Optical pen-size reflectometer for monitoring of early dental erosion in native and polished enamels

Application of the specular reflection intensity was previously reported for the quantification of early dental erosion. Further development of the technique and assembly of the miniaturized pen-size instrument are described. The optical system was adjusted to fit into a handy device which could potentially access different positions in the oral cavity. The assembled instrument could successfully detect early erosion progression in both polished (n=70) and native (n=20) human enamels. Different severities of enamel erosion were induced by varying incubation time of polished enamel in 1% citric acid (pH=3.60, 0.5 to 10 min), while the native incisors were treated in the commercial orange juice (Tropicana Pure Premium®, pH=3.85, 10 to 60 min). The instrument provided a good differentiation between various severities of the erosion in vitro. The size of the measurement spot affected the erosion monitoring in native enamel (human incisors). The erosion measurement in the 0.7-mm (diameter) cervical spots showed systematically lower reflection intensities compared with the analysis of central and incisal small spots. The application of larger spot areas (2.3 mm) for the erosion monitoring revealed no effect (p>0.05) of the spot position on the reflection signal. High variation of the teeth susceptibility toward in vitro erosion was detected in native enamel.

Monitoring of Urinary Calcium and Phosphorus Excretion in Preterm Infants - Comparison of two Methods

OBJECTIVES: Premature babies require supplementation with calcium and phosphorus to prevent metabolic bone disease of prematurity. To guide mineral supplementation, two methods of monitoring urinary excretion of calcium and phosphorus are used: urinary calcium or phosphorus concentration and calcium/creatinine or phosphorus/creatinine ratios. We compare these two methods in regards to their agreement on the need for mineral supplementation. METHODS: Retrospective chart review of 230 premature babies with birthweight <1500 g, undergoing screening of urinary spot samples from day 21 of life and fortnightly thereafter. Hypothetical cut-off values for urine calcium or phosphorus concentration (1 mmol/l) and urine calcium/creatinine ratio (0.5 mol/mol) or phosphorus/creatinine ratio (4 mol/mol) were applied to the sample results. The agreement on whether or not to supplement the respective minerals based on the results with the two methods was compared. Multivariate general linear models sought to identify patient characteristic to predict disagreeing results. RESULTS: 24.8% of cases disagreed on the indication for calcium supplementation, 8.8% for phosphorus. Total daily calcium intake was the only patient characteristic associated with discordant results. CONCLUSIONS: With the intention to supplement the respective mineral, comparison of urinary mineral concentration with mineral/creatinine ratio is moderate for Calcium and good for Phosphorus. The results do not allow to identify superiority of either method on the decision which babies require calcium and/or phosphorus supplements.

Multiplex Liquid Chromatography-Tandem Mass Spectrometry Assay for Simultaneous Therapeutic Drug Monitoring of Ribavirin, Boceprevir, and Telaprevir

New directly acting antivirals (DAAs) that inhibit hepatitis C virus (HCV) replication are increasingly used for the treatment of chronic hepatitis C. A marked pharmacokinetic variability and a high potential for drug-drug interactions between DAAs and numerous drug classes have been identified. In addition, ribavirin (RBV), commonly associated with hemolytic anemia, often requires dose adjustment, advocating for therapeutic drug monitoring (TDM) in patients under combined antiviral therapy. However, an assay for the simultaneous analysis of RBV and DAAs constitutes an analytical challenge because of the large differences in polarity among these drugs, ranging from hydrophilic (RBV) to highly lipophilic (telaprevir [TVR]). Moreover, TVR is characterized by erratic behavior on standard octadecyl-based reversed-phase column chromatography and must be separated from VRT-127394, its inactive C-21 epimer metabolite. We have developed a convenient assay employing simple plasma protein precipitation, followed by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) for the simultaneous determination of levels of RBV, boceprevir, and TVR, as well as its metabolite VRT-127394, in plasma. This new, simple, rapid, and robust HPLC-MS/MS assay offers an efficient method of real-time TDM aimed at maximizing efficacy while minimizing the toxicity of antiviral therapy.

