A candidate super-Earth planet orbiting near the snow line of Barnard's star.

Barnard's star is a red dwarf, and has the largest proper motion (apparent motion across the sky) of all known stars. At a distance of 1.8 parsecs1, it is the closest single star to the Sun; only the three stars in the α Centauri system are closer. Barnard's star is also among the least magnetically active red dwarfs known2,3 and has an estimated age older than the Solar System. Its properties make it a prime target for planetary searches; various techniques with different sensitivity limits have been used previously, including radial-velocity imaging4-6, astrometry7,8 and direct imaging9, but all ultimately led to negative or null results. Here we combine numerous measurements from high-precision radial-velocity instruments, revealing the presence of a low-amplitude periodic signal with a period of 233 days. Independent photometric and spectroscopic monitoring, as well as an analysis of instrumental systematic effects, suggest that this signal is best explained as arising from a planetary companion. The candidate planet around Barnard's star is a cold super-Earth, with a minimum mass of 3.2 times that of Earth, orbiting near its snow line (the minimum distance from the star at which volatile compounds could condense). The combination of all radial-velocity datasets spanning 20 years of measurements additionally reveals a long-term modulation that could arise from a stellar magnetic-activity cycle or from a more distant planetary object. Because of its proximity to the Sun, the candidate planet has a maximum angular separation of 220 milliarcseconds from Barnard's star, making it an excellent target for direct imaging and astrometric observations in the future.

A multiplanet system of super-Earths orbiting the brightest red dwarf star GJ 887.

The closet exoplanets to the Sun provide opportunities for detailed characterization of planets outside the Solar System. We report the discovery, using radial velocity measurements, of a compact multiplanet system of super-Earth exoplanets orbiting the nearby red dwarf star GJ 887. The two planets have orbital periods of 9.3 and 21.8 days. Assuming an Earth-like albedo, the equilibrium temperature of the 21.8-day planet is ~350 kelvin. The planets are interior to, but close to the inner edge of, the liquid-water habitable zone. We also detect an unconfirmed signal with a period of ~50 days, which could correspond to a third super-Earth in a more temperate orbit. Our observations show that GJ 887 has photometric variability below 500 parts per million, which is unusually quiet for a red dwarf.

The Mars Pathfinder atmospheric structure investigation/meteorology (ASI/MET) experiment.

The Mars Pathfinder atmospheric structure investigation/meteorology (ASI/MET) experiment measured the vertical density, pressure, and temperature structure of the martian atmosphere from the surface to 160 km, and monitored surface meteorology and climate for 83 sols (1 sol = 1 martian day = 24.7 hours). The atmospheric structure and the weather record are similar to those observed by the Viking 1 lander (VL-1) at the same latitude, altitude, and season 21 years ago, but there are differences related to diurnal effects and the surface properties of the landing site. These include a cold nighttime upper atmosphere; atmospheric temperatures that are 10 to 12 degrees kelvin warmer near the surface; light slope-controlled winds; and dust devils, identified by their pressure, wind, and temperature signatures. The results are consistent with the warm, moderately dusty atmosphere seen by VL-1.

Characterization of a 1-aminocyclopropane-1-carboxylate synthase gene from loblolly pine (Pinus taeda L.).

1-Aminocyclopropane-1-carboxylate (ACC) synthase catalyzes what is typically the rate-limiting step in the biosynthesis of ethylene, a gaseous plant growth regulator that plays numerous roles in the growth and development of higher plants. Although ACC synthase genes have been characterized from a wide variety of angiosperm plant species, no ACC synthase genes have been described previously for gymnosperms. Evidence suggests that ethylene helps to regulate wood formation in trees, and may also signal for the metabolic shifts that lead to compression wood formation on the undersides of branches and leaning stems in gymnosperm trees. Since compression wood is an inferior feedstock for the manufacturing of most wood products, a better understanding of the factors influencing its formation could lead to substantial economic benefits. This study describes the isolation and characterization of a putative ACC synthase gene, PtaACS1, from loblolly pine (Pinus taeda L.), an important commercial forest tree species. Also described is an apparent splice variant of PtaACS1 (PtaACS1s) that is missing 138 bp from the 5' end of the transcript, including bases that encode a conserved amino acid residue considered critical for ACC synthase activity. The two sequences share interesting homologies with a group of plant aminotransferases, in addition to ACC synthases, but structural models and the conservation of critical catalytic amino acid residues strongly support PtaACS1 as encoding an active ACC synthase. The two transcripts were differentially expressed in various tissues of loblolly pine, as well as in response to perturbations of pine seedling stems. Transcript levels of this ACC synthase gene increased rapidly in response to bending stress but returned to near starting levels within 30 min. It remains unclear to what extent bending-induced expression of this gene product plays a role in compression wood formation.

