24 research outputs found
OUTLINE OF QUATERNARY TECTONICS OF INDONESIA
Quaternary teetonics in fndonesia is conveniently grouped into four types comprising ( 1) uplift and subsidence, Q)warping and folding, (3) horizontal displacements, and (4) volcanotectonic deformations. Quaternary age of the various deformations is mostly inferred from horizontal to subhorizontal attitudes of strata or erosion surfaces, percentage of living mollusc and/or coral species in fossil assemblages, mammalian fauna, imglements, incomplete recrystallization or compaction of sediments, and incomplete devellopment of post Glacial "Daly levels". Radiometric dates for fndonesian Quaternary deposits are rare. Uplift is generally intermittentas is indicated by the presence of multfple coral reef terraces and other types of marine phenomena. The maximum uplift has exceeded 750 meter during the Quaternary. Subsidence implies similar rates of displacement but results in greater depths through absence of denudation. Quaternary folding has raised the land to about 300 meter elevation. Warping has even affected the "stable" regions like e.g. the Sunda Shelf. Horizontal displacements are important along transcurrent faults; e.g. the Lembang Fault near Bandurg, Java, displays a mean horizontal shift of L40 m in the last 6,000 years or even shorter. Vertical displacement through volcanotectonic collapse of the volcanoes and resulting folding through gravity tectonics of the bases are common features and has continued into subhistorical time. Contemporary tectonic diastrophism such as uplift and faulting is especially apparent in the Moluccas.
Effect of Food on the Steady-State Pharmacokinetics of Tenofovir and Emtricitabine plus Efavirenz in Ugandan Adults
We investigated the effect of food on the steady-state pharmacokinetics of a proprietary fixed-dose combination (FDC) tablet containing tenofovir disoproxil fumarate (TDF)/emtricitabine/efavirenz. Fifteen Ugandan HIV-1 patients at steady-state dosing with TDF/emtricitabine/efavirenz were admitted for 24-hour intensive pharmacokinetic sampling after dosing in the fasting state. Blood sampling was repeated seven days later with TDF/emtricitabine/efavirenz administered with food (19 g fat). Drug concentrations in plasma were determined by liquid chromatography and tandem mass spectrometry. Geometric mean ratios (GMRs) and confidence intervals (CIs) of parameters were calculated (reference, fasting). For efavirenz, GMRs (90% CIs) for
Cmax, AUC0−24, and C24 were 1.47 (1.24–1.75), 1.13 (1.03–1.23), and 1.01 (0.91–1.11), respectively. Corresponding GMRs were 1.04 (0.84–1.27), 1.19 (1.10–1.29), and 0.99 (0.82–1.19) for tenofovir, 0.83 (0.76–0.92), 0.87 (0.78–0.97), and 0.91 (0.73–1.14) for emtricitabine. Stable patients may take the FDC without meal restrictions. The FDC should be taken without food by patients experiencing central nervous system toxicities
Pharmacokinetics of lamivudine and lamivudine-triphosphate after administration of 300 milligrams and 150 milligrams once daily to healthy volunteers: Results of the ENCORE 2 Study
There is interest in evaluating the efficacy of lower doses of certain antiretrovirals for clinical care. We determined here the bio-equivalence of plasma lamivudine (3TC) and intracellular 3TC-triphosphate (3TC-TP) concentrations after the administration of two different doses. ENCORE 2 was a randomized crossover study. Subjects received 3TC at 300 and 150 mg once daily for 10 days (arm 1; n = 13) or vice versa (arm 2; n = 11), separated by a 10-day washout. Pharmacokinetic (PK) profiles (0 to 24 h) were assessed on days 10 and 30. Plasma 3TC and 3TC-TP levels in peripheral blood mononuclear cells were quantified by high-performance liquid chromatography-tandem mass spectrometry. Within-subject changes in PK parameters (the area under the concentration-time curve from 0 to 24 h [AUC0-24], the trough concentration of drug in plasma at 24 h [C24], and the maximum concentration of drug in plasma [Cmax]) were evaluated by determining the geometric mean ratios (GMRs) adjusted for study arm, period, and intra-individual variation. Regimens were considered bioequivalent if the 90% confidence interval (90% CI) fell within the range of 0.8 to 1.25. A total of 24 subjects completed the study. The GM (90% CI) 3TC AUC0-24), expressed as ng•h/ml, for the 300- and 