Titration and implementation of neurally adjusted ventilatory assist in critically ill patients

BACKGROUND: Neurally adjusted ventilatory assist (NAVA) delivers assist in proportion to the patient's respiratory drive as reflected by the diaphragm electrical activity (EAdi). We examined to what extent NAVA can unload inspiratory muscles, and whether unloading is sustainable when implementing a NAVA level identified as adequate (NAVAal) during a titration procedure. METHODS: Fifteen adult, critically ill patients with a Pao(2)/fraction of inspired oxygen (Fio(2)) ratio < 300 mm Hg were studied. NAVAal was identified based on the change from a steep increase to a less steep increase in airway pressure (Paw) and tidal volume (Vt) in response to systematically increasing the NAVA level from low (NAVAlow) to high (NAVAhigh). NAVAal was implemented for 3 h. RESULTS: At NAVAal, the median esophageal pressure time product (PTPes) and EAdi values were reduced by 47% of NAVAlow (quartiles, 16 to 69% of NAVAlow) and 18% of NAVAlow (quartiles, 15 to 26% of NAVAlow), respectively. At NAVAhigh, PTPes and EAdi values were reduced by 74% of NAVAlow (quartiles, 56 to 86% of NAVAlow) and 36% of NAVAlow (quartiles, 21 to 51% of NAVAlow; p < or = 0.005 for all). Parameters during 3 h on NAVAal were not different from parameters during titration at NAVAal, and were as follows: Vt, 5.9 mL/kg predicted body weight (PBW) [quartiles, 5.4 to 7.2 mL/kg PBW]; respiratory rate (RR), 29 breaths/min (quartiles, 22 to 33 breaths/min); mean inspiratory Paw, 16 cm H(2)O (quartiles, 13 to 20 cm H(2)O); PTPes, 45% of NAVAlow (quartiles, 28 to 57% of NAVAlow); and EAdi, 76% of NAVAlow (quartiles, 63 to 89% of NAVAlow). Pao(2)/Fio(2) ratio, Paco(2), and cardiac performance during NAVAal were unchanged, while Paw and Vt were lower, and RR was higher when compared to conventional ventilation before implementing NAVAal. CONCLUSIONS: Systematically increasing the NAVA level reduces respiratory drive, unloads respiratory muscles, and offers a method to determine an assist level that results in sustained unloading, low Vt, and stable cardiopulmonary function when implemented for 3 h.

A Geological Report on an Area Five Miles Southeast of Renova, Montana, and on an Area Seven Miles South of Jefferson Island, Montana

This trip was conducted to give those students working for their respective degrees an excellent opportunity to work under actual field conditions. A total of three weeks was taken to complete the required work. Two weeks were spent in the field gathering data, and making maps, and the last week was spent in the drawing room at the college preparing the final map.

The James Lind Library: explaining and illustrating the evolution of fair tests of medical treatments

The James Lind Library (www.jameslindlibrary.org) has been established to improve public and professional general knowledge about fair tests of treatments in healthcare and their history. Its foundation was laid ten years ago at the Royal College of Physicians of Edinburgh, and its administrative centre is in the College's Sibbald Library, one of the most important collections of historic medical manuscripts, papers and books in the world. The James Lind Library is a website that introduces visitors to the principles of fair tests of treatments, with a series of short, illustrated essays, which are currently available in English, Arabic, Chinese, French, Portuguese, Russian and Spanish. A 100-page book-- Testing Treatments--is now available free through the website, both in English and in Arabic and Spanish translations. To illustrate the evolution of ideas related to fair tests of treatments from 2000 BC to the present, the James Lind Library contains key passages and images from manuscripts, books and journal articles, many of them accompanied by commentaries, biographies, portraits and other relevant documents and images, including audio and video files. New material is being added to the website continuously, as relevant new records are identified and as methods for testing treatments evolve. A multinational, multilingual editorial team oversees the development of the website, which currently receives tens of thousands of visitors every month.

