Submodular Secretary Problems: {C}ardinality, Matching, and Linear Constraints

We study various generalizations of the secretary problem with submodular objective functions. Generally, a set of requests is revealed step-by-step to an algorithm in random order. For each request, one option has to be selected so as to maximize a monotone submodular function while ensuring feasibility. For our results, we assume that we are given an offline algorithm computing an $\alpha$-approximation for the respective problem. This way, we separate computational limitations from the ones due to the online nature. When only focusing on the online aspect, we can assume $\alpha = 1$. In the submodular secretary problem, feasibility constraints are cardinality constraints. That is, out of a randomly ordered stream of entities, one has to select a subset size $k$. For this problem, we present a $0.31\alpha$-competitive algorithm for all $k$, which asymptotically reaches competitive ratio $\frac{\alpha}{e}$ for large $k$. In submodular secretary matching, one side of a bipartite graph is revealed online. Upon arrival, each node has to be matched permanently to an offline node or discarded irrevocably. We give an $\frac{\alpha}{4}$-competitive algorithm. In both cases, we improve over previously best known competitive ratios, using a generalization of the algorithm for the classic secretary problem. Furthermore, we give an $O(\alpha d^{-\frac{2}{B-1}})$-competitive algorithm for submodular function maximization subject to linear packing constraints. Here, $d$ is the column sparsity, that is the maximal number of none-zero entries in a column of the constraint matrix, and $B$ is the minimal capacity of the constraints. Notably, this bound is independent of the total number of constraints. We improve the algorithm to be $O(\alpha d^{-\frac{1}{B-1}})$-competitive if both $d$ and $B$ are known to the algorithm beforehand

Wireless Network Stability in the SINR Model

We study the stability of wireless networks under stochastic arrival processes of packets, and design efficient, distributed algorithms that achieve stability in the SINR (Signal to Interference and Noise Ratio) interference model. Specifically, we make the following contributions. We give a distributed algorithm that achieves $\Omega(\frac{1}{\log^2 n})$-efficiency on all networks (where $n$ is the number of links in the network), for all length monotone, sub-linear power assignments. For the power control version of the problem, we give a distributed algorithm with $\Omega(\frac{1}{\log n(\log n + \log \log \Delta)})$-efficiency (where $\Delta$ is the length diversity of the link set).Comment: 10 pages, appeared in SIROCCO'1

Packing Returning Secretaries

We study online secretary problems with returns in combinatorial packing domains with $n$ candidates that arrive sequentially over time in random order. The goal is to accept a feasible packing of candidates of maximum total value. In the first variant, each candidate arrives exactly twice. All $2n$ arrivals occur in random order. We propose a simple 0.5-competitive algorithm that can be combined with arbitrary approximation algorithms for the packing domain, even when the total value of candidates is a subadditive function. For bipartite matching, we obtain an algorithm with competitive ratio at least $0.5721 - o(1)$ for growing $n$, and an algorithm with ratio at least $0.5459$ for all $n \ge 1$. We extend all algorithms and ratios to $k \ge 2$ arrivals per candidate. In the second variant, there is a pool of undecided candidates. In each round, a random candidate from the pool arrives. Upon arrival a candidate can be either decided (accept/reject) or postponed (returned into the pool). We mainly focus on minimizing the expected number of postponements when computing an optimal solution. An expected number of $\Theta(n \log n)$ is always sufficient. For matroids, we show that the expected number can be reduced to $O(r \log (n/r))$, where $r \le n/2$ is the minimum of the ranks of matroid and dual matroid. For bipartite matching, we show a bound of $O(r \log n)$, where $r$ is the size of the optimum matching. For general packing, we show a lower bound of $\Omega(n \log \log n)$, even when the size of the optimum is $r = \Theta(\log n)$.Comment: 23 pages, 5 figure

Potential and pitfalls in the genetic diagnosis of kidney diseases

Next-generation sequencing has dramatically decreased the cost of gene sequencing, facilitating the simultaneous analysis of multiple genes at the same time; obtaining a genetic result for an individual patient has become much easier. The article by Ars and Torra in this issue of the Clinical Kidney Journal provides examples of the ever-increasing ability to understand a given patient's disease on the molecular level, so that in some cases not only the causative variants in a disease gene are identified, but also potential modifiers in other genes. Yet, with increased sequencing, a large number of variants are discovered that are difficult to interpret. These so-called 'variants of uncertain significance' raise important questions: when and how can pathogenicity be clearly attributed? This is of critical importance, as there are potentially serious consequences attached: decisions about various forms of treatment and even about life and death, such as termination of pregnancy, may hinge on the answer to these questions. Geneticists, thus, need to use the utmost care in the interpretation of identified variants and clinicians must be aware of this problem. We here discuss the potential of genetics to facilitate personalized treatment, but also the pitfalls and how to deal with them