The effects of extracellular pH and calcium manipulation on protein synthesis and response to anoxia/aglycemia in the rat hippocampal slice.

Extracellular pH modulates the function of the N-methyl-D-aspartate (NMDA) receptor, which may influence pathophysiological responses to glutamate. While damage due to oxygen and glucose deprivation or glutamate exposure is attenuated by acidification of the incubating medium of cultured neurons, neuron damage is enhanced in vivo following ischemia in hyperglycemic animals. A persistent inhibition of protein synthesis (to less than 5% of normoxic levels) is a reliable index of damage to neurons both in vivo and in the rat hippocampal slice. We explored the influence of extracellular pH and calcium manipulation on protein synthesis inhibition and energy failure due to anoxia/aglycemia or exposure to N-methyl-D-aspartate in the rat hippocampal slice. Moderate acidification of the medium during anoxia/aglycemia did not reduce the damage to protein synthesis in hippocampal neurons (9% of normoxic levels) and did not alter basal ATP levels or the rate of ATP depletion during anoxia/aglycemia. However, when calcium levels were lowered during the acidification and following the anoxia/aglycemia, protein synthesis was almost completely protected (84% of normoxic levels). Calcium reduction itself also attenuated the protein synthesis inhibition due to anoxia/aglycemia (to 55.6% of normoxic controls), but the protection was not as complete. In contrast, moderate acidification of the medium significantly reduced the damage to protein synthesis due to a brief exposure to NMDA (37% of control with NMDA, 78.9% of control with acidification during NMDA), even in the presence of extracellular calcium. Alkalinization of the medium exacerbated the protein synthesis inhibition following anoxia/aglycemia, and significantly reduced basal ATP levels (to 52% of normoxic control levels). Thus, pHo changes influence neuronal metabolism and response to anoxia/aglycemia. In addition, while acidification can reduce the excitotoxic damage caused by direct exposure to NMDA, it cannot reduce damage due to anoxia/aglycemia unless calcium is lowered concomitantly. Thus, both NMDA receptor activation and calcium are involved in the damage due to oxygen and glucose deprivation in the slice.

Effects of volatile anesthetics on hippocampal slice metabolism, response to anoxia with and without glucose.

Anesthetics attenuate ischemic damage and so are often not used when preparing hippocampal slices for studies of ischemic or anoxic damage. In this study, we tested whether halothane, ether or isoflurane, when used briefly during slice preparation, have persistent effects on slice ATP metabolism, protein synthesis or morphology. We also tested the effects of anoxia with and without glucose on these slices. Five minutes of anoxia without glucose (anoxia-aglycemia) caused a dramatic depletion of ATP to less than 22% of control levels, a persistent inhibition of neuronal protein synthesis to less than 10% of control rates and severe morphological damage. Slices prepared using volatile anesthetics showed the same degree of damage due to anoxia-aglycemia, when compared with untreated tissue. In contrast, 5 min anoxia caused a 40% decrease in ATP levels in untreated tissue, but did not damage protein synthesis or morphology. While isoflurane-treated tissue responded identically to anoxia as untreated tissue, both halothane and ether prevented the anoxic ATP fall. These findings suggest that while halothane and ether may have persistent effects on slice responses to anoxia, isoflurane is a good candidate anesthetic for slice preparation procedures.

When should the "infected" subcutaneous infusion reservoir be removed?

