Liquid chromatography-tandem mass spectrometry - Application in the clinical laboratory

This review provides a concise survey of liquid chromatography tandem mass spectrometry (LCTMS) as an emerging technology in clinical chemistry. The combination of two mass spectrometers with an interposed collision cell characterizes LCTMS as an analytical technology on its own and not just as a more specific detector for HPLC compared with conventional techniques. In LCTMS, liquid chromatography is rather used for sample preparation but not for complete resolution of compounds of interest. The instrument technology of LCTMS is complex and comparatively expensive; however, in routine use, methods are far more rugged compared to conventional chromatographic techniques and enable highthroughput analyses with very limited manual handling steps. Moreover, compared to both gas chromatographymass spectrometry (GCMS) and conventional HPLC techniques, LCTMS is substantially more versatile with respect to the spectrum of analyzable compounds. For these reasons it is likely that LCTMS will gain far more widespread use in the clinical laboratory than HPLC and GCMS ever did. In this article, the key features of LCTMS are described, method development is explained, typical fields of application are discussed, and personal experiences are related

Damping of plasmons of closely coupled sphere chains due to disordered gaps

The damping of plasmons due to structural disorder may have important practical consequences. Here, we use spherical harmonic expansions to quantify the damping of plasmons of ensembles of closely coupled sphere chains with moderately disordered gaps. We show that the quadratic shift of average resonance position due to disorder is maintained in the transition from weak to close coupling, but the sensitivity to disorder increases. Further, we find that although the main peak is most often damped and broadened by disorder, it is possible for the optical extinction of disordered gold chains to increase slightly due to red-skew into a region with more favorable metal properties. © 2011 American Chemical Society

Access to and use of clinical services and disease-modifying therapies by people with progressive multiple sclerosis in the United Kingdom

Background: According to current UK guidelines everyone with progressive MS should have access to an MS Specialist but levels of access and use of clinical services is unknown. Our objective was to investigate access to MS Specialists, use of clinical services and disease-modifying therapies (DMTs) by people with progressive MS in the United Kingdom. Methods: A UK wide, online survey was conducted via the UK MS Register. Inclusion criteria: age over 18 years, primary or secondary progressive MS and a member of the UK MS Register. Participants were asked about access to MS Specialists; recent clinical service use; receipt of regular review and current and previous DMT use. Participant demographics; quality of life and disease impact measures were supplied from the UK MS Register. Results: In total 1298 participants responded: 5% were currently taking DMT; 23% had previously taken DMT; and 95% reported access to an MS Specialist. Most utilised services were: MS Doctor/Nurse (50%), General Practitioner (45%), and Physiotherapist (40%). Seventy-four percent received a regular review although 37% received theirs less than annually. Current DMT use was associated with better quality of life but past DMT use was associated with poorer quality of life and higher impact of disease. Conclusions: Access to, and use of, MS Specialists was high. However a gap in service provision was highlighted in both receiving and frequency of regular reviews

Ten Years of Experience Training Non-Physician Anesthesia Providers in Haiti.

Surgery is increasingly recognized as an effective means of treating a proportion of the global burden of disease, especially in resource-limited countries. Often non-physicians, such as nurses, provide the majority of anesthesia; however, their training and formal supervision is often of low priority or even non-existent. To increase the number of safe anesthesia providers in Haiti, Médecins Sans Frontières has trained nurse anesthetists (NAs) for over 10 years. This article describes the challenges, outcomes, and future directions of this training program. From 1998 to 2008, 24 students graduated. Nineteen (79%) continue to work as NAs in Haiti and 5 (21%) have emigrated. In 2008, NAs were critical in providing anesthesia during a post-hurricane emergency where they performed 330 procedures. Mortality was 0.3% and not associated with lack of anesthesiologist supervision. The completion rate of this training program was high and the majority of graduates continue to work as nurse anesthetists in Haiti. Successful training requires a setting with a sufficient volume and diversity of operations, appropriate anesthesia equipment, a structured and comprehensive training program, and recognition of the training program by the national ministry of health and relevant professional bodies. Preliminary outcomes support findings elsewhere that NAs can be a safe and effective alternative where anesthesiologists are scarce. Training non-physician anesthetists is a feasible and important way to scale up surgical services resource limited settings

Replication of LDL SWAs hits in PROSPER/PHASE as validation for future (pharmaco)genetic analyses

