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Matthew Walker

Publications and source records attributed to Matthew Walker.

15 recordsLinked to original sources
PubMed2026

Benchmarking DNA extraction protocols across use cases for culture-independent Nanopore metagenomics.

Oxford Nanopore Technologies (ONT) sequencing offers several advantages for metagenomics, including long reads, rapid turnaround, low upfront cost, scalability and portability. However, for ONT metagenomics, DNA yield, quality and integrity are important considerations when selecting an extraction method. Many metagenomic extraction methods use harsh lysis conditions to extract a wide range of species and provide an accurate community composition, but these conditions can compromise DNA fragment length. Therefore, extraction methods for ONT metagenomics must balance DNA shearing and recovery with representative community lysis. We systematically evaluated DNA extraction methods for ONT metagenomic sequencing using a use case-oriented framework. Among nearly 50 extraction methods screened, 7 were selected for detailed comparison based on suitability for metagenomics, variation in methodology, availability, cost and processing time: Norgen BioTek Corp's Stool DNA Isolation (NG), Zymo Research's ZymoBIOMICS Quick-DNA HMW MagBead (ZMG), Qiagen's DNeasy Blood and Tissue (QBT), Macherey-Nagel's NucleoMag DNA Microbiome (MN), Zymo Research's ZymoBIOMICS DNA Mini Prep (ZMI), Qiagen's DNeasy PowerSoil/QIAamp PowerFecal Pro (PS) and Qiagen's QIAamp Fast DNA Stool Mini (QIA). Methods were tested using Zymo Research's ZymoBIOMICS Microbial Community Standard (MCS), a matrix-free mock community with known composition. DNA extracts were sequenced on an ONT PromethION using the Rapid Barcoding Kit, except QIA due to insufficient DNA yield. Metrics for the method, DNA extracts, sequencing and genomes were evaluated, revealing trade-offs between methods. The two magnetic bead methods, MN and ZMG, produced the highest mean read length N50 values (13.9 and 16.5 kb, respectively) but showed apparent community compositions skewed towards Gram-negative bacteria. In contrast, ZMI and PS maintained a community composition close to expected, with reduced mean read length N50 values (4.5 vs. 7.5 kb). Performance across various metrics is presented in the context of the following use cases: maximizing genome coverage and assembly completeness, preserving composition accuracy, targeting specific species and limiting required resources (equipment, time or budget). The metrics and use case considerations presented offer practical guidance for informed selection of DNA extraction methods for ONT metagenomics. For accurate community composition, ZMI or PS are recommended, while PS and ZMG perform best at maximizing genome coverage and assembly completeness. NG and QBT may be the most economical options, though performance trade-offs were observed. Finally, PS may be the preferred method for time-sensitive diagnostic or field applications.

Metagenomics↗
PubMed2025

Cardiac Troponins and Cardiovascular Disease Risk Prediction: An Individual-Participant-Data Meta-Analysis.

BACKGROUND: The extent to which high-sensitivity cardiac troponin can predict cardiovascular disease (CVD) is uncertain. OBJECTIVES: We aimed to quantify the potential advantage of adding information on cardiac troponins to conventional risk factors in the prevention of CVD. METHODS: We meta-analyzed individual-participant data from 15 cohorts, comprising 62,150 participants without prior CVD. We calculated HRs, measures of risk discrimination, and reclassification after adding cardiac troponin T (cTnT) or I (cTnI) to conventional risk factors. The primary outcome was first-onset CVD (ie, coronary heart disease or stroke). We then modeled the implications of initiating statin therapy using incidence rates from 2.1 million individuals from the United Kingdom. RESULTS: Among participants with cTnT or cTnI measurements, 8,133 and 3,749 incident CVD events occurred during a median follow-up of 11.8 and 9.8 years, respectively. HRs for CVD per 1-SD higher concentration were 1.31 (95% CI: 1.25-1.37) for cTnT and 1.26 (95% CI: 1.19-1.33) for cTnI. Addition of cTnT or cTnI to conventional risk factors was associated with C-index increases of 0.015 (95% CI: 0.012-0.018) and 0.012 (95% CI: 0.009-0.015) and continuous net reclassification improvements of 6% and 5% in cases and 22% and 17% in noncases. One additional CVD event would be prevented for every 408 and 473 individuals screened based on statin therapy in those whose CVD risk is reclassified from intermediate to high risk after cTnT or cTnI measurement, respectively. CONCLUSIONS: Measurement of cardiac troponin results in a modest improvement in the prediction of first-onset CVD that may translate into population health benefits if used at scale.

