This is a cross-sectional, observational study to determine the frequency and associated features of HIV-associated neurocognitive disorders (HAND) in a large, diverse sample of infected individuals ...in the era of combination antiretroviral therapy (CART).
A total of 1,555 HIV-infected adults were recruited from 6 university clinics across the United States, with minimal exclusions. We used standardized neuromedical, psychiatric, and neuropsychological (NP) examinations, and recently published criteria for diagnosing HAND and classifying 3 levels of comorbidity (minimal to severe non-HIV risks for NP impairment).
Fifty-two percent of the total sample had NP impairment, with higher rates in groups with greater comorbidity burden (40%, 59%, and 83%). Prevalence estimates for specific HAND diagnoses (excluding severely confounded cases) were 33% for asymptomatic neurocognitive impairment, 12% for mild neurocognitive disorder, and only 2% for HIV-associated dementia (HAD). Among participants with minimal comorbidities (n = 843), history of low nadir CD4 was a strong predictor of impairment, and the lowest impairment rate on CART occurred in the subset with suppressed plasma viral loads and nadir CD4 ≥200 cells/mm(3) (30% vs 47% in remaining subgroups).
The most severe HAND diagnosis (HAD) was rare, but milder forms of impairment remained common, even among those receiving CART who had minimal comorbidities. Future studies should clarify whether early disease events (e.g., profound CD4 decline) may trigger chronic CNS changes, and whether early CART prevents or reverses these changes.
A suite of climate change indices derived from daily temperature and precipitation data, with a primary focus on extreme events, were computed and analyzed. By setting an exact formula for each index ...and using specially designed software, analyses done in different countries have been combined seamlessly. This has enabled the presentation of the most up‐to‐date and comprehensive global picture of trends in extreme temperature and precipitation indices using results from a number of workshops held in data‐sparse regions and high‐quality station data supplied by numerous scientists world wide. Seasonal and annual indices for the period 1951–2003 were gridded. Trends in the gridded fields were computed and tested for statistical significance. Results showed widespread significant changes in temperature extremes associated with warming, especially for those indices derived from daily minimum temperature. Over 70% of the global land area sampled showed a significant decrease in the annual occurrence of cold nights and a significant increase in the annual occurrence of warm nights. Some regions experienced a more than doubling of these indices. This implies a positive shift in the distribution of daily minimum temperature throughout the globe. Daily maximum temperature indices showed similar changes but with smaller magnitudes. Precipitation changes showed a widespread and significant increase, but the changes are much less spatially coherent compared with temperature change. Probability distributions of indices derived from approximately 200 temperature and 600 precipitation stations, with near‐complete data for 1901–2003 and covering a very large region of the Northern Hemisphere midlatitudes (and parts of Australia for precipitation) were analyzed for the periods 1901–1950, 1951–1978 and 1979–2003. Results indicate a significant warming throughout the 20th century. Differences in temperature indices distributions are particularly pronounced between the most recent two periods and for those indices related to minimum temperature. An analysis of those indices for which seasonal time series are available shows that these changes occur for all seasons although they are generally least pronounced for September to November. Precipitation indices show a tendency toward wetter conditions throughout the 20th century.
We compare global‐scale changes in satellite estimates of the temperature of the lower troposphere (TLT) with model simulations of forced and unforced TLT changes. While previous work has focused on ...a single period of record, we select analysis timescales ranging from 10 to 32 years, and then compare all possible observed TLT trends on each timescale with corresponding multi‐model distributions of forced and unforced trends. We use observed estimates of the signal component of TLT changes and model estimates of climate noise to calculate timescale‐dependent signal‐to‐noise ratios (S/N). These ratios are small (less than 1) on the 10‐year timescale, increasing to more than 3.9 for 32‐year trends. This large change in S/N is primarily due to a decrease in the amplitude of internally generated variability with increasing trend length. Because of the pronounced effect of interannual noise on decadal trends, a multi‐model ensemble of anthropogenically‐forced simulations displays many 10‐year periods with little warming. A single decade of observational TLT data is therefore inadequate for identifying a slowly evolving anthropogenic warming signal. Our results show that temperature records of at least 17 years in length are required for identifying human effects on global‐mean tropospheric temperature.