Deterministic Digital Clustering of Wireless Ad Hoc Networks

We consider deterministic distributed communication in wireless ad hoc networks of identical weak devices under the SINR model without predefined infrastructure. Most algorithmic results in this model rely on various additional features or capabilities, e.g., randomization, access to geographic coordinates, power control, carrier sensing with various precision of measurements, and/or interference cancellation. We study a pure scenario, when no such properties are available. As a general tool, we develop a deterministic distributed clustering algorithm. Our solution relies on a new type of combinatorial structures (selectors), which might be of independent interest. Using the clustering, we develop a deterministic distributed local broadcast algorithm accomplishing this task in $O(\Delta \log^*N \log N)$ rounds, where $\Delta$ is the density of the network. To the best of our knowledge, this is the first solution in pure scenario which is only polylog$(n)$ away from the universal lower bound $\Omega(\Delta)$, valid also for scenarios with randomization and other features. Therefore, none of these features substantially helps in performing the local broadcast task. Using clustering, we also build a deterministic global broadcast algorithm that terminates within $O(D(\Delta + \log^* N) \log N)$ rounds, where $D$ is the diameter of the network. This result is complemented by a lower bound $\Omega(D \Delta^{1-1/\alpha})$, where $\alpha > 2$ is the path-loss parameter of the environment. This lower bound shows that randomization or knowledge of own location substantially help (by a factor polynomial in $\Delta$) in the global broadcast. Therefore, unlike in the case of local broadcast, some additional model features may help in global broadcast

Generic but Expensive: Why Prices Can Remain High for Off-Patent Drugs

Brand-name prescription drugs are sold at extremely high prices in the US because patents and other market exclusivities provided by the government allow manufacturers to exclude direct competition. This period of market exclusivity was intended for pharmaceutical manufacturers to recoup costs associated with research and development of those products and make profits. The other intended outcome of this system is that the market exclusivity period for brand-name drugs should be self-limited, with competition being able to flourish after the market exclusivities end. Such competition has been most effectively supplied by generic drug manufacturers that produce Food and Drug Administration (FDA)-approved bioequivalent versions of the brand-name product. The market entry of these generic drugs—with market uptake augmented by automatic substitution of brand-name prescriptions at the pharmacy— remains the only market intervention that lowers prescription drug prices consistently and substantially. Generic manufacturers can make their drugs available at considerably lower cost because of various market advantages they have over brand-name drugs. When this process does not operate as intended, drug prices do not fall after market exclusivity expiration, or prices for generic drugs may actually increase. In this paper, we examine the variety of factors that mitigate the cost savings associated with introduction of interchangeable generic drugs, especially older, off-patent drugs. We then consider policy solutions that may help stabilize the generic drug marketplace, diminishing the frequency and impact of generic price increases

Distributed Deterministic Broadcasting in Uniform-Power Ad Hoc Wireless Networks

Development of many futuristic technologies, such as MANET, VANET, iThings, nano-devices, depend on efficient distributed communication protocols in multi-hop ad hoc networks. A vast majority of research in this area focus on design heuristic protocols, and analyze their performance by simulations on networks generated randomly or obtained in practical measurements of some (usually small-size) wireless networks. %some library. Moreover, they often assume access to truly random sources, which is often not reasonable in case of wireless devices. In this work we use a formal framework to study the problem of broadcasting and its time complexity in any two dimensional Euclidean wireless network with uniform transmission powers. For the analysis, we consider two popular models of ad hoc networks based on the Signal-to-Interference-and-Noise Ratio (SINR): one with opportunistic links, and the other with randomly disturbed SINR. In the former model, we show that one of our algorithms accomplishes broadcasting in $O(D\log^2 n)$ rounds, where $n$ is the number of nodes and $D$ is the diameter of the network. If nodes know a priori the granularity $g$ of the network, i.e., the inverse of the maximum transmission range over the minimum distance between any two stations, a modification of this algorithm accomplishes broadcasting in $O(D\log g)$ rounds. Finally, we modify both algorithms to make them efficient in the latter model with randomly disturbed SINR, with only logarithmic growth of performance. Ours are the first provably efficient and well-scalable, under the two models, distributed deterministic solutions for the broadcast task.Comment: arXiv admin note: substantial text overlap with arXiv:1207.673

