Antiretroviral therapy initiated soon after HIV diagnosis as standard care: potential to save lives?

In 2008, an estimated 33.4 million people were infected with human immunodeficiency virus (HIV) and ~4 million people were receiving antiretroviral therapy (ART). However, in 2007, an estimated 6.7 million people were in need of ART under the current World Health Organization guidelines, and 2.7 million more people became infected with HIV. Most of those not currently eligible for ART will become eligible within the next decade, making the current treatment strategy unsustainable. The development of cheaper, less toxic, and more potent antiretrovirals over the past decade has made it possible to consider novel strategies of arresting the HIV/AIDS epidemic. Evidence is growing that ART can be used to prevent HIV transmission and that earlier initiation of treatment is beneficial for those infected with HIV. A mathematical model predicts that by testing whole communities annually and treating all who are infected immediately, up to 7.2 million AIDS-related deaths could be prevented in the next 40 years, long-term funding required to fight the HIV epidemic could be reduced, and, most importantly, control of the HIV/ AIDS epidemic could be regained within 1–2 years of full-scale implementation of the strategy. We discuss the development of the concept of ART for the prevention of HIV transmission and the modeled impact that a test-and-treat strategy could have on the HIV epidemic, and consequently argue that a field trial should be carried out to confirm model parameters, highlight any practical problems, and test the model’s predictions

All duplicates are not equal: the difference between small-scale and genome duplication

The comparison of pairs of gene duplications generated by small-scale duplications with those created by large-scale duplications shows that they differ in quantifiable ways. It is suggested that this is directly due to biases on the paths to gene retention rather than association with different functional categories

"Resurrection of clinical efficacy" after resistance to endocrine therapy in metastatic breast cancer

BACKGROUND: In a significant proportion of metastatic breast cancer (MBC) patients whose tumour has progressed within 6 months of endocrine therapy (de novo resistance), it is generally believed that the chance of achieving clinical benefit (CB) with further endocrine therapy is minimal. METHODS: Data was retrieved from a prospectively updated database of metastatic breast cancer. Relevant data was exported to SPSS™ software for statistical analysis. RESULTS: In oestrogen receptor (ER) positive MBC patients with assessable disease, CB was achieved in 159 (71.3%) (1(st )line) patients. When these patients were put on further endocrine therapy, the CB rates were 63.2% (on 2(nd )line), 46.1% (on 3(rd )line) and 20% (on 4(th )line) with a median duration of response (DOR) in those with CB of 22, 12, 11 and 15 months respectively. The remaining 64(28.7%) patients had de novo resistance on 1(st )line endocrine therapy. Seventeen of these patients were treated with further endocrine therapy. The CB rates were 29.4% (on 2(nd )line) and 22.2% (on 3(rd )line) with a median DOR in those with CB of 22.7 months and 14 months respectively. CONCLUSION: The chance of further endocrine response continues to decrease with each line of therapy, yet CB is still seen with reasonable duration even with a 4(th )line agent. In addition, further endocrine response, with long duration, can be seen in a significant proportion of patients who have developed de novo resistance to 1(st )line endocrine therapy. The use of further endocrine therapy should not be excluded under these circumstances

Uncovering the Neural Signature of Lapsing Attention: Electrophysiological Signals Predict Errors up to 20 s before They Occur

The extent to which changes in brain activity can foreshadow human error is uncertain yet has important theoretical and practical implications. The present study examined the temporal dynamics of electrocortical signals preceding a lapse of sustained attention. Twenty-one participants performed a continuous temporal expectancy task, which involved continuously monitoring a stream of regularly alternating patterned stimuli to detect a rarely occurring target stimulus whose duration was 40% longer. The stimulus stream flickered at a rate of 25 Hz to elicit a steady-state visual-evoked potential (SSVEP), which served as a continuous measure of basic visual processing. Increasing activity in the band (8 –14 Hz) was found beginning20 s before a missed target. This was followed by decreases in the amplitude of two event-related components over a short pretarget time frame: the frontal P3 (3– 4 s) and contingent-negative variation (during the target interval). In contrast, SSVEP amplitude before hits and misses was closely matched, suggesting that the efficacy of ongoing basic visual processing was unaffected. Our results show that the specific neural signatures of attentional lapses are registered in the EEG up to 20 s before an error

