malarial pharmacological assays and some have been shown to be active.

Administration, Oral↗

Alarm treatment for childhood nocturnal enuresis: an investigation of within-treatment variables.

OBJECTIVE: The enuresis alarm has been widely advocated as an effective intervention in the treatment of childhood nocturnal enuresis. Although there is a body of evidence concerning which pretreatment variables are related to outcome, there is little evidence relating to influential within-treatment variables. This study sought to examine a series of treatment variables against outcome. MATERIAL AND METHODS: A total of 66 children with severe primary nocturnal enuresis but with no day-time wetting were treated with a body-worn enuresis alarm. Pre- and within-treatment variables were collected. Success was considered to be 14 consecutive dry nights during a 16-week period. RESULTS: A total of 54.5% of children achieved the success criterion, with 12.1% being classed as partial successes. Of the pretreatment variables, only low functional bladder capacity was significantly associated with failure. Inability to be woken by the alarm emerged as the most important within-treatment predictor of failure. CONCLUSIONS: The success of alarm treatment is dependent on the child's ability to be aroused by the alarm. Interestingly, of those who successfully became dry, 72.2% slept throughout the night for >80% of nights that they were dry, suggesting that the mode of action of the enuresis alarm is more complex than was previously thought.

Adolescent↗

Structure of the EMAPII domain of human aminoacyl-tRNA synthetase complex reveals evolutionary dimer mimicry.

The EMAPII (endothelial monocyte-activating polypeptide II) domain is a tRNA-binding domain associated with several aminoacyl-tRNA synthetases, which becomes an independent domain with inflammatory cytokine activity upon apoptotic cleavage from the p43 component of the multisynthetase complex. It comprises a domain that is highly homologous to bacterial tRNA-binding proteins (Trbp), followed by an extra domain without homology to known proteins. Trbps, which may represent ancient tRNA chaperones, form dimers and bind one tRNA per dimer. In contrast, EMAPII domains are monomers. Here we report the crystal structure at 1.14 Angstroms of human EMAPII. The structure reveals that the Trbp-like domain, which forms an oligonucleotide-binding (OB) fold, is related by degenerate 2-fold symmetry to the extra-domain. The pseudo-axis coincides with the dyad axis of bacterial TtCsaA, a Trbp whose structure was solved recently. The interdomain interface in EMAPII mimics the intersubunit interface in TtCsaA, and may thus generate a novel OB-fold-based tRNA-binding site. The low sequence homology between the extra domain of EMAPII and either its own OB fold or that of Trbps suggests that dimer mimicry originated from convergent evolution rather than gene duplication.

Amino Acid Sequence↗

Theory and practice in the design of physician payment incentives.

Combining the economic literature on principal-agent relationships with examples of marketplace innovations allows analysis of the evolution of methods for paying physicians. Agency theory and the economic principles of performance-based compensation are applied in the context of imperfect information, risk aversion, multiple interrelated tasks, and team production efficiencies. Fee-for-service and capitation are flawed methods of motivating physicians to achieve specific goals. Payment innovations that blend elements of fee-for-service, capitation, and case rates can preserve the advantages and attenuate the disadvantages of each. These innovations include capitation with fee-for-service carve-outs, department budgets with individual fee-for-service or "contact" capitation, and case rates for defined episodes of illness. The context within which payment incentives are embedded, includes such non-price mechanisms as screening and monitoring and such organizational relationships as employment and ownership. The analysis has implications for health services research and public policy with respect to physician payment incentives.

Capitation Fee↗

Organizational economics and health care markets.

As health policy emphasizes the use of private sector mechanisms to pursue public sector goals, health services research needs to develop stronger conceptual frameworks for the interpretation of empirical studies of health care markets and organizations. Organizational relationships should not be interpreted exclusively in terms of competition among providers of similar services but also in terms of relationships among providers of substitute and complementary services and in terms of upstream suppliers and downstream distributors. This article illustrates the potential applicability of transactions cost economics, agency theory, and organizational economics more broadly to horizontal and vertical markets in health care. Examples are derived from organizational integration between physicians and hospitals and organizational conversions from nonprofit to for-profit ownership.

