Emplacement of inflated Pāhoehoe flows in the Naude’s Nek Pass, Lesotho remnant, Karoo continental flood basalt province: use of flow-lobe tumuli in understanding flood basalt emplacement

Physical volcanological features are presented for a 710-m-thick section, of the Naude’s Nek Pass, within the lower part of the Lesotho remnant of the Karoo Large Igneous Province. The section consists of inflated pāhoehoe lava with thin, impersistent sedimentary interbeds towards the base. There are seven discreet packages of compound and hummocky pāhoehoe lobes containing flow-lobe tumuli, making up approximately 50% of the section. Approximately 45% of the sequence consists of 14 sheet lobes, between 10 and 52-m-thick. The majority of the sheet lobes are in two packages indicating prolonged periods of lava supply capable of producing thick sheet lobes. The other sheet lobes are as individual lobes or pairs, within compound flows, suggesting brief increases in lava supply rate. We suggest, contrary to current belief, that there is no evidence that compound flows are proximal to source and sheet lobes (simple flows) are distal to source and we propose that the presence of flow-lobe tumuli in compound flows could be an indicator that a flow is distal to source. We use detailed, previously published, studies of the Thakurvadi Formation (Deccan Traps) as an example. We show that the length of a lobe and therefore the sections that are ‘medial or distal to source’ are specific to each individual lobe and are dependent on the lava supply of each eruptive event, and as such flow lobe tumuli can be used as an indicator of relative distance from source

Considering the Case for Biodiversity Cycles: Reexamining the Evidence for Periodicity in the Fossil Record

Medvedev and Melott (2007) have suggested that periodicity in fossil biodiversity may be induced by cosmic rays which vary as the Solar System oscillates normal to the galactic disk. We re-examine the evidence for a 62 million year (Myr) periodicity in biodiversity throughout the Phanerozoic history of animal life reported by Rohde & Mueller (2005), as well as related questions of periodicity in origination and extinction. We find that the signal is robust against variations in methods of analysis, and is based on fluctuations in the Paleozoic and a substantial part of the Mesozoic. Examination of origination and extinction is somewhat ambiguous, with results depending upon procedure. Origination and extinction intensity as defined by RM may be affected by an artifact at 27 Myr in the duration of stratigraphic intervals. Nevertheless, when a procedure free of this artifact is implemented, the 27 Myr periodicity appears in origination, suggesting that the artifact may ultimately be based on a signal in the data. A 62 Myr feature appears in extinction, when this same procedure is used. We conclude that evidence for a periodicity at 62 Myr is robust, and evidence for periodicity at approximately 27 Myr is also present, albeit more ambiguous.Comment: Minor modifications to reflect final published versio

Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel

Introduction: Sorafenib, a multitarget kinase inhibitor, targets members of the mitogen-activated protein kinase (MAPK) pathway and VEGFR kinases. Here we assessed the association between expression of sorafenib targets and biomarkers of taxane sensitivity and response to therapy in pre-treatment tumors from patients enrolled in ECOG 2603, a phase III comparing sorafenib, carboplatin and paclitaxel (SCP) to carboplatin, paclitaxel and placebo (CP). Methods: Using a method of automated quantitative analysis (AQUA) of in situ protein expression, we quantified expression of VEGF-R2, VEGF-R1, VEGF-R3, FGF-R1, PDGF-Rβ, c-Kit, B-Raf, C-Raf, MEK1, ERK1/2, STMN1, MAP2, EB1 and Bcl-2 in pretreatment specimens from 263 patients. Results: An association was found between high FGF-R1 and VEGF-R1 and increased progression-free survival (PFS) and overall survival (OS) in our combined cohort (SCP and CP arms). Expression of FGF-R1 and VEGF-R1 was higher in patients who responded to therapy ((CR+PR) vs. (SD+PD+ un-evaluable)). Conclusions: In light of the absence of treatment effect associated with sorafenib, the association found between FGF-R1 and VEGF-R1 expression and OS, PFS and response might reflect a predictive biomarker signature for carboplatin/paclitaxel-based therapy. Seeing that carboplatin and pacitaxel are now widely used for this disease, corroboration in another cohort might enable us to improve the therapeutic ratio of this regimen. © 2013 Jilaveanu et al

