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Basal-bolus insulin (Multiple Daily Injections [MDI]) – General Description
This regimen refers to treatment with three or more injections per day using a basal insulin and prandial or bolus insulin. NPH, glargine or detemir insulin are generally used as basal insulin and may be administered as once or twice daily injections. The options for prandial insulin include regular insulin and rapid-acting insulin analogs such as lispro, aspart or glulisine. Regular insulin has a longer duration of action, slower onset and higher likelihood of hypoglycemia. Regular insulin should be given 30 minutes prior to eating. It peaks at 2 to 4 hours and can last 5 to 8 hours. The rapid-acting insulin analogs, such as lispro, aspart and glulisine, should be given 5 to 15 minutes prior to eating and adjusted based on pre-meal blood glucose levels, the carbohydrate content of the meal and anticipated activity. These shorter-acting insulins peak at 45 to 75 minutes and last 2 to 4 hours.
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All patients with type 1 diabetes should be started on basal-bolus insulin therapy as early as possible. Intensive therapy may slow the progression of beta cell dysfunction in type 1 diabetes. Patients with Type 2 diabetes, who are unable to achieve hemoglobin A1c, fasting/preprandial and 2-hour postprandial glycemic goals using oral agents plus or minus basal insulin are also good candidates.
This is the ideal regimen in terms of physiological action, flexibility and glycemic control. A basal-bolus regimen can be used to achieve glycemic control in patients with elevated fasting and/or postprandial glucose excursions, matched to any type of diet and any type of lifestyle.
Patients need to be motivated, able and willing to use 4-5 injections daily and perform frequent blood glucose monitoring at least four times per day prior to meals and at bedtime. Comprehensive training in matching insulin to food intake (carbohydrate counting) and insulin adjustment for elevated or low sugars is required. The incidence of hypoglycemia and weight gain is higher with MDI.
Initiation of the basal-bolus regimen in type 2 diabetes
Basal insulin
Several options exist for basal insulin:
NPH insulin is an intermediate-acting insulin with onset at about 2 hours, peak between 4-12 hours, and has a duration of action up to 24 hours, but closer to 12 to 16 hours.
Glargine or detemir insulin are longer-acting basal insulins, with onset of action at around 2 hours and duration of action of 6-24 hours for detemir and 24 hours or longer for glargine. Glargine is reported to be peakless. Detemir may have a slight peak at 3-9 hours.
Degludec insulin is ultra long acting basal insulin with a half-life of over 24 hours and a duration of effect of greater than 42 hours. There is a decrease in glycemic variability compared to glargine.
A common starting dose of basal insulin is 0.2 units/kg body weight, but most patients with Type 2 diabetes are insulin resistant and may require closer to 0.4 to 0.8 units/kg body weight. Bedtime intermediate-acting insulin (NPH insulin) or bedtime or morning long-acting insulin (glargine or detemir) can be initiated at a dose of 0.2 units/kg body weight or 10 units. Basal insulin should be titrated based on fasting blood glucose (FBG) readings.
The Treat-to-Target study in 2003 looked at adding bedtime NPH or glargine insulin to one or two oral agents. This study used an algorithm with an initial basal insulin dose of 10 units at bedtime and adjusted the dose weekly based on the mean FBG values from the preceding 2 days. The target FBG was less than or equal to 100 mg/dL. The dose increase for basal insulin was 8 units if FBG was above 180 mg/dL, 6 units if FBG was 140-180 mg/dL, 4 units if FBG was 120-140 mg/dL, and 2 units if FBG was 100-120 mg/dL. Most patients achieved A1c below 7% with greater hypoglycemia in the NPH group.
A 2005 study by the AT.LANTUS group evaluated a physician-led versus a patient-directed algorithm for titration of glargine insulin until fasting sugar was at a target of between 72-100 mg/dL. The physician-led group had titration of glargine every week versus every 3 days in the patient-directed group. The adjustment in daily basal insulin glargine dose was based on the mean FBG for the previous 3 days. In the physician-led group, the increase in glargine was 0-2 units for FBG between 100-119 mg/dL, 2 units for FBG 120-139 mg/dL, 4 units for FBG 140-179 mg/dL, and 6-8 units for FBG 180 mg/dL or above. In the patient-directed group, the increase in glargine was 0-2 units for FBG between 100-120 mg/dL and 2 units for every level after that. No significant differences in metabolic control or hypoglycemia were found, illustrating that patient-directed titration of basal insulin is safe and efficacious.
The PREDICTIVE 303 study used a simple self-titration algorithm for insulin detemir. The dose was to be reduced by 3 units if FBG was below 80 mg/dL, no change was made if FBG was 80-110 mg/dL, and the dose was increased by 3 units if FBG was above 110 mg/dL. Self-titration every 3 days was compared with standard of care and found to be safe and efficacious as well, with minimal hypoglycemia and no weight gain.
A nice primary care review by Hirsch et al. in 2005 recommends that basal insulin be titrated to keep FBG between 80-109 mg/dL. The dosage of basal insulin should be lowered by 2 units if FBG is below 80 mg/dL, increased by 2 units if FBG is 110-139 mg/dL, increased by 4 units if FBG is 140-179 mg/dL, and increased by 6 units if FBG is greater than 180 mg/dL.
Mooradian et al. describe a protocol for titration of basal insulin in a 2006 paper, recommending a goal FBG of 80-99 mg/dL. Their recommended adjustment of the basal insulin dose is: addition of 8 units for FBG above 180 mg/dL, addition of 6 units for FBG 160-180 mg/dL, addition of 4 units for FBG 140-159 mg/dL, addition of 2 units for FBG 120-139 mg/dL, addition of 1 unit for FBG 100-119 mg/dL, no change for FBG 80-99 mg/dL, subtraction of 2 units for FBG 60-79 mg/dL, and subtraction of 4 units for FBG below 60 mg/dL. The BEGIN trial used a similar, but slightly different titration algorithim
According to the American Diabetes Association / European Association for the Study of Diabetes (ADA/EASD) 2009 algorithm for initiation and adjustment of therapy, basal insulin should be increased by 2 units every 3 days until FBG is consistently in the target range of 70-130 mg/dL (3.9 to 7.2 mmol/L). If FBG is greater than 180 mg/dL (10 mmol/L), basal insulin may be titrated up by 4 units every 3 days.
Prandial insulin
Prandial insulin should be added in patients on basal insulin plus or minus oral agents with a hemoglobin A1c that is above 7% and fasting glucose levels that are at goal at 70-130 mg/dL. A "Basal Plus" regimen and a "Basal-Bolus" regimen have been described. "Basal Plus" refers to the addition of a single pre-prandial dose of insulin while continuing the basal insulin. "Basal-Bolus" refers to the addition of pre-prandial insulin to every meal.
Several methods exist for the initiation and titration of prandial insulin and have been summarized by Ampudia et al. (reference given at end of chapter under "What's the Evidence?").
One option based on the ADA/EASD 2009 algorithm is to use a fixed dose of a rapid-acting analog starting at 4 units before one or more meals depending on postprandial blood glucose levels (PPBG).
A second option is to use a weight-based dose of 0.05 units/kg body weight as the initial dose before a meal.
A third option is to use 10% of the basal insulin dose per meal. A fourth option is described by Owens et al., who recommend first determining the 3-day average of the 2-hour PPBG after each meal and then initiating prandial insulin only before the meal with the highest PPBG excursion. The initial dose is calculated using the PPBG of this main meal in mmol/L divided by 2 (1 mmol/L = 18 mg/dL). Additional prandial injections can be initiated if 2-hour PPBGs are not at goal.
A final option is to initiate prandial insulin based on carbohydrate content of the meal, the pre-meal blood sugar, and anticipated activity. This is a detailed method that is used in patients with type 1 diabetes, who are using an insulin pump or multiple daily injections. See below section on prandial insulin in type 1 diabetes, carbohydrate counting and insulin sensitivity factor (ISF).
Several algorithms have been studied for adjustment of prandial insulin dosage. The ADA/EASD recommend adjusting the prandial insulin by 2 units every three days until the pre-meal blood sugar is in the target range. The regimen by Owens et al. recommends that prandial insulin be increased by 2 units, if the 2-hour PPBG is above 10 mmol/L (180 mg/dL) after breakfast and dinner or above 7.8 mmol/L (140 mg/dL) after lunch.
More complicated titration regimens have also been described. Mooradian et al.'s algorithm is based on preprandial or bedtime glucose levels. Their regimen recommends addition of 3 units for glucose above 180 mg/dL, addition of 2 units for glucose 160-180 mg/dL, addition of 2 units for glucose 140-159 mg/dL, addition of 1 unit for glucose 120 to 139 mg/dL, no change for glucose 100-119 mg/dL, subtraction of 1 unit for glucose 80-99 mg/dL, subtraction of 2 units for glucose 60-79 mg/dL, and subtraction of 4 units for FBG below 60 mg/dL.
Other regimens involve increasing prandial insulin by 1 unit if PPBG level is above a target of 140 mg/dL, adjusting dose based on PPBG using a scale (1 unit is added if PPBG is 136 to 153 mg/dL, 2 units are added if PPBG is 154 to 180 mg/dL, and 3 units are added if PPBG is above 180 mg/dL), or adjustment based on previous prandial insulin dose if PPBG is above target (i.e., adding 1 unit if dose was below 10 units, 2 units if dose was 10 to 20 units, and 3 units if dose was above 20 units).
Initiation of the basal-bolus regimen in type 1 diabetes
The total daily insulin dose (TDD) is usually started at 0.1 to 0.2 units/kg body weight, but most patients will usually need 0.6 to 0.7 units/kg body weight per day. The accurate insulin management system (AIM) uses a calculation of 0.24 multiplied by body weight in pounds to obtain the TDD.
Basal insulin:
See above section on basal-bolus regimen in type 2 diabetes for information regarding NPH, glargine, and detemir insulins.
