Hematite-coated microfossils: primary ecological fingerprint or taphonomic oddity of the Paleoproterozoic?

Microfossils belonging to the 1.88-billion-year-old 'Gunflint-biota' are preserved as carbonaceous and hematitic filaments and spheres that are believed to represent ancient chemolithoautotrophic Fe(II) oxidizing bacteria that grew above a chemocline where ferruginous seawater upwelled into shallow, oxygenated waters. This 'biological' model posits that hematite formed during burial from dewatering of the precursor ferric oxyhydroxides that encrusted Fe(II)-oxidizing bacteria. Here, we present an alternate 'taphonomic' model in which iron-rich groundwaters discharged into buried stromatolites; thus, the mineralization reactions are more informative of diagenetic processes than they are for primary marine conditions. We sampled centimeter-scale columnar stromatolites from both the lower and upper stromatolite horizons of the Biwabik and Gunflint formations, across a range of metamorphic gradients including unaltered to prehnite-pumpellyite taconite, supergene altered ore, and amphibolite-pyroxene grade contact-metamorphic zones. Fossils are rare to very rare and comprise curved filaments that exist in clusters with similar orientations. The filaments from throughout the Biwabik are similar to well-preserved carbonaceous Gunflintia from Ontario. Spheres of Huroniospora are also found in both formations. Microfossils from the least altered sections are preserved as carbon. Prehnite-pumpellyite samples are composed of either carbon or hematite (Fe2 O3 ). Within the contact aureole, filaments are densely coated by magnetite (Fe3 O4 ); the highest grade samples are secondarily oxidized to martite. The consistency in stromatolite microstructure and lithofacies throughout the metamorphic grades suggests they formed under similar environmental conditions. Post-depositional alteration led to replacement of the carbon by iron oxide. The facies association, filament distribution, and lack of branching and attached spherical cells argue against Gunflintia being a direct analogue to common marine, chemolithoautotrophic Fe(II)-oxidizing bacteria. Instead, we propose that the presence of hematite-coated microfossils is a reflection of taphonomic processes and does not necessarily reflect the byproduct of an original microbial ecosystem.

7th International Immunoglobulin Conference: Immunoglobulin in clinical practice.

Immunoglobulin (Ig) replacement therapy has been the mainstay of primary immunodeficiencies (PID) treatment for more than 30 years and has substantially changed the lives of patients. This review focuses on aspects of Ig use in clinical practice in addition to discussing prioritizing future Ig use. Despite Ig therapy, PID patients continue to be predisposed to recurrent, subclinical respiratory tract infections, which may lead to chronic lung disease. Research has shown that one of the underlying reasons for this deterioration in lung function is the differential distribution and concentration of Ig isotypes in the airway lumen. Further to this, the relationship between Ig dose and infection outcome is explored, expanding on end-of-cycle loss of efficacy (wear-off) particularly with intravenous immunoglobulin (IVIg), how this can confound the determination of optimal IgG dose and how our aim of treatment should be to improve clinical outcome. This review goes on to discuss the safety of Ig replacement therapy, which is generally well tolerated by most patients, compares the rates of systemic adverse reactions between IVIg and SCIg and highlights the advantages of SCIg administration in this respect, including the use of pre-infused subcutaneous recombinant human hyaluronidase to aid subcutaneous infusion volumes. The growing demand for Ig replacement therapy is challenging physicians; here we show the development of prioritization algorithms to assist in identifying those who will benefit most from this clinically valuable therapy.

7th International Immunoglobulin Conference: Immunoglobulin in clinical practice.

Intravenous and subcutaneous immunoglobulins (IVIg and SCIg, respectively) are increasingly used in clinical practice, not only as replacement therapy but also for immunomodulation. Physicians have learned that primary immunodeficiency (PID) patients are susceptible to recurrent respiratory tract infections even when appropriately treated with immunoglobulin (Ig) therapy. Further investigation will establish whether a combined therapeutic approach including Ig dose optimization will prevent progressive lung disease in PID. The wear-off effects observed with IVIg can be minimized by adjusting the dosing regimen. It is also possible to avoid the cyclic wear-off following transition to SCIg administration. Consideration of benefit versus risk with Ig therapy includes evaluating the potential occurrence of thromboembolic and haemolytic events, which may be more frequent when Ig is administered in high doses and in the presence of pre-existing risk factors. The ability to select an administration method from IVIg, SCIg or hyaluronidase-facilitated SCIg infusions provides patient choice and alternatives if one or other administration route is not suitable for a patient. The evolution in indications, applications, and understanding of Ig therapy described here has reinforced the need for robust methods to prioritize Ig use.