Subcutaneous central venous infusion reservoirs (central venous catheters) are one of the primary devices for administration of intravenous chemotherapy. Usually these devices have few problems, and they provide dependable long term central venous access. Infection of these catheters is a significant problem that usually requires removal. When infection is suspected, it is often difficult to make this determination without actually removing the catheter. Thorough preoperative evaluation may help the surgeon decide which catheters are infected and should be removed. A total of 817 subcutaneous infusion reservoirs were placed at our institution from January 1, 1990 through November 1, 1994. During the same time period, 143 catheters were removed, 63 for suspected infection. The charts of these 63 patients were reviewed to determine to what extent available preoperative information could be used to predict which catheters were infected, thus avoiding unnecessary removal. Twenty-three preoperative parameters were assessed, including physical exam, body temperature, leukocyte count, platelet count, blood cultures from the catheter and peripheral blood, time from placement to removal, whether or not the catheter was functional, and whether it was currently in use. Forty catheters (65%) removed for suspected infection were infected, as demonstrated by a positive culture from the catheter or the wound. Staphylococcus was the most common microorganism. Physical exam (local erythema, tenderness, or swelling) correlated significantly with catheter infection (P = 0.0238). In contrast, blood culture data and the other clinical and laboratory parameters showed no significant association with catheter infection. We conclude that physical exam is the best indicator of catheter infection. Commonly used parameters such as fever, leukocytosis, and positive blood cultures are nonspecific, may not be due to catheter infection, and were not significant in our study. Removal and subsequent restoration of long term intravenous access is associated with significant morbidity and expense. Clinical decision making should not be based on isolated laboratory findings, but must be individualized in each patient with suspected catheter infection.

Inhalation toxicity of ammonium perfluorooctanoate.

Ammonium perfluorooctanoate (CAS Registry No. 3825-26-1) is a fine white powder which can become airborne; hence its inhalation toxicity was studied in the male rat. The compound was found to be moderately toxic following single 4-hr exposures, with an LC50 of 980 mg/m3. This concentration produced both an increase in liver size and corneal opacity. Both findings diminished with increasing time after exposure. Subchronic head-only inhalation exposures (6 hr/day on 5 days/wk for 2 wk to 0, 1, 8 or 84 mg/m3) suppressed body-weight gain at 84 mg/m3. Reversible liver-weight increases, reversible increases in serum enzyme activities, and microscopic liver pathology, including necrosis, occurred at exposure of 8 and 84 mg/m3. No ocular changes were produced. Concentrations of organofluoride in the blood showed a dose relationship with initial levels of 108 ppm in rats treated at 84 mg/m3 falling to 0.84 ppm after 84 days with a blood half-life of 5-7 days. The no-observed-effect level was 1 mg/m3 and a mean organofluoride blood level of 13 ppm was detected in rats immediately after the tenth exposure to an atmospheric level of 1 mg ammonium perfluorooctanoate/m3.

Angular deformity of the ankle with sparing of the distal fibula following meningococcal septicaemia: a case series involving 14 ankles in ten children.

Progressive angular deformity of an extremity due to differential physeal arrest is the most common late orthopaedic sequela following meningococcal septicaemia in childhood. A total of ten patients (14 ankles) with distal tibial physeal arrest as a consequence of meningococcal septicaemia have been reviewed. Radiological analysis of their ankles has demonstrated a distinct pattern of deformity. In 13 of 14 cases the distal fibular physis was unaffected and continued distal fibular growth contributed to a varus deformity. We recommend that surgical management should take account of this consistent finding during the correction of these deformities.

Distal tibial physeal arrest after meningococcal septicaemia: management and outcome in seven ankles.

Survivors of infantile meningococcal septicaemia often develop progressive skeletal deformity as a result of physeal damage at many sites, particularly in the lower limb. Distal tibial physeal arrest typically occurs with sparing of the distal fibular physis leading to a rapidly progressive varus deformity. There have been reports of isolated cases of this deformity, but to our knowledge there have been no papers which specifically describe the development of the deformity and the options for treatment. Surgery to correct this deformity is complex because of the patient's age, previous scarring and the multiplanar nature of the deformity. The surgical goal is to restore leg-length equality and the mechanical axis at the end of growth. Surgery should be planned and staged throughout growth in order to achieve the best functional results. We report our experience in six patients (seven ankles) with this deformity, who were managed by corrective osteotomy using a programmable circular fixator.

The impact of social marketing on HIV / AIDS.