Half of the TDD should be given as basal insulin. If NPH insulin is used, because it is an intermediate-acting insulin that lasts on average 12 to 16 hours, it can be divided up as 2/3 of the TDD in the morning before breakfast and 1/3 of the TDD at bedtime. If glargine or detemir insulin are chosen, they are longer-acting insulins and can be administered once daily. However, if blood sugar elevations 24 hours after the dose are suspected to be due to inadequate duration of action, the glargine or detemir dose may be divided into 2 doses and administered in the morning and at bedtime.
Titration of basal insulin is based on the fasting morning glucose. According to the ADA/EASD 2009 algorithm for initiation and adjustment of therapy, basal insulin should be increased by 2 units every 3 days until fasting glucose is consistently in the target range of 70 to 130mg/dL (3.9 to 7.2 mmol/L). If fasting glucose is greater than 180 mg/dL (10 mmol/L), basal insulin may be titrated up by 4 units every 3 days. Other titration algorithms exist, as discussed in the above section on basal-bolus regimens in type 2 diabetes.
Prandial insulin:
Pre-meal dosing should be calculated based on the carbohydrate content of the meal, pre-meal blood sugar, and anticipated activity. Various algorithms exist. Regular insulin should be given 30 minutes prior to eating. It peaks at 2 to 4 hours and can last 5 to 8 hours. Rapid-acting analogs such as lispro, aspart and glulisine should be given 5 to 15 minutes prior to eating. These shorter-acting insulins peak at 45 to 75 minutes and last 2 to 4 hours.
Several methods have been described regarding the initiation and titration of prandial insulin. The methods described below in the initiation of the basal-bolus regimen in type 2 diabetes, Prandial Insulin section, can also be used in type 1 diabetes, but the preferred method is using bolus calculation techniques that are generally used in insulin pump patients. These techniques involve carbohydrate counting, insulin-to-carbohydrate ratios, and insulin sensitivity factors.
1. Using carbohydrate counting and insulin-to-carbohydrate ratios:
With this method, patients will count the amount of carbohydrates they eat at each meal in grams and administer a calculated amount of insulin based on the grams of carbohydrates and their insulin-to-carbohydrate ratio (I:C). The two methods used for carbohydrate counting are reading food labels to obtain the grams of total carbohydrates per serving or using an exchange system. In the exchange system, foods are categorized into 3 groups: carbohydrates, meats, and fat. Foods in the carbohydrate group contain 12-15 gm of carbohydrates per serving. Patients who will be using this method should work with a registered dietician to learn this.
Several methods can be used to calculate the I:C ratio:
a) If blood sugars are at goal, the carbohydrate ratio can be determined by dividing the grams of carbohydrates eaten at the meal by the number of units of rapid-acting insulin administered. For example, if 50 gm of carbohydrates are eaten at a meal and 5 units is given for this meal, 50/5 = 10, resulting in an I:C of 1:10 or 1 unit of insulin given per 10 gm of carbohydrates.
b) The 450/500 rule can be used. The total daily dose of insulin (TDD) is divided by 500 or 450 to obtain the I:C. 500 is used for insulin-sensitive individuals, who comprise most patients with type 1 diabetes. 450 is used for insulin-resistant individuals, namely, patients with type 2 diabetes. For example, if the TDD = 60 units, in someone with type 1 diabetes, 60/500 is 0.12, so 1 unit of insulin should be administered for each 12 gm of carbohydrates.
c) The insulin sensitivity factor (ISF), described below, can be multiplied by 0.33 to obtain the I:C.
d) The ratio can be calculated using the 2.8 rule of the accurate insulin management system (AIM): 2.8 multiplied by body weight in pounds/TDD.
2. Insulin sensitivity factor (ISF):
Patients with Type 1 diabetes should use carbohydrate counting and I:C ratios to determine the amount of insulin to be given for each particular meal. The ISF is used to adjust the insulin dose for pre-meal sugars that are above goal. The calculation is 1500 to 1800 divided by the TDD. 1500 can be used for the calculation in patients with type 2 diabetes, who are more insulin-resistant, and 1800 can be used for the more insulin-sensitive type 1 diabetics.
The AIM system uses 1700 as the numerator for type 1 diabetes. For example, if the TDD is 50, and 1500 is used to calculate the ISF, the ISF is 1 unit of insulin for every 30mg/dL above goal.
U-500 Insulin for Severe Insulin Resistance
U-500 regular insulin (500 units/mL) is a highly concentrated form of U-100 regular insulin (100 units/mL). It has a delayed peak of action and longer duration compared with U-100 regular insulin. Its pharmacokinetic profile is similar to NPH insulin. It can be administered as multiple daily injections or via continuous subcutaneous insulin infusion. U-500 insulin can be used as basal and bolus insulin or can be used as bolus insulin added to an existing basal insulin regimen.
A vial of U-500 insulin contains 20 mL and 10,000 units of insulin compared with a vial of U-100 insulin, which contains 10 mL and 1,000 units of insulin. U-500 insulin is not available in an insulin pen form.
Candidates for U-500 insulin
Patients with diabetes and severe insulin resistance are candidates for U-500 insulin. Severe insulin resistance is defined as requiring greater than 200 units of insulin per day or a dose of 2 units/kg body weight per day. Specific conditions with severe insulin resistance in which U-500 could be considered for use include rare type A and B insulin resistance syndromes, acquired or congenital lipodystrophic diabetes, high-dose glucocorticoid use, post-transplant or post-surgical status, and severe systemic infections according to Lane et al. (cited in reference section at end of chapter).
Documentation of U-500 insulin and writing prescriptions
U-500 insulin should be prescribed by documenting the total number of units to be given and dose to be administered, written as volume to be injected and as insulin dose in U-100 syringe units. Errors occur when the prescription is written only in syringe units to be administered. The volume to be administered in a tuberculin syringe is calculated by dividing the insulin dose to be administered by 500. The amount of U-500 insulin to be administered in a U-100 syringe can be calculated by dividing the insulin dose by 5. For example, if a patient is to receive 100 units of U-500 insulin, the dose is drawn up in a U-100 syringe to the 20 unit mark or 0.20 mL drawn up in a tuberculin syringe. The prescription should designate 0.3 to 0.5 mL U-100 syringes to avoid inadvertent overdosage.
Algorithms for U-500 Insulin
When converting the U-100 dose to U-500 insulin, the new dose should be reduced by 10% to 20% if the hemoglobin A1c is below 8%, and increased by 10%-20% if the hemoglobin A1c is above 10%. If the hemoglobin A1c is between 8%-10%, a direct conversion can be made.
U-500 insulin should be injected 30 minutes prior to meals because its onset of action is similar to U-100 regular insulin.
Algorithms have been described by Lane et al. based on total units of insulin to be injected per day:
A. Total daily dose of 150 to 300 units:
U-500 can be divided into two to three pre-meal doses if used without basal insulin. If U-500 is given twice daily, 60% should be administered before the breakfast meal and 40% before the evening meal. If U-500 is given three times daily, 40%-45% should be given before breakfast, 30%-40% before lunch, and 20%-30% before the dinner meal. U-500 can also be used as the bolus component of a basal-bolus regimen. It would be added to an existing regimen that included glargine, detemir or NPH insulin. The proportion of basal and bolus insulin would be unchanged from the U-100 regimen.
B. Total daily dose of 300 to 600 units:
U-500 insulin should be divided and given three to four times per day. If administered as three times daily, the dosages should be as above in the 150 to 300 unit per day regimen. If fasting sugars are elevated, a fourth injection may be added at bedtime. In this case, 30% of the U-500 dose should be given at each meal with no greater than 10% of the dose added at bedtime. If bedtime U-500 insulin is given, 2 to 3 AM blood sugars should be checked to evaluate for nocturnal hypoglycemia. If basal insulin in the form of glargine, detemir, or NPH is used with U-500 insulin given as bolus therapy, continuous subcutaneous insulin therapy should be considered.
C. Total daily dose greater than 600 units:
Four daily injections are recommended, dividing the dose as 25% per dose given at meals and at bedtime or 30% prior to meals and 10% at bedtime.
Use of Glucagon-Like Peptide-1 Mimetics or Pramlintide with Insulin
Glucagon-like peptide-1 mimetics
Glucagon-like peptide (GLP)-1 mimetics are gastrointestinal hormones that target postprandial glucose and are an option for use with basal insulin instead of prandial insulin. GLP-1 mimetics lower postprandial glucose excursions by stimulating glucose-dependent insulin secretion, slowing gastric emptying, suppressing post-meal glucagon secretion, and increasing satiety.
The GLP-1 mimetics include liraglutide administered once daily independent of meals, exenatide given twice daily 30 minutes before meals, and extended-release exenatide, albiglutide, and dulaglutide given once weekly. GLP-1 mimetics are approved for use as add-on therapy in type 2 diabetics who have not achieved optimal glycemic control on one or two oral hypoglycemic agents. It can be considered as monotherapy in patients with contraindications or who experience adverse effects with the oral agents.
In October 2011, exenatide given twice daily before meals was approved by the Federal Drug Administration (FDA) as add-on therapy to glargine insulin. Liraglutide was approved for use with both glargine and detemir insulin in April of 2012. The extended-release once weekly exenatide has not yet been approved by the FDA for use with insulin. The package insert states that Albiglutide has not been studied for use with prandial insulin. Dulaglutide has been studied with prandial insulin, but not basal insulin.
Benefits of GLP-1 mimetics:
GLP-1 mimetics significantly improve postprandial glucose levels, lower hemoglobin A1c by up to 0.9%, have a low incidence of hypoglycemia, and can result in significant weight loss over time (about 2 kg). Further study needs to be done to determine the advantages of adding a GLP-1 mimetic to basal insulin versus using a standard basal-bolus regimen or twice daily premixed insulin.
