Cinacalcet-induced hypocalcemia in a cohort of European haemodialysis patients: predictors, therapeutic approaches and outcomes

BACKGROUND: Calcimimetic treatment of secondary hyperparathyroidism in chronic dialysis patients is often followed by hypocalcemia. METHODS: We investigated the frequency, predictors, consequences and therapeutic responses following cinacalcet-induced hypocalcemia in an incident European hemodialysis cohort of 1068 patients with a cinacalcet prescription. RESULTS: Of 905 normocalcemic patients initiating cinacalcet, 67% developed hypocalcemia within 12 months: 68% mild, 23% moderate, 9% severe. Compared to persistently normocalcemic patients, those with severe hypocalcemia were more often diabetic, overweight, had cardiovascular disease, shorter dialysis vintage, used a catheter dialysis access, had fewer active vitamin-D sterols, and exhibited higher CRP and iPTH and lower calcium levels. Multivariate predictors of hypocalcemia included a catheter for vascular access, low albumin and high iPTH. Generally, no therapeutic intervention to prevent hypocalcemia was taken prior to cinacalcet initiation. After the hypocalcemic event, the most common clinical response was no change of the dialysis or medical regimen. Following the hypocalcemic event, iPTH remained low even in those with severe hypocalcemia. The number of deaths and cardiovascular events did not differ between patients with and without hypocalcemia within six months following cinacalcet initiation. CONCLUSION: Two-thirds of cinacalcet initiated patients experienced hypocalcaemia with 9% being severe. Hypocalcemia was mostly asymptomatic, transient (with and without targeted intervention to correct it) and not associated with an increase in cardiovascular events or deaths

Half-Metallic Graphene Nanoribbons

Electrical current can be completely spin polarized in a class of materials known as half-metals, as a result of the coexistence of metallic nature for electrons with one spin orientation and insulating for electrons with the other. Such asymmetric electronic states for the different spins have been predicted for some ferromagnetic metals - for example, the Heusler compounds- and were first observed in a manganese perovskite. In view of the potential for use of this property in realizing spin-based electronics, substantial efforts have been made to search for half-metallic materials. However, organic materials have hardly been investigated in this context even though carbon-based nanostructures hold significant promise for future electronic device. Here we predict half-metallicity in nanometre-scale graphene ribbons by using first-principles calculations. We show that this phenomenon is realizable if in-plane homogeneous electric fields are applied across the zigzag-shaped edges of the graphene nanoribbons, and that their magnetic property can be controlled by the external electric fields. The results are not only of scientific interests in the interplay between electric fields and electronic spin degree of freedom in solids but may also open a new path to explore spintronics at nanometre scale, based on graphene

First direct observation of Dirac fermions in graphite

Originating from relativistic quantum field theory, Dirac fermions have been recently applied to study various peculiar phenomena in condensed matter physics, including the novel quantum Hall effect in graphene, magnetic field driven metal-insulator-like transition in graphite, superfluid in 3He, and the exotic pseudogap phase of high temperature superconductors. Although Dirac fermions are proposed to play a key role in these systems, so far direct experimental evidence of Dirac fermions has been limited. Here we report the first direct observation of massless Dirac fermions with linear dispersion near the Brillouin zone (BZ) corner H in graphite, coexisting with quasiparticles with parabolic dispersion near another BZ corner K. In addition, we report a large electron pocket which we attribute to defect-induced localized states. Thus, graphite presents a novel system where massless Dirac fermions, quasiparticles with finite effective mass, and defect states all contribute to the low energy electronic dynamics.Comment: Nature Physics, in pres

Errors in recall of age at first sex

Aims: To measure the degree and direction of errors in recall of age at first sex. Method: Participants were initially recruited in 1994–1995 (Wave I) with 3 subsequent follow-ups in: 1996 (Wave II); 2001– 2002 (Wave III); and 2007–2008 (Wave IV). Participants' individual errors in recall of their age at first sex at Wave IV were estimated by the paired difference between responses given for age at first sex in Wave I and Wave IV (recalled age at first sex obtained at Wave IV minus the age at first sex obtained at Wave I). Results: The mean of the recall-estimation of age at first sex at Wave IV was found to be slightly increased comparing to the age at first sex at Wave I (less than 1 year). The errors in the recalled age at first sex tended to increase in participants who had their first sex younger or older than the average, and the recalled age at first sex tended to bias towards the mean (i.e. participants who had first sex younger than the average were more likely to recall an age at first sex that was older than the age, and vice versa). Conclusions: In this U.S. population-based sample, the average recall error for age at first sex was small. However, the accuracy of recalled information varied significantly among subgroup populations