Cooperative Effects of Electron Donors and Acceptors for the Stabilization of Elusive Metal Cluster Frameworks: Synthesis and Solid-State Structures of Pt-19(CO)(24)(mu(4)-AuPPh3)(3)](-) and Pt-19(CO)(24){mu(4)-Au-2(PPh3)(2)}(2)]

The anionic cluster Pt-19(CO)(22)](4-) (1), of pentagonal symmetry, reacts with CO and AuPPh3+ fragments. Upon increasing the Au:Pt-19, molar ratio, different species are sequentially formed, but only the last two members of the series could be characterized by X-ray diffraction, namely, Pt-19(CO)(24)(mu(4)-AuPPh3)(3)](-) (2) and Pt-19(CO)(24){mu(4)-Au-2(PPh3)(2)}(2)] (3).The metallic framework of the starting cluster is completely modified after the addition of CO and AuL+, and both products display the same platinum core of trigonal symmetry, with closely packed metal atoms. The three AuL+ units cap three different square faces in 2, whereas four AuL+ fragments are grouped in two independent bimetallic units in the neutral cluster 3. Electrochemical and spectroelectrochemical studies on 2 showed that its redox ability is comparable with that of the homometallic 1.

A re-examination of petrogenesis and 40Ar/39Ar systematics in the the Chain of Ponds K-feldspar: "diffusion domain" archetype versus polyphase hygrochronology

K-feldspar (Kfs) from the Chain of Ponds Pluton (CPP) is the archetypal reference material, on which thermochronological modeling of Ar diffusion in discrete “domains” was founded. We re-examine the CPP Kfs using cathodoluminescence and back-scattered electron imaging, transmission electron microscopy, and electron probe microanalysis. 40Ar/39Ar stepwise heating experiments on different sieve fractions, and on handpicked and unpicked aliquots, are compared. Our results reproduce the staircase-shaped age spectrum and the Arrhenius trajectory of the literature sample, confirming that samples collected from the same locality have an identical Ar isotope record. Even the most pristine-looking Kfs from the CPP contains successive generations of secondary, metasomatic/retrograde mineral replacements that post-date magmatic crystallization. These chemically and chronologically distinct phases are responsible for its staircase-shaped age spectra, which are modified by handpicking. While genuine within-grain diffusion gradients are not ruled out by these data, this study demonstrates that the most important control on staircase-shaped age spectra is the simultaneous presence of heterochemical, diachronous post-magmatic mineral growth. At least five distinct mineral species were identified in the Kfs separate, three of which can be traced to external fluids interacting with the CPP in a chemically open system. Sieve fractions have size-shifted Arrhenius trajectories, negating the existence of the smallest “diffusion domains”. Heterochemical phases also play an important role in producing non-linear trajectories. In vacuo degassing rates recovered from Arrhenius plots are neither related to true Fick’s Law diffusion nor to the staircase shape of the age spectra. The CPP Kfs used to define the "diffusion domain" model demonstrates the predominance of metasomatic alteration by hydrothermal fluids and recrystallization in establishing the natural Ar distribution amongst different coexisting phases that gives rise to the staircase-shaped age spectrum. Microbeam imaging of textures is as essential for 40Ar-39Ar hygrochronology as it is for U-Pb geochronology.

Therapeutic drug monitoring of once daily aminoglycoside dosing: comparison of two methods and investigation of the optimal blood sampling strategy.

