Palaeolithic cave art in Borneo.

Figurative cave paintings from the Indonesian island of Sulawesi date to at least 35,000 years ago (ka) and hand-stencil art from the same region has a minimum date of 40 ka1. Here we show that similar rock art was created during essentially the same time period on the adjacent island of Borneo. Uranium-series analysis of calcium carbonate deposits that overlie a large reddish-orange figurative painting of an animal at Lubang Jeriji Saléh-a limestone cave in East Kalimantan, Indonesian Borneo-yielded a minimum date of 40 ka, which to our knowledge is currently the oldest date for figurative artwork from anywhere in the world. In addition, two reddish-orange-coloured hand stencils from the same site each yielded a minimum uranium-series date of 37.2 ka, and a third hand stencil of the same hue has a maximum date of 51.8 ka. We also obtained uranium-series determinations for cave art motifs from Lubang Jeriji Saléh and three other East Kalimantan karst caves, which enable us to constrain the chronology of a distinct younger phase of Pleistocene rock art production in this region. Dark-purple hand stencils, some of which are decorated with intricate motifs, date to about 21-20 ka and a rare Pleistocene depiction of a human figure-also coloured dark purple-has a minimum date of 13.6 ka. Our findings show that cave painting appeared in eastern Borneo between 52 and 40 ka and that a new style of parietal art arose during the Last Glacial Maximum. It is now evident that a major Palaeolithic cave art province existed in the eastern extremity of continental Eurasia and in adjacent Wallacea from at least 40 ka until the Last Glacial Maximum, which has implications for understanding how early rock art traditions emerged, developed and spread in Pleistocene Southeast Asia and further afield.

Visualising coordination chemistry: fluorescence X-ray absorption near edge structure tomography.

Coordination chemistry underlies the structure/function of biological metal complexes. Contextualising this chemical information within an organism's physiology is critical for enhancing the understanding of bioinorganic chemistry but few high-fidelity probes are available. Here we develop fluorescence X-ray absorption near-edge structure tomography as a means for studying the spatial arrangement of biological coordination chemistry within intact organisms, and demonstrate the approach by mapping the distribution of cuprous and cupric complexes within Drosophila melanogaster.

A multi-technique investigation of copper and zinc distribution, speciation and potential bioavailability in biosolids.

The use of biosolids in agriculture continues to be debated, largely in relation to their metal contents. Our knowledge regarding the speciation and bioavailability of biosolids metals is still far from complete. In this study, a multi-technique approach was used to investigate copper and zinc speciation and partitioning in one contemporary and two historical biosolids used extensively in previous research and field trials. Using wet chemistry and synchrotron spectroscopy techniques it was shown that copper/zinc speciation in the biosolids was largely equivalent despite the biosolids being derived from different countries over a 50 year period. Furthermore, copper speciation was consistently dominated by sorption to organic matter whereas Zn partitioned mainly to iron oxides. These data suggest that the results of historical field trials are still relevant for modern biosolids and that further risk assessment studies should concentrate particularly on Cu as this metal is associated with the mineralisable biosolids fraction.

Endovascular embolization of the swine rete mirabile with Eudragit-E 100 polymer.

BACKGROUND AND PURPOSE: Both adhesive and nonabrasive embolic agents are available for arteriovenous malformation (AVM) embolization. The purpose of this study was to evaluate a novel ethanol-based nonadhesive liquid embolic material in a swine AVM model. MATERIALS AND METHODS: Eudragit (copolymer of methyl and butyl methacrylate and dimethylaminoethyl methacrylate) was dissolved in 50% ethanol and 50% iopamidol. Eudragit was injected into 9 retia mirabilia (RMs). Ethanol and iopamidol mixture were injected into 4 RMs for comparison. Three RMs embolized with Eudragit mixture were evaluated both angiographically and histopathologically acutely (3-24 hours) and at 30 days and 90 days after embolization. RESULTS: No procedural complications from Eudragrit embolization were noted, including retention or adhesion of the microcatheter. Various degrees of inflammation were observed in the acute and 30-day specimens. Two RMs showed partial recanalization on both histopathology and follow-up angiography in the 30-day group. Arterial fibrosis and calcification were observed in the 30- and 90-day specimens. The internal elastic lamina was disrupted in the 30- and 90-day specimens, but there was no evidence of Eudragit extravasation or hemorrhage. Endothelial damage was seen in all specimens and was particularly severe in the 30- and 90-day specimens. CONCLUSION: Eudragit polymer induced inflammation in thrombosis similar to n-butyl 2-cyanoacrylate, but without the disadvantages of perivascular hemorrhage and extravasation of embolization material. Although recanalization of some embolized RMs was noted, further investigation into Eudragit as a potentially useful embolic material for brain AVMs is warranted.

