The precision medicine initiative has driven a substantial change in the way scientists and health care practitioners think about diagnosing and treating disease. While it has long been recognized that drug response is determined by the intersection of genetic, environmental, and disease factors, improvements in technology have afforded precision medicine guided dosing of drugs to improve efficacy and reduce toxicity. Pharmacometabolomics aims to evaluate small molecule metabolites in plasma and/or urine to help evaluate mechanisms that predict and/or reflect drug efficacy and toxicity. In this mini review, we provide an overview of pharmacometabolomic approaches and methodologies. Relevant examples where metabolomic techniques have been used to better understand drug efficacy and toxicity in major depressive disorder and cancer chemotherapy are discussed. In addition, the utility of metabolomics in drug development and understanding drug metabolism, transport, and pharmacokinetics is reviewed. Pharmacometabolomic approaches can help describe factors mediating drug disposition, efficacy, and toxicity. While important advancements in this area have been made, there remain several challenges that must be overcome before this approach can be fully implemented into clinical drug therapy.

Rare genetic conditions are challenging for the primary care provider to manage without proper guidelines. This clinical review is designed to assist the pediatrician, family physician, or internist in the primary care setting to manage the complexities of 16p11.2 deletion syndrome. A multidisciplinary medical home with the primary care provider leading the care and armed with up-to-date guidelines will prove most helpful to the rare genetic patient population. A special focus on technology to fill gaps in deficits, review of case studies on novel medical treatments, and involvement with the educational system for advocacy with an emphasis on celebrating diversity will serve the rare genetic syndrome population well.

Metastatic porocarcinomas (PCs) are vanishingly rare, highly aggressive skin adnexal tumors with mortality rates exceeding 70%. Their rarity has precluded the understanding of their disease pathogenesis, let alone the conduct of clinical trials to evaluate treatment strategies. There are no effective agents for unresectable PCs. Here, we successfully demonstrate how functional precision medicine was implemented in the clinic for a metastatic PC with no known systemic treatment options. Comprehensive genomic profiling of the tumor specimen did not yield any actionable genomic aberrations. However, ex vivo drug testing predicted pazopanib efficacy, and indeed, administration of pazopanib elicited remarkable clinicoradiological response. Pazopanib and its class of drugs should be evaluated for efficacy in other cases of PC, and the rationale for efficacy should be determined when PC tumor models become available. A functional precision medicine approach could be useful to derive effective treatment options for rare cancers.

Veterans are at an increased risk for prostate cancer, a disease with extraordinary clinical and molecular heterogeneity, compared with the general population. However, little is known about the underlying molecular heterogeneity within the veteran population and its impact on patient management and treatment. Using clinical and targeted tumor sequencing data from the National Veterans Affairs health system, we conducted a retrospective cohort study on 45 patients with advanced prostate cancer in the Veterans Precision Oncology Data Commons (VPODC), most of whom were metastatic castration-resistant. We characterized the mutational burden in this cohort and conducted unsupervised clustering analysis to stratify patients by molecular alterations. Veterans with prostate cancer exhibited a mutational landscape broadly similar to prior studies, including KMT2A and NOTCH1 mutations associated with neuroendocrine prostate cancer phenotype, previously reported to be enriched in veterans. We also identified several potential novel mutations in PTEN, MSH6, VHL, SMO, and ABL1. Hierarchical clustering analysis revealed two subgroups containing therapeutically targetable molecular features with novel mutational signatures distinct from those reported in the Catalogue of Somatic Mutations in Cancer database. The clustering approach presented in this study can potentially be used to clinically stratify patients based on their distinct mutational profiles and identify actionable somatic mutations for precision oncology.

Pilocytic astrocytomas are the most common pediatric brain tumors, typically presenting as low-grade neoplasms. We report two cases of pilocytic astrocytoma with atypical tumor progression. Case 1 involves a 12-yr-old boy with an unresectable suprasellar tumor, negative for BRAF rearrangement but harboring a BRAF p.V600E mutation. He experienced tumor size reduction and stable disease following dabrafenib treatment. Case 2 describes a 6-yr-old boy with a thalamic tumor that underwent multiple resections, with no actionable driver detected using targeted next-generation sequencing. Whole-genome and RNA-seq analysis identified an internal tandem duplication in FGFR1 and RAS pathway activation. Future management options include FGFR1 inhibitors. These cases demonstrate the importance of escalating molecular diagnostics for pediatric brain cancer, advocating for early reflexing to integrative whole-genome sequencing and transcriptomic profiling when targeted panels are uninformative. Identifying molecular drivers can significantly impact treatment decisions and improve patient outcomes.

