Risk of Lower Extremity Injury in a Military Cadet Population After a Supervised Injury-Prevention Program

Specific movement patterns have been identified as possible risk factors for noncontact lower extremity injuries. The Dynamic Integrated Movement Enhancement (DIME) was developed to modify these movement patterns to decrease injury risk

Seven Steps for Developing and Implementing a Preventive Training Program: Lessons Learned from JUMP-ACL and Beyond

Musculoskeletal injuries during military and sport-related training are common, costly and potentially debilitating. Thus, there is a great need to develop and implement evidence-based injury prevention strategies to reduce the burden of musculoskeletal injury. The lack of attention to implementation issues is a major factor limiting the ability to successfully reduce musculoskeletal injury rates using evidence-based injury prevention programs. We propose 7 steps that can be used to facilitate successful design and implementation of evidence-based injury prevention programs within the logical constraints of a real-world setting by identifying implementation barriers and associated solutions. Incorporating these 7 steps along with other models for behavioral health interventions may improve the overall efficacy of military and sport-related injury prevention programs

A code to Make Your Own Synthetic ObservaTIonS (MYOSOTIS)

We introduce our new code MYOSOTIS (Make Your Own Synthetic ObservaTIonS) which is designed to produce synthetic observations from simulated clusters. The code can synthesize observations from both ground-and spaced-based observatories, for a range of different filters, observational conditions and angular/spectral resolution. In this paper, we highlight some of the features of MYOSOTIS, creating synthetic observations from young massive star clusters. Our model clusters are simulated using NBODY6 code and have different total masses, halfmass radii, and binary fractions. The synthetic observations are made at the age of 2 Myr with Solar metallicity and under different extinction conditions. For each cluster, we create synthetic images of the Hubble Space Telescope (HST) in the visible (WFPC2/F555W) as well as Very Large Telescopes in the nearIR (SPHERE/IRDIS/Ks). We show how MYOSOTIS can be used to look at mass function (MF) determinations. For this aim we re-estimate stellar masses using a photometric analysis on the synthetic images. The synthetic MF slopes are compared to their actual values. Our photometric analysis demonstrate that depending on the adopted filter, extinction, angular resolution, and pixel sampling of the instruments, the power-law index of the underlying MFs can be shallower than the observed ones by at least ±0.25 dex which is in agreement with the observed discrepancies reported in the literature, specially for young star clusters

CSL–MAML-dependent Notch1 signaling controls T lineage–specific IL-7Rα gene expression in early human thymopoiesis and leukemia

Notch1 activation is essential for T-lineage specification of lymphomyeloid progenitors seeding the thymus. Progression along the T cell lineage further requires cooperative signaling provided by the interleukin 7 receptor (IL-7R), but the molecular mechanisms responsible for the dynamic and lineage-specific regulation of IL-7R during thymopoiesis are unknown. We show that active Notch1 binds to a conserved CSL-binding site in the human IL7R gene promoter and critically regulates IL7R transcription and IL-7R α chain (IL-7Rα) expression via the CSL–MAML complex. Defective Notch1 signaling selectively impaired IL-7Rα expression in T-lineage cells, but not B-lineage cells, and resulted in a compromised expansion of early human developing thymocytes, which was rescued upon ectopic IL-7Rα expression. The pathological implications of these findings are demonstrated by the regulation of IL-7Rα expression downstream of Notch1 in T cell leukemias. Thus, Notch1 controls early T cell development, in part by regulating the stage- and lineage-specific expression of IL-7Rα

A phase I trial of the selective oral cyclin-dependent kinase inhibitor seliciclib (CYC202; R-Roscovitine), administered twice daily for 7 days every 21 days

Seliciclib (CYC202; R-roscovitine) is the first selective, orally bioavailable inhibitor of cyclin-dependent kinases 1, 2, 7 and 9 to enter clinical trial. Preclinical studies showed antitumour activity in a broad range of human tumour xenografts. A phase I trial was performed with a 7-day b.i.d. p.o. schedule. Twenty-one patients (median age 62 years, range: 39–73 years) were treated with doses of 100, 200 and 800 b.i.d. Dose-limiting toxicities were seen at 800 mg b.i.d.; grade 3 fatigue, grade 3 skin rash, grade 3 hyponatraemia and grade 4 hypokalaemia. Other toxicities included reversible raised creatinine (grade 2), reversible grade 3 abnormal liver function and grade 2 emesis. An 800 mg portion was investigated further in 12 patients, three of whom had MAG3 renograms. One patient with a rapid increase in creatinine on day 3 had a reversible fall in renal perfusion, with full recovery by day 14, and no changes suggestive of renal tubular damage. Further dose escalation was precluded by hypokalaemia. Seliciclib reached peak plasma concentrations between 1 and 4 h and elimination half-life was 2–5 h. Inhibition of retinoblastoma protein phosphorylation was not demonstrated in peripheral blood mononuclear cells. No objective tumour responses were noted, but disease stabilisation was recorded in eight patients; this lasted for a total of six courses (18 weeks) in a patient with ovarian cancer

Notch signaling during human T cell development

Notch signaling is critical during multiple stages of T cell development in both mouse and human. Evidence has emerged in recent years that this pathway might regulate T-lineage differentiation differently between both species. Here, we review our current understanding of how Notch signaling is activated and used during human T cell development. First, we set the stage by describing the developmental steps that make up human T cell development before describing the expression profiles of Notch receptors, ligands, and target genes during this process. To delineate stage-specific roles for Notch signaling during human T cell development, we subsequently try to interpret the functional Notch studies that have been performed in light of these expression profiles and compare this to its suggested role in the mouse