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1.
Ann Oncol ; 32(12): 1626-1636, 2021 12.
Article in English | MEDLINE | ID: mdl-34606929

ABSTRACT

BACKGROUND: Tumor mutational burden (TMB) measurements aid in identifying patients who are likely to benefit from immunotherapy; however, there is empirical variability across panel assays and factors contributing to this variability have not been comprehensively investigated. Identifying sources of variability can help facilitate comparability across different panel assays, which may aid in broader adoption of panel assays and development of clinical applications. MATERIALS AND METHODS: Twenty-nine tumor samples and 10 human-derived cell lines were processed and distributed to 16 laboratories; each used their own bioinformatics pipelines to calculate TMB and compare to whole exome results. Additionally, theoretical positive percent agreement (PPA) and negative percent agreement (NPA) of TMB were estimated. The impact of filtering pathogenic and germline variants on TMB estimates was assessed. Calibration curves specific to each panel assay were developed to facilitate translation of panel TMB values to whole exome sequencing (WES) TMB values. RESULTS: Panel sizes >667 Kb are necessary to maintain adequate PPA and NPA for calling TMB high versus TMB low across the range of cut-offs used in practice. Failure to filter out pathogenic variants when estimating panel TMB resulted in overestimating TMB relative to WES for all assays. Filtering out potential germline variants at >0% population minor allele frequency resulted in the strongest correlation to WES TMB. Application of a calibration approach derived from The Cancer Genome Atlas data, tailored to each panel assay, reduced the spread of panel TMB values around the WES TMB as reflected in lower root mean squared error (RMSE) for 26/29 (90%) of the clinical samples. CONCLUSIONS: Estimation of TMB varies across different panels, with panel size, gene content, and bioinformatics pipelines contributing to empirical variability. Statistical calibration can achieve more consistent results across panels and allows for comparison of TMB values across various panel assays. To promote reproducibility and comparability across assays, a software tool was developed and made publicly available.


Subject(s)
Mutation , Neoplasms , Biomarkers, Tumor , Humans , Neoplasms/diagnosis , Neoplasms/genetics , Reproducibility of Results , Tumor Burden
2.
Phys Rev Lett ; 126(9): 091101, 2021 Mar 05.
Article in English | MEDLINE | ID: mdl-33750144

ABSTRACT

We perform a comprehensive study of Milky Way (MW) satellite galaxies to constrain the fundamental properties of dark matter (DM). This analysis fully incorporates inhomogeneities in the spatial distribution and detectability of MW satellites and marginalizes over uncertainties in the mapping between galaxies and DM halos, the properties of the MW system, and the disruption of subhalos by the MW disk. Our results are consistent with the cold, collisionless DM paradigm and yield the strongest cosmological constraints to date on particle models of warm, interacting, and fuzzy dark matter. At 95% confidence, we report limits on (i) the mass of thermal relic warm DM, m_{WDM}>6.5 keV (free-streaming length, λ_{fs}≲10h^{-1} kpc), (ii) the velocity-independent DM-proton scattering cross section, σ_{0}<8.8×10^{-29} cm^{2} for a 100 MeV DM particle mass [DM-proton coupling, c_{p}≲(0.3 GeV)^{-2}], and (iii) the mass of fuzzy DM, m_{ϕ}>2.9×10^{-21} eV (de Broglie wavelength, λ_{dB}≲0.5 kpc). These constraints are complementary to other observational and laboratory constraints on DM properties.

