Why drug shortages are an ethical issue

Drug shortages are a growing problem in developed countries. To some extent they are the result of technical and organisational failures, but to view drug shortages simply as technical and economic phenomena is to miss the fact that they are also ethical and political issues. This observation is important because it highlights both the moral and political imperative to respond to drug shortages as vigorously as possible, and the need for those addressing shortages to do so in ethically and politically sophisticated ways. This brief article outlines the ethical issues that need to be considered by anyone attempting to understand or address drug shortages

The characteristic blue spectra of accretion disks in quasars as uncovered in the infrared

Quasars are thought to be powered by supermassive black holes accreting surrounding gas. Central to this picture is a putative accretion disk which is believed to be the source of the majority of the radiative output. It is well known, however, that the most extensively studied disk model -- an optically thick disk which is heated locally by the dissipation of gravitational binding energy -- is apparently contradicted by observations in a few major respects. In particular, the model predicts a specific blue spectral shape asymptotically from the visible to the near-infrared, but this is not generally seen in the visible wavelength region where the disk spectrum is observable. A crucial difficulty was that, toward the infrared, the disk spectrum starts to be hidden under strong hot dust emission from much larger but hitherto unresolved scales, and thus has essentially been impossible to observe. Here we report observations of polarized light interior to the dust-emiting region that enable us to uncover this near-infrared disk spectrum in several quasars. The revealed spectra show that the near-infrared disk spectrum is indeed as blue as predicted. This indicates that, at least for the outer near-infrared-emitting radii, the standard picture of the locally heated disk is approximately correct. The model problems at shorter wavelengths should then be directed toward a better understanding of the inner parts of the revealed disk. The newly uncovered disk emission at large radii, with more future measurements, will also shed totally new light on the unanswered critical question of how and where the disk ends.Comment: published in Nature, 24 July 2008 issue. Supplementary Information can be found at http://www.mpifr-bonn.mpg.de/div/ir-interferometry/suppl_info.pdf Published version can be accessed from http://www.nature.com/nature/journal/v454/n7203/pdf/nature07114.pd

Unexpected features of branched flow through high-mobility two-dimensional electron gases

GaAs-based two-dimensional electron gases (2DEGs) show a wealth of remarkable electronic states, and serve as the basis for fast transistors, research on electrons in nanostructures, and prototypes of quantum-computing schemes. All these uses depend on the extremely low levels of disorder in GaAs 2DEGs, with low-temperature mean free paths ranging from microns to hundreds of microns. Here we study how disorder affects the spatial structure of electron transport by imaging electron flow in three different GaAs/AlGaAs 2DEGs, whose mobilities range over an order of magnitude. As expected, electrons flow along narrow branches that we find remain straight over a distance roughly proportional to the mean free path. We also observe two unanticipated phenomena in high-mobility samples. In our highest-mobility sample we observe an almost complete absence of sharp impurity or defect scattering, indicated by the complete suppression of quantum coherent interference fringes. Also, branched flow through the chaotic potential of a high-mobility sample remains stable to significant changes to the initial conditions of injected electrons.Comment: 22 pages, 4 figures, 1 tabl

Search algorithms as a framework for the optimization of drug combinations

Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms, originally developed for digital communication, modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs with only one third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6-9 interventions in 80-90% of tests, compared with 15-30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution.Comment: 36 pages, 10 figures, revised versio

Counting and effective rigidity in algebra and geometry

The purpose of this article is to produce effective versions of some rigidity results in algebra and geometry. On the geometric side, we focus on the spectrum of primitive geodesic lengths (resp., complex lengths) for arithmetic hyperbolic 2-manifolds (resp., 3-manifolds). By work of Reid, this spectrum determines the commensurability class of the 2-manifold (resp., 3-manifold). We establish effective versions of these rigidity results by ensuring that, for two incommensurable arithmetic manifolds of bounded volume, the length sets (resp., the complex length sets) must disagree for a length that can be explicitly bounded as a function of volume. We also prove an effective version of a similar rigidity result established by the second author with Reid on a surface analog of the length spectrum for hyperbolic 3-manifolds. These effective results have corresponding algebraic analogs involving maximal subfields and quaternion subalgebras of quaternion algebras. To prove these effective rigidity results, we establish results on the asymptotic behavior of certain algebraic and geometric counting functions which are of independent interest.Comment: v.2, 39 pages. To appear in Invent. Mat

Long-term complete responses after 131I-tositumomab therapy for relapsed or refractory indolent non-Hodgkin's lymphoma