Microbial biogeochemistry of Boiling Springs Lake: a physically dynamic, oligotrophic, low-pH geothermal ecosystem.

Boiling Springs Lake (BSL) in Lassen Volcanic National Park, California, is North America's largest hot spring, but little is known about the physical, chemical, and biological features of the system. Using a remotely operated vessel, we characterized the bathymetry and near-surface temperatures at sub-meter resolution. The majority of the 1.2 ha, pH 2.2 lake is 10 m deep and 50-52 °C, but temperatures reach 93 °C locally. We extracted DNA from water and sediments collected from warm (52 °C) and hot (73-83 °C) sites separated by 180 m. Gene clone libraries and functional gene microarray (GeoChip 3.0) were used to investigate the BSL community, and uptake of radiolabeled carbon sources was used to assess the relative importance of heterotrophic vs. autotrophic production. Microbial assemblages are similar in both sites despite the strong temperature differential, supporting observations of a dynamic, convectively mixed system. Bacteria in the Actinobacteria and Aquificales phyla are abundant in the water column, and Archaea distantly related to known taxa are abundant in sediments. The functional potential appears similar across a 5-year time span, indicating a stable community with little inter-annual variation, despite the documented seasonal temperature cycle. BSL water-derived DNA contains genes for complete C, N, and S cycles, and low hybridization to probes for N and S oxidation suggests that reductive processes dominate. Many of the detected genes for these processes were from uncultivated bacteria, suggesting novel organisms are responsible for key ecosystem services. Selection imposed by low nutrients, low pH, and high temperature appear to result in low diversity and evenness of genes for key functions involved in C, N, and S cycling. Conversely, organic degradation genes appear to be functionally redundant, and the rapid assimilation of radiolabeled organic carbon into BSL cells suggests the importance of allochthonous C fueling heterotrophic production in the BSL C cycle.

Coupling temperature sensing and development: Hsp90 regulates morphogenetic signalling in Candida albicans.

Hsp90 is environmentally contingent molecular chaperone that influences the form and function of diverse signal transducers. Here we discuss our recent findings that Hsp90 regulates the morphogenetic transition from yeast to filamentous forms required for virulence of the most prevalent fungal pathogen of humans, Candida albicans, and does so via cAMP-PKA signalling. This transition is normally regulated by environmental cues that are contingent upon elevated temperature to relieve Hsp90-mediated repression of the morphogenetic program. Intriguingly, Hsp90 inhibition induces filamentation independent of the canonical PKA transcription factor Efg1, in striking similarity to a select set of morphogenetic stimuli. Further investigation will determine the downstream transcription factors through which Hsp90 regulates morphogenesis and the precise mechanism of Hsp90's interaction with the cAMP-PKA pathway. C. albicans is one of many fungal species that undergo a morphological transition in a temperature-dependent manner, thus Hsp90's capacity to govern this key developmental program may provide insight into morphogenesis of diverse organisms.

Subcutaneous immunoglobulin: opportunities and outlook.

Immunoglobulin (Ig) administration via the subcutaneous (s.c.) route has become increasingly popular in recent years. The method does not require venous access, is associated with few systemic side effects and has been reported to improve patients' quality of life. One current limitation to its use is the large volumes which need to be administered. Due to the inability of tissue to accept such large volumes, frequent administration at multiple sites is necessary. Most studies conducted to date have investigated the use of subcutaneous immunoglobulin (SCIg) in patients treated previously with the intravenous (i.v.) formulation. New data now support the use of s.c. administration in previously untreated patients with primary immunodeficiencies. SCIg treatment may further be beneficial in the treatment of autoimmune neurological conditions, such as multi-focal motor neuropathy; however, controlled trials directly comparing the s.c. and i.v. routes are still to be performed for this indication. New developments may further improve and facilitate the s.c. administration route. For example, hyaluronidase-facilitated administration increases the bioavailability of SCIg, and may allow for the administration of larger volumes at a single site. Alternatively, more concentrated formulations may reduce the volume required for administration, and a rapid-push technique may allow for shorter administration times. As these developments translate into clinical practice, more physicians and patients may choose the s.c. administration route in the future.