3.
Int Nurs Rev ; 67(4): 476-483, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32767464

ABSTRACT

AIM: The purpose of this research was to determine the effectiveness of a mobile health or mHealth application to improve hypertension health literacy among vulnerable populations in India. Additionally, we sought to estimate relationships between participant knowledge on hypertension and sociodemographic variables. BACKGROUND: The World Health Organization advocates for the use of mobile technology to improve public health outcomes. INTRODUCTION: The incidence of hypertension is on the rise in India, and effective and sustainable interventions are needed. METHODS: A quantitative single arm pre-test post-test interventional and correlational design was used to test the hypertension mHealth application among participants in a limited resource setting. A paired t-test was performed to compare pre- and post-test results after participant use of the mHealth application. A regression model was used to estimate relationships between participant hypertension health literacy and sociodemographic variables. RESULTS: A statistically significant improvement in test scores among participants after use of the mHealth app was found. Sociodemographic characteristics such as living in an urban environment, married, increased number of people living in household and alcohol use were determined to have a statistically significant effect on improvement of test score. DISCUSSION: Results indicated the application was effective among participants with varied literacy and health literacy levels. These findings contribute to the potential widespread scalability of the app among populations with varied demographics. CONCLUSION: This application provides an effective and valuable culturally tailored educational resource for nurses and other health providers to use to improve hypertension health literacy among vulnerable populations in India. IMPLICATIONS FOR NURSING PRACTICE AND HEALTH POLICY: This study contributes to nursing and health policy by answering a call from the World Health Organization to implement and research mHealth interventions to improve health outcomes, particularly in a low and middle income country where preventive health access is limited.


Subject(s)
Health Literacy , Hypertension , Telemedicine , Humans , Hypertension/prevention & control , India
5.
Nat Genet ; 23(4): 413-9, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10581026

ABSTRACT

We report that mutation of COL11A2 causes deafness previously mapped to the DFNA13 locus on chromosome 6p. We found two families (one American and one Dutch) with autosomal dominant, non-syndromic hearing loss to have mutations in COL11A2 that are predicted to affect the triple-helix domain of the collagen protein. In both families, deafness is non-progressive and predominantly affects middle frequencies. Mice with a targeted disruption of Col11a2 also were shown to have hearing loss. Electron microscopy of the tectorial membrane of these mice revealed loss of organization of the collagen fibrils. Our findings revealed a unique ultrastructural malformation of inner-ear architecture associated with non-syndromic hearing loss, and suggest that tectorial membrane abnormalities may be one aetiology of sensorineural hearing loss primarily affecting the mid-frequencies.


Subject(s)
Collagen/genetics , Hearing Loss, Sensorineural/genetics , Mutation, Missense , Amino Acid Sequence , Animals , Base Sequence , Chromosomes, Human, Pair 6/genetics , DNA/genetics , Disease Models, Animal , Female , Genes, Dominant , Hearing Loss, Sensorineural/pathology , Hearing Loss, Sensorineural/physiopathology , Humans , In Situ Hybridization , Male , Mice , Mice, Knockout , Molecular Sequence Data , Pedigree , Polymorphism, Single-Stranded Conformational
6.
Am J Health Syst Pharm ; 79(1): e8-e13, 2022 Jan 01.
Article in English | MEDLINE | ID: mdl-34390237

ABSTRACT

PURPOSE: Thrombocytopenia can occur when using an Impella percutaneous ventricular assist device (pVAD), and heparin-induced thrombocytopenia (HIT) is often suspected. Data on heparin- and anticoagulant-free purge solutions in these devices are limited. Previous case reports have described argatroban-based purge solutions, both with and without systemic argatroban, at varying concentrations in patients with known or suspected HIT. SUMMARY: A 33-year-old male was transferred to our institution and emergently initiated on life support with venoarterial extracorporeal membrane oxygenation (ECMO), an Impella pVAD, and continuous venovenous hemofiltration to receive an urgent aortic valve replacement. Over the next several days, the patient's platelet count declined with a nadir of 17 × 103/µL on hospital day 13. The patient's 4T score for probability of HIT was calculated as 4. All heparin products were discontinued on hospital day 15, and the patient was initiated on systemic infusion with argatroban 1,000 µg/mL at a rate of 0.2 µg/kg/min with a purge solution of argatroban 0.05 mg/mL. The systemic infusion remained at a rate of 0.2 µg/kg/min, and the total argatroban dose was, on average, less than 0.25 µg/kg/min. On hospital day 21, the patient was transferred to another institution. CONCLUSION: Systemic infusion and a purge solution with argatroban were used in a patient with an Impella pVAD with multisystem organ dysfunction and suspected HIT. The patient achieved therapeutic activated partial thromboplastin times without adjustment of the systemic argatroban infusion and did not experience bleeding or thrombosis. Further studies concerning the safety and effectiveness of argatroban-based purge solutions in patients with pVADs are needed.


