Search PubMed⌕ Search

Biomedical subjects

Robert Miller

Publications and source records attributed to Robert Miller.

At least 19 recordsLinked to original sources
PubMed2025

Insights from farming Macrocystis pyrifera offshore: phenotypic analysis, genome-wide association studies, genomic selection.

Seaweed farming, as a part of aquaculture, offers a sustainable alternative to modern agricultural practices; however, genetic enhancement and breeding programs for most species are underdeveloped. We aimed to advance seaweed domestication by focusing on giant kelp (Macrocystis pyrifera), the fastest-growing haplodiplontic brown alga, which has significant ecological and commercial importance. We analyzed phenotypic data from two offshore experimental farms conducted in 2019 and 2020, which involved hundreds of outplanted genetically diverse sporophytes. We found that outplanting season and farm design had significant effects on giant kelp biomass. Broad-sense heritability estimates showed moderate (0.27-0.50) genetic contributions to two phenotypes, carbon content and total biomass. Genome-wide association studies for these phenotypes resulted in three statistically significant SNPs, located near or within genes involved in carbohydrate metabolism and cytoskeletal functions. In addition, we applied genomic selection models that integrated sporophyte phenotypes and parental gametophyte genotypes. These models utilized reduced sets of GWAS-ranked SNPs obtained by a procedure based on linkage disequilibrium estimations. Model testing yielded cross-validation accuracy values of up to 0.84 and predictive accuracy values of up to 0.40, demonstrating the potential of marker-assisted breeding for phenotype improvement. Our results provide foundational genomic resources and tools for domesticating and breeding M. pyrifera, offering a basis for developing giant kelp varieties with desirable traits.

Journal Article↗
PubMed2006

Theory of the normal waking EEG: from single neurones to waveforms in the alpha, beta and gamma frequency ranges.

The classic alpha rhythm, recorded intracortically, consists of alternating surface-negative troughs and briefer surface-positive peaks. The troughs are associated with neuronal hyperpolarization, the peaks with brief depolarization and burst firing. Each hyperpolarization is mainly a potassium potential, lasting approximately 100 ms. Depolarization and burst firing arise when this inactivates. In the desynchronized state, membrane potential is poised just below threshold. Firing in vivo is somewhat irregular and non-bursting. It is suggested that EEG bistability (classic alpha vs desynchronization) corresponds to bistability of single pyramidal cells. In vitro, paired pulses lead to depression of synaptic transmission in synapses linking two pyramidal cells, but to facilitation in synapses linking pyramidal cells to inhibitory neurones. These effects should be recruited by burst firing in vivo. Thus, enhancement of inhibitory and excitatory transmission occur respectively during the classic alpha rhythm, and the desynchronized state. As a result both states tend to be self-sustaining. In the desynchronized state high frequency (gamma or beta) activity predominates. In simulations, gamma activity has been modeled as the behaviour of cortical networks where populations of excitatory and inhibitory neurones interact. These simulations assume conduction times between neurones to be negligible. However, this is not true for long-distance interactions. Introduction into the models of plausible conduction delays should slow the oscillation frequency. The activated cortex can then produce not only gamma activity but also beta, and sometimes alpha activity. Thus, alpha frequencies can arise both in the "idling" cortex (classic alpha), and in the activated cortex, although the respective mechanisms are quite different.

Alpha Rhythm↗
PubMed2006

ULBPs, human ligands of the NKG2D receptor, stimulate tumor immunity with enhancement by IL-15.

ULBPs are human ligands for NKG2D, an activating receptor expressed on natural killer (NK) cells, NK1.1(+) T cells, and T cells. ULBPs are expressed by a variety of leukemias, carcinomas, melanomas, and tumor cell lines. ULBP expression correlates with improved survival in cancer patients, however, the nature of the immune response that ULBPs elicit is not well understood. We report that ectopic expression of ULBP1 or ULBP2 on murine EL4 or RMA tumor cells elicits potent antitumor responses in syngeneic C57BL/6 and SCID mice. Although binding of ULBP3 to murine NKG2D could not be demonstrated in vitro, ULBP3 can also stimulate antitumor responses, suggesting that ULBP3 binds to murine NKG2D or possibly another receptor in vivo. ULBP expression was found to recruit NK cells, NK1.1(+) T cells, and T cells to the tumor. IL-15 was found to strongly enhance the immune response directed against ULBP-expressing tumors. Tumors can evade NKG2D immunity by down-regulating expression of NKG2D. Our data suggest that IL-15 may be useful for overcoming this tumor-evasion strategy. Together, these results demonstrate that ULBP expression can elicit a potent immune response and suggest that ULBPs, alone or in combination with IL-15, can be exploited for antitumor therapy.

