Local and global spontaneous calcium events regulate neurite outgrowth and onset of GABAergic phenotype during neural precursor differentiation

Neural stem cells can generate in vitro progenitors of the three main cell lineages found in the CNS. The signaling pathways underlying the acquisition of differentiated phenotypes in these cells are poorly understood. Here we tested the hypothesis that Ca2+ signaling controls differentiation of neural precursors. We found low-frequency global and local Ca2+ transients occurring predominantly during early stages of differentiation. Spontaneous Ca2+ signals in individual precursors were not synchronized with Ca2+ transients in surrounding cells. Experimentally induced changes in the frequency of local Ca2+signals and global Ca2+ rises correlated positively with neurite outgrowth and the onset of GABAergic neurotransmitter phenotype, respectively. NMDA receptor activity was critical for alterations in neuronal morphology but not for the timing of the acquisition of the neurotransmitter phenotype. Thus, spontaneous Ca2+ signals are an intrinsic property of differentiating neurosphere-derived precursors. Their frequency may specify neuronal morphology and acquisition of neurotransmitter phenotype

Experimental tests on a new harvesting system for Burley tobacco

The globalization of the tobacco production has led to a drop in competitiveness of the Italian tobacco on the world market. Burley is the main variety of tobacco cropped in Campania region of Southern Italy. Its leaves have to be sewn, in the curing phase. Aim of this work is to show the results of the implementation of a new harvest machine prototype. Basically, the machine used for Bright tobacco, totally mechanical harvested, which doesn’t need to be sewn because it requires an indirect-fire treatment into the curing furnaces. The machine was modified in order to mechanize harvesting of Burley tobacco, and tested on four cultivars of Burley tobacco under three different planting layouts. The Burley tobacco leaves can be harvested mechanically by pulling individual leaves off the stalk; leaves are then sorted and tied in bundles prior to sewing. A mechanical burley tobacco harvesting system was evaluated. This machine consists in realizing a leaves orientation system based on the different weight between the leaf blade and the stalk enhanced by an air flow. The measurements taken were harvest timing, work capacity, and quality standards of the work carried out. The results, in terms of user time, range from 6.67 h/ha to 7.80 h/ha while in terms of operational efficiency are between 88% and 89%. The average user capacity recorded for the four cultivars is equal to 0.14 ha/h, a value far from the one recorded for the same harvesting machine used for Bright tobacco (0.25 ha/h). The harvest timing capacity, range from 0.51 t/h to 0.99 t/h. The work productivity goes from 0.17 t to 0.33 t per hour of human unit respectively. The average number of detached leaves, depending on the cultivar, has been between 523 and 744. Concerning the leaf orientation, a general percentage of 73% was achieved

Physicians’ Preferences for Bone Metastases Drug Therapy in the United States

AbstractObjectiveSeveral characteristics of bone-targeted agents are considered when making treatment decisions. This study evaluated physicians’ therapy preferences for preventing skeletal-related events (SREs) in patients with bone metastases secondary to solid tumors.MethodsA Web-enabled, discrete-choice experiment online survey was conducted among physicians who treated patients with bone metastases and solid tumors in the United States. Respondents chose between pairs of hypothetical medications defined by combinations of six attributes at varying levels for two hypothetical patients. Preference weights for attribute levels were estimated using a random-parameters logit model.ResultsIn total, 200 physicians completed the survey. Their mean age was 52 years, 57% were in practice for more than 15 years, 37% were oncologists, and 65% treated 10 or fewer patients with bone metastases weekly. Out-of-pocket cost to patients was the most important attribute overall. Among clinical outcomes, time to first SRE and risk of renal impairment were the most important attributes. Statistically significant preferences were observed for all attribute levels for time to first SRE, risk of renal impairment, and mode of administration. Predicted choice probability analysis showed that physicians preferred a hypothetical medication with attributes similar to those of denosumab over one with attributes similar to those of zoledronic acid.ConclusionsPhysicians indicated that clinical attributes are important when considering bone-targeting therapy for bone metastases, but consistent with the current health care landscape, patient out-of-pocket cost was the most important. With health care costs being increasingly shifted to patients, physicians require accurate information about co-pays and assistance programs to avoid patients receiving less costly, yet potentially inferior, treatment

The economic contribution of third sector initiatives for older people: a systematic review and development of a framework for evaluation

An ageing population has placed strains on health and social care systems. Innovative solutions have been sought to inject capacity and capability in order to deliver services to older people more efficiently and effectively. Over the last two decades, governments have actively encouraged third sector organisations to deliver public services on the assumption that they exhibit higher levels of innovation, efficiency and responsiveness. The evidence base, particularly for whether they provide better value for money, remains poor. We present the results of a systematic literature review on the costs and outcomes of services for older people delivered by third sector organisations. We combine this evidence with a framework for analysing the benefits and costs of third sector-led initiatives, and test this out empirically with a group of initiatives delivered for older people in an urban context. We find that our method may hold considerable promise for the evaluation of third sector initiatives