Establishment and expansion of Lake Malawi rock fish populations after a dramatic Late Pleistocene lake level rise

Major environmental events that fragment populations among multiple island habitats have potential to drive large-scale episodes of speciation and adaptive radiation. A recent palaeolimnological study of sediment cores indicated that Lake Malawi underwent major climate-driven desiccation events 75 000-135 000 years ago that lowered the water level to at least 580 m below the present state and severely reduced surface area. After this period, lake levels rose and stabilized, creating multiple discontinuous littoral rocky habitats. Here, we present evidence supporting the hypothesis that establishment and expansion of isolated philopatric rock cichlid populations occurred after this rise and stabilization of lake level. We studied the Pseudotropheus (Maylandia) species complex, a group with both allopatric and sympatric populations that differ in male nuptial colour traits and tend to mate assortatively. Using coalescent analyses based on mitochondrial DNA, we found evidence that populations throughout the lake started to expand and accumulate genetic diversity after the lake level rise. Moreover, most haplotypes were geographically restricted, and the greatest genetic similarities were typically among sympatric or neighbouring populations. This is indicative of limited dispersal and establishment of assortative mating among populations following the lake level rise. Together, this evidence is compatible with a single large-scale environmental event being central to evolution of spatial patterns of genetic and species diversity in P. (Maylandia) and perhaps other Lake Malawi rock cichlids. Equivalent climate-driven pulses of habitat formation and fragmentation may similarly have contributed to observed rapid and punctuated cladogenesis in other adaptive radiations.

IDENTIFICATION OF FACTORS INVOLVED IN DNA METHYLATION OF CPG-ISLAND-PROMOTERS

Repression of many tumor suppressor genes (TSGs) in cancer is mediated by aberrantly increased DNA methylation levels at promoter CpG islands (CGI). About one-fourth of empirically defined human promoters are surrounded by or contain clustered repetitive elements. It was previously observed that a sharp transition of methylation occurs between highly methylated repetitive elements (SINE or LINE) and unmethylated CGI-promoters (e.g. P16, VHL, CDH and RIL) in normal tissues. The functions that lead to increased CGI methylation in cancer remain poorly understood. We propose that CGI-promoters contain cis-elements for triggering de novo DNA methylation. In the first part of our project, we established a site-specific integration system with enforced local transcriptional repression in colorectal cancer cells and monitored the occurrence of de novo DNA methylation in exogenous fragments containing a CGI-promoter and repetitive elements. Initial de novo methylation was seeded at specific CG sites in a repetitive element, and accelerated by persistent binding of a KRAB-containing transcriptional repressor. Furthermore, additional repetitive elements (LINE and SINE) located adjacent to the promoter could confer DNA methylation spreading into the CGI particularly in the setting of KRAB-factor binding. However, a repressive chromatin alone was not sufficient to initiate DNA methylation, which required specific DNA sequences and was integration-site (and/or cell-line) specific. In addition, all the methylation observed showed slow and gradual accumulation over several months of culture. Overall, these results demonstrate a requirement for specific DNA sequences to trigger de novo DNA methylation, and repetitive elements as cis-regulatory factors to cooperate with strengthened transcriptional repression in promoting methylation spreading. In the second part, we re-introduced disrupted DNMT3B or DNMT1 into HCT116 DKO cells and mapped the remethylation pattern through a profiling method (DREAM). Moderate remethylation occurred when DNMT3B was re-expressed with a preference toward non-CGI and non-promoter regions. Hence, there exists a set of genomic regions with priority to be targets for DNMT3B in somatic cells.

Knowledge, beliefs, risk behaviors, and social skills for HIV/STD prevention in junior college students (grades 11--12) in Bombay, India