Immittance Matching for Multi-dimensional Open-system Photonic Crystals

An electromagnetic (EM) Bloch wave propagating in a photonic crystal (PC) is characterized by the immittance (impedance and admittance) of the wave. The immittance is used to investigate transmission and reflection at a surface or an interface of the PC. In particular, the general properties of immittance are useful for clarifying the wave propagation characteristics. We give a general proof that the immittance of EM Bloch waves on a plane in infinite one- and two-dimensional (2D) PCs is real when the plane is a reflection plane of the PC and the Bloch wavevector is perpendicular to the plane. We also show that the pure-real feature of immittance on a reflection plane for an infinite three-dimensional PC is good approximation based on the numerical calculations. The analytical proof indicates that the method used for immittance matching is extremely simplified since only the real part of the immittance function is needed for analysis without numerical verification. As an application of the proof, we describe a method based on immittance matching for qualitatively evaluating the reflection at the surface of a semi-infinite 2D PC, at the interface between a semi-infinite slab waveguide (WG) and a semi-infinite 2D PC line-defect WG, and at the interface between a semi-infinite channel WG and a semi-infinite 2D PC slab line-defect WG.Comment: 8 pages, 6 figure

Radio Sources in Galaxy Clusters at 28.5 GHz

We present serendipitous detections of radio sources at 28.5 GHz (1 cm), which resulted from our program to image thermal Sunyaev-Zeldovich (SZ) effect in 56 galaxy clusters. We find 64 radio sources with fluxes down to 0.4 mJy, and within 250 arcseconds from the pointing centers. The spectral indices (S ~ \nu^-\alpha) of 54 sources with published low frequency flux densities range from -0.6 to 2 with a mean of 0.77, and a median of 0.84. Extending low frequency surveys of radio sources towards galaxy clusters CL 0016+16, Abell 665, and Abell 2218 to 28.5 GHz, and selecting sources with 1.4 GHz flux density greater than 7 mJy to form an unbiased sample, we find a mean spectral index of 0.71 and a median of 0.71. We find 4 to 7 times more sources predicted from a low frequency survey in areas without galaxy clusters. This excess cannot be accounted for by gravitational lensing of a background radio population by cluster potentials, indicating most of the detected sources are associated with galaxy clusters. For the cluster Abell 2218, the presence of unsubtracted radio sources with 28.5 GHz flux densities less than 0.5 mJy, can only contribute to temperature fluctuations at a level of 10 to 25 \muK. The corresponding error due to radio point source contamination in the Hubble constant derived through a combined analysis of 28.5 GHz SZ images and X-ray emission observations ranges from 1% to 6%.Comment: 18 pages, 8 figures, to appear in April 1998 issue of A

The elastic constants of MgSiO3 perovskite at pressures and temperatures of the Earth's mantle

The temperature anomalies in the Earth's mantle associated with thermal convection1 can be inferred from seismic tomography, provided that the elastic properties of mantle minerals are known as a function of temperature at mantle pressures. At present, however, such information is difficult to obtain directly through laboratory experiments. We have therefore taken advantage of recent advances in computer technology, and have performed finite-temperature ab initio molecular dynamics simulations of the elastic properties of MgSiO3 perovskite, the major mineral of the lower mantle, at relevant thermodynamic conditions. When combined with the results from tomographic images of the mantle, our results indicate that the lower mantle is either significantly anelastic or compositionally heterogeneous on large scales. We found the temperature contrast between the coldest and hottest regions of the mantle, at a given depth, to be about 800K at 1000 km, 1500K at 2000 km, and possibly over 2000K at the core-mantle boundary.Comment: Published in: Nature 411, 934-937 (2001