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Despite advances in myocardial reperfusion therapies, acute myocardial ischaemia/reperfusion injury and consequent ischaemic heart failure represent the number one cause of morbidity and mortality in industrialized societies. Although different therapeutic interventions have been shown beneficial in preclinical settings, an effective cardioprotective or regenerative therapy has yet to be successfully introduced in the clinical arena. Given the complex pathophysiology of the ischaemic heart, large scale, unbiased, global approaches capable of identifying multiple branches of the signalling networks activated in the ischaemic/reperfused heart might be more successful in the search for novel diagnostic or therapeutic targets. High-throughput techniques allow high-resolution, genome-wide investigation of genetic variants, epigenetic modifications, and associated gene expression profiles. Platforms such as proteomics and metabolomics (not described here in detail) also offer simultaneous readouts of hundreds of proteins and metabolites. Isolated omics analyses usually provide Big Data requiring large data storage, advanced computational resources and complex bioinformatics tools. The possibility of integrating different omics approaches gives new hope to better understand the molecular circuitry activated by myocardial ischaemia, putting it in the context of the human ‘diseasome’. Since modifications of cardiac gene expression have been consistently linked to pathophysiology of the ischaemic heart, the integration of epigenomic and transcriptomic data seems a promising approach to identify crucial disease networks. Thus, the scope of this Position Paper will be to highlight potentials and limitations of these approaches, and to provide recommendations to optimize the search for novel diagnostic or therapeutic targets for acute ischaemia/reperfusion injury and ischaemic heart failure in the post-genomic era.
Background and aims: Spontaneous bacterial peritonitis (SBP) is a severe complication of decompensated cirrhosis. The prevalence of multidrug-resistant organisms (MDROs) in patients with cirrhosis is increasing. Identification of patients at risk for SBP due to MDROs (ie, SBP with the evidence of MDROs or Stenotrophomonas maltophilia in ascitic culture, MDRO-SBP) is crucial to the early adaptation of antibiotic treatment in such patients. We therefore investigated whether MDROs found in ascitic cultures can also be found in specimens determined by noninvasive screening procedures.
Patients and methods: This retrospective study was conducted at the liver center of the University Hospital Frankfurt, Germany. Between 2011 and 2016, patients with cirrhosis were included upon diagnosis of SBP and sample collection of aerobic/anaerobic ascitic cultures. Furthermore, the performance of at least one complete MDRO screening was mandatory for study inclusion.
Results: Of 133 patients diagnosed with SBP, 75 (56.4%) had culture-positive SBP and 22 (16.5%) had MDRO-SBP. Multidrug-resistant Escherichia coli (10/22; 45.5%) and vancomycin-resistant enterococci (7/22; 36.4%) resembled the major causatives of MDRO-SBP. Rectal swabs identified MDROs in 17 of 22 patients (77.3%) who developed MDRO-SBP with a time-dependent sensitivity of 77% and 87% after 30 and 90 days upon testing, while negative predictive value was 83% and 76%, respectively. The majority of patients were included from intensive care unit or intermediate care unit.
Conclusion: MDRO screening may serve as a noninvasive diagnostic tool to identify patients at risk for MDRO-SBP. Patients with decompensated cirrhosis should be screened for MDROs from the first day of inpatient treatment onward.
Simple Summary
Seizures are among the most common symptoms of meningioma patients even after surgery. This study sought to identify risk factors for early and late seizures in meningioma patients and to evaluate a modified version of a score to predict postoperative seizures on an independent cohort. The data underline that there are distinct factors identifying patients with a high risk of postoperative seizures following meningioma surgery which has been already shown before. We could further show that the high proportion of 43% of postoperative seizures occur as late seizures which are more dangerous because they may happen out of hospital. The modified STAMPE2 score could predict postoperative seizures when reaching very high scores but was not generally transferable to our independent cohort.