Drawbacks of GLP-1 mimetics:
Nausea is a common side effect, but wanes over time. Most patients can tolerate the nausea through slow dose titration. Post-marketing reports of pancreatitis and acute renal failure or renal insufficiency are also a concern. Thyroid C-cell tumors (medullary thyroid cancer) have been described in mice and rat studies with liraglutide, but human studies did not find any difference in calcitonin levels between patients taking liraglutide versus other diabetes medications. All of the longer acting GLP-1 agents share a similar warning for thyroid C-cell tumors. Concerns were also brought up findings of pre-cancerous lesions in the pancreas in patients taking these drugs. However, both the European Medicines Agency and the Food and Drug Administration (FDA) stated in 2015 that the available data do not confirm the concerns related to pancreatic cancer. The FDA will continue to review cases of pancreatitis and pancreatic cancer in ongoing studies. These medications tend to be costly since a generic version does not yet exist.
Candidates for GLP-1 agonists and basal insulin:
Most studies on this area have focused on use in obese patients with poor glycemic control. The ADA / EASD algorithm recommends consideration in patients failing lifestyle changes and metformin, although the preferred second-line therapy is a sulfonylurea or basal insulin alone. This regimen would best fit patients with fasting sugars controlled by basal insulin but poor postprandial glucose control, high risk of hypoglycemia, and obesity with high risk of further weight gain.
Exenatide can be started at 5 mcg twice daily injected 30 minutes before a meal. This dose should be continued for 1 month to improve gastrointestinal tolerability and then increased to 10 mcg twice daily. The dose of glargine may need to be reduced in the first 6 to 12 months of therapy and can be adjusted based on fasting sugars. Liraglutide is initiated at 0.6 mg once daily injection for one week. This dose does not provide effective glycemic control, but reduces the risk of gastrointestinal symptoms during dose titration.
After one week, the dose can be increased to 1.2 mg. A further increase in dose to 1.8 mg can be made if further glucose control is needed. Basal insulin dose may need to be reduced as with exenatide. Extended-release exenatide is given as a 2 mg subcutaneous injection once a week at any time of day with or without meals. Albiglutide is given at the same time of day once weekly with or without meals at a dose of 30 mg. If the glycemic response is felt to be inadequate, the dose can be increased to 50 mg once a week. Dulaglutide can be given once a week at any time of the day with a starting dose of 0.75 mg once a week. If this dose is not sufficient for glycemic control, the dose can be increased to 1.5 mg once a week.
Pramlintide is an injectable synthetic analog of human amylin. Amylin is a naturally occurring hormone cosecreted with insulin by the pancreatic beta cells. In type 1 and type 2 diabetes, beta cell dysfunction results not only in absolute and relative insulin deficiency respectively, but also decreased endogenous amylin secretion. Like the GLP-1 mimetics, amylin is most effective in lowering postprandial glucose levels. PPBGs are lowered through suppression of post-meal glucagon secretion, slowing gastric emptying, increasing satiety, and decreasing appetite.
Pramlintide is approved for use for adjunct treatment in type 1 and type 2 diabetics who are on basal insulin and prandial insulin. It may be used concomitantly with metformin and/or sulfonylureas.
Riddle et al. evaluated use of pramlintide in type 2 diabetic patients who take basal insulin only and found that pramlintide lowered A1c by 0.7% with 1.6-kg weight loss. However, the use of pramlintide in this manner is off-label. Huffman et al. also studied pramlintide off-label as a subcutaneous continuous infusion.
Benefits of pramlintide:
Pramlintide can reduce postprandial glucose between 43 to 90 mg/dL, hemoglobin A1c by 0.2 to 0.4% in type 1 diabetics and 0.4 to 0.6% in type 2 diabetics, total daily insulin dose, and weight by 0.5 to 1 kg.
Drawbacks of pramlintide:
The major drawbacks of pramlintide are its subcutaneous route of administration three times daily, nausea, and hypoglycemia if the meal-time insulin dose is not reduced. The degree of hemoglobin A1c lowering is also modest, as mentioned above.
Patients taking pramlintide along with their basal and prandial insulin will be injecting seven to eight times daily unless they are using the pramlintide with an insulin pump, in which case they will be injecting three times daily. Therefore, candidates must have the motivation, training, and ability to intensively manage their diabetes.
Pramlintide is not a good choice for patients with gastroparesis because it can cause nausea and will further slow gastric emptying. It is also not ideal for patients receiving medications that stimulate gastrointestinal motility, such as metoclopramide. The associated nausea should resolve over a period of a month and can be minimized by starting pramlintide only once daily with the largest meal and titrating up slowly over several weeks.
Pramlintide is available as the brand name SymlinPen 60 and 120. The SymlinPen 60 has fixed dosing to deliver 15, 30, 45, or 60 mcg per dose, while the SymlinPen 120 has fixed dosing to deliver 60 or 120 mcg per dose. Both pens should be kept refrigerated until they are opened. Once open, the pens can be kept at room temperature or in the refrigerator for up to 30 days. Both the 60 and 120 mcg pens contain pramlintide concentration of 1000 mcg/mL. The 60 mcg pen has 1.5 mL, while the 120 mcg pen has 2.7 mL.
When pramlintide is started, the meal-time insulin dose should be reduced by 50% to minimize the risk of hypoglycemia. Pramlintide is given with any meal that is over 250 kcal or 30 gms of carbohydrates. Pramlintide should be injected into the thigh or abdomen and a minimum of 2 inches away from the prandial insulin injection site.
Pramlintide is initiated at 15 mcg in type 1 diabetes and titrated up to 30 mcg or 60 mcg with meals as tolerated. In type 2 diabetes, pramlintide is initiated at 60 mcg and titrated up based on tolerability to 120 mcg before each meal. Pramlintide should be given initially once daily with the first bite of the largest meal of the day. The dose or dose frequency should be increased every 3 or more days as tolerated. The meal-time insulin can be given at the same time as pramlintide or can also be given after the meal if the amount of food intake may be less than anticipated due to increased satiety or nausea.
Inhaled Insulin
Using inhalation as a route of insulin delivery has been studied as far back as 1924. The FDA approved an inhaled insulin product named Exubera in 2006, but this was taken off the market in 2007 by the manufacturer after poor acceptance by patients and health care providers and concerns regarding lung cancer seen in previous smokers. Development of another inhaled insulin with the brand name Afrezza continued with approval in June 2014 and is currently available for use.
Afrezza is an inhaled insulin using Technosphere technology. This technology involves adsorption of peptides or proteins onto microparticles made of the excipient fumaryl diketopiperazine (FDKP). FDKP forms microspheres, drugs are microencapsulated within these microspheres, which are then freeze dried to form a powder suitable for inhalation.
Afrezza is a rapid-acting inhaled insulin indicated to improve glycemic control in adult patients with diabetes mellitus. It is not a substitute for long-acting basal insulin and it is not recommended for treatment of diabetic ketoacidosis. Afrezza is to be used with meals and must be used in combination with long-acting insulin in type 1 diabetics.
It is administered via oral inhalation with the Afrezza Inhaler using a single inhalation per cartridge. Single-use cartridges are available in a 4 unit dose, an 8 unit dose, and a 12 unit dose. Inhalations from multiple cartridges are necessary for doses exceeding 12 units.
Dose conversion of injected mealtime insulin to Afrezza is shown in Table I.
Table I.
|Injected Mealtime Insulin Dose
|Afrezza Dose
|Up to 4 units
|4 units
|4-8 units
|8 units
|9-12 units
|12 units
|13-16 units
|16 units
|17-20 units
|20 units
|21-24 units
|24 units
It has rapid absorption, achieving a maximum concentration in approximately 15 minutes with relative bioavailability of about 37% of subcutaneously administered regular human insulin. It has a faster elimination profile than subcutaneous regular insulin as well.
There is a 'Boxed Warning' advising that acute bronchospasm has been observed in patients with asthma and COPD. It should not be used in patients with asthma or COPD. It should also not be used in patients who smoke or who recently stopped smoking.
Lung function must be evaluated with a medical history, physical exam, and spirometry (FEV1) prior to initiating Afrezza. Spirometry should be assessed again after the first 6 months of therapy and annually thereafter even in the absence of pulmonary symptoms. In patients with decline in FEV1 of greater than or equal to 20% from baseline, discontinuation of Afrezza should be considered.
FEV1 has been found to decline 40ml within the first 3 months and persist for at least 2 years (the duration of the clinical trials examining this). There is not sufficient data regarding reversibility of this after discontinuation of the drug.
In clinical trials, 2 cases of lung cancer were observed in the participants exposed to Afrezza compared to no cases in the comparators. Both cases had prior heavy tobacco use. Two additional cases of lung cancer were reported after clinical trial completion. There is insufficient data to link Afrezza to lung cancer.
The most common adverse reactions in clinical trials were hypoglycemia, cough, and throat pain or irritation.
Afrezza has not been studied in pregnant women or patients younger than age 18 years of age. The effect of hepatic or renal impairment on the pharmacokinetics of Afrezza has also not been studied.
What's the Evidence?/References
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Hirsch, IB, Bergenstal, RM, Parkin, CG. "A real-world approach to insulin therapy in primary care practice". Clinical Diabetes. vol. 23. 2005. pp. 78-86.
Mooradian, AD, Bernbaum, M, Albert, SG. "Narrative review: a rational approach to starting insulin therapy". Ann Intern Med. vol. 145. 2006. pp. 125-34.
Nathan, DM, Buse, JB, Davidson, MB. "Medical management of hyperglycemia in type 2 diabetes: consensus algorithm for the initiation and adjustment of therapy. A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes". Diabetes Care. vol. 32. 2009. pp. 193-203.