From assembling delicate electronics to constructing safety-critical aerospace components, the margin for error has shrunk to almost nothing. To meet these rigorous standards, the manufacturing industry increasingly relies on robotic precision. Modern robotics, equipped with advanced sensors, grippers, and AI, allow manufacturers to complete intricate tasks with extraordinary accuracy. Technological Innovations Driving Robotic Precision Today’s […]

The post Robotic Precision in Manufacturing: Achieving High Accuracy for Complex Tasks appeared first on Chart Attack.

Tissue stiffness in HER2-negative breast cancer, the most common type, can directly contribute to disease progression and metastasis, which can have serious consequences on patients.

Researchers have introduced an innovative statistical tool enhancing the identification of disease-causing genetic variants. This tool combines information

Alterations in the SCN2A gene influence the age of seizure onset and the severity of neurological impairments in affected children, aiding in the identification

Most organisms rely on 20 standard medlinkamino acids/medlink to synthesize proteins, with few exceptions. Chemist Han Xiao's research focuses on

New study investigates how convolutional neural networks (CNNs) can enhance nasal endoscopy accuracy and efficiency. The study focuses on overcoming diagnostic

The war in Ukraine has shown that warfare changes by the day. It’s also clear that the tech used to make war today is costly: While larger countries can afford legions of tanks, helicopters, and precision-strike systems, smaller nations find themselves scrambling for cheaper ways to defend themselves. Origin, a new defense tech startup out of […]

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The company, 4baseCare, has come up with a gene panel for the Indian population after extensive research. This, according to the founders, will allow doctors to provide more evidence-based and data-backed treatment for cancer patients in the country

NCI has launched myeloMATCH, a precision medicine treatment trial that will test treatment combinations targeting specific genetic changes in people with acute myeloid leukemia and myelodysplastic syndromes.

The Hyderabad-based MSME, Raghu Vamsi Group, has completed the acquisition of British precision machining firm PMC GGroup, that traces its roots to over 100 years

Two Princeton University studies are opening important new windows into understanding an untreatable group of common genetic disorders known as RASopathies that affect approximately one child out of 1,000 and are characterized by distinct facial features, developmental delays, cognitive impairment and heart problems. The findings could help point the way toward personalized precision therapies for these conditions.

This article describes a high-efficiency experimental configuration for a self-referenced lattice comparator with a `brush beam' of synchrotron radiation from a bending magnet and two linear position-sensitive photon-counting-type X-ray detectors. The efficiency is more than ten times greater compared with the `pencil-beam' configuration and a pair of zero-dimensional detectors. A solution for correcting the systematic deviation of d-spacing measurements caused by the horizontal non-uniformity of the brush beam is provided. Also, the use of photon-counting-type one-dimensional detectors not only improves the spatial resolution of the measurements remarkably but can also adjust the sample's attitude angles easily.

Using echolocation alone the bats found, identified and captured insects perched motionless and silent on the leaves of plants.

The post Common tropical bat uses echolocation with precision previously considered impossible, new experiments reveal appeared first on Smithsonian Insider.

A new data network that integrates emerging research on the molecular makeup of diseases with clinical data on individual patients could drive the development of a more accurate classification of disease and ultimately enhance diagnosis and treatment, says a new report from the National Research Council.

Anaheim Automation expands its line of linear components

The OCMX™ is pleased to announce the listing of Rx-Precision, Inc. to its online portal which offers Investors and Advisors the ability to participate in this opportunity.

The accurate assembly of the system matrix is an important step in any code that solves partial differential equations on a mesh. We either explicitly set up a matrix, or we work in a matrix-free environment where we have to be able to quickly return matrix entries upon demand. Either way, the construction can become costly due to non-trivial material parameters entering the equations, multigrid codes requiring cascades of matrices that depend upon each other, or dynamic adaptive mesh refinement that necessitates the recomputation of matrix entries or the whole equation system throughout the solve. We propose that these constructions can be performed concurrently with the multigrid cycles. Initial geometric matrices and low accuracy integrations kickstart the multigrid, while improved assembly data is fed to the solver as and when it becomes available. The time to solution is improved as we eliminate an expensive preparation phase traditionally delaying the actual computation. We eliminate algorithmic latency. Furthermore, we desynchronise the assembly from the solution process. This anarchic increase of the concurrency level improves the scalability. Assembly routines are notoriously memory- and bandwidth-demanding. As we work with iteratively improving operator accuracies, we finally propose the use of a hierarchical, lossy compression scheme such that the memory footprint is brought down aggressively where the system matrix entries carry little information or are not yet available with high accuracy.

