BedMachine v3: Complete Bed Topography and Ocean Bathymetry Mapping of Greenland From Multibeam Echo Sounding Combined With Mass Conservation.

Greenland's bed topography is a primary control on ice flow, grounding line migration, calving dynamics, and subglacial drainage. Moreover, fjord bathymetry regulates the penetration of warm Atlantic water (AW) that rapidly melts and undercuts Greenland's marine-terminating glaciers. Here we present a new compilation of Greenland bed topography that assimilates seafloor bathymetry and ice thickness data through a mass conservation approach. A new 150 m horizontal resolution bed topography/bathymetric map of Greenland is constructed with seamless transitions at the ice/ocean interface, yielding major improvements over previous data sets, particularly in the marine-terminating sectors of northwest and southeast Greenland. Our map reveals that the total sea level potential of the Greenland ice sheet is 7.42 ± 0.05 m, which is 7 cm greater than previous estimates. Furthermore, it explains recent calving front response of numerous outlet glaciers and reveals new pathways by which AW can access glaciers with marine-based basins, thereby highlighting sectors of Greenland that are most vulnerable to future oceanic forcing.

The impact of substance abuse treatment modality on birth weight and health care expenditures.

During the 1990s, substance abuse treatment programs were developed for pregnant women to help improve infant birth outcomes, reduce maternal drug dependency and promote positive lifestyle changes. This study compared the relative impact of five treatment modalities--residential, outpatient, residential/outpatient, methadone and detoxification-only--on infant birth weight and perinatal health care expenditures for a sample of 445 Medicaid-eligible pregnant women who received treatment in Massachusetts between 1992 and 1997. Costs and outcomes were measured using the Addiction Severity Index and data from birth certificates, substance abuse treatment records and Medicaid claims. Multiple regression was used to control for intake differences between the groups. Results showed a near linear relationship between birth weight and amount of treatment received. Women who received the most treatment (the residential/outpatient group) delivered infants who were 190 grams heavier than those who received the least treatment (the detoxification-only group) for an additional cost of $17,211. Outpatient programs were the most cost-effective option, increasing birth weight by 139 grams over detoxification-only for an investment of only $1,788 in additional health care and treatment costs. A second regression using five intermediate treatment outcomes--prenatal care, weight gain, relapse, tobacco use and infection--suggested that increases in birth weight were due primarily to improved nutrition and reduced drug use, behaviors which are perhaps more easily influenced in residential settings.

Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease. Crohn's Disease IL-10 Cooperative Study Group.

BACKGROUND & AIMS: Interleukin (IL)-10 is a cytokine with potent anti-inflammatory properties. We investigated the safety and efficacy of different doses of human recombinant (rhu)IL-10 in patients with Crohn's disease (CD). METHODS: A prospective, multicenter, double-blind, placebo-controlled study was conducted in 329 therapy-refractory patients with CD. Clinical improvement was defined by a reduction of the Crohn's Disease Activity Index (CDAI) by 100 points or more and clinical remission by a decrease of the CDAI to <150 points. At selected centers, patients underwent ileocolonoscopies and activation of the nuclear factor-kappa B (NF-kappa B) system was assessed in biopsy specimens. RESULTS: Subcutaneous treatment with rhuIL-10 over 28 days induced a fully reversible, dose-dependent decrease in hemoglobin and thrombocyte counts but no clinically significant side effects. No differences in the induction of remission were observed between rhuIL-10 groups (1 microg, 18% [9.6-29.2]; 4 microg, 20% [11.3-32.2]; 8 microg, 20% [11.1-31.8]; 20 microg, 28% [18-40.7]; and placebo, 18% [9.6-29.6]). Clinical improvement was observed in 46% (33.7-59) in the 8-microg/kg rhuIL-10 group in comparison with 27% (17-39.6) in patients taking placebo. Responders to rhuIL-10 showed inhibition of NF-kappaB p65 activation in contrast to nonresponders. CONCLUSIONS: Up to 8 microg/kg of rhuIL-10 was well tolerated. A tendency toward clinical improvement but not remission was observed in the 8-microg/kg dose group. Further studies should delineate which subgroups of patients with CD benefit from rhuIL-10 therapy.

Bioavailability of four ursodeoxycholic acid preparations.