Ampudia-Biasco, FJ, Rossetti, P, Ascasco, JF. " Basal plus basal-bolus approach in type 2 diabetes". Diabetes Technol Ther. vol. 13. 2011. pp. S75-S83.
Owens, DR, Luzio, SD, Sert-Langeron, C, Riddle, MC. " Effects of initiation and titration of a single pre-prandial dose of insulin glulisine while continuing titrated insulin glargine in type 2 diabetes: a 6-month 'proof-of-concept' study". Diabetes Obes Metab. vol. 13. 2011. pp. 1020-7.
Owens, DR, van Schalkwyk, C, Smith, P. "Algorithm for the introduction of rapid-acting insulin analogues in patients with type 2 diabetes on basal insulin therapy". Practical Diabetes Int. vol. 26. 2009. pp. 70-7.
Jonassen, I, Havelund, S, Hoeg-Jensen, T, Steensgaard, DB, Wahlund, PO, Ribel, U. "Design of the novel protraction mechanism of insulin degludec, ultra-long-acting basal insulin". Pharm Res.. vol. 29. 2012. pp. 2104-14.
Kalra, S., Gupta, Y. "Clinical use of Insulin Degludec: Practical Experience and Pragmatic Suggestions". N Am J Med Sci. vol. 7. 2015 Mar. pp. 81-85.
Walsh, J, Roberts, R. "Pumping Insulin: Everything You Need for Success With An Insulin Pump". 2000.
Bolderman, K. "Putting Your Patients on the Pump". 2002.
Davidson, PC, Hebblewhite, HR, Steed, RD, Bode, BW. " Analysis of guidelines for basal-bolus insulin dosing: basal insulin, correction factor, and carbohydrate-to-insulin ratio". Endocr Pract. vol. 14. 2008. pp. 1095-101.
Dailey, AM, Tannock, LR. " Extreme insulin resistance: indications and approaches to the use of U-500 insulin in type 2 diabetes mellitus". Curr Diab Rep. vol. 11. 2011. pp. 77-82.
Lane, WS, Cochran, EK, Jackson, JA. "High dose insulin therapy: is it time for U-500 insulin?". Endocr Pract. vol. 15. 2009. pp. 71-9.
Perfetti, R. " Combining basal insulin analogs with glucagon-like peptide-1 mimetics". Diabetes Technol Ther. vol. 13. 2011. pp. 873-81.
Buse, JB, Bergenstal, RM, Glass, LC. "Use of twice-daily exenatide in basal insulin-treated patients with type 2 diabetes: a randomized, controlled trial". Ann Intern Med. vol. 154. 2011. pp. 103-12.
Traina, AN, Kane, MP. " Primer on pramlintide, an amylin analog". Diabetes Educ. vol. 37. 2011. pp. 426-31.
Riddle, M, Frias, J, Zhang, B. "Pramlintide improved glycemic control and reduced weight in patients with type 2 diabetes using basal insulin". Diabetes Care. vol. 30. 2007. pp. 2794-9.
Huffman, DM, McLean, GW, Seagrove, MA. " Continuous subcutaneous pramlintide infusion therapy in patients with type 1 diabetes: observations from a pilot study". Endocr Pract. vol. 15. 2009. pp. 689-95.
Pullman, J, Darsow, T, Frias, JP. "Pramlintide in the management of insulin-using patients with type 2 and type 1 diabetes". Vasc Health Risk Manag. vol. 2. 2006. pp. 203-12.
Neumiller, JJ, Campbell, RK, Wood, LD. " A review of inhaled technosphere insulin". Ann Pharmacotherapy. vol. 44(7-8). 2010. pp. 1231-9.
Copyright © 2017, 2013 Decision Support in Medicine, LLC. All rights reserved.
No sponsor or advertiser has participated in, approved or paid for the content provided by Decision Support in Medicine LLC. The Licensed Content is the property of and copyrighted by DSM.
- Basal-bolus insulin (Multiple Daily Injections [MDI]) - General Description
- Initiation of the basal-bolus regimen in type 2 diabetes
- Initiation of the basal-bolus regimen in type 1 diabetes
- U-500 Insulin for Severe Insulin Resistance
- Use of Glucagon-Like Peptide-1 Mimetics or Pramlintide with Insulin
- What's the Evidence?/References


text:
i have been packing up a quarter century of my life, my ex-husband's life, my two stepchildren's lives, my own children's lives. it's sometimes surprising to come across a book, a drawing, a sportsmanship award for which kid and what sport? i have cried looking at little blobs of clay that were once handed to me with great pride and an "i made this for you, mommy!" but i don't have to worry about the next phase of my life, because at least i have my job.
well, i have a job on facebook!
i am friends with f2fb friend #318 arthur frank, the father of the delightful gal in the video. he owns round table books and he was just as surprised to discover that i am now listed as being employed at his establishment. oddly, he has not offered me a salary. or a corner office. on the other hand, i haven't offered to show up and do actual, like, work. one of the very odd things about being fifty one is that a lot of employment skills are difficult to implement or to prove to a potential employer without some major practice. for instance, if i were set loose behind a starbucks espresso machine, i'm sure the company's share price would drop as precipitously as facebook's share price.
still, he has even more of a problem–mr. z. set off an italian controversy worthy of a tempermento tantrum enorme! he doesn't tip. no, not at all. not a a euro at the coffee shop. not a euro at the cozy sidewalk cafe. not a euro at the little corner romantic pasta joint. i went around the world to meet my facebook friends last year and i tipped everywhere. i gotta ask . . .
arthur might not want to employ me, but he is the owner of a business that will help me. help me with disposing of the many books i have acquired over the last twenty five years. round table books takes books on consignment, sells them, and if it can't sell them, it donates the books to charity. go visit their website–maybe they can help you find a book you're looking for or take care of a book you need to find a new home for! www.roundtablebooks.com right now they have a lot of arlynn presser and vivian leiber books–i wrote under the name vivian leiber for many years.
but arthur's not doing this alone. he is employing my f2fb friend #319 eric c. carley who reminded me that there is a very honorable means for a femme seul to live in winnetka–for free!
so next time you look at my facebook page, you'll notice that i'm employed at round table books. i wonder if mark zuckerberg would like to give me a job. . . at least on facebook!

subset: commoncrawl


text:
Get it with: pip install nrn-glia
It allows you to install package with either pip install <package-name> or glia install <package-name> and will automatically discover and compile the mod files within, ready for immediate use.
Using it in your Python scripts is as easy as importing glia! No more manual compiling or messing about with mod files in different folders required. Glia will prevent all naming conflicts for you.
Glia will resolve all naming conflicts between packages and allows you to install multiple packages that provide an implementation of for example Kv1, you can select which one to use by default using glia select <name> <package> <variant> to use the variant from package as default implementation for Kv1.
Code: Select all
from neuron import h
import glia as g
section = h.Section()
g.insert(section, "Kv1")
You can still select different implementations at runtime like so:
Feel free to leave comments, feedback or report issues on GitHub: https://github.com/dbbs-lab/glia
Code: Select all
g.insert(section, "Kv1", pkg="other_package", variant="leaky")
Astrocyte is a packager for Glia and will help you distribute glia packages. Distributing your own glia package is as simple as:
astro create package <name>
cd <name>
astro add mod <mod-file>
astro build
astro upload
Repeat astro add mod as much as you like and after these few simple steps you will have uploaded a bundle of publicly available mod files that others can use immediatly simply by typing glia install <name>


text:
Pokemon 2010 Stamp Retusden Series #9 Hippowdon Ink Stamper
Pokemon 2010 Stamp Retsuden series #9 Hippowdon ink stamper. This ink stamper was only sold in Japan for a very limited time, in April, 2010. They were sold in random sealed wrappers, so there was no way to know which one you would get until you opened it. NOTE: I had to open the wrapper to see which character, so you will receive the stamp only. Plastic wrapper NOT INCLUDED. The bottom of the ink stamper unscrews and inside is a stamper with ink built in to it. See "additional images" to see what the actual stamp looks like when stamped on paper. When the ink runs out, you can just buy a separate ink pad and continue to use the stamper. There was a total of 36 different characters in this series of stamps. Out of production.
Height: 1.5" (4cm)
Width: 1" (2.75cm) width of stamper
Stamper #: 320
Condition: Brand new. Never been played with, but not in sealed package. I had to open it to find out which stamper was inside the wrapper.


text:
Christie vetoes gay marriage bill as vowed
TRENTON (AP) — Gov. Chris Christie has followed through on his promise to reject a bill allowing same-sex marriage in New Jersey by quickly vetoing the measure Friday and renewing his call for a ballot question to decide the issue.
The veto came a day after the state Assembly passed the bill. The state Senate had passed it on Monday. Christie, a Republican who opposes same-sex marriage, had vowed "very swift action" once the measure reached his desk.
In returning the bill to the Legislature, Christie reaffirmed his view that voters should decide whether to change the definition of marriage in New Jersey. His veto also proposed creating an ombudsman to oversee compliance with the state's civil union law, which same-sex couples have said is flawed and promotes discrimination.
"I am adhering to what I've said since this bill was first introduced — an issue of this magnitude and importance, which requires a constitutional amendment, should be left to the people of New Jersey to decide," Christie said in a statement. "I continue to encourage the Legislature to trust the people of New Jersey and seek their input by allowing our citizens to vote on a question that represents a profoundly significant societal change. This is the only path to amend our State Constitution and the best way to resolve the issue of same-sex marriage in our state.
"I have been just as adamant that same-sex couples in a civil union deserve the very same rights and benefits enjoyed by married couples — as well as the strict enforcement of those rights and benefits," the statement continued. "Discrimination should not be tolerated and any complaint alleging a violation of a citizen's right should be investigated and, if appropriate, remedied. To that end, I include in my conditional veto the creation of a strong Ombudsman for Civil Unions to carry on New Jersey's strong tradition of tolerance and fairness."