Subject(s)
Heart-Assist Devices , Thrombocytopenia , Adult , Arginine/analogs & derivatives , Humans , Pipecolic Acids , Sulfonamides , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Thrombocytopenia/drug therapy
7.
J Frailty Aging ; 11(2): 214-223, 2022.
Article in English | MEDLINE | ID: mdl-35441200

ABSTRACT

BACKGROUND: Frailty in older adults is a rapidly growing unmet medical need. It is an aging-related syndrome characterized by physical decline leading to higher risk of adverse health outcomes. OBJECTIVES: To evaluate the efficacy of Lomecel-B, an allogeneic medicinal signaling cell (MSC) formulation, in older adults with frailty. DESIGN: This multicenter, randomized, parallel-arm, double-blinded, and placebo-controlled phase 2b trial is designed to evaluate dose-range effects of Lomecel-B for frailty on physical functioning, patient-reported outcomes (PROs), frailty status, and biomarkers. SETTING: Eight enrolling clinical research centers, including the Miami Veterans Affairs Medical Center. PARTICIPANTS: Target enrollment is 150 subjects aged 70-85 years of any race, ethnicity, or gender. Enrollment criteria include a Clinical Frailty Score of 5 ("mild") or 6 ("moderate"), a 6MWT of 200-400 m, and serum tumor necrosis factor-alpha (TNF-α) ≥2.5 pg/mL. INTERVENTION: A single intravenous infusion of Lomecel-B (25, 50, 100, or 200 million cells) or placebo (N=30/arm). Patients are followed for 365 days for safety, and the efficacy assessments performed at 90, 180, and 270 days. MEASUREMENTS: The primary endpoint is change in 6MWT in the Lomecel-B-treated arms versus placebo at 180 days post-infusion. Secondary and exploratory endpoints include change in: 6MWT and other physical function measures at all time points; PROs; frailty status; cognitive status; and an inflammatory biomarkers panel. A pre-specified sub-study examines vascular/endothelial biomarkers. Safety is evaluated throughout the trial. RESULTS: The trial is conducted under a Food and Drug Administration Investigational New Drug (IND), with Institutional Review Board approval, and monitoring by an NIH-appointed independent Data Safety Monitoring Board. CONCLUSION: This clinical trial investigates the use of a regenerative medicine strategy for frailty in older adults. The results will further the understanding of the potential for Lomecel-B in the geriatric condition of frailty.


Subject(s)
COVID-19 , Frailty , Aged , Biomarkers , Double-Blind Method , Humans , SARS-CoV-2 , Treatment Outcome
8.
Clin Radiol ; 66(8): 748-51, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21546010

ABSTRACT

AIM: To investigate knowledge of the use of ionizing radiation in 2010 and whether there has been any change in this knowledge since the study was first undertaken over 7 years ago. MATERIALS AND METHODS: In both studies a single chest x-ray was classed as one unit of radiation. Doctors from all grades were asked to evaluate the average radiation dose incurred with 13 commonly undertaken radiological procedures, including magnetic resonance imaging (MRI), computed tomography (CT), etc. Answers within 20% of the actual dose were marked as correct. RESULTS: Two hundred and forty-two questionnaires were completed (130 in 2003; 112 in 2010). Equal numbers of juniors, middle grades, and consultants were questioned, and scores were comparable (23.3% in 2003; 29.4% in 2010). The majority of doctors (92% in 2003; 86% in 2010) correctly noted that ultrasound and MRI involve no radiation. Doctors underestimated the radiation doses of all investigations by a smaller margin in 2010 compared to 2003 (i.e., more accurately), with only one exception: CT of the abdomen. CONCLUSION: Despite evidence of some improvement, doctors of all grades still have a very poor knowledge of radiation exposure even with the most common investigations. The worsening appreciation of the radiation involved in CT scanning is especially worrying considering its increasing use in practice today.


