In situ turning defects of exfoliated Ti3C2 MXene into Fenton-like catalytic active sites.

Controllable in situ formation of nanoclusters with discrete active sites is highly desirable in heterogeneous catalysis. Herein, a titanium oxide-based Fenton-like catalyst is constructed using exfoliated Ti3C2 MXene as a template. Theoretical calculations reveal that a redox reaction between the surface Ti-deficit vacancies of the exfoliated Ti3C2 MXene and H2O2 molecules facilitates the in situ conversion of surface defects into titanium oxide nanoclusters anchoring on amorphous carbon (TiOx@C). The presence of mixed-valence Tiδ+ (δ = 0, 2, 3, and 4) within TiOx@C is confirmed by X-ray photoelectron spectroscopy (XPS) and X-ray absorption fine structure (XAFS) characterizations. The abundant surface defects within TiOx@C effectively promote the generation of reactive oxygen species (ROS) leading to superior and stable Fenton-like catalytic degradation of atrazine, a typical agricultural herbicide. Such an in situ construction of Fenton-like catalysts through defect engineering also applies to other MXene family materials, such as V2C and Nb2C.

A hospital-wide group approach to promote open dialogues of workplace issues and staff wellbeing with Schwartz Rounds.

OBJECTIVES: This study aims to explore the feasibility and impact of Schwartz Rounds® led by psychiatrists/mental health professionals in an urban Australian public hospital setting and to develop strategies for optimising participants' experiences. METHODS: Being a mixed-methods study collecting qualitative and quantitative data through post-Rounds evaluation surveys, this study thematically analysed responses from 105 participants attending four consecutive monthly Rounds between February and May 2023 to assess the perceived benefits and challenges of Schwartz Rounds. RESULTS: Respondents highly valued the Rounds and felt cared for by the healthcare organisation. Themes related to perceived benefits included (i) Connectedness and shared experience; (ii) Understanding other professionals; (iii) Normalisation of emotional distress, validation and a safe space for vulnerability; and (iv) Fostering authenticity and humanitarian aspects of healthcare. Challenges included (i) Fear of exposure and judgment; (ii) Emotional discomfort; (iii) Unfamiliarity with reflection; and (iv) Safety concerns. CONCLUSIONS: This study suggests acceptability and feasibility of implementing Schwartz Rounds within an Australian public health setting, particularly when facilitated by skilled mental health professionals. The outcomes provide preliminary support for the use of group interventions to enhance staff collegiality and culture in healthcare settings, thereby addressing critical needs for health professional wellbeing.

Objections to assisted dying within institutions: systemic solutions for rapprochement.

In this Matters Arising article, we outline how the recent article "The impact on patients of objections by institutions to assisted dying: a qualitative study of family caregivers' perceptions" (White et al., 2023 Mar 13;24(1):22) informed Voluntary Assisted Dying (VAD) implementation in our large Australian public health setting, where objections do not emanate from, but within, the institution. In reporting the harms to patients and caregivers created by institutional objection, White et al. provide an evidenced-based road map for potential potholes or risks associated with VAD implementation. We discuss the complexities emerging from the diverse views of health professionals and the ethical tensions arising from such, especially within certain specialties, and how we developed systemic strategies that support patients, caregivers and staff alike. We highlighted the need to shift from "Do you support VAD?" to "How can we support you as healthcare professionals to integrate VAD into your practice, in a way that complies with the legislation, meets the needs of patients and caregivers, and feels safe and does not compromise your moral stance?"

Post-traumatic stress disorder in doctors: Origins, approach and Eye Movement Desensitisation and Reprocessing therapy.

OBJECTIVES: Navigating a high-stakes clinical environment, medical doctors tend to consider trauma and adverse workplace events as 'part of their job'. This often leads to delays in help-seeking in doctors who develop acute traumatic stress symptoms (ATSS), post-traumatic stress disorder (PTSD) and their comorbidities. This article outlines the prevalence of acute traumatic stress and PTSD in this population and summarises the emerging evidence base for Eye Movement Desensitisation and Reprocessing (EMDR) early-intervention protocols of this population. CONCLUSION: Doctors have higher prevalence rates of ATSS and PTSD than the general public. Eye Movement Desensitisation and Reprocessing therapy's early-intervention protocols for recent, prolonged and ongoing traumatic stress have the potential to be a widely acceptable, timely and cost-effective intervention for doctors and other healthcare workers (HCWs), as highlighted in the emerging evidence base, which has grown considerably in response to the impact of the COVID pandemic on HCWs' mental health. These evidence-based interventions could potentially be routinely offered to doctors and other HCWs within 1 month of an adverse workplace experience to reduce ATSS, PTSD and other comorbidities.

