Ethical hurdles in the prioritization of oncology care

With finite resources, healthcare payers must make difficult choices regarding spending and the ethical distribution of funds. Here, we describe some of the ethical issues surrounding inequity in healthcare in nine major European countries, using cancer care as an example. To identify relevant studies, we conducted a systematic literature search. The results of the literature review suggest that although prevention, access to early diagnosis, and radiotherapy are key factors associated with good outcomes in oncology, public and political attention often focusses on the availability of pharmacological treatments. In some countries this focus may divert funding towards cancer drugs, for example through specific cancer drugs funds, leading to reduced expenditure on other areas of cancer care, including prevention, and potentially on other diseases. In addition, as highly effective, expensive agents are developed, the use of value-based approaches may lead to unacceptable impacts on health budgets, leading to a potential need to re-evaluate current cost-effectiveness thresholds. We anticipate that the question of how to fund new therapies equitably will become even more challenging in the future, with the advent of expensive, innovative, breakthrough treatments in other therapeutic areas

CCR5AS lncRNA variation differentially regulates CCR5, influencing HIV disease outcome.

Multiple genome-wide studies have identified associations between outcome of human immunodeficiency virus (HIV) infection and polymorphisms in and around the gene encoding the HIV co-receptor CCR5, but the functional basis for the strongest of these associations, rs1015164A/G, is unknown. We found that rs1015164 marks variation in an activating transcription factor 1 binding site that controls expression of the antisense long noncoding RNA (lncRNA) CCR5AS. Knockdown or enhancement of CCR5AS expression resulted in a corresponding change in CCR5 expression on CD4+ T cells. CCR5AS interfered with interactions between the RNA-binding protein Raly and the CCR5 3' untranslated region, protecting CCR5 messenger RNA from Raly-mediated degradation. Reduction in CCR5 expression through inhibition of CCR5AS diminished infection of CD4+ T cells with CCR5-tropic HIV in vitro. These data represent a rare determination of the functional importance of a genome-wide disease association where expression of a lncRNA affects HIV infection and disease progression

Pulsation in the atmosphere of the roAp star HD 24712. I. Spectroscopic observations and radial velocity measurements

We have investigated the structure of the pulsating atmosphere of one of the best studied rapidly oscillating Ap stars, HD 24712. For this purpose we analyzed spectra collected during 2001-2004. An extensive data set was obtained in 2004 simultaneously with the photometry of the Canadian MOST mini-satellite. This allows us to connect directly atmospheric dynamics observed as radial velocity variations with light variations seen in photometry. We directly derived for the first time and for different chemical elements, respectively ions, phase shifts between photometric and radial velocity pulsation maxima indicating, as we suggest, different line formation depths in the atmosphere. This allowed us to estimate for the first time the propagation velocity of a pulsation wave in the outer stellar atmosphere of a roAp star to be slightly lower than the sound speed. We confirm large pulsation amplitudes (150-400 m/s) for REE lines and the Halpha core, while spectral lines of the other elements (Mg, Si, Ca, and Fe-peak elements) have nearly constant velocities. We did not find different pulsation amplitudes and phases for the lines of rare-earth elements before and after the Balmer jump, which supports the hypothesis of REE concentration in the upper atmosphere above the hydrogen line-forming layers. We also discuss radial velocity amplitudes and phases measured for individual spectral lines as tools for a 3D tomography of the atmosphere of HD 24712.Comment: accepted by A&

Multiperiodicity in the newly discovered mid-late Be star V2104 Cygni

We obtained the first long, homogenous time-series of V2104Cyg, consisting of 679 datapoints, with the uvbybeta photometers of Sierra Nevada and San Pedro Martir Observatories with the aim to detect and subsequently interpret the intrinsic frequencies of this previously unstudied variable star, which turned out to be a Be star. We try to figure out its place among the variable B stars on the upper Main Sequence. In order to obtain additional information on physical parameters we collected a few spectra with the ELODIE and FIES instruments. We searched for frequencies in the uvby passbands using 2 different frequency analysis methods and used the S/N>4 criterion to select the significant periodicities. We obtained an estimate of the physical parameters of the underlying B star of spectral type between B5 and B7, by correcting for the presence of a circumstellar disk, using a formalism based on the strenght of the Halpha line emission. We detected 3 independent frequencies with amplitudes below 0.01mag, f1 = 4.7126 c/d, f2 = 2.2342 c/d and f3 = 4.671 c/d, and discovered that V2104Cyg is a Be star. The fast rotation (vsini=290+/-10 km/s, and 27<i<45) hampered the investigation of the associated pulsational parameters l. Nevertheless, the most plausible explanation for the observed variability of this mid-late type Be star is a non-radial pulsation model. This paper is based on observations obtained at the Observatorio Astronomico Nacional San Pedro Martir (Mexico), Observatorio de Sierra Nevada (Spain), Observatoire de Haute Provence (France), and on observations made with the Nordic Optical Telescope, Observatorio Roque de los Muchachos, La Palma, Spain.Comment: 7 pages, 4 figures, A&A accepte