<p><b>Background:</b> The PHArmacogenetic study of Statins in the Elderly at risk (PHASE) is a genome wide association study in the PROspective Study of Pravastatin in the Elderly at risk for vascular disease (PROSPER) that investigates the genetic variation responsible for the individual variation in drug response to pravastatin. Statins lower LDL-cholesterol in general by 30%, however not in all subjects. Moreover, clinical response is highly variable and adverse effects occur in a minority of patients. In this report we first describe the rationale of the PROSPER/PHASE project and second show that the PROSPER/PHASE study can be used to study pharmacogenetics in the elderly.</p> <p><b>Methods:</b> The genome wide association study (GWAS) was conducted using the Illumina 660K-Quad beadchips following manufacturer's instructions. After a stringent quality control 557,192 SNPs in 5,244 subjects were available for analysis. To maximize the availability of genetic data and coverage of the genome, imputation up to 2.5 million autosomal CEPH HapMap SNPs was performed with MACH imputation software. The GWAS for LDL-cholesterol is assessed with an additive linear regression model in PROBABEL software, adjusted for age, sex, and country of origin to account for population stratification.</p> <p><b>Results:</b> Forty-two SNPs reached the GWAS significant threshold of p = 5.0e-08 in 5 genomic loci (APOE/APOC1; LDLR; FADS2/FEN1; HMGCR; PSRC1/CELSR5). The top SNP (rs445925, chromosome 19) with a p-value of p = 2.8e-30 is located within the APOC1 gene and near the APOE gene. The second top SNP (rs6511720, chromosome 19) with a p-value of p = 5.22e-15 is located within the LDLR gene. All 5 genomic loci were previously associated with LDL-cholesterol levels, no novel loci were identified. Replication in WOSCOPS and CARE confirmed our results.</p> <p><b>Conclusion:</b> With the GWAS in the PROSPER/PHASE study we confirm the previously found genetic associations with LDL-cholesterol levels. With this proof-of-principle study we show that the PROSPER/PHASE study can be used to investigate genetic associations in a similar way to population based studies. The next step of the PROSPER/PHASE study is to identify the genetic variation responsible for the variation in LDL-cholesterol lowering in response to statin treatment in collaboration with other large trials.</p&gt

Classical and semi-classical energy conditions

The standard energy conditions of classical general relativity are (mostly) linear in the stress-energy tensor, and have clear physical interpretations in terms of geodesic focussing, but suffer the significant drawback that they are often violated by semi-classical quantum effects. In contrast, it is possible to develop non-standard energy conditions that are intrinsically non-linear in the stress-energy tensor, and which exhibit much better well-controlled behaviour when semi-classical quantum effects are introduced, at the cost of a less direct applicability to geodesic focussing. In this article we will first review the standard energy conditions and their various limitations. (Including the connection to the Hawking--Ellis type I, II, III, and IV classification of stress-energy tensors). We shall then turn to the averaged, nonlinear, and semi-classical energy conditions, and see how much can be done once semi-classical quantum effects are included.Comment: V1: 25 pages. Draft chapter, on which the related chapter of the book "Wormholes, Warp Drives and Energy Conditions" (to be published by Springer), will be based. V2: typos fixed. V3: small typo fixe

Vitamin D and subsequent all-age and premature mortality: a systematic review

<br>Background: All-cause mortality in the population < 65 years is 30% higher in Glasgow than in equally deprived Liverpool and Manchester. We investigated a hypothesis that low vitamin D in this population may be associated with premature mortality via a systematic review and meta-analysis.</br> <br>Methods: Medline, EMBASE, Web of Science, the Cochrane Library and grey literature sources were searched until February 2012 for relevant studies. Summary statistics were combined in an age-stratified meta-analysis.</br> <br>Results: Nine studies were included in the meta-analysis, representing 24,297 participants, 5,324 of whom died during follow-up. The pooled hazard ratio for low compared to high vitamin D demonstrated a significant inverse association (HR 1.19, 95% CI 1.12-1.27) between vitamin D levels and all-cause mortality after adjustment for available confounders. In an age-stratified meta-analysis, the hazard ratio for older participants was 1.25 (95% CI 1.14-1.36) and for younger participants 1.12 (95% CI 1.01-1.24).</br> <br>Conclusions: Low vitamin D status is inversely associated with all-cause mortality but the risk is higher amongst older individuals and the relationship is prone to residual confounding. Further studies investigating the association between vitamin D deficiency and all-cause mortality in younger adults with adjustment for all important confounders (or using randomised trials of supplementation) are required to clarify this relationship.</br&gt