Using dust shed from asteroids as microsamples to link remote measurements with meteorite classes.

Given the compositional diversity of asteroids, and their distribution in space, it is impossible to consider returning samples from each one to establish their origin. However, the velocity and molecular composition of primary minerals, hydrated silicates, and organic materials can be determined by in situ dust detector instruments. Such instruments could sample the cloud of micrometer-scale particles shed by asteroids to provide direct links to known meteorite groups without returning the samples to terrestrial laboratories. We extend models of the measured lunar dust cloud from LADEE to show that the abundance of detectable impact-generated microsamples around asteroids is a function of the parent body radius, heliocentric distance, flyby distance, and speed. We use Monte Carlo modeling to show that several tens to hundreds of particles, if randomly ejected and detected during a flyby, would be a sufficient number to classify the parent body as an ordinary chondrite, basaltic achondrite, or other class of meteorite. Encountering and measuring microsamples shed from near-Earth and Main Belt asteroids, coupled with complementary imaging and multispectral measurements, could accomplish a thorough characterization of small, airless bodies.

Determining best practices in reconnoitering sites for habitability potential on Mars using a semi-autonomous rover: A GeoHeuristic Operational Strategies Test.

We tested science operations strategies developed for use in remote mobile spacecraft missions, to determine whether reconnoitering a site of potential habitability prior to in-depth study (a walkabout-first strategy) can be a more efficient use of time and resources than the linear approach commonly used by planetary rover missions. Two field teams studied a sedimentary sequence in Utah to assess habitability potential. At each site one team commanded a human "rover" to execute observations and conducted data analysis and made follow-on decisions based solely on those observations. Another team followed the same traverse using traditional terrestrial field methods, and the results of the two teams were compared. Test results indicate that for a mission with goals similar to our field case, the walkabout-first strategy may save time and other mission resources, while improving science return. The approach enabled more informed choices and higher team confidence in choosing where to spend time and other consumable resources. The walkabout strategy may prove most efficient when many close sites must be triaged to a smaller subset for detailed study or sampling. This situation would arise when mission goals include finding, identifying, characterizing or sampling a specific material, feature or type of environment within a certain area.

A computational analysis of whole-genome expression data reveals chromosomal domains of gene expression.

Chromosome correlation maps display correlations between the expression patterns of genes on the same chromosome. Using these maps, we show here that adjacent pairs of genes, as well as nearby non-adjacent pairs of genes, show correlated expression independent of their orientation. We present specific examples of adjacent pairs with highly correlated expression patterns, in which the promoter of only one of the two genes contains an upstream activating sequence (UAS) known to be associated with that expression pattern. Finally, we show that genes with similar functions tend to occur in adjacent positions along the chromosomes. Our results suggest that, in certain chromosomal expression domains, an UAS can affect the transcription of genes that are not immediately downstream from it.

An olivine cumulate outcrop on the floor of Jezero crater, Mars.

The geological units on the floor of Jezero crater, Mars, are part of a wider regional stratigraphy of olivine-rich rocks, which extends well beyond the crater. We investigated the petrology of olivine and carbonate-bearing rocks of the Séítah formation in the floor of Jezero. Using multispectral images and x-ray fluorescence data, acquired by the Perseverance rover, we performed a petrographic analysis of the Bastide and Brac outcrops within this unit. We found that these outcrops are composed of igneous rock, moderately altered by aqueous fluid. The igneous rocks are mainly made of coarse-grained olivine, similar to some martian meteorites. We interpret them as an olivine cumulate, formed by settling and enrichment of olivine through multistage cooling of a thick magma body.

Impact Melt Facies in the Moon's Crisium Basin: Identifying, Characterizing, and Future Radiogenic Dating.