150-mg doses were 8,354 (7,609 to 9,172) and 4,773 (4,408 to 5,169), respectively. Bioequivalence in 3TC PK following the administration of 300 and 150 mg was not demonstrated: the GMRs for AUC0-24, C24, and Cmax were 0.57 (0.55 to 0.60), 0.63 (0.59 to 0.67), and 0.56 (0.53 to 0.60), respectively. The GM (90% CI) 3TC-TP AUC0-24 values (pmol•h/106 cells) for the 300- and 150-mg doses were 59.5 (51.8 to 68.3) and 44.0 (38.0 to 51.0), respectively. Bioequivalence in 3TC-TP PK following the administration of 300 and 150 mg was not demonstrated: the GMRs for AUC0-24, C24, and Cmax were 0.73 (0.64 to 0.83), 0.82 (0.68 to 0.99), and 0.70 (0.61 to 0.82), respectively. We found that 3TC at 150 mg is not bioequivalent to the standard regimen of 300 mg, indicating that saturation of cytosine phosphorylation pathways is not achieved at a dose of 150 mg
Persistent elastic behavior above a megathrust rupture patch: Nias island, West Sumatra
We quantify fore-arc deformation using fossil reefs to test the assumption commonly made in seismic cycle models that anelastic deformation of the fore arc is negligible. Elevated coral microatolls, paleoreef flats, and chenier plains show that the Sumatran outer arc island of Nias has experienced a complex pattern of relatively slow long-term uplift and subsidence during the Holocene epoch. This same island rose up to 2.9 m during the Mw 8.7 Sunda megathrust rupture in 2005. The mismatch between the 2005 and Holocene uplift patterns, along with the overall low rates of Holocene deformation, reflects the dominance of elastic strain accumulation and release along this section of the Sunda outer arc high and the relatively subordinate role of upper plate deformation in accommodating long-term plate convergence. The fraction of 2005 uplift that will be retained permanently is generally <4% for sites that experienced more than 0.25 m of coseismic uplift. Average uplift rates since the mid-Holocene range from 1.5 to −0.2 mm/a and are highest on the eastern coast of Nias, where coseismic uplift was nearly zero in 2005. The pattern of long-term uplift and subsidence is consistent with slow deformation of Nias along closely spaced folds in the north and trenchward dipping back thrusts in the southeast. Low Holocene tectonic uplift rates provide for excellent geomorphic and stratigraphic preservation of the mid-Holocene relative sea level high, which was under way by ∼7.3 ka and persisted until ∼2 ka
Conducting High-Value Secondary Dataset Analysis: An Introductory Guide and Resources
Secondary analyses of large datasets provide a mechanism for researchers to address high impact questions that would otherwise be prohibitively expensive and time-consuming to study. This paper presents a guide to assist investigators interested in conducting secondary data analysis, including advice on the process of successful secondary data analysis as well as a brief summary of high-value datasets and online resources for researchers, including the SGIM dataset compendium (www.sgim.org/go/datasets). The same basic research principles that apply to primary data analysis apply to secondary data analysis, including the development of a clear and clinically relevant research question, study sample, appropriate measures, and a thoughtful analytic approach. A real-world case description illustrates key steps: (1) define your research topic and question; (2) select a dataset; (3) get to know your dataset; and (4) structure your analysis and presentation of findings in a way that is clinically meaningful. Secondary dataset analysis is a well-established methodology. Secondary analysis is particularly valuable for junior investigators, who have limited time and resources to demonstrate expertise and productivity
PRE-CRISIS AND POST-CRISIS ANALYSIS OF THE MOST DIVERSIFIED PORTFOLIO ON THE HONG KONG MARKET
Bachelor'sBACHELOR OF SCIENCE (HONOURS
Medication Exposure and Risk of Recurrent Clostridium difficile Infection in Community-Dwelling Older People and Nursing Home Residents
BACKGROUND/OBJECTIVES: It is unclear how medication exposures differ in their association with recurrent Clostridium difficile infection (rCDI) in elderly nursing home (NH) residents and community-dwelling individuals. This study examined these exposures to determine whether the risk of rCDI differs according to living environment.