An integrated ICP-MS-based analytical approach to fractionate and characterize ionic and nanoparticulate Ce species.

Cerium dioxide nanoparticles (CeO2 NPs) are widely used in various fields, leading to concern about their effect on human health. When conducting in vivo investigations of CeO2 NPs, the challenge is to fractionate ionic Ce and CeO2 NPs and to characterize CeO2 NPs without changing their properties/state. To meet this challenge, we developed an integrated inductively coupled plasma-mass spectrometry (ICP-MS)-based analytical approach in which ultrafiltration is used to fractionate ionic and nanoparticulate Ce species while CeO2 NPs are characterized by single particle-ICP-MS (sp-ICP-MS). We used this technique to compare the effects of two sample pretreatment methods, alkaline and enzymatic pretreatments, on ionic Ce and CeO2 NPs. Results showed that enzymatic pretreatment was more efficient in extracting ionic Ce or CeO2 NPs from animal tissues. Moreover, results further showed that the properties/states of all ionic and nanoparticulate Ce species were well preserved. The rates of recovery of both species were over 85%; the size distribution of CeO2 NPs was comparable to that of original NPs. We then applied this analytical approach, including the enzymatic pretreatment and ICP-MS-based analytical techniques, to investigate the bioaccumulation and biotransformation of CeO2 NPs in mice. It was found that the thymus acts as a "holding station" in CeO2 NP translocation in vivo. CeO2 NP biotransformation was reported to be organ-specific. This is the first study to evaluate the impact of enzymatic and alkaline pretreatment on Ce species, namely ionic Ce and CeO2 NPs. This integrated ICP-MS-based analytical approach enables us to conduct in vivo biotransformation investigations of CeO2 NPs.

Joint Effects of Multiple UV Filters on Zebrafish Embryo Development.

The widespread use of UV filters has resulted in significant amounts of these chemicals appearing not only in the environment but also in organisms. This study first assessed the levels of nine UV filters in waters along the coast of Shenzhen, China, in tapwater, and in a nearby reservoir. UV filters were found to be high, in both winter and summer at most locations. Then, using zebrafish as a model, the influence of a UV filter mixture after dietary and aqueous exposure was assessed. After exposing artemia to three dominant UV filters at two levels and then feeding these artemia to zebrafish adults, concentrations in both were up to 4 times higher when exposed to the mixtures than when exposed to only a single UV filter. A short-term 25-day dietary exposure to the zebrafish adults did not appear to significantly influence early life stage development of the second generation; however, relatively long exposure over 47 days had significant adverse effects on embryo development. Aqueous exposure of fish embryos to mixtures of the three UV filters demonstrated a general trend of decreased heart/hatching rate as doses increased, coupled with significant changes in activities of catalase and malate dehydrogenase.

Presymptomatic atrophy in autosomal dominant Alzheimer's disease: A serial magnetic resonance imaging study.

INTRODUCTION: Identifying at what point atrophy rates first change in Alzheimer's disease is important for informing design of presymptomatic trials. METHODS: Serial T1-weighted magnetic resonance imaging scans of 94 participants (28 noncarriers, 66 carriers) from the Dominantly Inherited Alzheimer Network were used to measure brain, ventricular, and hippocampal atrophy rates. For each structure, nonlinear mixed-effects models estimated the change-points when atrophy rates deviate from normal and the rates of change before and after this point. RESULTS: Atrophy increased after the change-point, which occurred 1-1.5 years (assuming a single step change in atrophy rate) or 3-8 years (assuming gradual acceleration of atrophy) before expected symptom onset. At expected symptom onset, estimated atrophy rates were at least 3.6 times than those before the change-point. DISCUSSION: Atrophy rates are pathologically increased up to seven years before "expected onset". During this period, atrophy rates may be useful for inclusion and tracking of disease progression.

White matter hyperintensities are associated with disproportionate progressive hippocampal atrophy.

