Attribute ranging as a coordinated strategy between drug substance and drug product to accelerate commercial process nomination.

To make investigational drug candidates available to patients sooner, timelines for drug development are becoming shorter. Synthesis route scouting for active pharmaceutical ingredients (API) and drug product development often must occur simultaneously, requiring formulators to make decisions regarding drug product process selection before commercial API route finalization. Alternatively, the formulation strategy may be locked, thereby constraining drug substance processes with strict API attribute requirements.

Nineteen-Year-Old Woman with Symptomatic Intramuscular Thigh Hemangioma-Radiographic Changes and Management: A Case Report.

Case: We report a case of an intramuscular thigh hemangioma in a 19-year-old woman with a several year history of atraumatic thigh pain. Radiographs obtained by her primary care physician demonstrated periosteal bone reaction, prompting referral to Orthopaedic Oncology department. The patient had successful symptomatic management with propranolol.

Improving the routine analysis of siderite for δ C and δ O in environmental change research.

Rationale: The carbon (δ C) and oxygen (δ O) isotope composition of siderite (FeCO ) is used widely to understand and quantify geochemical processes to reconstruct past climate and environmental change. However, few laboratories follow precisely the same protocol for the preparation and analysis of siderite-bearing materials, which combined with the absence of international reference materials and mineral-specific acid fractionation factors, leads potentially to significant differences in isotope data generated by individual laboratories. Here we examine procedures for the isotope analysis of siderite and discuss factors potentially contributing to inconsistencies in sample measurement data.

Rehabilitation Variability Following Osteochondral Autograft and Allograft Transplantation of the Knee.

Objective: The aim of this study is to assess the variability of postoperative rehabilitation protocols used by orthopedic surgery residency programs for osteochondral autograft transplantation (OAT) and osteochondral allograft transplantation (OCA) of the knee.

Design: Online postoperative OAT and OCA rehabilitation protocols from US orthopedic programs and the scientific literature were reviewed. A custom scoring rubric was developed to analyze each protocol for the presence of discrete rehabilitation modalities and the timing of each intervention.

Rehabilitation Variability Following Femoral Condyle and Patellofemoral Microfracture Surgery of the Knee.

Objective: To assess the variability of postoperative rehabilitation protocols used by orthopedic surgery residency programs for microfracture of femoral condyle and patellofemoral lesions of the knee.

Design: Online postoperative microfracture rehabilitation protocols from US orthopedic programs and the scientific literature were reviewed. A custom scoring rubric was developed to analyze each protocol for the presence of discrete rehabilitation modalities and the timing of each intervention.

Improving philosophical dialogue interventions to better resolve problematic value pluralism in collaborative environmental science.

Environmental problems often outstrip the abilities of any single scientist to understand, much less address them. As a result, collaborations within, across, and beyond the environmental sciences are an increasingly important part of the environmental science landscape. Here, we explore an insufficiently recognized and particularly challenging barrier to collaborative environmental science: value pluralism, the presence of non-trivial differences in the values that collaborators bring to bear on project decisions.

Eponyms in Pediatric Sports Medicine: A Historical Review.

The use of eponyms in the orthopedics literature has come under scrutiny, and there is a growing body of literature evaluating the utility of these terms in modern healthcare delivery. Although the field of pediatric orthopedic sports medicine is a relatively modern subspecialty, it is built on a foundation of over 100 years of pediatric musculoskeletal medicine. As a result, eponyms account for a significant portion of the vernacular used in the field.

Computer Navigation for Pediatric Femoral ACL Tunnel Placement.

Background: To compare accuracy, time and radiation exposure of pediatric femoral tunnel placement using computer navigation with a traditional freehand technique.

Methods: A single all-epiphyseal femoral tunnel was placed in the distal femur of 20 Sawbones™ adolescent knee models. Ten tunnels were drilled using standard fluoroscopic guidance (FG).