Animals↗
PubMed2006

A pilot study of cytokine levels and white blood cell counts in the diagnosis of necrotizing fasciitis.

STUDY OBJECTIVES: To characterize the early cytokine response of patients presenting to the emergency department with necrotizing fasciitis (NF) and to determine whether serum cytokine levels and white blood cell (WBC) counts may be useful in distinguishing NF from other severe soft-tissue infections. METHODS: White blood cell counts and cytokine levels (IL-1beta, IL-1Ra, IL-6, IL-8, IL-18, and IFN-gamma) were measured in patients presenting to the emergency department with severe soft-tissue infections and high suspicion of NF. Necrotizing fasciitis was confirmed intraoperatively and by surgical pathology. Cytokines were measured via the liquid-phase electrochemiluminescence method. RESULTS: Thirty-five patients were enrolled, 18 were diagnosed with NF, and 17 were diagnosed with cellulitis and/or abscess (CAB). On admission, patients with NF had significantly higher WBC counts and lower levels of interleukin 1beta (IL-1beta) compared with patients with CAB. There were no statistically significant differences in the levels of the other cytokines between the 2 groups. CONCLUSION: Patients with NF have higher WBC counts and lower IL-1beta levels compared with patients with CAB.

Abscess↗
PubMed2006

Early experiences with e-health services (1999-2002): promise, reality, and implications.

BACKGROUND: E-health services may improve the quality and efficiency of care; however, there is little quantitative data on e-health use. OBJECTIVE: The objective of this study was to examine trends in e-health use and user characteristics. RESEARCH DESIGN: This was a longitudinal study of e-health use (1999-2002) within an integrated delivery system (IDS). We classified 4 e-health services into transactional (drug refills and appointment scheduling) and care-related (medical and medication advice) services. SUBJECTS: Approximately 3.3 million members of a large, prepaid IDS. MEASUREMENTS: Amount and frequency of e-health use over time and characteristics of users. RESULTS: The number of members registered for access to e-health increased from 20,617 (0.7% of all members) in Q1 1999 to 270,987 (8.6%) in Q3 2002. Between Q1 and Q3 2002, 42,845 members (1.3%) used the drug refill service and 55,901 (1.7%) used the appointment scheduling service compared with 10,756 members (0.3%) who used the medical advice service and 3069 (0.1%) who used the medication advice service. Over the same period, transactional service users averaged 3.5 uses/user versus 1.6 uses/user among care-related service users. Members most likely to use e-health services had a high level of clinical need, a regular primary care provider, were 30 to 64 years old, female, white, and lived in a nonlow socioeconomic status neighborhood. These findings were consistent across e-health service types. CONCLUSIONS: Although use of all e-health services grew rapidly, use of care-related services lagged significantly behind use of transactional services. Subjects with greater clinical need and better ties to the health system were more likely to use both types of e-health services.

Adolescent↗
PubMed2006

Pulmonary alveolar proteinosis associated with a disease-modifying antirheumatoid arthritis drug.

Pulmonary alveolar proteinosis is an uncommon disorder marked by the abnormal accumulation of surfactant within the alveoli. Secondary pulmonary alveolar proteinosis develops in patients who are immunosuppressed, usually with corticosteroids. We present a case of biopsy-proven pulmonary alveolar proteinosis in a patient undergoing therapy with the disease-modifying antirheumatoid arthritis drug leflunomide (Arava; Aventis Pharmaceuticals, Bridgewater, NJ). He was treated with whole lung lavage and discontinuation of leflunomide with good results. This is the first reported association of secondary pulmonary alveolar proteinosis with leflunomide therapy. Pulmonary alveolar proteinosis should be considered in patients with diffuse lung disease that develops while on disease-modifying antirheumatoid arthritis drug therapy.