Democrats who had pushed the bill forward said they were disappointed, but not surprised, by Christie's action.
"It's unfortunate that the governor would let his own personal ideology infringe on the rights of thousands of New Jerseyans," said Reed Gusciora, one of two openly gay New Jersey lawmakers and a sponsor of the bill. "For all those who oppose marriage equality, their lives would have been completely unchanged by this bill, but for same-sex couples, their lives would have been radically transformed. Unfortunately, the governor couldn't see past his own personal ambitions to honor this truth."
Senate President Steve Sweeney was more blunt in his criticism of the governor.
"He had a chance to do the right thing, and failed miserably," Sweeney said.
Lambda Legal, a civil rights organization focusing on gay rights issues that last year filed a lawsuit for marriage equality in New Jersey, called Christie's veto "an unfortunate detour" in the quest for gay marriage.
"We are disappointed that Governor Christie did not do what is right for New Jersey families, but we are not discouraged," said Hayley Gorenberg, the group's deputy legal director. "We'll continue to make our case for equality with our plaintiffs in court."
Proponents of the bill said gay marriage is a civil right being denied to gay couples, while opponents said the definition of marriage as a heterosexual institution should not be expanded. The legislation contains a religious opt-out clause, meaning no church clergy would be required to perform gay marriages and places of worship would not have to allow same-sex weddings at their facilities.
Steven Goldstein, chairman of the state's largest gay rights group, Garden State Equality, said Christie's national political ambitions guided his action.
"He won't veto the bill because he's anti-gay," Goldstein said in a statement issued before the veto was issued Friday. "He'll veto the bill because the 2016 South Carolina presidential primary electorate is anti-gay."
Goldstein, who said he has a cordial relationship with the governor, promised to continue fighting him vigorously on the issue. "And we will win, so help me God," he said.
Another gay marriage supporter, Washington state Democratic Gov. Chris Gregoire, also reached out to Christie, a practicing Catholic. Gregoire sent the governor a letter last month offering to talk about gay marriage because, in her words, "while I am a Governor, I am also a Catholic."
The Roman Catholic Church opposes same-sex marriage.
Gregoire signed a gay marriage measure into law in Washington on Monday. Her spokeswoman, Karina Shagren, said Christie hasn't responded to the letter.
Thirty states, including South Carolina, have adopted constitutional amendments banning same-sex marriages, most by defining marriage as a union between a man and a woman.
Six states and Washington, D.C., allow gay marriage. Washington state's new gay marriage law is set to go into effect in June.
Lawmakers in New Jersey have until the end of the legislative session in January 2014 to override the veto.
They would need two-thirds of the lawmakers in the Assembly and Senate to agree. Both votes to pass it fell short of that mark. Christie has virtually guaranteed that no override would succeed because Republicans wouldn't cross him.
The Democratic-controlled Legislature has failed in every previous attempt to override Christie, most notably on a cut to women's health care and an effort to reinstate a tax surcharge on millionaires.
Christie — and most Republican lawmakers — want to put the issue to a public vote. One GOP lawmaker, Sen. Kip Bateman of Somerset, has proposed a ballot question asking voters to allow same-sex nuptials. However, the most powerful Democrat in the Legislature, Senate President Steve Sweeney, has said that won't happen.
Democrats are hoping that support for gay marriage — 52 percent for gay marriage, 42 against it, in New Jersey, according to one recent voter poll — will continue growing.
If same-sex couples can't win gay marriage through legislation, they have engaged in a parallel fight in the courts. Seven gay couples and several of their children have sued, claiming that the state's civil union law doesn't work as intended.
Civil unions were designed to provide the benefits of marriage to gay couples without the title. They were adopted after the Supreme Court instructed the Legislature to provide marriage equality to same-sex couples.
The state's own review commission has since found problems with the law, and same-sex couples have backed that up with testimony before the Legislature.
John Grant and Daniel Weiss, an Asbury Park couple who are in a civil union, are among those who testified in support of gay marriage.
When Grant was in a life-threatening automobile accident and rushed to a New York hospital in 2010 — before that state legalized gay marriage — Weiss said he couldn't authorize badly needed surgery or even go through his partner's wallet to find his health insurance card. He said their civil union was essentially worthless; Grant's neurosurgeon even asked, "What is a civil union?"
A gay marriage bill was defeated in the Senate two years ago, just before Gov. Jon Corzine, a Democrat who supported the measure, left office. Advocates' hopes dimmed with the arrival of Christie, who spoke against gay marriage when asked about it during his campaign.


text:
This Sunday, two individuals tragically lost their lives in a senseless attack. And yesterday, a well-known Japanese journalist tried to connect the stabbings to otaku (geek) culture. Well, that didn't take long.
On TV Asahi's Super J Channel, freelance journalist Akihiro Otani said, "The location where the stabbing happened is close to a known otaku district, Nipponbashi." (Nipponbashi, which is known as Den-Den Town, is the Osaka equivalent of Tokyo's Akihabara.)
Continuing, Otani added, "It's necessary to investigate to see if there isn't a connection to otaku culture."
This is not a throwaway remark. It's another example of Otani's feeble attempts to draw connections between otaku culture and crime—something he's been trying to do for years.
Back in 2004, Otani tried to connect a grisly crime to otaku figurine collecting on the rationale that collecting plastic figurines was like collecting corpses—or something. The killer, who was not an otaku, murdered a young girl, and Otani incorrectly labeled him a figure collecting otaku. While Otani said he wasn't blaming otaku, he did say all otaku could be potential criminals because they lost themselves in anime and video games. (Keep in mind, Otani has authored several manga!)
Online in Japan, people took to Twitter, voicing their disapproval of Otani and the latest garbage he spewed and pointing out that Kyozo Isohi, the attacker, was already proven to be a former biker gang member and not an otaku. That isn't saying all bikers are bad (they are not!), but what does otaku subculture have to do with anything?
Drug addiction, money problems, a criminal record, and a deeply troubled individual are in play here, not the Japanese nerd culture sold in nearby Nipponbashi.
To add insult to injury, one of the deceased, Shingo Minamino, worked for a game company. He worked on otaku music. His company churns outs entertainment tailored specifically for otaku. Yet, this is also unrelated to the attack. It is related to Minamino's life and work. Otani's attempt to connect the attacker's motive and otaku subculture isn't only misguided, but it's an affront to the work and memory of Shingo Minamino.


text:
Dear Twilight,
Now that we're all coming down off the high of having watched hours upon hours of special features, extended scenes, music videos, commentary (Jacob Black's romantic fails!), Edward in fast forward and mostly just a lot of sighing and swooning I think it's time we relive actually purchasing the DVD and seeing Chris Weitz and Nikki Reed at the New Moon DVD release party. *needle skips* maybe I should ACTUALLY say ATTEMPT to Chris Weitz and Nikki Reed and ALMOST buy a New Moon DVD… let's back up shall we?
I think it's time for Storytime with Moon:
After it was announced that CeeDubs and NReed would be gracing us with their presence here in LA for a NM DVD release party us LA gals emailed back and forth trying to narrow down where we thought it would be. Not Hot Topic like last year, they didn't even have a DVD. Probably not a blockbuster… too small for LA folks so it had to be the Borders in Hollywood, right? The one that a previous Twilight event had taken place. WRONG! WRONG! WRONG! @Twilight announce it would actually be in SANTA CLARITA which is about an hour north of Los Angeles at a WalMart. Because you see, Los Angeles doesn't actually have a WalMart. So with our LA DVD release party not actually occuring in LA we organized the great Roadtrip of 2010 to Santa Clarita to meet our lover Chris Weitz and to see Nikki Reed again.
We arrived and being used to shopping in small shops, grocery stores or the 3 story Target for our toiletries, food and clothes we ran from aisle to aisle looking at everything WalMart had to offer.
Cases of Red Bull next to a copy of New Moon. Cause you'll need artificial stimulants to make it through the entire saga in 2 days. AND GO!
And then we found these gems on the Barbie aisle. The Bella Barbie next to the Joan Jett Barbie?! What other unintentional hilarity would we find?
And then we found it! The Twilight "store" inside of WalMart and I did a leap for joy! Awkward TShirts for 9 dollars? Necklaces of fangs?! Dripping blood earrings? Oh WalMart you know this saga SOOOO well.
Filed under: chris weitz, DVD, LTT, New Moon movie, Nikki Reed, Storytime, Twilight | Tagged: Ashley Greene, cast, chris weitz, cupcakes, DVD, DVD Release Party, FacePunch, fail, Hot Topic, Los Angeles, Midnight, New Moon, nikki reed, pictures, raffles, Roadtrip, Santa Clarita, store, Storytime, summit, summit entertainment, Twilight, Walmart | 101 Comments »


text:
Seems like the reunited Kimerald will have to pay their dues in the late mornings.
Once a successful duo on ABS-CBN's Primetime Bida, the tandem of Kim Chiu and Gerald Anderson will now take their act to the 11:30 a.m. slot with a new series that centers around the world of triathlon. This new series is called 'Ikaw Lang ang Iibigin'.
Starring alongside another tandem in Jake Cuenca and Coleen Garcia, 'Ikaw Lang ang Iibigin' centers around childhood friends Bianca (Kim) and Gabriel (Gerald), both of whom aspire to become successful triathletes in order to support their families.
Along the way, the duo encounter some obstacles that will test their love for each other. 'Ikaw Lang ang Iibigin' will feature the following storylines:
- Bianca distances herself from Gabriel in hopes of saving her father's life
- After a long period of separation, Bianca and Gabriel met anew in a triathlon event headlined by Carlos (Jake), a top triathlete in the country
- Carlos hires Bianca as an endorser of Tigershark, then falls in love with her to the dismay of his ex-girlfriend Isabelle (Coleen)
- Carlos and Gabriel become archrivals in both triathlon and in Bianca's heart, but some secrets from the past soon threaten their lives
'Ikaw Lang ang Iibigin' will also star Gina Pareño, Bing Loyzaga, Ayen Munji-Laurel, Michael De Mesa, Daniel Fernando, Dante Rivero, Nicco Manalo, Ivan Carapiet, Andrea Brillantes, and Grae Fernandez. The series will be directed by Dan Villegas and Onat Diaz.