A comparison of noninvasive objective and subjective measurements of the optical density of human ocular media.

BACKGROUND: It is important for both researchers and clinicians to know the spectral composition of the light that reaches the retina. With this in mind, Johnson et al. developed a quick, objective instrument called the Lens Absorption Monitor (LAM) to measure the attenuation of light by the ocular media. Using a more refined method of measuring and correcting for scatter, we compared the results of the LAM against those with a subjective method utilizing a bipartite scotopic brightness-matching procedure (BIP). METHODS: We tested 41 healthy subjects (mean age, 35.9 years) with the LAM and BIP. RESULTS: Intereye correlation coefficients for the LAM were 0.70 at 410 nm and 0.83 at both 430 and 450 nm; for BIP, intereye correlation coefficients were 0.56 at 410 nm, 0.42 at 430 nm, and 0.38 at 450 nm. For optical density as a function of age, there was no statistically significant difference between the two instruments at 410 nm in either the slope (p > 0.43) or y intercept (p > 0.75). However, at both 430 and 450 nm, there was a significant difference in both slope (p < 0.001) and y intercept (p < 0.05) for the two instruments. CONCLUSIONS: With the latest refinements, LAM density measures correlated well with BIP estimates at 410 nm, but not at 430 or 450 nm. This underscores the fact that the LAM measures the spectral density of the anterior segment, whereas the BIP method is a measure of all the ocular media except for macular pigment. The difference between these two measures is consistent with the existence of a prereceptoral, presumably intraretinal, pigment (or pigments) located outside the anatomic fovea that absorbs light at short wavelengths.

Frequency doubling perimetry using a liquid crystal display.

PURPOSE: To compare frequency doubling contrast thresholds using a new liquid crystal window display with those obtained with the commercial video-based Frequency Doubling Technology perimeter. METHODS: One eye of 49 glaucoma patients and one eye of 49 normal controls were tested with the liquid crystal window and Frequency Doubling Technology systems. Both displays employed identical stimulus conditions and test strategies, although the dynamic range of the liquid crystal window-based display was approximately 30% smaller than that of the Frequency Doubling Technology system. Measurements were repeated using the video-based Frequency Doubling Technology perimeter in a subset of 21 eyes. Relationships between and within displays were assessed using a chance-corrected agreement measure (quadratic weighted kappa) and paired measurement differences. Variability was quantified using standard deviation from the mean paired measurement difference. RESULTS: Over the restricted operating range of the liquid crystal display system, between-display and within-video display variability was 2.3 dB and 3.2 dB, respectively, between-display agreement was 0.66, and within-display agreement (test-retest for Frequency Doubling Technology) was 0.65. CONCLUSIONS: Levels of agreement and variability between the two frequency doubling displays were of similar magnitude to repeated (test-retest) Frequency Doubling Technology measures, suggesting that contrast threshold measurements made using the two displays may be used interchangeably. However, the operating range of the current liquid crystal window-based display is smaller.

Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy.