DESIGN: Retrospective.
SETTING: Academic and community healthcare settings.
PARTICIPANTS: Individuals aged 65 and older with CDI (N = 616).
MEASUREMENTS: Information on participant characteristics and medications was extracted from the electronic medical record (EMR). We used separate extended Cox models according to living environment to identify the association between medication use and risk of rCDI.
RESULTS: Of the 616 elderly adults treated for CDI, 24.1% of those living in the community and 28.1% of NH residents experienced recurrence within 1 year. For community-dwelling participants, the risk of rCDI was 1.6 times as high with antibiotic exposure and 2.5 times as high with acid-reducing medication exposure, but corticosteroid exposure was associated with a 39% lower risk of recurrence. For NH residents, the risk of rCDI was 2.9 times as high with acid-reducing medication exposure and 5.9 times as high with corticosteroid medication exposure. Antibiotic exposure was associated with an increased risk of recurrence only in community-dwelling participants (adjusted hazard ratio = 1.63, 95% confidence interval = 1.00-2.67).
CONCLUSION: Risk of rCDI is greater with acid-reducing medication use than antibiotic use after initial CDI treatment, although the risk varied depending on living environment. Corticosteroid use is associated with greater risk of recurrence in NH residents but lower risk in community-dwelling elderly adults
Elderly patients are at increased risk for treatment failure in outpatient management of purulent skin infections
OBJECTIVE: Current Infectious Disease Society of America (IDSA) guidelines for the management of purulent skin or soft tissue infections do not account for patient age in treatment recommendations. The study objective was to determine if age was associated with outpatient treatment failure for purulent skin infection after adjusting for IDSA treatment guidelines.
METHODS: We conducted a multicenter retrospective study of adult patients treated for a purulent skin infection and discharged home from four emergency departments between April and September 2014. Patients were followed for one month to assess for treatment failure (defined as need for a change in antibiotics, surgical intervention, or hospitalization). We used multivariable logistic regression to examine the role of patient age on treatment failure adjusting for demographic variables (gender, race), comorbidities and severity of infection.
RESULTS: A total of 467 patients met inclusion criteria (mean age 37.9years [SD 14.0], 48.2% of whom were women). Overall, 12.4% failed initial therapy. Patients 65 years and older (n=35) were almost 4 times more likely to fail initial ED therapy in follow-up compared with younger patients (adjusted Odds Ratio (OR) 3.87, 95% Confidence Interval (CI) 1.24-12.10). After adjustment, for every 10years of advancing age there was a 43% increased odds of failing initial treatment (OR 1.43 95% CI 1.09-1.88).
CONCLUSION: Elderly patients with purulent skin infections, whose providers followed the 2014 IDSA guidelines, were more likely to fail initial treatment than younger patients. This study suggests that there is a need to re-evaluate treatment guidelines in elderly patients
Pharmacokinetic interactions of nevirapine and methadone and guidelines for use of nevirapine to treat injection drug users.
Administration of nevirapine to HIV-infected injection drug users who also receive methadone results in a significant reduction in methadone exposure after 710 days of therapy. Many patients require an increase in methadone dose to counteract this effect. Eight patients (4 men and 4 women) attending the National Drug Treatment Clinic, Trinity Court (Dublin, Ireland), who were receiving stable daily methadone maintenance therapy, were HIV infected, and fulfilled standard criteria for commencement of antiretroviral therapy were recruited into the study.Pharmacokinetic data show a reduction in AUC for methadone of 57% and 51% and a reduction in maximum concentration of 48% and 36% when it is administered in combination with EFV and NVP, respectively. However, the possibility that a process of "induction-detoxification" occurs during the first 2-3 weeks of therapy indicates that the increase in methadone dose required is not as significant as is suggested by these data. A mean increase in methadone dose of 16%-22% may be required in some, but not all, patients after 7-10 days of antiretroviral therapy