Subject(s)
Clinical Competence/standards , Education, Medical/standards , Radiology , Clinical Competence/statistics & numerical data , Female , Humans , Male , Radiation Dosage , Radiation, Ionizing , Surveys and Questionnaires , United Kingdom
9.
Noise Health ; 13(55): 432-43, 2011.
Article in English | MEDLINE | ID: mdl-22122960

ABSTRACT

Noise-induced hearing loss (NIHL) is a significant clinical, social, and economic issue. The development of novel therapeutic agents to reduce NIHL will potentially benefit multiple very large noise-exposed populations. Oxidative stress has been identified as a significant contributor to noise-induced sensory cell death and NIHL, and several antioxidant strategies have now been suggested for potential translation to human subjects. One such strategy is a combination of beta-carotene, vitamins C and E, and magnesium, which has shown promise for protection against NIHL in rodent models, and is being evaluated in a series of international human clinical trials using temporary (military gunfire, audio player use) and permanent (stamping factory, military airbase) threshold shift models (NCT00808470). The noise exposures used in the recently completed Swedish military gunfire study described in this report did not, on average, result in measurable changes in auditory function using conventional pure-tone thresholds and distortion product otoacoustic emission (DPOAE) amplitudes as metrics. However, analysis of the plasma samples confirmed significant elevations in the bloodstream 2 hours after oral consumption of active clinical supplies, indicating the dose is realistic. The plasma outcomes are encouraging, but clinical acceptance of any novel therapeutic critically depends on demonstration that the agent reduces noise-induced threshold shift in randomized, placebo-controlled, prospective human clinical trials. Although this noise insult did not induce hearing loss, the trial design and study protocol can be applied to other populations exposed to different noise insults.


Subject(s)
Hearing Loss, Noise-Induced/prevention & control , Micronutrients/administration & dosage , Military Personnel , Oxidative Stress/drug effects , Adult , Ascorbic Acid/administration & dosage , Ascorbic Acid/blood , Ascorbic Acid/physiology , Audiometry, Pure-Tone , Cross-Over Studies , Female , Hearing Loss, Noise-Induced/blood , Hearing Loss, Noise-Induced/physiopathology , Humans , Magnesium/administration & dosage , Magnesium/blood , Magnesium/physiology , Male , Micronutrients/blood , Micronutrients/physiology , Otoacoustic Emissions, Spontaneous/drug effects , Otoacoustic Emissions, Spontaneous/physiology , Oxidative Stress/physiology , Sweden , Vitamin E/administration & dosage , Vitamin E/blood , Vitamin E/physiology , Young Adult , beta Carotene/administration & dosage , beta Carotene/blood , beta Carotene/physiology
10.
Ann R Coll Surg Engl ; 103(6): 385-389, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33955275

ABSTRACT

INTRODUCTION: National selection for higher surgical training (ST3+) recruitment in the UK is competitive. The process must prioritise patient safety while being credible, impartial and fair. During the COVID-19 pandemic, all face-to-face interviews were cancelled. Selection was based on a controversial isolated self-assessment score with no evidence checking taking place. From 2021, selection will take place entirely online. Although this has cost and time advantages, new challenges emerge. METHODS: We review surgical selection as it transitions to an online format and suggest validated methods that could be adapted from High Reliability Organisations (HRO). FINDINGS: Virtual selection methods include video interviewing, online examinations and aptitude testing. These tools have been used in business for many years, but their predictive value in surgery is largely unknown. In healthcare, the established online Multi-Specialty Recruitment Assessment (MSRA) examines generic professional capabilities. Its scope, however, is too limited to be used in isolation. Candidates and interviewers alike may have concerns about the technical aspects of virtual recruitment. The significance of human factors must not be overlooked in the online environment. Surgery can learn from HROs, such as aviation. Pilot and air traffic control selection is integral to ensuring safety. These organisations have already established digital selection methods for psychological aptitude, professional capabilities and manual dexterity. CONCLUSION: National selection for higher surgical training (ST3+) can learn from HROs, using validated methods to prioritise patient safety while being acceptable to candidates, trainers and health service recruiters.


