Fetal Mesenchymal Stromal Cells: an Opportunity for Prenatal Cellular Therapy

PURPOSE OF REVIEW: The aim of the study is to provide an overview on the possibility of treating congenital disorders prenatally with mesenchymal stromal cells (MSCs). RECENT FINDINGS: MSCs have multilineage potential and a low immunogenic profile and are immunomodulatory and more easy to expand in culture. Their ability to migrate, engraft and differentiate, or act via a paracrine effect on target tissues makes MSCs candidates for clinical therapies. Fetal and extra-fetal MSCs offer higher therapeutic potential compared to MSCs derived from adult sources. SUMMARY: MSCs may be safely transplanted prenatally via ultrasound-guided injection into the umbilical cord. Due to these characteristics, fetal MSCs are of great interest in the field of in utero stem cell transplantation for treatment of congenital disease

Chemistry with Photons, Protons, and Electrons

This is an account of the research activities of our group during the first two years of its existence. First results from our work on proton-coupled electron transfer and long-range charge tunneling reactions are presented. This includes a hydrogen-bonded cation–anion pair in which a proton-coupled electron transfer process can be phototriggered and followed by simple optical spectroscopic means, as well as a series of rigid rod-like donor-bridge-acceptor molecules which we use to investigate physical phenomena associated with the tunneling of electrons or holes. A unifying feature of this research is the use of light (photons) to induce proton and/or electron transfer

Alternate Fuels for Use in Commercial Aircraft

The engine and aircraft Research and Development (R&D) communities have been investigating alternative fueling in near-term, midterm, and far-term aircraft. A drop in jet fuel replacement, consisting of a kerosene (Jet-A) and synthetic fuel blend, will be possible for use in existing and near-term aircraft. Future midterm aircraft may use a biojet and synthetic fuel blend in ultra-efficient airplane designs. Future far-term engines and aircraft in 50-plus years may be specifically designed to use a low- or zero-carbon fuel. Synthetic jet fuels from coal, natural gas, or other hydrocarbon feedstocks are very similar in performance to conventional jet fuel, yet the additional CO2 produced during the manufacturing needs to be permanently sequestered. Biojet fuels need to be developed specifically for jet aircraft without displacing food production. Envisioned as midterm aircraft fuel, if the performance and cost liabilities can be overcome, biofuel blends with synthetic jet or Jet-A fuels have near-term potential in terms of global climatic concerns. Long-term solutions address dramatic emissions reductions through use of alternate aircraft fuels such as liquid hydrogen or liquid methane. Either of these new aircraft fuels will require an enormous change in infrastructure and thus engine and airplane design. Life-cycle environmental questions need to be addressed

Comparison of surveillance methods applied to a situation of low malaria prevalence at rural sites in The Gambia and Guinea Bissau

BACKGROUND: Health record-based observations from several parts of Africa indicate a major decline in malaria, but up-to-date information on parasite prevalence in West-Africa is sparse. This study aims to provide parasite prevalence data from three sites in the Gambia and Guinea Bissau, respectively, and compares the usefulness of PCR, rapid diagnostic tests (RDT), serology and slide-microscopy for surveillance. METHODS: Cross-sectional surveys in 12 villages at three rural sites were carried out in the Gambia and Guinea Bissau in January/February 2008, shortly following the annual transmission season. RESULTS: A surprisingly low microscopically detectable parasite prevalence was detected in the Gambia (Farafenni: 10.9%, CI95%: 8.7-13.1%; Basse: 9.0%, CI95%: 7.2-10.8%), and Guinea Bissau (Caio: 4%, CI95%: 2.6-5.4%), with low parasite densities (geometric mean: 104 parasites/microl, CI95%: 76-143/microl). In comparison, PCR detected a more than three times higher proportion of parasite carriers, indicating its usefulness to sensitively identify foci where malaria declines, whereas the RDT had very low sensitivity. Estimates of force of infection using age sero-conversion rates were equivalent to an EIR of approximately 1 infectious bite/person/year, significantly less than previous estimates. The sero-prevalence profiles suggest a gradual decline of malaria transmission, confirming their usefulness in providing information on longer term trends of transmission. A greater variability in parasite prevalence among villages within a site than between sites was observed with all methods. The fact that serology equally captured the inter-village variability, indicates that the observed heterogeneity represents a stable pattern. CONCLUSION: PCR and serology may be used as complementary tools to survey malaria in areas of declining malaria prevalence such as the Gambia and Guinea Bissau

PfHPRT: a new biomarker candidate of acute Plasmodium falciparum infection.