PedGenie: meta genetic association testing in mixed family and case-control designs

<p>Abstract</p> <p>Background-</p> <p>PedGenie software, introduced in 2006, includes genetic association testing of cases and controls that may be independent or related (nuclear families or extended pedigrees) or mixtures thereof using Monte Carlo significance testing. Our aim is to demonstrate that PedGenie, a unique and flexible analysis tool freely available in Genie 2.4 software, is significantly enhanced by incorporating meta statistics for detecting genetic association with disease using data across multiple study groups.</p> <p>Methods-</p> <p>Meta statistics (chi-squared tests, odds ratios, and confidence intervals) were calculated using formal Cochran-Mantel-Haenszel techniques. Simulated data from unrelated individuals and individuals in families were used to illustrate meta tests and their empirically-derived p-values and confidence intervals are accurate, precise, and for independent designs match those provided by standard statistical software.</p> <p>Results-</p> <p>PedGenie yields accurate Monte Carlo p-values for meta analysis of data across multiple studies, based on validation testing using pedigree, nuclear family, and case-control data simulated under both the null and alternative hypotheses of a genotype-phenotype association.</p> <p>Conclusion-</p> <p>PedGenie allows valid combined analysis of data from mixtures of pedigree-based and case-control resources. Added meta capabilities provide new avenues for association analysis, including pedigree resources from large consortia and multi-center studies.</p

SALL4 Expression in Gonocytes and Spermatogonial Clones of Postnatal Mouse Testes

The spermatogenic lineage is established after birth when gonocytes migrate to the basement membrane of seminiferous tubules and give rise to spermatogonial stem cells (SSC). In adults, SSCs reside within the population of undifferentiated spermatogonia (Aundiff) that expands clonally from single cells (Asingle) to form pairs (Apaired) and chains of 4, 8 and 16 Aaligned spermatogonia. Although stem cell activity is thought to reside in the population of Asingle spermatogonia, new research suggests that clone size alone does not define the stem cell pool. The mechanisms that regulate self-renewal and differentiation fate decisions are poorly understood due to limited availability of experimental tools that distinguish the products of those fate decisions. The pluripotency factor SALL4 (sal-like protein 4) is implicated in stem cell maintenance and patterning in many organs during embryonic development, but expression becomes restricted to the gonads after birth. We analyzed the expression of SALL4 in the mouse testis during the first weeks after birth and in adult seminiferous tubules. In newborn mice, the isoform SALL4B is expressed in quiescent gonocytes at postnatal day 0 (PND0) and SALL4A is upregulated at PND7 when gonocytes have colonized the basement membrane and given rise to spermatogonia. During steady-state spermatogenesis in adult testes, SALL4 expression overlapped substantially with PLZF and LIN28 in Asingle, Apaired and Aaligned spermatogonia and therefore appears to be a marker of undifferentiated spermatogonia in mice. In contrast, co-expression of SALL4 with GFRα1 and cKIT identified distinct subpopulations of Aundiff in all clone sizes that might provide clues about SSC regulation. Collectively, these results indicate that 1) SALL4 isoforms are differentially expressed at the initiation of spermatogenesis, 2) SALL4 is expressed in undifferentiated spermatogonia in adult testes and 3) SALL4 co-staining with GFRα1 and cKIT reveals distinct subpopulations of Aundiff spermatogonia that merit further investigation. © 2013 Gassei, Orwig

Calpain system protein expression in carcinomas of the pancreas, bile duct and ampulla

Background: Pancreatic cancer, including cancer of the ampulla of Vater and bile duct, is very aggressive and has a poor five year survival rate; improved methods of patient stratification are required. Methods: We assessed the expression of calpain-1, calpain-2 and calpastatin in two patient cohorts using immunohistochemistry on tissue microarrays. The first cohort was composed of 68 pancreatic adenocarcinomas and the second cohort was composed of 120 cancers of the bile duct and ampulla. Results: In bile duct and ampullary carcinomas an association was observed between cytoplasmic calpastatin expression and patient age (P = 0.036), and between nuclear calpastatin expression and increased tumour stage (P = 0.026) and the presence of vascular invasion (P = 0.043). In pancreatic cancer, high calpain-2 expression was significantly associated with improved overall survival (P = 0.036), which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.342; 95% confidence interva l = 0.157-0.741; P = 0.007). In cancers of the bile duct and ampulla, low cytoplasmic expression of calpastatin was significantly associated with poor overall survival (P = 0.012), which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.595; 95% confidence interval = 0.365-0.968; P = 0.037). Conclusion: The results suggest that calpain-2 and calpastatin expression is important in pancreatic cancers, influencing disease progression. The findings of this study warrant a larger follow-up study. Keywords: Calpain, Calpastatin, Pancreas, Ampulla, Bile duct, Cance