There is provided an automatic tool changer which, in a precision roll turning lathe which feeds a tool post at a high speed, can automatically change a tool, such as a cutting tool, without stopping the machine, thereby enabling highly efficient ultra-Precision machining of a roll mold for molding of a large-sized plastic sheet. The automatic tool changer includes: a change device including a vertically movable pivot arm having a pivot axis and which pivots in a horizontal plane, a hand portion, mounted at the front end of the arm, for detachably gripping a tool holder, a pivot drive section for pivoting the pivot arm, and a lifting drive section for vertically moving the pivot arm; a tool holder stocker, having a plurality of circumferentially-arranged stages disposed at a predetermined distance from the pivot axis, each stage detachably holding a tool holder; a holder base, mounted to the tool post, for fixing and unfixing a tool holder through the rotation of a clamp shaft; and a clamp shaft operating device including an operating portion for clamping/unclamping the tool holder by rotating the clamp shaft.

A method in a portable data carrier for executing a cryptographic operation on security-relevant data comprises a step of determining a remainder (r) of a dividend (a) modulo a divisor (b). In so doing, the remainder (r) is determined iteratively by means of a division device of the data carrier. In each iteration there is carried out a Montgomery multiplication with the divisor (b) as the modulus and an additive linkage of an output value of the Montgomery multiplication with a coefficient (ai) derived from the dividend (a) and associated with the respective iteration. The Montgomery multiplication is carried out here by means of a multiplication device of the data carrier, preferably a corresponding coprocessor. The Montgomery multiplication of a subsequent iteration receives a result of a preceding iteration as an input value.

A tool cartridge for a material removal tool has a cartridge body with, among other things, a recess extending through at least a portion of the cartridge body from a first side toward a second side, a long axis of the recess non-parallel to a long axis of the cartridge body and at least a portion of the recess open to a bottom side of the cartridge body, and a threaded opening for a differential screw proximate a second end of the tool body and positioned longitudinally between an opening for a clamping screw and at least a portion of a seat for a cutting tool insert. A thread axis of the threaded opening is at an angle G relative to a long axis of the tool cartridge. A material removal tool, a tool, and a method of adjusting a cutting tool insert are also disclosed.

Wood particles having fibers aligned in a grain, wherein: the wood particles are characterized by a length dimension (L) aligned substantially parallel to the grain, a width dimension (W) normal to L and aligned cross grain, and a height dimension (H) normal to W and L; the L×H dimensions define two side surfaces characterized by substantially intact longitudinally arrayed fibers; the W×H dimensions define two cross-grain end surfaces characterized individually as aligned either normal to the grain or oblique to the grain; the L×W dimensions define two substantially parallel top and bottom surfaces; and, a majority of the W×H surfaces in the mixture of wood particles have end checking.

Embodiments of digital high-speed bi-phase modulator and method for bi-phase modulation are generally described herein. In some embodiments, the digital high-speed bi-phase modulator comprises a high-speed digital divider, a high-speed digital multiplexer, and matched signal paths provided between the divider and the multiplexer. The high-speed digital divider is configured to receive a carrier signal and generate complementary output signals. The high-speed digital multiplexer is configured to switch between the complementary output signals and generate a bi-phase modulated output at a carrier frequency (fc) modulated with a bi-phase code. The bi-phase code may be provided to control inputs of the multiplexer.

In various embodiments, systems and methods for generating high-precision pulse-width modulation include a delay-locked loop comprising multiple delay units having time-variable delays, control logic for selecting a subset S of the multiple delay units to thereby generate a time-invariant shift amount having a precision finer than that of a system clock and circuitry for applying the shift amount to rising and falling edges of a pulse-width modulation waveform to thereby generate a high-precision pulse-width modulation waveform.