Plasmodium falciparum is a protozoan parasite that causes human malaria. This parasitic infection accounts for approximately 655,000 deaths each year worldwide. Most deaths could be prevented by diagnosing and treating malaria promptly. To date, few parasite proteins have been developed into rapid diagnostic tools. We have combined a shotgun and a targeted proteomic strategy to characterize the plasma proteome of Gambian children with severe malaria (SM), mild malaria, and convalescent controls in search of new candidate biomarkers. Here we report four P. falciparum proteins with a high level of confidence in SM patients, namely, PF10_0121 (hypoxanthine phosphoribosyltransferase, pHPRT), PF11_0208 (phosphoglycerate mutase, pPGM), PF13_0141 (lactate dehydrogenase, pLDH), and PF14_0425 (fructose bisphosphate aldolase, pFBPA). We have optimized selected reaction monitoring (SRM) assays to quantify these proteins in individual patients. All P. falciparum proteins were higher in SM compared with mild cases or control subjects. SRM-based measurements correlated markedly with clinical anemia (low blood hemoglobin concentration), and pLDH and pFBPA were significantly correlated with higher P. falciparum parasitemia. These findings suggest that pHPRT is a promising biomarker to diagnose P. falciparum malaria infection. The diagnostic performance of this marker should be validated prospectively

Longitudinal Development of Reasons for Living and Dying With Suicide Attempters: A 2-Year Follow-Up Study

Background: Clinical interventions for patients after a suicide attempt might include a focus on Reasons for Living (RFL) and/or Reasons for Dying (RFD). The present study examined the longitudinal development of RFL and RFD in patients with and without a suicide-specific intervention - the Attempted Suicide Short Intervention Program (ASSIP). Methods: In this secondary analysis of a 2-year follow-up randomized controlled study, participants completed the Suicide Status Form II to assess RFL and RFD, at baseline, as well as at 6-, 12-, 18-, and 24-months follow-up. Growth models and latent class analysis were used to investigate longitudinal developments in RFL and RFD. Regression models were used to test the association between RFL, RFD and suicidal reattempts and ideation. Results: Cross-sectionally and longitudinally, RFD, but not RFL, were associated with suicide reattempts and suicidal ideation. The number of RFD decreased significantly across the 24 month period (from 1.90 at t1 to 1.04 at t5 in the control group and from 2.32 at t1 to 0.51 at t5 in the intervention group), and this decrease was stronger (b = −0.02; p = 0.004) in the ASSIP group than in the control group. There was no overall change in RFL. Three latent trajectories of RFD were identified: a decreasing (n = 77), a steady high (n = 17) and a trajectory with first increasing and then decreasing RFD (n = 26). The proportion of patients in the ASSIP intervention was highest in the decreasing trajectory and lowest in the steady high trajectory. Patients in the steady high trajectory were characterized by worse mental health and fewer social obligations (partner, children) at baseline. Conclusion: The results confirm the importance of RFD within the suicidal process and show that the number of RFD can be further reduced over the period of 24 months with short interventions such as ASSIP. The relevance of number of RFL in the suicidal process, as protective factor, was not confirmed. In the subgroup of patients whose RFD did not decrease over a long period of time, there is a particularly high risk of suicidal ideation/behavior. Clinical interventions should focus more closely on RFD, their etiology and maintenance

Oral activated charcoal prevents experimental cerebral malaria in mice and in a randomized controlled clinical trial in man did not interfere with the pharmacokinetics of parenteral artesunate.

BACKGROUND: Safe, cheap and effective adjunct therapies preventing the development of, or reducing the mortality from, severe malaria could have considerable and rapid public health impact. Oral activated charcoal (oAC) is a safe and well tolerated treatment for acute poisoning, more recently shown to have significant immunomodulatory effects in man. In preparation for possible efficacy trials in human malaria, we sought to determine whether oAC would i) reduce mortality due to experimental cerebral malaria (ECM) in mice, ii) modulate immune and inflammatory responses associated with ECM, and iii) affect the pharmacokinetics of parenteral artesunate in human volunteers. METHODS/PRINCIPAL FINDINGS: We found that oAC provided significant protection against P. berghei ANKA-induced ECM, increasing overall survival time compared to untreated mice (p<0.0001; hazard ratio 16.4; 95% CI 6.73 to 40.1). Protection from ECM by oAC was associated with reduced numbers of splenic TNF(+) CD4(+) T cells and multifunctional IFNgamma(+)TNF(+) CD4(+) and CD8(+) T cells. Furthermore, we identified a whole blood gene expression signature (68 genes) associated with protection from ECM. To evaluate whether oAC might affect current best available anti-malarial treatment, we conducted a randomized controlled open label trial in 52 human volunteers (ISRCTN NR. 64793756), administering artesunate (AS) in the presence or absence of oAC. We demonstrated that co-administration of oAC was safe and well-tolerated. In the 26 subjects further analyzed, we found no interference with the pharmacokinetics of parenteral AS or its pharmacologically active metabolite dihydroartemisinin. CONCLUSIONS/SIGNIFICANCE: oAC protects against ECM in mice, and does not interfere with the pharmacokinetics of parenteral artesunate. If future studies succeed in establishing the efficacy of oAC in human malaria, then the characteristics of being inexpensive, well-tolerated at high doses and requiring no sophisticated storage would make oAC a relevant candidate for adjunct therapy to reduce mortality from severe malaria, or for immediate treatment of suspected severe malaria in a rural setting. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN64793756

