Investigation of the physico-chemical properties of Ni-Mg-Al-La catalysts from ultrasound-assisted synthesis.

This work reports on the ultrasonic synthesis of layered double hydroxides (LDH), also known as hydrotalcite-type materials. We have studied the influence of ultrasonic irradiation parameters (power, time, temperature) on the physicochemical properties of Ni2Mg4Al1.8La0.2 hydrotalcite-type precursors and related mixed oxides (MO). The low-frequency acoustic cavitation (22 kHz) was applied during the precipitation and aging steps of co-precipitation synthesis and the results were compared to the classical preparation route. The materials were characterized by ATR-FTIR, XRD, N2 adsorption-desorption, SEM-EDX, S/TEM-HAADF, and XPS. Using the combination of acoustic cavitation-assisted precipitation and aging steps, XRD experiments show a higher purity hydrotalcite phase and a better incorporation of lanthanum ions into the LDH structure. As expected, morphological characterization shows a reduction in average crystallite size and an increase in surface area and pore volume, combined with a drastic reduction in synthesis time (45 min at room temperature versus 19 h at 60 °C in conventional synthesis). The insertion of a larger quantity of La is observed by S/TEM-EDSX mapping which also shows a better distribution of lanthanum atoms within the LDH and mixed oxide structures.

[Pain management in osteoporosis]. / Schmerztherapie bei Osteoporose.

Osteoporosis is a very common disease all over the world, in which a reduction in bone density can lead to an increased risk of fractures and a diminished physical height. Osteoporosis is also associated with acute and chronic pain, which especially occurs in the back and can significantly reduce the quality of life. To provide sufficient care for affected patients, it is essential to know the particularities of pain management in osteoporosis, such as pharmacological and nonpharmacological treatment options. This article gives a comprehensive review of pain management in osteoporosis and also explains the underlying pathomechanisms, risk factors, and diagnostic procedures.

[Pain management in osteoporosis]. / Schmerztherapie bei Osteoporose.

Osteoporosis is a very common disease all over the world, in which a reduction in bone density can lead to an increased risk of fractures and a diminished physical height. Osteoporosis is also associated with acute and chronic pain, which especially occurs in the back and can significantly reduce the quality of life. To provide sufficient care for affected patients, it is essential to know the particularities of pain management in osteoporosis, such as pharmacological and nonpharmacological treatment options. This article gives a comprehensive review of pain management in osteoporosis and also explains the underlying pathomechanisms, risk factors, and diagnostic procedures.

[Influence of the trauma mechanism on cervical spine injuries]. / Einfluss des Unfallmechanismus auf die Verletzungen der Halswirbelsäule.

BACKGROUND: The influence of trauma-related kinematics on the injury pattern of the cervical spine is currently not considered in the available classification systems, only the force vector. Whether the strength of the trauma has an additional influence on the number and complexity of the injuries and whether this can be classified, has not yet been finally investigated. OBJECTIVE: What influence do different kinematics apart from the traumatic force vector have on injuries of the cervical spine? MATERIAL AND METHODS: Based on the AOSpine classification system for the upper and subaxial cervical spine, data from 134 trauma patients from a first level trauma center were retrospectively analyzed. Analogue to the S3 guidelines on polytrauma, patients were assigned to six trauma groups and the injuries were classified on the basis of computed tomography (CT) cross-sectional imaging. RESULTS: A higher trauma energy had a significant impact on the number of cervical spine injuries (p = 0.005). In low velocity accidents C2 was the most frequently injured vertebra (51%; p = 0.022) and high velocity accidents showed more C7 fractures (37%; p = 0.017). Furthermore, upper cervical spine injuries occurred more often in low energy trauma and older female patients (e.g. falling from a standing position). Subaxial cervical spine involvement was found significantly more often in high velocity accidents and younger male patients (p = 0.012). CONCLUSION: Exact knowledge of the trauma mechanism is helpful in the primary treatment of an injured person. Injury patterns can be better estimated and the appropriate diagnostics can be initiated. The results underline the importance of immediate cervical spine immobilization even after minor trauma. In high velocity trauma, patients more often suffer from lower cervical spine injuries, especially C7. Due to the accumulation of multilevel spinal injuries in high velocity trauma, radiographic imaging of the whole spine is advisable.