Adult↗
PubMed2005

U.K. Controlled trial of intrapleural streptokinase for pleural infection.

BACKGROUND: Intrapleural fibrinolytic agents are used in the drainage of infected pleural-fluid collections. This use is based on small trials that did not have the statistical power to evaluate accurately important clinical outcomes, including safety. We conducted a trial to clarify the therapeutic role of intrapleural streptokinase. METHODS: In this double-blind trial, 454 patients with pleural infection (defined by the presence of purulent pleural fluid or pleural fluid with a pH below 7.2 with signs of infection or by proven bacterial invasion of the pleural space) were randomly assigned to receive either intrapleural streptokinase (250,000 IU twice daily for three days) or placebo. Patients received antibiotics and underwent chest-tube drainage, surgery, and other treatment as part of routine care. The number of patients in the two groups who had died or needed surgical drainage at three months was compared (the primary end point); secondary end points were the rates of death and of surgery (analyzed separately), the radiographic outcome, and the length of the hospital stay. RESULTS: The groups were well matched at baseline. Among the 427 patients who received streptokinase or placebo, there was no significant difference between the groups in the proportion of patients who died or needed surgery (with streptokinase: 64 of 206 patients [31 percent]; with placebo: 60 of 221 [27 percent]; relative risk, 1.14 [95 percent confidence interval, 0.85 to 1.54; P=0.43), a result that excluded a clinically significant benefit of streptokinase. There was no benefit to streptokinase in terms of mortality, rate of surgery, radiographic outcomes, or length of the hospital stay. Serious adverse events (chest pain, fever, or allergy) were more common with streptokinase (7 percent, vs. 3 percent with placebo; relative risk, 2.49 [95 percent confidence interval, 0.98 to 6.36]; P=0.08). CONCLUSIONS: The intrapleural administration of streptokinase does not improve mortality, the rate of surgery, or the length of the hospital stay among patients with pleural infection.

Anti-Bacterial Agents↗
PubMed2005

Practice parameter: utility of electrodiagnostic techniques in evaluating patients with suspected peroneal neuropathy: an evidence-based review.

An evidence-based review of electrodiagnostic (EDX) techniques in the evaluation of peroneal neuropathy was conducted to determine whether these techniques are useful for diagnosis and prognostication in this disorder. A Medline search and a review of relevant sources were performed in 1999 and updated through July 2003 to identify articles describing the use of EDX in patients suspected to have peroneal neuropathy. From the 499 articles identified, 112 articles describing motor and sensory nerve conduction studies and needle electromyography in peroneal neuropathy were reviewed in detail; 11 articles met the predetermined literature inclusion criteria for the adequacy of EDX techniques employed. Six articles provided Class III evidence in support of a role for nerve conduction studies in making the diagnosis of peroneal neuropathy; five articles provided Class IV evidence. Implicit in making the diagnosis were normal EDX findings outside the distribution of the peroneal nerve. The current literature supports the use of EDX in patients with suspected peroneal neuropathy (Level C recommendation).

Electrodiagnosis↗
PubMed2005

Integrating preferences into health status assessment for amyotrophic lateral sclerosis: the ALS Utility Index.

We developed a preference-based measure, the Amyotrophic Lateral Sclerosis Utility Index (ALSUI), allowing computation of US population-based utility weights for the wide range of health states observed among ALS patients. A multi-attribute utility approach was used. An ALS Health State Classification System was developed comprising the following attributes with different severity levels: Speech and Swallowing (A1); Eating, Dressing, and Bathing (A2); Leg Function (A3); and Respiratory Function (A4). An internet-based survey was administered to a random sample of the US population to assess preferences for ALS health states based on this system using visual analog scale (VAS) and standard gamble (SG) questions. Using the VAS and SG data from 1374 individuals in the general population, utility functions were computed that corresponded to each severity level within A1, A2, A3, and A4. ALSUI scores for a given patient are computed by inputting his corresponding utility functions into the following multiplicative formula: ALSUI score = 1.06 x (A1 x A2 x A3 x A4) - 0.06 on a scale where 0.0 reflects death and 1.0 reflects healthy. This study provides a useful tool for classifying ALS patients and determining a general public-based utility score for ALS health states.

