Mandatory HIV testing and prostitution: the world's oldest profession and the world's newest deadly disease.
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AIDS Serodiagnosis↗
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Results for “Adams v. State”
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Epidemiological approaches to safety investigations.
This paper considers the different approaches to post-authorisation safety monitoring of veterinary medicinal products that is essential to ensure confidence in their safety. Most safety testing is undertaken prior to granting of a marketing authorisation and is generally on a small scale. Field trials are usually much larger, but still involve relatively low numbers of animals compared to the number to which authorised products are administered. Safety testing is generally aimed at detecting common events; the numbers of animals used in the tests are too small for detection of all but the most common reactions. The efficiency of the tests depends on the frequency and severity of the adverse reaction and the ability to associate the adverse event with the product. The latter is affected by the period of time between administration and the event, as well as by its underlying frequency. Adverse reaction surveillance is critical in monitoring the safety of a marketed product. Most is entirely passive and so reporting rates are likely to underestimate true incidence. It is relatively efficient for rare, serious adverse effects and for those with a low underlying frequency in the population, but it is less useful when there is long period between administration and the event, or where the event has a relatively high underlying frequency. Greater emphasis should be placed on active surveillance after production registration. Detailed epidemiological investigations, including cohort, case control and cross-sectional designs, offer the only approaches that provide more information on the association between a product and events that have a high underlying frequency in the population or where there is a long period between administration and the adverse event. The relative merits of different approaches are discussed, with particular reference to our recently published study of the temporal association between canine vaccination and non-specific signs of ill health and plans to undertake studies of associations with feline injection site sarcoma. Emphasis is placed on the need for clearly stated hypotheses and the consideration of equivalence, rather than significance testing when considering safety studies.
Adverse Drug Reaction Reporting Systems↗
Striatal dopaminergic and serotonergic markers in human heroin users.
To establish whether chronic opiate exposure might impair brain dopaminergic or serotonergic function in humans, we assessed biochemical indices of monoaminergic neurotransmitter activity and integrity in post mortem striatum of nine chronic heroin users and 14 control subjects. Striatal levels of the vesicular monoamine transporter were normal, suggesting that the density of dopamine nerve terminals is not reduced in heroin users. In nucleus accumbens, levels of tyrosine hydroxylase protein (-25%) and those of the dopamine metabolite homovanillic acid (-33%) were reduced significantly together with a trend for decreased dopamine (-32%) concentration. These changes could reflect either a compensatory downregulation of dopamine biosynthesis in response to prolonged dopaminergic stimulation caused by heroin, or reduced axoplasmic transport of tyrosine hydroxylase. Striatal levels of serotonin were either normal or elevated whereas concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid were decreased by 27-38%. Our data suggest that chronic heroin exposure might produce a modest reduction in dopaminergic and serotonergic activity that could affect motivational state and impulse control, respectively.
Adult↗
Rejecting criminal liability for life-shortening palliative care.
Is it possible that a physician who administers life-shortening palliative care, even to a terminally ill patient with the patient's consent, commits murder? The Law Reform Commission of Canada, as part of its proposals on recodifying criminal law, has recommended that criminal liability not attach to the administration of life-shortening palliative care "appropriate in the circumstances." The author submits that while the aim of the Commission's recommendation is good, the phrase "appropriate in the circumstances" should be replaced with more specific criteria for determining when life-shortening palliative care may be administered. Failure to do so would leave physicians in almost as uncertain a situation as is presently the case, preventing them from administering such care without fear of criminal liability.
Adult↗
Grassroots participation on your own turf: developing a personal political action plan.
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Humans↗
Observation of exotic meson production in the reaction pi- p --> eta'pi- p at 18 GeV/c.