Subject(s)
COVID-19/epidemiology , General Surgery/education , School Admission Criteria , Humans , Interviews as Topic/methods , Patient Safety , Reproducibility of Results , United Kingdom , Videoconferencing
11.
mBio ; 12(4): e0049021, 2021 08 31.
Article in English | MEDLINE | ID: mdl-34340550

ABSTRACT

The marine lithospheric subsurface is one of the largest biospheres on Earth; however, little is known about the identity and ecological function of microorganisms found in low abundance in this habitat, though these organisms impact global-scale biogeochemical cycling. Here, we describe the diversity and metabolic potential of sediment and endolithic (within rock) microbial communities found in ultrasmall amounts (101 to 104 cells cm-3) in the subsurface of the Atlantis Massif, an oceanic core complex on the Mid-Atlantic Ridge that was sampled on International Ocean Discovery Program (IODP) Expedition 357. This study used fluorescence-activated cell sorting (FACS) to enable the first amplicon, metagenomic, and single-cell genomic study of the shallow (<20 m below seafloor) subsurface of an actively serpentinizing marine system. The shallow subsurface biosphere of the Atlantis Massif was found to be distinct from communities observed in the nearby Lost City alkaline hydrothermal fluids and chimneys, yet similar to other low-temperature, aerobic subsurface settings. Genes associated with autotrophy were rare, although heterotrophy and aerobic carbon monoxide and formate cycling metabolisms were identified. Overall, this study reveals that the shallow subsurface of an oceanic core complex hosts a biosphere that is not fueled by active serpentinization reactions and by-products. IMPORTANCE The subsurface rock beneath the ocean is one of the largest biospheres on Earth, and microorganisms within influence global-scale nutrient cycles. This biosphere is difficult to study, in part due to the low concentrations of microorganisms that inhabit the vast volume of the marine lithosphere. In spite of the global significance of this biosphere, little is currently known about the microbial ecology of such rock-associated microorganisms. This study describes the identity and genomic potential of microorganisms in the subsurface rock and sediment at the Atlantis Massif, an underwater mountain near the Mid-Atlantic Ridge. To enable our analyses, fluorescence-activated cell sorting (FACS) was used as a means to concentrate cells from low biomass environmental samples for genomic analyses. We found distinct rock-associated microorganisms and found that the capacity for microorganisms to utilize organic carbon was the most prevalent form of carbon cycling. We additionally identified a potential role for carbon monoxide metabolism in the subsurface.


Subject(s)
Geologic Sediments/microbiology , Microbiota/genetics , Oceans and Seas , Genomics
12.
Neuroimage ; 50(3): 1126-41, 2010 Apr 15.
Article in English | MEDLINE | ID: mdl-20026230

ABSTRACT

Functional MRI provides a unique perspective of neuronal organization; however, these data include many complex sources of spatiotemporal variability, which require spatial preprocessing and statistical analysis. For the latter, Bayesian models provide a promising alternative to classical inference, which uses results from Gaussian random field theory to assess the significance of spatially correlated statistic images. A Bayesian approach generalizes the application of these ideas in that (1) random fields are used to model all spatial parameters, not solely observation error, (2) their smoothness is optimized, and (3) a broader class of models can be compared. The main problem, however, is computational, due to the large number of voxels in a brain volume. Sampling methods are time-consuming; however, approximate inference using variational Bayes (VB) offers a principled and transparent way to specify assumptions necessary for computational tractability. Penny et al. (2005b) described such a scheme using a joint spatial prior and approximated the joint posterior density with one that factorized over voxels. However, a further computational bottleneck is encountered when evaluating the log model evidence used to compare models. This has lead to dividing a brain volume into slices and treating each independently. This amounts to approximating the spatial prior over a full volume with stacked 2D priors. That is, smoothness along the z-axis is not included in the model. Here we describe a VB scheme that approximates the zero mean joint spatial prior with a non-zero mean empirical prior that factors over voxels, thereby overcoming this problem. We do this by modifying the original VB algorithm of Penny et al. using the conditional form of a so-called conditional autoregressive (CAR) prior to update a marginal prior over voxels. We refer to this as a spatially-informed voxel-wise prior (SVP) and use them to spatially regularise general linear model (GLM) and autoregressive (AR) coefficients (over time to model serial correlations). This algorithm scales more favourably with the number of voxels providing a truly 3D spatiotemporal model over volumes containing tens of thousands of voxels. We compare the scaling of compute times with the number of voxels and performance with a joint prior applied to synthetic and single-subject data.


