We present observations of the A7 IV-V star Alderamin (a Cep, HR 8162, HD 203280) from the Georgia State University CHARA Array. These infrared interferometric angular size measurements indicate a ...noncircular projected disk brightness distribution for this known rapid rotator. The interferometric observations are modeled as arising from an elongated rigid atmosphere, with apparent polar and equatorial radii of r sub(p) = 0.6753 super(+) sub(-) super(0) sub(0) super(.) sub(.) super(0) sub(0) super(1) sub(1) super(1) sub(3) super(9) sub(5) and r sub(e) = 0.8767 super(+) sub(-) super(0) sub(0) super(.) sub(.) super(0) sub(0) super(2) sub(1) super(9) sub(8) super(3) sub(3) mas, respectively, for a difference of 201 c 32 kas, and with an axial ratio of r sub(e)/r sub(p) = 1.298 c 0.051. Using the Hipparcos distance of 14.96 c 0.11 pc, these angular measures translate to 2.18 c 0.05 and 2.82 c 0.10 R sub( )The inclination of + 1.S Alderamin to the line of sight indicated by this modeling is effectively edge-on (i = 88.2 super(+) sub(-) super(1) sub(1) super(.) sub(3) super(8) sub(.3) deg). The star has a true rotational velocity of 283 c10 km s super(-1) (683% of breakup velocity) and a polar temperature of roughly 8400 K. Significantly, a necessary aspect of this modeling is a determination of the gravity-darkening coefficient, which at a value of b = 0.084 -0.049 is consistent with a convective photosphere, as expected for an A7 IV-V star. Our detailed characterization of this object allows us to investigate various scenarios for the angular momentum history of Alderamin and the appropriateness of certain stellar evolution models.
Considerable research has been conducted seeking risk factors and constructing prediction models for transition to psychosis in individuals at ultra-high risk (UHR). Nearly all such research has only ...employed baseline predictors, i.e. data collected at the baseline time point, even though longitudinal data on relevant measures such as psychopathology have often been collected at various time points. Dynamic prediction, which is the updating of prediction at a post-baseline assessment using baseline and longitudinal data accumulated up to that assessment, has not been utilized in the UHR context. This study explored the use of dynamic prediction and determined if it could enhance the prediction of frank psychosis onset in UHR individuals. An emerging statistical methodology called joint modelling was used to implement the dynamic prediction. Data from the NEURAPRO study (n = 304 UHR individuals), an intervention study with transition to psychosis study as the primary outcome, were used to investigate dynamic predictors. Compared with the conventional approach of using only baseline predictors, dynamic prediction using joint modelling showed significantly better sensitivity, specificity and likelihood ratios. As dynamic prediction can provide an up-to-date prediction for each individual at each new assessment post entry, it can be a useful tool to help clinicians adjust their prognostic judgements based on the unfolding clinical symptomatology of the patients. This study has shown that a dynamic approach to psychosis prediction using joint modelling has the potential to aid clinicians in making decisions about the provision of timely and personalized treatment to patients concerned.
Background and Aims
Predicted impacts of climate change—increased temperature, decreased rainfall, and reduced water availability—are expected to increase irrigation‐related salinity in Australia's ...major wine regions. Breeding of new abiotic stress‐tolerant rootstocks will help to mitigate these effects on viticulture. Here, we investigated the impact of elevated temperature on key salt tolerance traits of two contrasting rootstocks and a population of experimental rootstock hybrids.
Methods and Results
A high‐throughput facility was used to phenotype the rootstocks, K51‐40, 140 Ruggeri and 68 K51‐40 derived hybrids, all ungrafted, under factorial salinity and temperature treatments. Elevated temperature led to increased chloride concentration in the mature laminae of most genotypes, likely driven by increased transpiration, with large differences between genotypes in the extent of the temperature response. Genetic differences were also observed for the influence of temperature on laminae sodium accumulation. Growth rate response to salinity was variable between genotypes and was independent of laminae chloride and sodium accumulation.
Conclusions
High‐throughput phenomics provides a promising tool to simultaneously assess new rootstock selections for ion exclusion and growth rate response under abiotic stresses.
