Blood and CSF Biomarker Dynamics in Multiple Sclerosis: Implications for Data Interpretation

Background. Disability in multiple sclerosis (MS) is related to neuroaxonal degeneration. A reliable blood biomarker for neuroaxonal degeneration is needed. Objectives. To explore the relationship between cerebrospinal fluid (CSF) and serum concentrations of a protein biomarker for neuroaxonal degeneration, the neurofilaments heavy chain (NfH). Methods. An exploratory cross-sectional (n = 51) and longitudinal (n = 34) study on cerebrospinal fluid (CSF) and serum NfH phosphoform levels in patients with MS. The expanded disability status scale (EDSS), CSF, and serum levels of NfH-SMI34 and NfH-SMI35 were quantified at baseline. Disability progression was assessed at 3-year followup. Results. At baseline, patients with primary progressive MS (PPMS, EDSS 6) and secondary progressive MS (SPMS, EDSS 6) were more disabled compared to patients with relapsing remitting MS (RRMS, EDSS 2, P < .0001). Serum and CSF NfH phosphoform levels were not correlated. Baseline serum levels of the NfH-SMI34 were significantly (P < .05) higher in patients with PPMS (2.05 ng/mL) compared to SPMS (0.03 ng/mL) and RRMS (1.56 ng/mL). In SPMS higher serum than CSF NfH-SMI34 levels predicted disability progression from baseline (ΔEDSS 2, P < .05). In RRMS higher CSF than serum NfH-SMI35 levels predicted disability progression (ΔEDSS 2, P < .05). Conclusion. Serum and CSF NfH-SMI34 and NfH-SMI35 levels did not correlate with each other in MS. The quantitative relationship of CSF and serum NfH levels suggests that neuroaxonal degeneration of the central nervous system is the likely cause for disability progression in RRMS. In more severely disabled patients with PP/SPMS, subtle pathology of the peripheral nervous system cannot be excluded as an alternative source for blood NfH levels. Therefore, the interpretation of blood protein biomarker data in diseases of the central nervous system (CNS) should consider the possibility that pathology of the peripheral nervous system (PNS) may influence the results

Some exact non-vacuum Bianchi VI0 and VII0 instantons

We report some new exact instantons in general relativity. These solutions are K\"ahler and fall into the symmetry classes of Bianchi types VI0 and VII0, with matter content of a stiff fluid. The qualitative behaviour of the solutions is presented, and we compare it to the known results of the corresponding self-dual Bianchi solutions. We also give axisymmetric Bianchi VII0 solutions with an electromagnetic field.Comment: latex, 15 pages with 3 eps figure

Usefulness of Plasmodium falciparum-specific rapid diagnostic tests for assessment of parasite clearance and detection of recurrent infections after artemisinin-based combination therapy

Background: Rapid diagnostic test (RDT) is an important tool for parasite-based malaria diagnosis. High specificity of RDTs to distinguish an active Plasmodium falciparum infection from residual antigens from a previous infection is crucial in endemic areas where residents are repeatedly exposed to malaria. The efficiency of two RDTs based on histidine-rich protein 2 (HRP2) and lactate dehydrogenase (LDH) antigens were studied and compared with two microscopy techniques (Giemsa and acridine orange-stained blood smears) and real-time polymerase chain reaction (PCR) for assessment of initial clearance and detection of recurrent P. falciparum infections after artemisinin-based combination therapy (ACT) in a moderately high endemic area of rural Tanzania. Methods: In this exploratory study 53 children \u3c five years with uncomplicated P. falciparum malaria infection were followed up on nine occasions, i.e., day 1, 2, 3, 7, 14, 21, 28, 35 and 42, after initiation of artemether-lumefantrine treatment. At each visit capillary blood samples was collected for the HRP2 and LDH-based RDTs, Giemsa and acridine orange-stained blood smears for microscopy and real-time PCR. Assessment of clearance times and detection of recurrent P. falciparum infections were done for all diagnostic methods. Results: The median clearance times were 28 (range seven to \u3e42) and seven (two to 14) days for HRP2 and LDH-based RDTs, two (one to seven) and two (one to 14) days for Giemsa and acridine orange-stained blood smear and two (one to 28) days for real-time PCR. RDT specificity against Giemsa-stained blood smear microscopy was 21% for HRP2 on day 14, reaching 87% on day 42, and ≥96% from day 14 to 42 for LDH. There was no significant correlation between parasite density at enrolment and duration of HRP2 positivity (r = 0.13, p = 0.34). Recurrent malaria infections occurred in ten (19%) children. The HRP2 and LDH-based RDTs did not detect eight and two of the recurrent infections, respectively. Conclusion: The LDH-based RDT was superior to HRP2-based for monitoring of treatment outcome and detection of recurrent infections after ACT in this moderately high transmission setting. The results may have implications for the choice of RDT devices in similar transmission settings for improved malaria case management. Trial registration. Clinicaltrials.gov, NCT01843764. © 2013 Aydin-Schmidt et al.; licensee BioMed Central Ltd