This study investigates relationships between white matter hyperintensity (WMH) volume, cerebrospinal fluid (CSF) Alzheimer's disease (AD) pathology markers, and brain and hippocampal volume loss. Subjects included 198 controls, 345 mild cognitive impairment (MCI), and 154 AD subjects with serial volumetric 1.5-T MRI. CSF Aß42 and total tau were measured (n = 353). Brain and hippocampal loss were quantified from serial MRI using the boundary shift integral (BSI). Multiple linear regression models assessed the relationships between WMHs and hippocampal and brain atrophy rates. Models were refitted adjusting for (a) concurrent brain/hippocampal atrophy rates and (b) CSF Aß42 and tau in subjects with CSF data. WMH burden was positively associated with hippocampal atrophy rate in controls (P = 0.002) and MCI subjects (P = 0.03), and with brain atrophy rate in controls (P = 0.03). The associations with hippocampal atrophy rate remained following adjustment for concurrent brain atrophy rate in controls and MCIs, and for CSF biomarkers in controls (P = 0.007). These novel results suggest that vascular damage alongside AD pathology is associated with disproportionately greater hippocampal atrophy in nondemented older adults. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.

Glucuronide and Sulfate Conjugates of Bisphenol A: Chemical Synthesis and Correlation Between Their Urinary Levels and Plasma Bisphenol A Content in Voluntary Human Donors.

Bisphenol A (BPA) glucuronide and sulfate conjugates are major products of Phase II metabolism of BPA in humans. In the past, their determination in body fluids usually involves tedious enzymatic hydrolysis and multiresidual analysis. The recent availability of authentic standards of these conjugates enables our better understand of the human metabolism of BPA and the distribution of their metabolites in body fluids. In this work, we report the chemical synthesis and purification of BPA mono- and di-glucuronide and BPA mono- and di-sulfate. Their levels, as well as that of BPA, in 140 paired human plasma and urine samples collected randomly from voluntary donors in Hong Kong SAR, China, were determined by solid-phase extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS). BPA was found in more than 135 human plasma and urine samples. Its Phase II metabolites, ranging from N.D. to 36.7 µg g-1-creatinine, also were detected in 139 of the 140 urine samples. Good correlation (r = 0.911) between molar concentration of BPA in the plasma and that of "total urinary BPA" (i.e., ln [(BPA + ∑ BPA phase II conjugate)molar concentration]) was observed. Direct quantification of Phase II metabolites of BPA in human urine can be a useful assessment tool for population exposure to this potent endocrine disrupting chemical.

Elemental Analysis of Chinese Black Inks on Xuan Paper by ArF Laser-Excited Plume Fluorescence.

Chemical analysis of Chinese black ink on xuan paper is useful for the authentication of Asian artwork. The analysis has to be nondestructive and has to accommodate artworks of all sizes. We apply three analytical techniques, ArF laser-induced plume fluorescence, Fourier transform infrared (FTIR) spectroscopy, and portable X-ray fluorescence (pXRF) to analyze five commercial Chinese black inks on two kinds of xuan paper. The FTIR signal is found to be interfered by the substrate which is inevitable because the pigments diffuse extensively into the xuan fiber network. The XRF signal is shown to be feeble and no signal can be registered until the samples are stacked and when the analytes are present at tens of percent. In contrast, the plume fluorescence technique can detect the minor and trace signature elements. The method is based on a two-laser-pulse scheme performed on a high precision optical setup: the first 355 nm laser pulse ablates a thin layer of the ink to create a plume; the second 193 nm laser pulse induces multi analytes in the plume to fluoresce. Partial-least-squares discriminant analysis of the fluorescence spectra unambiguously sorts the ink-xuan combinations while the sampled area is not visibly damaged even under the microscope. The laser probe can handle samples of arbitrary size and shape, is air compatible, and no sample pretreatment is necessary.

Accurate automatic estimation of total intracranial volume: a nuisance variable with less nuisance.