Microcystic features at US: a nonspecific sign for microcystic adenomas of the pancreas.

Microcystic adenoma of the pancreas is a benign tumor with no malignant potential and may not require surgery if it is asymptomatic. In the past, a mass containing more than six small (<2-cm) cysts at ultrasonography (US) has been considered to be diagnostic for microcystic adenoma. However, a retrospective study of 36 patients with focal or diffuse pancreatic lesions containing over six small cysts demonstrated that this finding can occur in a wide variety of neoplastic and inflammatory lesions, most of which are malignant. These lesions included adenocarcinoma (n = 18), mucinous cystadenocarcinoma (n = 2), islet cell carcinoma (n = 1), lymphoma (n = 1), sarcoma (n = 1), metastases (n = 2), pancreatitis (n = 4), and adenoma (n = 7). Thus, a finding of multiple small cysts in a pancreatic mass is not specific for microcystic adenoma, and if diagnosis is based on US findings alone, many malignant tumors will be misdiagnosed as microcystic adenomas. Furthermore, computed tomography provides only limited assistance in this setting due to overlapping findings. Needle biopsy can be highly accurate in diagnosing both microcystic adenoma and other malignant lesions and should generally be performed for all lesions with the US features described earlier.

Compound spatial sonography of the thyroid gland: evaluation of freedom from artifacts and of nodule conspicuity.

OBJECTIVE: The purpose of this study was to compare compound spatial sonography with conventional sonography of the thyroid gland with respect to freedom from sonographic artifacts and conspicuity of thyroid nodules. SUBJECTS AND METHODS: A prospective study was performed on 50 thyroid nodules (in 43 patients). Each nodule was examined using compound spatial sonography and conventional sonography. The sonographic techniques were then compared with respect to freedom from sonographic artifacts and thyroid nodule conspicuity. RESULTS: For freedom from artifacts, compound spatial sonography was superior in 45 cases (90%), and conventional sonography was superior in five cases (10%). Statistical analysis showed that compound spatial sonography was superior to conventional sonography for freedom from artifacts (p < 0.001). For thyroid nodule conspicuity, compound spatial sonography was superior in 37 cases (74%), and conventional sonography was superior in 13 cases (26%). Statistical analysis showed that compound spatial sonography was superior to conventional sonography for thyroid nodule conspicuity (p < 0.001). CONCLUSION: Compound spatial sonography of the thyroid displays greater freedom from artifacts and better nodule conspicuity than does conventional sonography.

Use of intraoperative Doppler ultrasound to diagnose hepatic venous obstruction in a right lobe living donor liver transplant.

Right lobe liver transplantation is a relatively new and technically challenging method of living donor transplantation. Integrity of the hepatic venous anastomosis is crucial for successful transplantation. We describe the use of intraoperative Doppler sonography to diagnose stenosis of the hepatic vein anastomosis, with associated compromise of venous drainage and graft perfusion.

Ethical issues surrounding adult-to-adult living donor liver transplantation.

1. The ethical principle of utility is enhanced by living donor liver transplantation (LDLT). LDLT carries the potential to optimize efficient use of organs, minimize pretransplant morbidity and mortality, and increase availability of cadaveric organs. 2. The most serious ethical concerns in LDLT focus on the risks to the donor and relate to the principle of nonmaleficence-"do no harm". Although exact risk remains uncertain, there is potential for significant donor morbidity and even mortality. 3. Careful consideration must be given to development of the best approach to obtaining truly informed consent. 4. Specific criteria for LDLT should be developed for transplant centers, donors, and recipients. Informed consent should be standardized. 5. A national registry for donors and recipients of LDLT is needed.

Recruitment maneuvers in three experimental models of acute lung injury. Effect on lung volume and gas exchange.