Abstract
Seizures are among the most common symptoms of meningioma. This retrospective study sought to identify risk factors for early and late seizures in meningioma patients and to evaluate a modified STAMPE2 score. In 556 patients who underwent meningioma surgery, we correlated different risk factors with the occurrence of postoperative seizures. A modified STAMPE2 score was applied. Risk factors for preoperative seizures were edema (p = 0.039) and temporal location (p = 0.038). For postoperative seizures preoperative tumor size (p < 0.001), sensomotory deficit (p = 0.004) and sphenoid wing location (p = 0.032) were independent risk factors. In terms of postoperative status epilepticus; sphenoid wing location (p = 0.022), tumor volume (p = 0.045) and preoperative seizures (p < 0.001) were independent risk factors. Postoperative seizures lead to a KPS deterioration and thus an impaired quality of life (p < 0.001). Late seizures occurred in 43% of patients with postoperative seizures. The small sub-cohort of patients (2.7%) with a STAMPE2 score of more than six points had a significantly increased risk for seizures (p < 0.001, total risk 70%). We concluded that besides distinct risk factors, high scores of the modified STAMPE2 score could estimate the risk of postoperative seizures. However, it seems not transferable to our cohort
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers potential cure to acute myeloid leukemia (AML) patients. However, infections with commensal bacteria are an important cause for non-relapse mortality (NRM). We have previously described the impact of multidrug-resistant organism (MDRO) colonization on the survival of allo-HSCT patients. In the aforementioned publication, according to consensus, we there did not consider the opportunistic gram-negative bacterium Stenotrophomonas maltophilia (S. maltophilia) to be an MDRO. Since rate of S. maltophilia colonization is increasing, and it is not known whether this poses a risk for allo-HSCT patients, we here analyzed here its effect on the previously described and now extended patient cohort. We report on 291 AML patients undergoing allo-HSCT. Twenty of 291 patients (6.9%) were colonized with S. maltophilia. Colonized patients did not differ from non-colonized patients with respect to their age, remission status before allo-HSCT, donor type and HSCT-comorbidity index. S. maltophilia colonized patients had a worse overall survival (OS) from 6 months up to 60 months (85% vs. 88.1% and 24.7% vs. 59.7%; p = 0.007) due to a higher NRM after allo-HSCT (6 months: 15% vs. 4.8% and 60 months: 40.1% vs. 16.2% p = 0.003). The main cause of mortality in colonized patients was infection (46.2% of all deaths) and in non-colonized patients relapse (58.8% of all deaths). 5/20 colonized patients developed an invasive infection with S. maltophilia. The worse OS after allo-HSCT due to higher infection related mortality might implicate the screening of allo-HSCT patients for S. maltophilia and a closer observation of colonized patients as outpatients.
Organoboranes are among the most versatile and widely used reagents in synthetic chemistry. A significant further expansion of their application spectrum would be achievable if boron-containing reactive intermediates capable of inserting into C–H bonds or performing nucleophilic substitution reactions were readily available. However, current progress in the field is still hampered by a lack of universal design concepts and mechanistic understanding. Herein we report that the doubly arylene-bridged diborane(6) 1H2 and its B[double bond, length as m-dash]B-bonded formal deprotonation product Li2[1] can activate the particularly inert C(sp3)–H bonds of added H3CLi and H3CCl, respectively. The first case involves the attack of [H3C]− on a Lewis-acidic boron center, whereas the second case follows a polarity-inverted pathway with nucleophilic attack of the B[double bond, length as m-dash]B double bond on H3CCl. Mechanistic details were elucidated by means of deuterium-labeled reagents, a radical clock, α,ω-dihaloalkane substrates, the experimental identification of key intermediates, and quantum-chemical calculations. It turned out that both systems, H3CLi/1H2 and H3CCl/Li2[1], ultimately funnel into the same reaction pathway, which likely proceeds past a borylene-type intermediate and requires the cooperative interaction of both boron atoms.
Background: Preclinical studies demonstrate synergism between cancer immunotherapy and local radiation, enhancing anti-tumor effects and promoting immune responses. BI1361849 (CV9202) is an active cancer immunotherapeutic comprising protamine-formulated, sequence-optimized mRNA encoding six non-small cell lung cancer (NSCLC)-associated antigens (NY-ESO-1, MAGE-C1, MAGE-C2, survivin, 5T4, and MUC-1), intended to induce targeted immune responses.
Methods: We describe a phase Ib clinical trial evaluating treatment with BI1361849 combined with local radiation in 26 stage IV NSCLC patients with partial response (PR)/stable disease (SD) after standard first-line therapy. Patients were stratified into three strata (1: non-squamous NSCLC, no epidermal growth factor receptor (EGFR) mutation, PR/SD after ≥4 cycles of platinum- and pemetrexed-based treatment [n = 16]; 2: squamous NSCLC, PR/SD after ≥4 cycles of platinum-based and non-platinum compound treatment [n = 8]; 3: non-squamous NSCLC, EGFR mutation, PR/SD after ≥3 and ≤ 6 months EGFR-tyrosine kinase inhibitor (TKI) treatment [n = 2]). Patients received intradermal BI1361849, local radiation (4 × 5 Gy), then BI1361849 until disease progression. Strata 1 and 3 also had maintenance pemetrexed or continued EGFR-TKI therapy, respectively. The primary endpoint was evaluation of safety; secondary objectives included assessment of clinical efficacy (every 6 weeks during treatment) and of immune response (on Days 1 [baseline], 19 and 61).