Humans↗
PubMed2005

Cognitive performance by humans during a smoked cocaine binge-abstinence cycle.

Five cocaine-dependent individuals completed a 22-day inpatient study of sleep and cognition. Following 3 days of drug-free baseline, participants underwent 3 days of twice-daily smoked cocaine base self-administration (6 50-mg doses, 14 minutes apart), followed by 15 days of abstinence. Each morning and afternoon, the CDR repeatable, multiple-version, computerized cognitive battery (whose stability following practice has been documented) was administered. During abstinence, performance deteriorated on vigilance tasks (especially reaction time) as well as on immediate and delayed verbal recognition tasks but not on working memory tasks. Declines were most evident in the afternoon. Data suggest that abstinence can unmask cognitive deficits induced by chronic cocaine use and circadian factors may mediate their severity.

Adult↗
PubMed2005

Status epilepticus in idiopathic generalized epilepsy.

Status epilepticus (SE) can take various forms in idiopathic generalized epilepsy (IGE), some of which forms also occur in symptomatic or focal epilepsies. Although the clinical semiology of the SE episodes may be similar in these different epilepsies, the frequency, response to treatment and prognosis differ. (a) Convulsive SE is surprisingly uncommon in IGE and much less common than in the secondarily generalized or partial epilepsies. Also, when it does occur, it usually responds rapidly to treatment. (b) Typical absence SE occurs only in patients with IGE (the subcategories with typical absence seizures) and also in the syndrome of de novo absence SE of late onset. This form of nonconvulsive SE should be differentiated from atypical absence SE, which occurs in the secondarily generalized epilepsy encephalopathies, and from complex partial SE which occurs in focal epilepsy. The clinical symptoms of these three types overlap but the prognosis and response to treatment are different. The mechanisms underlying absence SE are uncertain and may include both genetic and environmental factors. The termination of absence seizures has been hypothesized to be due to persistent activation of a depolarizing current in thalamocortical neurons that inactivates T-type calcium channels. SE could thus result from dysfunction of this channel or mechanisms that hyperpolarize thalamocortical neurons-these include decreased cortical inhibition, increased reticular thalamic neuronal activity or increased thalamocortical neuron GABA(B)-receptor activation. (c) Generalized electrographic SE is encountered in IGE in the syndrome of phantom absence with GTCS. It also occurs in ESES and in the Landau-Kleffner syndrome. The seizure phenomenology overlaps with the focal SE of temporal or frontal lobe epilepsy. (d) Myoclonic SE is also uncommon in IGE but occurs in juvenile myoclonic epilepsy. It is more commonly encountered in progressive myoclonic epilepsies, myoclonic-astatic epilepsy and in the Dravet syndrome. (e) Autonomic status occurs largely in the Panayiotopoulos syndrome. It is included here under the rubric of IGE, although the epilepsy has focal as well as generalized features and its nosological position is controversial. Fifty percent of seizures in this syndrome could be classified as status epilepticus. There is no doubt that convulsive SE can result in cerebral damage. In animal models of focal SE, nonconvulsive forms can also result in cerebral damage, but cerebral damage is not observed in animal models of absence SE. Similarly, cerebral damage seems not to occur in the forms of nonconvulsive SE in human IGE.

Animals↗
PubMed2005

The effect of nonsteroidal anti-inflammatory agents on spinal fusion.