Subject(s)
Bayes Theorem , Brain/physiology , Magnetic Resonance Imaging/methods , Models, Statistical , Signal Processing, Computer-Assisted , Algorithms , Computer Simulation , Humans , Imaging, Three-Dimensional/methods , Linear Models , Normal Distribution , Regression Analysis , Time Factors
13.
J Exp Med ; 180(1): 341-6, 1994 Jul 01.
Article in English | MEDLINE | ID: mdl-8006592

ABSTRACT

Vascular permeability factor (VPF, also known as vascular endothelial growth factor or VEGF), is a potent microvascular permeability enhancing cytokine and a selective mitogen for endothelial cells. It has been implicated in tumor angiogenesis and ascites fluid accumulation. Since development of the destructive synovial pannus in rheumatoid arthritis (RA) is associated with changes in vascular permeability (synovial fluid accumulation), synovial cell hyperplasia, and angiogenesis, we examined synovial fluids (SFs) and joint tissue for the expression and local accumulation of VPF/VEGF. VPF/VEGF was detected in all of 21 synovial fluids examined and when measured by an immunofluorimetric assay, ranged from 6.9 to 180.5 pM. These levels are biologically significant, since < 1 pM VPF/VEGF can elicit responses from its target cells, endothelial cells. Levels of VPF/VEGF were highest in rheumatoid arthritis fluids (n = 10), with a mean value (+/- SEM) of 59.1 +/- 18.0 pM, vs. 21.4 +/- 2.3 pM for 11 SFs from patients with other forms of arthritis (p = 0.042). In situ hybridization studies that were performed on joint tissues from patients with active RA revealed that synovial lining macrophages strongly expressed VPF/VEGF mRNA, and that microvascular endothelial cells of nearby blood vessels strongly expressed mRNA for the VPF/VEGF receptors, flt-1 and KDR. Immunohistochemistry performed on inflamed rheumatoid synovial tissue revealed that the VPF/VEGF peptide was localized to macrophages within inflamed synovium, as well as to microvascular endothelium, its putative target in the tissue. Together, these findings indicate that VPF/VEGF may have an important role in the pathogenesis of RA.


Subject(s)
Arthritis, Rheumatoid/metabolism , Endothelial Growth Factors/analysis , Lymphokines/analysis , Synovial Fluid/chemistry , Synovial Membrane/chemistry , Adult , Aged , Arthritis, Rheumatoid/etiology , Endothelial Growth Factors/genetics , Endothelial Growth Factors/physiology , Female , Humans , Lymphokines/genetics , Lymphokines/physiology , Male , Middle Aged , RNA, Messenger/analysis , Receptor Protein-Tyrosine Kinases/analysis , Receptor Protein-Tyrosine Kinases/genetics , Receptors, Growth Factor/analysis , Receptors, Growth Factor/genetics , Receptors, Vascular Endothelial Growth Factor , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
14.
Science ; 162(3855): 810-1, 1968 Nov 15.
Article in English | MEDLINE | ID: mdl-5686223

ABSTRACT

Phagocytosis of bacteria by rabbit alveolar macrophages is inhibited quantitatively by cigarette smoke in vitro. This phagocytoxic effect was abolished by addition of 0.2 to 0.4 micromole of glutathione or cysteine per milliliter of cigarette smoke. Serum protein was required to obtain both the toxic effect of the smoke and the protective action of the sulfhydryl compounds. The protective role of the sulfhydryl agents suggests an oxidant action of the cigarette smoke on these pulmonary cells.