Results: Study treatment was well tolerated; injection site reactions and flu-like symptoms were the most common BI1361849-related adverse events. Three patients had grade 3 BI1361849-related adverse events (fatigue, pyrexia); there was one grade 3 radiation-related event (dysphagia). In comparison to baseline, immunomonitoring revealed increased BI1361849 antigen-specific immune responses in the majority of patients (84%), whereby antigen-specific antibody levels were increased in 80% and functional T cells in 40% of patients, and involvement of multiple antigen specificities was evident in 52% of patients. One patient had a partial response in combination with pemetrexed maintenance, and 46.2% achieved stable disease as best overall response. Best overall response was SD in 57.7% for target lesions.
Conclusion: The results support further investigation of mRNA-based immunotherapy in NSCLC including combinations with immune checkpoint inhibitors.
Trial registration: ClinicalTrials.gov identifier: NCT01915524.
Selective BRAF inhibitors such as vemurafenib have become a treatment option in patients with Langerhans cell Histiocytosis (LCH). To date, only 14 patients receiving vemurafenib for LCH have been reported. Although vemurafenib can stabilize the clinical condition of these patients, it does not seem to cure the patients, and it is unknown, when and how to stop vemurafenib treatment. We present a girl with severe multisystem LCH who responded only to vemurafenib. After 8 months of treatment, vemurafenib was tapered and replaced by prednisone and vinblastine, a strategy which has not been described to date. Despite chemotherapy, early relapse occurred, but remission was achieved by re-institution of vemurafenib. Further investigation needs to address the optimal duration of vemurafenib therapy in LCH and whether and which chemotherapeutic regimen may prevent disease relapse after cessation of vemurafenib.
Double reduction of the THF adduct of 9H-9-borafluorene (1⋅THF) with excess alkali metal affords the dianion salts M2[1] in essentially quantitative yields (M=Li–K). Even though the added charge is stabilized through π delocalization, [1]2− acts as a formal boron nucleophile toward organoboron (1⋅THF) and tetrel halide electrophiles (MeCl, Et3SiCl, Me3SnCl) to form B−B/C/Si/Sn bonds. The substrate dependence of open-shell versus closed-shell pathways has been investigated.
Two subvalent, redox-active diborane(4) anions, [3]4− and [3]2−, carrying exceptionally high negative charge densities are reported: Reduction of 9-methoxy-9-borafluorene with Li granules without stirring leads to the crystallization of the B(sp3)−B(sp2) diborane(5) anion salt Li[5]. [5]− contains a 2,2′-biphenyldiyl-bridged B−B core, a chelating 2,2′-biphenyldiyl moiety, and a MeO substituent. Reduction of Li[5] with Na metal gives the Na+ salt of the tetraanion [3]4− in which two doubly reduced 9-borafluorenyl fragments are linked via a B−B single bond. Comproportionation of Li[5] and Na4[3] quantitatively furnishes the diborane(4) dianion salt Na2[3], the doubly boron-doped congener of 9,9′-bis(fluorenylidene). Under acid catalysis, Na2[3] undergoes a formal Stone–Wales rearrangement to yield a dibenzo[g,p]chrysene derivative with B=B core. Na2[3] shows boron-centered nucleophilicity toward n-butyl chloride. Na4[3] produces bright blue chemiluminescence when exposed to air.
Pediatric patients with recurrent, refractory or advanced soft tissue sarcoma (STS) who are simultaneously showing signs of cumulative treatment toxicity are in need of novel therapies. In this preclinical analysis, we identified ErbB2 as a targetable antigen on STS cells and used cytokine-induced killer (CIK) cells transduced with the lentiviral 2nd-generation chimeric antigen receptor (CAR) vector pS-5.28.z-IEW to target ErbB2-positive tumors. Solely CIK cell subsets with the CD3+ T cell phenotype showed up to 85% cell surface expression of the respective CAR. A comparison of wildtype (WT), mock-vector and ErbB2-CAR-CIK cells showed, that engineered cells exhibited diminished in vitro expansion, retained WT CIK cell phenotype with higher percentages of differentiated effector memory/effector cells. Activating natural killer (NK) cell receptor NKG2D-restricted target cell recognition and killing of WT and ErbB2-CAR-CIK cells was maintained against ErbB2-negative tumors, while ErbB2-CAR-CIK cells demonstrated significantly increased cytotoxicity against ErbB2-positive targets, including primary tumors. ErbB2-CAR- but not WT CIK cells proliferated, infiltrated and efficiently lysed tumor cell monolayers as well as 3D tumor spheroids.