Data Collection↗

Macromolecular assemblage of aminoacyl-tRNA synthetases: quantitative analysis of protein-protein interactions and mechanism of complex assembly.

The structure of the mammalian multi-synthetase complex was investigated in vitro using qualitative and quantitative approaches. This macromolecular assemblage comprises the bifunctional glutamyl-prolyl-tRNA synthetase, the seven monospecific isoleucyl, leucyl, methionyl, glutaminyl, lysyl, arginyl and aspartyl-tRNA synthetases, and the three auxiliary p43, p38 and p18 proteins. The scaffold p38 protein was expressed in Escherichia coli and purified to homogeneity as a His-tagged protein. The different components of the complex were shown to associate in vitro with p38 immobilized on Ni(2+)-coated plates. Interactions between peripheral enzymes and p38 are referred to as central interactions, as opposed to lateral interactions between peripheral enzymes. Kinetic parameters of the interactions were determined by the means of a biosensor-based approach. The two dimeric proteins LysRS and AspRS were found to tightly bind to p38, with a K(d) value of 0.3 and 4.7 nM, respectively. These interactions involved the catalytic core of the enzymes. By contrast, binding of ArgRS or GlnRS to p38 was much weaker (>5 microM). ArgRS and p43, two peripheral components, were shown to interact with moderate affinity (K(d)=93 nM). Since all the components of the complex are tightly associated within this particle, lateral interactions were believed to contribute to the stabilization of this assemblage. Using an in vitro binding assay, concomitant association of several components of the complex on immobilized p38 could be demonstrated, and revealed the involvement of synergistic effects for association of weakly interacting proteins. Taking into account the possible synergy between central and lateral contributions, a sub-complex containing p38, p43, ArgRS and GlnRS was reconstituted in vitro. These data provide compelling evidence for an ordered and concerted mechanism of complex assembly.

Amino Acyl-tRNA Synthetases↗

Accuracy of glaucoma detection with frequency-doubling perimetry.

PURPOSE: To determine the accuracy of glaucoma detection by frequency-doubling perimetry. METHODS: Stereoview optic nerve photographs, visual field examination, intraocular pressure measurements, medical and ocular history, and a screening and full threshold frequency-doubling perimetry examination were performed in a prospective study of consecutive subjects. Inclusion criteria included age of 45 years or older, absence of ocular disease other than glaucoma, cataract, or mild drusen, and Snellen visual acuity of 20/60 or better. A total of 125 eyes in 102 glaucoma subjects and 95 eyes of 95 normal subjects were included. Each eye was classified as "normal," "glaucoma," or "uncertain" by each of three ophthalmologists on the basis of all available clinical information with the exception of frequency-doubling perimetry results. Those in the glaucoma group were subclassified as having early (n = 51), moderate (n = 42), or severe (n = 32) glaucoma on the basis of automated Humphrey visual field criteria. In the glaucoma group, two eyes from a subject were allowed to be included (23 of 102 subjects) if they differed in level of damage because they were never analyzed within the same statistical analysis. RESULTS: Several diagnostic algorithms were evaluated. Algorithms based on the most depressed single point, pair of adjacent points, and cluster of three points performed nearly identically. For the screening test, if any abnormality was identified, specificity was 95%, whereas sensitivity was 39%, 86%, and 100% for early, moderate, and severe glaucoma, respectively. For the full threshold test, with at least one point depressed to the P < 0.5% level, specificity measured 91%, whereas sensitivity was 35%, 88%, and 100% for early, moderate, and severe glaucoma, respectively. The two global indices, mean deviation and pattern standard deviation, were also evaluated and were generally less accurate. CONCLUSION: Frequency-doubling perimetry, which is rapid and easily administered, is effective at detecting moderate and severe disease and appears well suited for glaucoma screening.