An amplitude analysis of an exclusive sample of 5765 events from the reaction pi- p-->eta'pi- p at 18 GeV/c is described. The eta'pi- production is dominated by natural parity exchange and by three partial waves: those with J(PC) = 1(-+), 2(++), and 4(++). A mass-dependent analysis of the partial-wave amplitudes indicates the production of the a2(1320) meson as well as the a4(2040) meson, observed for the first time decaying to eta'pi-. The dominant, exotic (non- qq) 1(-+) partial wave is shown to be resonant with a mass of 1.597+/-0.010(+0.045)(-0.010) GeV/c2 and a width of 0.340+/-0.040+/-0.050 GeV/c2. This exotic state, the pi1(1600), is produced with a t dependence which is different from that of the a2(1320) meson, indicating differences between the production mechanisms for the two states.
Journal Article↗
To preempt or not to preempt: HMO liability pre and post Pegram v. Herdrich.
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Consumer Advocacy↗
Observation of an exotic baryon with S=+1 in photoproduction from the proton.
The reaction gamma p-->pi(+)K(-)K(+)n was studied at Jefferson Laboratory using a tagged photon beam with an energy range of 3-5.47 GeV. A narrow baryon state with strangeness S=+1 and mass M=1555+/-10 MeV/c(2) was observed in the nK(+) invariant mass spectrum. The peak's width is consistent with the CLAS resolution (FWHM=26 MeV/c(2)), and its statistical significance is (7.8+/-1.0)sigma. A baryon with positive strangeness has exotic structure and cannot be described in the framework of the naive constituent quark model. The mass of the observed state is consistent with the mass predicted by the chiral soliton model for the Theta(+) baryon. In addition, the pK(+) invariant mass distribution was analyzed in the reaction gamma p-->K(-)K(+)p with high statistics in search of doubly charged exotic baryon states. No resonance structures were found in this spectrum.
Journal Article↗
Measurement of ep-->e' ppi+ pi- and baryon resonance analysis.
The cross section for the reaction ep-->e(')ppi(+)pi(-) was measured in the resonance region for 1.4<W<2.1 GeV and 0.5<Q2<1.5 GeV(2)/c(2) using the CLAS detector at Jefferson Laboratory. The data show resonant structures not visible in previous experiments. The comparison of our data to a phenomenological prediction using available information on N(*) and Delta states shows an evident discrepancy. A better description of the data is obtained either by a sizable change of the properties of the P13(1720) resonance or by introducing a new baryon state, not reported in published analyses.
Journal Article↗
NEW LEPTOSPIRAL SEROTYPE IN THE PYROGENES SEROGROUP.
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Antigen-Antibody Reactions↗
Search for exclusive multibody non- decays at the resonance.
Using data collected at the psi(3770) resonance with the CLEO-c detector at the Cornell e+e- storage ring, we present searches for 25 charmless decay modes of the psi(3770), mostly multibody final states. No evidence for charmless decays is found.
Journal Article↗
Hypercoagulability: a cause of vascular access failure.
In a group of 58 patients requiring tertiary vascular access procedures for maintenance of hemodialysis, 29 patients who thrombosed well-functioning fistulas were evaluated for both antithrombin deficiencies as well as platelet hyperaggreability. Thirteen of these 29 patients were found to have one or more coagulation defects. Following correction of the hypercoagulable state, tertiary vascular access procedures, using autologous tissues, were 100% successful in these 13 patients.
Antithrombin III Deficiency↗
Coagulation and fibrinolysis in patients undergoing operation for ruptured and nonruptured infrarenal abdominal aortic aneurysms.
