Covering Pairs in Directed Acyclic Graphs

The Minimum Path Cover problem on directed acyclic graphs (DAGs) is a classical problem that provides a clear and simple mathematical formulation for several applications in different areas and that has an efficient algorithmic solution. In this paper, we study the computational complexity of two constrained variants of Minimum Path Cover motivated by the recent introduction of next-generation sequencing technologies in bioinformatics. The first problem (MinPCRP), given a DAG and a set of pairs of vertices, asks for a minimum cardinality set of paths "covering" all the vertices such that both vertices of each pair belong to the same path. For this problem, we show that, while it is NP-hard to compute if there exists a solution consisting of at most three paths, it is possible to decide in polynomial time whether a solution consisting of at most two paths exists. The second problem (MaxRPSP), given a DAG and a set of pairs of vertices, asks for a path containing the maximum number of the given pairs of vertices. We show its NP-hardness and also its W[1]-hardness when parametrized by the number of covered pairs. On the positive side, we give a fixed-parameter algorithm when the parameter is the maximum overlapping degree, a natural parameter in the bioinformatics applications of the problem

On the Complexity of tt-Closeness Anonymization and Related Problems

An important issue in releasing individual data is to protect the sensitive information from being leaked and maliciously utilized. Famous privacy preserving principles that aim to ensure both data privacy and data integrity, such as $k$-anonymity and $l$-diversity, have been extensively studied both theoretically and empirically. Nonetheless, these widely-adopted principles are still insufficient to prevent attribute disclosure if the attacker has partial knowledge about the overall sensitive data distribution. The $t$-closeness principle has been proposed to fix this, which also has the benefit of supporting numerical sensitive attributes. However, in contrast to $k$-anonymity and $l$-diversity, the theoretical aspect of $t$-closeness has not been well investigated. We initiate the first systematic theoretical study on the $t$-closeness principle under the commonly-used attribute suppression model. We prove that for every constant $t$ such that $0\leq t<1$, it is NP-hard to find an optimal $t$-closeness generalization of a given table. The proof consists of several reductions each of which works for different values of $t$, which together cover the full range. To complement this negative result, we also provide exact and fixed-parameter algorithms. Finally, we answer some open questions regarding the complexity of $k$-anonymity and $l$-diversity left in the literature.Comment: An extended abstract to appear in DASFAA 201

Structured self-monitoring of blood glucose is associated with more appropriate therapeutic interventions than unstructured self-monitoring: A novel analysis of data from the PRISMA trial

Aims: To investigate the relationship between single therapeutic interventions and indicators of glycemic control in the PRISMA trial, a large study comparing the effects of intensive structured SMBG (ISM) vs. active control (AC) in non-insulin-treated type 2 diabetes (T2D). Methods: Information was collected at four time points, corresponding to months 3, 6, 9, and 12 and visits 2, 3, 4, and 5, respectively. Data on therapeutic interventions, HbA1c levels and the number of hypoglycemic episodes at each visit were analyzed. Results: Intensification of drug therapy occurred in 20.3% vs. 15.6%, and no change in 71.8% vs. 78.7% of visits for the ISM and AC groups, respectively. On the other hand, de-intensification and redistribution of drugs and/or drug dose occurred in a similar proportion of visits. Intensification of drug therapy in both groups was associated with significant reductions in HbA1c vs. the previous visit, while de-intensification of therapy led to a significant increase in HbA1c in the AC group only. Conclusions. Our data strongly support that structured SMBG has clinical value in reducing HbA1c in non-insulin-treated T2D and suggest that this clinical benefit may be mediated by more appropriate and timely changes in drug therapy

Insights into an unexplored component of the mosquito repeatome: Distribution and variability of viral sequences integrated into the genome of the arboviral vector aedes albopictus