Matrix stimulation in cancer pain: Methodology, safety and effectiveness.

BACKGROUND: This feasibility study addresses the applicability of matrix electrodes for the reduction of ongoing pain in cancer patients via low-frequency electrical stimulation (LFS). METHODS: Low-frequency matrix stimulation (4 Hz) was applied to the skin within the 'Head's zones' referring to the tumour localization of cancer pain patients. Pain at baseline was compared to a 3-day treatment interval consisting of 5 min of matrix stimulation in the morning and evening followed by a 3-day follow-up period without therapy. Main outcome parameters included numeric rating scale values (rating scale 0-100), painDETECT, HADS, and German pain questionnaire, as well as the opioid intake, calculated as the oral morphine equivalent (OME). RESULTS: Twenty patients with cancer pain (aged 64.4 ± 10.3; 9 women) were examined. In the majority of patients, the pain was classified as nociceptive. The mean pain reduction achieved by matrix therapy was 30%, under stable daily controlled-release opioid doses between 177 and 184 mg/day (OME). Seventeen patients (85%) were responders, defined by a pain reduction of at least 30%, while four responders experienced a pain reduction of over 50%. The only side effect was short-term erythema. CONCLUSION: Findings are consistent with the concept of synaptic long-term depression in cancer pain induced after conditioning LFS. Despite the short, but well-tolerated, treatment duration of 2 × 5 min/day, effects persisted throughout the 3-day follow-up. SIGNIFICANCE: Cutaneous neuromodulation using LFS via a matrix electrode has been shown to be a safe intervention for effectively reducing cancer pain in palliative care patients.

[Neuromodulation using matrix stimulation : A treatment for acute pain?] / Neuromodulation mittels Matrixstimulation : Ein Therapieansatz für akute Schmerzen?

BACKGROUND: There is currently a lack of studies that evaluate the effects of matrix electrode neuromodulation on acute pain. In this prospective and randomized cross-over study, we investigated the efficacy of 4 Hz-matrix stimulation on venipuncture-induced pain in 30 healthy subjects. METHODS: We compared two conditions of neurostimulation: in EC1 (experimental condition 1), we performed venipuncture during stimulation, with 2.5 min of prestimulation with 600 stimuli; in EC2 (experimental condition 2), the length of stimulation was 5 min, at 1200 stimuli, with subsequent venipuncture. A group with no stimulation was used as control condition. RESULTS: The EC2 group did not only show a 77% reduction in puncture pain when compared to the control group (p < 0.001; effect size [ES] d = 1.45), but also had a significant effect compared with EC1 (p < 0.001; ES d = 1.33). EC1, on the other hand, did not demonstrate a significant difference to the control group. The status of the veins was evaluated based on visibility and did not differ significantly between the conditions. CONCLUSION: The results of this study showed for the first time that pre-emptive matrix stimulation could be an effective way to reduce acute pain. The duration of stimulation seems to play a key role in the effectiveness of the neurophysiological mechanism of action. Matrix stimulation is a therapeutic intervention with very few side effects, which could, in the future, expand our pain-management options for the treatment of acute pain.

Diagnostic and prognostic value of low percentage of glycosylated ferritin in acquired hemophagocytic lymphohistiocytosis: A single-center study.

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and life-threatening syndrome characterized by an excessive immune activation. Glycosylated ferritin (GF) level has been proposed as highly specific of HLH. METHODS: We have studied 12 subjects with HLH according to the HLH-04 trial criteria and 11 patients with a clinical and laboratoristic suspicion of HLH. The percentage of GF was measured by an in-house assay. RESULTS: The only biomarkers that were significantly different in the two groups were fraction of GF (P<.001) and the presence of hemophagocytosis in bone marrow (P=.006). Subjects with HLH had significantly lower percentage of GF than patients with other inflammatory conditions mimicking HLH. A fraction of GF ≤20% was strongly consistent with a diagnosis of HLH. CONCLUSIONS: Fraction of GF is useful to identify subjects at high risk for early death and therefore in need of early treatment.

[Knee joint pain with signs of arthrosis]. / Kniegelenkschmerzen bei Arthrosezeichen.