Here, we demonstrate a potential cell therapeutic approach using ErbB2-CAR-CIK cells for the recognition and elimination of tumor cells expressing ErbB2, which we identified as a targetable antigen on high-risk STS cells.
Background: Prolonged immunosuppression or delayed T-cell recovery may favor Epstein-Barr virus (EBV) infection or reactivation after allogeneic hematopoietic stem cell transplantation (HSCT), which can lead to post-transplant lymphoproliferative disease (PTLD) and high-grade malignant B-cell lymphoma. Cytokine-induced killer (CIK) cells with dual specific anti-tumor and virus-specific cellular immunity may be applied in this context.
Methods: CIK cells with EBV-specificity were generated from peripheral blood mononuclear cells (PBMCs), expanded in the presence of interferon-γ, anti-CD3, interleukin (IL)-2 and IL-15 and were pulsed twice with EBV consensus peptide pool. CIK cells with EBV-specificity and conventional CIK cells were phenotypically and functionally analyzed. Additionally, CIK cells with EBV-specificity were applied to a patient with EBV-related PTLD rapidly progressing to highly aggressive B-cell lymphoma on a compassionate use basis after approval and agreement by the regulatory authorities.
Results: Pre-clinical analysis showed that generation of CIK cells with EBV-specificity was feasible. In vitro cytotoxicity analyses showed increased lysis of EBV-positive target cells, enhanced proliferative capacity and increased secretion of cytolytic and proinflammatory cytokines in the presence of EBV peptide-displaying target cells. In addition, 1 week after infusion of CIK cells with EBV-specificity, the patient's highly aggressive B-cell lymphoma persistently disappeared. CIK cells with EBV-specificity remained detectable for up to 32 days after infusion and infusion did not result in acute toxicity.
Discussion: The transfer of both anti-cancer potential and T-cell memory against EBV infection provided by EBV peptide-induced CIK cells might be considered a therapy for EBV-related PTLD.
Neuroblastoma (NB) is the most common solid extracranial tumor in childhood. Despite therapeutic progress, prognosis in high-risk NB is poor and innovative therapies are urgently needed. Therefore, we addressed the potential cytotoxic capacity of interleukin (IL)-activated natural killer (NK) cells compared to cytokine-induced killer (CIK) cells for the treatment of NB. NK cells were isolated from peripheral blood mononuclear cells (PBMCs) by indirect CD56-enrichment or CD3/CD19-depletion and expanded with different cytokine combinations, such as IL-2, IL-15, and/or IL-21 under feeder-cell free conditions. CIK cells were generated from PBMCs by ex vivo stimulation with interferon-γ, IL-2, OKT-3, and IL-15. Comparative analysis of expansion rate, purity, phenotype and cytotoxicity was performed. CD56-enriched NK cells showed a median expansion rate of 4.3-fold with up to 99% NK cell content. The cell product after CD3/CD19-depletion consisted of a median 43.5% NK cells that expanded significantly faster reaching also 99% of NK cell purity. After 10–12 days of expansion, both NK cell preparations showed a significantly higher median cytotoxic capacity against NB cells relative to CIK cells. Remarkably, these NK cells were also capable of efficiently killing NB spheroidal 3D culture in long-term cytotoxicity assays. Further optimization using a novel NK cell culture medium and a prolonged culturing procedure after CD3/CD19-depletion for up to 15 days enhanced the expansion rate up to 24.4-fold by maintaining the cytotoxic potential. Addition of an IL-21 boost prior to harvesting significantly increased the cytotoxicity. The final cell product consisted for the major part of CD16−, NCR-expressing, poly-functional NK cells with regard to cytokine production, CD107a degranulation and antitumor capacity. In summary, our study revealed that NK cells have a significantly higher cytotoxic potential to combat NB than CIK cell products, especially following the synergistic use of IL-15 and IL-21 for NK cell activation. Therefore, the use of IL-15+IL-21 expanded NK cells generated from CD3/CD19-depleted apheresis products seems to be highly promising as an immunotherapy in combination with haploidentical stem cell transplantation (SCT) for high-risk NB patients.
