Childhood maltreatment or abuse is a major risk factor for mood, anxiety, substance abuse, psychotic, and personality disorders, and it is associated with reduced adult hippocampal volume, ...particularly on the left side. Translational studies show that the key consequences of stress exposure on the hippocampus are suppression of neurogenesis in the dentate gyrus (DG) and dendritic remodeling in the cornu ammonis (CA), particularly the CA3 subfield. The hypothesis that maltreatment is associated with volume reductions in 3-T MRI subfields containing the DG and CA3 was assessed and made practical by newly released automatic segmentation routines for FreeSurfer. The sample consisted of 193 unmedicated right-handed subjects (38% male, 21.9 ± 2.1 y of age) selected from the community. Maltreatment was quantified using the Adverse Childhood Experience study and Childhood Trauma Questionnaire scores. The strongest associations between maltreatment and volume were observed in the left CA2-CA3 and CA4-DG subfields, and were not mediated by histories of major depression or posttraumatic stress disorder. Comparing subjects with high vs. low scores on the Childhood Trauma Questionnaire and Adverse Childhood Experience study showed an average volume reduction of 6.3% and 6.1% in the left CA2-CA3 and CA4-DG, respectively. Volume reductions in the CA1 and fimbria were 44% and 60% smaller than in the CA2-CA3. Interestingly, maltreatment was associated with 4.2% and 4.3% reductions in the left presubiculum and subiculum, respectively. These findings support the hypothesis that exposure to early stress in humans, as in other animals, affects hippocampal subfield development.
Network perspectives, in their emphasis on components and their interactions, might afford the best approach to the complexities of the ASD realm. Categorical approaches are unlikely to be fruitful ...as one should not expect to find a single or even predominant underlying cause of autism behavior across individuals. It is possible that the complex, highly interactive, heterogeneous and individualistic nature of the autism realm is intractable in terms of identifying clinically useful biomarker tests. It is hopeful from an emergenic perspective that small corrective changes in a single component of a deleterious network/configuration might have large beneficial consequences on developmental trajectories and in later treatment. It is suggested that the relationship between ASD and intellectual disability might be fundamentally different in single-gene versus nonsyndromic ASD. It is strongly stated that available biomarker “tests” for autism/ASD will do more harm than good. Finally, the serotonin–melatonin-oxidative stress-placental intersection might be an especially fruitful area of biological investigation.
The organization and integrity of epithelial tight junctions depend on interactions between claudins, ZO scaffolding proteins, and the cytoskeleton. However, although binding between claudins and ...ZO-1/2/3 and between ZO-1/2/3 and numerous cytoskeletal proteins has been demonstrated in vitro, fluorescence recovery after photobleaching analysis suggests interactions in vivo are likely highly dynamic. Here we use superresolution live-cell imaging in a model fibroblast system to examine relationships between claudins, ZO-1, occludin, and actin. We find that GFP claudins make easily visualized dynamic strand patches between two fibroblasts; strand dynamics is constrained by ZO-1 binding. Claudin association with actin is also dependent on ZO-1, but colocalization demonstrates intermittent rather than continuous association between claudin, ZO-1, and actin. Independent of interaction with ZO-1 or actin, claudin strands break and reanneal; pulse-chase-pulse analysis using SNAP-tagged claudins showed preferential incorporation of newly synthesized claudins into break sites. Although claudin strand behavior in fibroblasts may not fully recapitulate that of epithelial tight junction strands, this is the first direct demonstration of the ability of ZO-1 to stabilize claudin strands. We speculate that intermittent tethering of claudins to actin may allow for accommodation of the paracellular seal to physiological or pathological alterations in cell shape or movement.
Canonical correlation analysis (CCA) has become a key tool for population neuroimaging, allowing investigation of associations between many imaging and non-imaging measurements. As age, sex and other ...variables are often a source of variability not of direct interest, previous work has used CCA on residuals from a model that removes these effects, then proceeded directly to permutation inference. We show that a simple permutation test, as typically used to identify significant modes of shared variation on such data adjusted for nuisance variables, produces inflated error rates. The reason is that residualisation introduces dependencies among the observations that violate the exchangeability assumption. Even in the absence of nuisance variables, however, a simple permutation test for CCA also leads to excess error rates for all canonical correlations other than the first. The reason is that a simple permutation scheme does not ignore the variability already explained by previous canonical variables. Here we propose solutions for both problems: in the case of nuisance variables, we show that transforming the residuals to a lower dimensional basis where exchangeability holds results in a valid permutation test; for more general cases, with or without nuisance variables, we propose estimating the canonical correlations in a stepwise manner, removing at each iteration the variance already explained, while dealing with different number of variables in both sides. We also discuss how to address the multiplicity of tests, proposing an admissible test that is not conservative, and provide a complete algorithm for permutation inference for CCA.