Activities of Daily Living↗
PubMed2005

Tardive dyskinesia in the era of typical and atypical antipsychotics. Part 1: pathophysiology and mechanisms of induction.

OBJECTIVE: Tardive dyskinesia (TD) is the principal adverse effect of long-term treatment with conventional antipsychotic agents. Several mechanisms may exist for this phenomenon. Mechanisms for the lower incidence of TD with atypical antipsychotics also remain to be fully understood. We undertook to explore and better understand these mechanisms. METHODS: We conducted a comprehensive review of TD pathophysiology literature from January 1, 1965, to January 31, 2004, using the terms tardive dyskinesia, neuroleptics, antipsychotics, pathophysiology, and mechanisms. Additional articles were obtained by searching the bibliographies of relevant references. Articles were considered if they contributed to the current understanding of the pathophysiology of TD. RESULTS: Current TD vulnerability models include genetic vulnerability, disease-related vulnerability, and decreased functional reserve. Mechanisms of TD induction include prolonged blockade of postsynaptic dopamine receptors, postsynaptic dopamine hypersensitivity, damage to striatal GABA interneurons, and damage of striatal cholinergic interneurons. Atypical antipsychotics may cause less TD because they have less impact on the basal ganglia and are less likely to cause postsynaptic dopamine hypersensitivity. CONCLUSION: Although the ultimate model for TD is not yet understood, it is plausible that several of these vulnerabilities and mechanisms act together to produce TD. The lower incidence of TD with atypical antipsychotics has helped to elucidate the,mechanisms of TD.

Antipsychotic Agents↗
PubMed2005

Tardive dyskinesia in the era of typical and atypical antipsychotics. Part 2: Incidence and management strategies in patients with schizophrenia.

OBJECTIVE: Tardive dyskinesia (TD), the principal adverse effect of long-term conventional antipsychotic treatment, can be debilitating and, in many cases, persistent. We sought to explore the incidence and management of TD in the era of atypical antipsychotics because it remains an important iatrogenic adverse effect. METHODS: We conducted a review of TD incidence and management literature from January 1, 1965, to January 31, 2004, using the terms tardive dyskinesia, management, therapy, neuroleptics, antipsychotics, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole. Additional articles were obtained by searching the bibliographies of relevant references. We considered articles that contributed to the current understanding of both the incidence of TD with atypical antipsychotics and management strategies for TD. RESULTS: The incidence of TD is significantly lower with atypical, compared with typical, antipsychotics, but cases of de novo TD have been identified. Evidence suggests that atypical antipsychotic therapy ameliorates long-standing TD. This paper outlines management strategies for TD in patients with schizophrenia. CONCLUSION: The literature supports the recommendation that atypical antipsychotics should be the first antipsychotics used in patients who have experienced TD as a result of treatment with conventional antipsychotic agents. The other management strategies discussed may prove useful in certain patients.

Antipsychotic Agents↗
PubMed2005

Adverse oral sequelae to bisphosphonate administration.

Osteonecrosis of the jaws following the administration of bisphosphonate class drugs, both intravenous and oral, has recently been reported in the literature. A case series of five patients is presented. The clinical presentation, management, and proposed etiology of this adverse reaction are reviewed. Recommendations for identifying patients who may be at risk via medical history, present and past medications, specific drugs involved and recommended precautions involving various dental interventions are also discussed.

Aged↗
PubMed2004

Use of e-Health services between 1999 and 2002: a growing digital divide.

OBJECTIVE: To evaluate the patterns of e-Health use over a four-year period and the characteristics of users. DESIGN: Longitudinal, population-based study (1999-2002) of members of a prepaid integrated delivery system. Available e-Health services included ordering prescription drug refills, scheduling appointments, and asking medical questions. MEASUREMENTS: Rates of known access to e-Health services, and of e-Health use each quarter. RESULTS: The number of members with known e-Health access increased from 51,336 (1.6%) in 1999 to 324,522 (9.3%), in 2002. The percentage of households in which at least one person in the household had access increased from 2.7% to 14.1%. Among the subjects with known access, the percentage of subjects that used e-Health at least once increased from 25.7% in 1999 to 36.2% in 2002. In the multivariate analysis, subjects who had a low expected clinical need, were nonwhite, or lived in low socioeconomic status (SES) neighborhoods were less likely to have used e-Health services in 2002. Disparities by race/ethnicity and SES persisted after controlling for access to e-Health and widened over time. CONCLUSION: Access to and use of e-Health services are growing rapidly. Use of these services appears to be greatest among persons with more medical need. The majority of subjects, however, do not use any e-Health services. More research is needed to determine potential reasons for disparities in e-Health use by race/ethnicity and SES as well as the implications of these disparities on clinical outcomes.