Chronic pain in the knee joint is most commonly caused by osteoarthritis, especially in elderly patients but can be due to other causes, such as rheumatoid arthritis. The diagnostics include an exact patient medical history and a clinical examination, which often already provide clear indications of the cause of the knee pain. Subsequently, further diagnostics can then be considered, such as radiological procedures and laboratory diagnostics. The treatment is determined by the cause and the individual patient and aims to reduce pain and to preserve the mobility of the joint. Generally, therapy consists of pain management and physiotherapy as well as alternative therapeutic procedures, mostly in combination. Proximal tibial opening wedge osteotomy can be useful; however, partial or total knee arthroplasty should only be considered when conservative treatment options have been exhausted.

[High-intensity focused ultrasound (HIFU) for tumor pain relief in inoperable pancreatic cancer : Evaluation with the pain sensation scale (SES)]. / Hochintensiver fokussierter Ultraschall (HIFU) zur Linderung tumorbedingter Schmerzen bei inoperablem Pankreaskarzinom : Evaluation anhand der Schmerzempfindungsskala (SES).

BACKGROUND: High-intensity focused ultrasound (HIFU) in combination with palliative standard therapy is an innovative and effective treatment option for pain reduction in patients with inoperable pancreatic cancer. OBJECTIVE: Evaluation of the effects of additive ultrasound (US)-guided HIFU treatment in inoperable pancreatic cancer on the sensory and affective pain perception using validated questionnaries. MATERIAL AND METHODS: In this study 20 patients with locally advanced inoperable pancreatic cancer and tumor-related pain were treated by US-guided HIFU (6 stage III, 12 stage IV according to UICC and 2 with local recurrence after surgery). Ablation was performed using the JC HIFU system (HAIFU, Chongqing, China) with an ultrasonic device for real-time imaging. Clinical assessment included evaluation of pain severity using validated questionnaires with particular attention to the pain sensation scale (SES) with its affective and sensory component and the numeric rating scale (NRS). RESULTS: The average pain reduction after HIFU was 2.87 points on the NRS scale and 57.3 % compared to the mean baseline score (n = 15, 75 %) in 19 of 20 treated patients. Four patients did not report pain relief, however, the previous opioid medication could be stopped (n = 2) or the analgesic dosage could be reduced (n = 2). No pain reduction was achieved in one patient. Furthermore, after HIFU emotional as well as sensory pain aspects were significantly reduced (before vs. 1 week after HIFU, p < 0.05 for all pain scales). CONCLUSION: US-guided HIFU can be used for effective and early pain relief and reduction of emotional and sensory pain sensation in patients with locally advanced pancreatic cancer.

Clinical Use of High-Intensity Focused Ultrasound (HIFU) for Tumor and Pain Reduction in Advanced Pancreatic Cancer.

PURPOSE: Evaluation of ultrasound-guided high-intensity focused ultrasound (HIFU) used for the first time in Germany in patients with inoperable pancreatic cancer for reduction of tumor volume and relief of tumor-associated pain. MATERIALS AND METHODS: 15 patients with locally advanced inoperable pancreatic cancer and tumor-related pain symptoms were treated by HIFU (n = 6 UICC stage III, n = 9 UICC stage IV). 13 patients underwent simultaneous standard chemotherapy. Ablation was performed using the JC HIFU system (Chongqing, China HAIFU Company) with an ultrasonic device for real-time imaging. Imaging follow-up (US, CT, MRI) and clinical assessment using validated questionnaires (NRS, BPI) was performed before and up to 15 months after HIFU. RESULTS: Despite biliary or duodenal stents (4/15) and encasement of visceral vessels (15/15), HIFU treatment was performed successfully in all patients. Treatment time and sonication time were 111 min and 1103 s, respectively. The applied total energy was 386 768 J. After HIFU ablation, contrast-enhanced imaging showed devascularization of treated tumor regions with a significant average volume reduction of 63.8 % after 3 months. Considerable pain relief was achieved in 12 patients after HIFU (complete or partial pain reduction in 6 patients). CONCLUSION: US-guided HIFU with a suitable acoustic pathway can be used for local tumor control and relief of tumor-associated pain in patients with locally advanced pancreatic cancer. KEY POINTS: • US-guided HIFU allows an additive treatment of unresectable pancreatic cancer.• HIFU can be used for tumor volume reduction.• Using HIFU, a significant reduction of cancer-related pain was achieved.• HIFU provides clinical benefit in patients with pancreatic cancer. Citation Format: • Strunk HM, Henseler J, Rauch M et al. Clinical Use of High-Intensity Focused Ultrasound (HIFU) for Tumor and Pain Reduction in Advanced Pancreatic Cancer. Fortschr Röntgenstr 2016; 188: 662 - 670.