BACKGROUND: Previous studies of the prognosis of patients with heart failure due to cardiomyopathy categorized patients according to whether they had ischemic or nonischemic disease. The prognostic value of identifying more specific underlying causes of cardiomyopathy is unknown. METHODS: We evaluated the outcomes of 1230 patients with cardiomyopathy. The patients were grouped into the following categories according to underlying cause: idiopathic cardiomyopathy (616 patients), peripartum cardiomyopathy (51); and cardiomyopathy due to myocarditis (111), ischemic heart disease (91), infiltrative myocardial disease (59), hypertension (49), human immunodeficiency virus (HIV) infection (45), connective-tissue disease (39), substance abuse (37), therapy with doxorubicin (15), and other causes (117). Cox proportional-hazards analysis was used to assess the association between the underlying cause of cardiomyopathy and survival. RESULTS: During a mean follow-up of 4.4 years, 417 patients died and 57 underwent cardiac transplantation. As compared with the patients with idiopathic cardiomyopathy, the patients with peripartum cardiomyopathy had better survival (adjusted hazard ratio for death, 0.31; 95 percent confidence interval, 0.09 to 0.98), and survival was significantly worse among the patients with cardiomyopathy due to infiltrative myocardial disease (adjusted hazard ratio, 4.40; 95 percent confidence interval, 3.04 to 6.39), HIV infection (adjusted hazard ratio, 5.86; 95 percent confidence interval, 3.92 to 8.77), therapy with doxorubicin (adjusted hazard ratio, 3.46; 95 percent confidence interval, 1.67 to 7.18), and ischemic heart disease (adjusted hazard ratio, 1.52; 95 percent confidence interval, 1.07 to 2.17). CONCLUSIONS: The underlying cause of heart failure has prognostic value in patients with unexplained cardiomyopathy. Patients with peripartum cardiomyopathy appear to have a better prognosis than those with other forms of cardiomyopathy. Patients with cardiomyopathy due to infiltrative myocardial diseases, HIV infection, or doxorubicin therapy have an especially poor prognosis.

In vitro translation of a 2.3-kb splicing variant of the hamster pgp1 gene whose presence in transfectants is associated with decreased drug resistance.

PURPOSE: P-glycoprotein (P-gp), a product of the Chinese hamster pgpl gene, confers multidrug resistance to mammalian cells in which it is overexpressed either by transfection or as a result of drug selection. It is encoded by a 4.3-kb mRNA and in its unglycosylated form has a predicted molecular weight of approximately 141 kDa. When a cDNA containing this sequence is transfected into drug-sensitive Chinese hamster lung cells and is expressed under the control of the beta-actin promoter, both the full-length 4.3-kb mRNA and a 2.3-kb transcript are produced. The latter results from a splicing event that utilizes near consensus 5' and 3' splicing signals resident in the full-length mRNA, and it has also been found to be present in cell lines that express the native gene. Therefore, it is a splicing product of pgpl per se. This report is concerned with the biological relevance of this transcript. METHODS: In vitro transcription and translation experiments were used to show that the putative open reading frame of the 2.3-kb transcript encodes a novel 57-kDa protein (p57pgp1) that contains transmembrane domains 9-12 and the C-terminal ATP binding fold of P-gp. To elucidate the function of p57pgp1, expression vectors containing cDNAs representing (1) the 2.3-kb transcript, (2) the full-length 4.3-kb mRNA, and (3) a splice-disabled 4.3-kb transcript in which production of the 2.3-kb transcript is eliminated by an in-frame mutation at the 3' splice site, were constructed and transfected into DC-3F cells. Additional expression vectors in which p57pgp1 represented the N-terminus of a green fluorescent protein fusion construct were also prepared and used for transient expression studies. RESULTS: Overexpression of the 2.3-kb transcript alone did not confer multidrug resistance. Transfectants in which both the 4.3-kb transcript and the 2.3-kb transcript were present, compared with transfectants in which no 2.3-kb transcript was expressed, but in which the level of expression of the 4.3-kb mRNA alone was the same, showed little change in cross-resistance pattern. However, the overall level of resistance in the latter cells was increased by approximately twofold. Hence the presence of the 2.3-kb transcript was associated with a decrease in drug resistance. In vitro transcription and translation experiments and transient expression studies indicate that p57pgp1 can be expressed both in vitro and in vivo. CONCLUSION: These results demonstrate that a splicing variant of pgp1 contains an open reading frame capable of translation in vitro and in vivo and suggest that alterations in splicing may contribute both directly and indirectly to the overall mechanism of pgp1-mediated multidrug resistance in CHL cells.

Disaggregating the effects of race on breast cancer survival.