Multidrug-resistant Gram-negative bacteria (MDR GNB) were found to colonise 60.8% (95% confidence interval: 52.3–68.9) of 143 refugee patients mainly from Syria (47), Afghanistan (29), and Somalia (14) admitted to the University Hospital Frankfurt, Germany, between June and December 2015. This percentage exceeds the prevalence of MDR GNB in resident patients four–fold. Healthcare personnel should be aware of this and the need to implement or adapt adequate infection control measures.
Ecological networks are more sensitive to plant than to animal extinction under climate change
(2016)
Impacts of climate change on individual species are increasingly well documented, but we lack understanding of how these effects propagate through ecological communities. Here we combine species distribution models with ecological network analyses to test potential impacts of climate change on >700 plant and animal species in pollination and seed-dispersal networks from central Europe. We discover that animal species that interact with a low diversity of plant species have narrow climatic niches and are most vulnerable to climate change. In contrast, biotic specialization of plants is not related to climatic niche breadth and vulnerability. A simulation model incorporating different scenarios of species coextinction and capacities for partner switches shows that projected plant extinctions under climate change are more likely to trigger animal coextinctions than vice versa. This result demonstrates that impacts of climate change on biodiversity can be amplified via extinction cascades from plants to animals in ecological networks.
From July 2002 to March 2004 the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) aboard the European Space Agency´s Environmental Satellite (Envisat) measured nearly continuously mid infrared limb radiance spectra. These measurements are utilised to retrieve the global distribution of the chlorofluorocarbon CFC-11 by applying a new fast forward model for Envisat MIPAS and an accompanying optimal estimation retrieval processor. A detailed analysis shows that the total retrieval errors of the individual CFC-11 volume mixing ratios are typically below 10% in the altitude range 10 to 25 km and that the systematic components dominate. Contribution of a priori information to the retrieval results are less than 5 to 10% and the vertical resolution of the observations is about 3 to 4 km in the same vertical range. The data are successfully validated by comparison with several other space experiments, an air-borne in-situ instrument, measurements from ground-based networks, and independent Envisat MIPAS analyses. The retrieval results from 425 000 Envisat MIPAS limb scans are compiled to provide a new climatological data set of CFC-11. The climatology shows significantly lower CFC-11 abundances in the lower stratosphere compared with the Reference Atmospheres for MIPAS (RAMstan V3.1) climatology. Depending on the atmospheric conditions the differences between the climatologies are up to 30 to 110 ppt (45 to 150%) at 19 to 27 km altitude. Additionally, time series of CFC-11 mean abundance and variability for five latitudinal bands are presented. The observed CFC-11 distributions can be explained by the residual mean circulation and large-scale eddy-transports in the upper troposphere and lower stratosphere. The new CFC-11 data set is well suited for further scientific studies.
Background: The most frequent therapy of hydrocephalus is the implantation of ventriculoperitoneal shunts for diverting cerebrospinal fluid from the ventricles into the peritoneum. We compared two adjustable valves, the proGAV and proGAV 2.0, for complications which resulted in revision operations.
Methods: Four hundred patients who underwent primary shunt implantation between 2014 and 2020 were analyzed for overall revision rate, one-year revision rate, revision free survival and overall survival observing patient age group, gender, etiology of hydrocephalus, implantation site, prior diversion of cerebrospinal fluid and cause of revision.
Results: All data were available of all 400 patients (female/male 208/192). Overall, 99 patients underwent revision surgery after primary implantation. ProGAV valve was implanted in 283 patients, proGAV 2.0 in 117 patients. There was no significant difference between the two shunt valves concerning revision rate (p=0.8069), one-year revision rate (p=0.9077), revision free survival (p=0.6921) and overall survival (p=0.3232). Furthermore, regarding one-year revision rate, we observed no significant difference between the two shunt valves in pediatric patients (40.7% vs 27.6%; p=0.2247). Revision operation had to be performed more frequently in pediatric patients (46.6% vs 24.8%; p=0.0093) with a significant higher number of total revisions with proGAV than proGAV 2.0 (55.9% vs. 27.6%; p=0.0110) most likely due to longer follow up in the proGAV -group.