Strong interactions between g- and p-modes in the hybrid gamma Doradus-delta Scuti CoRoT star ID105733033

CoRoT ID 105733033 is an excellent example of hybrid pulsators as it shows g- and p-modes with almost similar amplitudes in two clearly distinct frequency domains. Classical Fourier analysis allows the dectection of frequencies with an amplitude as small as 0.1 mmag up to 50c/d. The frequency spectrum of CoRoT ID 105733033 clearly consists of two distinct ranges, which are typical of gamma Doradus and delta Scuti pulsation. Focus was placed on the identification of linear combinations and frequencies due to the coupling between gamma Doradus and delta Scuti modes. We detect 198 gamma Doradus type frequencies in the range [0.25;4]c/d, of which 180 are not combination frequencies, and 24 of them are separated by a constant period-interval Delta P=0.03074d. According to the asymptotic theory, these 24 frequencies correspond to a series of g-modes of the same ell-degree and different radial orders n. We also detect 246 delta Scuti type frequencies in the range [10.1;63.4]c/d. The dominant frequency F=12.6759c/d was identified as the fundamental radial mode. Our most noteworthy result is that all the main gamma Doradus frequencies f_i are also detected in the delta Scuti domain as F +- f_i with four times smaller amplitudes. Once these frequencies were removed, only 59 can be considered as individual delta Scuti frequencies. A coupling between g- and p-modes is proposed to be a tool for detecting g-modes in the Sun, but this coupling has never yet been observed. Our present study may be valuable input to theoretical studies, addressing the mutual influence of g- and p-mode cavities and the deviation from classical theory. Furthermore, we identify a sequence of g-modes belonging to the same ell but with consecutive orders n

Anopheles gambiae: historical population decline associated with regional distribution of insecticide-treated bed nets in western Nyanza Province, Kenya

<p>Abstract</p> <p>Background</p> <p>High coverage of insecticide-treated bed nets in Asembo and low coverage in Seme, two adjacent communities in western Nyanza Province, Kenya; followed by expanded coverage of bed nets in Seme, as the Kenya national malaria programme rolled out; provided a natural experiment for quantification of changes in relative abundance of two primary malaria vectors in this holoendemic region. Both belong to the <it>Anopheles gambiae sensu lato (s.l.) </it>species complex, namely <it>A. gambiae sensu stricto (s.s.) </it>and <it>Anopheles arabiensis</it>. Historically, the former species was proportionately dominant in indoor resting collections of females.</p> <p>Methods</p> <p>Data of the relative abundance of adult <it>A. gambiae s.s. </it>and <it>A. arabiensis </it>sampled from inside houses were obtained from the literature from 1970 to 2002 for sites west of Kisumu, Kenya, to the region of Asembo ca. 50 km from the city. A sampling transect was established from Asembo (where bed net use was high due to presence of a managed bed net distribution programme) eastward to Seme, where no bed net programme was in place. Adults of <it>A. gambiae s.l. </it>were sampled from inside houses along the transect from 2003 to 2009, as were larvae from nearby aquatic habitats, providing data over a nearly 40 year period of the relative abundance of the two species. Relative proportions of <it>A. gambiae s.s. </it>and <it>A. arabiensis </it>were determined for each stage by identifying species by the polymerase chain reaction method. Household bed net ownership was measured with surveys during mosquito collections. Data of blood host choice, parity rate, and infection rate for <it>Plasmodium falciparum </it>in <it>A. gambiae s.s. </it>and <it>A. arabiensis </it>were obtained for a sample from Asembo and Seme from 2005.</p> <p>Results</p> <p><it>Anopheles gambiae s.s. </it>adult females from indoor collections predominated from 1970 to 1998 (ca. 85%). Beginning in 1999, <it>A. gambiae </it>s.s decreased proportionately relative to <it>A. arabiensis</it>, then precipitously declined to rarity coincident with increased bed net ownership as national bed net distribution programmes commenced in 2004 and 2006. By 2009, <it>A. gambiae s.s. </it>comprised proportionately ca. 1% of indoor collections and <it>A. arabiensis </it>99%. In Seme compared to Asembo in 2003, proportionately more larvae were <it>A. gambiae s.s.</it>, larval density was higher, and more larval habitats were occupied. As bed net use rose in Seme, the proportion of <it>A. gambiae </it>larvae declined as well. These trends continued to 2009. Parity and malaria infection rates were lower in both species in Asembo (high bed net use) compared to Seme (low bed net use), but host choice did not vary within species in both communities (predominantly cattle for <it>A. arabiensis</it>, humans for <it>A. gambiae s.s.</it>).</p> <p>Conclusions</p> <p>A marked decline of the <it>A. gambiae s.s. </it>population occurred as household ownership of bed nets rose in a region of western Kenya over a 10 year period. The increased bed net coverage likely caused a mass effect on the composition of the <it>A. gambiae s.l. </it>species complex, resulting in the observed proportionate increase in <it>A. arabiensis </it>compared to its closely related sibling species, <it>A. gambiae s.s. </it>These observations are important in evaluating the process of regional malaria elimination, which requires sustained vector control as a primary intervention.</p