PIP: An article focuses on the influence of social marketing, particularly of condoms and efforts to fight the HIV/AIDS epidemic. Condom sales have increased, especially in Africa. These sales are a good reflection of condoms purchased and used. Concerning the prevention of HIV/AIDS, availability of condoms is the most significant achievement of condom social marketing programs; however, HIV/AIDS prevalence has not declined. The marketing of condoms has been observed to be insufficient compared to the theoretical demand for condoms. All social marketing programs should be focused on marketing and communications, expressing messages that promote safer sexual behavior. Products and services aimed at safe sexual activity are being searched as tools in the fight against AIDS. In Uganda for instance, a kit called "Clear Seven" includes a large dose of pyprofloxin, a seven-day course of doxycycline, seven condoms and partner referral cards. The Population Services International is doing voluntary counseling and testing in Zimbabwe to prevent HIV transmission and contribute to destigmatizing people living with AIDS. It is too soon to assess the effectiveness of the program, yet many countries are already planning to duplicate it.^ieng

Thyroid tumors in rats from tetramethylthiourea.

Tetramethylthiourea (TMTU) was added to the diet of male and female ChR-CD rats for up to 2 years at levels of 0, 30 and 300 ppm. Fifty rats of each sex were used at each dietary level. High-level males and females and low-level males had a lower body weight and consumed less diet than did the controls. A slight anemia was found in the high-level males and females. Polyuria of a low osmolality was found in high level males and females. Serum thyroxine was lower in high-level males and females than in controls. TMTU-related gross and histologic changes were detected only in the thyroids of high-level males and females. After 3 months on test, the thyroids were enlarged and dark on gross examination. Histologically, there was an increase in follicle lumen size, loss of colloid staining, hypertrophy and hyperplasia of follicular cells, together with hyperemia. These early lesions were diffuse in distribution. Eight (28 percent) of 29 female high level rats, 18 to 24 months on test, developed follicular cell carcinomas with no such tumors in 26 comparable controls (p less than 0.005, Fisher's Exact Test, one tail). Although no metastases were found, capsular and vascular invasion by tumor cells was seen. TMTU was considered to be carcinogenic for the female rat under the conditions of this test.

Toxicity of N-methyl-2-pyrrolidone (NMP): teratogenic, subchronic, and two-year inhalation studies.

Pregnant rats were exposed to N-methyl-2-pyrrolidone (NMP) at atmospheric concentrations of 0.1 and 0.36 mg/liter for 6 hr/day on Days 6 through 15 of gestation. Except for sporadic lethargy and irregular respiration in several rats the first 3 days of exposure, there were neither abnormal clinical signs nor pathological lesions in the maternal rats. Exposure did not affect either the outcome of pregnancy or embryonal growth rate. No abnormal development was detected in the vital organs and skeletons of the fetuses. Rats were exposed to an aerosol-vapor mixture of NMP at concentrations of 0, 0.1, 0.5, and 1.0 mg/liter for 6 hr/day, 5 days/week for 4 weeks. At 0.1 and 0.5 mg/liter exposure levels, rats did not show any significant clinical signs or pathological lesions. However, lethargy, respiratory difficulty, and excessive mortality were found in rats exposed to 1.0 mg/liter. These rats had focal pneumonia, bone marrow hypoplasia, and atrophy of lymphoid tissue in the spleen and thymus. These lesions were reversible in surviving rats following 2 weeks of recovery. Increases in the relative and absolute numbers of neutrophils were observed during exposure at 1.0 mg/liter, but returned to normal limits after 2 weeks of recovery. Rats were exposed to vapor of NMP at concentrations of 0, 0.04, or 0.4 mg/liter for 6 hr/day, 5 days/week for 2 years. Male rats at 0.4 mg/liter showed slightly reduced mean body weight. No life-shortening toxic or carcinogenic effects were observed in rats exposed for 2 years to 0.04 or 0.4 mg/liter of NMP.

Re-engineering drug development: integrating pharmacoeconomic research into the drug development process.

Pharmacoeconomic research will be an increasingly important aspect of drug development as providers, third-party payers, and worldwide government health agencies use cost-effectiveness and quality-of-life data to assist in making decisions on optimal pharmaceutical treatment protocols, formulary listings, and reimbursement. It is in the best interest of pharmaceutical companies to have an established, well-integrated pharmacoeconomic research program that can respond to the dynamic health-care environment and proactively plan a program to optimize patient care. The new paradigm for pharmacoeconomic research will require establishment and successful management of many internal and external customer relationships. This article discusses one company's organization of these relationships and how they are integrated into the drug development process during each stage of the product life cycle.