Mechanistic Insights into Catalytic Ethanol Steam Reforming Using Isotope-Labeled Reactants.

The low-temperature ethanol steam reforming (ESR) reaction mechanism over a supported Rh/Pt catalyst has been investigated using isotope-labeled EtOH and H2 O. Through strategic isotope labeling, all nonhydrogen atoms were distinct from one another, and allowed an unprecedented level of understanding of the dominant reaction pathways. All combinations of isotope- and non-isotope-labeled atoms were detected in the products, thus there are multiple pathways involved in H2 , CO, CO2 , CH4 , C2 H4 , and C2 H6 product formation.

On the nature of cross-disciplinary integration: A philosophical framework.

Meeting grand challenges requires responses that constructively combine multiple forms of expertise, both academic and non-academic; that is, it requires cross-disciplinary integration. But just what is cross-disciplinary integration? In this paper, we supply a preliminary answer by reviewing prominent accounts of cross-disciplinary integration from two literatures that are rarely brought together: cross-disciplinarity and philosophy of biology. Reflecting on similarities and differences in these accounts, we develop a framework that integrates their insights-integration as a generic combination process the details of which are determined by the specific contexts in which particular integrations occur.

Staphylococcus aureus sepsis induces early renal mitochondrial DNA repair and mitochondrial biogenesis in mice.

Acute kidney injury (AKI) contributes to the high morbidity and mortality of multi-system organ failure in sepsis. However, recovery of renal function after sepsis-induced AKI suggests active repair of energy-producing pathways. Here, we tested the hypothesis in mice that Staphyloccocus aureus sepsis damages mitochondrial DNA (mtDNA) in the kidney and activates mtDNA repair and mitochondrial biogenesis.

How to talk to strangers: facilitating knowledge sharing within translational health teams with the Toolbox dialogue method.

Translational behavioral medicine involves experts from different disciplines and professions interacting to solve complex problems. Coordinating this expertise can be frustrated by the partially tacit nature of expertise and by the various ways in which it manifests in different communities. We describe a method-the Toolbox dialogue method-for addressing these challenges by means of a structured dialogue among team members concerning their respective approaches to complex problems.

Fish as major carbonate mud producers and missing components of the tropical carbonate factory.

Carbonate mud is a major constituent of recent marine carbonate sediments and of ancient limestones, which contain unique records of changes in ocean chemistry and climate shifts in the geological past. However, the origin of carbonate mud is controversial and often problematic to resolve. Here we show that tropical marine fish produce and excrete various forms of precipitated (nonskeletal) calcium carbonate from their guts ("low" and "high" Mg-calcite and aragonite), but that very fine-grained (mostly < 2 μm) high Mg-calcite crystallites (i.

Oxygen isotope analysis of carbonates in the calcite-dolomite-magnesite solid-solution by high-temperature pyrolysis: initial results.

Accurate and efficient measurement of the oxygen isotope composition of carbonates (delta(C) (18)O) based on the mass spectrometric analysis of CO(2) produced by reacting carbonate samples with H(3)PO(4) is compromised by: (1) uncertainties associated with fractionation factors (alpha(CO)(2)C) used to correct measured oxygen isotope values of CO(2)(delta(CO(2)(18)O) to delta(C) (18)O; and (2) the slow reaction rates of many carbonates of geological and environmental interest with H(3)PO(4). In contrast, determination of delta(C) (18)O from analysis of CO produced by high-temperature (>1400 degrees C) pyrolytic reduction, using an elemental analyser coupled to continuous-flow isotope-ratio mass spectrometry (TC/EA CF-IRMS), offers a potentially efficient alternative that measures the isotopic composition of total carbonate oxygen and should, therefore, theoretically be free of fractionation effects. The utility of the TC/EA CF-IRMS technique was tested by analysis of carbonates in the calcite-dolomite-magnesite solid-solution and comparing the results with delta(C) (18)O measured by conventional thermal decomposition/fluorination (TDF) on the same materials.