Both Earth and the Moon share a common history regarding the epoch of large basin formation, though only the lunar geologic record preserves any appreciable record of this Late Heavy Bombardment. The emergence of Earth's first life is approximately contemporaneous with the Late Heavy Bombardment; understanding the latter informs the environmental conditions of the former, which are likely necessary to constrain the mechanisms of abiogenesis. While the relative formation time of most of the Moon's large basins is known, the absolute timing is not. The timing of Crisium Basin's formation is one of many important events that must be constrained and would require identifying and dating impact melt formed in the Crisium event. To inform a future lunar sample dating mission, we thus characterized possible outcrops of impact melt. We determined that several mare lava-embayed kipukas could contain impact melt, though the rim and central peaks of the partially lava-flooded Yerkes Crater likely contain the most pure and intact Crisium impact melt. It is here where future robotic and/or human missions could confidently add a key missing piece to the puzzle of the combined issues of early Earth-Moon bombardment and the emergence of life.

Acetyl-l-carnitine and nucleoside reverse transcriptase inhibitor-associated neuropathy in HIV infection.

OBJECTIVES: Antiretroviral toxic neuropathy (ATN) is associated with dideoxynucleoside reverse transcriptase inhibitor use in patients infected with HIV, possibly as a result of mitochondrial toxicity. Acetyl-l-carnitine (ALC) has been linked to symptomatic improvement in ATN. We present an open-label single-arm pilot study to evaluate changes in intra-epidermal nerve fibre (IENF) density and mitochondrial DNA (mtDNA) copies/cell among subjects treated with 3000 mg ALC daily. METHODS: Punch skin biopsies were examined at baseline and after 24 weeks of therapy. Participants reported neuropathic symptoms using the Gracely Pain Intensity Score. Neurological examinations were completed. RESULTS: Twenty-one subjects completed the study. ALC was generally well tolerated. The IENF density did not change in cases completing 24 weeks of ALC therapy, with median (90% confidence interval) IENF changes of -1.70 (-3.50, infinity) (P=0.98) and 2.15 (-0.10, infinity) (P=0.11) for the distal leg and proximal thigh, respectively. Fat mtDNA copies/cell did not change with therapy. Improvements in neuropathic pain (P<0.01), paresthesias (P=0.01), and symptoms of numbness (P<0.01) were noted. Similarly, improvement was noted on the Gracely Pain Intensity Score. CONCLUSIONS: ALC therapy coincided with improvements in subjective measures of pain in this open-label single-arm study. However, changes were not observed in objective measures of IENF density or mtDNA levels, providing little objective support for use of ALC in this setting.

Support for the lunar cataclysm hypothesis from lunar meteorite impact melt ages.

Lunar meteorites represent a more random sampling of lunar material than the Apollo or Luna collections and, as such, lunar meteorite impact melt ages are the most important data in nearly 30 years with which to reexamine the lunar cataclysm hypothesis. Within the lunar meteorite breccias MAC 88105, QUE 93069, DaG 262, and DaG 400, seven to nine different impact events are represented with 40Ar-39Ar ages between 2.76 and 3.92 billion years ago (Ga). The lack of impact melt older than 3.92 Ga supports the concept of a short, intense period of bombardment in the Earth-moon system at approximately 3.9 Ga. This was an anomalous spike of impact activity on the otherwise declining impact- frequency curve.

Proton MR spectroscopy and MRI-volumetry in mild traumatic brain injury.

