The rate of CD4 decline as a determinant of progression to AIDS independent of the most recent CD4 count

The data of two cohort studies of HIV-infected individuals were used to examine whether the rate of CD4 decline is a determinant of HIV progression, independent of the most recent CD4 count. Time from seroconversion to clinical AIDS was the main outcome measure. Rates of CD4 decline were estimated using the ordinary least squares regression method. AIDS incidences were compared in individuals who had previously experienced either a steeper or a less steep rate of CD4 decline. Cox proportional hazards model including a time-dependent covariate for the rate of CD4 decline was performed. The rate of prior CD4 decline was significantly associated with the risk of developing AIDS independently from the most recent CD4 count, with a 2 % increase in hazard of AIDS (P < 0.01) for a difference of 10 cells/mm(3) in the estimated yearly drop in CD4 count. This finding gives scientific credit to the belief that individuals with a prior steeper CD4 decline consistently have a higher subsequent risk of developing AIDS than those with a less steep prior decline

Optimizing Stimulation and Analysis Protocols for Neonatal fMRI

The development of brain function in young infants is poorly understood. The core challenge is that infants have a limited behavioral repertoire through which brain function can be expressed. Neuroimaging with fMRI has great potential as a way of characterizing typical development, and detecting abnormal development early. But, a number of methodological challenges must first be tackled to improve the robustness and sensitivity of neonatal fMRI. A critical one of these, addressed here, is that the hemodynamic response function (HRF) in pre-term and term neonates differs from that in adults, which has a number of implications for fMRI. We created a realistic model of noise in fMRI data, using resting-state fMRI data from infants and adults, and then conducted simulations to assess the effect of HRF of the power of different stimulation protocols and analysis assumptions (HRF modeling). We found that neonatal fMRI is most powerful if block-durations are kept at the lower range of those typically used in adults (full on/off cycle duration 25-30s). Furthermore, we show that it is important to use the age-appropriate HRF during analysis, as mismatches can lead to reduced power or even inverted signal. Where the appropriate HRF is not known (for example due to potential developmental delay), a flexible basis set performs well, and allows accurate post-hoc estimation of the HRF

Diagnosing deep vein thrombosis in the lower extremity: correlation of clinical and duplex scan findings.

OBJECTIVE: To identify factors that predict a positive duplex scan examination result in patients with suspected deep vein thrombosis of the lower extremity. DESIGN: Retrospective study. SETTING: Vascular laboratory in a university teaching hospital. PATIENTS AND METHODS: The results of 345 lower extremity duplex venous scans performed between August 1994 and November 1998 were reviewed. All patients were in-patients referred from different specialties due to clinical suspicion of lower extremity deep vein thrombosis. Positive duplex scans were correlated with patients' demographic data (sex, age), medical history (history of malignancy, deep vein thrombosis, and pulmonary embolism) and clinical features (leg swelling, venous insufficiency, calf pain, and leg ulcer). Univariate analysis was performed using the Chi squared test. RESULTS: A total of 345 scans were performed for 313 patients. The mean age was 55 years (range, 19-92 years). Sixty-three patients (49 male, 14 female) had a positive scan, giving a yield of 18.3%. Four factors had a significant association with a positive scan: male sex (P=0.0102), history of malignancy (P=0.0040), history of deep vein thrombosis (P=0.0001), and history of pulmonary embolism (P=0.0265). CONCLUSIONS: Common presenting clinical features do not predict the result of ultrasonographic investigation for deep vein thrombosis. The chance of having a positive scan is significantly higher in male patients and those with a history of malignancy, deep vein thrombosis, or pulmonary embolism.published_or_final_versio

Identifying specific prefrontal neurons that contribute to autism-associated abnormalities in physiology and social behavior.

Functional imaging and gene expression studies both implicate the medial prefrontal cortex (mPFC), particularly deep-layer projection neurons, as a potential locus for autism pathology. Here, we explored how specific deep-layer prefrontal neurons contribute to abnormal physiology and behavior in mouse models of autism. First, we find that across three etiologically distinct models-in utero valproic acid (VPA) exposure, CNTNAP2 knockout and FMR1 knockout-layer 5 subcortically projecting (SC) neurons consistently exhibit reduced input resistance and action potential firing. To explore how altered SC neuron physiology might impact behavior, we took advantage of the fact that in deep layers of the mPFC, dopamine D2 receptors (D2Rs) are mainly expressed by SC neurons, and used D2-Cre mice to label D2R+ neurons for calcium imaging or optogenetics. We found that social exploration preferentially recruits mPFC D2R+ cells, but that this recruitment is attenuated in VPA-exposed mice. Stimulating mPFC D2R+ neurons disrupts normal social interaction. Conversely, inhibiting these cells enhances social behavior in VPA-exposed mice. Importantly, this effect was not reproduced by nonspecifically inhibiting mPFC neurons in VPA-exposed mice, or by inhibiting D2R+ neurons in wild-type mice. These findings suggest that multiple forms of autism may alter the physiology of specific deep-layer prefrontal neurons that project to subcortical targets. Furthermore, a highly overlapping population-prefrontal D2R+ neurons-plays an important role in both normal and abnormal social behavior, such that targeting these cells can elicit potentially therapeutic effects