BACKGROUND AND OBJECTIVES: This study examines differences in breast cancer survival between African-American and white women to determine whether there is a racial difference in survival after accounting for established influences on outcome, such as stage of cancer, health status, health behavior, utilization patterns, access to care, quality of care, and the doctor-patient relationship. METHODS: This study is a retrospective review of clinical records. The sample consists of 246 patients of three staff model HMOs who had mastectomies at stage II or above. Data on patient demographics, stage of cancer, health status, and health behavior and utilization, including preventive care, were extracted from patient records. Multivariate logistic regression was used to predict the determinants of advanced stage of cancer. Cox survival analysis was used to predict the determinants of survival. RESULTS: Missed appointments and stage of cancer were the key determinants of survival. The effect of race on survival was marginal after adjusting for these factors. Race, patients who missed appointments, and patients who delayed in reporting breast cancer symptoms were determinants of advanced stage. African-Americans were overrepresented among patients who missed appointments. CONCLUSIONS: Missed appointments was a determinant of both advanced stage and shorter survival. This measure is an important component of how race affects survival. Compliance with appointment keeping and alleviating reasons for noncompliance must be considered as factors in breast cancer survival.

Identification of a lipopolysaccharide inducible transcription factor in murine macrophages.

To study macrophage genes activated by lipopolysaccharide (LPS) we have constructed a cDNA library using the mouse macrophage cell line, RAW 264.7. By differential screening, a gene, designated LRG-21, was identified that showed nucleic acid sequence homology to rat liver regenerating factor-1 (LRF-1) and human activating transcription factor-3 (ATF3). Both LRG-21 and LRF-1 are transcribed within an hour following stimulation and in the absence of protein synthesis. The predicted protein sequence of LRG-21 consists of 181 amino acids with a molecular weight of 20.7 kDa. All three sequences contain basic and leucine zipper regions characteristic of the c-Fos and c-Jun family of transcription factors, but the remainder of the sequences are unrelated to this family. Recombinant LRG-21 has been shown to bind to a phorbol ester promoter element. Additional experiments have shown that LRG-21 is also induced by interferon-gamma (IFN-gamma) and by interleukin-4 (IL-4) in both RAW264.7 cells and murine peritoneal macrophages. Based on these observations, it is likely that LRG-21 plays an important role in macrophage activation.

The treatment effectiveness of outpatient substance misuse treatment organizations between court-mandated and voluntary clients.

Do outpatient substance misuse treatment organizations have different outcomes for court-mandated and voluntary clients depending on the mix of those clients? Do client characteristics, organizational factors, and treatment practices predict organizational treatment outcome rates? A nationally representative sample of 330 nonmethadone outpatient substance misuse treatment organizations was surveyed in 1990. Sixty-four of the organizations had 75% or more court-mandated clients; 122 of the organizations had 25% or less court-mandated clients. Organizations with 75% or greater court-mandated clients had a greater rate of clients failing to comply with their treatment plan than organizations with 25% or less court-mandated clients, but there were no differences in clients meeting the goals of their treatment. Client characteristics, organizational factors, and treatment practices are evaluated through multivariate regression to determine their impact on organizational rates of treatment success and failure among clients.

The effect of social environment on treatment outcomes in outpatient substance misuse treatment organizations: does race really matter?

This study examines whether the racial mix of clients is related to treatment organization outcome rates after controlling for the social environment in which the organization operates. A nationally representative sample of 326 nonmethadone outpatient substance misuser treatment organizations was surveyed in 1990. Unit analysis is the treatment organization. Outcome measures are the percentages of clients who completed and dropped out of treatment. The percent of Black clients treated at the organization, the socioeconomic status of the organization's area, and other client characteristics, organizational factors, and treatment practices are evaluated through multivariate regression to determine their impact on organizational rates of treatment success and failure among clients. Ordinary least-squares regression analysis indicates that race is not a predictor of treatment success once socioenvironmental factors are included in the analysis. Treatment organizations must be wary of defining a person for treatment only in terms of his or her racial or ethnic group membership. Treatment approaches should place more emphasis on the socioenvironmental influences to which the client is exposed and less emphasis on a client's race.

Variation in access to outpatient substance abuse treatment: organizational factors and conceptual issues.

Access is a multidimensional concept representing the ease with which health services are initiated and sustained. In this study, conceptual domains of access--affordability, acceptability, accommodation, availability, service diversity, and competitive stance--are hypothesized to predict the time clients wait to receive services. A large, recently surveyed, nationally representative sample of outpatient substance abuse treatment organizations provided the data. Multivariate regression analysis of 326 organizations was conducted with the conceptual domains sequentially predicting the time clients waited to receive service. Results show that increased waiting time was positively associated with treatment staff case overload and the average number of months clients spent in treatment and negatively associated with the percent of a treatment organization's client base on public assistance. Implications for policy makers and clinicians concerning client selection strategies by organizations and problems with the organizational capacity to treat clients are discussed. Areas for future research also are highlighted.