BACKGROUND AND PURPOSE: More than 85% of brain traumas are classified as "mild"; MR imaging findings are minimal if any and do not correspond to clinical symptoms. Our goal, therefore, was to quantify the global decline of the neuronal marker N-acetylaspartate (NAA), as well as gray (GM) and white matter (WM) atrophy after mild traumatic brain injury (mTBI). MATERIALS AND METHODS: Twenty patients (11 male, 9 female; age range, 19-57 years; median, 35 years) with mTBI (Glasgow Coma Scale score 13-15 with loss of consciousness for at least 30 seconds) and 19 age- and sex-matched control subjects were studied. Seven patients were studied within 9 days of TBI; the other 13 ranged from 1.2 months to 31.5 years (average and median of 4.6 and 1.7 years, respectively) after injury. Whole-brain NAA (WBNAA) concentration was obtained in all subjects with nonlocalizing proton MR spectroscopy. Brain volume and GM and WM fractions were segmented from T1-weighted MR imaging and normalized to the total intracranial volume, suitable for intersubject comparisons. The data were analyzed with least squares regression. RESULTS: Patients with mTBI exhibited, on average, a 12% WBNAA deficit that increased with age, compared with the control subjects (p<.05). Adjusted for age effects, patients also suffered both global atrophy (-1.09%/year; P=.029) and GM atrophy (-0.89%/year; P=.042). Patients with and without visible MR imaging pathology, typically punctate foci of suspected shearing injury, were indistinguishable in both atrophy and WBNAA. CONCLUSION: WBNAA detected neuronal/axonal injury beyond the minimal focal MR-visible lesions in mTBI. Combined with GM atrophy, the findings may provide further, noninvasive insight into the nature and progression of mTBI.

Skin care practices in newborn nurseries and mother-baby units in Maryland.

OBJECTIVE: Skin provides several important homeostatic functions to the developing neonate. However, no consensus guidelines exist in the United States for skin care in the healthy term newborn. STUDY DESIGN: We performed a study of skin and umbilical cord care (including bathing practices, vernix removal and antiseptic cord application) in newborn nurseries and mother-baby units throughout the state of Maryland to determine practices in a variety of clinical settings and assess if uniformity in skin care exists. These data were then assessed in the context of a review of the current literature. RESULTS: We received responses from over 90% of nurseries across the state. In our cohort, practices varied widely between institutions and specific populations, and often were not evidence-based or were contrary to best practices discussed in the scientific literature. CONCLUSION: The frequent departures from evidence that occur regarding the aforementioned practices are likely due to a lack of consensus on these issues as well as limited data on such practices, further highlighting the need for data-driven guidelines on newborn skin care.

Palliative CT-Guided Cordotomy for Medically Intractable Pain in Patients with Cancer.

Palliative cervical cordotomy can be performed via percutaneous radiofrequency ablation of the lateral C1-2 spinothalamic tract. This rare procedure can be safe, effective, and advantageous in mitigating medically intractable unilateral extremity pain for selected patients with end-stage cancer. This report reviews the indications, techniques, risks, and potential benefits of cordotomy. We describe our recent experience treating 3 patients with CT-guided C1-2 cordotomy and provide the first characterization of spinal cord diffusion MR imaging changes associated with successful cordotomy.

Diffusion alterations in corpus callosum of patients with HIV.

BACKGROUND AND PURPOSE: Diffusion alterations have been identified in the corpus callosum and frontal white matter of patients infected with human immunodeficiency virus (HIV), though the relevance of these findings to cognitive deterioration has not yet been determined. This study tested the hypothesis that diffusion tensor imaging can detect tissue status alterations in these regions in cognitively impaired patients infected with HIV and the acquired measurements correlate with the severity of cognitive impairment. METHODS: Fractional anisotropy (FA) and mean diffusivity (MD) were determined for corpus callosum (genu and splenium) and frontal white matter (FWM). The DTI measurements were compared in 11 HIV and 11 control participants. Patterns of relationship were examined with cognitive status measures from concurrent neurologic and neuropsychologic evaluations. RESULTS: FA values for the splenium were significantly reduced in the patients infected with HIV and correlated with dementia severity and deficits in motor speed. MD values for the splenium were significantly increased in the patients infected with HIV and correlated with deficits in motor speed. FA measurements were also significantly correlated with performance on visual memory (genu), visuoconstruction (FWM), and verbal memory (FWM) tasks. CONCLUSION: Diffusion abnormalities were identified in the splenium of the corpus callosum in patients infected with HIV, and these alterations were associated with dementia severity and motor speed losses. In vivo assessment of callosal integrity by using quantitative neuroimaging may have potential utility as a marker of brain injury in patients infected with HIV.