The invention relates to a high-precision revolving center (10) for machine tools. Prestressed bearings 40 and 45 are brought into abutment on the one hand against internal 33 and external 25 cylindrical surfaces whose deviation, at any point on the surface, with respect to the theoretical surfaces centered on the axis, is less than 1 μm, and on the other hand against reference surfaces 26 and 34 perpendicular to the axis. Threaded elements 50, 55 enable the bearings 40, 45 to be stressed. Once the center 10 has been assembled and the bearings stressed, the revolving center is mounted on a grinder in order to give a precision finish to the tip 90, the concentricity reference surface 91 and the perpendicularity reference surface 92.

A precision coaxial water jet disruption explosive device system that holds a blasting cap precisely to the surface of a cylindrically cut positioned plastic explosive that couples a detonation shock wave into water surrounding a hollow forming cavity. A pressure relief vent enables the water filled system to be assembled without deforming the thin walled hollow jet forming cavity, enabling forming repeatable supersonic jets on centerline axis. This system is positioned with two triangular pivot legs and aligned with two fan light beams or a line sight to define a projected jet route to deliver a water jet that can cut through over 1 inch of steel and disrupt target objects more than 9 feet away. This system is used to disable improvised explosive devices, and other dangerous objects, without detonating the targeted explosives and electronic devices such that the contents are destroyed without explosion sequences occurring.

An improved cartridge case completely produced net shape on a progressive cold former that includes a trim to lengthy station with an internal shearing tool.

An XY all-directional precision alignment platform is provided and includes an XY-axes moving platform including X-axis moving platform and Y-axis moving platform, the X-axis and Y-axis moving platforms being stacked together, and a θ-angle rotating platform, the θ-angle rotating platform stacked onto the carrier surface thereof; wherein the θ-angle rotating platform is driven to perform precise θ-angle rotation achieving 360° and is of a four-layered thickness only, achieving the goal of having a light and thin product.

JOBS are at risk at a well-known Hampshire engineering company.

JOBS are at risk at a well-known Hampshire engineering company.

Jason Snell returns to the show. Life during the COVID-19 pandemic, WWDC going online-only, Apple's in-person on-campus workplace culture, speculation on upcoming Apple product releases, and more.

(California Court of Appeal) - Affirmed. Plaintiff performed framing work on a commercial building owned by Defendant. Plaintiff was not paid for his work and filed a mechanic’s lien. Defendant complained of problems with some of the framing and Plaintiff performed repair work. Plaintiff filed this action to foreclose on its mechanic’s lien. The trial court granted Defendant summary judgment ruling that the mechanic’s lien was filed prematurely, before Plaintiff had ceased work. The appeals court agreed.

(California Court of Appeal) - Affirmed. Plaintiff performed framing work on a commercial building owned by Defendant. Plaintiff was not paid for his work and filed a mechanic’s lien. Defendant complained of problems with some of the framing and Plaintiff performed repair work. Plaintiff filed this action to foreclose on its mechanic’s lien. The trial court granted Defendant summary judgment ruling that the mechanic’s lien was filed prematurely, before Plaintiff had ceased work. The appeals court agreed.

The renaissance of complement diagnostics and therapeutics has introduced precision medicine into a widened field of complement-mediated diseases. In particular, complement-mediated diseases (or complementopathies) with ongoing or published clinical trials of complement inhibitors include paroxysmal nocturnal hemoglobinuria, cold agglutinin disease, hemolytic uremic syndrome, nephropathies, HELLP syndrome, transplant-associated thrombotic microangiopathy, antiphospholipid antibody syndrome, myasthenia gravis, and neuromyelitis optica. Recognizing that this field is rapidly expanding, we aim to provide a state-of-the-art review of (a) current understanding of complement biology for the clinician, (b) novel insights into complement with potential applicability to clinical practice, (c) complement in disease across various disciplines (hematology, nephrology, obstetrics, transplantation, rheumatology, and neurology), and (d) the potential future of precision medicine. Better understanding of complement diagnostics and therapeutics will not only facilitate physicians treating patients in clinical practice but also provide the basis for future research toward precision medicine in this field.

Компания Precision Hydration, помогающая спортсменам избежать обезвоживания, станет партнёром и официальным поставщиком команды Williams.

With their gaze fixed fully on the playoffs for months, the Clippers have been guilty of appearing disinterested at times during the regular season.