1230 year 11 and 12 college students, modal age 16 and 17, in three colleges in Bombay, India, were studied on sexual behaviors or risk of sexual behaviors, beliefs about sex, HIV/STD knowledge, perceived norms regarding sexual behaviors, and the relationships between social skills/anxieties in HIV/STD prevention and actual and anticipated sexual behaviors. A quantitative questionnaire examining HIV/STD risk behaviors, knowledge, attitudes and beliefs, and the AIDS Social Assertiveness Scale (ASAS) were administered to these 1230 college students. Data indicated that 8% of males and 1% of females had had sexual experience, but over one third were not sure at all of being able to abstain from sexual activity with either steady or casual partners. Perceived norms were slanted toward sexual abstinence for the majority of the sample. Knowledge of protective effects of condoms was high, although half of those who had had sex did not use condoms. Logistic regression showed knowledge was higher among males, those who believed it was OK to have sex with a steady partner and that they should not wait until they were older, those who believed that condoms should be used even if the partner is known, and those who believed it was acceptable to have multiple partners. Gender differences in sexual activity and beliefs about sexual activity showed males were less likely to believe in abstaining from sexual activity. The 5 scales of the ASAS were scored and compared on ANOVA on: those who had had sexual experience (HS), those who anticipated being unable to refuse sex (AS), and those who did not anticipate problems in refusing sex (DS). Those in the AS group had greater anxieties about refusing sexual or other risk behaviors than HS and DS groups. There were greater anxieties about dealing with condoms in the AS and DS groups compared with the HS group. Confiding sexual or HIV/STD-related problems to significant others was more anxiety-provoking for the AS group compared with the HS group, and the AS group were more anxious about interactions with people with HIV. Factor analysis produced the same 5 factors as those found in previous studies. Of these, condom interactions and confiding in significant others were most anxiety provoking, and condom interactions most variable based on demographic and attitudinal factors.^ This age group is appropriate for HIV/STD reduction education given the low rate of sexual activity but despite knowledge of the importance of condom use, social skills to apply this knowledge are lacking. Social skills training in sexual negotiations, condom negotiations, and confiding HIV/STD-related concerns to significant others should reduce the risks of Indian college students having unwanted or unprotected sex. ^

A quality of life subscale for terminally ill cancer patients

A subscale was developed to assess the quality of life of cancer patients with a life expectancy of six months or less. Phase I of this study identified the major concerns of 74 terminally ill cancer patients (19 with breast cancer, 19 with lung cancer, 18 with colorectal cancer, 9 with renal cell cancer, 9 with prostate cancer), 39 family caregivers, and 20 health care professionals. Patients interviewed were being treated at the University of Texas M. D. Anderson Cancer Center or at the Hospice at the Texas Medical Center in Houston. In Phase II, 120 patients (30 with breast cancer, 30 with lung cancer, 30 with colorectal cancer, 15 with prostate cancer, and 15 with renal cell cancer) rated the importance of these concerns for quality of life. Items retained for the subscale were rated as "extremely important" or "very important" by at least 60% of the sample and were reported as being applicable by at least two-thirds of the sample. The 61 concerns that were identified were formatted as a questionnaire for Phase III. In Phase III, 356 patients (89 with breast cancer, 88 with lung cancer, 88 with colorectal cancer, 44 with prostate cancer, and 47 with renal cell cancer) were interviewed to determine the subscale's reliability and sensitivity to change in clinical status. Both factor analysis and item response theory supported the inclusion of the same 35 items for the subscale. Internal consistency reliability was moderate to high for the subscale's domains: spiritual (0.87), existential (0.76), medical care (0.68), symptoms (0.67), social/family (0.66), and emotional (0.61). Test-retest correlation coefficients also were high for the domains: social/family (0.86), emotional (0.83), medical care (0.83), spiritual (0.75), existential (0.75), and symptoms (0.81).^ In addition, concurrent validity was supported by the high correlation between the subscale's symptom domain and symptom items from the European Organization for Research and Treatment of Cancer (EORTC) scale (r = 0.74). Patients' functional status was assessed with the Eastern Cooperative Oncology Group (ECOG) Performance status rating. When ECOG categories were compared to subscale domains, patients who scored lower in functional status had lower scores in the spiritual, existential, social/family, and emotional domains. Patients who scored lower in physical well-being had higher scores in the symptom domain. Patient scores in the medical care domain were similar for each ECOG category. The results of this study support the subscale's use in assessing quality of life and the outcomes of palliative treatment for cancer patients in their last six months of life. ^

High exchangeable calcium concentrations in soils on Barro Colorado Island, Panama