Glutamine is a major dietary amino acid that is both a fuel and nitrogen donor for healing tissues damaged by chemotherapy and radiation. Evidence supports the benefit of oral (enteral) glutamine to ...reduce symptoms and improve and/or maintain quality of life of cancer patients. Benefits include not only better nutrition, but also decreased mucosal damage (mucositis, stomatitis, pharyngitis, esophagitis, and enteritis). Glutamine supplementation in a high protein diet (10 grams/day) + disaccharides, such as sucrose and/or trehalose, is a combination that increases glutamine uptake by mucosal cells. This increased topical effect can reduce painful mucosal symptoms and ulceration associated with chemotherapy and radiation in the head and neck region, esophagus, stomach and small intestine. Topical and oral glutamine seem to be the preferred routes for this amino acid to promote mucosal healing during and after cancer treatment.
Tending the wild Anderson, Kat
2005, 20050515, 2005-06-14
eBook, Book
John Muir was an early proponent of a view we still hold today-that much of California was pristine, untouched wilderness before the arrival of Europeans. But as this groundbreaking book ...demonstrates, what Muir was really seeing when he admired the grand vistas of Yosemite and the gold and purple flowers carpeting the Central Valley were the fertile gardens of the Sierra Miwok and Valley Yokuts Indians, modified and made productive by centuries of harvesting, tilling, sowing, pruning, and burning. Marvelously detailed and beautifully written,Tending the Wildis an unparalleled examination of Native American knowledge and uses of California's natural resources that reshapes our understanding of native cultures and shows how we might begin to use their knowledge in our own conservation efforts. M. Kat Anderson presents a wealth of information on native land management practices gleaned in part from interviews and correspondence with Native Americans who recall what their grandparents told them about how and when areas were burned, which plants were eaten and which were used for basketry, and how plants were tended. The complex picture that emerges from this and other historical source material dispels the hunter-gatherer stereotype long perpetuated in anthropological and historical literature. We come to see California's indigenous people as active agents of environmental change and stewardship.Tending the Wild persuasively argues that this traditional ecological knowledge is essential if we are to successfully meet the challenge of living sustainably.
Summary Background Artemisinin-resistant Plasmodium falciparum has been reported in Pailin, western Cambodia, detected as a slow parasite clearance rate in vivo. Emergence of this phenotype in ...western Thailand and possibly elsewhere threatens to compromise the effectiveness of all artemisinin-based combination therapies. Parasite genetics is associated with parasite clearance rate but does not account for all variation. We investigated contributions of both parasite genetics and host factors to the artemisinin-resistance phenotype in Pursat, western Cambodia. Methods Between June 19 and Nov 28, 2009, and June 26 and Dec 6, 2010, we enrolled patients aged 10 years or older with uncomplicated falciparum malaria, a density of asexual parasites of at least 10 000 per μL of whole blood, no symptoms or signs of severe malaria, no other cause of febrile illness, and no chronic illness. We gave participants 4 mg/kg artesunate at 0, 24, and 48 h, 15 mg/kg mefloquine at 72 h, and 10 mg/kg mefloquine at 96 h. We assessed parasite density on thick blood films every 6 h until undetectable. The parasite clearance half-life was calculated from the parasite clearance curve. We genotyped parasites with 18 microsatellite markers and patients for haemoglobin E, α-thalassaemia, and a mutation of G6PD , which encodes glucose-6-phosphate dehydrogenase. To account for the possible effects of acquired immunity on half-life, we used three surrogates for increased likelihood of exposure to P falciparum : age, sex, and place of residence. This study is registered with ClinicalTrials.gov , number NCT00341003. Findings We assessed 3504 individuals from all six districts of Pursat province seeking treatment for malaria symptoms. We enrolled 168 patients with falciparum malaria who met inclusion criteria. The geometric mean half-life was 5·85 h (95% CI 5·54–6·18) in Pursat, similar to that reported in Pailin (p=0·109). We identified two genetically different parasite clone groups: parasite group 1 (PG1) and parasite group 2 (PG2). Non-significant increases in parasite clearance half-life were seen in patients with haemoglobin E (0·55 h; p=0·078), those of male sex (0·96 h; p=0·064), and in 2010 (0·68 h; p=0·068); PG1 was associated with a significant increase (0·79 h; p=0·033). The mean parasite heritability of half-life was 0·40 (SD 0·17). Interpretation Heritable artemisinin resistance is established in a second Cambodian province. To accurately identify parasites that are intrinsically susceptible or resistant to artemisinins, future studies should explore the effect of erythrocyte polymorphisms and specific immune responses on half-life variation. Funding Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.
Debate over the cardiometabolic risk associated with metabolically healthy obesity (MHO) continues. Many studies have investigated this relationship by examining MHO at baseline with longitudinal ...follow-up, with inconsistent results.
The authors hypothesized that MHO at baseline is transient and that transition to metabolic syndrome (MetS) and duration of MetS explains heterogeneity in incident cardiovascular disease (CVD) and all-cause mortality.