PURPOSE: Hemorrhage and thrombosis predisposing to myocardial infarction, multiple organ failure, and thromboembolism account for the majority of the morbidity and mortality associated with repair of ruptured and nonruptured abdominal aortic aneurysms (AAAs). The aim of this study was to examine coagulation and fibrinolysis in patients operated on for ruptured and nonruptured infrarenal AAAs. METHODS: Ten patients operated on for ruptured and 9 patients operated on for nonruptured AAAs were studied. Tissue plasminogen activator (t-PA) antigen, thrombin-antithrombin (TAT), and D-dimer were measured before induction of anesthesia. Plasminogen activator inhibitor (PAI) activity, t-PA activity, and prothrombin fragment (PF) 1+2 were measured before induction of anesthesia, immediately before aortic clamp release, and 5 minutes and 24 hours after aortic clamp release. RESULTS: Preoperatively, ruptured AAA was associated with significantly elevated t-PA antigen (median 15.7 ng/mL, range 9. 0 to 22.1 ng/mL versus nonrupture: median 6.6 ng/mL, range 4.7 to 16. 4 ng/mL; P <.01, Mann-Whitney test), increased PAI activity (median 36.5 arbitrary units/mL, range 20.6 to 38.8 arbitrary units/mL versus nonrupture: median 8.2 arbitrary units/mL, range 3.2 to 21.7 arbitrary units/mL; P <.001), reduced t-PA activity (median 0.12 IU/mL, range 0.06 to 0.4 IU/mL versus nonrupture: median 0.49 IU/mL, range 0.14 to 3.2 IU/mL; P <.01), elevated TAT (median 135.5 microg/L, range 61.2 to 209.4 microg/L versus nonrupture: median 21. 6 microg/L, range 6.6 to 180.4 microg/L; P <.02) and elevated PF 1+2 (median 9.0 nmol/L, range 5.4 to 11.6 nmol/L versus nonrupture: median 2.2 nmol/L, range 0.7 to 7.1 nmol/L, P <.001). There was no significant difference in preoperative D-dimer levels (median 3460 ng/mL, range 1236 to 7860 ng/mL versus nonrupture: median 1642 ng/mL, range 728 to 5334 ng/mL; P =.07). The differences in PAI activity, t-PA activity, and PF 1+2 persisted throughout the course of surgery, but there was no significant difference between the groups at 24 hours. CONCLUSION: These novel data demonstrate that ruptured AAA repair is associated with inhibition of systemic fibrinolysis and intense thrombin generation. Similar changes are seen in nonruptured AAA but are of a lesser magnitude. This procoagulant state may contribute to the microvascular and macrovascular thrombosis that leads to myocardial infarction, multiple organ failure, and thromboembolism.
Aged↗
Estimating the cost of new drug development: is it really 802 million dollars?
This paper replicates the drug development cost estimates of Joseph DiMasi and colleagues ("The Price of Innovation"), using their published cost estimates along with information on success rates and durations from a publicly available data set. For drugs entering human clinical trials for the first time between 1989 and 2002, the paper estimated the cost per new drug to be 868 million dollars. However, our estimates vary from around 500 million dollars to more than 2,000 million dollars, depending on the therapy or the developing firm.
Clinical Trials as Topic↗
Decline of childhood Haemophilus influenzae type b (Hib) disease in the Hib vaccine era.
OBJECTIVE: Effective Haemophilus influenzae type b (Hib) conjugate vaccines were first licensed for use in US children at least 18 months old in December 1987 and for infants at least 2 months old in October 1990. We evaluated trends in Hib disease associated with licensure of Hib conjugate vaccines. DESIGN: Data from two sources, an intensive laboratory-based active surveillance system and the National Bacterial Meningitis Reporting System (NBMRS), were used separately to evaluate disease incidence. Data from vaccine manufacturers on Hib vaccine doses distributed in the United States were compared with trends in Hib disease incidence. RESULTS: The age-specific incidence of Hib disease among children less than 5 years old decreased by 71% from 37 per 100,000 persons in 1989 to 11 per 100,000 persons in 1991 (active surveillance data). Haemophilus influenzae meningitis incidence decreased by 82% between 1985 and 1991 (NBMRS data). Increases in doses of Hib vaccine distributed in the United States coincided with steep declines in Hib disease. Both surveillance systems showed decreased rates of Hib disease in infants less than 1 year old before vaccine was licensed for use in this age group. Haemophilus influenzae type b disease incidence in persons at least 12 years old and pneumococcal meningitis incidence in children less than 5 years old did not change substantially during the same period; therefore, decreased Hib disease in children less than 5 years old is not likely to be explained solely by changes in surveillance sensitivity or decreases in bacterial disease due to changes in medical practice. CONCLUSION: Our data suggest that conjugate vaccines have already had a marked impact on the incidence of Hib disease in the United States, preventing an estimated 10,000 to 16,000 cases of Hib disease in 1991. The decline of disease in infants less than 1 year old before licensure for this age group warrants further investigation.
