A comparison of role-related physical fitness between British Army trainees and trained soldiers.

British Army basic training (BT) and initial trade training (ITT) enable personnel to develop role-related physical capability to perform in-service job-roles. The study aimed to compare physical performance of trainees (completing ITT) and trained soldiers, on a series of gym-based fitness tests and representative military tasks. A total of 316 British Army personnel [68 trainees (63 men: 22 ± 3 years, 71.

External workload and cognitive performance of a tactical military scenario-based field exercise.

Introduction: Military personnel must manage a multitude of competing physiological and cognitive stressors while maintaining high levels of performance. Quantifying the external workload and cognitive demands of tactical military field exercises closely simulating operational environments, will provide a better understanding of stressors placed on personnel to inform evidence-based interventions.

Methods: Thirty-one soldiers completing a dismounted 48 hours tactical field exercise, participated in the study.

Development of an evidence-based swimming representative military task to assess swimming competency in the British Army.

Background: There is a requirement for British Army personnel to operate in/around water. Assessing role-related swimming/water competence will support personnel to conduct their job-roles safely and effectively.

Objective: To undertake a Job-Task Analysis (JTA) of British Army personnel when working in/around water and use this information to develop a Swimming Representative Military Task (RMT) to assess swimming/water competence.

Beyond change scores: Employing an improved statistical approach to analyze the impact of entry fitness on physical performance during British Army basic training in men and women.

The aim was to use a robust statistical approach to examine whether physical fitness at entry influences performance changes between men and women undertaking British Army basic training (BT). Performance of 2 km run, seated medicine ball throw (MBT) and isometric mid-thigh pull (MTP) were assessed at entry and completion of Standard Entry (SE), Junior Entry-Short (JE-Short), and Junior Entry-Long (JE-Long) training for 2350 (272 women) recruits. Performance change was analyzed with entry performance as a covariate (ANCOVA), with an additional interaction term allowing different slopes for courses and genders (p < 0.

Venetoclax Cooperates with Ionizing Radiation to Attenuate Diffuse Midline Glioma Tumor Growth.

Purpose: Tumor relapse after radiotherapy is a major hurdle in treating pediatric H3K27M-mutant diffuse midline gliomas (DMG). Radiotherapy-induced stress increases association of BCL2 family of proteins with BH3 pro-apoptotic activators preventing apoptosis. We hypothesized that inhibition of radiotherapy-induced BCL2 with a clinically relevant inhibitor, venetoclax, will block BCL2 activity leading to increased apoptosis.

Field validation of The Heat Strain Decision Aid during military load carriage.

Objectives: We aimed to determine the agreement between actual and predicted core body temperature, using the Heat Strain Decision Aid (HSDA), in non-Ground Close Combat (GCC) personnel wearing multi terrain pattern clothing during two stages of load carriage in temperate conditions.

Design: Cross-sectional.

Methods: Sixty participants (men = 49, women = 11, age 31 ± 8 years; height 171.

NTRK Fusions Can Co-Occur With H3K27M Mutations and May Define Druggable Subclones Within Diffuse Midline Gliomas.

Diffuse midline gliomas (DMGs) are incurable pediatric tumors with extraordinarily limited treatment options. Decades of clinical trials combining conventional chemotherapies with radiation therapy have failed to improve these outcomes, demonstrating the need to identify and validate druggable biologic targets within this disease. NTRK1/2/3 fusions are found in a broad range of pediatric cancers, including high-grade gliomas and a subset of DMGs.

Pathologic Shear and Elongation Rates Do Not Cause Cleavage of Von Willebrand Factor by ADAMTS13 in a Purified System.

Introduction: Pathological flows in patients with severe aortic stenosis are associated with acquired von Willebrand syndrome. This syndrome is characterized by excessive cleavage of von Willebrand factor by its main protease, A Disintegrin and Metalloproteinase with a Thrombospondin Type 1 Motif, Member 13 (ADAMTS13) leading to decreased VWF function and mucocutaneous bleeding. Aortic valve replacement and correction of the flow behavior to physiological levels reverses the syndrome, supporting the association between pathological flow and acquired von Willebrand syndrome.

