Rapid expansion of Greenland's low-permeability ice slabs.

In recent decades, meltwater runoff has accelerated to become the dominant mechanism for mass loss in the Greenland ice sheet1-3. In Greenland's high-elevation interior, porous snow and firn accumulate; these can absorb surface meltwater and inhibit runoff4, but this buffering effect is limited if enough water refreezes near the surface to restrict percolation5,6. However, the influence of refreezing on runoff from Greenland remains largely unquantified. Here we use firn cores, radar observations and regional climate models to show that recent increases in meltwater have resulted in the formation of metres-thick, low-permeability 'ice slabs' that have expanded the Greenland ice sheet's total runoff area by 26 ± 3 per cent since 2001. Although runoff from the top of ice slabs has added less than one millimetre to global sea-level rise so far, this contribution will grow substantially as ice slabs expand inland in a warming climate. Runoff over ice slabs is set to contribute 7 to 33 millimetres and 17 to 74 millimetres to global sea-level rise by 2100 under moderate- and high-emissions scenarios, respectively-approximately double the estimated runoff from Greenland's high-elevation interior, as predicted by surface mass balance models without ice slabs. Ice slabs will have an important role in enhancing surface meltwater feedback processes, fundamentally altering the ice sheet's present and future hydrology.

Current status of minimally invasive esophagectomy.

Minimally invasive esophagectomy is emerging as an option in the management of benign and malignant esophageal diseases. With minimally invasive esophagectomy, the conventional laparotomy is substituted with laparoscopy and the open thoracotomy with thoracoscopy. This article discusses the surgical techniques and outcomes for a variety of minimally invasive esophagectomy options.

Changes of knowledge, attitudes, beliefs, and preference of bar owner and staff in response to a smoke-free bar law.

OBJECTIVE: To examine attitudinal changes of bar owners and staff regarding a smoke-free bar law. DESIGN: Bar owners and staff were random selected and telephone interviewed in June 1998, shortly after a smoke-free bar law was enacted, and October 2002. Similar instruments were used in both surveys to collect data on attitudes related to secondhand smoke (SHS) and behaviours related to the smoke-free bar law. PARTICIPANTS: 651 and 650 respondents worked for either stand alone bars or combination bars. MEASURES: Preference of working in a smoke-free environment, concerns of the effect of SHS, and how to comply with the law. RESULTS: The percentage of bar owners or staff working in stand alone bars who prefer to work in a smoke-free environment increased from 17.3% in 1998 to 50.9% in 2002 (p < 0.001). Significantly more respondents (45.5%) working in stand alone bars were concerned about the effects of SHS on their health, comparing to 21.6% in 1998 (p < 0.001). When patrons smoked in the bar, 82.1% of stand alone bar owners or staff in the 2002 survey would ask them to stop or to smoke outside, increased from only 43.0% in the 1998 survey (p < 0.001). CONCLUSION: A positive and significant attitudinal change related to the smoke-free bar law occurred among California bars.

Effects of pneumoperitoneum on intraoperative pulmonary mechanics and gas exchange during laparoscopic gastric bypass.

BACKGROUND: Hypercarbia and elevated intraabdominal pressure resulting from carbon dioxide (CO2) pneumoperitoneum can adversely affect respiratory mechanics. This study examined the changes in mechanical ventilation, CO2 homeostasis, and pulmonary gas exchange in morbidly obese patients undergoing a laparoscopic or open gastric bypass (GBP) procedure. METHODS: In this study, 58 patients with a body mass index (BMI) of 40 to 60 kg/m2 were randomly allocated to laparoscopic ( n = 31) or open ( n = 27) GBP. Minute ventilation was adjusted to maintain a low normal arterial partial pressure of CO2 (PaCO2), low normal end-tidal partial pressure of CO2 (ETCO2), and low airway pressure. Respiratory compliance, ETCO2, peak inspiratory pressure (PIP), total exhaled CO2 per minute (VCO2), and pulse oximetry (SO2) were measured at 30-min intervals. The acid-base balance was determined by arterial blood gas analysis at 1-h intervals. The pulmonary gas exchange was evaluated by calculation of the alveolar dead space-to-tidal volume ratio (V(Dalv)/V(T)) and alveolar-arterial oxygen gradient (PAO2-PaO2). RESULTS: The two groups were similar in age, gender, and BMI. As compared with open GBP, laparoscopic GBP resulted in higher ETCO2, PIP, and VCO2, and a lower respiratory compliance. Arterial blood gas analysis demonstrated higher PaCO2 and lower pH during laparoscopic GBP than during open GBP ( p < 0.05). The V(Dalv)/V(T) ratio and PAO2-PaO2 gradient did not change significantly during laparoscopic GBP. Intraoperative oxygen desaturation (SO2 < 90%) did not develop in any of the patients in either group. CONCLUSIONS: Laparoscopic GBP alters intraoperative pulmonary mechanics and acid-base balance but does not significantly affect pulmonary oxygen exchange. Changes in pulmonary mechanics are well tolerated in morbidly obese patients when proper ventilator adjustments are maintained.