[Dose-finding for treatment with a transdermal fentanyl patch : Titration with oral transmucosal fentanyl citrate and morphine sulfate]. / Dosisfindung zur Behandlung mit transdermalem Fentanylpflaster : Titration mit oralem, transmukosalem Fentanylcitrat und Morphinsulfat.

To date, no studies investigating titration with oral transmucosal fentanyl for the dose-finding of transdermal fentanyl treatment have been published. In an open randomized study 60 patients with chronic malignant (n = 39) or nonmalignant pain (n = 21), who required opioid therapy according to step three of the guidelines of the World Health Organization (WHO), were investigated. In two groups of 30 patients each titration with immediate release morphine (IRM) or oral transmucosal fentanyl citrate (OTFC) was undertaken. For measurement purposes the Brief Pain Inventory (BPI) and Minimal Documentation System (MIDOS) were used. After a 24-h titration phase, in which patients documented the intensity of pain, nausea, and tiredness, treatment with transdermal fentanyl was evaluated over a 10-day period by means of the necessary dose adaptation (responder ≤ 1 dose adaptation; conversion formula 1:1 [OTFC group] vs 100:1 [IRM group]).The pain reduction over the first 24 h (titration phase) did not differ significantly between the groups. The number of responders (17 OTFC vs. 21 IRM) over the 10-day period did not show any difference either. In both groups there was a significant reduction in pain intensity (p < 0.001). Over the course of the study, there were significantly more drop-outs because of adverse effects in the OTFC group than in the IRM group (8 vs 1, p = 0.028).Oral transmucosal fentanyl citrate can be applied for the titration of transdermal fentanyl, but it does not show any clinically relevant advantage. For example, the risk of side effects-induced drop-outs was greater in the present study. Whether the unnecessary opioid switching to treat chronic pain and breakthrough pain is advantageous with regard to minimizing conversion errors cannot be definitively answered within the scope of this study.

Novel Non-invasive Treatment With High-intensity Focused Ultrasound (HIFU).

Ultrasound is not only used for diagnostic purposes but it also can be applied therapeutically so far that nowadays high-intensity focused ultrasound (HIFU) even represents a novel non-invasive treatment modality for various solid tumors. HIFU works by causing selectively deep tissue destruction of target lesions within the body without harming adjacent and overlying structures. In this article, we present an overview on both the mode of action and requirements for a HIFU treatment as well as on the safety and the current status of indications and possible applications with regard to benign and malignant gynecological diseases. Based on numerous studies and original articles, HIFU proved to be an effective and low-risk treatment option particularly for uterine fibroids and adenomyosis, but it also seems to be effective for breast fibroadenomas or even for breast cancer in special cases and other rare entities.

Midlatitude ice-rich ground on mars as a target in the search for evidence of life and for in situ resource utilization on human missions.

Midlatitude ground ice on Mars is of significant scientific interest for understanding the history and evolution of ice stability on Mars and is relevant for human exploration as a possible in situ resource. For both science and exploration, assessing the astrobiological potential of the ice is important in terms of (1) understanding the potential for life on Mars and (2) evaluating the presence of possible biohazards in advance of human exploration. In the present study, we review the evidence for midlatitude ground ice on Mars, discuss the possible explanations for its occurrence, and assess its potential habitability. During the course of study, we systematically analyzed remote-sensing data sets to determine whether a viable landing site exists in the northern midlatitudes to enable a robotic mission that conducts in situ characterization and searches for evidence of life in the ice. We classified each site according to (1) presence of polygons as a proxy for subsurface ice, (2) presence and abundance of rough topographic obstacles (e.g., large cracks, cliffs, uneven topography), (3) rock density, (4) presence and abundance of large boulders, and (5) presence of craters. We found that a suitable landing site exists within Amazonis Planitia near ground ice that was recently excavated by a meteorite impact.

Reaching 1 m deep on Mars: the Icebreaker drill.