Unlike previous romantic late-morning series in 'Be Careful with My Heart' and 'Be My Lady', 'Ikaw Lang ang Iibigin' will have a more serious tone that is uncharacteristic for the slot. The storyline would have been a perfect fit for primetime, but with no slots available at the moment, ABS-CBN has no choice but to place this series before noontime.
Still, considering the past success of the Kapamilya network at the said slot, ratings should not be a problem for 'Ikaw Lang ang Iibigin'. That said, the network only hope to see the viewers fall in love with this pensive drama.
'Ikaw Lang ang Iibigin airs weekdays before 'It's Showtime' on ABS-CBN's PrimeTanghali.


text:
Princeton Review names RIT among best colleges
High marks for academics, innovation and opportunities for real-world work experience
Rochester Institute of Technology is again being recognized by The Princeton Review as one of the nation's best universities for undergraduate education. The education-services company features RIT in the just-published 2015 edition of its annual book The Best 379 Colleges. Within the edition, RIT was also ranked as having the ninth best college radio station.
In its profile on RIT, The Princeton Review quotes extensively from students at the university who were surveyed for the book.
According to a summary of student comments, "Rochester Institute of Technology is bursting at the seams with a myriad of fantastic academic opportunities. Students here greatly value the fact that the university maintains a strong 'focus on innovation' and heavily encourages 'collaboration [between] business and technology.'…Moreover, an RIT education isn't merely theoretical. Indeed, undergrads have many chances to participate in (all) manner of labs and workshops, applying what they study and participating in a number of hands-on experiences."
The publication also cites "RIT's fabulous co-op program which allows students to get real-world experience while still in school. And with amazing departments ranging from game design and animation to computer science and biotechnology, your academic needs and interests are guaranteed to be met."
"RIT offers outstanding academics, which is the chief reason we selected it for the book," said Robert Franek, Princeton Review's senior vice president, publisher and author of the publication. "We base our choices primarily on data we obtain in our annual surveys of administrators at these schools and at hundreds of other colleges. We take into account input we get from our staff, our 27-member National College Counselor Advisory Board, our personal visits to schools, and the sizable amount of feedback we get from our surveys of students attending these schools. We also work to maintain a wide representation of colleges in the book by region, size, selectivity and character."
The Princeton Review is an education-services company known for its test-prep courses, tutoring, books and other student resources. School profiles and ranking lists in The Best 379 Colleges are available at the Princeton Review website.
The Princeton Review is just one of several national rankings received by RIT.


text:
Featured Item
Welcome to Transcendental Stage.
Featured Item
Rejuvenate Forever
Mar 16, 2008.
For those of you that celebrate St. Patrick's Day -- have a good one. Just don't do anything too crazy. Sure, drinking your own weight in green beer sounds like a good idea at first, but when you wake up the next morning lying in a ditch, wearing someone else's clothes, with some unidentifiable substance in your pocket, you might not think it was such a good idea.
For more on the subject of binge drinking, you should go read the latest Ed Fur's Dream comic.
And make sure you come back to visit Transcendental Stage after you've recovered from your celebration. There will be a number of new content items added to the site in the next little while.
J.N. Rowan
Go to this post in the Forum
Feb 14, 2008.
Happy Valentine's Day everyone. I know some people think that Valentine's Day was just made up to sell more cards, chocolates, and flowers, but what can I say, I love all Holidays. Any excuse to make a day special, to have a celebration, or just to have some candy, is a good thing in my books.
And besides, Valentine's Day is at least a more meaningful holiday than St. Patrick's Day (unless maybe you're Irish), although I have every intention of celebrating St. Patrick's Day as well. And if anyone else knows of any other good days to celebrate between know and then, feel free to let me know.
So in honour of Valentine's Day, I've added a new poem to the Literature section entitled We Are. Is it a love poem, or is it just some random poem that has nothing to do with Valentine's Day? You'll have to read it and decide for yourself.
J.N. Rowan
Go to this post in the Forum
Jan 16, 2008.
Happy New Year!
OK, so I know it's a little late to be saying Happy New Year, but I haven't had a chance to say it yet, so I'm saying it now. And who says that the year doesn't start on January 16th anyway. January 16th is as good a day as any to start the year, plus it's also the anniversary date for Transcendental Stage, and I'm sure most of you would agree that time didn't really mean anything before Transcendental Stage started.
Hopefully the new year will bring good things for all of you. I have all sorts of things planed for the site in the coming year, and although last year fell a little short in my goals for the site, I really think this year will bring some great things to Transcendental Stage. So keep checking back for all the fun and exciting additions. If you want to be kept up to date on everything that is going on at Transcendental Stage, you should join the newsletter mailing list. I know it hasn't even come close to being the monthly newsletter it was planned to be, but that is all going to change this year. The next newsletter should be coming out this month, and should be followed by another one next month.
And if I somehow fail to make all the regular updates to the site that I have planned, don't worry, I have a backup plan. I'll just embed some sort of hidden message on the site that tells your brains to erase all memories of Transcendental Stage after you leave the site, so that the next you come back everything will seem new. I've always felt people should live their lives based on the motto "If I haven't seen it before, it's new to me", and this would just be my way of helping out. So whatever happens, everyone wins, or possibly everyone loses, I always get those two confused.
J.N. Rowan
Go to this post in the Forum
Dec 16, 2007.
I've been so busy in my workshop this month, getting everything ready for my big sleigh ride on the 24th ... oh wait, that's not me. Well, I've been busy doing something this month, which has had the unfortunate side effect of leaving Transcendental Stage a little neglected. The site has lost a lot of weight and is starting to look mangy. It also keeps making this yelping noise every time I say the phrase 'chestnuts roasting on an open fire', but I don't know what that's all about.
OK, none of that made any sense, but the point is, there haven't been many updates this month, and unfortunately, there probably won't be that many more until next year (although there should be at least a couple). But you should all be out enjoying this wonderful time of year anyway. So go out and roll around in the snow (but dress warmly because dying of hypothermia isn't as fun as it sounds, trust me), and if you don't have any snow where you live, then pour a bunch of salt into a mound and roll around in that, it's pretty much the same thing except for the part where you get horribly scratched by all the salt grains, and then end up rubbing salt into your own wounds.
Once you've recovered from your ill advised roll in the 'snow' (which should be sometime around mid 2008), you should come back to the site and there will be all sorts of fun new things to check out.
Happy Holidays,
J.N. Rowan
Go to this post in the Forum
Nov 09, 2007.
Halloween is long over, but for those of you that may not have had a chance to see some of the latest Halloween content that was added to the site (which may have been because some of it wasn't added to the site until after Halloween), here are some of the recent additions to the site.
Ed Fur's Dreams #86 - cooking up some special treats for Halloween.
And a new addition to the imagery section - Carving Interruption
It's a little too early to start talking about any of the big Holidays in December, but if people can have Santa Claus parades in November, then I guess it's OK for me to mention that there will be all sorts of new items added to the shop this month just in time for gift giving, if you're into that sort of thing.
But while you're waiting for all that Holiday cheer to arrive, keep checking the site for many non-holiday related updates this month.
J.N. Rowan
Go to this post in the Forum
Oct 04, 2007.
Halloween Month is here again, and as usual, that means some fun Halloween content will be added to the site this month. It's still early, so there will be more coming later, but to start things off, here is the latest Ed Fur's Dream: Never Want to Eat Sardines featuring the return of the ghost.
Fortunately for me, the gremlins that always seem to be impeding my progress on this site, are usually too busy during Halloween month to bother me, so it should be a good month full of updates to the site. A few items that will be coming soon might not all be Halloween themed, which I know seems crazy -- how could anyone think of anything other than Halloween during Halloween month -- but don't worry, by the end of the month there should be plenty of Halloween goodness to keep you satisfied. Or at least hold you over until you have bags of candy goodness to really keep you satisfied.
J.N. Rowan
Go to this post in the Forum
Sep 13, 2007.
There are some cool new things coming to Transcendental Stage, but since they are still a little ways off, I won't waste time talking about them now. Why did I bother mentioning it then? That's a very good question. I'm going to leave it up to you to answer the question, but to make it easier, I'll give you a few possible suggestions:
a) The Devil made me do it
b) A man in a large yellow cowboy hat offered me a bucket full of money to include the phrase 'cool new things'
c) I've gone completely crazy and can no longer control what I write
d) I like to pretend that I am actually making progress with the site, and quite frankly, I couldn't think of anything else to say
e) All of the above
Of course, if you don't like any of those answers, feel free to come up with one of your own.
But, enough of that nonsense, the point is, you are going to have to wait a little while for all the cool new stuff, but in the meantime you can check out some of the newest content on the site. Such as a new photography piece called Resa Anblicken. Or a new poem called Relative Despair. And of course there is the latest EFD comic.
J.N. Rowan
Go to this post in the Forum
Aug 02, 2007.
Well, I hate to constantly admit my own failure at updating the site as often as I should, but since I've already established a theme of apologizing for my lateness, I might as well stick with the theme. So once again, I'm sorry for not updating more often, and I'll try to do better in the future.
Unfortunately, that future is going to be at least two weeks away because I'm going to be gone for a while. I could tell you where I'm going, but making something up will be much more interesting, so it's probably best that you just assume I'm going on an intergalactic adventure the likes of which have never been seen (which means there will most likely be intense life or death situations, and someone will end up happily ever after, though probably not me)
Hopefully my intergalactic adventure will give me all sorts of inspiration and new material to work with so that I can add many new and exciting additions to the site.