Adolescent↗
cis-Stilbene and (1 alpha,2 beta,3 alpha)-(2-ethenyl-3-methoxycyclopropyl)benzene as mechanistic probes in the Mn(III)(salen)-catalyzed epoxidation: influence of the oxygen source and the counterion on the diastereoselectivity of the competitive concerted and radical-type oxygen transfer.
cis-Stilbene (1) has been epoxidized by a set of diverse oxygen donors [OxD], catalyzed by the Mn(III)(salen)X complexes 3 (X = Cl, PF(6)), to afford a mixture of cis- and trans-epoxides 2. The cis/trans ratios range from 29:71 (extensive isomerization) to 92:8, which depends both on the oxygen source [OxD] and on the counterion X of the catalyst. When (1 alpha,2 beta,3 alpha)-(2-ethenyl-3-methoxycyclopropyl)-benzene (4) is used as substrate, a mechanistic probe which differentiates between radical and cationic intermediates, no cationic ring-opening products are found in this epoxidation reaction; thus, isomerized epoxide product arises from intermediary radicals. The dependence of the diastereoselectivity on the oxygen source is rationalized in terms of a bifurcation step in the catalytic cycle, in which concerted Lewis-acid-activated oxygen transfer competes with stepwise epoxidation by the established Mn(V)(oxo) species. The experimental counterion effect is attributed to the computationally assessed ligand-dependent reaction profiles and stereoselectivities of the singlet, triplet, and quintet spin states available to the manganese species.
Journal Article↗
Health department costs of managing persons with suspected and noncounted tuberculosis in New York City, Three Texas counties, and Massachusetts.
OBJECTIVES: To describe persons with suspected (did not meet the national tuberculosis [TB] surveillance case definition) and noncounted TB (met the TB case definition but transferred and were counted by another jurisdiction) and estimate costs incurred by public health departments for managing them. METHODS: We reviewed TB registry, medical records, budgets, bills, salaries, organizational charts, and travel/activity logs from the year 2000 at health departments in New York City (NYC), three Texas (TX) counties (El Paso, Hidalgo, and Webb), and Massachusetts (MA). We also interviewed or observed personnel to estimate the time spent on activities for these patients. RESULTS: In 2000, NYC and MA had more persons with suspected (n = 2,996) and noncounted (n = 163) TB than with counted (n = 1,595) TB. TX counties had more persons with counted TB (n = 179) than with suspected (n = 55) and noncounted (n = 15) TB. Demographic and clinical characteristics varied widely. For persons with suspected TB, NYC spent an estimated $1.7 million, with an average cost of $636 for each person; TX counties spent $60,928 ($1,108 per patient); and MA spent $1.1 million ($3,330 per patient). For persons with noncounted TB, NYC spent $303,148 ($2,180 per patient), TX counties spent $40,002 ($2,667 per patient), and MA spent $84,603 ($3,525 per patient). CONCLUSIONS: Health departments incurred substantial costs in managing persons with suspected and noncounted TB. These costs should be considered when allocating TB program resources.
Health Care Costs↗
Towards a tunable molecular memory that fits into a (10 A)3 cube.
Using DFT calculations we predict a novel family of small amino acid-based memory-exhibiting molecules, namely complexes of triply deprotonated cysteine (or its derivatives) with selected hexavalent transition metals. We show that the energy difference of the 0 and 1 electromers--corresponding to two chemically distinct oxidation states of a metal, M(VI) and M(IV)--can be tuned towards the thermodynamic equilibrium via deliberate chemical substitutions in the cysteine ligand. Although the thermal stability of both electromers is computed to be rather small at ambient temperatures (due to facile interchange of states 0 and 1 via a low-lying M(V) configuration), we hope to improve stability in related systems. [Figure: see text]. We propose novel kind of tunable molecular memory, based on intramolecular 2e- redox reaction.
Models, Molecular↗