Subject(s)
Cysteine/pharmacology , Glutathione/pharmacology , Macrophages/cytology , Phagocytosis/drug effects , Pulmonary Alveoli/cytology , Smoking , Animals , Depression, Chemical , Macrophages/drug effects , Pulmonary Alveoli/drug effects , Rabbits , Staphylococcus
15.
Science ; 185(4155): 951-3, 1974 Sep 13.
Article in English | MEDLINE | ID: mdl-17841775

ABSTRACT

Toxicity in sponges and holothurians is inversely related to latitude and may reach 100 percent for holothurians in high-diversity coral reefs. Evidence from approximately 700 experiments and from underwater observations suggests that predation by fish has resulted in natural selection for noxious and toxic chemical compounds in species within these taxa.

16.
Science ; 248(4952): 212-5, 1990 Apr 13.
Article in English | MEDLINE | ID: mdl-17740137

ABSTRACT

Madagascar is biologically one of the richest areas on Earth, and its plants and animals are among the most endangered. Satellite images and vegetation maps based on earlier aerial photographs were used to determine the extent of eastern rain forests in Madagascar and to monitor the rate of deforestation over a 35-year period. In 1985, 3.8 million hectares of rain forest remained, representing only 50 percent of the 7.6 million hectares existing in 1950 and 34 percent of the estimated orignal extent (11.2 million hectares). Between 1950 and 1985, the rate of deforestation averaged 111,000 hectares per year. Deforestation was most rapid in areas with low topographic relief and high population density. If cutting of forests continues at the same pace, only forests on the steepest slopes will survive the next 35 years.

17.
Trends Biochem Sci ; 17(6): 223-7, 1992 Jun.
Article in English | MEDLINE | ID: mdl-1502725

ABSTRACT

Two species of histones in sea urchin sperm (Sp H1 and Sp H2B) are chimeric molecules whose highly basic amino-terminal domains are dephosphorylated at the last stage of sperm cell differentiation, and rephosphorylated immediately following fertilization. The phosphorylated regions consist largely of repeating tetrapeptides with two basic residues flanking Ser-Pro residues ('SPKK' motifs) and are predicted to have beta-turn secondary structures. Alteration of the charge and structure of the SPKK sites may play a role in the unusually dense DNA packaging of the mature sperm chromatin. The motif resembles the target site of cell-cycle-associated cdc2 kinases and is found in several other proteins whose nucleic acid affinities may be altered during the cell cycle.


Subject(s)
Genome , Sea Urchins/genetics , Amino Acid Sequence , Animals , CDC2 Protein Kinase/genetics , Cell Cycle/physiology , DNA/physiology , Histones/genetics , Histones/physiology , Male , Molecular Sequence Data , Phosphorylation , Spermatozoa
18.
Nat Neurosci ; 1(1): 74-9, 1998 May.
Article in English | MEDLINE | ID: mdl-10195113

ABSTRACT

Changes in the delay (phase) and amplitude of sound at the ears are cues for the analysis of sound movement. The detection of these cues depends on the convergence of the inputs to each ear, a process that first occurs in the brainstem. The conscious perception of these cues is likely to involve higher centers. Using novel stimuli that produce different perceptions of movement in the presence of identical phase and amplitude modulation components, we have demonstrated human brain areas that are active specifically during the perception of sound movement. Both functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) demonstrated the involvement of the right parietal cortex in sound movement perception with these stimuli.