Among 6,809 participants of the MESA (Multi-Ethnic Study of Atherosclerosis) the authors used Cox proportional hazards and logistic regression models to investigate the joint association of obesity (≥30 kg/m2) and MetS (International Diabetes Federation consensus definition) with CVD and mortality across a median of 12.2 years. We tested for interaction and conducted sensitivity analyses for a number of conditions.
Compared with metabolically healthy normal weight, baseline MHO was not significantly associated with incident CVD; however, almost one-half of those participants developed MetS during follow-up (unstable MHO). Those who had unstable MHO had increased odds of CVD (odds ratio OR: 1.60; 95% confidence interval CI: 1.14 to 2.25), compared with those with stable MHO or healthy normal weight. Dose response for duration of MetS was significantly and linearly associated with CVD (1 visit with MetS OR: 1.62; 95% CI: 1.27 to 2.07; 2 visits, OR: 1.92; 95% CI: 1.48 to 2.49; 3+ visits, OR: 2.33; 95% CI: 1.89 to 2.87; p value for trend <0.001) and MetS mediated approximately 62% (44% to 100%) of the relationship between obesity at any point during follow-up and CVD.
Metabolically healthy obesity is not a stable or reliable indicator of future risk for CVD. Weight loss and lifestyle management for CVD risk factors should be recommended to all individuals with obesity.
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The efficiency of generating electricity from heat using concentrated solar power plants (which use mirrors or lenses to concentrate sunlight in order to drive heat engines, usually involving ...turbines) may be appreciably increased by operating with higher turbine inlet temperatures, but this would require improved heat exchanger materials. By operating turbines with inlet temperatures above 1,023 kelvin using closed-cycle high-pressure supercritical carbon dioxide (sCO
) recompression cycles, instead of using conventional (such as subcritical steam Rankine) cycles with inlet temperatures below 823 kelvin
, the relative heat-to-electricity conversion efficiency may be increased by more than 20 per cent. The resulting reduction in the cost of dispatchable electricity from concentrated solar power plants (coupled with thermal energy storage
) would be an important step towards direct competition with fossil-fuel-based plants and a large reduction in greenhouse gas emissions
. However, the inlet temperatures of closed-cycle high-pressure sCO
turbine systems are limited
by the thermomechanical performance of the compact, metal-alloy-based, printed-circuit-type heat exchangers used to transfer heat to sCO
. Here we present a robust composite of ceramic (zirconium carbide, ZrC) and the refractory metal tungsten (W) for use in printed-circuit-type heat exchangers at temperatures above 1,023 kelvin
. This composite has attractive high-temperature thermal, mechanical and chemical properties and can be processed in a cost-effective manner. We fabricated ZrC/W-based heat exchanger plates with tunable channel patterns by the shape-and-size-preserving chemical conversion of porous tungsten carbide plates. The dense ZrC/W-based composites exhibited failure strengths of over 350 megapascals at 1,073 kelvin, and thermal conductivity values two to three times greater than those of iron- or nickel-based alloys at this temperature. Corrosion resistance to sCO
at 1,023 kelvin and 20 megapascals was achieved
by bonding a copper layer to the composite surface and adding 50 parts per million carbon monoxide to sCO
. Techno-economic analyses indicate that ZrC/W-based heat exchangers can strongly outperform nickel-superalloy-based printed-circuit heat exchangers at lower cost.
We present the discovery of a nuclear transient with the Caltech–NRAO Stripe 82 Survey (CNSS), a dedicated radio transient survey carried out with the Karl G.Jansky Very Large Array (VLA). This ...transient, CNSS J001947.3+003527, exhibited a turn-on over a timescale of <~1 yr, increasing in flux density at 3 GHz from <0.14 mJy in 2014 February to 4.4 ± 0.1 mJy in 2015 March, reaching a peak luminosity of 5 x 10^28 erg s-1 Hz-1 around 2015 October. The association of CNSS J0019+00 with the nucleus (Gaia and
our very-long baseline interferometry positions are consistent to within 1 pc) of a nearby S0 Seyfert galaxy at 77 Mpc, together with the radio spectral evolution, implies that this transient is most likely a tidal disruption event (TDE). Our equipartition analysis indicates the presence of a ∼15,000 km s−1 outflow, having energy ∼1049 erg. We derive the radial density profile for the circumnuclear material in the host galaxy to be proportional to R−2.5. All of these properties suggest resemblance with radio-detected thermal TDEs like ASASSN-14li and XMMSL1 J0740-85. No significant X-ray or optical emission is detected from CNSS J0019+00, although this may simply be due to the thermal emission being weak during our late-time follow-up observations. From the CNSS survey we have obtained the first unbiased measurement of the rate of radio TDEs, R(>500μJy) of about 2 × 10−3 deg−2, or equivalently a volumetric rate of about 10 Gpc−3 yr−1. This rate implies that all-sky radio surveys such as the VLA Sky Survey and those planned with ASKAP, will find many tens of radio TDEs over the next few years.
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