Key Points
Models run with human forcing can produce 10‐year periods with little warming
S/N ratios for tropospheric temp. are ∼1 for 10‐yr trends, ∼4 for 32‐yr trends
Trends >17 yrs are required for identifying human effects on tropospheric temp
ABSTRACT The evolution of a coronal loop is studied by means of numerical simulations of the fully compressible three-dimensional magnetohydrodynamic equations using the HYPERION code. The footpoints ...of the loop magnetic field are advected by random motions. As a consequence, the magnetic field in the loop is energized and develops turbulent nonlinear dynamics characterized by the continuous formation and dissipation of field-aligned current sheets: energy is deposited at small scales where heating occurs. Dissipation is nonuniformly distributed so that only a fraction of the coronal mass and volume gets heated at any time. Temperature and density are highly structured at scales that, in the solar corona, remain observationally unresolved: the plasma of our simulated loop is multithermal, where highly dynamical hotter and cooler plasma strands are scattered throughout the loop at sub-observational scales. Numerical simulations of coronal loops of 50,000 km length and axial magnetic field intensities ranging from 0.01 to 0.04 T are presented. To connect these simulations to observations, we use the computed number densities and temperatures to synthesize the intensities expected in emission lines typically observed with the Extreme Ultraviolet Imaging Spectrometer on Hinode. These intensities are used to compute differential emission measure distributions using the Monte Carlo Markov Chain code, which are very similar to those derived from observations of solar active regions. We conclude that coronal heating is found to be strongly intermittent in space and time, with only small portions of the coronal loop being heated: in fact, at any given time, most of the corona is cooling down.
• Studies of ectomycorrhizal fungal communities in forest soils are usually restricted to the uppermost organic horizons. Boreal forest podzols are highly stratified and little is known about the ...vertical distribution of ectomycorrhizal communities in the underlying mineral horizons. • Ectomycorrhizal root tips were sampled from seven horizons in three continuous columns of a 52-cm deep podzol profile. Root tips were sorted into morphological groups and the colonising fungi identified by sequencing of the rDNA ITS region. The vertical distribution of mycorrhizal taxa was examined. • A relationship between ectomycorrhizal species composition and soil horizon was found. Tomentellopsis submollis, three Piloderma species and Dermocybe spp. were found predominantly in the upper horizons while Suillus luteus, Lactarius utilis and three undescribed Piloderma species were associated with the mineral horizons. • Two thirds of the root tips were found in the mineral soil and half of the taxa were restricted to the mineral horizons. The results highlight the need to include the mineral soil in order to gain a more accurate representation of the ectomycorrhizal community.
Based upon preclinical synergy in murine models, we carried out a phase I trial to determine the maximum tolerated dose (MTD), toxicities, pharmacokinetics, and biomarkers of response for the ...combination of BKM120, a PI3K inhibitor, and olaparib, a PARP inhibitor.
Olaparib was administered twice daily (tablet formulation) and BKM120 daily on a 28-day cycle, both orally. A 3 + 3 dose-escalation design was employed with the primary objective of defining the combination MTD, and secondary objectives were to define toxicities, activity, and pharmacokinetic profiles. Eligibility included recurrent breast (BC) or ovarian cancer (OC); dose-expansion cohorts at the MTD were enrolled for each cancer.
In total, 69 of 70 patients enrolled received study treatment; one patient never received study treatment because of ineligibility. Twenty-four patients had BC; 46 patients had OC. Thirty-five patients had a germlineBRCA mutation (gBRCAm). Two DLTs (grade 3 transaminitis and hyperglycemia) were observed at DL0 (BKM120 60 mg/olaparib and 100 mg b.i.d.). The MTD was determined to be BKM120 50 mg q.d. and olaparib 300 mg b.i.d. (DL8). Additional DLTs included grade 3 depression and transaminitis, occurring early in cycle 2 (DL7). Anticancer activity was observed in BC and OC and in gBRCAm and gBRCA wild-type (gBRCAwt) patients.
BKM120 and olaparib can be co-administered, but the combination requires attenuation of the BKM120 dose. Clinical benefit was observed in both gBRCAm and gBRCAwt pts. Randomized phase II studies will be needed to further define the efficacy of PI3K/PARP-inhibitor combinations as compared with a PARP inhibitor alone.
Visual neurons respond selectively to features that become increasingly complex from the eyes to the cortex. Retinal neurons prefer flashing spots of light, primary visual cortical (V1) neurons ...prefer moving bars, and those in higher cortical areas favor complex features like moving textures. Previously, we showed that V1 simple cell tuning can be accounted for by a basic model implementing temporal prediction - representing features that predict future sensory input from past input (Singer et al., 2018). Here, we show that hierarchical application of temporal prediction can capture how tuning properties change across at least two levels of the visual system. This suggests that the brain does not efficiently represent all incoming information; instead, it selectively represents sensory inputs that help in predicting the future. When applied hierarchically, temporal prediction extracts time-varying features that depend on increasingly high-level statistics of the sensory input.