Aged↗

Blended payment methods in physician organizations under managed care.

CONTEXT: Independent practice associations (IPAs) are developing new methods of physician reimbursement to balance the objectives of encouraging individual productivity and clinical cooperation. The economic literature on payment incentives, derived from nonhealth industries, predicts that methods blending elements of fee-for-service and capitation will outperform exclusive reliance on either form of payment. OBJECTIVE: To identify emerging payment methods within IPA physician groups that contract with managed care organizations. DESIGN AND SETTING: Case studies of 7 large IPAs in the San Francisco, Calif, metropolitan region that served 826000 health maintenance organization (HMO) patients during the summer and fall of 1998. MAIN OUTCOME MEASURE: Payment methods of IPAs for primary care physicians, specialists, and physicians grouped by specialty department within the overall IPA structure. RESULTS: All the IPAs contracted with multiple HMOs for the full range of primary and specialty care physicians' services but paid member physicians using methods that blended elements of fee-for-service and subcapitation. For primary care, most IPAs used monthly capitation adjusted for patient age, sex, and selected diagnoses, supplemented with fee-for-service payment for a wide range of visits and procedures, including patient visits in subacute, skilled nursing facility, emergency department, or home settings; for preventive care services; for office procedures requiring expensive supplies; and, most importantly, for borderline primary care procedures that either could be performed directly or referred to specialty care. All the IPAs paid specialty departments on a capitated basis and delegated to the departments responsibility for allocating the budget among individuals. Allocation mechanisms for individual specialists included adjusted fee-for-service, referral-based capitation, and blends of both. CONCLUSION: Our results and case studies indicate that IPAs are developing payment methods that blend elements of fee-for-service and capitation in innovative ways for primary care and specialty physicians.

Budgets↗

Macromolecular assemblage of aminoacyl-tRNA synthetases: identification of protein-protein interactions and characterization of a core protein.

In eukaryotes, from fly to human, nine aminoacyl-tRNA synthetases contribute a multienzyme complex of defined and conserved structural organization. This ubiquitous multiprotein assemblage comprises a unique bifunctional aminoacyl-tRNA synthetase, glutamyl-prolyl-tRNA synthetase, as well as the monospecific isoleucyl, leucyl, glutaminyl, methionyl, lysyl, arginyl, and aspartyl-tRNA synthetases. Three auxiliary proteins of apparent molecular masses of 18, 38 and 43 kDa are invariably associated with the nine tRNA synthetase components of the complex. As part of an inquiry into the molecular and functional organization of this macromolecular assembly, we isolated the cDNA encoding the p38 non-synthetase component and determined its function. The 320 amino acid residue encoded protein has been shown to have no homolog in yeast, bacteria and archaea, according to the examination of the complete genomic sequences available. The p38 protein is a moderately hydrophobic protein, displays a putative leucine-zipper motif, and shares a sequence pattern with protein domains that are involved in protein-protein interactions. We used the yeast two-hybrid system to register protein connections between components of the complex. We performed an exhaustive search of interactive proteins, involving 10 of the 11 components of the complex. Twenty-one protein pairs have been unambiguously identified, leading to a global view of the topological arrangement of the subunits of the multisynthetase complex. In particular, p38 was found to associate with itself to form a dimer, but also with p43, with the class I tRNA synthetases ArgRS and GlnRS, with the class II synthetases AspRS and LysRS, and with the bifunctional GluProRS. We generated a series of deletion mutants to localize the regions of p38 mediating the identified interactions. Mapping the interactive domains in p38 showed the specific association of p38 with its different protein partners. These findings suggest that p38, for which no homologous protein has been identified to date in organisms devoid of multisynthetase complexes, plays a pivotal role for the assembly of the subunits of the eukaryotic tRNA synthetase complex.

Amino Acid Sequence↗

Accuracy of scanning laser polarimetry in the diagnosis of glaucoma.

