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In 2017, the US Army Public Health Center (USAPHC) at Aberdeen Proving Ground, Maryland, celebrated its 75th Anniversary. The organization began in 1942 at The Johns Hopkins University School of Hygiene and Public Health in Baltimore, Maryland, as the US Army Industrial Hygiene Laboratory to provide Occupational Medicine, Industrial Hygiene and other Occupational Health services in support of the World War II military industrial base. In 1945, the organization moved to the Edgewood Area of Aberdeen Proving Ground and underwent organizational changes, mission changes and name changes. In 1960 it was renamed the US Army Environmental Hygiene Agency or AEHA, and under that name was widely recognized for significant accomplishments in Occupational and Environmental Health. In 1994, it became the US Army Center for Health Promotion and Preventive Medicine (USACHPPM) and took on an expanded role in Public Health. A later reorganization brought in Veterinary services. In 2015, it became the USAPHC. This publication provides a timeline of important accomplishments, mission modifications, administrative changes, challenges and threats in the organization's first 75 years. To help readers put these events in perspective, abbreviated timelines of significant events in military and civilian Preventive, Occupational and Environmental Medicine and Public Health history, legal and regulatory actions related to Public Health and US military history are also included.

Pimasertib is a selective, potent mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor.

The aim of this study was to describe the efficacy, safety, and pharmacodynamics of pimasertib at pharmacologically active doses in a cohort of patients with locally advanced/metastatic melanoma from a first-in-human study of pimasertib.

This was a phase I, open-label, two-part, dose-escalation study. Part 1 was conducted in patients with solid tumors and identified the maximum tolerated dose, while Part 2 was restricted to patients with advanced/metastatic melanoma. Endpoints included safety, pharmacodynamics, and antitumor activity. We present data for patients with melanoma only from both parts of the study.

In total, 93 patients with melanoma received pimasertib, 89 of whom received pharmacologically active doses (28-255 mg/day) across four dose regimens in the two parts of the study. The objective response rate was 12.4% (11/89) complete response (n=1) and partial response (PR; n=10). Six patients responded for > 24 weeks. Nine of the 11 responders had tumors with B-Raf Proto-Oncogene, Serine/Threonine Kinase (BRAF; n=6) and/or NRAS Proto-Oncogene, GTPase (NRAS; n=3) mutations. Forty-six patients had stable disease (SD). In patients with ocular melanoma (n=13), best overall response was PR (n=1), SD (n=11), and disease progression (n=1). Phosphorylated extracellular signal-regulated kinase (pERK) levels were substantially reduced within 2h of treatment and inhibition was sustained with continuous twice-daily dosing. Treatment-related, recurrent, grade 3 or higher adverse events were reported in eight patients, including diarrhea, and skin and ocular events.

Results from this phase I study indicate that pimasertib has clinical activity in patients with locally advanced/metastatic melanoma, particularly BRAF- and NRAS-mutated tumors, at clinically relevant doses associated with pERK inhibition in peripheral blood mononuclear cells.

ClinicalTrials.gov, NCT00982865.

ClinicalTrials.gov, NCT00982865.

Palbociclib is indicated for hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC).

Exposure-response analyses were conducted to evaluate efficacy in Asian versus non-Asian patients and in patients with versus without dose reduction in PALOMA-2.

PALOMA-2 compared palbociclib plus letrozole versus placebo plus letrozole in patients with ABC. Population pharmacokinetic analysis provided apparent palbociclib clearance (CL/F) for each patient. The time-varying exposure metric, C

, was calculated using average dose intensity and CL/F at the time of each progression-free survival (PFS) event. A Cox proportional model characterized PFS and palbociclib C

relationships. Significant prognostic factors for PFS were identified by univariate analysis, which were subsequently included in multivariate analyses, in addition to the C

effect on PFS. PFS profiles in Asian/non-Asian patients and patients with/without dose reduction were simulated and compared using observed palbociclib exposures and established exposure-response relationships.

Patients (n = 421) received palbociclib plus letrozole (Asian = 64, non-Asian = 357; no dose reduction = 272, dose reduction = 149). Based on univariate analyses, significant prognostic factors were Ki67 score, age, and baseline aspartate aminotransferase (BAST), tumor size, alkaline phosphatase, and albumin levels. In multivariate analysis, only Ki67 and BAST remained significant. Palbociclib exposure did not significantly affect PFS in either univariate (P = 0.12) or multivariate (P=0.44) analyses.

This analysis suggests that palbociclib exposure has no impact on PFS when the dose reduction algorithm from palbociclib clinical trials is used. There is no difference in efficacy between Asians and non-Asians, despite the higher level of dose reductions in Asians.

NCT01740427.

NCT01740427.Augmented Reality (AR) applied to surgical guidance is gaining relevance in clinical practice. AR-based image overlay surgery (i.e. the accurate overlay of patient-specific virtual images onto the body surface) helps surgeons to transfer image data produced during the planning of the surgery (e.g. find more the correct resection margins of tissue flaps) to the operating room, thus increasing accuracy and reducing surgery times. We systematically reviewed 76 studies published between 2004 and August 2018 to explore which existing tracking and registration methods and technologies allow healthcare professionals and researchers to develop and implement these systems in-house. Most studies used non-invasive markers to automatically track a patient's position, as well as customised algorithms, tracking libraries or software development kits (SDKs) to compute the registration between patient-specific 3D models and the patient's body surface. Few studies combined the use of holographic headsets, SDKs and user-friendly game engines, and described portable and wearable systems that combine tracking, registration, hands-free navigation and direct visibility of the surgical site.