A large body of information suggests NSAIDS have a negative impact on the healing of bone. Although each clinical healing scenario presents a slightly different level of challenge, the healing of a posterolateral spinal fusion is one of the most difficult challenges in bony healing. Clinically, this results in a relatively high rate of nonunions using traditional fusion techniques. Spinal fusion models have confirmed NSAIDS have a definite inhibitory effect on healing of the fusion. Although data are limited, it appears this effect is most severe when NSAIDS are administered in the early postoperative period. Moreover, the effect may be worse with certain types initial inflammatory, subsequent reparative, and final remodeling phases. Because of the anti-inflammatory activity of NSAIDS, one might assume their effects would be worse when administered in the inflammatory phase. Indeed, the study by Riew et al suggests the inhibitory effects are more significant when NSAIDS are administered earlier following fusion. Other studies conducted with non-spinal models also suggest early administration of NSAIDS results in greater inhibition of bone formation (Goodman et al). Unfortunately, the length of the inflammatory phase in humans is not well known. This leaves the clinician unsure about the safe time to allow resumption of NSAID usage clinically. It appears likely NSAID use following a spinal fusion procedure will increase the rate of pseudarthrosis. The literature suggests that avoidance of NSAIDS in the postoperative period may avoid nonunion. Additionally, we propose that chronic NSAID usage should be addressed in a similar manner to cigarette smoking. While neither are absolute contraindications to elective spinal fusion, patients should be counseled to discontinue the use of NSAIDS in the peri- and postoperative period to maximize their chance for a successful fusion.

Animals↗
PubMed2005

Nonconvulsive status epilepticus: Epilepsy Research Foundation workshop reports.

In April 2004, a group of physicians with an interest in nonconvulsive status epilepticus representing a spectrum of opinion met in Oxford, sponsored by the Epilepsy Research Foundation (a charitable organization), to discuss and debate the definition, diagnosis and treatment of nonconvulsive status epilepticus. We felt that such a meeting would be useful, as nonconvulsive status epilepticus is a subject that provokes strong reactions, perhaps largely due to the relative lack of evidence and the surfeit of opinion. The meeting was arranged such that there were formal talks followed by a discussion led by one of the attendees. We present here the extended abstracts of the main talks with the points raised by the discussants. Despite disagreements on certain issues there was much in the way of consensus. First, it was agreed that nonconvulsive status epilepticus is a term that covers a range of disparate conditions with varying prognoses and treatments. The agreed definition was thus suitably vague, A< >. Secondly, it was agreed that even within a specific condition (e.g. complex partial status epilepticus), the prognosis and treatment depends upon the context in which the condition occurs (e.g. in the critically ill, in coma, in the A< > and in people with prior epilepsy). Perhaps, most importantly it was agreed that we lacked good clinical data, and the challenge was to design good studies for a condition that is underrecognised and often difficult to diagnose.

Brain Damage, Chronic↗
PubMed2004

Myosin VI: cellular functions and motor properties.

Myosin VI has been localized in membrane ruffles at the leading edge of cells, at the trans-Golgi network compartment of the Golgi complex and in clathrin-coated pits or vesicles, indicating that it functions in a wide variety of intracellular processes. Myosin VI moves along actin filaments towards their minus end, which is the opposite direction to all of the other myosins so far studied (to our knowledge), and is therefore thought to have unique properties and functions. To investigate the cellular roles of myosin VI, we identified various myosin VI binding partners and are currently characterizing their interactions within the cell. As an alternative approach, we have expressed and purified full-length myosin VI and studied its in vitro properties. Previous studies assumed that myosin VI was a dimer, but our biochemical, biophysical and electron microscopic studies reveal that myosin VI can exist as a stable monomer. We observed, using an optical tweezers force transducer, that monomeric myosin VI is a non-processive motor which, despite a relatively short lever arm, generates a large working stroke of 18 nm. Whether monomer and/or dimer forms of myosin VI exist in cells and their possible functions will be discussed.

Actins↗
PubMed2004

A monomeric myosin VI with a large working stroke.