Strategies and Practices in Off-Label Marketing of Pharmaceuticals: A Retrospective Analysis of Whistleblower Complaints

Aaron Kesselheim and colleagues analyzed unsealed whistleblower complaints against pharmaceutical companies filed in US federal fraud cases that contained allegations of off-label marketing, and develop a taxonomy of the various off-label practices

Proliferation-dependent differential regulation of the dolichol pathway genes in Saccharomyces cerevisiae

The dolichol pathway serves in the synthesis of the dolichol-linked oligosaccharide precursor for protein N-glycosylation. Recently, we reported that mRNAs of genes that function at the early steps in the dolichol pathway in yeast, ALG7, ALG1 and ALG2, were co-ordinately induced following growth stimulation of G0-arrested cells in a manner similar to that of the transcripts of the early growth response genes (Kukuruzinska,M.A. and Lennon,K. Glycobiology, 4, 437-443, 1994). To determine whether the entire dolichol pathway was co-ordinately regulated with growth, we examined the expression of genes functioning late in the pathway, including two genes encoding oligosaccharyltransferase subunits, at two critical control points in the G1 phase of cell cycle: G0/G1 and START. We show that early in G1, at the G0/G1 transition point, the late ALG genes and the two oligosaccharyltransferase-encoding genes examined were regulated co-ordinately with the early ALG genes: they were downregulated upon exit from the mitotic cell cycle into G0, and they were induced following growth stimulation in the absence of de novo protein synthesis. All the dolichol pathway genes produced transcripts with short, half-lives that were rapidly stabilized in the presence of cycloheximide. In contrast, cell division arrest late in G1, at START, was accompanied by a selective downregulation of only the first dolichol pathway gene, ALG7, and not of the genes functioning later in the pathway. These results indicate that, depending on their position in G1, cells either co-ordinately or differentially regulate the dolichol pathway gene

Use of generic medicines in Latvia : Awareness, opinions and experiences of the population

Funding Information: Funding was provided by EEA Financial Mechanism and Latvian state (award number 2012.EEZ/DAP/MIC/183). The project is financially supported by Iceland, Liechtenstein and Norway. Publisher Copyright: © 2019 The Author(s).Background: To stimulate use of generic medicines a combination of supply and demand side mechanisms are employed in the Latvian reimbursement system. It is reported that patients have high out-of-pocket pharmaceutical spending and that they overpay by not choosing generic medicines. Patient preferences may be an important obstacle in implementing generic policy. Objective of this study was to assess awareness, opinions and experience of the Latvian population regarding use of generic medicines. Methods: Survey of representative sample of the population of Latvia (n = 1005) aged 18-74 was conducted in March 2015. The survey was distributed in Latvian and Russian languages using Computer Assisted Web Interviews. Associations between experience with generic medicines, preference for medicines, and sociodemographic variables were tested with Pearson Chi-square statistics. Associations between the previous experience and information given by different sources versus choice between medicines were tested with Spearman's correlation test. Results: 72.3% of the population were informed about generic medicines. Men (66.9%) and respondents with primary or secondary education (58.3%; 69.3%) were less informed compared to total (72.3%). From those who recalled using generic medicines (n = 441), 94.4% evaluated their experience as positive or neutral. Despite this, only 21% of the population would opt for generic medicines. The strongest preference for brand-name medicines was in the age group > 55 (40.5%). Opinion of a physician was the most important factor when choosing between generic and brand-name medicines (88.7%). The more positive the information provided by general practitioners, physician specialists, pharmacists, family members, friends and internet is perceived, the more likely respondents are to choose generic medicines (p < 0.001). Conclusion: This study demonstrates that people in Latvia are aware of generic medicines but only a minority of the population would choose them when presented with a choice. It is therefore important that health care professionals provide objective and unbiased information about generic medicines to their patients. Interventions should aim to reach groups that are less informed and to improve providers' understanding and communication with patients about generics.publishersversionPeer reviewe