Thrombin-stimulated phosphatidylinositol 3-kinase activity in platelets is associated with activation of PYK2 tyrosine kinase: activation of both enzymes is aggregation independent.

In this study, we investigated the activation of a new member of the focal adhesion kinase family of tyrosine kinases, the proline-rich tyrosine kinase, or PYK2, in platelets. We show that PYK2 is tyrosine phosphorylated and its activity is increased during early stages of platelet aggregation. This activation coincided with increased association of phosphatidylinositol (PI) 3-kinase and PYK2, as determined by both anti-PI 3-kinase and anti-PYK2 immunoprecipitates. However, under basal conditions, some association of PYK2 and PI 3-kinase was consistently observed, even though little or no tyrosine phosphorylated PYK2 could be detected. In addition, both increased PI 3-kinase activity and increased PYK2 activity could be detected in immunoprecipitates following thrombin stimulation. All of these events were unaffected by blocking platelet aggregation with arginine-glycine-aspartate-serine (RGDS) peptide, which interferes with binding of the platelet integrin alpha(IIb)beta(3) to fibrinogen. Neither was the activation of the PYK2 kinase activity affected by blocking PI 3-kinase activity. These results support a model in which PYK2 is associated with PI 3-kinase in unstimulated platelets and following activation of platelets, there is an increase in tyrosine phosphorylation of PYK2, increased PYK2 activity, and increased association of PYK2 with PI 3-kinase, which may contribute to the increase in PI 3-kinase activity. All of these were found to be early events independent of subsequent platelet aggregation.

A role for phosphatidylinositol 3-kinase in platelet aggregation in response to low, but not high, concentrations of PAF or thrombin.

In this study we show that platelet activating factor (PAF) activates PI 3-kinase over a rapid time course that correlates closely with the aggregation response. Tyrosine kinases are involved in this response, since there is increased PI 3-kinase activity associated with tyrosine-phosphorylated proteins. PI 3-kinase inhibitors were used to probe the dependence of PAF-induced aggregation on PI 3-kinase. Both wortmannin and LY-294002 inhibited PAF-induced aggregation that correlated with PI 3-kinase inhibition only when using lower concentrations of PAF giving reversible aggregation (primary phase). Similar results were obtained with human platelets using thrombin or thrombin receptor activating peptide. The same pattern of response was observed when activation of GPIIbIIIa was assessed by flow cytometry, i.e., PI 3-kinase inhibitors blocked integrin activation only when lower concentrations of agonist were used. We suggest that PI 3-kinase is important for reversible (primary) aggregation of platelets in response to PAF or thrombin, perhaps by contributing to the 'inside-out' activation of the platelet integrin GPIIbIIIa, only when submaximal concentrations of agonists are used. The lack of effect of PI 3-kinase inhibitors, when high concentrations of agonist are used, suggests that PI 3-kinase-independent pathways contribute to aggregation under these conditions.

Improved recovery of antibiotic-stressed microorganisms on inclusion of saponin in aerobic blood culture media.

