https://journal.chestnet.org/article/S0012-3692(08)60117-8/pdf

Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

This paper is a review of research in product development, which we define as the transformation of a market opportunity into a product available for sale. Our review is broad, encompassing work in the academic fields of marketing, operations management, and engineering design. The value of this breadth is in conveying the shape of the entire research landscape. We focus on product development projects within a single firm. We also devote our attention to the development of physical goods, although much of the work we describe applies to products of all kinds. We look inside the "black box" of product development at the fundamentaldecisions that are made by intention or default. In doing so, we adopt the perspective of product development as a deliberate business process involving hundreds of decisions, many of which can be usefully supported by knowledge and tools. We contrast this approach to prior reviews of the literature, which tend to examine the importance of environmental and contextual variables, such as market growth rate, the competitive environment, or the level of top-management support.

/pdf/product-development-decisions-a-review-of-the-literature-1jhatri7bn.pdf

Product Development Decisions: A Review of the Literature

Micronutrients are essential to sustain life and for optimal physiological function. Widespread global micronutrient deficiencies (MNDs) exist, with pregnant women and their children under 5 years at the highest risk. Iron, iodine, folate, vitamin A, and zinc deficiencies are the most widespread MNDs, and all these MNDs are common contributors to poor growth, intellectual impairments, perinatal complications, and increased risk of morbidity and mortality. Iron deficiency is the most common MND worldwide and leads to microcytic anemia, decreased capacity for work, as well as impaired immune and endocrine function. Iodine deficiency disorder is also widespread and results in goiter, mental retardation, or reduced cognitive function. Adequate zinc is necessary for optimal immune function, and deficiency is associated with an increased incidence of diarrhea and acute respiratory infections, major causes of death in those <5 years of age. Folic acid taken in early pregnancy can prevent neural tube defects. Folate is essential for DNA synthesis and repair, and deficiency results in macrocytic anemia. Vitamin A deficiency is the leading cause of blindness worldwide and also impairs immune function and cell differentiation. Single MNDs rarely occur alone; often, multiple MNDs coexist. The long-term consequences of MNDs are not only seen at the individual level but also have deleterious impacts on the economic development and human capital at the country level. Perhaps of greatest concern is the cycle of MNDs that persists over generations and the intergenerational consequences of MNDs that we are only beginning to understand. Prevention of MNDs is critical and traditionally has been accomplished through supplementation, fortification, and food-based approaches including diversification. It is widely accepted that intervention in the first 1,000 days is critical to break the cycle of malnutrition; however, a coordinated, sustainable commitment to scaling up nutrition at the global level is still needed. Understanding the epidemiology of MNDs is critical to understand what intervention strategies will work best under different conditions.

/pdf/the-epidemiology-of-global-micronutrient-deficiencies-25uuiypoa9.pdf

The Epidemiology of Global Micronutrient Deficiencies

https://journal.chestnet.org/article/S0012-3692(12)60118-4/pdf

Parenteral Anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

Heparin and Low-Molecular-Weight Heparin: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy

The neutralizing effect of protamine sulfate on enoxaparin-induced bleeding was compared in two rat models: one employing the gastric mucosa, and the other the tail skin, using a 2:1 ratio of protamin

Incomplete Reversal of Enoxaparin-Induced Bleeding by Protamine Sulfate

Day-to-day variations in serum iron, serum iron binding capacity, serum ferritin and erythrocyte protoporphyrin were determined on 2 successive days in 48 patients with anaemia. The correlation coefficients between the paired determinations were 0.86, 0.89, 0.95 and 0.95, and the day-to-day coefficients of variation (in per cent) were 33, 11, 12 and 13 for serum iron, serum iron binding capacity, erythrocyte protoporphyrin and serum ferritin, respectively. Thus, in patients with anaemia, day-to-day variations in serum iron, serum iron binding capacity, erythrocyte protoporphyrin and serum ferritin are at least as high as in healthy controls. The results indicate important limitations in the use, particularly, of serum iron in the clinical investigation of anaemia.

Day-to-day variations in serum iron, serum iron binding capacity, serum ferritin and erythrocyte protoporphyrin concentrations in anaemic subjects.

When exposed to zymosan or latex particles or heat-inactivated staphylococci, freshly prepared human blood monocytes and granulocytes rapidly released a large fraction of their lysozyme content. Within 24 hours the total lysozyme activity in the monocyte suspensions tripled, while it doubled in the granulocyte suspensions, indicating synthesis of the enzyme following release. The monocytes in particular seemed to release and synthesize lysozyme without any other stimulus than contact with lymphocytes and the tube walls. Potassium caseinate in solution did not influence the lysozyme release. Myeloperoxidase and beta-glucuronidase, which in the granulocytes are kept in lysosomal fractions separate from most of the lysozyme, were neither released nor synthesized to a significant degree. Moreover, the minute amount of lactate dehydrogenase released indicated that the lysozyme release was not the result of cell lysis. Accordingly, the monocytes, which are not already stimulated by adherence to nonphagocytosable surfaces, are capable of selective enzyme release similar to that of the granulocytes.

In vitro release of lysozyme from monocytes and granulocytes.

A linear relation between heparin concentrations and the dosage of heparin/kg body weight (r = 0.91, N = 47) was found after bolus injections of 2,500, 5,000, or 10,000 U heparin; the heparin concentrations agreed with plasma distribution. The maintenance therapy showed linearity between heparin concentrations and the dosage of heparin/kg body weight and 24 hours; however, the sensitivity for maintenance therapy differed between patients. The mean dosage required for maintaining heparin at 0.5 U/mL was 400 but ranged between 250 and 600 U heparin/kg body weight and 24 hours. A bolus dose of 75 U heparin/kg body weight, followed by a maintenance dose of 400 U heparin/kg body weight and 24 hours, showed therapeutic heparin response in 78% of patients, however, heparin monitoring two times daily is necessary for adjustment of dosage.

Heparin therapy adjusted for body weight.

A patient with acute lymphocytic leukemia (ALL) who was treated with high-dose cytosine arabinoside (Ara-C) 3 g/m2 twice daily, developed reversible acute aseptic meningitis and signs of cerebellar dysfunction after a total dose of 24 g Ara-C. To our knowledge this is the first case report of meningitis complicating intravenous high-dose Ara-C therapy.

Acute meningitis and cerebellar dysfunction complicating high-dose cytosine arabinoside therapy.

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