BACKGROUND: Ursodeoxycholic acid (UDCA) is the drug of choice for treating primary biliary cirrhosis and dissolving cholesterol gallstones. OBJECTIVES: The objective of this study was to compare the bioavailability of four commercially available ursodeoxycholic acid formulations in standardized doses. METHODS: Twenty-four healthy subjects were studied in groups of four, and received each of the different UDCA preparations in random order, with a 1-week washout or more in-between. Serum UDCA levels were determined for a 6-h period. The mean area under the curve (AUC), Cmax and Tmax were determined for each drug formulation, and the results compared. Dose proportionality was determined using the Canadian Ursofalk tablet using either 250 mg, 500 mg or 750 mg dosing. The intraparticipant variability was assessed by asking each participant to repeat the last drug that they took the second time, 1 week later. RESULTS: The mean AUC was 68.99 micromol/1.6 h-1 for the USA UDCA tablet, 59.34 micromol/1.6 h-1 for the Canadian UDCA tablet, 55.55 micromol/1.6 h-1 for Ursolvan capsules, and 46.66 micromol/1.6 h-1 for Actigall capsules. The mean Cmax values were 24.29, 17.85, 16.63 and 413.32 nmol/mL, respectively. The mean Tmax was 1.82, 2.3, 2.79 and 3.39 h, respectively. Linear aggression analysis assessing the direct proportionality of AUC on the dose for the Canadian UDCA tablet gave an estimate of 0.063 + 0.0164 (standard error, P-value=0.0117), e.g. if the dose increases from 250 mg to 500 mg, the serum ursodeoxycholic acid increases by 250 x 0.063=15.75. There was excellent reproducibility for the AUC for the North American tablets (0.97, 0.88) compared to the two capsules (0.32, 0.15). CONCLUSIONS: The significantly higher AUC and Cmax and shorter Tmax for the Canadian Ursofalk tablets compared to the UDCA capsule preparations supports better bioavailability.

Long-term use of mesalamine (Rowasa) suppositories in remission maintenance of ulcerative proctitis.

OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of a single nightly 500-mg Rowasa (mesalamine) suppository as maintenance therapy for patients with ulcerative proctitis in remission. METHODS: In this 24-month, multicenter, double-blind trial, 65 patients with ulcerative proctitis in clinical and endoscopic remission were randomized to receive either a single nightly 500-mg rectal mesalamine (Rowasa) suppository or matching placebo as sole therapy. Efficacy was assessed by time to relapse (defined as rectal bleeding or increase in stool frequency for > or =1 wk and active inflammation upon endoscopy). RESULTS: Mean time to relapse was 453.4 days for mesalamine-treated patients and 158.0 days for placebo-treated patients. Survival analysis demonstrated that time to relapse was significantly greater for mesalamine-treated patients than for placebo-treated patients (p < 0.001). In addition, at both 12 and 24 months, the proportion of placebo-treated patients (86% at 12 months and 89% at 24 months) who relapsed was significantly (p < or = 0.001) greater than mesalamine-treated patients (32% and 46%, respectively). No statistically significant differences occurred between treatment groups in the reporting of any particular adverse event or the number of patients reporting adverse events. CONCLUSIONS: The results demonstrate that mesalamine suppositories are efficacious, well tolerated, and safe for the long-term maintenance of remission of ulcerative proctitis.

Genomewide search in Canadian families with inflammatory bowel disease reveals two novel susceptibility loci.

The chronic inflammatory bowel diseases (IBDs)-Crohn disease (CD) and ulcerative colitis (UC)-are idiopathic, inflammatory disorders of the gastrointestinal tract. These conditions have a peak incidence in early adulthood and a combined prevalence of approximately 100-200/100,000. Although the etiology of IBD is multifactorial, a significant genetic contribution to disease susceptibility is implied by epidemiological data revealing a sibling risk of approximately 35-fold for CD and approximately 15-fold for UC. To elucidate the genetic basis for these disorders, we undertook a genomewide scan in 158 Canadian sib-pair families and identified three regions of suggestive linkage (3p, 5q31-33, and 6p) and one region of significant linkage to 19p13 (LOD score 4.6). Higher-density mapping in the 5q31-q33 region revealed a locus of genomewide significance (LOD score 3.9) that contributes to CD susceptibility in families with early-onset disease. Both of these genomic regions contain numerous genes that are important to the immune and inflammatory systems and that provide good targets for future candidate-gene studies.

The costs of crime and the benefits of substance abuse treatment for pregnant women.

Although many pregnant, drug-dependent women report extensive criminal justice involvement, few studies have examined reductions in crime as an outcome of substance abuse treatment programs for pregnant women. This is unfortunate, because maternal criminal involvement can have serious health and cost implications for the unborn child, the mother and society. Using the Addiction Severity Index, differences in pre- and posttreatment criminal involvement were measured for a sample of 439 pregnant women who entered publicly funded treatment programs in Massachusetts between 1992 and 1997. Accepted cost of illness methods were supplemented with information from the Bureau of Justice Statistics to estimate the costs and benefits of five treatment modalities: detoxification only (used as a minimal treatment comparison group), methadone only, residential only, outpatient only, and residential/outpatient combined. Projected to a year, the net benefits (avoided costs of crime net of treatment costs) ranged from US$32,772 for residential only to US$3,072 for detoxification. Although all five modalities paid for themselves by reducing criminal activities, multivariate regressions controlling for baseline differences between the groups showed that reductions in crime and related costs were significantly greater for women in the two residential programs. The study provides economic justification for the continuation and possible expansion of residential substance abuse treatment programs for criminally involved pregnant women.