Multidimensional Cosmology: Spatially Homogeneous models of dimension 4+1

In this paper we classify all 4+1 cosmological models where the spatial hypersurfaces are connected and simply connected homogeneous Riemannian manifolds. These models come in two categories, multiply transitive and simply transitive models. There are in all five different multiply transitive models which cannot be considered as a special case of a simply transitive model. The classification of simply transitive models, relies heavily upon the classification of the four dimensional (real) Lie algebras. For the orthogonal case, we derive all the equations of motion and give some examples of exact solutions. Also the problem of how these models can be compactified in context with the Kaluza-Klein mechanism, is addressed.Comment: 24 pages, no figures; Refs added, typos corrected. To appear in CQ

A Note on Inflation with Tachyon Rolling on the Gauss-Bonnet Brane

In this paper we study the tachyonic inflation in brane world cosmology with Gauss-Bonnet term in the bulk. We obtain the exact solution of slow roll equations in case of exponential potential. We attempt to implement the proposal of Lidsey and Nunes, astro-ph/0303168, for the tachyon condensate rolling on the Gauss-Bonnet brane and discuss the difficulties associated with the proposal.Comment: RevTex4, 5 pages, no figures, Minor clarifications added and references updated, To appear in PR

Obstetric and perinatal risks after the use of donor sperm : A systematic review and meta-analysis

Donor sperm is widely used in infertility treatments. The purpose of the study was to investigate, whether use of donor sperm in intrauterine insemination (IUI) or in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatments affect maternal and perinatal risks compared with spontaneously conceived pregnancies or use of partner sperm in IUI, IVF or ICSI. We provide a systematic review and meta-analyses on the most clinically relevant obstetric and perinatal outcomes after use of donor sperm compared with partner sperm: hypertensive disorders of pregnancy, preeclampsia, low birth weight, and preterm birth. Our meta-analyses showed an increased risk for preeclampsia (pooled adjusted odds ratio (aOR) 1.77, 95% CI 1.26-2.48) and hypertensive disorders of pregnancy (pooled aOR 1.55, 95%, CI 1.20-2.00) in pregnancies resulting from IUI with donor sperm compared with IUI with partner sperm. No increased risk was seen for low birth weight or preterm birth after the use of donor sperm in IUI compared with the use of partner sperm in IUI. Subgroup analysis for singletons only did not change these results. The meta-analysis on low birth weight showed a lower risk after in IVF with donor sperm compared with IVF with partner sperm (pooled aOR 0.89, 95% CI 0.83-0.94). For hypertensive disorders of pregnancy, preeclampsia and preterm birth, no difference was found between IVF with donor sperm vs. partner sperm. Patients need to be informed about the moderately increased risk of hypertensive disorders of pregnancy and preeclampsia in pregnancies after IUI with donor sperm.Peer reviewe

Isotropization of Bianchi-Type Cosmological Solutions in Brans-Dicke Theory

The cosmic, general analitic solutions of the Brans--Dicke Theory for the flat space of homogeneous and isotropic models containing perfect, barotropic, fluids are seen to belong to a wider class of solutions --which includes cosmological models with the open and the closed spaces of the Friedmann--Robertson--Walker metric, as well as solutions for models with homogeneous but anisotropic spaces corresponding to the Bianchi--Type metric clasification-- when all these solutions are expressed in terms of reduced variables. The existence of such a class lies in the fact that the scalar field, $\phi$, times a function of the mean scale factor or ``volume element'', $a^3 = a_1 a_2 a_3$, which depends on time and on the barotropic index of the equation of state used, can be written as a function of a ``cosmic time'' reduced in terms of another function of the mean scale factor depending itself again on the barotropic index but independent of the metrics here employed. This reduction procedure permites one to analyze if explicitly given anisotropic cosmological solutions ``isotropize'' in the course of their time evolution. For if so can happen, it could be claimed that there exists a subclass of solutions that is stable under anisotropic perturbations.Comment: 15 pages, Late

Microphysical and optical properties of dust and tropical biomass burning aerosol layers in the Cape Verde region – An overview of the airborne in-situ and lidar measurements during SAMUM-2

In the framework of the Saharan Mineral Dust Experiment (SAMUM) airborne High Spectral Resolution Lidar and in situ measurements of the particle size, aerosol mixing state and absorption coefficient were conducted. Here, the properties of mineral dust and tropical biomass burning layers in the Cape Verde region in January/February 2008 are investigated and compared with the properties of fresh dust observed in May/June 2006 close the Sahara. In the Cape Verde area, we found a complex stratification with dust layers covering the altitude range below 2 km and biomass burning layers aloft. The aerosol type of the individual layers was classified based on depolarization and lidar ratios and, in addition, on in situ measured Ångström exponents of absorption °aap. The dust layers had a depth of 1.3 ± 0.4 km and showed a median °aap of 3.95. The median effective diameter Deff was 2.5 μm and the dust layers over Cape Verde yielded clear signals of aging: large particles were depleted due to gravitational settling and the accumulation mode diameter was shifted towards larger sizes as a result of coagulation. The tropical biomass layers had a depth of 2.0 ± 1.1 km and were characterized by a median °aap of 1.34. They always contained a certain amount of large dust particles and showed a median Deff of 1.1 μm and a fine mode Deff,fine of 0.33. The dust and biomass burning layers had a median aerosol optical depth (AOD) of 0.23 and 0.09, respectively. The median contributions to the AOD of the total atmospheric column below 10 km were 75 and 37%, respectively