Confirmation of simultaneous p and g mode excitation in HD 8801 and Gamma Peg from time-resolved multicolour photometry of six candidate "hybrid" pulsators

We carried out a multi-colour time-series photometric study of six stars claimed as "hybrid" p and g mode pulsators in the literature. Gamma Peg was confirmed to show short-period oscillations of the Beta Cep type and simultaneous long-period pulsations typical of Slowly Pulsating B (SPB) stars. From the measured amplitude ratios in the Stromgren uvy passbands, the stronger of the two short period pulsation modes was identified as radial; the second is l=1. Three of the four SPB-type modes are most likely l=1 or 2. Comparison with theoretical model calculations suggests that Gamma Peg is either an 8.5 solar mass radial fundamental mode pulsator or a 9.6 solar mass first radial overtone pulsator. HD 8801 was corroborated as a "hybrid" Delta Sct Gamma Dor star; four pulsation modes of the Gamma Dor type were detected, and two modes of the Delta Sct type were confirmed. Two pulsational signals between the frequency domains of these two known classes of variables were confirmed and another was newly detected. These are either previously unknown types of pulsation, or do not originate from HD 8801. The O-type star HD 13745 showed small-amplitude slow variability on a time scale of 3.2 days. This object may be related to the suspected new type of supergiant SPB stars, but a rotational origin of its light variations cannot be ruled out at this point. 53 Psc is an SPB star for which two pulsation frequencies were determined and identified with low spherical degree. The behaviour of 53 Ari and Iota Her is consistent with non-variability during our observations, and we could not confirm light variations of the comparison star 34 Psc previously suspected. The use of signal-to-noise criteria in the analysis of data sets with strong aliasing is critically discussed.Comment: 14 pages, 10 figures, accepted by MNRA

Limited Durability of Viral Control following Treated Acute HIV Infection

BACKGROUND: Early treatment of acute HIV infection with highly active antiretroviral therapy, followed by supervised treatment interruption (STI), has been associated with at least transient control of viremia. However, the durability of such control remains unclear. Here we present longitudinal follow-up of a single-arm, open-label study assessing the impact of STI in the setting of acute HIV-1 infection. METHODS AND FINDINGS: Fourteen patients were treated during acute HIV-1 infection and subsequently subjected to an STI protocol that required retreatment if viral load exceeded 50,000 RNA copies/ml plasma or remained above 5,000 copies/ml for more than three consecutive weeks. Eleven of 14 (79%) patients were able to achieve viral loads of less than 5,000 RNA copies/ml for at least 90 d following one, two, or three interruptions of treatment. However, a gradual increase in viremia and decline in CD4+ T cell counts was observed in most individuals. By an intention-to-treat analysis, eight (57%), six (43%), and three (21%) of 14 patients achieved a maximal period of control of 180, 360, and 720 d, respectively, despite augmentation of HIV-specific CD4+ and CD8+ T cell responses. The magnitude of HIV-1-specific cellular immune responses before treatment interruption did not predict duration of viremia control. The small sample size and lack of concurrent untreated controls preclude assessment of possible clinical benefit despite failure to control viremia by study criteria. CONCLUSIONS: These data indicate that despite initial control of viremia, durable viral control to less than 5,000 RNA copies/ml plasma in patients following treated acute HIV-1 infection occurs infrequently. Determination of whether early treatment leads to overall clinical benefit will require a larger and randomized clinical trial. These data may be relevant to current efforts to develop an HIV-1 vaccine designed to retard disease progression rather than prevent infection since they indicate that durable maintenance of low-level viremia may be difficult to achieve