Entropically Driven Formation of Hierarchically Ordered Nanocomposites

Using theoretical models, we undertake the first investigation into the rich behavior that emerges when binary particle mixtures are blended with microphase-separating copolymers. We isolate an example of coupled self-assembly in such materials, where the system undergoes a nanoscale ordering of the particles along with a phase transformation in the copolymer matrix. Furthermore, the self-assembly is driven by entropic effects involving all the different components. The results reveal that entropy can be exploited to create highly ordered nanocomposites with potentially unique electronic and photonic properties. © 2002 The American Physical Society

Binary hard sphere mixtures in block copolymer melts

We perform a self-consistent-field/density-functional-theory hybrid analysis for a system of diblock copolymers mixed with polydisperse, hard, spherical particles of various chemical species. We apply this theory to study the equilibrium morphologies of two different binary sphere/diblock melts. First, we examine the case where the particles have two different sizes, but both types are preferentially wetted by one of the copolymer blocks. We find that the single-particle distributions for the two species do not track one another and that the particles show a degree of entropically generated separation based on size, due to confinement within the diblock matrix. Second, we study the case where the particles are all the same size, but are of two different chemical species. We find that, as expected, the particle distributions reveal a degree of enthalpically driven separation, due to the spheres’ preferential affinities for different blocks of the copolymer. © 2002 The American Physical Society

Self-assembly of a binary mixture of particles and diblock copolymers

Using theoretical models, we undertake the first investigation into the synergy and rich phase behavior that emerges when binary particle mixtures are blended with microphase-separating copolymers. We isolate an example of spontaneous hierarchical self-assembly in such hybrid materials, where the system exhibits both nanoscopic ordering of the particles and macroscopic phase transformation in the copolymer matrix. Furthermore, the self-assembly is driven by entropic effects involving all the different components. The results reveal that entropy can be exploited to create highly ordered nanocomposites with potentially unique electronic and photonic properties. © 2003 The Royal Society of Chemistry

Cooperative Carbon Dioxide Adsorption in Alcoholamine- and Alkoxyalkylamine-Functionalized Metal-Organic Frameworks.

A series of structurally diverse alcoholamine- and alkoxyalkylamine-functionalized variants of the metal-organic framework Mg2 (dobpdc) are shown to adsorb CO2 selectively via cooperative chain-forming mechanisms. Solid-state NMR spectra and optimized structures obtained from van der Waals-corrected density functional theory calculations indicate that the adsorption profiles can be attributed to the formation of carbamic acid or ammonium carbamate chains that are stabilized by hydrogen bonding interactions within the framework pores. These findings significantly expand the scope of chemical functionalities that can be utilized to design cooperative CO2 adsorbents, providing further means of optimizing these powerful materials for energy-efficient CO2 separations

Multiple Stellar Populations in the Globular Cluster omega Centauri as Tracers of a Merger Event

The discovery of the Sagittarius dwarf galaxy, which is being tidally disrupted by and merging with the Milky Way, supports the view that the halo of the Galaxy has been built up at least partially by the accretion of similar dwarf systems. The Sagittarius dwarf contains several distinct populations of stars, and includes M54 as its nucleus, which is the second most massive globular cluster associated with the Milky Way. The most massive globular cluster is omega Centauri, and here we report that omega Centauri also has several distinct stellar populations, as traced by red-giant-branch stars. The most metal-rich red-giant-branch stars are about 2 Gyr younger than the dominant metal-poor component, indicating that omega Centauri was enriched over this timescale. The presence of more than one epoch of star formation in a globular cluster is quite surprising, and suggests that omega Centauri was once part of a more massive system that merged with the Milky Way, as the Sagittarius dwarf galaxy is in the process of doing now. Mergers probably were much more frequent in the early history of the Galaxy and omega Centauri appears to be a relict of this era.Comment: 7 pages, 3 figures, Latex+nature.sty (included), To appear in November 4th issue of Natur

Densest Subgraph in Dynamic Graph Streams

In this paper, we consider the problem of approximating the densest subgraph in the dynamic graph stream model. In this model of computation, the input graph is defined by an arbitrary sequence of edge insertions and deletions and the goal is to analyze properties of the resulting graph given memory that is sub-linear in the size of the stream. We present a single-pass algorithm that returns a $(1+\epsilon)$ approximation of the maximum density with high probability; the algorithm uses O(\epsilon^{-2} n \polylog n) space, processes each stream update in \polylog (n) time, and uses \poly(n) post-processing time where $n$ is the number of nodes. The space used by our algorithm matches the lower bound of Bahmani et al.~(PVLDB 2012) up to a poly-logarithmic factor for constant $\epsilon$. The best existing results for this problem were established recently by Bhattacharya et al.~(STOC 2015). They presented a $(2+\epsilon)$ approximation algorithm using similar space and another algorithm that both processed each update and maintained a $(4+\epsilon)$ approximation of the current maximum density in \polylog (n) time per-update.Comment: To appear in MFCS 201