Total intracranial volume (TIV/ICV) is an important covariate for volumetric analyses of the brain and brain regions, especially in the study of neurodegenerative diseases, where it can provide a proxy of maximum pre-morbid brain volume. The gold-standard method is manual delineation of brain scans, but this requires careful work by trained operators. We evaluated Statistical Parametric Mapping 12 (SPM12) automated segmentation for TIV measurement in place of manual segmentation and also compared it with SPM8 and FreeSurfer 5.3.0. For T1-weighted MRI acquired from 288 participants in a multi-centre clinical trial in Alzheimer's disease we find a high correlation between SPM12 TIV and manual TIV (R(2)=0.940, 95% Confidence Interval (0.924, 0.953)), with a small mean difference (SPM12 40.4±35.4ml lower than manual, amounting to 2.8% of the overall mean TIV in the study). The correlation with manual measurements (the key aspect when using TIV as a covariate) for SPM12 was significantly higher (p<0.001) than for either SPM8 (R(2)=0.577 CI (0.500, 0.644)) or FreeSurfer (R(2)=0.801 CI (0.744, 0.843)). These results suggest that SPM12 TIV estimates are an acceptable substitute for labour-intensive manual estimates even in the challenging context of multiple centres and the presence of neurodegenerative pathology. We also briefly discuss some aspects of the statistical modelling approaches to adjust for TIV.

Effects of changing from non-accelerated to accelerated MRI for follow-up in brain atrophy measurement.

Stable MR acquisition is essential for reliable measurement of brain atrophy in longitudinal studies. One attractive recent advance in MRI is to speed up acquisition using parallel imaging (e.g. reducing volumetric T1-weighted acquisition scan times from around 9 to 5 min). In some studies, a decision to change to an accelerated acquisition may have been deliberately taken, while in others repeat scans may occasionally be accidentally acquired with an accelerated acquisition. In ADNI, non-accelerated and accelerated scans were acquired in the same scanning session on each individual. We investigated the impact on brain atrophy as measured by k-means normalized boundary shift integral (KN-BSI) and deformation-based morphometry when changing from non-accelerated to accelerated MRI acquisitions over a 12-month interval using scans of 422 subjects from ADNI. KN-BSIs were calculated using both a non-accelerated baseline scan and non-accelerated 12-month scans (i.e. consistent acquisition), and a non-accelerated baseline scan and an accelerated 12-month scan (i.e. changed acquisition). Fluid-based non-rigid registration was also performed on those scans to estimate the brain atrophy rate. We found that the effect on KN-BSI and fluid-based non-rigid registration depended on the scanner manufacturer. For KN-BSI, in Philips and Siemens scanners, the change had very little impact on the measured atrophy rate (increase of 0.051% in Philips and -0.035% in Siemens from consistent acquisition to changed acquisition), whereas, in GE, the change caused a mean reduction of 0.65% in the brain atrophy rate. This is likely due to the difference in tissue contrast between gray matter and cerebrospinal fluid in the non-accelerated and accelerated scans in GE, which uses IR-FSPGR instead of MP-RAGE. For fluid-based non-rigid registration, the change caused a mean increase of 0.29% in the brain atrophy rate in the changed acquisition compared with consistent acquisition in Philips, whereas in GE and Siemens, the change had less impact on the mean atrophy rate (increase of 0.18% in GE and 0.049% in Siemens). Moving from non-accelerated baseline scans to accelerated scans for follow-up may have surprisingly little effect on computed atrophy rates depending on the exact sequence details and the scanner manufacturer; even accidentally inconsistent scans of this nature may still be useful.

Assessing atrophy measurement techniques in dementia: Results from the MIRIAD atrophy challenge.