Bone marrow diffusion measures correlate with dementia severity in HIV patients.

BACKGROUND AND PURPOSE: Escalation in monocyte trafficking from the bone marrow into the brain may play a critical role in central nervous system injury and cognitive deterioration in patients with HIV infection. This study tested the hypothesis that the mean diffusivity is sensitive to marrow changes in HIV patients and that these quantitative imaging measurements correlate with the severity of dementia. METHODS: The mean diffusivity (MD), determined for clival and calvarial marrow regions, was compared in 11 HIV-infected patients and 9 control subjects. The imaging measurements were also evaluated for relationships with dementia severity and markers of disease progression (CD4 and viral load in plasma). RESULTS: The MD was significantly reduced in both clival and calvarial marrow in HIV-infected patients (P =.006). Diffusion measurements for clival (P =.02) and for calvarial (P =.03) regions were significantly correlated with the severity of dementia. CONCLUSION: The results of this investigation support the utility of diffusion strategies for monitoring the marrow and provide further evidence of a relationship between marrow status changes and neurologic progression in HIV patients.

Therapy Optimization in Multiple Sclerosis: a cohort study of therapy adherence and risk of relapse.

OBJECTIVES: The objective of the Therapy Optimization in MS (TOP MS) Study was to prospectively assess the relationship between MS disease-modifying therapy (DMT) adherence and MS relapse risk over 2 years. METHODS: Potential participants were recruited for TOP MS by specialty pharmacies who dispensed glatiramer acetate and beta interferons for MS nationwide. Signed IRB-approved informed consents were returned to the pharmacies. TOP MS used electronic data capture with monthly patient entries. Adherence, measured by medication possession ratio (MPR), was derived from pharmacy shipment records. Logistic regression examined the association between protocol-defined relapses and DMT MPR (<0.5; >0.5-<0.9; >0.9). RESULTS: TOP MS enrolled 3151 persons with MS, and 2410 completed the full 2 years. Across all therapies, the mean MPR for the 2-year completer cohort of 2049 who maintained the same DMT was 0.9+0.2 (range: 0.1-1.0), with 63.8% reaching a 2-year MPR >0.9. Evaluated by categories of MPR, the proportion of participants remaining relapse-free for 24 months increased with increasing MPR, and the proportion with >1 relapses declined with increasing levels of MPR (p<0.0008). Regression analysis revealed the odds of relapse for a patient in the MPR >0.9 MPR group was 64% that of a patient in the MPR <0.5 category (p=0.02). Use of >1 DMT prior to the current one was an independent predictor of relapse. CONCLUSIONS: The study provides class III evidence that improvement in adherence to DMT for MS is associated with improved clinical outcomes as measured by relapse reduction.

Incidental white matter hyperintensities on magnetic resonance imaging in HIV-1 infection. Multicenter AIDS Cohort Study.

Magnetic resonance (MR) scans were performed as part of a prospective neuropsychological study within the Multicenter AIDS Cohort Study. Fifty HIV-1-seronegative men, 85 HIV-1-seropositive men without constitutional symptoms, and 14 with symptomatic HIV disease underwent MR imaging using a uniform protocol. Scans were rated by neuroradiologists blinded to all clinical details except age. The majority of MR scans were normal in all of the clinical groups and no covert mass lesions or diffuse white matter abnormalities were identified. Focal hyperintensities in the white matter were observed in 24% of the HIV-1 seronegatives, 26% of HIV-1 asymptomatic seropositives (CDC II/III), and 17% of those with ARC/AIDS. No significant associations were noted between the white matter hyperintensities and HIV-1 serostatus, neurological abnormalities, CD4 count, alcohol or drug use, hypertension, or smoking. In one individual classified with early HIV-1 dementia, MR demonstrated several hyperintensities in the deep parietal white matter, but at autopsy no microscopic abnormalities corresponding to the MR findings were identified. Our studies imply that focal white matter hyperintensities identified on MR are not specific for HIV-1 infection and are probably incidental and of no clinical significance.