The Asian tiger mosquito Aedes albopictus is an invasive mosquito and a competent vector for public-health relevant arboviruses such as Chikungunya (Alphavirus), Dengue and Zika (Flavivirus) viruses. Unexpectedly, the sequencing of the genome of this mosquito revealed an unusually high number of integrated sequences with similarities to non-retroviral RNA viruses of the Flavivirus and Rhabdovirus genera. These Non-retroviral Integrated RNA Virus Sequences (NIRVS) are enriched in piRNA clusters and coding sequences and have been proposed to constitute novel mosquito immune factors. However, given the abundance of NIRVS and their variable viral origin, their relative biological roles remain unexplored. Here we used an analytical approach that intersects computational, evolutionary and molecular methods to study the genomic landscape of mosquito NIRVS. We demonstrate that NIRVS are differentially distributed across mosquito genomes, with a core set of seemingly the oldest integrations with similarity to Rhabdoviruses. Additionally, we compare the polymorphisms of NIRVS with respect to that of fast and slow-evolving genes within the Ae. albopictus genome. Overall, NIRVS appear to be less polymorphic than slow-evolving genes, with differences depending on whether they occur in intergenic regions or in piRNA clusters. Finally, two NIRVS that map within the coding sequences of genes annotated as Rhabdovirus RNA-dependent RNA polymerase and the nucleocapsid-encoding gene, respectively, are highly polymorphic and are expressed, suggesting exaptation possibly to enhance the mosquito's antiviral responses. These results greatly advance our understanding of the complexity of the mosquito repeatome and the biology of viral integrations in mosquito genomes

Use of complementary medicine among patients with allergic rhinitis: an Italian nationwide survey.

Background: A growing use of complementary alternative medicine (CAM) has been found in Europe as well in Italy for chronic diseases, including the allergic rhinitis. The study aims at investigating the prevalence and the pattern of use of CAM amongst patient with allergic rhinitis. Methods: A 12-item questionnaire was developed by a panel of experts and administered to patients with moderate/severe allergic rhinitis consecutively referring during the study time-frame to seven allergy clinics placed all around Italy. The items covered several topics including reason for choosing CAM, its clinical efficacy, schedule of treatment, costs, type of therapy. Results: Overall 359 questionnaires were analysed. 20% of patients declared CAM use. A significant correlation between the use of CAM and female sex (p\u2009&lt;\u20090.01) and with a higher level of education (p\u2009&lt;\u20090.01) was observed. CAM users were adults (36% in the range between 20 and 40 years and 32% between 41 and 60 years). Youngsters (&lt;\u200920 years) (7%) and elderly (&gt;\u200960) (25%) less frequently used CAM.The most used type of CAM was homoeopathy (77% of patients). 60% of users would recommend CAM despite a poor clinical efficacy according to 67% of them. Conclusions: Although no evidence supports CAM efficacy and safety, the number of patients who relies on it is not negligible. As allergic rhinitis is not a trivial disease, the use of CAM as the only treatment for it should be discouraged at any level, but by general practitioner and specialist in particular

Coade, Blashfield or Doulton? The in situ identification of ceramic garden statuary and ornament from three eighteenth and nineteenth century manufacturers

In the eighteenth century, the emergence of a neo-classical style in architecture created a growing demand for a range of classically-inspired products - not only for architectural decoration but also for ornamentation of the garden. Producing individual items in stone, however, was time-consuming and expensive, so cheaper clay-based alternatives were adopted, most notably from manufacturers such as Coade (1769-1830), Blashfield (1840s-1875) and Doulton (1854-1890s). The artefacts of these manufacturers are now considered of high historic value and significance and their identification is important, not only for the historical record, but also for provision of the evidence necessary to carry out informed conservation. As the sale and copy of moulds was common practice during the eighteenth and nineteenth centuries, stylistic considerations do not provide reliable identification. Through the analysis of 24 historic objects of garden statuary and ornamentation, this research evaluates the use of portable X-ray fluorescence spectroscopy (pXRF), and more specifically element profiles, in identifying, and differentiating between the products of Coade, Blashfield and Doulton. Key questions around heterogeneity and representative material analysis are addressed. Despite the inherent heterogeneity of these materials, it is shown that discrimination is nevertheless possible using pXRF, primarily due to the significant differences observed across a range of elements at both macro- and trace-level. Objects of known provenance from Coade, Blashfield and Doulton produced three distinct and statistically significant groups demonstrating that the data reflect the composition of the bulk material – rather than surface characteristics. Through identifying the main discriminators for the Coade, Blashfield and Doulton materials, a simple presumptive test is proposed that can be used in an initial evaluation of any unsigned works. Analysis of a selection of unsigned objects with a probable Coade, Blashfield or Doulton provenance was in many cases successful in confirming the documentary evidence. A few objects, however, presented anomalous element profiles. These most likely result from past conservation treatments or polychromy - the two major limitations of the technique

Should clinicians always administer dexamethasone beyond 24 h after chemotherapy to control delayed nausea and vomiting caused by moderately emetogenic regimens? : insight from the re-evaluation of two randomized studies