The recovery rates and times to detection of microorganisms isolated from two similar blood culture media, one containing saponin, were compared. A total of 2117 blood cultures were analysed in a prototype automated blood culture system. Significantly more gram-positive organisms (P<0.05) and gram-negative organisms (P<0.05), including Enterobacteriaceae (P<0.05) were recovered from the lytic medium. Average time to detection in the lytic medium was 15.8 h, compared to 22.7 h in the other medium (P<0.001). The improved recovery of microorganisms was most pronounced in blood samples obtained from patients being treated with antibiotics at the time of venesection. In vitro experiments on antibiotic affected bacteria confirmed the protective effect of saponin.

Interactions between needles of Pinus resinosa and ectomycorrhizal fungi.

Relatively little is known about the factors controlling ectomycorrhizal fungal communities. One possible factor is forest litter chemistry. In a series of experiments we demonstrated that the growth of ectomycorrhizal fungi able to colonize red pine (Pinus resinosa Ait.) are differentially affected by red pine needles and needle chemical components. For example, water extracts of pine needles stimulated the growth of Suillus intermedius (Smith & Thiers) Smith & Thiers and inhibited the growth of Amanita rubescens Pers. Catechin and epicatechin gallate, components of the water extract, acted similarly to the extract. The volatile compounds α- and ß-pinene also had differential effects on the growth of the various species of ectomycorrhizal fungi. Our results suggest that forest litter chemistry has the potential differentially to affect the growth of ectomycorrhizal fungal species and so could affect the structure of ectomycorrhizal fungal communities.

Smoking and cycle control among oral contraceptive users.

OBJECTIVE: Because cigarette smoking has a variety of antiestrogenic actions, we investigated the possibility that smoking may adversely affect spotting and bleeding among women using oral contraceptives. STUDY DESIGN: Three open-label, randomized clinical trials involving 16,506 cycles among 2956 oral contraceptive users were performed. RESULTS: Smokers reported a consistently higher frequency of spotting or bleeding than did nonsmokers. After recency and consistency of oral contraceptive use and progestin component were controlled for, smokers were, on average, 47% more likely to have spotting or bleeding than nonsmokers were over six cycles of oral contraceptive use, with higher levels of smoking associated with a greater frequency of spotting or bleeding. By the sixth cycle women who smoked > or = 16 cigarettes per day were almost three times more likely to have spotting or bleeding than were nonsmokers. CONCLUSION: Cigarette smoking adversely affects cycle control among oral contraceptive users, possibly by increasing estrogen catabolism. Although these findings also raise the possibility that oral contraceptive efficacy may also be impaired in smokers, an immediate concern is that oral contraceptive users who have spotting and bleeding are more likely to discontinue their use, placing them at risk of unintended pregnancy.

PIP: Three open-label, randomized clinical trials involving 16,506 cycles among 2956 oral contraceptive (OC) users were conducted in order to investigate whether smoking may adversely affect spotting and bleeding among women using OCs. Included were 1480 women and 8292 cycles of experience with gestodene preparations, 1384 women and 7691 cycles with OCs containing desogestrel, and 92 women and 523 cycles with the norgestimate preparation. Among smokers, the proportion who reported spotting or bleeding varied from 59% in the first cycle to 14% in the sixth cycle, averaging 23%. In contrast, the proportion of nonsmokers who reported bleeding ranged from 52% in the first cycle to 9% in the sixth cycle, averaging 19% for all six cycles. Although the proportion of smokers and nonsmokers with spotting or bleeding decreased significantly with time (p = .000), nonsmokers had a slight but consistent increase in spotting or bleeding for each cycle after the first, whereas spotting or bleeding in smokers decreased during the first two cycles and remained constant thereafter. After recency and consistency of OC use and progestin components were controlled for, smokers were 47% more likely to have spotting or bleeding than nonsmokers over six cycles of OC use with higher levels of smoking associated with a greater frequency of spotting or bleeding. By the sixth cycle women who smoked or= 16 cigarettes/day were almost three times more likely to have spotting or bleeding than nonsmokers. For women with any smoking, the relative risk (RR) was elevated for every cycle, with the difference being significant in five of six cycles. The RR for any smoking varied from 1.30 in the first cycle (an increase in risk of 30% compared with nonsmokers) to 1.86 (86% increase) by cycle six. Cigarette smoking adversely affects cycle control among OC users, possibly by increasing estrogen catabolism. Women who have spotting or bleeding are more likely to discontinue OC use, which places them at increased risk of unintended pregnancy.