Significance of the Study
Understanding the effect of temperature on salinity tolerance traits, and the development of novel screening tools, will help breed new rootstocks better suited to a hotter and drier future climate.
There has been limited research into the predictive value of basic symptoms and their relationship with other psychopathology in patients identified using the ‘ultra high risk’ (UHR) for psychosis ...approach. The current study investigated whether basic symptoms, specifically cognitive disturbances (COGDIS), were associated with a greater risk of transition to psychotic disorder and persistent attenuated psychotic symptoms (APS) at medium term follow-up (mean = 3.4 years) in UHR patients, as well as with general psychopathology at baseline. The sample included 304 UHR participants (mean age = 19.12 years) involved in an international multicenter trial of omega-3 fatty acids. UHR individuals who also met the COGDIS criteria (basic symptoms risk criteria) did not have a greater risk of transition than those who met the UHR criteria alone. However, meeting COGDIS risk criteria was associated with a greater likelihood of meeting the UHR attenuated psychotic symptoms risk group (i.e., having persistent attenuated psychotic symptoms) at 12-month follow-up (odds ratio = 1.85; 95% CI = 1.03, 3.32). Greater severity of cognitive basic symptoms was also independently associated with more severe general psychopathology at study entry. The findings do not support the notion that combined risk identification approaches (UHR and basic symptoms) aid in the identification of individuals at greatest risk of psychosis, although this interpretation is limited by the modest transition to psychosis rate (13%) and the time of follow up. However, the findings indicate that basic symptoms may be a clinically useful marker of more severe general psychopathology in UHR groups and risk for persistent attenuated psychotic symptoms.
Antiretroviral therapy is unable to eliminate HIV infection in a small, long-lived population of latently infected T cells, providing a source for renewed viral replication following cessation of ...therapy. Analysis of individual latently infected cells generated in the SCID-hu (Thy/Liv) mouse demonstrated no functional viral RNA produced in the latent state. Following reactivation viral expression was dramatically increased, rendering the infected cells susceptible to an anti-HIV immunotoxin. Treatment with the immunotoxin in conjunction with agents that activate virus expression without inducing cell division (IL-7 or the non-tumor-promoting phorbol ester prostratin) depleted the bulk of the latent reservoir and left uninfected cells able to respond to subsequent costimulation. We demonstrate that activation of latent virus is required for targeting by antiviral agents and provide the basis for future therapeutic strategies to eradicate the latent reservoir.
The complete genome sequence of Geobacter sulfurreducens, a δ-proteobacterium, reveals unsuspected capabilities, including evidence of aerobic metabolism, one-carbon and complex carbon metabolism, ...motility, and chemotactic behavior. These characteristics, coupled with the possession of many two-component sensors and many c-type cytochromes, reveal an ability to create alternative, redundant, electron transport networks and offer insights into the process of metal ion reduction in subsurface environments. As well as playing roles in the global cycling of metals and carbon, this organism clearly has the potential for use in bioremediation of radioactive metals and in the generation of electricity.
The Commander complex is required for endosomal recycling of diverse transmembrane cargos and is mutated in Ritscher-Schinzel syndrome. It comprises two sub-assemblies: Retriever composed of VPS35L, ...VPS26C, and VPS29; and the CCC complex which contains twelve subunits: COMMD1-COMMD10 and the coiled-coil domain-containing (CCDC) proteins CCDC22 and CCDC93. Combining X-ray crystallography, electron cryomicroscopy, and in silico predictions, we have assembled a complete structural model of Commander. Retriever is distantly related to the endosomal Retromer complex but has unique features preventing the shared VPS29 subunit from interacting with Retromer-associated factors. The COMMD proteins form a distinctive hetero-decameric ring stabilized by extensive interactions with CCDC22 and CCDC93. These adopt a coiled-coil structure that connects the CCC and Retriever assemblies and recruits a 16th subunit, DENND10, to form the complete Commander complex. The structure allows mapping of disease-causing mutations and reveals the molecular features required for the function of this evolutionarily conserved trafficking machinery.