In the mean time, you can check out some of the more recent additions to the site, like Rejuvenate Forever and High Tide Sanity in the Imagery section. Or It can be nice Not to Know in the Literature section. And of course the latest EFD comic strips can always be found here.
J.N. Rowan
Go to this post in the Forum
Mar 27, 2007.
While everyone is eagerly anticipating all the things I keep promising will be coming soon, I thought I would mention a few things that have actually been added to the site recently.
A couple new images have been added to the Imagery section: Ripped from the Sky
There are also several new T-shirt designs available in the Words for Wear section of the shop, including shirts for Rabbit Races, and He's not Diseased
And finally there is another new strip for Ed Fur's Dreams here.
J.N. Rowan
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Feb 14, 2007.
Happy Valentine's Day
Sure Valentine's Day may have been invented to sell chocolate, flowers, cards, teddy bears, and jewelry, but all Holidays are good days (it's a rule). There may not be ghosts, elves, or leprechauns, but I'm sure you can find something to enjoy about the day *wink* *wink*.
And what says Valentine's Day like roses.
Or you could check out the Poetry section. They aren't necessarily love poems, but poetry is always open to interpretation, so you can believe that they are about romance and love, or death, or drunk wallabies, whatever floats your boat.
Or if you just don't like Valentine's Day, then why not check out Ed Fur's Dreams for a good laugh, or at least some good scratch-your-head attempts at humour.
J.N. Rowan
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Jan 11, 2007.
Due to the all the hectic 'craziness' of the holidays, Transcendental Stage suffered from a somewhat early Holiday break that also went a little longer than expected. So some of the items that were supposed to be added during December are just being added now. But I'm sure you're all thinking, "this is perfect, I was hoping to find some way to stretch the holidays out a little longer." So maybe the delay was all part of my ingenious plan. (Or at least that is what I'm going to tell myself.)
So enjoy some holiday fun in January with EFD #59 - Wish you had Three Tongues
And get into The Spirit of Things
I've got big plans for 2007, so keep visiting the site to see all the new and exciting additions (or just to see if I actually manage to get anything done on time)
Happy New Year
J.N. Rowan
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Dec 07, 2006.
I'm going to try to ignore the fact that it's getting very cold outside, and try to focus on the good -- the Holiday Season has started. Everyone loves the Holiday Season, and when I say 'everyone', I'm excluding those people that don't love the Holiday Season, because those people don't really count, now do they.
So if I can pry myself away from watching all the specials on TV, I'm going to try to add some fun Holiday inspired content to the site this month. And if you can pry yourself away from those same specials, you can come visit Transcendental Stage and check them out.
And for those of you still looking to do some gift shopping, there's still enough time to browse the shop and find some fantastic gifts that everyone will love, and when I say 'everyone', I'm excluding those people that won't love those gifts, because those people don't really count, now do they.
J.N. Rowan
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Nov 08, 2006.
Halloween's over, and probably most of the candy is gone by now. Even the Simpsons Halloween special has aired. So it's time to move on to other things.
I was so busy with all the Halloween themed content I added last month that I have been neglecting some of the other areas of the site, so I hope to correct that over the next couple of months.
I'm also going to be adding a number of new items to the shop that will be available in time for the holidays. Everyone loves a fun T-shirt, and they go great with any gift. A video game, and a fun T-shirt. A movie, and a fun T-shirt. A new car, and a fun T-shirt. Whatever gifts you may be giving this holiday season, you can't go wrong by adding in a fun T-shirt.
But it's not just T-shirts, there are all sorts of items in the shop that would go great with that new waffle iron, TV, or even socks.
So keep visiting Transcendental Stage for all new content, and check out the shop for some great gift ideas.
J.N. Rowan
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Oct 13, 2006.
It's Friday the 13th. And in October no less.
So I figured what better time to add a bunch of Halloween themed content.
Ed Fur's Dreams #51
Featuring the return of the Ghost.
Shackled in Shadows
A creepy 3D rendering.
And Friends of Necessity
A new short story. (Which isn't really Halloween themed, but I finally got it done, so it made sense to upload it now. However, I do have a Halloween story planned for later in the month, so hopefully I'll get that done in time, or I may have to be like The Simpsons and release my Halloween stuff in November.)
Halloween always inspires me, so I still have a few more things planned for this month. Although, I always have more ideas than time, but I'll try to do my best to get it all out there so you good people can enjoy some wonderful Halloween goodness.
J.N. Rowan
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Oct 02, 2006.
It's October now, which means it's Halloween month.
Everyone loves Halloween (right?) so I'm sure you're all excited about all the Halloween related items that will be added to the site this month.
October is always a busy month, but I'll try my best to get everything done sooner rather than later.
J.N. Rowan
Go to this post in the Forum


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Evolutionary and Revolutionary Innovation
Triggered by a couple of recent discussions, I've been pondering for a while now over the question how evolution relates to revolution when it comes to innovation. In the following, I'll try to develop my view on this. Let's define evolution as continuous and incremental innovations of a firm's existing business. Whereas revolution can be described as radical and discontinuous leaps to completely novel offerings, opening up new business and growth trajectories. Jeff Stibel writes:
Evolutionary innovators ask questions based on the limitations of existing solutions; revolutionary innovators ask questions no one else has thought of. This sentiment was eloquently captured by Robert Kennedy when he paraphrased a quote by George Bernard Shaw: "Some people see things as they are and say why? I dream things that never were and say why not.
I've noticed time and again that this issue often leads to either-or positions. It can be argued that evolutionary innovators can be highly successful with limited risk – in large part, innovation returns come from evolution. Moreover, evolution accounts for the majority of innovation activities in most firms. The problem: evolutionary innovation only optimizes and exploits existing businesses and prolongs their trajectories. Revolutionary innovation, in turn, explores new-to-the-world opportunities and creates new business potential. Both types of innovation require dedicated conditions, capabilities and mindsets in order to thrive. Whereas evolution strongly depends on customer insght capabilites, revolution is mainly fed by visionary foresight. Revolutionary innovation is closely connected with high uncertainty as it addresses a future that doesn't exist yet, but is going to emerge through the innovation itself. The concept of customer orientation can be considered twofold:
• Evolutionary innovation focuses on orientation TOWARDS today's customers
• Revolutionary innovation focuses on orientation OF tomorrow's customers
Basically, firms need both, revolutions and evolutions in order to operate sustainable and profitable on the long term. At some point in time it becomes mandatory for every organization to operate "ambidextrously". Those organizations are at risk of failing because innovations might be driven in the wrong system. Consequence: the existing business dies, the novel idea dies, or both. Organizational and individual capabilities to integrate opposing innovation systems prove to be increasingly crucial. Grant McCracken proposes, every company should build a second corporation:
The first corporation exists to win. It exists to find, extract, and capture available value. Leave this just as it is. But let's acknowledge that this first corporation exposes us to risk. After all, it is designed to work with the world as it is. So it must be out of alignment with the worlds that may be. It make us a prisoner of the moment. The second corporation is looking for those worlds that may be. It's task is not to win, but survive.
According to Don Norman and Roberto Verganti, the complementary relation of incremental innovation (within a given frame of solutions) and radical innovation (change of frame) can be depicted as hill-climbing paradigm (see figure). They write:
Although the hill-climbing procedure guarantees continual improvement with eventual termination at the peak of the hill, it has a well-known limit: there is no way to know whether there might be even higher hills in some other part of the design space. Hill-climbing methods get trapped in local maxima. Incremental innovation attempts to reach the highest point on the current hill. Radical innovation seeks the highest hill. (…)
Without radical innovation, incremental innovation reaches a limit. Without incremental innovation, the potential enabled by radical change is not captured.
"Revolutionary ideas rely on evolution to survive", says Rieva Lesonsky in a great post on that issue. This important interplay also becomes obvious upon considering the innovation adoption cycle, as discussed by Greg Satell. He writes:
When an early innovation comes to market, there will undoubtedly be a small amount of people who are excited about it. After all, it can do things nothing else has been able to do before. That's cool and the "cool crowd" gets it immediately. They are enchanted by their new toy and start advocating it to friends. Adoption increases.
There is, however, a problem. The new product doesn't work very well, it's hard to use and it's expensive as many disruptive innovations tend to be. Many people can't see the point in shelling out big money to buy a product that confuses them, makes them feel stupid and the final product experience doesn't seem worth the effort.
That's when a change in the basis of competition happens. Success begins to become less a matter of features and functions and depends more on the interaction with the user. In other words, less on engineering (in the classical sense of the word) and more on design.
The point is: at the outset, radical innovation attracts early adopters due to its novelty. In order to cross the chasm and capture the mass market, the innovation needs to get optimized in terms of customer needs and user experience. That's accomplished through steady incremental steps, typically leveraging insights gained by employing customer-centered methodologies. Drawing on the model of Norman and Verganti above, launching a revolution is like leaping to a new hill. Eventually succeeding in the marketplace, however, requires climbing up the hill to the peak through evolutionary progress. "Breakthroughs don't pay", summarizes James Gardner the fact that research suggests: a first-mover advantage doesn't seem to exist. Therefore, innovators don't necessarily need to be first-to-market, but first-to-scale.
Another take comes from Jeff Stibel:
While both types of innovation play a vital role in the developmental ecosystem of technology, industry and business, it is the non-linear or revolutionary innovations that make the most significant advances. These are the ones that make the real difference. The really huge achievements in technology and the world at large are the result of visionary activists who imagine and then build something none of us had previously thought possible. (…)
Reasonable people can debate whether a particular innovation belongs in the first category or the second. What is not debatable is that while both play a role in the ecology of innovation, it is the truly revolutionary innovations that make all subsequent incremental improvements possible.