PURPOSE Therapeutic drug monitoring of patients receiving once daily aminoglycoside therapy can be performed using pharmacokinetic (PK) formulas or Bayesian calculations. While these methods produced comparable results, their performance has never been checked against full PK profiles. We performed a PK study in order to compare both methods and to determine the best time-points to estimate AUC0-24 and peak concentrations (C max). METHODS We obtained full PK profiles in 14 patients receiving a once daily aminoglycoside therapy. PK parameters were calculated with PKSolver using non-compartmental methods. The calculated PK parameters were then compared with parameters estimated using an algorithm based on two serum concentrations (two-point method) or the software TCIWorks (Bayesian method). RESULTS For tobramycin and gentamicin, AUC0-24 and C max could be reliably estimated using a first serum concentration obtained at 1 h and a second one between 8 and 10 h after start of the infusion. The two-point and the Bayesian method produced similar results. For amikacin, AUC0-24 could reliably be estimated by both methods. C max was underestimated by 10-20% by the two-point method and by up to 30% with a large variation by the Bayesian method. CONCLUSIONS The ideal time-points for therapeutic drug monitoring of once daily administered aminoglycosides are 1 h after start of a 30-min infusion for the first time-point and 8-10 h after start of the infusion for the second time-point. Duration of the infusion and accurate registration of the time-points of blood drawing are essential for obtaining precise predictions.

Monitoring of emergency and intensive care patients: simple diagnostic aids

This article describes in short sections the use and interpretation of indirect blood pressure measurements, central venous pressure, body temperature, pulse oximetry, end tidal CO2 measurements, pulse and heart rate, urine production and emergency laboratory values. Most of these parameters are directly or indirectly linked to the perfusion of the patient. Optimizing these values are one of the most important goals in emergency and critical care medicine.

Characteristics and comprehensiveness of adult HIV care and treatment programmes in Asia-Pacific, sub-Saharan Africa and the Americas: results of a site assessment conducted by the International epidemiologic Databases to Evaluate AIDS (IeDEA) Collaboration

INTRODUCTION HIV care and treatment programmes worldwide are transforming as they push to deliver universal access to essential prevention, care and treatment services to persons living with HIV and their communities. The characteristics and capacity of these HIV programmes affect patient outcomes and quality of care. Despite the importance of ensuring optimal outcomes, few studies have addressed the capacity of HIV programmes to deliver comprehensive care. We sought to describe such capacity in HIV programmes in seven regions worldwide. METHODS Staff from 128 sites in 41 countries participating in the International epidemiologic Databases to Evaluate AIDS completed a site survey from 2009 to 2010, including sites in the Asia-Pacific region (n=20), Latin America and the Caribbean (n=7), North America (n=7), Central Africa (n=12), East Africa (n=51), Southern Africa (n=16) and West Africa (n=15). We computed a measure of the comprehensiveness of care based on seven World Health Organization-recommended essential HIV services. RESULTS Most sites reported serving urban (61%; region range (rr): 33-100%) and both adult and paediatric populations (77%; rr: 29-96%). Only 45% of HIV clinics that reported treating children had paediatricians on staff. As for the seven essential services, survey respondents reported that CD4+ cell count testing was available to all but one site, while tuberculosis (TB) screening and community outreach services were available in 80 and 72%, respectively. The remaining four essential services - nutritional support (82%), combination antiretroviral therapy adherence support (88%), prevention of mother-to-child transmission (PMTCT) (94%) and other prevention and clinical management services (97%) - were uniformly available. Approximately half (46%) of sites reported offering all seven services. Newer sites and sites in settings with low rankings on the UN Human Development Index (HDI), especially those in the President's Emergency Plan for AIDS Relief focus countries, tended to offer a more comprehensive array of essential services. HIV care programme characteristics and comprehensiveness varied according to the number of years the site had been in operation and the HDI of the site setting, with more recently established clinics in low-HDI settings reporting a more comprehensive array of available services. Survey respondents frequently identified contact tracing of patients, patient outreach, nutritional counselling, onsite viral load testing, universal TB screening and the provision of isoniazid preventive therapy as unavailable services. CONCLUSIONS This study serves as a baseline for on-going monitoring of the evolution of care delivery over time and lays the groundwork for evaluating HIV treatment outcomes in relation to site capacity for comprehensive care.