Recruitment maneuvers (RM), consisting of sustained inflations at high airway pressures, have been advocated as an adjunct to mechanical ventilation in acute respiratory distress syndrome (ARDS). We studied the effect of baseline ventilatory strategy and RM on end-expiratory lung volume (EELV) and oxygenation in 18 dogs, using three models of acute lung injury (ALI; n = 6 in each group): saline lavage (LAV), oleic acid injury (OAI), and intratracheal instillation of Escherichia coli (pneumonia; PNM). All three models exhibited similar degrees of lung injury. The PNM model was less responsive to positive end-expiratory pressure (PEEP) than was the LAV or OAI model. Only the LAV model showed an oxygenation response to increasing tidal volume (VT). After RM, there were transient increases in Pa(O(2)) and EELV when ventilating with PEEP = 10 cm H(2)O. At PEEP = 20 cm H(2)O the lungs were probably fully recruited, since the plateau airway pressures were relatively high ( approximately 45 cm H(2)O) and the oxygenation was similar to preinjury values, thus making the system unresponsive to RM. Sustained improvement in oxygenation after RM was seen in the LAV model when ventilating with PEEP = 10 cm H(2)O and VT = 15 ml/kg. Changes in EELV correlated with changes in Pa(O(2)) only in the OAI model with PEEP = 10 cm H(2)O. We conclude that responses to PEEP, VT, and RM differ among these models of ALI. RM may have a role in some patients with ARDS who are ventilated with low PEEP and low VT.

Microbialite morphostratigraphy as a tool for correlating Late Cambrian-Early Ordovician sequences.

Microbialite morphostratigraphy is a new tool for intrabasinal correlation using diverse microbialite structures (morphotypes). The recognition of the succession of morphotypes over constrained temporal intervals and broad areas is a function of the complex interactions that operate to create the structure. Because so many nonlinked variables (e.g., biotic, sedimentological, physicochemical) are involved, similar morphotypes do not reoccur over long temporal intervals. To demonstrate the technique, the upper Cambrian-lowermost Ordovician shelf strata of the Great Basin, United States, were correlated using both morphostratigraphy and standard lithostratigraphy. Six morphozones and one morphosubzone were recognized, as were four main lithologic successions. Because the boundaries between the morphozones and lithologic successions did not coincide, it is inferred that the characteristics of the various microbialite structures are not solely controlled by physical factors. The principles for establishing a morphostratigraphy outlined in this article allow for the potential to correlate along other ancient marine margins in both the same Cambrian and Ordovician interval, as well as any interval in the Phanerozoic in which diverse microbialite structures occur.

Prone positioning attenuates and redistributes ventilator-induced lung injury in dogs.

BACKGROUND: We previously demonstrated a markedly dependent distribution of ventilator-induced lung injury in oleic acid-injured supine animals ventilated with large tidal volumes and positive end-expiratory pressure > or =10 cm H2O. Because pleural pressure distributes more uniformly in the prone position, we hypothesized that the extent of injury induced by purely mechanical forces applied to the lungs of normal animals might improve and that the distribution of injury might be altered with prone positioning. OBJECTIVE: To compare the extent and distribution of histologic changes and edema resulting from identical patterns of high end-inspiratory/low end-expiratory airway pressures in both supine and prone normal dogs. DESIGN/SETTING: We ventilated 10 normal dogs (5 prone, 5 supine) for 6 hrs with identical ventilatory patterns (a tidal volume that generated a peak transpulmonary pressure of 35 cm H2O when implemented in the supine position before randomization, positive end-expiratory pressure = 3 cm H2O). Ventilator-induced lung injury was assessed by gravimetric analysis and histologic grading. MEASUREMENTS AND MAIN RESULTS: Wet weight/dry weight ratios (WW/DW) and histologic scores were greater in the supine than the prone group (8.8+/-2.8 vs. 6.1+/-0.7; p = .01 and 1.4+/-0.3 vs. 1+/-0.3; p = .037, respectively). In the supine group, WW/DW and histologic scores were significantly greater in dependent than nondependent regions (9.4+/-1.9 vs. 6.7+/-0.9; p = .01 and 2.0+/-0.4 vs. 0.9+/-0.4; p = .043, respectively). In the prone group, WW/DW also was greater in dependent regions (6.7+/-1.1 vs. 5.8+/-0.5; p = .054), but no significant differences were found in histologic scores between dependent and nondependent regions (p = .42). CONCLUSION: In this model of lung injury induced solely by mechanical forces, the prone position resulted in a less severe and more homogeneous distribution of ventilator-induced lung injury. These results parallel those previously obtained in oleic acid-preinjured animals ventilated with higher positive end-expiratory pressure.

Small cis-acting sequences that specify secondary structures in a chloroplast mRNA are essential for RNA stability and translation.