Myosin VI is involved in a wide variety of intracellular processes such as endocytosis, secretion and cell migration. Unlike almost all other myosins so far studied, it moves towards the minus end of actin filaments and is therefore likely to have unique cellular properties. However, its mechanism of force production and movement is not understood. Under our experimental conditions, both expressed full-length and native myosin VI are monomeric. Electron microscopy using negative staining revealed that the addition of ATP induces a large conformational change in the neck/tail region of the expressed molecule. Using an optical tweezers-based force transducer we found that expressed myosin VI is nonprocessive and produces a large working stroke of 18 nm. Since the neck region of myosin VI is short (it contains only a single IQ motif), it is difficult to reconcile the 18 nm working stroke with the classical 'lever arm mechanism', unless other structures in the molecule contribute to the effective lever. A possible model to explain the large working stroke of myosin VI is presented.

Actins↗
PubMed2004

To sleep, perchance to gain creative insight?

The development of mathematical insight, the knack for discovering novel solutions to mathematical problems, might be one of the most erudite forms of learning that we can hope to achieve. However, Wagner and his colleague now report that a night of sleep after being exposed to a class of mathematical problems more than doubles the likelihood of discovering just such a novel solution.

Creativity↗
PubMed2004

Gadolinium leakage into the surgical bed mimicking residual enhancement following spinal cord surgery. Case report.

Intramedullary spinal cord surgery can disrupt the blood-spinal cord barrier and cause intravascular contents to leak into the surgical cavity. Immediate postoperative Gd-enhanced magnetic resonance (MR) imaging can demonstrate leakage of contrast into the surgical bed and complicate the assessment of whether a residual enhancing tumor is present. The authors report a case in which the preoperative lesion was nonenhancing and not expected to enhance on postoperative imaging. A Gd-enhanced MR imaging study obtained less than 24 hours after surgery revealed that the intramedullary surgical cavity was filled with contrast material. Because of the time course and the lesion's preoperative appearance, this "enhancement" was known to be caused by the leakage of medium into the resection cavity rather than of pathological soft-tissue enhancement.

Cysts↗
PubMed2004

Temporary balloon occlusion to test adequacy of collateral flow to the retina and tolerance for endovascular aneurysmal coiling.

Two carotid ophthalmic artery aneurysms with incorporation of the artery into the neck were referred for endovascular assessment. Temporary balloon occlusion at the aneurysm neck was performed in an attempt to assess the adequacy of collateral flow to the retina. During inflation, the patients reported visual deterioration that resolved upon deflation, which indicates that collateral blood flow was insufficient. The patients were referred for surgical clipping to ensure preservation of the ophthalmic artery.

Aneurysm↗
PubMed2003

Efficacy of autologous growth factors in lumbar intertransverse fusions.

STUDY DESIGN AND OBJECTIVES: A retrospective, consecutive series with "blinded" radiographic review was performed to evaluate two groups undergoing lumbar fusion: one with and one without autologous growth factors (AGF). SUMMARY OF BACKGROUND DATA: AGF has been shown to promote bone formation in vitro and in vivo in animal studies. Accordingly, it has been promoted to augment lumbar intertransverse fusions. To date, however, no controlled studies have been performed to assess its ability to do so in humans. This article presents the first such study. MATERIALS AND METHODS: Two groups were studied. The control group consisted of 27 consecutive patients who underwent a single-level intertransverse lumbar fusion using iliac crest bone graft for either degenerative disk disease (DDD) or degenerative spondylolisthesis from January 1999 to November 1999. The AGF group consisted of 32 consecutive patients undergoing an identical procedure for the same indications with iliac crest bone graft augmented with AGF from January 2000 to November 2000. Fusions were assessed radiographically at 1 and 2 years by two independent spine surgeons on AP and lateral flexion/extension radiographs. RESULTS: The fusion rate for the control group was 24 of 27, or 91%. The fusion rate for the AGF group was 18 of 32 or 62%. CONCLUSIONS: In this study, the use of AGF resulted in inferior rates of arthrodesis compared with autogenous bone graft alone. Although it is important to note there are several techniques available to produce AGF and that the concentration of AGF may differ between individuals, based on the authors' findings, they cannot recommend the use of AGF for this indication until further clinical studies, perhaps altering these variables, prove otherwise.