Etiology and management of recurrent parotid pleomorphic adenoma

The objective of this review study was to encompass the relevant literature and current best practice options for this challenging, sometimes incurable problem. The source of the data was Ovid MEDLINE from 1946 to 2014. Review methods consisted of articles with clinical correlates. The most important cause of recurrence is enucleation with rupture and incomplete tumor excision at operation. Incomplete pseudocapsule, extracapsular extension, pseudopods of pleomorphic adenoma tissue, and satellite pleomorphic beyond the pseudocapsule are also likely linked to recurrent pleomorphic adenoma. Most recurrent pleomorphic adenoma are multinodular. Magnetic resonance imaging is the imaging study of choice for recurrent pleomorphic adenoma. Nerve integrity monitoring may reduce morbidity for recurrent pleomorphic adenoma. Treatment of recurrent pleomorphic adenoma must be individualized. Total parotidectomy, given the multicentricity of recurrent pleomorphic adenoma, is appropriate in many patients, but may be inadequate to control recurrent pleomorphic. There is accumulating evidence from retrospective series that postoperative radiation therapy results in significantly better local control. LEVEL OF EVIDENCE NA Laryngoscope, 2014.

VirB6 is required for stabilization of VirB5 and VirB3 and formation of VirB7 homodimers in Agrobacterium tumefaciens.

VirB6 from Agrobacterium tumefaciens is an essential component of the type IV secretion machinery for T pilus formation and genetic transformation of plants. Due to its predicted topology as a polytopic inner membrane protein, it was proposed to form the transport pore for cell-to-cell transfer of genetic material and proteinaceous virulence factors. Here, we show that the absence of VirB6 leads to reduced cellular levels of VirB5 and VirB3, which were proposed to assist T pilus formation as minor component(s) or assembly factor(s), respectively. Overexpression of virB6 in trans restored levels of cell-bound and T pilus-associated VirB5 to wild type but did not restore VirB3 levels. Thus, VirB6 has a stabilizing effect on VirB5 accumulation, thereby regulating T pilus assembly. In the absence of VirB6, cell-bound VirB7 monomers and VirB7-VirB9 heterodimers were reduced and VirB7 homodimer formation was abolished. This effect could not be restored by expression of VirB6 in trans. Expression of TraD, a component of the transfer machinery of the IncN plasmid pKM101, with significant sequence similarity to VirB6, restored neither protein levels nor bacterial virulence but partly permitted T pilus formation in a virB6 deletion strain. VirB6 may therefore regulate T pilus formation by direct interaction with VirB5, and wild-type levels of VirB3 and VirB7 homodimers are not required.

An initiative for participatory monitoring of large scale acquisitions: Opportunities and results thus far

Increasing commercial pressures on land are provoking fundamental and far-reaching changes in the relationships between people and land. Much knowledge on land-oriented investments projects currently comes from the media. Although this provides a good starting point, lack of transparency and rapidly changing contexts mean that this is often unreliable. The International Land Coalition, in partnership with Oxfam Novib, Centre de coopération internationale en recherche agronomique pour le développement (CIRAD), University of Pretoria, Centre for Development and Environment of the University of Bern (CDE), and GIZ, started to compile an inventory of land-related investments. This project aims to better understand the extent, trends and impacts of land-related investments by supporting an ongoing and systematic stocktaking exercise of the various investment projects currently taking place worldwide. It involves a large number of organizations and individuals working in areas where land transactions are being made, and able to provide details of such investments. The project monitors land transactions in rural areas that imply a transformation of land use rights from communities and smallholders to commercial use, and are made both by domestic and foreign investors (private actors, governments, government-back private investors). The focus is on investments for food or agrofuel production, timber extraction, carbon trading, mineral extraction, conservation and tourism. A novel way of using ITC to document land acquisitions in a spatially explicit way and by using an approach called “crowdsourcing” is being developed. This approach will allow actors to share information and knowledge directly and at any time on a public platform, where it will be scrutinized in terms of reliability and cross checked with other sources. Up to now, over 1200 deals have been recorded across 96 countries. Details of such transactions have been classified in a matrix and distributed to over 350 contacts worldwide for verification. The verified information has been geo-referenced and represented in two global maps. This is an open database enabling a continued monitoring exercise and the improvement of data accuracy. More information will be released over time. The opportunities arise from overcoming constraints by incomplete information by proposing a new way of collecting, enhancing and sharing information and knowledge in a more democratic and transparent manner. The intention is to develop interactive knowledge platform where any interested person can share and access information on land deals, their link to involved stakeholders, and their embedding into a geographical context. By making use of new ICT technologies that are more and more in the reach of local stakeholders, as well as open access and web-based spatial information systems, it will become possible to create a dynamic database containing spatial explicit data. Feeding in data by a large number of stakeholders, increasingly also by means of new mobile ITC technologies, will open up new opportunities to analyse, monitor and assess highly dynamic trends of land acquisition and rural transformation.