Purpose Data from two noninferiority trials of a dexamethasone-sparing regimen were assessed for the impact of acute nausea and vomiting on delayed outcome in patients undergoing moderately emetogenic chemotherapy (MEC) or anthracycline plus cyclophosphamide (AC). Methods Chemo-naive patients were randomized to receive palonosetron (0.25 mg IV) plus dexamethasone (8 mg IV) on day 1 of chemotherapy, or the same regimen followed by oral dexamethasone on days 2 and 3 in the MEC (n = 237) and AC (n = 380) cohorts. Patients were divided into two groups according to whether or not they experienced vomiting and/or moderate-to-severe nausea during the acute phase (high- and low-risk groups, respectively). Primary efficacy endpoint was the complete protection (CP) against delayed vomiting and moderate-to-severe nausea. Patient's satisfaction (0-100 mm visual analog scale) was also analyzed. Results Among the 209 low-risk patients undergoing MEC, delayed CP occurred in 82.9 % of those who received single-dose dexamethasone and 89.8 % of those who received 3-day dexamethasone (P = 0.165). Of the 271 low-risk patients undergoing AC, CP was achieved in 71.7 % of those treated with single-dose dexamethasone and 84.2 % treated with 3-day dexamethasone (P = 0.019). In spite of these observations, the patient satisfaction data was not influenced by dexamethasone regimen. In both cohorts, occurrence of acute vomiting or moderate-to-severe nausea was the key independent-predictor for delayed vomiting or nausea, respectively. Conclusions The dexamethasone-sparing regimen provides adequate delayed protection in patients undergoing MEC who are at low risk for delayed symptoms, and can still be discussed for low-risk AC patients as the daily difference in control is modest. Additional dexamethasone doses can be customized on the basis of occurrence or absence of acute symptoms in the first cycle of MEC and even AC

ASPicDB: a database of annotated transcript and protein variants generated by alternative splicing

Alternative splicing is emerging as a major mechanism for the expansion of the transcriptome and proteome diversity, particularly in human and other vertebrates. However, the proportion of alternative transcripts and proteins actually endowed with functional activity is currently highly debated. We present here a new release of ASPicDB which now provides a unique annotation resource of human protein variants generated by alternative splicing. A total of 256 939 protein variants from 17 191 multi-exon genes have been extensively annotated through state of the art machine learning tools providing information of the protein type (globular and transmembrane), localization, presence of PFAM domains, signal peptides, GPI-anchor propeptides, transmembrane and coiled-coil segments. Furthermore, full-length variants can be now specifically selected based on the annotation of CAGE-tags and polyA signal and/or polyA sites, marking transcription initiation and termination sites, respectively. The retrieval can be carried out at gene, transcript, exon, protein or splice site level allowing the selection of data sets fulfilling one or more features settled by the user. The retrieval interface also enables the selection of protein variants showing specific differences in the annotated features. ASPicDB is available at http://www.caspur.it/ASPicDB/

Insights Into an Unexplored Component of the Mosquito Repeatome: Distribution and Variability of Viral Sequences Integrated Into the Genome of the Arboviral Vector Aedes albopictus.

The Asian tiger mosquito Aedes albopictus is an invasive mosquito and a competent vector for public-health relevant arboviruses such as Chikungunya (Alphavirus), Dengue and Zika (Flavivirus) viruses. Unexpectedly, the sequencing of the genome of this mosquito revealed an unusually high number of integrated sequences with similarities to non-retroviral RNA viruses of the Flavivirus and Rhabdovirus genera. These Non-retroviral Integrated RNA Virus Sequences (NIRVS) are enriched in piRNA clusters and coding sequences and have been proposed to constitute novel mosquito immune factors. However, given the abundance of NIRVS and their variable viral origin, their relative biological roles remain unexplored. Here we used an analytical approach that intersects computational, evolutionary and molecular methods to study the genomic landscape of mosquito NIRVS. We demonstrate that NIRVS are differentially distributed across mosquito genomes, with a core set of seemingly the oldest integrations with similarity to Rhabdoviruses. Additionally, we compare the polymorphisms of NIRVS with respect to that of fast and slow-evolving genes within the Ae. albopictus genome. Overall, NIRVS appear to be less polymorphic than slow-evolving genes, with differences depending on whether they occur in intergenic regions or in piRNA clusters. Finally, two NIRVS that map within the coding sequences of genes annotated as Rhabdovirus RNA-dependent RNA polymerase and the nucleocapsid-encoding gene, respectively, are highly polymorphic and are expressed, suggesting exaptation possibly to enhance the mosquito's antiviral responses. These results greatly advance our understanding of the complexity of the mosquito repeatome and the biology of viral integrations in mosquito genomes