Subject(s)
Auditory Perception/physiology , Dominance, Cerebral/physiology , Parietal Lobe/physiology , Acoustic Stimulation/methods , Brain Mapping , Cues , Humans , Loudness Perception/physiology , Magnetic Resonance Imaging , Parietal Lobe/anatomy & histology , Parietal Lobe/diagnostic imaging , Psychophysics/methods , Time Perception/physiology , Tomography, Emission-Computed
19.
Zoonoses Public Health ; 65(5): 490-500, 2018 08.
Article in English | MEDLINE | ID: mdl-29603886

ABSTRACT

Baylisascaris procyonis, the raccoon roundworm, is a zoonotic ascarid of importance to human and animal health. Wildlife rehabilitators who care for raccoons may be at an increased risk for exposure to the parasite, especially if proper precautions are not taken. In a wider effort to evaluate awareness regarding B. procyonis in the wildlife rehabilitation community, an online survey (38-39 questions) including questions about B. procyonis knowledge and attitudes was developed and administered to wildlife rehabilitators. To assess precautions taken among raccoon rehabilitators, participants who rehabilitated raccoons (n = 447) answered additional questions about use of personal protective equipment (PPE) and infection control practices (ICPs). Reported use of gloves was variable, but hand hygiene was generally consistent. Masks and gowns were seldom used. Part-time or infrequent volunteers and rehabilitators located in the Central, Midwest and Southeast were significantly less likely to report consistent use of PPE. A total knowledge score from the survey was used to predict the likelihood of reporting the use of particular ICPs/PPE. Knowledge score had a highly significant but small effect on the likelihood of prophylactic use of anthelmintics, anthelmintics use for B. procyonis specifically, cleaning appropriately, and using species-dedicated housing. Risk factor analysis was performed on data from a prior serologic survey to evaluate factors associated with exposure to B. procyonis and inconsistent handwashing after contact with live raccoons and their faeces; practising rehabilitation in B. procyonis hyperendemic regions and practising rehabilitation in the western region were significant risk factors for being seropositive. These data further demonstrate that correct PPE/ICPs are critical in mitigating the risk of B. procyonis exposure among raccoon rehabilitators and among other captive species.


Subject(s)
Ascaridida Infections/prevention & control , Ascaridoidea , Infection Control/methods , Personal Protective Equipment , Raccoons/parasitology , Zoonoses , Adult , Animal Husbandry , Animals , Animals, Wild , Feces/parasitology , Female , Humans , Male , Risk Factors
20.
Zoonoses Public Health ; 65(1): e130-e142, 2018 02.
Article in English | MEDLINE | ID: mdl-29124901

ABSTRACT

Wildlife rehabilitators are at risk of zoonotic diseases because they often have prolonged contact with many species of wildlife and their bodily fluids. Raccoon roundworm (Baylisascaris procyonis) is a common zoonotic parasite of raccoons that has the potential to cause severe or fatal neurologic disease in a broad variety of hosts if the eggs within raccoon faeces are ingested. We administered an online survey to wildlife rehabilitators to assess their knowledge regarding aspects of transmission, biology and disease caused by B. procyonis, and also to evaluate attitudes towards wildlife diseases and B. procyonis as an occupational hazard. Knowledge was assessed using multiple choice and true-false questions; attitudes were measured using Likert-type items. A total of 659 complete or near-complete responses (missing fewer than three knowledge or attitudes items and/or non-response to some demographic fields) were collected. The median knowledge score was 7/14 questions correct (range: 0-14 correct). Generally, individuals with higher levels of education and rehabilitation experience, veterinary professionals and those who are members of professional wildlife rehabilitation groups scored above the median significantly more often (p < .01). Significantly more rehabilitators who were located in the south-east and those with part-time or infrequent commitments scored below the median overall knowledge score. There was general agreement that B. procyonis is a health risk of rehabilitators and that measures should be taken to control transmission to people and animals. Some factors explaining differences in attitudes include setting of rehabilitation (home versus animal care facility), veterinary profession, region, membership in a wildlife rehabilitation group and rehabilitation of raccoons. Findings emphasize the importance of awareness and mentorship to inform rehabilitators on the potential risks of B. procyonis and other potential zoonoses within captive wildlife settings, and the important role of professional wildlife rehabilitator groups in disseminating educational materials.


Subject(s)
Ascaridoidea , Raccoons/parasitology , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Animals, Wild , Ascaridida Infections/transmission , Data Collection , Female , Health Knowledge, Attitudes, Practice , Humans , Internet , Male , Middle Aged , Risk Factors , Surveys and Questionnaires , Young Adult , Zoonoses
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