Super Elongation Complex as a Targetable Dependency in Diffuse Midline Glioma.

Histone 3 gene mutations are the eponymous drivers in diffuse midline gliomas (DMGs), aggressive pediatric brain cancers for which no curative therapy currently exists. These recurrent oncohistones induce a global loss of repressive H3K27me3 residues and broad epigenetic dysregulation. In order to identify therapeutically targetable dependencies within this disease context, we performed an RNAi screen targeting epigenetic/chromatin-associated genes in patient-derived DMG cultures.

Advances in Directly Amplifying Nucleic Acids from Complex Samples.

Advances in nucleic acid amplification technologies have revolutionized diagnostics for systemic, inherited, and infectious diseases. Current assays and platforms, however, often require lengthy experimental procedures and multiple instruments to remove contaminants and inhibitors from clinically-relevant, complex samples. This requirement of sample preparation has been a bottleneck for using nucleic acid amplification tests (NAATs) at the point of care (POC), though advances in "lab-on-chip" platforms that integrate sample preparation and NAATs have made great strides in this space.

Turbulent Flow Promotes Cleavage of VWF (von Willebrand Factor) by ADAMTS13 (A Disintegrin and Metalloproteinase With a Thrombospondin Type-1 Motif, Member 13).

Objective- Acquired von Willebrand syndrome is defined by excessive cleavage of the VWF (von Willebrand Factor) and is associated with impaired primary hemostasis and severe bleeding. It often develops when blood is exposed to nonphysiological flow such as in aortic stenosis or mechanical circulatory support. We evaluated the role of laminar, transitional, and turbulent flow on VWF cleavage and the effects on VWF function.

Strategy for Generating Sequence-Defined Aptamer Reagent Sets for Detecting Protein Contaminants in Biotherapeutics.

Biologic drugs are typically manufactured in mammalian host cells, and it is critical from a drug safety and efficacy perspective to detect and remove host cell proteins (HCPs) during production. This is currently achieved with sets of polyclonal antibodies (pAbs), but these suffer from critical shortcomings because their composition is inherently undefined, and they cannot detect nonimmunogenic HCPs. In this work, we report a high-throughput screening and array-based binding characterization strategy that we employed to generate a set of aptamers that overcomes these limitations to achieve sensitive, broad-spectrum detection of HCPs from the widely used Chinese hamster ovary (CHO) cell line.

Transformation of personal computers and mobile phones into genetic diagnostic systems.

Molecular diagnostics based on the polymerase chain reaction (PCR) offer rapid and sensitive means for detecting infectious disease, but prohibitive costs have impeded their use in resource-limited settings where such diseases are endemic. In this work, we report an innovative method for transforming a desktop computer and a mobile camera phone--devices that have become readily accessible in developing countries--into a highly sensitive DNA detection system. This transformation was achieved by converting a desktop computer into a de facto thermal cycler with software that controls the temperature of the central processing unit (CPU), allowing for highly efficient PCR.

Quantitative selection and parallel characterization of aptamers.

Aptamers are promising affinity reagents that are potentially well suited for high-throughput discovery, as they are chemically synthesized and discovered via completely in vitro selection processes. Recent advancements in selection, sequencing, and the use of modified bases have improved aptamer quality, but the overall process of aptamer generation remains laborious and low-throughput. This is because binding characterization remains a critical bottleneck, wherein the affinity and specificity of each candidate aptamer are measured individually in a serial manner.

Design and self-assembly of siRNA-functionalized RNA nanoparticles for use in automated nanomedicine.

Individual genes can be targeted with siRNAs. The use of nucleic acid nanoparticles (NPs) is a convenient method for delivering combinations of specific siRNAs in an organized and programmable manner. We present three assembly protocols to produce two different types of RNA self-assembling functional NPs using processes that are fully automatable.

Differences in defensive volatiles of the forked fungus beetle, Bolitotherus cornutus, living on two species of fungus.

Forked fungus beetles, Bolitotherus cornutus, feed, mate, and live on the brackets of several species of shelf fungus that grow on decaying logs. In response to the specific threat stimulus of mammalian breath, B. cornutus beetles produce a volatile defensive secretion.