The soils on four lithologies (basaltic conglomerates, Bohio; Andesite; volcanoclastic sediments with basaltic agglomerates, Caimito volcanic; foraminiferal limestone, Caimito marine) on Barro Colorado Island (BCI) have high exchangeable Ca concentrations and cation-exchange capacities (CEC) compared to other tropical soils on similar parent material. In the 0–10 cm layer of 24 mineral soils, pH values ranged from 5.7 (Caimito volcanic and Andesite) to 6.5 (Caimito marine), concentrations of exchangeable Ca from 134 mmolc kg− 1 (Caimito volcanic) to 585 mmolc kg− 1 (Caimito marine), and cation exchange capacities from 317 mmolc kg− 1 (Caimito volcanic) to 933 mmolc kg− 1 (Caimito marine). X-ray diffractometry of the fraction < 2 μm revealed that smectites dominated the clay mineral assemblage in soil except on Caimito volcanic, where kaolinite was the dominant clay mineral. Exchangeable Ca concentrations decreased with increasing soil depth except on Caimito marine. The weathering indices Chemical Index of Alteration (CIA), Plagioclase Index of Alteration (PIA) and Weathering Index of Parker (WIP) determined for five soils on all geological formations, suggested that in contrast to expectation the topsoil (0–10 cm) appeared to be the least and the subsoil (50–70 cm) and saprolite (isomorphically weathered rock in the soil matrix) the most weathered. Additionally, the weathering indices indicated depletion of base cations and enrichment of Al-(hydr)oxides throughout the soil profile. Tree species did not have an effect on soil properties. Impeded leaching and the related occurrence of overland flow seem to be important in determining clay mineralogy. Our results suggest that (i) edaphic conditions favor the formation of smectites on most lithologies resulting in high CEC and thus high retention capacity for Ca and (ii) that there is an external source such as dust or sea spray deposition supplying Ca to the soils.

The Effects of Flowline Length Evolution on Chemistry-Delta O-18 Profiles from Penny Ice Cap, Baffin Island, Canada

The isotopic and chemical signatures for ice-age and Holocene ice from Summit, Greenland and Penny Ice Cap, Baffin Island, Canada, arc compared. The usual pattern of low delta(18)O, high Ca2+ and high Cl- is presented in the Summit records, but Penny Ice Cap has lower than present Cl- in its ice-age ice. A simple extension of the Hansson model (Hansson, 1994) is developed and used to simulate these signatures. The low ice-age Cl- from Penny Ice Cap is explained by having the ice-age ice originating many thousands of km inland near the centre of the Laurentide ice sheet and much further from the marine sources. Summit's flowlines all start close to the present site. The Penny Ice Cap early-Holocene delta(18)O's had to be corrected to offset the Laurentide meltwater distortion. The analysis suggests that presently the Summit and Penny Ice Cap marine impurity originates about,500 km away, and that presently Penny Ice Cap receives a significant amount of local continental impurity.

Tertiary Minette and Melanephelinite Dikes, Wasatch Plateau, Utah - Records of Mantle Heterogeneities and Changing Tectonics

A swarm of minette and melanephelinite dikes is exposed over 2500 km2 in and near the Wasatch Plateau, central Utah, along the western margin of the Colorado Plateaus in the transition zone with the Basin and Range province. To date, 110 vertical dikes in 25 dike sets have been recognized. Strikes shift from about N80-degrees-W for 24 Ma dikes, to about N60-degrees-W for 18 Ma, to due north for 8-7 m.y. These orientations are consistent with a shift from east-west Oligocene compression associated with subduction to east-west late Miocene crustal extension. Minettes are the most common rock type; mica-rich minette and mica-bearing melanephelinite occurs in 24 Ma dikes, whereas more ordinary minette is found in 8-7 Ma dikes. One melanephelinite dike is 18 Ma. These mafic alkaline rocks are transitional to one another in modal and major element composition but have distinctive trace element patterns and isotopic compositions; they appear to have crystallized from primitive magmas. Major, trace element, and Nd-Sr isotopic data indicate that melanephelinite, which has similarities to ocean island basalt, was derived from small degree melts of mantle with a chondritic Sm/Nd ratio probably located in the asthenosphere, but it is difficult to rule out a lithospheric source. In contrast, mica-bearing rocks (mica melanephelinite and both types of minette) are more potassic and have trace element patterns with strong Nb-Ta depletions and Sr-Nd isotopic compositions caused by involvement with a component from heterogeneously enriched lithospheric mantle with long-term enrichment of Rb or light rare earth elements (REE) (epsilon Nd as low as - 15 in minette). Light REE enrichment must have occurred anciently in the mid-Proterozoic when the lithosphere was formed and is not a result of Cenozoic subduction processes. After about 25 Ma, foundering of the subducting Farallon plate may have triggered upwelling of warm asthenospheric mantle to the base of the lithosphere. Melanephelinite magma may have separated from the asthenosphere and, while rising through the lithosphere, provided heat for lithospheric magma generation. Varying degrees of interaction between melanephelinite and small potassic melt fractions derived from the lithospheric mantle can explain the gradational character of the melanephelinite to minette suite.