Long-term changes in extreme temperatures and precipitation in Spain

La creació de les bases de dades de temperatura i precipitació diàries anomenades, respectivament, Spanish Daily Adjusted Temperature Series (SDATS) i Spanish Daily Adjusted Precipitation Series (SDAPS), en el marc del projecte finançat per la Comissió Europea EMULATE (European and North Atlantic daily to MULtidecadal climATE variability), ha permès als autors analitzar el canvi a llarg termini que s'ha produït en el comportament anual dels extrems climàtics a l'Espanya peninsular durant el període 1901-2005. El conjunt de procediments desenvolupats pels autors per tal de crear registres homogenis de la temperatura i de la precipitació diàries són descrits de manera breu abans d'analitzar els canvis observats en l'ocurrència d'extrems climàtics. S'han utilitzat els indicadors se - güents per a dur a terme aquest estudi: excedències dels percentils inferiors i superiors de les temperatures màximes (Tmax) i mínimes (Tmin) diàries, excedències de la precipitació diària per sobre dels percentils 95è i 99è, l'índex simple d'intensitat diària (SDII) i els indicadors d'1 i 5 dies amb la precipitació més alta de l'any. Tant l'anàlisi dels percentils superiors de les temperatures com la dels inferiors mostren que s'ha produït un escalfament important sobre l'Espanya peninsular al llarg del segle XX, i que aquest ha estat més important en les temperatures màximes que en les temperatures mínimes. No obstant això, aquest patró presenta un lleuger canvi en el període més recent d'escalfament, en el qual la tendència d'ambdues variables presenta valors similars. Els canvis en els indicadors pluviomètrics no són tan clars com els estimats per la temperatura, però s'ha detectat una tendència cap a l'ocurrència de pluges més intenses.The development of the Spanish daily adjusted temperature series (SDATS) and the Spanish daily adjusted precipitation series (SDAPS) datasets in the framework of the European Community (EC)-funded project EMULATE (European and North Atlantic daily to MULtidecadal climATE variability) enabled the assessment of long-term annual changes of extreme temperature and precipitation indices over peninsular Spain for the period 1901–2005. Within this framework, a set of procedures was developed to generate long-term (1850–2005) daily adjusted temperature and precipitation series and to use them to assess changes in climatic extremes. The present report describes details of the data employed to analyze the behavior of Spanish climate extremes and discusses the results of investigations into the annual changes in selected indices that occurred during the 20th century: exceedances of upper and lower percentiles of daily maximum (Tmax) and minimum (Tmin) temperatures, cold-spell duration index (CSDI), warm-spell duration index (WSDI), daily rainfall (R) exceeding the 95th and 99th percentiles, simple daily intensity index (SDII), and greatest 1- and 5-day total precipitation. Upper and lower temperature percentiles increased during the 20th century over mainland Spain, but changes in daytime extreme temperatures were larger than changes in night-time extreme temperatures. This pattern, however, shifted slightly in the recent period of strong warming, with more similar rates of change among daytime and night-time extreme temperatures. Changes in extreme precipitation indices were not as evident as those in extremetemperature indices, but there was a tendency towards heavier precipitation

Time-separated entangled light pulses from a single-atom emitter

The controlled interaction between a single, trapped, laser-driven atom and the mode of a high-finesse optical cavity allows for the generation of temporally separated, entangled light pulses. Entanglement between the photon-number fluctuations of the pulses is created and mediated via the atomic center-of-mass motion, which is interfaced with light through the mechanical effect of atom-photon interaction. By means of a quantum noise analysis we determine the correlation matrix which characterizes the entanglement, as a function of the system parameters. The scheme is feasible in experimentally accessible parameter regimes. It may be easily extended to the generation of entangled pulses at different frequencies, even at vastly different wavelengths.Comment: 17 pages, 5 figures. Modified version, to appear in the New Journal of Physic

A new era of wide-field submillimetre imaging: on-sky performance of SCUBA-2

SCUBA-2 is the largest submillimetre wide-field bolometric camera ever built. This 43 square arc-minute field-of-view instrument operates at two wavelengths (850 and 450 microns) and has been installed on the James Clerk Maxwell Telescope on Mauna Kea, Hawaii. SCUBA-2 has been successfully commissioned and operational for general science since October 2011. This paper presents an overview of the on-sky performance of the instrument during and since commissioning in mid-2011. The on-sky noise characteristics and NEPs of the 450 and 850 micron arrays, with average yields of approximately 3400 bolometers at each wavelength, will be shown. The observing modes of the instrument and the on-sky calibration techniques are described. The culmination of these efforts has resulted in a scientifically powerful mapping camera with sensitivities that allow a square degree of sky to be mapped to 10 mJy/beam rms at 850 micron in 2 hours and 60 mJy/beam rms at 450 micron in 5 hours in the best weather.Comment: 18 pages, 15 figures.SPIE Conference series 8452, Millimetre, Submillimetre and Far-infrared Detectors and Instrumentation for Astronomy VI 201