Urinary bladder tumors in dogs from 4,4'-methylene-bis (2-chloroaniline) (MOCA).

Six female beagle dogs were given a daily dose of 100 mg MOCA, by capsule, 3 days per week for the first 6 weeks and then 5 days per week continuously for periods up to 9.0 years. The dose varied from 8 to 15 mg/kg body weight/day among the dogs. Six female beagle dogs were kept as untreated controls. The test was terminated after 9.0 years of treatment. The average plasma glutamic-pyruvic transaminase activity of the dogs fed MOCA was higher than that of the controls during the first and last two years on test. During the eighth and ninth years the urine sediment from MOCA dogs contained excessive numbers of erythrocytes, leukocytes, and epithelial cells. Some epithelial cells contained abnormalities that suggested neoplasia in the genitourinary tract. One MOCA dog, sacrificed after 8.3 years on test was found to have a papillary transitional cell carcinoma of the urinary bladder. Of four MOCA dogs sacrificed after 9.0 years on test, three were found to have papillary transitional cell carcinomas of the urinary bladder and one had a combined transitional cell carcinoma and adenocarcinoma of the urethra. The urethral tumor had metastasized to the liver, but the papillary transitional cell carcinomas found in the other four dogs did not invade the muscle layers of the bladder wall and did not metastasize. Since no urinary bladder tumors were found in the six control dogs, MOCA was considered to be carcinogenic for the urinary bladder of dogs under the conditions employed (p less than 0.025, Fisher's Exact Test, one tail). Three of five MOCA dogs contained hyperplastic nodules in the liver with no such nodules in six control dogs (p greater than 0.05, Fisher's Exact Test, one tail). This was considered to be suggestive of an effect of MOCA treatment.

Kidney and liver tumors in rats from 4,4'-methylene bis (2-carbomethoxyaniline).

4,4'-Methylene bis (2-carbomethoxyaniline), also known as methylene-bis methyl anthranilate (MBMA), was added to the diet of male and female ChR-CD rats for up to two years at levels of 0, 1500, and 15,000 ppm. Fifty rats of each sex were used at each dietary level. Female rats at both dietary levels of MBMA had a lower body weight gain and lower food efficiency values than did the controls. High-level males and females showed a slight anemia; all other clinical laboratory tests were within normal limits. MBMA caused slight degenerative histologic changes in the liver and kidney of both sexes at both dietary levels. High-level males developed a statistically significant increase in kidney and liver tumors when compared to controls (p less than 0.05, Fisher's Exact Test, one tail). High-level females had an elevated kidney tumor incidence compared with controls (p less than 0.10). There was a statistically significant lower incidence in pituitary tumors in high-level males (p less than 0.05) and in high-level females (p less than 0.10) than in controls. High-level females had a lower incidence of mammary tumors (p less than 0.05) compared to controls. MBMA was considered to be a carcinogen of moderate potency in rats, since tumors were not found until 18 months on test using a comparative large dose (1.5% of diet).

Liver and lung tumors in dogs from 4,4'-methylene-bis(2-methylaniline).

Six female beagle dogs were given, by capsule, a daily dose of 100 mg 4,4'-methylene-bis(2-methylaniline) (MeMDA), 3 times per week for 6 weeks, then 5 times per week for 5 weeks, at which time the dose was reduced to 50 mg 5 times per week, continuously for periods up to 7.0 years. Six female beagle dogs were kept as untreated controls for several studies and were sacrificed after 8.3 to 9 years test. MeMDA dogs developed renal atrophy with an elevated blood urea nitrogen during an approximate six-month period prior to death or being sacrificed in extremis. As three of three MeMDA dogs that survived for 5.2 years to 7.0 years developed hepatocellular carcinomas and two of the three dogs also developed primary lung tumors, with no liver or lung tumor in six control dogs, MeMDA was considered to be carcinogenic for the dog (liver tumors: p less than .05; lung tumors: p less than 10; Fisher's Exact Test, one tail).