The future exploration of Mars will require access to the subsurface, along with acquisition of samples for scientific analysis and ground-truthing of water ice and mineral reserves for in situ resource utilization. The Icebreaker drill is an integral part of the Icebreaker mission concept to search for life in ice-rich regions on Mars. Since the mission targets Mars Special Regions as defined by the Committee on Space Research (COSPAR), the drill has to meet the appropriate cleanliness standards as requested by NASA's Planetary Protection Office. In addition, the Icebreaker mission carries life-detection instruments; and in turn, the drill and sample delivery system have to meet stringent contamination requirements to prevent false positives. This paper reports on the development and testing of the Icebreaker drill, a 1 m class rotary-percussive drill and triple redundant sample delivery system. The drill acquires subsurface samples in short, approximately 10 cm bites, which makes the sampling system robust and prevents thawing and phase changes in the target materials. Autonomous drilling, sample acquisition, and sample transfer have been successfully demonstrated in Mars analog environments in the Arctic and the Antarctic Dry Valleys, as well as in a Mars environmental chamber. In all environments, the drill has been shown to perform at the "1-1-100-100" level; that is, it drilled to 1 m depth in approximately 1 hour with less than 100 N weight on bit and approximately 100 W of power. The drilled substrate varied and included pure ice, ice-rich regolith with and without rocks and with and without 2% perchlorate, and whole rocks. The drill is currently at a Technology Readiness Level (TRL) of 5. The next-generation Icebreaker drill weighs 10 kg, which is representative of the flightlike model at TRL 5/6.

Compartment-specific gene regulation of the CAR inducer efavirenz in vivo.

Nuclear receptors such as the constitutive androstane receptor (CAR) are central factors that link drug exposure to the activities of drug metabolism and elimination. In order to determine the in vivo effects of efavirenz, a CAR activator, the expression of target genes was determined in duodenal biopsies obtained from 12 healthy volunteers before treatment and after 10 days of treatment with efavirenz; concomitant administration of the cholesterol inhibitor ezetimibe produced no significant difference. However, in in vitro studies, efavirenz significantly increased CYP2B6 expression in several cell types, suggesting that the drug transactivates CAR. This hypothesis is supported by our findings that there is significant induction of CAR target genes in in vivo peripheral blood mononuclear cells (PBMCs) isolated from healthy volunteers treated with multiple doses of efavirenz. The impact of efavirenz on hepatic metabolism in vivo was confirmed by significant changes in plasma 4ß-hydroxycholesterol and bilirubin levels and the area under the curve (AUC) of efavirenz. Induction of CYP2B6 mRNA expression correlated with the decrease in the AUC of efavirenz (r = 0.61; P = 0.036). Taken together, our results provide evidence that efavirenz exerts compartment-specific inductive capacity in vivo.

Impact of efavirenz on intestinal metabolism and transport: insights from an interaction study with ezetimibe in healthy volunteers.

Hypercholesterolemia frequently occurs in patients treated with efavirenz who cannot be treated adequately with statins because of drug interactions. These patients may benefit from cholesterol-lowering therapy with ezetimibe. This study determined the influence of single-dose and multiple-dose efavirenz (400 mg/day for 9 days) on the pharmacokinetics and sterol-lowering of ezetimibe (10 mg) in 12 healthy subjects. In addition, the influence of efavirenz on genome-wide intestinal expression and in vitro function of ABCB1, ABCC2, UGT1A1, and OATP1B1 was studied. Efavirenz (multiple dose) had no influence on the pharmacokinetics and lipid-lowering functions of ezetimibe. Intestinal expression of enzymes and transporters (e.g., ABCB1, ABCC2, and UGT1A1) was not affected by chronic efavirenz. Efavirenz (single dose) slightly increased ezetimibe absorption and markedly decreased exposure to ezetimibe-glucuronide (single dose and multiple dose), which may be explained by inhibition of UGT1A1 and ABCB1 (in vitro data). Ezetimibe had no effect on the disposition of efavirenz. Consequently, ezetimibe may be a safe and efficient therapeutic option in patients with HIV infection.

4beta-hydroxycholesterol as a marker of CYP3A4 inhibition in vivo - effects of itraconazole in man.