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•CryoEM, crystal and modeled structure of the trimeric Retriever complex•Crystal and CryoEM structures of the CCC complex•Model and functional validation of the holo-Commander complex•Disease-causing mutations in Commander perturb stability and subunit interactions
Complete structural model and functional validation of the sixteen-subunit human Commander complex reveals mechanisms of assembly and how mutations causing Ritscher-Schinzel syndrome perturb stability and subunit interactions of this evolutionarily conserved trafficking machinery.
Lack of standardized criteria measuring therapeutic response remains an obstacle to the development of better treatments for chronic GVHD (cGVHD). This cross-sectional prospective study examined the ...concurrent and predictive validity of 18 clinician-reported ('Form A') and 8 patient-reported ('Form B') response measures proposed by NIH criteria. Concurrent parameters of interest were NIH global score, cGVHD activity, Lee symptom score and SF36 PCS. Patient cohort included 193 adults with moderate-to-severe cGVHD. Measures associated with the highest number of outcomes were lung function score (LFS), 2-min walk, grip strength, 4-point health-care provider (HCP) and patient global scores, 11-point clinician- and patient-reported global symptom severity scores, and Karnofsky performance score (KPS). Measures associated with survival in univariate analyses led to a Cox model containing skin erythema, LFS, KPS, eosinophil count and interval from cGVHD diagnosis to enrollment as jointly associated with survival. In conclusion, 4-point HCP and patient global scores and 11-point clinician- and patient-reported global symptom severity scores are associated with the majority of concurrent outcomes. Skin erythema is a potentially reversible sign of cGVHD that is associated with survival. These results define a subset of measures that should be prioritized for evaluation in future studies.
Aortic intramural hematoma (IMH) is a variant of overt aortic dissection. The predictors of progression of IMH to dissection and rupture are still unknown, and strategies for management are not ...established.
A multicenter study was conducted comprising 66 patients with IMH and hospital admission <or=48 hours after onset of initial symptoms. Among these, progression to aortic dissection or rupture occurred in 30 (45%) and death occurred in 13 (20%) patients within 30 days. Late progression was noted in 14 (21%) and death in 11 (17%) patients, yielding a 1-, 2-, and 5-year survival of 76%, 73%, and 43%, respectively. In a set of 9 variables, multivariate analysis identified IMH location in the ascending aorta (type A; P=0.02) and moderately ectatic aortic diameters (49+/-13 mm with progression versus 57+/-16 mm without progression; P=0.03) as independent predictors of early progression. In type A IMH, early mortality was 8% with swift surgery versus 55% without surgery (P=0.004). The risk of late progression of IMH was independently associated with age at index diagnosis (P=0.01) and absence of beta-blocker therapy during follow-up (P=0.03). Kaplan-Meier analysis confirmed improved 1-year survival of IMH with beta-blocker therapy (95% versus 67% without beta-blockers; P=0.004).
Regardless of aortic diameter, IMH of the ascending aorta (type A) is at high risk for early progression, and, thus, undelayed surgical repair should be performed. Moreover, oral beta-blocker therapy may improve long-term prognosis of IMH independent of anatomical location.
Immunoglobulin (Ig) administration via the subcutaneous (s.c.) route has become increasingly popular in recent years. The method does not require venous access, is associated with few systemic side ...effects and has been reported to improve patients' quality of life. One current limitation to its use is the large volumes which need to be administered. Due to the inability of tissue to accept such large volumes, frequent administration at multiple sites is necessary. Most studies conducted to date have investigated the use of subcutaneous immunoglobulin (SCIg) in patients treated previously with the intravenous (i.v.) formulation. New data now support the use of s.c. administration in previously untreated patients with primary immunodeficiencies. SCIg treatment may further be beneficial in the treatment of autoimmune neurological conditions, such as multi-focal motor neuropathy; however, controlled trials directly comparing the s.c. and i.v. routes are still to be performed for this indication. New developments may further improve and facilitate the s.c. administration route. For example, hyaluronidase-facilitated administration increases the bioavailability of SCIg, and may allow for the administration of larger volumes at a single site. Alternatively, more concentrated formulations may reduce the volume required for administration, and a rapid-push technique may allow for shorter administration times. As these developments translate into clinical practice, more physicians and patients may choose the s.c. administration route in the future.
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