Conclusion: According to the target variables we analyzed, aside from lifetime revision rate in pediatric patients there is no significant difference between the two shunt valves. From our subjective point of view, implantation of the newer proGAV 2.0 valve is preferable due to higher adjustment comfort for both patients and physicians.
This paper uses unique administrative data and a quasi-field experiment of exogenous allocation in Sweden to estimate medium- and longer-run effects on financial behavior from exposure to financially literate neighbors. It contributes evidence of causal impact of exposure and of a social multiplier of financial knowledge, but also of unfavorable distributional aspects of externalities. Exposure promotes saving in private retirement accounts and stockholding, especially when neighbors have economics or business education, but only for educated households and when interaction possibilities are substantial. Findings point to transfer of knowledge rather than mere imitation or effects through labor, education, or mobility channels.
The authors present evidence of a new propagation mechanism for wealth inequality, based on differential responses, by education, to greater inequality at the start of economic life. The paper is motivated by a novel positive cross-country relationship between wealth inequality and perceptions of opportunity and fairness, which holds only for the more educated. Using unique administrative micro data and a quasi-field experiment of exogenous allocation of households, the authors find that exposure to a greater top 10% wealth share at the start of economic life in the country leads only the more educated placed in locations with above-median wealth mobility to attain higher wealth levels and position in the cohort-specific wealth distribution later on. Underlying this effect is greater participation in risky financial and real assets and in self-employment, with no evidence for a labor income, unemployment risk, or human capital investment channel. This differential response is robust to controlling for initial exposure to fixed or other time-varying local features, including income inequality, and consistent with self-fulfilling responses of the more educated to perceived opportunities, without evidence of imitation or learning from those at the top.
The Eurozone fiscal crisis has created pressure for institutional harmonization, but skeptics argue that cultural predispositions can prevent convergence in behavior. Our paper derives a robust cultural classification of European countries and utilizes unique data on natives and immigrants to Sweden. Classification based on genetic distance or on Hofstede’s cultural dimensions fails to identify a single ‘southern’ culture but points to a ‘northern’ culture. Significant differences in financial behavior are found across cultural groups, controlling for household characteristics. Financial behavior tends to converge with longer exposure to common institutions, but is slowed down by longer exposure to original institutions.
Background: The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC. Methods: The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 3-year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating. Discussion: If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection, patients should experience less post-transplant problems with HCC recurrence, and therefore could expect a longer and better quality of life. A positive outcome will likely change the standard of posttransplant immunosuppressive care for LT patients with HCC. (trial registered at www.clinicaltrials.gov: NCT00355862) (EudraCT Number: 2005-005362-36)
The New World genus Dysmerus Casey, currently with one valid species, is revised. Lectotypes are designated for two species, Dysmerus caseyi (Grouvelle), new status, and Dysmerus sulcicollis Grouvelle, new status. Both are revived from synonymy with D. basalis Casey. Twelve new species are described: Dysmerus boliviensis Thomas, new species, Dysmerus curvicornis Thomas, new species, Dysmerus genaspinosus Thomas, new species, Dysmerus hamaticornis Thomas, new species, Dysmerus impolitus Thomas, new species, Dysmerus skelleyi Thomas, new species, Dysmerus mexicanus Thomas, new species, Dysmerus monstrosus Thomas, new species, Dysmerus politus Thomas, new species, Dysmerus rondoniensis Thomas, new species, Dysmerus symphilus Thomas, new species, and Dysmerus trinidadensis Thomas, new species. A key to adults of the species and illustrations are provided.
Australophanus, new genus, is described and illustrated for Cryptamorpha redtenbacheri (Reitter). Platamus Erichson is synonymized under Telephanus Erichson, new synonymy. Euplatamus Sharp, new status, replaces Platamus Erichson as the genus name. Type species are designated for Aplatamus Grouvelle and Euplatamus Sharp. Telephanus velox (Haldeman) is synonymized under Telephanus atricapillus Erichson. A diagnosis of the tribe Telephanini, a key to the described telephanine genera of the world is presented, and a phylogeny of the family Silvanidae is proposed.
This article outlines changes in procedures and production policies for the journal Insecta Mundi. Background data and discussions leading to these necessary changes are explained. Updated instructions for authors are presented. A full current version of author instructions will be posted on the latest Center for Systematic Entomology URL.