We present the long-term results of 18 chemotherapy relapsed indolent (N=12) or transformed (N=6) NHL patients of a phase II anti-CD20 131I-tositumomab (Bexxar®) therapy study. The biphasic therapy included two injections of 450 mg unlabelled antibody combined with 131I-tositumomab once as dosimetric and once as therapeutic activity delivering 75 or 65 cGy whole-body radiation dose to patients with normal or reduced platelet counts, respectively. Two patients were not treated due to disease progression during dosimetry. The overall response rate was 81% in the 16 patients treated, including 50% CR/CRu and 31% PR. Median progression free survival of the 16 patients was 22.5 months. Median overall survival has not been reached after a median observation of 48 months. Median PFS of complete responders (CR/CRu) has not been reached and will be greater than 51 months. Short-term side effects were mainly haematological and transient. Among the relevant long-term side effects, one patient previously treated with CHOP chemotherapy died from secondary myelodysplasia. Four patients developed HAMA. In conclusion, 131I-tositumomab RIT demonstrated durable responses especially in those patients who achieved a complete response. Six of eight CR/CRu are ongoing after 46–70 months

The Dung Beetle Dance: An Orientation Behaviour?

An interesting feature of dung beetle behaviour is that once they have formed a piece of dung into a ball, they roll it along a straight path away from the dung pile. This straight-line orientation ensures that the beetles depart along the most direct route, guaranteeing that they will not return to the intense competition (from other beetles) that occurs near the dung pile. Before rolling a new ball away from the dung pile, dung beetles perform a characteristic “dance,” in which they climb on top of the ball and rotate about their vertical axis. This dance behaviour can also be observed during the beetles' straight-line departure from the dung pile. The aim of the present study is to investigate the purpose of the dung beetle dance. To do this, we explored the circumstances that elicit dance behaviour in the diurnal ball-rolling dung beetle, Scarabaeus (Kheper) nigroaeneus. Our results reveal that dances are elicited when the beetles lose control of their ball or lose contact with it altogether. We also find that dances can be elicited by both active and passive deviations of course and by changes in visual cues alone. In light of these results, we hypothesise that the dung beetle dance is a visually mediated mechanism that facilitates straight-line orientation in ball-rolling dung beetles by allowing them to 1) establish a roll bearing and 2) return to this chosen bearing after experiencing a disturbance to the roll path

Socio-demographic factors and edentulism: the Nigerian experience

BACKGROUND: The rate of total edentulism is said to be increasing in developing countries and this had been attributed mainly to the high prevalence of periodontal diseases and caries. Several reports have shown that non-disease factors such as attitude, behavior, dental attendance, characteristics of health care systems and socio-demographic factors play important roles in the aetiopathogenesis of edentulism. The aim of this study was to assess the relationship between socio-demographic factors and edentulism. METHODS: A total of 152 patients made up of 80 (52.6%) males and 72 (47.4%) females who presented in two prosthetic clinics located in an urban and a rural area were included in the study. The relationship between gender, age, socio-economic status and edentulism in this study population was established. RESULTS: No significant relationship between gender and denture demand was noted in the study. The demand for complete dentures increased with age while the demand for removable partial dentures also increased with age until the 3(rd )decade and then started to decline. A significant relationship was found between denture demand and the level of education with a higher demand in lower educational groups (p < 0.001). In addition, the lower socio-economic group had a higher demand more for prostheses than the higher group. CONCLUSIONS: The findings in this study revealed a significant relationship between socio-demographic variables and edentulism with age, educational level and socio-economic status playing vital roles in edentulism and denture demand

Pneumococcal carriage in sub-Saharan Africa--a systematic review.

BACKGROUND: Pneumococcal epidemiology varies geographically and few data are available from the African continent. We assess pneumococcal carriage from studies conducted in sub-Saharan Africa (sSA) before and after the pneumococcal conjugate vaccine (PCV) era. METHODS: A search for pneumococcal carriage studies published before 2012 was conducted to describe carriage in sSA. The review also describes pneumococcal serotypes and assesses the impact of vaccination on carriage in this region. RESULTS: Fifty-seven studies were included in this review with the majority (40.3%) from South Africa. There was considerable variability in the prevalence of carriage between studies (I-squared statistic = 99%). Carriage was higher in children and decreased with increasing age, 63.2% (95% CI: 55.6-70.8) in children less than 5 years, 42.6% (95% CI: 29.9-55.4) in children 5-15 years and 28.0% (95% CI: 19.0-37.0) in adults older than 15 years. There was no difference in the prevalence of carriage between males and females in 9/11 studies. Serotypes 19F, 6B, 6A, 14 and 23F were the five most common isolates. A meta-analysis of four randomized trials of PCV vaccination in children aged 9-24 months showed that carriage of vaccine type (VT) serotypes decreased with PCV vaccination; however, overall carriage remained the same because of a concomitant increase in non-vaccine type (NVT) serotypes. CONCLUSION: Pneumococcal carriage is generally high in the African continent, particularly in young children. The five most common serotypes in sSA are among the top seven serotypes that cause invasive pneumococcal disease in children globally. These serotypes are covered by the two PCVs recommended for routine childhood immunization by the WHO. The distribution of serotypes found in the nasopharynx is altered by PCV vaccination