Low education as a possible risk factor for cognitive abnormalities in HIV-1: findings from the multicenter AIDS Cohort Study (MACS).

The present study reports new and unexpected results of cognitive abnormalities among human immunodeficiency virus type 1 (HIV-1) asymptomatic subjects in the Multicenter AIDS Cohort Study. The major purpose of our analyses is to estimate the separate and combined effects of serostatus and education level on the prevalence of cognitive abnormality. Cognitive "abnormality" was defined as performance that deviated > or = 2 SDs below the mean of the total seronegative group on at least one of the five neuropsychological screening tests (Grooved Pegboard, Verbal Fluency, Digit Span, Symbol Digit Modalities, Rey Auditory Verbal Learning). The predicted prevalence of cognitive abnormality was 38% in seropositive individuals with no more than 12 years of education, compared with < 17% in the other education-serostatus groups. This interaction between education level and serostatus remained after controlling for the possible confounding effects of age, ethnicity, CD4 level, depression, prior drug history, and learning disability using logistic regression. To account for these findings, we suggest that low education might reflect an indirect index of lower reserve capacity (i.e., a risk factor) that lowers the threshold for neuropsychological abnormalities in cases of early HIV-1 infection.

Prognosis and response to therapy of cytomegalovirus encephalitis and meningomyelitis in AIDS.

Effective diagnosis and treatment of cytomegalovirus infection of the nervous system in AIDS patients has been limited by a lack of sensitive diagnostic measures. Retrospective series suggest a poor prognosis for cytomegalovirus encephalitis with rapid mortality. Polymerase chain reaction amplification of cytomegalovirus DNA allows detection in CSF that appears specific for CNS infection. In this series of seven patients with CNS cytomegalovirus infection in AIDS, four patients responded to therapy. Serial determinations of cytomegalovirus DNA in CSF in five patients revealed persistent detection in two treatment failures and absence of detection in three responders on subsequent CSF samples. A prospective trial to determine optimal therapy and to confirm the utility of cytomegalovirus DNA in CSF as a marker of the course of cytomegalovirus infection in the CNS is warranted and should consider prior therapy for cytomegalovirus, prior opportunistic infections, and leukoencephalopathy as potential prognostic variables.

Angiographic comparison of carotid arteries in unilateral cerebral ischemia.

We reviewed bilateral carotid angiograms of 74 patients with strictly unilateral carotid ischemic symptoms to evaluate asymptomatic atherosclerosis. Symptomatic arteries showed more stenosis than the asymptomatic counterparts, especially in patients with multiple TIAs, amaurosis fugax, or TIAs lasting less than 60 minutes. However, the frequency or degree of ulceration did not differ, and the proportion of stenotic lesions that appeared ulcerated was nearly equal on the symptomatic and asymptomatic sides.

Neurologic prognosis of cytomegalovirus polyradiculomyelopathy in AIDS.

Cytomegalovirus (CMV) polyradiculomyelopathy is an uncommon but distinctive clinical syndrome in HIV-infected patients in which ascending motor weakness, areflexia, loss of sphincter control, paresthesias, and varying sensory impairment develop subacutely in association with a polymorphonuclear pleocytosis, increased protein, and hypoglycorrhachia in CSF. Responses to treatment with ganciclovir have varied in reported cases. We report three additional cases: two of these patients responded to treatment and the third was demonstrated to have CMV resistant to ganciclovir. We review other reported cases and identify factors predictive of ganciclovir resistance, which include persistent polymorphonuclear pleocytosis and hypoglycorrhachia on serial CSF studies, and positive CMV cultures from CSF or blood after induction therapy. We conclude that ganciclovir may be an effective therapy for CMV polyradiculomyelopathy, but the presence of these factors, or the development of the syndrome in a patient already being treated with ganciclovir, should prompt consideration of alternative antiviral therapy.