The species of the genus Lathropus Erichson are reviewed for Florida and the West Indies, excluding the Lesser Antilles. Seven species are recorded from this region, three of which are described as new: Lathropus chickcharnie Thomas, new species, Lathropus jamaicensis Thomas, new species, and Lathropus rhabdophloeoides Thomas, new species. A lectotype is designated for Lathropus vernalis Casey, and Lathropus striatus Casey is synonymized under Lathropus vernalis Casey, new synonymy. Illustrations and a key to the species of this geographgic region are provided.
The key description and illustrations of mouthparts, ocelli, and terminal abdominal segments by Bovinq & Craighead (1931) have been the only information on the larval stages of the genus Hemipeplus Latreille, except for the observation by van Emden (1942) that individuals of the genus would not key properly in Boving & Craighead's key. Their example was of an undescribed species from Cuba. The semidiagrammatic illustrations make it difficult to identify the species illustrated, although it may be H. marginipennis (LeConte). This paper is based on larvae collected by the authors, in each case associated with adults. From the family diagnosis of larval Mycteridae (Crowson & Viedma 1964). Hemipeplus larvae differ noticeably in the form of the sensorium, which Crowson & Viedma describe as “very short, dome-shaped”; in Hemipeplus it is elongate and conical. From the larva of Mycterus (described by Crowson & Viedma 1964) those of Hemipeplus also differ in having five ocelli on each side (cf. two), mala with an uncus and medial pit (cf. without uncus or medial pit), mola ridged (cf. not ridged), cardines not divided (cf. distinctly divided, labial palpi with only one distinct palpomere (cf. with two palpomeres), abdominal asperities absent (cf. asperities present), and different form of spiracle (compare fig. 13 with fig. 4 in Crowson & Viedma 1964). Larvae of Hemipeplus are more similar to that of Eurypus muelleri Seldlitz (described by Costa & Vanin 1977) than to that of Mycterus. As in Hemipeplus, Eurypus larvae possess five ocelli arranged in rows of three and two on each side; two pairs of tubercles at posterior margin of abdominal sternite IX; mala with an uncus, and cardines divided. Hemipeplus larvae differ from those of Mycterus most notably in the form of abdominal tergite IX (see Costa & Vanin 1977:fig. 2 ) . The uncus is located on the mesal margin of the mala in Hemipeplus, whereas it is located on the ventral aspect of the mala in Eurypus.
The New World species of Cryptolestes Ganglbauer are revised and keys, diagnoses, descriptions, and illustrations are provided for the 13 non-economic species. Six stored products species of the genus are also keyed and illustrated. Two species, Laemophloeus pubescens Casey and L. bicolor Chevrolat, are reassigned to Cryptolestes. Eight new species are described: C. dissimulatus (southwestern United States); C. dybasi (Florida); C. mexicanus (Mexico and Guatemala); C. capillulus (Brazil); C. spatulifer (Argentina); C. trinidadensis (Trinidad); C. ampiyacus (Peru); and C. calabozus (Venezuela). Cryptolestes uncicornis (Reitter) is revived from synonymy under C. punctatus (LeConte), C. schwarzi (Casey) is revived from synonymy under C. weisei (Reitter), and four specific names are synonymized: C. quadratus (Casey) [ = C. uncicornis (Reitter)]; C. extricatus (Casey) and C. adumbratus Casey [ = C. punctatus (LeConte)]; and Laemophloeus concavus (Reitter) [ = C. bicolor (Chevrolat)]. Cyptolestes horni (Casey) and C. disseptus Casey are removed from Cryptolestes and reassigned to Rhabdophloeus Sharp. Lectotypes are designated for Laemophloeus geminatus LeConte, Cryptolestes adumbratus Casey, and Laemophloeus quadratus Casey.
A specimen of Rhizophagus sayi Schaeffer collected in a flight trap at 29°34½'N82°29'W in Alachua County, Florida, on 23-1-1993, by R.W. Lundgren prompted a search of unidentified specimens in the Florida State Collection of Arthropods. The search resulted in the discovery of seven additional Florida specimens with the following data: "FLA., Dixie Co. 3.5mi. N. Old Town 13-1-1980 Coll. M.C. Thomas", 2; "FLORIDA: Alachua Co. Gainesville 3-XII-1983 Coll. M.C. Thomas", 1; "FLORIDA: Alachua Co. San Felasco Hammock 4-11-1983 M.C. Thomasn, 3; same, except date is 12-II-1983. These specimens comprise a new state record for R. sayi, which Bousquet (1990) recorded from most of the eastern United States except for Florida and Georgia.