OBJECTIVE: To determine the diagnostic accuracy of scanning laser polarimetry. SUBJECTS AND METHODS: A total of 95 healthy subjects and 102 patients with glaucoma met all inclusion criteria. Data collected on each participant included an automated visual field examination, stereoview optic nerve head photographs, intraocular pressure measurement, and a screening and full scanning laser polarimetry study. Each participant was classified as "normal," "glaucoma," or "uncertain" by each of 3 ophthalmologists based on all available clinical information, with the exception of the scanning laser polarimetry results. Before data analysis, 4 diagnostic algorithms for the full-test mode and 2 for the screening mode were chosen to be evaluated for their sensitivity and specificity in detecting glaucoma. RESULTS: Of the 4 algorithms tested for the full-test mode, "the number" (abnormal test score, >35) had sensitivities of 57%, 71%, and 81% for early, moderate, and severe glaucoma, respectively. Specificity was 89%. For the screening test, sensitivities were much lower, particularly for those with severe glaucoma damage. CONCLUSIONS AND CLINICAL RELEVANCE: Scanning laser polarimetry can help to differentiate subjects with normal findings from patients with glaucomatous damage. Even the best algorithm tested, however, failed to detect a substantial number of subjects with severe damage. Further study is needed before scanning laser polarimetry can be recommended as a screening method for glaucoma.

Aged↗

Dynamical localization of ultracold sodium atoms.

We report a study of atomic motion in time-dependent optical potentials. We measure momentum transfer in parameter regimes for which the classical dynamics are chaotic, and observe the quantum suppression of chaos by dynamical localization. The high degree of control over the experimental parameters enables detailed comparisons with theoretical predictions, and opens new avenues for investigating quantum chaos.

Journal Article↗

Consolidation of medical groups into physician practice management organizations.

CONTEXT: Medical groups are growing and merging to improve efficiency and bargaining leverage in the competitive managed care environment. An increasing number are affiliating with physician practice management (PPM) firms that offer capital financing, expertise in utilization management, and global capitation contracts with health insurance entities. These physician organizations provide an alternative to affiliation with a hospital system and to individual physician contracting with health plans. OBJECTIVE: To describe the growth, structure, and strategy of PPM organizations that coordinate medical groups in multiple markets and contract with health maintenance organizations (HMOs). DESIGN: Case studies, including interviews with administrative and clinical leaders, review of company documents, and analysis of documents from investment bankers, the Securities and Exchange Commission, and industry observers. SETTING: Medical groups and independent practice associations (IPAs) in California and New Jersey affiliated with MedPartners, FPA Medical Management, and UniMed. OUTCOME MEASURES: Growth in number of primary care and specialty care physicians employed by and contracting with affiliated medical groups; growth in patient enrollment from commercial, Medicare, and Medicaid HMOs; growth in capitation and noncapitation revenues; structure and governance of affiliated management service organizations and professional corporations; and contracting strategies with HMOs. RESULTS: Between 1994 and 1996, medical groups and IPAs affiliated with 3 PPMs grew from 3787 to 25763 physicians; 65% of employed physicians provide primary care, while the majority of contracting physicians provide specialty care. Patient enrollment in HMOs grew from 285503 to 3028881. Annual capitation revenues grew from $190 million to $2.1 billion. Medical groups affiliated with PPMs are capitated for most professional, hospital, and ancillary clinical services and are increasingly delegated responsibility by HMOs for utilization management and quality assurance. COMMENT: Physician practice management organizations and their affiliated medical groups face the challenge of continuing rapid growth, sustaining stock values, and improving practice efficiencies while maintaining the loyalty of physicians and patients.

California↗

Reproductive health care: services oriented to couples.

Historically, the combination of women's rights to care, population concerns and the development of female-oriented contraceptive methods resulted in family planning programs focusing on women's contraceptive needs and little else. The 1994 United Nations Population Conference in Cairo called for an expansion of programs to cover reproductive health in its broadest interpretation. As this concept has developed and been put into practice it has become evident that a key element in reproductive health services should be the inclusion of the sexually active couple.

Adult↗