Adolescent↗
PubMed2004

Perspectives on adherence and simplicity for HIV-infected patients on antiretroviral therapy: self-report of the relative importance of multiple attributes of highly active antiretroviral therapy (HAART) regimens in predicting adherence.

BACKGROUND: Adherence to highly active antiretroviral therapy (HAART) of 95% or greater seems to be required for successful treatment of HIV/AIDS. Efforts to simplify regimens to improve adherence are ongoing, including the advent of once-daily (QD) dosing regimens, which are presumed to be beneficial, although data regarding their overall impact on adherence are not yet available. OBJECTIVE: To assess patient perceptions of the impact on adherence of 10 attributes of HAART, including QD dosing, and to compare 7 actual regimens based on patients' perceptions of their likelihood to promote adherence. METHODS: Two hundred ninety-nine highly treatment-experienced patients with HIV/AIDS completed a questionnaire that evaluated perceptions of the impact on adherence of 10 HAART regimen attributes using a modified adaptive conjoint analysis. Patients' perceptions of the likelihood that they would adhere to 7 actual HAART regimens were scored on Likert scales. RESULTS: : Pill count, dosing frequency, and adverse events had the greatest impact on patients' perceived ability to adhere to antiretroviral medication regimens. QD was the preferred dosing frequency, but QD dosing regimens did not score better than other regimens. Among actual regimens, predicted adherence was highest for a twice-daily (BID) regimen with 2 pills daily, no dietary restrictions, and 1 prescription and copayment and lowest for a BID regimen with 13 pills daily, food requirements, and 3 prescriptions and copayments. CONCLUSIONS: All HAART regimen attributes studied were perceived to have an impact on adherence, but pill count, dosing frequency, and adverse events had the greatest perceived impact. These data are of potential importance to clinicians as they seek to structure HAART regimens to which their patients are most likely to adhere.

Adolescent↗
PubMed2004

Management of sexually acquired reactive arthritis in 19 North Thames GUM clinics.

Our objective was to describe how genitourinary medicine (GUM) clinics in the North Thames region manage sexually acquired reactive arthritis (SARA), and to compare management with national guidelines. A self-completed questionnaire survey and retrospective case note review was conducted between September and October 2001. Clinicians in 33 clinics were asked to describe their clinic's policy on the management of SARA, and to review the last five cases seen or the last cases seen in the preceding two years, if less than five. Nineteen (58%) clinics took part. There were inter-clinic variations in the investigation and management of patients, with only 63% (12/19) of clinics offering non-steroidal anti-inflammatory drugs (NSAIDs) and 58% (11/19) giving doxycycline 1001mg. twice daily for two weeks for urethritis - the rest using any of three other antibiotic regimens. There was no consistent policy of referral between other specialties and GUM for genital screening and partner notification. A total of 36 male and female case notes were reviewed. Patients without arthritis or joint swelling (5/38, 13%), or with non-typical symptoms such as diarrhoea (5/38, 13%) were diagnosed inappropriately with SARA. Only 33 (87%) had evidence of a sexually transmitted infection (STI) with at least two (5%) of patients being treated with antibiotics despite no apparent indication being present. Only 21 (55%) had documented NSAID therapy. Case identification was difficult due to the lack of a national disease code (KC60) for SARA. The data suggest that a diagnosis of SARA is sometimes being made with no identifiable STI, or where symptoms are more suggestive that another route of infection is likely. A clear guideline within clinics to standardize prescribing of antibiotics is needed and collaborative policies with GUM are needed for other specialties to use when investigating and managing patients with seronegative arthritis. GUM should consider re-introducing a KC60 code for SARA for better case identification.

Adolescent↗