Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

Why barcode? High-throughput multiplex sequencing of mitochondrial genomes for molecular systematics

Mitochondrial genome sequences are important markers for phylogenetics but taxon sampling remains sporadic because of the great effort and cost required to acquire full-length sequences. Here, we demonstrate a simple, cost-effective way to sequence the full complement of protein coding mitochondrial genes from pooled samples using the 454/Roche platform. Multiplexing was achieved without the need for expensive indexing tags (‘barcodes’). The method was trialled with a set of long-range polymerase chain reaction (PCR) fragments from 30 species of Coleoptera (beetles) sequenced in a 1/16th sector of a sequencing plate. Long contigs were produced from the pooled sequences with sequencing depths ranging from ∼10 to 100× per contig. Species identity of individual contigs was established via three ‘bait’ sequences matching disparate parts of the mitochondrial genome obtained by conventional PCR and Sanger sequencing. This proved that assembly of contigs from the sequencing pool was correct. Our study produced sequences for 21 nearly complete and seven partial sets of protein coding mitochondrial genes. Combined with existing sequences for 25 taxa, an improved estimate of basal relationships in Coleoptera was obtained. The procedure could be employed routinely for mitochondrial genome sequencing at the species level, to provide improved species ‘barcodes’ that currently use the cox1 gene only

Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin

Firefly genomes illuminate parallel origins of bioluminescence in beetles

Fireflies and their luminous courtships have inspired centuries of scientific study. Today firefly luciferase is widely used in biotechnology, but the evolutionary origin of bioluminescence within beetles remains unclear. To shed light on this long-standing question, we sequenced the genomes of two firefly species that diverged over 100 million-years-ago: the North American Photinus pyralis and Japanese Aquatica lateralis. To compare bioluminescent origins, we also sequenced the genome of a related click beetle, the Caribbean Ignelater luminosus, with bioluminescent biochemistry near-identical to fireflies, but anatomically unique light organs, suggesting the intriguing hypothesis of parallel gains of bioluminescence. Our analyses support independent gains of bioluminescence in fireflies and click beetles, and provide new insights into the genes, chemical defenses, and symbionts that evolved alongside their luminous lifestyle

A revision and phylogenetic analysis of the subfamily Platerodinae with regional revisions of the genus Melaneros (Coleoptera, Lycidae)

The thesis on phylogeny and classification of Platerodinae is another contribution to higher level systematic and phylogeny of Lycidae. The first part of the thesis is a taxonomic revision and phylogenetic analysis of the genus-group taxa of Platerodinae itself. The paper deals with interrelationships of its three tribes Lyponiini, Libnetini and Platerodini, as well as with the relatedness of individual genera, and besides includes some species revisions of some small, formerly monotypic genera. The generic revision is followed by two species revisions of the genus Melaneros from China and New Guinea and by another two contributions on Melaneros species from the Himalayas and Sri Lanka.Available from STL, Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Lolodorfus Bocakova, 2014, gen. nov.

Lolodorfus gen. nov. (Figs. 1–3) Type species: Lolodorfus flavus sp. n. (by present designation). Diagnosis. Lolodorfus gen. nov. differs from Mimolibnetis Pic, 1936 in having 11 -segmented antennae while those of Mimolibnetis are 10 -segmented. Among other Dexorinae genera, Lolodorfus gen. nov., Mimolibnetis and Lampyrolycus can be easily recognized by elytra presenting 4 longitudinal costae and intercostal intervals with irregular reticulate cells. These genera differ in the length of elytral costa 1, which is fully developed in Lampyrolycus, while medially shortened in Lolodorfus gen. nov. and Mimolibnetis. Dexoris and Elgodexoris have a completely different arrangement of the elytra presenting irregular setiferous tubercles, while reticulate cells and elytral costae are absent. Description. Eyes large, interocular distance 1.1 x wider than eye diameter. Antennae filiform, 11 -segmented. Antennomere 1 large, 2 half as long as 1, 3 about 1.4 x longer than 2, 4 twice as long as 3 and 1.15 longer than 5, 4 longer than remainder. Antennomeres 4-10 diminishing in length (Figs. 1, 2). Mandibles and labrum reduced, vestigial. Maxillary and labial palpi elongate, apices of terminal palpomeres pointed. Pronotum trapezoidal, strongly widened posteriorly, 1.5 x wider basally, anterior margin weakly stretched forwards, lateral margins elevated dorsally, posterior angles acute. Pronotal carinae conspicuously flattened, reduced in pronotal folds forming broadly rhomboidal areola medially (Fig. 3). Discal area of pronotum punctate. Scutellum slightly emarginate distally. Elytra elongate, subparallel-sided, 3 x longer than humeral width. Each elytron with 4 longitudinal costae, primary costa 1 absent in distal third. Intercostal intervals with more or less double rows of irregular reticulate cells anteriorly, posterior half of elytra presenting single row of reticulate cells between longitudinal costae. Prosternum narrow, strongly transverse. Legs slender, compressed, trochanters elongate, as long as 1 / 3 of femur, obliquely attached to femora, tibiae straight. Female unknown. Etymology. The generic name is masculine and is latinised from the locality, Lolodorf in the Cameroon, where the species was collected. Distribution. Cameroon.Published as part of Bocakova, Milada, 2014, Lolodorfus, a new genus of net-winged beetles (Coleoptera: Lycidae: Dexorinae) from Cameroon, pp. 374-380 in Zootaxa 3811 (3) on pages 375-376, DOI: 10.11646/zootaxa.3811.3.8, http://zenodo.org/record/22920

New Melaneros-species from the Himalayas (Coleoptera: Lycidae)

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Lolodorfus, a new genus of net-winged beetles (Coleoptera: Lycidae: Dexorinae) from Cameroon

Bocakova, Milada (2014): Lolodorfus, a new genus of net-winged beetles (Coleoptera: Lycidae: Dexorinae) from Cameroon. Zootaxa 3811 (3): 374-380, DOI: 10.11646/zootaxa.3811.3.