Where do the elderly die? The impact of nursing home utilisation on the place of death. Observations from a mortality cohort study in Flanders

BACKGROUND: Most of the research concerning place of death focuses on terminally ill patients (cancer patients) while the determinants of place of death of the elderly of the general population are not intensively studied. Studies showed the influence of gender, age, social-economical status and living arrangements on the place of death, but a facet not taken into account so far is the influence of the availability of nursing homes. METHODS: We conducted a survey of deaths, between January 1999 and December 2000 in a small densely populated area in Belgium, with a high availability of nursing homes (within 5 to 10 km of the place of residence of every elderly). We determined the incidence of total mortality (of subjects >60 years) from local official death registers that we consulted via the priest or the mortician of the local parish, to ask where the decedent had died and whether the deceased had lived in a nursing home. We compared the distribution of the places of death between parishes with a nursing home and with parishes without nursing home. RESULTS: 240 women and 217 men died during the two years study period. Only 22% died at home, while the majority (78%) died in an institutional setting, either a hospital (50%) or a nursing home (28%). Place of death was influenced by individual factors (age and gender) and the availability of a nursing home in the 'own' parish. The chance of in-hospital death was 65% higher for men (95% Confidence Interval [CI]: 14 to 138%; p = 0.008) and decreased by 4% (CI: -5.1% to -2.5%; p < 0.0001) for each year increase in age. Independent of gender and age, the chance of in-hospital death was 41% (CI: -60% to -13%; p = 0.008) lower in locations with a nursing home. CONCLUSION: Demographic, but especially social-contextual factors determine where elderly will end their life. The majority of elderly in Flanders die in an institution. Age, gender and living situation are predictors of the place of death but the embedment of a nursing home in the local community seems to be a key predictor

Is the Good Polity Attainable? Measuring the Quality of Democracy

This article introduces a discussion on defining, measuring, and assessing the quality of democracy. Providing a short overview of the papers of the Symposium, it places them within a broader context of current academic debate on various methodological, theoretical, and policy outreach dimensions of the topic

Probing Chemical Space with Alkaloid-Inspired Libraries

Screening of small molecule libraries is an important aspect of probe and drug discovery science. Numerous authors have suggested that bioactive natural products are attractive starting points for such libraries, due to their structural complexity and sp3-rich character. Here, we describe the construction of a screening library based on representative members of four families of biologically active alkaloids (Stemonaceae, the structurally related cyclindricine and lepadiformine families, lupin, and Amaryllidaceae). In each case, scaffolds were based on structures of the naturally occurring compounds or a close derivative. Scaffold preparation was pursued following the development of appropriate enabling chemical methods. Diversification provided 686 new compounds suitable for screening. The libraries thus prepared had structural characteristics, including sp3 content, comparable to a basis set of representative natural products and were highly rule-of-five compliant

Search for Gravitational Waves from Primordial Black Hole Binary Coalescences in the Galactic Halo

We use data from the second science run of the LIGO gravitational-wave detectors to search for the gravitational waves from primordial black hole (PBH) binary coalescence with component masses in the range 0.2--$1.0 M_\odot$. The analysis requires a signal to be found in the data from both LIGO observatories, according to a set of coincidence criteria. No inspiral signals were found. Assuming a spherical halo with core radius 5 kpc extending to 50 kpc containing non-spinning black holes with masses in the range 0.2--$1.0 M_\odot$, we place an observational upper limit on the rate of PBH coalescence of 63 per year per Milky Way halo (MWH) with 90% confidence.Comment: 7 pages, 4 figures, to be submitted to Phys. Rev.