Structural MRI is widely used for investigating brain atrophy in many neurodegenerative disorders, with several research groups developing and publishing techniques to provide quantitative assessments of this longitudinal change. Often techniques are compared through computation of required sample size estimates for future clinical trials. However interpretation of such comparisons is rendered complex because, despite using the same publicly available cohorts, the various techniques have been assessed with different data exclusions and different statistical analysis models. We created the MIRIAD atrophy challenge in order to test various capabilities of atrophy measurement techniques. The data consisted of 69 subjects (46 Alzheimer's disease, 23 control) who were scanned multiple (up to twelve) times at nine visits over a follow-up period of one to two years, resulting in 708 total image sets. Nine participating groups from 6 countries completed the challenge by providing volumetric measurements of key structures (whole brain, lateral ventricle, left and right hippocampi) for each dataset and atrophy measurements of these structures for each time point pair (both forward and backward) of a given subject. From these results, we formally compared techniques using exactly the same dataset. First, we assessed the repeatability of each technique using rates obtained from short intervals where no measurable atrophy is expected. For those measures that provided direct measures of atrophy between pairs of images, we also assessed symmetry and transitivity. Then, we performed a statistical analysis in a consistent manner using linear mixed effect models. The models, one for repeated measures of volume made at multiple time-points and a second for repeated "direct" measures of change in brain volume, appropriately allowed for the correlation between measures made on the same subject and were shown to fit the data well. From these models, we obtained estimates of the distribution of atrophy rates in the Alzheimer's disease (AD) and control groups and of required sample sizes to detect a 25% treatment effect, in relation to healthy ageing, with 95% significance and 80% power over follow-up periods of 6, 12, and 24months. Uncertainty in these estimates, and head-to-head comparisons between techniques, were carried out using the bootstrap. The lateral ventricles provided the most stable measurements, followed by the brain. The hippocampi had much more variability across participants, likely because of differences in segmentation protocol and less distinct boundaries. Most methods showed no indication of bias based on the short-term interval results, and direct measures provided good consistency in terms of symmetry and transitivity. The resulting annualized rates of change derived from the model ranged from, for whole brain: -1.4% to -2.2% (AD) and -0.35% to -0.67% (control), for ventricles: 4.6% to 10.2% (AD) and 1.2% to 3.4% (control), and for hippocampi: -1.5% to -7.0% (AD) and -0.4% to -1.4% (control). There were large and statistically significant differences in the sample size requirements between many of the techniques. The lowest sample sizes for each of these structures, for a trial with a 12month follow-up period, were 242 (95% CI: 154 to 422) for whole brain, 168 (95% CI: 112 to 282) for ventricles, 190 (95% CI: 146 to 268) for left hippocampi, and 158 (95% CI: 116 to 228) for right hippocampi. This analysis represents one of the most extensive statistical comparisons of a large number of different atrophy measurement techniques from around the globe. The challenge data will remain online and publicly available so that other groups can assess their methods.

Differential hippocampal shapes in posterior cortical atrophy patients: A comparison with control and typical AD subjects.

Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by predominant visual deficits and parieto-occipital atrophy, and is typically associated with Alzheimer's disease (AD) pathology. In AD, assessment of hippocampal atrophy is widely used in diagnosis, research, and clinical trials; its utility in PCA remains unclear. Given the posterior emphasis of PCA, we hypothesized that hippocampal shape measures may give additional group differentiation information compared with whole-hippocampal volume assessments. We investigated hippocampal volume and shape in subjects with PCA (n = 47), typical AD (n = 29), and controls (n = 48). Hippocampi were outlined on MRI scans and their 3D meshes were generated. We compared hippocampal volume and shape between disease groups. Mean adjusted hippocampal volumes were ∼ 8% smaller in PCA subjects (P < 0.001) and ∼ 22% smaller in tAD subject (P < 0.001) compared with controls. Significant inward deformations in the superior hippocampal tail were observed in PCA compared with controls even after adjustment for hippocampal volume. Inward deformations in large areas of the hippocampus were seen in tAD subjects compared with controls and PCA subjects, but only localized shape differences remained after adjusting for hippocampal volume. The shape differences observed, even allowing for volume differences, suggest that PCA and tAD are each associated with different patterns of hippocampal tissue loss that may contribute to the differential range and extent of episodic memory dysfunction in the two groups.

The effect of citrate dialysate on intradialytic heparin dose in haemodialysis patients: study design of a randomised controlled trial.

BACKGROUND: Unfractionated heparin is the most common anticoagulant used in haemodialysis (HD), although it has many potential adverse effects. Citrate dialysate (CD) has an anticoagulant effect which may allow reduction in cumulative heparin dose (CHD) compared to standard acetate dialysate (AD). METHODS: This double-blinded, randomised, cross-over trial of chronic haemodialysis patients determines if CD allows reduction in CHD during HD compared with AD. After enrolment, intradialytic heparin is minimised during a two-week run-in period using a standardised protocol based on a visual clotting score. Patients still requiring intradialytic heparin after the run-in period are randomised to two weeks of HD with AD followed by two weeks of CD (Sequence 1) or two weeks of HD with CD followed by two weeks of AD (Sequence 2). The primary outcome is the change in CHD with CD compared with AD. Secondary outcomes include metabolic and haemodynamic parameters, and dialysis adequacy. DISCUSSION: This randomised controlled trial will determine the impact of CD compared with AD on CHD during HD. TRIAL REGISTRATION: ClinicalTrials.gov NCT01466959.