Development of o.a.s.i.s., a new automated blood culture system in which detection is based on measurement of bottle headspace pressure changes.

o.a.s.i.s. (Unipath Ltd., Basingstoke, United Kingdom) is a new automated blood culture system. The metabolism of microorganisms is detected by measuring changes in the pressure of the headspace of blood culture bottles. These changes are measured by monitoring the position of a flexible sealing septum, every 5 min, with a scanning laser sensor. This noninvasive system can detect both gas absorption and production and does not rely solely on measuring increasing carbon dioxide levels. A research prototype instrument was used to carry out an evaluation of the media, the detection system, and its associated detection algorithm. In simulated blood cultures, o.a.s.i.s. supported growth and detected a range of clinical isolates. Times to positivity were significantly shorter in o.a.s.i.s. than in the BACTEC 460 system. Results of a clinical feasibility study, with a manual blood culture system as a control, confirmed that o.a.s.i.s. was able to support the growth and detection of a variety of clinically significant organisms. On the basis of these findings, full-scale comparative clinical trials of o.a.s.i.s. with other automated blood culture systems are warranted.

Introductory small cash incentives to promote child spacing in India.

The Ammanpettai Family Welfare Program began in 1985 as a pilot program to determine whether offering small monthly cash incentives for a limited period would be a cost-effective way to increase the use of modern temporary methods of contraception among rural Indian women who do not want to become pregnant but are not ready to adopt sterilization. The program has demonstrated that a modest cash incentive for 3-5 months attracts very large numbers of women to a clinic where they learn about and are provided with the pill, condoms, or the IUD. In catchment areas where official government reports showed temporary-methods prevalence rates of 3-5 percent at best, the Ammanpettai incentive program has attracted up to 70 percent of eligible women to join the program and try the method of their choice. By requiring that participants bring their youngest child to the clinic, the program provides for mother and child health surveillance, including immunizations. The great majority of rural women who join the program work as field laborers, have little or no schooling, and have little knowledge of or experience with modern contraceptive methods. Continuation rates are 25-50 percent at one year if follow-up is maintained by village resident women distributors. The program has been extended to several rural primary health centers in Thanjavur District, to 14 government health posts in the city of Madras, and to a semiurban area and several rural areas in Bihar. The cost-effectiveness of this program compares favorably with that of the current government family welfare program.

Characterization of a sporulation gene, spoIVA, involved in spore coat morphogenesis in Bacillus subtilis.

Mutations in the spoIVA locus of Bacillus subtilis abolish cortex synthesis and interfere with the synthesis and assembly of the spore coat. We have characterized the cloned spoIVA locus in terms of its physical structure and regulation during sporulation. The locus contains a single gene capable of encoding an acidic protein of 492 amino acids (molecular weight, 55,174). The gene is transcribed from a sigma E-dependent promoter soon after the formation of the spore septum. A genetic test indicated that expression of spoIVA is only necessary in the mother cell compartment for the formation of a mature spore. This, together with the phenotypic properties of spoIVA mutations, would be in accord with the hypothesis that sigma E is only active after septation and in the mother cell compartment.

Differential gene expression during sporulation in Bacillus subtilis: structure and regulation of the spoIIID gene.

The gene spoIIID, which is essential for spore formation in Bacillus subtilis, was cloned and sequenced. It consists of one open reading frame which would encode a 93-amino-acid protein with a classic helix-turn-helix motif, characteristic of sequence-specific DNA-binding proteins. SpoIIID protein is a previously identified transcription factor, capable of altering the specificity of RNA polymerase containing sigma K in vitro (Kroos et al., 1989). The spoIIID83 mutation (by which the locus was originally identified), was sequenced and found to be a single base substitution in the ribosome binding site upstream of the spoIIID open reading frame. A transcriptional fusion to lacZ was constructed and used to examine the regulation of spoIIID. Expression of spoIIID occurred only during sporulation, beginning 1.5 to 2 hours after the initiation of sporulation. The dependence of spoIIID expression on other spo loci suggests that it is mother-cell-specific, and that it is transcribed by sigma E-containing RNA polymerase.