Gate-Controlled Ionization and Screening of Cobalt Adatoms on a Graphene Surface

We describe scanning tunneling spectroscopy (STS) measurements performed on individual cobalt (Co) atoms deposited onto backgated graphene devices. We find that Co adatoms on graphene can be ionized by either the application of a global backgate voltage or by the application of a local electric field from a scanning tunneling microscope (STM) tip. Large screening clouds are observed to form around Co adatoms ionized in this way, and we observe that some intrinsic graphene defects display a similar behavior. Our results provide new insight into charged impurity scattering in graphene, as well as the possibility of using graphene devices as chemical sensors.Comment: 19 pages, 4 figure

Anisotropic behaviors of massless Dirac fermions in graphene under periodic potential

Charge carriers of graphene show neutrino-like linear energy dispersions as well as chiral behavior near the Dirac point. Here we report highly unusual and unexpected behaviors of these carriers in applied external periodic potentials, i.e., in graphene superlattices. The group velocity renormalizes highly anisotropically even to a degree that it is not changed at all for states with wavevector in one direction but is reduced to zero in another, implying the possibility that one can make nanoscale electronic circuits out of graphene not by cutting it but by drawing on it in a non-destructive way. Also, the type of charge carrier species (e.g. electron, hole or open orbit) and their density of states vary drastically with the Fermi energy, enabling one to tune the Fermi surface-dominant properties significantly with gate voltage. These results address the fundamental question of how chiral massless Dirac fermions propagate in periodic potentials and point to a new possible path for nanoscale electronics.Comment: 10 pages, 9 figure

Human Papilloma Virus (HPV) Oral Prevalence in Scotland (HOPSCOTCH):a feasibility study in dental settings

The purpose of this study was to test the feasibility of undertaking a full population investigation into the prevalence, incidence, and persistence of oral Human Papilloma Virus (HPV) in Scotland via dental settings. Male and female patients aged 16-69 years were recruited by Research Nurses in 3 primary care and dental outreach teaching centres and 2 General Dental Practices (GDPs), and by Dental Care Teams in 2 further GDPs. Participants completed a questionnaire (via an online tablet computer or paper) with socioeconomic, lifestyle, and sexual history items; and were followed up at 6-months for further questionnaire through appointment or post/online. Saline oral gargle/rinse samples, collected at baseline and follow-up, were subject to molecular HPV genotyping centrally. 1213 dental patients were approached and 402 individuals consented (participation rate 33.1%). 390 completed the baseline questionnaire and 380 provided a baseline oral specimen. Follow-up rate was 61.6% at 6 months. While recruitment was no different in Research Nurse vs Dental Care Team models the Nurse model ensured more rapid recruitment. There were relatively few missing responses in the questionnaire and high levels of disclosure of risk behaviours (99% answered some of the sexual history questions). Data linkage of participant data to routine health records including HPV vaccination data was successful with 99.1% matching. Oral rinse/gargle sample collection and subsequent HPV testing was feasible. Preliminary analyses found over 95% of samples to be valid for molecular HPV detection prevalence of oral HPV infection of 5.5% (95%CI 3.7, 8.3). It is feasible to recruit and follow-up dental patients largely representative / reflective of the wider population, suggesting it would be possible to undertake a study to investigate the prevalence, incidence, and determinants of oral HPV infection in dental settings

In vitro hypoxia-conditioned colon cancer cell lines derived from HCT116 and HT29 exhibit altered apoptosis susceptibility and a more angiogenic profile in vivo

Hypoxia is an important selective force in the clonal evolution of tumours. Through HIF-1 and other transcription factors combined with tumour-specific genetic alterations, hypoxia is a dominant factor in the angiogenic phenotype. Cellular adaptation to hypoxia is an important requirement of tumour progression independent of angiogenesis. The adaptive changes, insofar as they alter hypoxia-induced apoptosis, are likely to determine responsiveness to antiangiogenic strategies. To investigate this adaptation of tumour cells to hypoxia, we recreated in vitro the in vivo situation of chronic intermittent exposure to low-oxygen levels. The colon carcinoma cell lines HT29 and HCT116 were subjected to 40 episodes of sublethal hypoxia (4 h) three times a week. The resulting two hypoxia-conditioned cell lines have been maintained in culture for more than 2 years. In both cell lines changes in doubling times occurred: in HT29 an increase, and in HCT116 a decrease. Cell survival in response to hypoxia and to DNA damage differed strikingly in the two cell lines. The HT29 hypoxia-conditioned cells were more resistant than the parental line to a 24 h hypoxic challenge, while those from HCT116 surprisingly were more sensitive. Sensitivity to cisplatin in vitro was also significantly different for the hypoxia-conditioned compared with the parental lines, suggesting a change in pathways leading to apoptosis following DNA damage signaling. The growth of both conditioned cell lines in vivo as xenografts in immunodeficient (SCID) mice was more rapid than their parental lines, and was accompanied in each by evidence of enhanced vascular proliferation as a consequence of the hypoxia-conditioning. Thus the changes in apoptotic susceptibility were independent of altered angiogenesis. The derivation of these lines provides a model for events within hypoxic regions of colon cancers, and for the acquisition of resistance and sensitivity characteristics that may have therapeutic implications for the use of antiangiogenesis drugs