Nucleus-encoded proteins interact with cis-acting elements in chloroplast transcripts to promote RNA stability and translation. We have analyzed the structure and function of three such elements within the Chlamydomonas petD 5' untranslated region; petD encodes subunit IV of the cytochrome b(6)/f complex. These elements were delineated by linker-scanning mutagenesis, and RNA secondary structures were investigated by mapping nuclease-sensitive sites in vitro and by in vivo dimethyl sulfate RNA modification. Element I spans a maximum of 8 nucleotides (nt) at the 5' end of the mRNA; it is essential for RNA stability and plays a role in translation. This element appears to form a small stem-loop that may interact with a previously described nucleus-encoded factor to block 5'-->3' exoribonucleolytic degradation. Elements II and III, located in the center and near the 3' end of the 5' untranslated region, respectively, are essential for translation, but mutations in these elements do not affect mRNA stability. Element II is a maximum of 16 nt in length, does not form an obvious secondary structure, and appears to bind proteins that protect it from dimethyl sulfate modification. Element III spans a maximum of 14 nt and appears to form a stem-loop in vivo, based on dimethyl sulfate modification and the sequences of intragenic suppressors of element III mutations. Furthermore, mutations in element II result in changes in the RNA structure near element III, consistent with a long-range interaction that may promote translation.

In re Edna MF: case law confusion in surrogate decision making.

I review the recent case of Edna Folz, a 73 year-old woman who was suffering through the end stages of very advanced Alzheimer's dementia when her case was adjudicated by the Wisconsin Supreme Court. I consider this case as an example of how courts are increasingly misinterpreting the ethical and legal decision-making-standards known as "substituted judgment" and "best interests" and thereby threatening individuals' treatment decision-making rights as developed by other courts over the past two decades and creating serious roadblocks to health-care providers' ability to render appropriate patient care. The Wisconsin Supreme Court held that Edna's legal guardian could not authorize withdrawal of Edna's treatment, ruling that as a matter of law, if an incompetent person is not in a persistent vegetative state, it is not in his or her best interests for life-sustaining treatment to be withdrawn unless (s)he has executed an advance directive or other statement clearly indicating his or her desires.

Massive pneumatosis intestinalis: CT diagnosis.

Pneumatosis cystoides intestinalis is a rare condition characterized by multiple subserosal or submucosal gas filled cysts within the wall of a segment of bowel. It is associated with numerous conditions, both intra and extraabdominal in nature. The condition may be asymptomatic or may present clinically as nausea, vomiting, diarrhea or other signs of intestinal obstruction. With rupture of the cysts, pneumoperitoneum may be a finding. In a patient with vague clinical presentation, this finding radiographically may lead to a clinical dilemma as many of these patients have comorbid conditions which are also associated with intestinal perforation. The authors present the case of a 47-year-old obese black female found to have massive pneumatosis intestinalis of the tranverse colon with a small amount of free intraperitoneal air. This case highlights the importance of recognizing pneumatosis intestinalis as a possible mimic of free intraabdominal air as well as a possible cause of benign pneumoperitoneum.

B cell lymphoproliferative disorders following hematopoietic stem cell transplantation: risk factors, treatment and outcome.

Twenty-six cases of B cell lymphoproliferative disorder (BLPD) were identified among 2395 patients following hematopoietic stem cell transplants (HSCT) for which an overall incidence of BLPD was 1.2%. The true incidence was probably higher, since 9/26 of the diagnoses were made at autopsy. No BLPD was observed following autologous HSCT, so risk factor analyses were confined to the 1542 allogeneic HSCT. Factors assessed were HLA-mismatching (> or = 1 antigen), T cell depletion (TCD), presence of acute GvHD (grades II-IV), donor type (related vs unrelated), age of recipient and donor, and underlying disease. Factors found to be statistically significant included patients transplanted for immune deficiency and CML, donor age > or = 18 years, TCD, and HLA-mismatching, with recipients of combined TCD and HLA-mismatched grafts having the highest incidence. Factors found to be statistically significant in a multiple regression analysis were TCD, donor age and immune deficiency, although 7/8 of the patients with immunodeficiencies and BLPD received a TCD graft from a haploidentical parent. The overall mortality was 92% (24/26). One patient had a spontaneous remission, but subsequently died >1 year later of chronic GVHD. Thirteen patients received therapy for BLPD. Three patients received lymphocyte infusions without response. The only patients with responses and longterm survival received alpha interferon (alphaIFN). Of seven patients treated with alphaIFN there were four responses (one partial and three complete). These data demonstrate that alphaIFN can be an effective agent against BLPD following HSCT, if a timely diagnosis is made.