The isotopic composition of methane in polar ice cores.

Air bubbles in polar ice cores indicate that about 300 years ago the atmospheric mixing ratio of methane began to increase rapidly. Today the mixing ratio is about 1.7 parts per million by volume, and, having doubled once in the past several hundred years, it will double again in the next 60 years if current rates continue. Carbon isotope ratios in methane up to 350 years in age have been measured with as little as 25 kilograms of polar ice recovered in 4-meter-long ice-core segments. The data show that (i) in situ microbiology or chemistry has not altered the ice-core methane concentrations, and (ii) that the carbon-13 to carbon-12 ratio of atmospheric CH(4) in ice from 100 years and 300 years ago was about 2 per mil lower than at present. Atmospheric methane has a rich spectrum of isotopic sources: the ice-core data indicate that anthropogenic burning of the earth's biomass is the principal cause of the recent (13)CH(4) enrichment, although other factors may also contribute.

Analgesic regimens for third molar surgery: pharmacologic and behavioral considerations.

The level of pain following the extraction of impacted third molars was evaluated in 75 patients. Participants were administered acetaminophen 1,000 mg or a placebo before surgery. After surgery, acetaminophen 650 mg was administered either at fixed intervals or as needed to relieve pain. When acetaminophen was administered before surgery, the onset of peak pain was delayed and patient discomfort was decreased 3, 4, and 5 hours after surgery. Patients following the fixed interval regimen after surgery experienced more pain overall and requested the backup narcotic analgesic more frequently. Of the regimens tested, patients preferred the regimen of acetaminophen 1,000 mg administered before surgery with acetaminophen administered as needed for pain after surgery.

Evaluation of bleomycin, chlorozotocin, MGBG, and bruceantin in patients with advanced soft tissue sarcoma, bone sarcoma, or mesothelioma.

Patients with objectively measurable soft tissue sarcoma, bone sarcoma, or mesothelioma who had failed at least one prior chemotherapy regimen received either bleomycin (20 U/M2 i.v. day 1 each week), chlorozotocin (150 mg/M2 i.v. q6 weeks), MGBG (500 mg/M2 i.v. each week, escalated in 50 mg/M2 weekly increments to a maximum dose of 700 mg/M2), or bruceantin (5.5 mg/M2 days 1, 8, 15, and 22, with cycles repeated every 6 weeks). One hundred eighty patients were evaluable: 53 on bleomycin, 51 on chlorozotocin, 38 on MGBG, and 38 on bruceantin. Two partial responses resulted from bleomycin, and one each from chlorozotocin and MGBG. Both responders on bleomycin had mesothelioma. Seventy-four percent of the patients were of ECOG performance status 0 or 1, and over half on each arm had moderate or worse toxicity. At these doses and schedules, none of the four drugs tested was active against previously treated sarcomas. Bleomycin, however, should be considered for further evaluation in mesothelioma patients.

In vitro conversion of leucine to valine: configurational assignment of [5-13C]leucines.

Chiral (2S)-[5-13C]leucine was obtained from Escherichia coli deficient in the synthesis of acetolactate when cultures were supplemented with (RS)-[2-13CH3]acetolactate. The carbon-13 nuclear magnetic resonance spectrum showed one strong peak with a chemical shift of 21.4 ppm relative to tetramethylsilane [Sylvester, S. R., & Stevens, C. M. (1979) Biochemistry 18, 4529-4531]. Silver picolinate oxidation of the labeled leucine gave isovaleric acid which was then brominated at the alpha position to give (2RS)-2-bromo[3-13CH3]-isovaleric acid (2-bromo-3-[13C]methylbutanoic acid). Aminolysis afforded (2RS)-[4-13C]valine which was treated with D-amino acid oxidase in the presence of catalase. The final product was identified as (2S,3S)-[4-13C]valine by the specificity of D-amino acid oxidase, by amino acid analysis, and by the persistence of a strong signal at gamma 17.8 in the carbon-13 magnetic resonance spectrum. These results establish the absolute configuration of the biosynthetic leucine to be (2S,4S)-[5-13C]leucine.