Monitoring and Switching of First-line Antiretroviral Therapy in sub-Saharan Africa: Collaborative Analysis of Adult Treatment Cohorts.

BACKGROUND HIV-1 viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not universally available. We examined monitoring of first-line and switching to second-line ART in sub-Saharan Africa, 2004-2013. METHODS Adult HIV-1 infected patients starting combination ART in 16 countries were included. Switching was defined as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to a protease inhibitor (PI)-based regimen, with a change of ≥1 NRTI. Virological and immunological failures were defined per World Health Organization criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% confidence intervals (CI) comparing routine VL monitoring, targeted VL monitoring, CD4 cell monitoring and clinical monitoring, adjusted for programme and individual characteristics. FINDINGS Of 297,825 eligible patients, 10,352 patients (3·5%) switched during 782,412 person-years of follow-up. Compared to CD4 monitoring hazard ratios for switching were 3·15 (95% CI 2·92-3·40) for routine VL, 1·21 (1·13-1·30) for targeted VL and 0·49 (0·43-0·56) for clinical monitoring. Overall 58.0% of patients with confirmed virological and 19·3% of patients with confirmed immunological failure switched within 2 years. Among patients who switched the percentage with evidence of treatment failure based on a single CD4 or VL measurement ranged from 32·1% with clinical to 84.3% with targeted VL monitoring. Median CD4 counts at switching were 215 cells/µl under routine VL monitoring but lower with other monitoring (114-133 cells/µl). INTERPRETATION Overall few patients switched to second-line ART and switching occurred late in the absence of routine viral load monitoring. Switching was more common and occurred earlier with targeted or routine viral load testing.

Risk charts to guide targeted HIV-1 viral load monitoring of ART: development and validation in patients from resource-limited settings.

BACKGROUND HIV-1 RNA viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not available in many resource-limited settings. We developed and validated CD4-based risk charts to guide targeted VL testing. METHODS We modeled the probability of virologic failure up to 5 years of ART based on current and baseline CD4 counts, developed decision rules for targeted VL testing of 10%, 20% or 40% of patients in seven cohorts of patients starting ART in South Africa, and plotted cut-offs for VL testing on colour-coded risk charts. We assessed the accuracy of risk chart-guided VL testing to detect virologic failure in validation cohorts from South Africa, Zambia and the Asia-Pacific. FINDINGS 31,450 adult patients were included in the derivation and 25,294 patients in the validation cohorts. Positive predictive values increased with the percentage of patients tested: from 79% (10% tested) to 98% (40% tested) in the South African, from 64% to 93% in the Zambian and from 73% to 96% in the Asia-Pacific cohorts. Corresponding increases in sensitivity were from 35% to 68% in South Africa, from 55% to 82% in Zambia and from 37% to 71% in Asia-Pacific. The area under the receiver-operating curve increased from 0.75 to 0.91 in South Africa, from 0.76 to 0.91 in Zambia and from 0.77 to 0.92 in Asia Pacific. INTERPRETATION CD4-based risk charts with optimal cut-offs for targeted VL testing may be useful to monitor ART in settings where VL capacity is limited.