Unmanned aerial vehicle (UAV)-based remote sensing is gaining momentum in a variety of agricultural and environmental applications. Very-high-resolution remote sensing image sets collected repeatedly ...throughout a crop growing season are becoming increasingly common. Analytical methods able to learn from both spatial and time dimensions of the data may allow for an improved estimation of crop traits, as well as the effects of genetics and the environment on these traits. Multispectral and geometric time series imagery was collected by UAV on 11 dates, along with ground-truth data, in a field trial of 866 genetically diverse biomass sorghum accessions. We compared the performance of Convolution Neural Network (CNN) architectures that used image data from single dates (two spatial dimensions, 2D) versus multiple dates (two spatial dimensions + temporal dimension, 3D) to estimate lodging detection and severity. Lodging was detected with 3D-CNN analysis of time series imagery with 0.88 accuracy, 0.92 Precision, and 0.83 Recall. This outperformed the best 2D-CNN on a single date with 0.85 accuracy, 0.84 Precision, and 0.76 Recall. The variation in lodging severity was estimated by the best 3D-CNN analysis with 9.4% mean absolute error (MAE), 11.9% root mean square error (RMSE), and goodness-of-fit (R2) of 0.76. This was a significant improvement over the best 2D-CNN analysis with 11.84% MAE, 14.91% RMSE, and 0.63 R2. The success of the improved 3D-CNN analysis approach depended on the inclusion of “before and after” data, i.e., images collected on dates before and after the lodging event. The integration of geometric and spectral features with 3D-CNN architecture was also key to the improved assessment of lodging severity, which is an important and difficult-to-assess phenomenon in bioenergy feedstocks such as biomass sorghum. This demonstrates that spatio-temporal CNN architectures based on UAV time series imagery have significant potential to enhance plant phenotyping capabilities in crop breeding and Precision agriculture applications.
Genera of phytopathogenic fungi: GOPHY 2 Marin-Felix, Y.; Hernández-Restrepo, M.; Wingfield, M.J. ...
Studies in mycology,
03/2019, Volume:
92, Issue:
1
Journal Article
Peer reviewed
Open access
This paper represents the second contribution in the Genera of Phytopathogenic Fungi (GOPHY) series. The series provides morphological descriptions and information regarding the pathology, ...distribution, hosts and disease symptoms for the treated genera. In addition, primary and secondary DNA barcodes for the currently accepted species are included. This second paper in the GOPHY series treats 20 genera of phytopathogenic fungi and their relatives including: Allantophomopsiella, Apoharknessia, Cylindrocladiella, Diaporthe, Dichotomophthora, Gaeumannomyces, Harknessia, Huntiella, Macgarvieomyces, Metulocladosporiella, Microdochium, Oculimacula, Paraphoma, Phaeoacremonium, Phyllosticta, Proxypiricularia, Pyricularia, Stenocarpella, Utrechtiana and Wojnowiciella. This study includes the new genus Pyriculariomyces, 20 new species, five new combinations, and six typifications for older names.
Metastatic outgrowth in breast cancer can occur years after a seeming cure. Existing model systems of dormancy are limited as they do not recapitulate human metastatic dormancy without exogenous ...manipulations and are unable to query early events of micrometastases.
Here, we describe a human ex vivo hepatic microphysiologic system. The system is established with fresh human hepatocytes and non-parenchymal cells (NPCs) creating a microenvironment into which breast cancer cells (MCF7 and MDA-MB-231) are added.
The hepatic tissue maintains function through 15 days as verified by liver-specific protein production and drug metabolism assays. The NPCs form an integral part of the hepatic niche, demonstrated within the system through their participation in differential signalling cascades and cancer cell outcomes. Breast cancer cells intercalate into the hepatic niche without interfering with hepatocyte function. Examination of cancer cells demonstrated that a significant subset enter a quiescent state of dormancy as shown by lack of cell cycling (EdU(-) or Ki67(-)). The presence of NPCs altered the cancer cell fraction entering quiescence, and lead to differential cytokine profiles in the microenvironment effluent.
These findings establish the liver microphysiologic system as a relevant model for the study of breast cancer metastases and entry into dormancy.
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