Direct imaging of correlated defect nanodomains in a metal-organic framework

Defect engineering can enhance key properties of metal-organic frameworks (MOFs). Tailoring the distribution of defects, for example in correlated nanodomains, requires characterization across length scales. However, a critical nanoscale characterization gap has emerged between the bulk diffraction techniques used to detect defect nanodomains and the sub-nanometer imaging used to observe individual defects. Here, we demonstrate that the emerging technique of scanning electron diffraction (SED) can bridge this gap uniquely enabling both nanoscale crystallographic analysis and the lowdose formation of multiple diffraction contrast images for defect analysis in MOFs. We directly image defect nanodomains in the MOF UiO-66(Hf) over an area of ca. 1 000 nm and with a spatial resolution ca. 5 nm to reveal domain morphology and distribution. Based on these observations, we suggest possible crystal growth processes underpinning synthetic control of defect nanodomains. We also identify likely dislocations and small angle grain boundaries, illustrating that SED could be a key technique in developing the potential for engineering the distribution of defects, or “microstructure”, in functional MOF design

Development and evaluation of a wearable peripheral vascular compensation sensor in a swine model of hemorrhage

Postpartum hemorrhage (PPH) is the leading and most preventable cause of maternal mortality, particularly in low-resource settings. PPH is currently diagnosed through visual estimation of blood loss or monitoring of vital signs. Visual assessment routinely underestimates blood loss beyond the point of pharmaceutical intervention. Quantitative monitoring of hemorrhage-induced compensatory processes, such as the constriction of peripheral vessels, may provide an early alert for PPH. To this end, we developed a low-cost, wearable optical device that continuously monitors peripheral perfusion via laser speckle flow index (LSFI) to detect hemorrhage-induced peripheral vasoconstriction. The measured LSFI signal produced a linear response in phantom models and a strong correlation coefficient with blood loss averaged across subjects (\u3e0.9) in a large animal model, with superior performance to vital sign metrics

Novel nut and bolt task quantifies motor deficits in premanifest and manifest Huntington's Disease

BACKGROUND: We investigated the use of a simple novel nut and bolt task in premanifest and manifest Huntington's disease (HD) patients to detect and quantify motor impairments at all stages of the disease. METHODS: Premanifest HD (n=24), manifest HD (n=27) and control (n=32) participants were asked to screw a nut onto a bolt in one direction, using three different sized bolts with their left and right hand in turn. RESULTS: We identified some impairments at all stages of HD and in the premanifest individuals, deficits in the non-dominant hand correlated with disease burden scores. CONCLUSION: This simple, cheap motor task was able to detect motor impairments in both premanifest and manifest HD and as such might be a useful quantifiable measure of motor function for use in clinical studies

Iron amino-bis(phenolate) complexes for the formation of organic carbonates from CO2 and oxiranes

A series of iron(III) compounds supported by tetradentate amino-bis(phenolate) ligands were synthesized and characterized using electronic absorption spectroscopy, magnetic moment measurement and MALDI-TOF mass spectrometry. The solid-state structures of 1 and 2 were determined by X-ray diffraction and reveal iron(III) square pyramidal compounds. The complexes were studied as catalysts for the reaction of carbon dioxide and epoxides in the presence of a co-catalyst, under solvent free conditions to yield cyclic carbonates. Catalytic testing with TBAB as a co-catalyst shows that 4 bearing electron withdrawing groups in the ortho and para-positions of the phenolate ring exhibits the highest catalytic activity. Kinetic studies using 1 revealed that the cycloaddition reaction is affected by temperature as expected and the activation energy for propylene carbonate formation is 98.4 kJ mol−1

A Study of Ligand Coordination at Lanthanide and Group 4 Metal Centers by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry

Reactions of lanthanide amide reagents Ln{N(SiMe3)2}3 (where Ln = Sm, Gd, Ho, or Yb) with amine-bis(phenol) ligands were probed using inert atmosphere matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) (anthracene matrix); the technique rapidly confirms ligand coordination, giving excellent agreement with theoretical isotope patterns for lanthanide(amine-phenolate) fragments. Spectra on isolated lanthanide amine-bis(phenolate) amido complexes are similar to those seen from small scale parallel reactions of metal amides and protonated ligands. Although in all cases molecular ion peaks are not observed, peaks for lanthanide arene complexes, [M + arene]+•, formed in situ, are seen. The lack of molecular ion peak is due to difficulties in ionizing Ln3+ complexes by charge transfer. However, if Nujol is used to disperse the analyte and matrix prior to analysis rather than toluene, arene adducts are not observed. Similar phenol-derived ligands can be reacted with diamagnetic M(NMe2)4 (where M = Ti or Zr), and amine-phenolate complex formation is again confirmed easily by MALDI-TOF MS or LDI-TOF MS (no matrix). These complexes were also characterized by NMR spectroscopy and elemental analysis on isolated samples