Sustainable innovation isn't about either evolution or revolution – it's about both/and. Organizations are required to develop a "complementary innovation system" by integrating opposing approaches, capabilities and mindsets.
• Evolution tends to optimize the world as is. Revolution aims at creating the world as it could be.
• Evolution needs revolution in order to explore further potential to be tapped.
• Revolution needs evolution in order to survive and thrive.
image credit: sarahkocischeilz.com
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Dr. Ralph-Christian Ohr has extensive experience in product/innovation management for international technology-based companies. His particular interest is targeted at the intersection of organizational and human innovation capabilities. You can follow him on Twitter @Ralph_Ohr.
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13 Comments
Ralph, very nice, and exactly right, and what a challenge to manage to be (and do) X even as we are being (and doing) Not-X. Thanks for including me! Best, Grant


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Can Biologics Make You Rich?
Editor's note: In a previous version of this article, it was stated that Teva's lipegfilgrastim and balugrastim were approved by the FDA, but they are still in clinical development. The Fool regrets the error.
The patent cliff is forcing big pharma to scramble for solutions, both short and long term, to falling R&D productivity and blockbuster-less pipelines. A recent study by IMS Health estimates that loss of exclusivity will result in $79 billion in lost sales for brand-name drugs in the next three years. So it's kind of a big deal.
The urgency will be met with strategic acquisitions -- more than usual, anyway -- to inject promising new drugs into pipelines, and with a reevaluation of R&D departments. Management teams across the industry are pegging their hopes for finding the next basket of blockbuster drugs on one field in particular: biologics.
They aren't crazy for doing so. According to IMS Health, the top 10 biologics generated more than $53 billion in revenue in 2011.Spending on biologic therapies is expected to grow 45% from 2010 to 2015 -- accounting for more than 25% of all growth in pharmaceutical spending. With that much money being thrown around, can biologics make you rich?
What is a biologic?
A biologic is a compound produced by a cell line derived from a living organism such as an animal, plant, bacterium, or virus. It may freak you out, but Chinese hamster ovary lines are the easiest to scale at the moment and are used in seven of the top 10 biologics. This production method differs from traditional small molecules that must be chemically synthesized. Generic biologics are called biosimilars (please don't use the term "follow-on biologics").
Chasing compounds or ailments?
To develop a new biologic, the traditional way of developing small molecule pharmaceuticals must be turned on its head. Small molecules are synthesized and then applied to a range of applications. This process can be costly, as companies don't know which indications will respond best to treatment. A small molecule that fails in phase 2 or phase 3 trials could cost a company billions of dollars and up to 10 years of effort.
Biologics are created by finding an ailment first, and then looking for cell-regulating proteins or antibodies involved in intracellular processes. This revolution in development bodes well for establishing a new guard at R&D facilities across big pharma.
The players
To get a feel for the top companies, let's take a quick look at the top five selling biologics from 2011.
2011 Worldwide Sales
$7.932 billion
$7.367 billion
Biogen Idec
$6.772 billion
Johnson & Johnson
$6.751 billion
$5.968 billin
Source: Nature Biotechnology 2011.
This doesn't include Teva's $400 million acquisition of CoGenesys in 2008, as it looks to corner the empty U.S. market for biosimilars. Last year, the FDA approved the company's drug Tbo-filgrastim for the treatment of neutropenia in some cancer patients. The biologic, which is not a biosimilar, will be launched in the U.S. in late 2013 to compete with Amgen's Neuopogen, which brought in $1.26 billion ($959 million U.S.) in sales in 2011. The drug is already cutting into international sales.
AbbVie took the biologics and ran after a recent spinoff from Abbott Laboratories. The company's top biologic, Humira, is locked in a fierce battle with Amgen's Enbrel for the U.S. arthritis market. Although as fellow Fool Keith Speights pointed out, Enbrel generates 25% of Amgen's total sales while Humira accounts for more than half of AbbVie's total revenue.
Biogen is one of the purest biologic plays on the market, with four approved treatments for multiple conditions and a pipeline stocked full of potential. At just $35 billion, the biologics company is smaller than peers AbbVie ($59 billion) and Amgen ($64 billion). In terms of efficiency and profitability, however, Biogen (38.4% operating margin) compares favorably with the two (35.4% for AbbVie and 33.9% for Amgen).
And of course, a talk about biologics doesn't amount to much if it doesn't mention the ginormous $20.4 billion deal for Sanofi's acquisition of Genzyme, announced in 2011. The sticker shock among shareholders was quickly abated when Sanofi released 2011 financial results: revenue growth of 5.3% with Genzyme, revenue contraction of 1.2% without. Looking ahead, Genzyme currently has six biologics in the pipeline (half are in phase 2 or higher) and markets an additional six approved therapies.
In Syracuse, N.Y., Bristol-Myers Squibb is wrecking the old-world view of pharmaceuticals in favor of biologics. Literally. The company plans to regenerate its aging East Syracuse facility, which supplied the Allied Forces with antibiotics in World War II, and transform the site into a biotechnology research campus. Those plans may have to wait (who knew tearing down giant steel drums from 60 years ago could release toxic amounts of antibiotics into the environment?), but Bristol has forged ahead with its biggest biologic, ipilimumab.
The drug treats melanoma skin cancer and brought in $514 million in its first 12 months on the market. A slow start, but the company hopes it can generate peak sales of up to $1.5 billion for the indication and is currently testing the antibody in lung and prostate cancers.
Limited generic competition
The patent cliff has heightened the IP awareness of pharmaceutical investors, so it's fair to question the viability of biologics that have lost, or are about to lose, market exclusivity to biosimilars. For instance, Humira begins losing protection in 2016, while Amgen is already being confronted by competition to Neuopogen.
While the loss of patent protection does have an effect on sales of biologics, it won't be as steep of a cliff traversed by small molecules. Sales for Bristol and Sanofi's blockbuster blood-clot drug Plavix fell 96% in the first full quarter with generic competition. Amgen's Neuopogen, which competes with 10 other companies globally, saw international sales drop only 15% from 2009 to 2010.
Why can't biosimilars pack the same punch as small-molecule generics? Consider that large-scale manufacturing of biologics is a notoriously difficult thing to master. Displaying biomanufacturing competence to the FDA will be a big challenge for smaller firms that have gained traditional generic market share. Even Genzyme's world-class facilities became infected with a virus in 2009, which caused drug stocks to plummet in the following months.
Perhaps the biggest reason for softer competition from biosimilars is price. Genzyme's newest facility in Framingham, Germany, cost $175 million to build, or about $22,000 per liter of bioreactor. Without big technology breakthroughs, the cost of manufacturing is unlikely to drop significantly, which will keep biosimilar prices close to their originator biologic predecessors. This will allow successful biologics to remain relevant after protection expires.
Foolish bottom line
Big pharma is turning to biologics as yesterday's blockbuster small molecules lose protection and market share. The current complexities involved in biomanufacturing provide a sizable moat for early adopters, while also giving incentives for smaller companies to innovate their way into the market. Until that happens, investors should be able to look forward to market-beating growth and steady returns.
While I don't believe Humira will become obsolete overnight after losing exclusivity, it is worrisome that more than 50% of AbbVie's revenue comes from the world's best-selling biologic. The Fool's brand-new premium report on the company answers the high-profile questions that AbbVie investors are asking, and as a bonus, you'll receive a full year of free analyst updates as significant news hits. Simply click here now to claim your copy today.
The article Can Biologics Make You Rich? originally appeared on Fool.com.
Fool contributor Maxx Chatsko has no position in any stocks mentioned. Check out his personal portfolio or follow him on Twitter, @BlacknGoldFool, to keep up with his writing on energy, bioprocessing, and emerging technologies.The Motley Fool has no position in any of the stocks mentioned. Try any of our Foolish newsletter services free for 30 days. We Fools don't all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors. The Motley Fool has a disclosure policy.
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Trump and first lady prepare to commemorate Sept. 11
WASHINGTON (AP) — President Donald Trump is preparing to preside over his first 9/11 commemoration in office, a solemn and nonpartisan occasion in which he will be joined by first lady Melania Trump.
The Trumps plan to observe a moment of silence at the White House on Monday in remembrance of the nearly 3,000 people who were killed when hijackers flew commercial airplanes into New York's World Trade Center, the Pentagon and a field near Shanksville, Pennsylvania.
The morning remembrance is scheduled for about the time the first plane struck one of the Twin Towers on the morning of Sept. 11, 2001.
Trump and his wife also are to pay their respects at a Pentagon ceremony led by Defense Secretary Jim Mattis and Gen. Joseph Dunford, chairman of the Joint Chiefs of Staff. The observances come as Trump grapples with the death and destruction caused by two hurricanes in three weeks.
Vice President Mike Pence is to represent the administration at an observance at the 9/11 memorial in Shanksville.
A native New Yorker, Trump has a mixed history with 9/11. He frequently uses the terrorist strikes to praise the city's response but also makes unsubstantiated claims about what he did and saw on that day.
Trump often lauds the bravery of New York police officers, firefighters and other emergency responders who rushed to the Twin Towers, in some cases knowing they probably wouldn't make it out alive, as an example of the resilience of the city where he made a name for himself.
But Trump has criticized President George W. Bush's handling of the attacks, accusing his fellow Republican of failing to keep Americans safe.
Trump has also made dubious claims about Sept. 11, particularly saying when talking about Muslims that "thousands of people were cheering" in Jersey City, New Jersey, across the Hudson River from lower Manhattan, as the towers collapsed. There is no evidence in news archives of mass celebrations there by Muslims.
Trump has also said he lost "hundreds of friends" in the attack and that he helped clear rubble afterward. Trump has not provided the names of those he knew who perished in the attack, but has mentioned knowing a Catholic priest who died while serving as a chaplain to the city's fire department.
Follow Darlene Superville on Twitter: http://www.twitter.com/dsupervilleap


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