Identification of an endotoxin and IFN-inducible cDNA: possible identification of a novel protein family.

The response of macrophages to agents such as lipopolysaccharide (LPS) and interferon (IFN) includes the transcriptional activation of numerous genes. We have used the method of differential screening of a RAW 264.7 macrophage cell line cDNA library to isolate and characterize LPS-induced messages. One such message, LRG-47, is induced by LPS, IFN-gamma, and IFN-alpha/beta, but not by a panel of other cytokines or pharmacological activating agents. LRG-47 is homologous to two other IFN-gamma-induced genes, IRG-47 and Mg21. The LRG-47 sequence is approximately 33% identical and 52% similar to both these putative protein products. All three putative proteins, particularly Mg21, bear homology to a T cell product, Tgtp, induced by T cell receptor cross-linking. The three macrophage-derived proteins share areas of homology with GTP-binding proteins, are approximately 415 amino acids in length, and have similar kinetics of induction by IFN-gamma. This suggests that these genes may be members of a new family of IFN-inducible proteins.

A noninvasive video-based method for measuring lens transmission properties of the human eye.

The Lens Absorption Monitor (LAM) is an automated video-based system for obtaining rapid objective noninvasive measurements of the spectral transmission properties of the human lens. The technique is based on intensity measurements of the 4th Purkinje image for different wavelengths, and incorporates several features that overcome some of the difficulties associated with previous studies using this approach. LAM transmission measures for the visible spectrum can be obtained in approximately 2 s, and in most instances can be obtained without having to dilate the subject's eye. This paper describes the technique and presents our initial findings for 40 normal observers between the ages of 24 and 77 years. Results of the LAM technique show that it is able to measure the wavelength-dependent properties of the lens accurately and to identify age-related changes in "yellowing" of the lens. Test-retest reliability of the LAM is better than for psychophysical estimates of ocular media transmission. LAM and psychophysical measures in the same subjects were found to be correlated, although LAM measures produced consistently lower values of lens density than the psychophysical determinations. There was only moderate agreement between LAM and psychophysical measures of lens density. Possible explanations for these differences are discussed. Future research will determine whether this technique is able to detect and quantify early cataract development.

A phrenic nerve-actuated electronically controlled positive-pressure ventilator.

We have constructed an electronically controlled positive-pressure ventilator actuated by phrenic neural activity for use in open-chested or paralyzed experimental animals for the study of breathing pattern. A Bird Mark 14 positive-pressure ventilator was modified such that flow is a linear function of a command signal. Flow is delivered by advancing an air valve with a servo-motor that is controlled by one of three different operational modes. In two of the modes, the difference between the electronic average of inspiratory phrenic activity (moving average) and a feedback signal determines the inspiratory flow. The feedback signal is derived from either tracheal pressure or an electronic measure of inspired volume. In the third mode, the moving average is differentiated to provide control of inspiratory flow and volume. Physiological flow profiles were created using all three operational modes. Integration of an air-valve position signal provides an electronic measure of tidal volume. An additional feature of this ventilator allows inspiratory flow and duration to be predetermined for a given breath.

A double-blind crossover evaluation of ketoprofen (Orudis) and placebo in rheumatoid arthritis with assessment of long-term tolerance.

A two-week double-blind crossover study of ketoprofen, a non-steroidal antiinflammatory agent, and placebo was done in ten patients with active rheumatoid arthritis in order to obtain a preliminary efficacy estimate of this new drug. Even after only one week of treatment, joint activity was significantly reduced while other parameters of disease activity showed strong clinical trends in favour of the drug. Only one adverse reaction (mild nausea) was reported during ketoprofen therapy. At the conclusion of the double-blind study, seven patients volunteered to continue on ketoprofen to evaluate the tolerance of the drug during proptracted administration. All patients completed over twelve months of treatment. Overall, ketoprofen gave good control of pain and inflammation, gastro-intestinal disturbance was reported in a single instance and laboratory values were not adversely affected by the drug.