Different Early Post-Settlement Strategies Between American Lobsters Homarus Americanus and Rock Crabs Cancer Irroratus in the Gulf of Maine

The abundance of many invertebrates with planktonic larval stages can be determined shortly after they reach the benthos. In this study, we quantified patterns of abundance and habitat utilization of early benthic phases of the American lobster Homarus americanus and the rock crab Cancer irroratus. These 2 decapods are among the most common and abundant macroinvertebrates in coastal zones of the Gulf of Maine, with similar densities of larger individuals. Settlement and early postsettlement survival indicate that lobsters are highly substrate-specific early in life, settling predominantly in cobble beds. Crabs appear to be less selective, setting both in cobble and sand. Cumulative settlement of crabs, inferred from weekly censuses over the summer, was an order of magnitude greater than that of lobsters over the same time period. However, only crabs showed significant postsettlement losses. Although the identity of specific predators is unknown, predator exclusion experiments and placement of vacant uninhabited nursery habitat suggested that post-settlement mortality rather than emigration was responsible for these losses. The selective habitat-seeking behavior and lower post-settlement mortality of lobsters is consistent with their lower fecundity and later onset of reproductive maturity. The patterns observed for crabs, however, suggest a different strategy which is more in accordance with their higher fecundity and earlier onset of maturity. It is possible that lower fecundity but greater per-egg investment, along with strict habitat selection at settlement and lower post-settlement mortality, allows adult lobster populations to equal adult populations of crabs. This occurs despite crabs being more fecund and less habitat-selective settlers but sustaining higher postsettlement mortality.

The Underwater Photic Environment of Cape Maclear, Lake Malawi: Comparison Between Rock- and Sand-Bottom Habitats and Implications for Cichlid Fish Vision

Lake Malawi boasts the highest diversity of freshwater fishes in the world. Nearshore sites are categorized according to their bottom substrate, rock or sand, and these habitats host divergent assemblages of cichlid fishes. Sexual selection driven by mate choice in cichlids led to spectacular diversification in male nuptial coloration. This suggests that the spectral radiance contrast of fish, the main determinant of visibility under water, plays a crucial role in cichlid visual communication. This study provides the first detailed description of underwater irradiance, radiance and beam attenuation at selected sites representing two major habitats in Lake Malawi. These quantities are essential for estimating radiance contrast and, thus, the constraints imposed on fish body coloration. Irradiance spectra in the sand habitat were shifted to longer wavelengths compared with those in the rock habitat. Beam attenuation in the sand habitat was higher than in the rock habitat. The effects of water depth, bottom depth and proximity to the lake bottom on radiometric quantities are discussed. The radiance contrast of targets exhibiting diffused and spectrally uniform reflectance depended on habitat type in deep water but not in shallow water. In deep water, radiance contrast of such targets was maximal at long wavelengths in the sand habitat and at short wavelengths in the rock habitat. Thus, to achieve conspicuousness, color patterns of rock-and sand-dwelling cichlids would be restricted to short and long wavelengths, respectively. This study provides a useful platform for the examination of cichlid visual communication.

Prospectus of the Library of Ephraim Deinard at New Orleans, Louisiana : also a list of Jewish antiquities, depicting the "history of religion", on exhibition at the Smithsonian Institution at Washington, D. C., and at New Orleans, Louisiana

Devir Efrayim

A Hebrew Deluge story in cuneiform : and other epic fragments in the Pierpont Morgan Library

by Albert T. Clay