One of the rarest U.S. cerambycids, Romulus globosus, was described by Knull in 1948 based on four specimens collected in peninsular Florida. No new records have been reported in the literature since. Linsley (1963) apparently saw no specimens, since he merely quoted the original description, and gave the distribution as "Southern Florida."
Neoma, a new genus of Cerambycidae (Coleoptera: Cerambycidae: Prioninae: Macrotomini) is described for Mallodonopsis corrosus Bates, 1879, compared to related genera (Aplagiognathus Thomson, 1861; Archodontes Lameere, 1903; and Mallodonopsis Thomson, 1861), and its tribal position discussed. A lectotype for Mallodonopsis corrosus is here designated with the species redescribed and figured.
Several Coleopterists have been asked to revise the family sections, working from diskettes modified and provided from the original "Beetles of the United States." They will rewrite these sections, and will be recognized as the author of the section. They are asked to sign a writing contract with the publisher. Other Coleopterists have been asked to review the family sections of the new book. These persons are acknowledged in the family section text.
The Mesoamerican species of Telephanus distinguished by the presence eight lateral pronotal spines
and long temples are reviewed. The group includes T. serratus Nevermann and two previously undescribed species
that are described herein: T. bellus Thomas, new species, from Costa Rica, and the flightless T. monstrosus
Thomas, new species, from Mexico.
The Guadeloupe Archipelago, the French overseas Département de Guadeloupe, is a geographically associated group of islands and a natural biogeographic unit. The islands have been available for terrestrial colonization since the late Tertiary. From the viewpoint of beetle systematics and biodiversity, this is the most important set of islands of the Lesser Antilles because more species have been described or recorded from Guadeloupe than any other island or group in the Lesser Antilles. We present a summary of the 1338 beetle species recorded in the literature from the archipelago, in 60 families, and 719 genera. The families with the largest numbers of species are Curculionidae (420), Staphylinidae (153), Chrysomelidae (75), Cerambycidae (69), Scarabaeidae (64), and Tenebrionidae (59). Four hundred eighty two species are known only from one or more islands of the Guadeloupe group and likely speciated there. Guadeloupe is the type locality for an additional 59 species. At least 61 species have been accidentally introduced by human activities. A total of 261 species are known only from the Lesser Antilles including Guadeloupe. The remaining species are naturally more widespread in the Lesser Antilles, or the West Indies, and elsewhere in the New World. The actual number of species on the Guadeloupe Archipelago is estimated to be around 1850 or more species.
The genus Pediacus Shuckard is revised for America north of Mexico. Seven species are recorded: P. andrewsi Thomas, n. sp.; P. fuscus Erichson; P. gracilis Thomas, n. sp.; P. hesperoglaber Thomas, n. sp.; P. ommatodon Thomas, n. sp.; P. stephani Thomas, n. sp.; and P. subglaber LeConte, new status. The species are described and illustrated, and a key is presented for their identification. The described European and Neotropical species are reviewed and illustrated.
The following new species of Cryptolestes Ganglbauer are described and illustrated: Cryptolestes obesus Thomas, new species, Brazil; Cryptolestes turnbowi Thomas, new species, Honduras and Mexico; Cryptolestes inyoensis Thomas, new species, California; Cryptolestes spectabilis Thomas, new species, Ecuador. A revised key to the New World species is provided. The male genitalia are illustrated and the female of C. calabozus Thomas is characterized, and new distribution records are provided for it, C. cornutus Thomas and Zimmerman, C. trinidadensis Thomas, C. curus Lefkovitch, and C. hlapperichi Lefkovitch.
Four species of Anchonus Schonherr occur in Florida: A. flol'idanus Schwarz, A. dul'yi Blatchley, A. blatchleyi Sleeper, and A. suillus (Fabricius), which is recorded from Florida and the continental United States for the first time. The species are distinguished in a key and illustrated. A lectotype is selected for A. floridanus.
New distribution records for two species of Cryptolestes Ganglbauer (Coleoptera: Laemophloeidae)
(2005)
The nine Nearctic species of Laemophloeus Dejean (Coleoptera: Laemophloeidae) are reviewed, keyed, and illustrated. One species, L. apache Thomas, n. sp., is described as new. Two previously described species are synonymized: L. californicus Casey (= L. biguttatus (Say), n. syn.) and L. woodruffi Thomas (= L. fervidus Casey, n. syn.). A neotype is designated for L. biguttatus (Say), and lectotypes are designated for L. terminalis Casey and L. fervidus Casey. A checklist of the described world species is provided.