Magnetic resonance imaging in Alzheimer's Disease Neuroimaging Initiative 2.

INTRODUCTION: Alzheimer's Disease Neuroimaging Initiative (ADNI) is now in its 10th year. The primary objective of the magnetic resonance imaging (MRI) core of ADNI has been to improve methods for clinical trials in Alzheimer's disease (AD) and related disorders. METHODS: We review the contributions of the MRI core from present and past cycles of ADNI (ADNI-1, -Grand Opportunity and -2). We also review plans for the future-ADNI-3. RESULTS: Contributions of the MRI core include creating standardized acquisition protocols and quality control methods; examining the effect of technical features of image acquisition and analysis on outcome metrics; deriving sample size estimates for future trials based on those outcomes; and piloting the potential utility of MR perfusion, diffusion, and functional connectivity measures in multicenter clinical trials. DISCUSSION: Over the past decade the MRI core of ADNI has fulfilled its mandate of improving methods for clinical trials in AD and will continue to do so in the future.

What can qualitative studies reveal about recruitment into psychiatry?

OBJECTIVE: Studies examining recruitment problems in psychiatry have been mostly quantitative and limited in their ability to elucidate perceptions and day-to-day influences that may affect recruitment. This review aimed to identify factors on recruitment into psychiatry by appraising available qualitative studies. METHODS: The authors searched MEDLINE, PsycINFO, and Embase using Health Database Advanced Search tool on NHS Evidence. Inclusion criteria were qualitative studies and English-language published papers. The authors appraised 10 qualitative studies and identified common themes. RESULTS: The ten qualitative studies used thematic analysis, phenomenology, and narrative study methods. Populations studied were medical students, foundation doctors, residents/trainees, psychiatrists, and undergraduate psychiatry teachers from the USA, UK, Australia, Canada, and Ghana. The studies highlighted importance of role models, mentorship, and supervision in improving recruitment. Additional factors included stigmatization in mental illness, satisfaction rates, interactive nature, and academic interest within psychiatry. CONCLUSION: The appraised studies were limited in their number and methodology. More qualitative studies are needed to inform policy on recruitment into psychiatry.

Divergent palate morphology in turtles and birds correlates with differences in proliferation and BMP2 expression during embryonic development.

During embryonic development, amniotes typically form outgrowths from the medial sides of the maxillary prominences called palatal shelves or palatine processes. In mammals the shelves fuse in the midline and form a bony hard palate that completely separates the nasal and oral cavities. In birds and lizards, palatine processes develop but remain unfused, leaving a natural cleft. Adult turtles do not possess palatine processes and unlike other amniotes, the internal nares open into the oral cavity. Here we investigate craniofacial ontogeny in the turtle, Emydura subglobosa to determine whether vestigial palatine processes develop and subsequently regress, or whether development fails entirely. We found that the primary palate in turtles develops similarly to other amniotes, but secondary palate ontogeny diverges. Using histology, cellular dynamics and in situ hybridization we found no evidence of palatine process development at any time during ontogeny of the face in the turtle. Furthermore, detailed comparisons with chicken embryos (the model organism most closely related to turtles from a molecular phylogeny perspective), we identified differences in proliferation and gene expression patterns that correlate with the differences in palate morphology. We propose that, in turtles, palatine process outgrowth is never initiated due to a lack of mesenchymal bone morphogenetic protein 2 (BMP2) expression in the maxillary mesenchyme, which in turn fails to induce the relatively higher cellular proliferation required for medial tissue outgrowth. It is likely that these differences between turtles and birds arose after the divergence of the lineage leading to modern turtles.

LC-MS/MS in the routine clinical laboratory: has its time come?

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been increasingly used in routine clinical laboratories during the last two decades. The high specificity, sensitivity, and multi-analyte potential make it an ideal alternative to immunoassays or conventional high-performance liquid chromatography (HPLC). It also provides higher throughput than gas chromatography-mass spectrometry (GC-MS). LC-MS/MS also offers higher flexibility than immunoassays because LC-MS/MS assays are typically developed in-house. In addition, abundant information can be obtained from a single LC-MS/MS run which can produce a large amount of quantitative or qualitative data. In this review, typical LC-MS/MS clinical applications are presented, personal experiences are shared, and strengths and weakness are discussed. It is foreseeable that LC-MS/MS will become a key instrument in routine clinical laboratories.