Adult↗
PubMed2002

The lateral buttress: an anatomic feature of the lumbar pars interarticularis.

STUDY DESIGN: A morphometric study of the lateral buttress region of the lumbar pars interarticularis from L1-L5 on 10 dried lumbar spines was performed. OBJECTIVE: To qualitatively describe and quantitatively evaluate this portion of the pars and to discuss its clinical and surgical relevance. BACKGROUND: The "lateral buttress" is a bony bridge connecting the superolateral edge of the inferior facet to the pedicle/transverse process junction, offering structural support to the pars interarticularis at upper lumbar levels. To date, no anatomic study has evaluated this structure. METHODS: Direct measurements using vernier calipers were taken at each level, L1-L5, from 10 dried lumbar spines. Surface area of the buttress was calculated and compared statistically for differences between each level, as well as normalized relative to L3. RESULTS: The surface areas of the buttresses at L1-L3 were similar, measuring near 80 +/- 10 mm2. At L4, it measured 50 +/- 10 mm2. And at L5, it measured 15 +/- 5 mm2. These differences were statistically significant. Normalized data showed the buttress at L4 to be 40% smaller and at L5 to be 80% smaller than at upper levels. CONCLUSIONS: This study provides descriptive and anatomic data regarding the lateral buttress portion of lumbar pars interarticularis. The broad buttress of the upper lumbar levels offers support to the pars but can confuse anatomic guidelines for pedicle screw placement and paraspinal approaches. The narrow buttress of lower lumbar levels makes pedicle screw placement and the paraspinal approach easier, but it lessens support to the pars, making spondylolysis and iatrogenic instability more likely.

Humans↗
PubMed2002

Systemic inflammation induced by lipopolysaccharide increases neointimal formation after balloon and stent injury in rabbits.

BACKGROUND: Emerging data indicate that the inflammatory response after mechanical arterial injury correlates with the severity of neointimal hyperplasia in animal models and postangioplasty restenosis in humans. The present study was designed to examine whether a nonspecific stimulation of the innate immune system, induced in close temporal proximity to the vascular injury, would modulate the results of the procedure. Methods and Results- Rabbits subjected to iliac artery balloon injury (balloon denudation with or without stent deployment) were injected twice with a bacterial lipopolysaccharide (LPS) (500 ng/rabbit) before and after surgery. The dose was chosen to be sufficient to induce systemic inflammation but not septic shock. A systemic marker of inflammation (serum interleukin-1beta levels measured by ELISA) and monocytic stimulation (CD14 levels on monocytes measured by flow cytometry) were increased after LPS administration. Arterial macrophage infiltration at 7 days after injury was 1.7+/-1.2% of total cells in controls and 4.2+/-1.8% in LPS-treated rabbits (n=4, P<0.05). Morphometric analysis of the injured arteries 4 weeks after injury revealed significantly increased luminal stenosis (38+/-4.2% versus 23+/-2.6, mean+/- SEM; n=8, P<0.05) and neointima-to-media ratio (1.26+/-0.21 versus 0.66+/- 0.09, P<0.05) in LPS-treated animals compared with controls. This effect was abolished by anti-CD14 Ab administration. Serum interleukin-1beta levels and monocyte CD14 expression were significantly increased in correlation with the severity of intimal hyperplasia. LPS treatment increased neointimal area after stenting from 0.57+/-0.07 to 0.77+/- 0.1 mm(2) and stenosis from 9+/-1% to 13+/-1.7% (n=5, P< 0.05). CONCLUSIONS: Nonspecific systemic stimulation of the innate immune system concurrently with arterial vascular injury facilitates neointimal formation, and conditions associated with increased inflammation may increase restenosis.

Angioplasty, Balloon↗