OBJECTIVE: Itraconazole, a triazole antifungal agent, has been demonstrated to act as an inhibitor of the ligand induced pregnane X receptor-mediated transcriptional regulation of the CYP3A4 gene. Here, we study the potential endogenous serum marker of CYP3A4 activity, 4beta-hydroxycholesterol, during therapy with itraconazole. PATIENTS AND METHODS: 8 male patients with onychomycosis received two 1-week cycles of treatment with 400 mg itraconazole once daily in an open, prospective exploratory trial. Fasting serum samples were taken at the beginning and at the end of each cycle. The levels of cholesterol were measured using gas chromatography-flame ionization detection, while cholesterol and bile acid precursors were quantified by gas chromatography-mass spectrometry. RESULTS: Total cholesterol decreased by 10% (p < 0.0005) during the itraconazole treatment. Concentrations of the cholesterol precursor lanosterol and 24, 25-dihydrolanosterol increased 10- and 240-fold, respectively (p < 0.001 for both). Interestingly, the ratio of serum lathosterol to cholesterol, an indicator of endogenous cholesterol synthesis downstream from lanosterol, remained unchanged. Absolute and cholesterol-corrected concentrations of 4beta-hydroxycholesterol, formed by CYP3A4-mediated oxidation, decreased significantly during both cycles, on average by 29.1% (p = 0.0006) and 20.8% (p = 0.0062), respectively. The brain-specific cholesterol metabolite 24S-hydroxycholesterol as well as its ratio to cholesterol increased by 19.7% (p = 0.0422) and 34.9% (p = 0.0013), respectively, while the concentrations of the other bile acid precursors, 7alpha-hydroxycholesterol and 27-hydroxycholesterol, remained unchanged. CONCLUSIONS: In conclusion, 4beta-hydroxycholesterol appears to be a sensitive endogenous surrogate marker in human serum for inhibition of CYP3A4 by itraconazole.

Raman scattering of Si matrix with randomly distributed nanoparticles of semiconducting silicides.

Samples, representing Si matrix with nanoformations of the semiconducting silicides beta-FeSi2 and Mg2Si are studied by Raman scattering. The unpolarized Raman spectra of the samples are interpreted in the framework of the appearance of interface-phonon polaritons. The theoretical dispersion relations of the interface-phonon polaritons in the system Si/silicide/Si are obtained from the Maxwell equations. The correspondence of the theoretical calculations and the experimental observations appeared to be sufficiently good. An evolution of the features in the Raman spectra on the experimental conditions is observed.

Resonant Raman and micro-Raman scattering from Si matrix with unburied beta-FeSi2 nanolayers.

Samples, representing Si matrix with nanolayers of the semiconducting beta-FeSi2 silicide are studied by Raman scattering. The unpolarized Raman spectra of the samples are measured in two different configurations. It is found that the characteristic beta-FeSi2 Raman modes are seen in the spectra, taken at incident angle of about 45 degrees , while only comparatively intensive broad feature is detected in a back-scattering geometry. The difference in the spectra is interpreted with the appearance of surface polariton modes of the optical phonons in the nanosized layers in near back-scattering geometry. The resonant Raman scattering is investigated at incident light angle of about 45 degrees and the energies of the interband transitions in the investigated energy range are determined. It is known that the resonant Raman scattering appears to be even more precise method for the determination of the interband transitions energies than the modulation spectroscopy. Thus we claim that the energies determined here are firstly determined with such a precision.

The physics, biology, and environmental ethics of making mars habitable.

The considerable evidence that Mars once had a wetter, more clement, environment motivates the search for past or present life on that planet. This evidence also suggests the possibility of restoring habitable conditions on Mars. While the total amounts of the key molecules--carbon dioxide, water, and nitrogen--needed for creating a biosphere on Mars are unknown, estimates suggest that there may be enough in the subsurface. Super greenhouse gases, in particular, perfluorocarbons, are currently the most effective and practical way to warm Mars and thicken its atmosphere so that liquid water is stable on the surface. This process could take approximately 100 years. If enough carbon dioxide is frozen in the South Polar Cap and absorbed in the regolith, the resulting thick and warm carbon dioxide atmosphere could support many types of microorganisms, plants, and invertebrates. If a planet-wide martian biosphere converted carbon dioxide into oxygen with an average efficiency equal to that for Earth's biosphere, it would take > 100,000 years to create Earth-like oxygen levels. Ethical issues associated with bringing life to Mars center on the possibility of indigenous martian life and the relative value of a planet with or without a global biosphere.